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Background: Hypertension is an established risk factor for mild cognitive impairment (MCI) in elderly individuals. Nevertheless, the impact of different levels of blood pressure on the progression of MCI remains uncertain. This study aims to investigate the non-linear relationship between blood pressure and MCI in the elderly and detect the critical blood pressure threshold, thus, improving blood pressure management for individuals at high risk of MCI. Methods: Data was obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) cohort. We chose normal cognitive elderly individuals who entered the cohort in 2014 for a 5-year follow-up to observe the progression of MCI. Subsequently, we utilized the Cox regression model to identify risk factors for MCI and conducted a Cox-based restricted cubic spline regression (RCS) model to examine the non-linear relationship between systolic blood pressure (SBP) and diastolic blood pressure (DBP) with MCI, determining the critical blood pressure threshold for MCI progression. Results: In the elderly population, female (HR = 1.489, 95% CI: 1.017–2.180), lacking of exercise in the past (HR = 1.714, 95% CI: 1.108–2.653), preferring animal fats (HR = 2.340, 95% CI: 1.348–4.061), increased age (HR = 1.061, 95% CI: 1.038–1.084), increased SBP (HR = 1.036, 95% CI: 1.024–1.048), and increased DBP (HR = 1.056, 95% CI: 1.031–1.081) were associated with MCI progression. After adjusting factors such as gender, exercise, preferred types of fats, and age, both SBP (P non-linear < 0.001) and DBP (P non-linear < 0.001) in elderly individuals exhibited a non-linear association with MCI. The risk of MCI rose when SBP exceeded 135 mmHg and DBP was in the range of 80–88 mmHg. However, when DBP exceeded 88 mmHg, there was a declining trend in MCI progression, although the HR remained above 1. The identified critical blood pressure management threshold for MCI was 135/80 mmHg. Conclusion: In this study, we discovered that risk factors affecting the progression of MCI in elderly individuals comprise gender (female), preferring to use animal fat, lack of exercise in the past, increased age, increased SBP, and increased DBP. Additionally, a non-linear relationship between blood pressure levels and MCI progression was confirmed, with the critical blood pressure management threshold for MCI onset falling within the prehypertensive range. [ABSTRACT FROM AUTHOR]

Carsharing has received considerable attention as a sustainable mobility paradigm. Various service designs and dynamic business environments have increased the decision complexity for the carsharing business. Therefore, carsharing operators require a tool for assessing business development from holistic perspectives. This research provides a framework for outlining the requirements of the carsharing system with holistic perspectives of stakeholders being considered, as well as to derive assessment metrics for examining carsharing development. To create the framework, the system modeling tool, context diagram, was adopted to map out the interactions of externalities with the system and the requirements of the system. Eight assessment metrics: the market condition, business advantage, parking condition, electric vehicle deployment, self-serving configuration, vehicle reservation, vehicle maintenance, and pricing scheme, were eventually identified from the system modeling. From these dimensions, we review 24 carsharing cases from China, Europe, Japan, and the United States, and we summarize discrepancies among different marketplaces and some managerial insights on carsharing development, such as carsharing motivators and inhibitors, innovations in respect of different business backgrounds, approaches of increasing parking privileges, approaches of increasing electrifications, essential digital features, reservation regimes, methods of vehicle maintenances, and service pricing regimes. [ABSTRACT FROM AUTHOR]

The global positioning system (GPS) trajectory data are extensively utilized in various fields, such as driving behavior analysis, vehicle navigation systems, and traffic management. GPS sensors installed in numerous driving recorders and smartphones facilitate data collection on a large-scale in a high-frequency manner. Therefore, map-matching algorithms are indispensable to identify the GPS trajectories on a road network. Although the local map-matching algorithm reduces computation time, it lacks sufficient accuracy. Conversely, the global map-matching algorithm enhances matching accuracy; however, the computations are time consuming in the case of large-scale data. Therefore, this study proposes a method to improve the accuracy of the local map-matching algorithm without affecting its efficiency. The proposed method first executes the incremental map-matching algorithm. It then identifies the mismatching links in the results based on the connectivity of the links. Finally, the shortest path algorithm and the longest common subsequence are used to correct these error links. An elderly driver's driving recorder data were used to conduct the experiment to compare the proposed method with four state-of-the-art map-matching algorithms in terms of accuracy and efficiency. The experimental results indicate that the proposed method can significantly increase the accuracy and efficiency of the map-matching process when considering high-frequency and large-scale data. Particularly, compared with the two-benchmark global map-matching algorithms, the proposed method can reduce the error rate of map-matching by nearly half, only consuming 18% and 58% of the computation time of the two global algorithms, respectively. [ABSTRACT FROM AUTHOR]

