Table1_Promoter Specific Methylation of SSTR4 is Associated With Alcohol Dependence in Han Chinese Males.XLSX

Alcohol dependence (AD), a disease can be affected by environmental factors with epigenetic modification like DNA methylation changes, is one of the most serious and complex public health problems in China and worldwide. Previous findings from our laboratory using the Illumina Infinium Human Methylation450 BeadChip suggested that methylation at the promoter of SSTR4 was one of the major form of DNA modification in alcohol-dependent populations. To investigate whether DNA methylation levels of the SSTR4 promoter influence alcohol-dependent behaviors, genomic DNA was extracted from the peripheral blood sample of 63 subjects with AD and 65 healthy controls, and pyrosequencing was used to verify the results of BeadChip array. Linear regression was used to analyze the correlation between the methylation levels of SSTR4 promoter and the scores of alcohol dependence scales. Gene expression of SSTR4 in brain tissue was obtained from the Genotype-Tissue Expression (GTEx) project and Human Brain Transcriptome database (HBT). We found the methylation levels of SSTR4 in AD group were significantly lower than healthy controls (two-tailed t-test, t = 14.723, p 2= 0.35, p 2 = 0.27, p 2 = 0.49, p < 0.001). The hypomethylated status of SSTR4 may involve in the development of AD and increase the risk of AD persistence in Han Chinese males.</p

Table2_Promoter Specific Methylation of SSTR4 is Associated With Alcohol Dependence in Han Chinese Males.XLS

Alcohol dependence (AD), a disease can be affected by environmental factors with epigenetic modification like DNA methylation changes, is one of the most serious and complex public health problems in China and worldwide. Previous findings from our laboratory using the Illumina Infinium Human Methylation450 BeadChip suggested that methylation at the promoter of SSTR4 was one of the major form of DNA modification in alcohol-dependent populations. To investigate whether DNA methylation levels of the SSTR4 promoter influence alcohol-dependent behaviors, genomic DNA was extracted from the peripheral blood sample of 63 subjects with AD and 65 healthy controls, and pyrosequencing was used to verify the results of BeadChip array. Linear regression was used to analyze the correlation between the methylation levels of SSTR4 promoter and the scores of alcohol dependence scales. Gene expression of SSTR4 in brain tissue was obtained from the Genotype-Tissue Expression (GTEx) project and Human Brain Transcriptome database (HBT). We found the methylation levels of SSTR4 in AD group were significantly lower than healthy controls (two-tailed t-test, t = 14.723, p 2= 0.35, p 2 = 0.27, p 2 = 0.49, p < 0.001). The hypomethylated status of SSTR4 may involve in the development of AD and increase the risk of AD persistence in Han Chinese males.</p

Photoelectrochemical Detection of Exosomal miRNAs by Combining Target-Programmed Controllable Signal Quenching Engineering

MicroRNAs extracted from exosomes (exosomal miRNAs) have recently emerged as promising biomarkers for early prognosis and diagnosis. Thus, the development of an effective approach for exosomal miRNA monitoring has triggered extensive attention. Herein, a sensitive photoelectrochemical (PEC) biosensing platform is demonstrated for exosomal miRNA assay via the target miRNA-powered λ-exonuclease for the amplification strategy. The metal–organic framework (MOF)-decorated WO3 nanoflakes heterostructure is constructed and implemented as the photoelectrode. Also, a target exosomal miRNA-activatable programmed release nanocarrier was fabricated, which is responsible for signal control. Hemin that acted as the electron acceptor was prior entrapped into the programmed control release nanocarriers. Once the target exosomal miRNAs-21 was introduced, the as-prepared programmed release nanocarriers were initiated to trigger the release of hemin, which enabled the quenching of the photocurrent. Under the optimized conditions, the level of exosomal miRNAs-21 could be accurately tracked ranging from 1 fM to 0.1 μM with a low detection limit of 0.5 fM. The discoveries illustrate the possibility for the rapid and efficient diagnosis and prognosis prediction of diseases based on the detection of exosomal miRNAs-21 and would provide feasible approaches for the fabrication of an efficient platform for clinical applications

Table_1_Self-Healable, Fast Responsive Poly(ω-Pentadecalactone) Thermogelling System for Effective Liver Cancer Therapy.DOCX

