A universal aptameric system based on the taking advantage of double-stranded DNA/perylene diimide (dsDNA/PDI) as the signal probe was developed for multiplexed detection of small molecules. Aptamers ...are single-stranded DNA or RNA oligonucleotides which are selected in vitro by a process known as systematic evolution of ligands by exponential enrichment. In this work, we synthesized a new kind of PDI and reported this aggregated PDI could quench the double-stranded DNA (dsDNA)-labeled fluorophores with a high quenching efficiency. The quenching efficiencies on the fluorescence of FAM, TAMRA and Cy5 could reach to 98.3%±0.9%, 97.2%±0.6% and 98.1%±1.1%, respectively. This broad-spectrum quencher was then adopted to construct a multicolor biosensor via a label-free approach. A structure-switching-triggered enzymatic recycling amplification was employed for signal amplification. High quenching efficiency combined with autocatalytic target recycling amplification afforded the biosensor with high sensitivity towards small analytes. For other targets, changing the corresponding aptamer can achieve the goal. The quencher did not interfere with the catalytic activity of nuclease. The biosensor could be manipulated with similar sensitivity no matter in pre-addition or post-addition manner. Moreover, simultaneous and multiplexed analysis of several small molecules in homogeneous solution was achieved, demonstrating its potential application in the rapid screening of multiple biotargets.
•A universal aptameric system based on double-stranded DNA/perylene diimide as the signal probe was developed for multiplexed detection of small molecules.•The new synthesized PDI could quench the dsDNA-labeled fluorophores with high quenching efficiency.•The quenching efficiencies on the fluorescence of FAM, TAMRA and Cy5 reached to 98.3% ± 0.9%, 97.2% ± 0.6% and 98.1% ± 1.1%, respectively.•Multiplexed analysis of several targets in homogeneous solution was achieved, demonstrating its potential application in the rapid screening of multiple biotargets.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The morphogenesis of the cerebral cortex depends on the precise control of gene expression during development. Small non-coding RNAs, including microRNAs and other groups of small RNAs, play profound ...roles in various physiological and pathological processes via their regulation of gene expression. A systematic analysis of the expression profile of small non-coding RNAs in developing cortical tissues is important for clarifying the gene regulation networks mediating key developmental events during cortical morphogenesis.
Global profiling of the small RNA transcriptome was carried out in rat cerebral cortex from E10 till P28 using next-generation sequencing technique. We found an extraordinary degree of developmental stage-specific expression of a large group of microRNAs. A group of novel microRNAs with functional hints were identified, and brain-enriched expression and Dicer-dependent production of high-abundant novel microRNAs were validated. Profound editing of known microRNAs at "seed" sequence and flanking sequence was observed, with much higher editing events detected at late postnatal stages than embryonic stages, suggesting the necessity of microRNA editing for the fine tuning of gene expression during the formation of complicated synaptic connections at postnatal stages.
Our analysis reveals extensive regulation of microRNAs during cortical development. The dataset described here will be a valuable resource for clarifying new regulatory mechanisms for cortical development and diseases and will greatly contribute to our understanding of the divergence, modification, and function of microRNAs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A karst groundwater system ranks among the most sensitive and vulnerable types of groundwater systems. Coal mining and tunnel excavation can greatly change the natural hydrogeological flow system, ...groundwater-dependent vegetation, soil, as well as hydrology of surface water systems. Abandoned coal mine caves and proposed highway tunnels may have significant influences on groundwater systems. This study employs MODFLOW, a 3D finite-difference groundwater model software, to simulate the groundwater system's response to coal mining and tunnel excavation impact in Zhongliang Mountain, Chongqing, from 1948 to 2035. The results show a regional decline in groundwater levels within the study area following mining and tunnel construction. The groundwater flow system in the study area evolves from the Jialing River groundwater flow system to encompass the Jialing River, Moxinpo highway tunnel, Moxinpo, and the Liujiagou coal mine cave groundwater flow systems between 1948 and 2025. With the completion of tunnel construction, the groundwater level at the top of the tunnel is gradually restored to the water level in the natural state. The model also predicts groundwater level variations between 2025 and 2035. The groundwater level will rise further initially, however, it may take about 10 years for the system to stabilize and reach a new equilibrium. In light of these findings, it is advised that changes in groundwater flow systems caused by tunnel construction should be modeled prior to the practical construction. This approach is crucial for evaluating potential engineering and environmental implications.