Background: Maternal gestational diabetes mellitus (GDM) had long-term influences on the health of their children. However, the influences of GDM on the oral microbiota, which was closely related to oral and systemic health in offspring, were less documented. The present study aimed to explore the oral microbiota of neonates born to mothers with GDM is differentially colonized compared with those born to mothers without GDM, and whether any such differences persist to 1 month of age. Methods: Oral samples were collected from children of mothers with (n = 20) and without GDM (n = 34) at birth and again at an average age of 1 month. The oral microbiota was characterized by 16S rRNA sequencing (V3-V4). Differences in diversity and composition according to maternal GDM status were assessed, and different metabolic functional pathways and microbial ecological networks were also analyzed. Results: Although no significant differences were observed in diversity metrics between GDM and non-GDM groups (P > 0.05), we found significant differences in the taxonomic composition of oral microbiota from phylum to genus level between the two groups, with the GDM group exhibiting less abundance of Veillonella in both “Day 1” (P < 0.001) and “Day 30” (P < 0.05) phases. Metabolic pathways analysis showed that 5-aminoimidazole ribonucleotide biosynthesis and inosine-5'-phosphate biosynthesis were enriched in GDM subjects in the “Day 30” phase. Moreover, ecological network analysis revealed apparent differences between GDM and control groups, with the non-GDM group containing more high-degree nodes and microbial interactions compared with the GDM group. Conclusion: Maternal GDM was associated with an altered oral microbial composition in neonates, although the distinct difference between GDM and non-GDM groups diminished in infancy. The oral microbiota functions and ecological networks differed dramatically between the two groups, highlighting the importance of maternal GDM status on initial oral microbiota in offspring. [ABSTRACT FROM AUTHOR]

Introduction. Changes in eating habits have made gout a metabolic disease of increasing concern. Previous studies have indicated that there are significant differences in species composition and abundance of gut microbiome in gout patients compared with average. Considering that traditional Chinese medicine has a momentous effect in treating gout, the research study aimed to explore the differences of genomic and metabolomics of gut microbiome before and after traditional Chinese medicine treatment in patients with gout. Method. 30 patients with gout and 29 matched controls were recruited of which 16 patients took H treatment and 14 patients took T treatment. Stools were collected twice for patients before and after treatment and only once for controls. A total of 89 samples were annotated with metagenomic species and functions, and the enrichment analysis of differential genes and KO pathway was carried out. Result. The results showed a decrease in the diversity of gut microbiome in gout patients and the gene abundance and metabolomics had great differences among study groups. The number of bacterial genera also had significant differences among treatment groups. Moreover, among different groups, the regulation of different species was variously correlated. The correlation between species and clinical laboratory indicators in the rising group was stronger than that in the decreasing group and the upregulation of some strain was related to the content of urea nitrogen. Conclusion. After the traditional Chinese medicine treatment, the glutathione pathway was significantly enriched and some pathogenic bacteria were significantly inhibited. The study suggests that traditional Chinese medicine treatment may exert its therapeutic effect by inhibiting relevant pathways. [ABSTRACT FROM AUTHOR]