A polyurethane based thermogelling system comprising poly(ω-pentadecalactone) (PPDL), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG), termed as PDEP, was synthesized. The incorporation of PPDL lowers critical micelle concentration (CMC) as well as critical gelation concentration (CGC) of the novel copolymers compared to commercial Pluronic® F127. The thermogels showed excellent thermal stability at high temperature up to 80°C, fast response to temperature change in a time frame of less than second, as well as remarkable self-healing properties after being broken at high strain. In vitro drug release studies using docetaxel (DTX) and cell uptake studies using doxorubicin (DOX) show high potential of the hydrogel as drug reservoir for sustainable release profile of payloads, while the in vivo anti-tumor evaluation using mice model of hepatocellular carcinoma further demonstrated the significant inhibition on the growth of tumor. Together with its excellent biocompatibility in different organs, the novel PDPE thermogelling copolymers reported in this work could potentially be utilized as in situ-forming hydrogels for liver cancer therapy.</p

Chemical Bond-Modulated Interfacial Energy Band Structures of Heterojunctions for Efficient Photoelectrochemical Water Splitting

Understanding the interfacial interaction of a nanostructure heterojunction and improving the efficiency of photoanodes are of great significance to develop photoelectrochemical (PEC) water splitting. Herein, taking BiVO4 and Bi2S3 as model materials, we investigate the modulation effect of a chemical bond at the heterojunction interface on the energy band structure. A BiVO4/Bi2S3 heterojunction is favorably constructed by a convenient chemical technique of successive ionic layer absorption and reaction (SILAR) method. We find that a Bi–O chemical bond is reasonably introduced at the BiVO4 and Bi2S3 interface, which is different from the physical contact heterojunction of BiVO4/Bi2S3(DC). Experimental and theoretical studies reveal that the Bi–O bond at the heterojunction interface distinctly downshifts the Fermi level of the BiVO4 surface and reverses the bending direction of the interfacial band from the former type II structure to a direct Z-scheme structure. Due to the excellent charge separation efficiency and high redox potential, the heterojunction of BiVO4/Bi2S3 (SILAR) exhibits a significantly raised photocurrent density of 2.71 mA cm–2 at 1.23 VRHE, 11.29 times higher than that of BiVO4/Bi2S3(DC). This study emphasizes the modulation effect of interfacial chemical bonds in the fabrication of heterojunctions and provides a reference to construct high-activity photoanodes for PEC water splitting

Enhanced Antiglioblastoma Efficacy of Neovasculature and Glioma Cells Dual Targeted Nanoparticles

Combining treatment of anticancer cells and antiangiogenesis is considered to be a potential targeted strategy for brain glioblastoma therapy. In this study, by utilizing the overexpression of Interleukin 13 receptor α2 (IL-13Rα2) on the glioma cells and heparan sulfate on neovascular endothelial cells, we developed a paclitaxel (PTX) loaded Pep-1 and CGKRK peptide-modified PEG–PLGA nanoparticle (PC-NP-PTX) for glioma cells and neovasculature dual-targeted chemotherapy to enhance the antiglioma efficacy. There were significant differences both on the enhancement of cellular uptake in HUVEC and C6 cells and on the improvement of <i>in vitro</i> antiglioma activity in the respect of proliferation, tumor spheroid growth, tube formation, and migration between PC-NP-PTX and Taxol and NP-PTX. As for C6 cells, the IC₅₀ were 3.59 ± 0.056, 2.37 ± 0.044, 1.38 ± 0.028, 1.82 ± 0.035, and 1.00 ± 0.016 μg/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, and for HUVEC cells, the IC₅₀ were 0.44 ± 0.006, 0.33 ± 0.005, 0.25 ± 0.005, 0.19 ± 0.004, and 0.16 ± 0.004 μg/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, respectively. <i>In vivo</i> distribution assays confirmed that PC-NP-PTX targeted and accumulated effectively at glioma site. PC-NP-PTX showed a longer median survival time of 61 days when compared with Taxol (22 days), NP-PTX (24 days), Pep-NP-PTX (32 days), and CGKRK-NP-PTX (34 days). The <i>in vivo</i> antiglioma efficacy and safety evaluation showed PC-NP-PTX significantly enhanced the antiglioma efficacy and displayed negligible acute toxicity

DataSheet_1_Within-host acquisition of colistin-resistance of an NDM-producing Klebsiella quasipneumoniae subsp. similipneumoniae strain through the insertion sequence-903B-mediated inactivation of mgrB gene in a lung transplant child in China.docx