This study is a first report on the identification of multidrug-resistant (MDR) Acinetobacter bereziniae among non-baumannii acinetobacters that had previously escaped automated laboratory detection, ...and characterize their clinical courses of infection at two tertiary-care hospitals in Shenzhen city, China (2015–2017). Herein, definitive identification by PCR was performed with universal and species-specific primers targeting 16S rDNA and rpoB genes, respectively, followed by Sanger sequencing and blast analysis. Antimicrobial susceptibility of A. bereziniae isolates was assessed accordingly. Three of the five identified A. bereziniae isolates exhibited carbapenem-resistance and were subjected to a multiplex PCR assay to detect drug-resistance genes. Sequences of the rpoB amplicon were aligned with curated sequences from global databases for phylogenetic analysis on evolutionary relations. Five clinical isolates of A. bereziniae were thereby re-identified, whose infections were primarily nosocomial. Automated identification and susceptibility testing systems (Phoenix-100 and VITEK 2) proved insufficient for discriminating A. bereziniae from other acinetobacters such as Acinetobacter baumannii and Acinetobacter guillouiae. Among these isolates, three exhibited carbapenem-resistant phenotypes indistinguishable from that of carbapenem-resistant A. baumannii. The carbapenem-resistant A. bereziniae isolates were subsequently confirmed to carry a blaNDM-1 (New Delhi metallo-β-lactamase-1) gene downstream of ISAba125. Phylogenetic analysis revealed that A. bereziniae isolates evolved slowly but independently in local habitats. A. bereziniae isolates are difficult to distinguish by traditional automated detection systems. PCR-based identification via amplification and sequencing of selected house-keeping genes provides sufficient resolution for discriminating the isolates.
Acinetobacter bereziniae, NDM-1 (New Delhi metallo-β-lactamase-1), healthcare-associated infection, antimicrobial resistance, emerging pathogen.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Young neurons in the developing brain establish a polarized morphology for proper migration. The PIWI family of piRNA processing proteins are considered to be restrictively expressed in germline ...tissues and several types of cancer cells. They play important roles in spermatogenesis, stem cell maintenance, piRNA biogenesis, and transposon silencing. Interestingly a recent study showed that de novo mutations of PIWI family members are strongly associated with autism.
Here, we report that PIWI-like 1 (PIWIL1), a PIWI family member known to be essential for the transition of round spermatid into elongated spermatid, plays a role in the polarization and radial migration of newborn neurons in the developing cerebral cortex. Knocking down PIWIL1 in newborn cortical neurons by in utero electroporation of specific siRNAs resulted in retardation of the transition of neurons from the multipolar stage to the bipolar stage followed by a defect in their radial migration to the proper destination. Domain analysis showed that both the RNA binding PAZ domain and the RNA processing PIWI domain in PIWIL1 were indispensable for its function in neuronal migration. Furthermore, we found that PIWIL1 unexpectedly regulates the expression of microtubule-associated proteins in cortical neurons.
PIWIL1 regulates neuronal polarization and radial migration partly via modulating the expression of microtubule-associated proteins (MAPs). Our finding of PIWIL1's function in neuronal development implies conserved functions of molecules participating in morphogenesis of brain and germline tissue and provides a mechanism as to how mutations of PIWI may be associated with autism.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Postoperative resorption of vascularized bone grafts jeopardizes the success of dental implant(s) and functional rehabilitation of the jaw. Recent evidence supports the crucial role of innervation in ...bone regeneration and turnover.
This study reports a new technique for simultaneous innervation of vascularized iliac flaps in mandibular reconstruction, through neurorrhaphy between ilioinguinal nerves, which innervate iliac bone, and inferior alveolar nerves or great auricular nerves. Twenty-two patients (aged 50 to 69 years) with postoncologic continuity defects of the mandible underwent mandibular reconstruction (10 innervated flaps and 12 control flaps). Graft bone resorption was analyzed by computed tomographic scans at 6 and 12 months postoperatively, and bone quality was evaluated for dental implantation, with histologic and histomorphometric analyses for graft samples.