Background: Increasing studies have demonstrated potential disproportionate functional and ecological contributions of rare taxa in a microbial community. However, the study of the microbial rare biosphere is hampered by their inherent scarcity and the deficiency of currently available techniques. Sample-wise cross contaminations might be introduced by sample index misassignment in the most widely used metabarcoding amplicon sequencing approach. Although downstream bioinformatic quality control and clustering or denoising algorithms could remove sequencing errors and non-biological artifact reads, no algorithm could eliminate high quality reads from sample-wise cross contaminations introduced by index misassignment, making it difficult to distinguish between bona fide rare taxa and potential false positives in metabarcoding studies. Results: We thoroughly evaluated the rate of index misassignment of the widely used NovaSeq 6000 and DNBSEQ-G400 sequencing platforms using both commercial and customized mock communities, and observed significant lower (0.08% vs. 5.68%) fraction of potential false positive reads for DNBSEQ-G400 as compared to NovaSeq 6000. Significant batch effects could be caused by stochastically introduced false positive or false negative rare taxa. These false detections could also lead to inflated alpha diversity of relatively simple microbial communities and underestimated that of complex ones. Further test using a set of cow rumen samples reported differential rare taxa by different sequencing platforms. Correlation analysis of the rare taxa detected by each sequencing platform demonstrated that the rare taxa identified by DNBSEQ-G400 platform had a much higher possibility to be correlated with the physiochemical properties of rumen fluid as compared to NovaSeq 6000 platform. Community assembly mechanism and microbial network correlation analysis indicated that false positive or negative rare taxa detection could lead to biased community assembly mechanism and identification of fake keystone species of the community. Conclusions: We highly suggest proper positive/negative/blank controls, technical replicate settings, and proper sequencing platform selection in future amplicon studies, especially when the microbial rare biosphere would be focused. [ABSTRACT FROM AUTHOR]

In the past decade, the incidence of recurrent pregnancy loss (RPL) has increased significantly, and immunological disorders have been considered as one of the possible causes contributing to RPL. The presence of antinuclear antibodies (ANAs) is regarded as a typical antibody of autoimmunity. However, the relationship between the presence of ANAs and RPL, the underlying mechanism, and the possible role of immunotherapy is still controversial. The aim of this mini review is to assess the association between ANAs and RPL and the effects of immunotherapy on pregnancy outcomes in women with positive ANAs and a history of RPL from the available data and to provide a relevant reference basis for clinical application in this group of women. [ABSTRACT FROM AUTHOR]

Background: Maternal gestational diabetes mellitus (GDM) had long-term influences on the health of their children. However, the influences of GDM on the oral microbiota, which was closely related to oral and systemic health in offspring, were less documented. The present study aimed to explore the oral microbiota of neonates born to mothers with GDM is differentially colonized compared with those born to mothers without GDM, and whether any such differences persist to 1 month of age. Methods: Oral samples were collected from children of mothers with (n = 20) and without GDM (n = 34) at birth and again at an average age of 1 month. The oral microbiota was characterized by 16S rRNA sequencing (V3-V4). Differences in diversity and composition according to maternal GDM status were assessed, and different metabolic functional pathways and microbial ecological networks were also analyzed. Results: Although no significant differences were observed in diversity metrics between GDM and non-GDM groups (P > 0.05), we found significant differences in the taxonomic composition of oral microbiota from phylum to genus level between the two groups, with the GDM group exhibiting less abundance of Veillonella in both "Day 1" (P < 0.001) and "Day 30" (P < 0.05) phases. Metabolic pathways analysis showed that 5-aminoimidazole ribonucleotide biosynthesis and inosine-5'-phosphate biosynthesis were enriched in GDM subjects in the "Day 30" phase. Moreover, ecological network analysis revealed apparent differences between GDM and control groups, with the non-GDM group containing more high-degree nodes and microbial interactions compared with the GDM group. Conclusion: Maternal GDM was associated with an altered oral microbial composition in neonates, although the distinct difference between GDM and non-GDM groups diminished in infancy. The oral microbiota functions and ecological networks differed dramatically between the two groups, highlighting the importance of maternal GDM status on initial oral microbiota in offspring. [ABSTRACT FROM AUTHOR]

This study proposes a two-sided matching decision-making (TSMDM) approach by combining the regret theory under the intuitionistic fuzzy environment. At first, according to the Hamming distance of intuitionistic fuzzy sets and regret theory, superior and inferior flows are defined to describe the comparative preference of subjects. Hereafter, the satisfaction degrees are obtained by integrating the superior and inferior flows of the subjects. The comprehensive satisfaction degrees are calculated by aggregating the satisfaction degrees, based on which, a multi-objective TSMDM model is built. Furthermore, the multi-objective TSMDM model is converted to a single-objective model, the optimal solution of the latter is derived. Finally, an illustrative example and several analyses are provided to verify the feasibility and the effectiveness of the proposed approach. [ABSTRACT FROM AUTHOR]

