Solvothermal Subcomponent Self-Assembly of Cubic Metal–Imidazolate Cages and Their Coordination Polymers

A series of Ni–imidazolate cubic cages, one-dimensional and two-dimensional coordination polymers based on the cubic cages, have been prepared by solvothermal <i>subcomponent self-assembly</i> of 5-methyl-4-formylimidazole, <i>m</i>-xylylenediamine, and Ni^II salts with varied anions. These compounds have been characterized by single-crystal X-ray diffractions, elemental analysis, IR spectra, and powder X-ray diffractions. The formation of an oligomerized coordination cage or an infinite coordination polymer depends on the anions chosen. An oligomerized 8-nuclear Ni–imidazolate cubic cage is formed when the anion Cl^–, Br^–, I^–, SCN^–, NO₂^–, or NO₃^– is utilized in the reactions, and a two-dimensional coordination polymer based on the Ni–imidazolate cubic cage will be obtained when N₃^–, (CN)₂N^–, or (CN)₃C^– act as the anions. When only ClO₄^– or both ClO₄^– and [Ni­(C₄N₂S₂)₂]^2– (C₄N₂S₂ = dimercaptomaleonitrile) as anions exist in the reaction mixture, a ladder-like one-dimensional coordination polymer based on the Ni–imidazolate cubic cage and formate is formed unpredictably

Local and Sustained Activity of Doxycycline Delivered with Layer-by-Layer Microcapsules

Achieving localized delivery of small molecule drugs has the potential to increase efficacy and reduce off target and side effects associated with systemic distribution. Herein, we explore the potential use of layer-by-layer (LbL) assembled microcapsules for the delivery of doxycycline. Absorbance of doxycycline onto core dextran sulfate of preassembled microcapsules provides an efficient method to load both synthetic and biodegradable microcapsules with the drug. Application of an outer layer lipid coat enhances the sustained in vitro release of doxycycline from both microcapsule types. To monitor doxycycline delivery in a biological system, C2C12 mouse myoblasts are engineered to express EGFP under the control of the optimized components of the tetracycline regulated gene expression system. Microcapsules are not toxic to these cells, and upon delivery to the cells, EGFP is more efficiently induced in those cells that contain engulfed microcapsules and monitored EGFP expression clearly demonstrates that synthetic microcapsules with a DPPC coat are the most efficient for sustain intracellular delivery. Doxycycline released from microcapsules also displayed sustained activity in an antimicrobial growth inhibition assay compared with doxycycline solution. This study reveals the potential for LbL microcapsules in small molecule drug delivery and their feasible use for achieving prolonged doxycycline activity

Table_7_Geological and Climatic Factors Affect the Population Genetic Connectivity in Mirabilis himalaica (Nyctaginaceae): Insight From Phylogeography and Dispersal Corridors in the Himalaya-Hengduan Biodiversity Hotspot.doc

The genetic architecture within a species in the Himalaya-Hengduan Mountains (HHM) region was considered as the consolidated consequence of historical orogenesis and climatic oscillations. The visualization of dispersal corridors as the function of population genetic connectivity became crucial to elucidate the spatiotemporal dynamics of organisms. However, geodiversity and physical barriers created by paleo geo-climatic events acted vigorously to impact notable alterations in the phylogeographic pattern and dispersal corridors. Therefore, to achieve detailed phylogeography, locate dispersal corridors and estimate genetic connectivity, we integrated phylogeography with species distribution modelling and least cost path of Mirabilis himalaica (Edgew.) Heimerl in the HHM. We amplified four cpDNA regions (petL-psbE, rps16-trnK, rps16 intron, trnS-trnG), and a low copy nuclear gene (G3pdh) from 241 individuals of 29 populations. SAMOVA, genealogical relationships, and phylogenetic analysis revealed four spatially structured phylogroups for M. himalaica with the onset of diversification in late Pliocene (c. 3.64 Ma). No recent demographic growth was supported by results of neutrality tests, mismatch distribution analysis and Bayesian skyline plot. Paleo-distribution modelling revealed the range dynamics of M. himalaica to be highly sensitive to geo-climatic change with limited long-distance dispersal ability and potential evolutionary adaptation. Furthermore, river drainage systems, valleys and mountain gorges were identified as the corridors for population genetic connectivity among the populations. It is concluded that recent intense mountain uplift and subsequent climatic alterations including monsoonal changes since Pliocene or early Pleistocene formulated fragmented habitats and diverse ecology that governed the habitat connectivity, evolutionary and demographic history of M. himalaica. The integrative genetic and geospatial method would bring new implications for the evolutionary process and conservation priority of HHM endemic species.</p

Table1_Novel end-to-side one-layer continuous pancreaticojejunostomy vs. end-to-end invaginated pancreaticojejunostomy in pancreatoduodenectomy: A single-center retrospective study.docx