At 12-month follow-up, graft bone density loss in the control group was significantly higher than in the innervated group (p < 0.05). Bone quality evaluation indicated a suitable condition for dental implantation in all patients in the innervated group but in 41.7 percent of patients in the control group. Histologic and histomorphometric analyses showed successful innervation in the innervated group but not in the control group. Osteoclast activity was significantly higher in the control group than in the innervated group (p < 0.05).
Innervated iliac flaps may effectively prevent bone resorption of grafts in mandible reconstruction that otherwise jeopardize the success of dental implants. This new strategy of innervation of bone flaps appears clinically valuable and provides insights into the homeostasis of grafts for functional reconstruction.
Therapeutic, III.
Background. Early screening for syphilis among pregnant women and the effective treatment of maternal syphilis is fundamental to prevent congenital syphilis (CS). Methods. We obtained data from the ...Shenzhen Program for Prevention of CS (SPPCS) and estimated incidence rates of CS among infants born to syphilis-seropositive women treated with different regimens or untreated for maternal syphilis. Results. A total of 4746 matched cases of syphilis-seropositive mothers and their infants were included for analyses, and 162 infants were diagnosed with CS, providing an overall incidence of 3.41% (95% confidence interval CI, 2.91%–3.98%). Among infants born to syphilis-seropositive women who had syphilis and were adequately treated before pregnancy, the incidence was 0.22% (95% CI, .05%–.66%). There were 159 cases of CS occurring in 3519 infants born to women who were syphilis-seropositive during their pregnancies, for an incidence of 4.52% (95% CI, 3.84%–5.28%). The incidence of CS was 1.82%–11.90% lower among infants born to the women treated with early benzathine penicillin G (BPG) compared with those treated with late BPG (adjusted odds ratio aOR, 8.06 95% CI, 2.93–22.21; P < .001), other antibiotics (aOR, 7.71 95% CI, .86–69.28; P = .068), or those untreated (aOR, 68.28 95% CI, 29.64–157.28; P < .001). The incidence rates were 0.22% (95% CI, .06%–.80%) and 0.59% (95% CI, .35%–1.02%) in infants born to women treated with 2 courses and 1 course of BPG, respectively, corresponding to a risk difference of 0.37% (aOR, 1.74; 95% CI, .37–8.26). Conclusions. Treatment of syphilis-seropositive pregnant women with 1 course of intramuscular BPG before 28 gestational weeks is critical for prevention of CS.
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BFBNIB, NUK, PNG, UL, UM, UPUK
The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of ...causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two‐stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT‐PCR analysis (qRT‐PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10−19). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.
A novel SNP rs117565607_A of TRIM26 gene was significantly associated with NPC. SNP rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1), and the expression was suppressed if YY1 binds to the A allele of rs117565607. Downexpression of TRIM26 is related to low immune response in NPC.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Gas disasters always restrict the tunnel constructions in mountain area, which becomes a major geological barrier against the development of underground engineering. China is rich in coal resources ...and has a large amount of gas with a wide range of distribution. However, China experienced not only adverse effects on coal mining but also gas disasters in underground engineering construction, such as tunnels and chambers. With the increased number of tunnels passing through coal-bearing strata, the incidence of gas accidents is also rising. Therefore, the significance of preventing and mitigating gas disasters should be emphasized, and an effective risk assessment method for gas disasters should be established. On the basis of research on over 100 gas tunnels in China, a relatively ideal gas disaster risk assessment method and system for tunnels are established through the following measures. Firstly, geo-environmental conditions and gas situations were analyzed during construction. Secondly, qualitative analysis was combined with quantitative analysis. Finally, the influencing factors of gas disasters, including geological conditions, gas,and human factors, were investigated. The gas tunnel risk assessment system includes three levels：（1） the grading assessment of a gas tunnel during the planning stage,（2） the risk assessment of gas tunnel construction during the design and construction stages,（3） the gas tunnel outburst risk assessment during the coal uncovering stage. This system was applied to the dynamic assessment of gas disaster during the construction of the Zipingpu tunnel of Dujiangyan–Wenchuan Highway（in Sichuan, Southwest China）. The assessment results were consistent with the actual excavation, which verified the rationality and feasibility of the system. The developed system was believed to be back-up and applied for risk assessment of gas disaster in the underground engineering construction.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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