Clinically significant copy-number variants (CNVs) known to cause human diseases are routinely detected by chromosomal microarray analysis (CMA). Recently, genome sequencing (GS) has been introduced for CNV analysis; however, sequencing depth (determined by sequencing read-length and read-amount) is a variable parameter across different laboratories. Variating sequencing depths affect the CNV detection resolution and also make it difficult for cross-laboratory referencing or comparison. In this study, by using data from 50 samples with high read-depth GS (30×) and the reported clinically significant CNVs, we first demonstrated the optimal read-amount and the most cost-effective read-length for CNV analysis to be 15 million reads and single-end 50 bp (equivalent to a read-depth of 0.25-fold), respectively. In addition, we showed that CNVs at mosaic levels as low as 30% are readily detected, furthermore, CNVs larger than 2.5 Mb are also detectable at mosaic levels as low as 20%. Herein, by conducting a retrospective back-to-back comparison study of low-pass GS versus routine CMA for 532 prenatal, miscarriage, and postnatal cases, the overall diagnostic yield was 22.4% (119/532) for CMA and 23.1% (123/532) for low-pass GS. Thus, the overall relative improvement of the diagnostic yield by low-pass GS versus CMA was ~ 3.4% (4/119). Identification of cryptic and clinically significant CNVs among prenatal, miscarriage, and postnatal cases demonstrated that CNV detection at higher resolutions is warranted for clinical diagnosis regardless of referral indications. Overall, our study supports low-pass GS as the first-tier genetic test for molecular cytogenetic testing. [ABSTRACT FROM AUTHOR]

Studies have assessed early population-level impact of human papillomavirus (HPV) vaccination programs for preventing cervical cancer. Through a case study in Hong Kong we examined stakeholder engagement and interactions to promote a universal HPV vaccination program using the Health Policy Triangle framework for structured health policy analysis. Using data from a document review and semi-structured in-depth interviews, we used thematic and stakeholder analyses to describe the process of policy formation. Given Hong Kong's political and health system, and a mix of Chinese and Western values, stakeholders judged legitimacy of the process differently. We discuss their varied ethical stances and the role of research evidence for informing policy-making. For effective HPV vaccination policy and promotion of universal free HPV vaccination among adolescent girls, new strategies are needed to broaden acceptance of the process, to frame policies in terms of facts and values, and to connect research to policy-making and improve coalition-building. [ABSTRACT FROM AUTHOR]

Meckel syndrome (MKS) is a pre‐ or perinatal multisystemic ciliopathic lethal disorder with an autosomal recessive mode of inheritance. Meckel syndrome is usually manifested with meningo‐occipital encephalocele, polycystic kidney dysplasia, postaxial polydactyly and hepatobiliary ductal plate malformation. Germline variants in CEP290 cause MKS4. In this study, we investigated a 35‐years‐old Chinese female who was 17+1 weeks pregnant. She had a history of adverse pregnancy of having foetus with multiple malformations. We performed ultrasonography and identified the foetus with occipital meningoencephalocele and enlarged cystic dysplastic kidneys. So, she decided to terminate her pregnancy and further genetic molecular analysis was performed. We identified the aborted foetus without postaxial polydactyly. Histological examination of foetal kidney showed cysts in kidney and thinning of the renal cortex with glomerular atrophy. Whole exome sequencing identified a novel homozygous variant (c.2144T>G; p.L715*) in exon 21 of the CEP290 in the foetus. Sanger sequencing confirmed that both the parents of the foetus were carrying this variant in a heterozygous state. This variant was not identified in two elder sisters of the foetus as well as in the 100 healthy individuals. Western blot analysis showed that this variant leads to the formation of truncated CEP290 protein with the molecular weight of 84 KD compared with the wild‐type CEP290 protein of 290 KD. Hence, it is a loss‐of‐function variant. We also found that the mutant cilium appears longer in length than the wild‐type cilium. Our present study reported the first variant of CEP290 associated with MKS4 in Chinese population. [ABSTRACT FROM AUTHOR]