Background and ObjectivePostoperative pancreatic fistula (POPF) is the most common critical complication after pancreatoduodenectomy (PD) and is the primary reason for increased mortality and morbidity after PD. We aim to investigate the clinical significance of a novel approach, i.e., end-to-side one-layer continuous pancreaticojejunostomy, for patients with PD.MethodsThe clinical data of 65 patients who underwent pancreatoduodenectomy at the Xiangya Hospital, Central South University, from September 2020 to December 2021 were retrospectively analyzed.ResultsForty patients underwent end-to-end invaginated pancreaticojejunostomy, and 25 underwent the novel end-to-side one-layer continuous pancreaticojejunostomy. No significant differences were observed in pancreatic fistula, intraperitoneal infection, intraperitoneal bleeding, reoperation, postoperative hospital stay, or perioperative death between the two groups. However, the novel end-to-side one-layer continuous pancreaticojejunostomy group had significantly shorter operation duration (32.6 ± 5.1 min vs. 8.3 ± 2.2 min, p ConclusionsThe novel anastomosis method leads to a shorter operation duration than the traditional anastomosis method and does not increase postoperative complications. In conclusion, it is a simplified and feasible method for pancreatic anastomosis.</p

Overall dexmedetomidine vs. midazolam analysis.

<p>Incidence of EA was similar for the two groups, with no significant difference. However, the requirment of a rescue drug was less in the dexmedetomidine group than in the midazolam group. D, dexmedetomidine; M, midazolam</p

Table_7_NR2F1-AS1 Promotes Pancreatic Ductal Adenocarcinoma Progression Through Competing Endogenous RNA Regulatory Network Constructed by Sponging miRNA-146a-5p/miRNA-877-5p.XLSX

The role of NR2F1-AS1 in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Therefore, we aimed to investigate the biological mechanism of NR2F1-AS1 in PDAC. The expression of NR2F1-AS1 was measured by using microarray data and real-time PCR. The effects of NR2F1-AS1 knockdown on proliferation, cell cycle progression, invasion in vitro and tumorigenesis in vivo were investigated. The mechanism of competitive endogenous RNAs was determined from bioinformatics analyses and validated by a dual-luciferase reporter gene assay. Potential target mRNAs from TargetScan 7.2 were selected for subsequent bioinformatics analysis. Key target mRNAs were further identified by screening hub genes and coexpressed protein-coding genes (CEGs) of NR2F1-AS1. NR2F1-AS1 was highly expressed in PDAC, and the overexpression of NR2F1-AS1 was associated with overall survival and disease-free survival. The knockdown of NR2F1-AS1 impaired PDAC cell proliferation, migration, invasion and tumorigenesis. NR2F1-AS1 competitively sponged miR-146a-5p and miR-877-5p, and low expression of the two miRNAs was associated with a poor prognosis. An integrative expression and survival analysis of the hub genes and CEGs demonstrated that the NR2F1-AS1–miR-146a-5p/miR-877-5p–GALNT10/ZNF532/SLC39A1/PGK1/LCO3A1/NRP2/LPCAT2/PSMA4 and CLTC ceRNA networks were linked to the prognosis of PDAC. In conclusion, NR2F1-AS1 overexpression was significantly associated with poor prognosis. NR2F1-AS1 functions as an endogenous RNA to construct a novel ceRNA network by competitively binding to miR-146a-5p/miR-877-5p, which may contribute to PDAC pathogenesis and could represent a promising diagnostic biomarker or potential novel therapeutic target in PDAC.</p

Image_2_NR2F1-AS1 Promotes Pancreatic Ductal Adenocarcinoma Progression Through Competing Endogenous RNA Regulatory Network Constructed by Sponging miRNA-146a-5p/miRNA-877-5p.JPEG

The role of NR2F1-AS1 in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Therefore, we aimed to investigate the biological mechanism of NR2F1-AS1 in PDAC. The expression of NR2F1-AS1 was measured by using microarray data and real-time PCR. The effects of NR2F1-AS1 knockdown on proliferation, cell cycle progression, invasion in vitro and tumorigenesis in vivo were investigated. The mechanism of competitive endogenous RNAs was determined from bioinformatics analyses and validated by a dual-luciferase reporter gene assay. Potential target mRNAs from TargetScan 7.2 were selected for subsequent bioinformatics analysis. Key target mRNAs were further identified by screening hub genes and coexpressed protein-coding genes (CEGs) of NR2F1-AS1. NR2F1-AS1 was highly expressed in PDAC, and the overexpression of NR2F1-AS1 was associated with overall survival and disease-free survival. The knockdown of NR2F1-AS1 impaired PDAC cell proliferation, migration, invasion and tumorigenesis. NR2F1-AS1 competitively sponged miR-146a-5p and miR-877-5p, and low expression of the two miRNAs was associated with a poor prognosis. An integrative expression and survival analysis of the hub genes and CEGs demonstrated that the NR2F1-AS1–miR-146a-5p/miR-877-5p–GALNT10/ZNF532/SLC39A1/PGK1/LCO3A1/NRP2/LPCAT2/PSMA4 and CLTC ceRNA networks were linked to the prognosis of PDAC. In conclusion, NR2F1-AS1 overexpression was significantly associated with poor prognosis. NR2F1-AS1 functions as an endogenous RNA to construct a novel ceRNA network by competitively binding to miR-146a-5p/miR-877-5p, which may contribute to PDAC pathogenesis and could represent a promising diagnostic biomarker or potential novel therapeutic target in PDAC.</p