BackgroundColistin, as the antibiotic of “last resort” for carbapenem-resistant Klebsiella, develop resistance during administration of this antimicrobial agent. We identified an NDM-1-producing Klebsiella quasipneumonuae subsp. similipneumoniae (KQSS) strain KQ20605 recovered from a child, which developed resistance to colistin (KQ20786) through acquiring an IS903B element between the -27th and -26th bp of mgrB promoter region after 6-day colistin usage.ObjectivesThe aim of this study is to explore the source of IS903B in the disruptive mgrB gene and its underlying mechanisms.Materials and methodsAntibiotics susceptibility testing was conducted via microbroth dilution method. The in vitro colistin-induced experiment of KQ20605 was performed to mimic the in vivo transition from colistin-sensitive to resistant. Whole-genome sequencing was used to molecular identification of colistin resistance mechanism.ResultsThe IS903B element integrated into mgrB gene of KQ20786 had a 100% nucleotide identity and coverage match with one IS903B on plasmid IncR, and only 95.1% (1005/1057) identity to those on chromosome. In vitro, upon the pressure of colistin, KQ20605 could also switch its phenotype from colistin-sensitive to resistant with IS elements (e.g., IS903B and IS26) frequently inserted into mgrB gene at “hotspots”, with the insertion site of IS903B nearly identical to that of KQ20786. Furthermore, IS26 elements in this isolate were only encoded by plasmids, including IncR and conjugative plasmid IncN harboring blaNDM.ConclusionMobilizable IS elements on plasmids tend to be activated and integrated into mgrB gene at “hotspots” in this KQSS, thereby causing the colistin resistance emergence and further dissemination.</p

Table_1_Within-host acquisition of colistin-resistance of an NDM-producing Klebsiella quasipneumoniae subsp. similipneumoniae strain through the insertion sequence-903B-mediated inactivation of mgrB gene in a lung transplant child in China.docx

BackgroundColistin, as the antibiotic of “last resort” for carbapenem-resistant Klebsiella, develop resistance during administration of this antimicrobial agent. We identified an NDM-1-producing Klebsiella quasipneumonuae subsp. similipneumoniae (KQSS) strain KQ20605 recovered from a child, which developed resistance to colistin (KQ20786) through acquiring an IS903B element between the -27th and -26th bp of mgrB promoter region after 6-day colistin usage.ObjectivesThe aim of this study is to explore the source of IS903B in the disruptive mgrB gene and its underlying mechanisms.Materials and methodsAntibiotics susceptibility testing was conducted via microbroth dilution method. The in vitro colistin-induced experiment of KQ20605 was performed to mimic the in vivo transition from colistin-sensitive to resistant. Whole-genome sequencing was used to molecular identification of colistin resistance mechanism.ResultsThe IS903B element integrated into mgrB gene of KQ20786 had a 100% nucleotide identity and coverage match with one IS903B on plasmid IncR, and only 95.1% (1005/1057) identity to those on chromosome. In vitro, upon the pressure of colistin, KQ20605 could also switch its phenotype from colistin-sensitive to resistant with IS elements (e.g., IS903B and IS26) frequently inserted into mgrB gene at “hotspots”, with the insertion site of IS903B nearly identical to that of KQ20786. Furthermore, IS26 elements in this isolate were only encoded by plasmids, including IncR and conjugative plasmid IncN harboring blaNDM.ConclusionMobilizable IS elements on plasmids tend to be activated and integrated into mgrB gene at “hotspots” in this KQSS, thereby causing the colistin resistance emergence and further dissemination.</p

sj-docx-1-tag-10.1177_17562848231177156 – Supplemental material for Artificial intelligence in endoscopic ultrasonography: risk stratification of gastric gastrointestinal stromal tumors

Supplemental material, sj-docx-1-tag-10.1177_17562848231177156 for Artificial intelligence in endoscopic ultrasonography: risk stratification of gastric gastrointestinal stromal tumors by Yi Lu, Lu Chen, Jiachuan Wu, Limian Er, Huihui Shi, Weihui Cheng, Ke Chen, Yuan Liu, Bingfeng Qiu, Qiancheng Xu, Yue Feng, Nan Tang, Fuchuan Wan, Jiachen Sun and Min Zhi in Therapeutic Advances in Gastroenterology</p