Aims: To investigate the differences and international connections between the human cervical cancer cell line (HeLa cells) and the Taxol-resistant HeLa cell line (HeLa/Taxol).Materials and Methods: As parental cells, HeLa cells were cultured in stepwise escalating concentration of Taxol from 0.01 μg/ml (11.7 × 10-9 mol/L) to 0.5 μg/ml (585 × 10-9 mol/L). The drug resistance of HeLa/Taxol cells was detected by methyl-thiazolyl-tetrazolium assay. Real time-polymerase chain reaction (RT-PCR) was conducted to detect the messenger RNA levels of drug resistance genes and apoptosis-related genes. The proteins levels were detected through immunofluorescence and Western blot.Results: Compared with parental HeLa cells, HeLa/Taxol with Taxol resistance had the following biological characteristics: first, they had a lower growth velocity; second, the expression of P-glycoprotein and glutathione S-transferases was significantly increased; Third, the expression of antiapoptotic protein Bcl-2 and apoptosis inhibitor protein survivin was prominently increased.Conclusions: The drug-resistance in HeLa/Taxol is mainly associated with the high expression of multidrug resistance genes, antiapoptotic protein Bcl-2, and apoptosis inhibitor protein survivin as an important reason for the failure of chemotherapy of tumor tissue. [ABSTRACT FROM AUTHOR]

Background: Increased nuchal translucency (NT) is an important biomarker associated with increased risk of fetal structural anomalies. It is known to be contributed by a wide range of genetic etiologies from single-nucleotide variants to those affecting millions of base pairs. Currently, prenatal diagnosis is routinely performed by karyotyping and chromosomal microarray analysis (CMA); however, both of them have limited resolution. The diversity of the genetic etiologies warrants an integrated assay such as genome sequencing (GS) for comprehensive detection of genomic variants. Herein, we aim to evaluate the feasibility of applying GS in prenatal diagnosis for the fetuses with increased NT. Methods: We retrospectively applied GS (> 30-fold) for fetuses with increased NT (≥3.5 mm) who underwent routine prenatal diagnosis. Detection of single-nucleotide variants, copy number variants, and structural rearrangements was performed simultaneously, and the results were integrated for interpretation in accordance with the guidelines of the American College of Medical Genetics and Genomics. Pathogenic or likely pathogenic (P/LP) variants were selected for validation and parental confirmation, when available. Results: Overall, 50 fetuses were enrolled, including 34 cases with isolated increased NT and 16 cases with other fetal structural malformations. Routine CMA and karyotyping reported eight P/LP CNVs, yielding a diagnostic rate of 16.0% (8/50). In comparison, GS provided a twofold increase in diagnostic yield (32.0%, 16/50), including one mosaic turner syndrome, eight cases with microdeletions/microduplications, and seven cases with P/LP point mutations. Moreover, GS identified two cryptic insertions and two inversions. Follow-up study further demonstrated the potential pathogenicity of an apparently balanced insertion that disrupted an OMIM autosomal dominant disease-causing gene at the insertion site. Conclusions: Our study demonstrates that applying GS in fetuses with increased NT can comprehensively detect and delineate the various genomic variants that are causative to the diseases. Importantly, prenatal diagnosis by GS doubled the diagnostic yield compared with routine protocols. Given a comparable turnaround time and less DNA required, our study provides strong evidence to facilitate GS in prenatal diagnosis, particularly in fetuses with increased NT. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the leading cause of mortality resulting from gynecologic cancer. A common anti-ovarian tumor drug is cisplatin; however, repeated use of cisplatin causes severe resistance and leads to poor long-term survival rate in ovarian cancer patients. Recently, it was reported that lanthanum chloride (LaCl3) may inhibit tumor growth and induce apoptosis in certain cancer cells. In the present study, the effect of LaCl3 on ovarian cancer was determined in vivo and in vitro. A cisplatin-sensitive human ovarian cancer cell line, COC1, was used in the current study. A xenograft animal model of ovarian cancer was established injecting COC1 or cisplatin-resistant COC1 cells (COC1/DDP) cells into mice. A TUNEL assay was used to determine the apoptosis of the COC1 or COC1/DDP cells and a immunohistochemical assay was conducted to measure the expression of B-cell lymphoma-2, Ki67, breast cancer 1 (BRCA)1, BRCA2 and excision repair cross-complementation group 1 in COC1 or COC1/DDP cells. It was observed that LaCl3 promoted apoptosis in COC1 and COC1/DDP cells. In addition, LaCl3 plus cisplatin led to further increase in the expression levels of tumor suppressor genes and decrease in the expression of oncogenes. Furthermore, application of LaCl3 and cisplatin inhibited tumor growth in vivo in a xenograft animal model. These results indicated the synergistic role of LaCl3 on cisplatin-induced inhibition of cancer cell proliferation and tumor growth, providing a potential and effective candidate for the treatment of ovarian tumors. [ABSTRACT FROM AUTHOR]