Table_2_NR2F1-AS1 Promotes Pancreatic Ductal Adenocarcinoma Progression Through Competing Endogenous RNA Regulatory Network Constructed by Sponging miRNA-146a-5p/miRNA-877-5p.XLSX

The role of NR2F1-AS1 in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Therefore, we aimed to investigate the biological mechanism of NR2F1-AS1 in PDAC. The expression of NR2F1-AS1 was measured by using microarray data and real-time PCR. The effects of NR2F1-AS1 knockdown on proliferation, cell cycle progression, invasion in vitro and tumorigenesis in vivo were investigated. The mechanism of competitive endogenous RNAs was determined from bioinformatics analyses and validated by a dual-luciferase reporter gene assay. Potential target mRNAs from TargetScan 7.2 were selected for subsequent bioinformatics analysis. Key target mRNAs were further identified by screening hub genes and coexpressed protein-coding genes (CEGs) of NR2F1-AS1. NR2F1-AS1 was highly expressed in PDAC, and the overexpression of NR2F1-AS1 was associated with overall survival and disease-free survival. The knockdown of NR2F1-AS1 impaired PDAC cell proliferation, migration, invasion and tumorigenesis. NR2F1-AS1 competitively sponged miR-146a-5p and miR-877-5p, and low expression of the two miRNAs was associated with a poor prognosis. An integrative expression and survival analysis of the hub genes and CEGs demonstrated that the NR2F1-AS1–miR-146a-5p/miR-877-5p–GALNT10/ZNF532/SLC39A1/PGK1/LCO3A1/NRP2/LPCAT2/PSMA4 and CLTC ceRNA networks were linked to the prognosis of PDAC. In conclusion, NR2F1-AS1 overexpression was significantly associated with poor prognosis. NR2F1-AS1 functions as an endogenous RNA to construct a novel ceRNA network by competitively binding to miR-146a-5p/miR-877-5p, which may contribute to PDAC pathogenesis and could represent a promising diagnostic biomarker or potential novel therapeutic target in PDAC.</p

Image_3_Geological and Climatic Factors Affect the Population Genetic Connectivity in Mirabilis himalaica (Nyctaginaceae): Insight From Phylogeography and Dispersal Corridors in the Himalaya-Hengduan Biodiversity Hotspot.jpeg

The genetic architecture within a species in the Himalaya-Hengduan Mountains (HHM) region was considered as the consolidated consequence of historical orogenesis and climatic oscillations. The visualization of dispersal corridors as the function of population genetic connectivity became crucial to elucidate the spatiotemporal dynamics of organisms. However, geodiversity and physical barriers created by paleo geo-climatic events acted vigorously to impact notable alterations in the phylogeographic pattern and dispersal corridors. Therefore, to achieve detailed phylogeography, locate dispersal corridors and estimate genetic connectivity, we integrated phylogeography with species distribution modelling and least cost path of Mirabilis himalaica (Edgew.) Heimerl in the HHM. We amplified four cpDNA regions (petL-psbE, rps16-trnK, rps16 intron, trnS-trnG), and a low copy nuclear gene (G3pdh) from 241 individuals of 29 populations. SAMOVA, genealogical relationships, and phylogenetic analysis revealed four spatially structured phylogroups for M. himalaica with the onset of diversification in late Pliocene (c. 3.64 Ma). No recent demographic growth was supported by results of neutrality tests, mismatch distribution analysis and Bayesian skyline plot. Paleo-distribution modelling revealed the range dynamics of M. himalaica to be highly sensitive to geo-climatic change with limited long-distance dispersal ability and potential evolutionary adaptation. Furthermore, river drainage systems, valleys and mountain gorges were identified as the corridors for population genetic connectivity among the populations. It is concluded that recent intense mountain uplift and subsequent climatic alterations including monsoonal changes since Pliocene or early Pleistocene formulated fragmented habitats and diverse ecology that governed the habitat connectivity, evolutionary and demographic history of M. himalaica. The integrative genetic and geospatial method would bring new implications for the evolutionary process and conservation priority of HHM endemic species.</p