Background. This study aims to evaluate the diagnostic value of nuclear-enriched abundant transcript 1 (NEAT1) expression in peripheral blood mononuclear cells (PBMCs) for the early diagnosis of sepsis. Methods. A total of 59 patients with sepsis, 52 noninfectious SIRS patients, and 56 healthy controls were recruited fort this study. The levels of NEAT1 expression in PBMCs were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Results. Compared with healthy controls, NEAT1 expression of PBMCs in sepsis and SIRS groups were significantly increased (3.76 ± 0.71- and 1.64 ± 0.43-fold, resp.) (P<0.01), but NEAT1 levels are significantly lower in the SIRS group than in the sepsis group, and there was no statistical significant relevance between survivors and nonsurvivors in patients with sepsis. NEAT1 with an area under the curve (AUC) of 0.851 (95% CI: 0.812–0.935) indicated sensitivity (67.85%) and specificity (87.27%) for the diagnosis for sepsis, the positive predictive value (PPV) was 83.3%, and the negative predictive value (NPV) was 71.6%. The AUC for NEAT1 in the diagnosis of SIRS versus healthy controls was 0.755 (95% CI: 0.664–0.847), with 69.23% sensitivity and 70.91% specificity, the PPV was 72.3%, and the NPV was 72.49%. Conclusion. Measurement of NEAT1 expression in PBMCs could be considered as a good additive marker for the diagnosis of sepsis. [ABSTRACT FROM AUTHOR]

Background/Amis: Long non-coding RNAs (lncRNAs), a novel class of transcripts, have been shown to play critical roles in diverse cellular biological processes, including tumorigenesis. Small nucleolar RNA host gene 6 (SNHG6) regulates various biological processes in cancer cells. However, the biological role of SNHG6 in gastric cancer still remains to be explored. The aim of this study is to investigate the characteristic of the SNHG6 in gastric cancer. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of SNHG6 in gastric cancer tissues and cell lines. MTT assays, colony formation assays were used to determine the impact of SNHG6 on tumorigenesis . Flow cytometric analysis of cell cycle and apoptosis was performed to measure the effect of SNHG6 on cell cycle and apoptosis rate. Transwell assay was performed to measure the effect of SNHG6 on cell migration. Western blotting and immunofluorescence were utilized to examine the effect of SNHG6 on epithelial-mesenchymal transition (EMT) of GC cells. Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), RNA-pulldown and luciferase reporter assays were employed to dissect molecular mechanisms. Results: In this study, we revealed that SNHG6 was overexpressed in gastric cancer tissues and cell lines. High expression levels of SNHG6 wereassociated with invasion depth, lymph node metastasis, distant metastasis and tumor/node/metastasis (TNM) stage, and predicted poor prognosis. Loss-of-function assays revealed that silenced SNHG6 obviously inhibited gastric cancer cell growth, weakened cell migration capacity and suppressed the EMT processes of gastric cancer cells. Additionally, ChIP, RIP, RNA-pulldown and luciferase reporter assays evidenced that SNHG6 could epigenetically silenced p27 and could competitively sponging miR-101-3p thereby regulating zinc finger E-box-binding homeobox 1 (ZEB1). Conclusion: In summary, our findings demonstrated that SNHG6 acted as an oncogene in gastric cancer cells through regulating miR-101-3p/ZEB1 at a post-transcriptional level and silencing expression at a transcriptional level by recruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p27. SNHG6 might serve as a candidate prognostic biomarker and a target for novel therapies of gastric cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Our previous study used freeze-drying and biotin-avidin binding methods and obtained nontargeted nanobubbles (N-NBs) and ovarian cancer-targeting nanobubbles (LHRH-NBs, luteinizing hormone-releasing hormone nanobubbles). Our study also identified the physical and chemical properties of these two contrast agents, and validated the targeting ability and underlying mechanisms of LHRH-NBs in vitro. The present study investigated the imaging of N-NBs and LHRH-NBs in nude mice and their binding with tissues.Methods: The nude mice models of xenografts were divided into three groups, N-NB, LHRH-NB, and SonoVue. These contrast agents were injected via the caudal vein to observe the imaging of ovarian cancer. Fluorescence microscope was used to observe the penetration of N-NBs and LHRH-NBs through the vascular endothelial gaps. Immunofluorescence was used to observe the penetration of N-NBs and LHRH-NBs through vascular endothelial gaps and binding to the tumor cells.Results: The imaging intensity and duration were not significantly different between N-NBs and LHRH-NBs. The imaging intensity in the N-NB and LHRH-NB groups was not significantly different compared with the SonoVue group; however, the imaging duration in the N-NB and LHRH-NB groups was significantly longer than in the SonoVue group (P < 0.001). Both N-NBs and LHRH-NBs penetrated through the vascular endothelial gaps. After penetrating through the vascular endothelial gapes, LHRH-NBs could target and bind to the tumor cells.Conclusions: N-NBs and LHRH-NBs are of good imaging effectiveness and relatively long imaging duration. LHRH-NB is a potent contrast agent for imaging ovarian cancer, while achieving targeted delivery of drugs to the site of ovarian cancer. [ABSTRACT FROM AUTHOR]

It is known that fluoride-resistant microorganisms are different from fluoride-sensitive ones in growth, adherence and metabolic activity. It was hypothesized that these phenotypic differences were due to stable genotypic changes in the fluoride-resistant strains. However, until now, no studies have reported these genotypic changes. The aim of this study is to identify such changes in a fluoride-resistant Streptococcus mutans strain (C180-2FR) using whole-genome shotgun (WGS) sequencing and to examine the potential function of the identified mutations by comparing gene expression between the fluoride-sensitive (C180-2) and C180-2FR strains. We performed 50 bp paired-end Illumina shotgun sequencing for both strains. Through extensive bioinformatic analysis, we were able to identify 8 single nucleotide polymorphisms (SNPs) in the genome of C180-2FR, which were further confirmed by Sanger sequencing. Expression of the genes containing or in proximity to the SNPs in C180-2 and C180-2FR was then quantified by real-time PCR. A gene cluster containing genes coding for fluoride antiporters was up-regulated 10-fold in C180-2FR when compared to that in C180-2, independent of growth phase. Two SNPs are located in this gene cluster, one in its promoter region and the other in its protein-coding region. In addition, one gene, which codes for a putative glycerol uptake facilitator protein, was found to be down-regulated by 60% in C180-2FR at an early growth phase. The promoter region of this gene contained a SNP. No difference in expression was found for the other SNP-containing genes. In summary, using WGS sequencing, we were able to uncover genetic changes in the genome of a fluoride-resistant strain. These findings can provide new insights into the mechanism of microbial fluoride resistance. [ABSTRACT FROM AUTHOR]

The worldwide emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis threatens to make this disease incurable. Drug resistance mechanisms are only partially understood, and whether the current understanding of the genetic basis of drug resistance in M. tuberculosis is sufficiently comprehensive remains unclear. Here we sequenced and analyzed 161 isolates with a range of drug resistance profiles, discovering 72 new genes, 28 intergenic regions (IGRs), 11 nonsynonymous SNPs and 10 IGR SNPs with strong, consistent associations with drug resistance. On the basis of our examination of the dN/dS ratios of nonsynonymous to synonymous SNPs among the isolates, we suggest that the drug resistance-associated genes identified here likely contain essentially all the nonsynonymous SNPs that have arisen as a result of drug pressure in these isolates and should thus represent a near-complete set of drug resistance-associated genes for these isolates and antibiotics. Our work indicates that the genetic basis of drug resistance is more complex than previously anticipated and provides a strong foundation for elucidating unknown drug resistance mechanisms. [ABSTRACT FROM AUTHOR]

isic acid (ABA) plays pivotal roles in plant biotic and abiotic stress responses, where calcium ions are important second messengers. Calcium/calmodulin-dependent protein kinase (CCaMK) is essential for nodulation in legumes, but whether it will perceive calcium signals from abiotic stresses is not clear, especially in non-legume plants. Here we report the isolation and characterization of the D-genome copy of wheat CCaMK gene TaCCaMK. TaCCaMK was predominantly expressed in root tissues of wheat seedlings, and its proteins were located both on the cytoplasm membrane and in the nucleus as shown in the onion epidermis cells. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) assay showed that the expression of TaCCaMK was downregulated by ABA, as well as NaCl and PEG treatments in wheat seedling roots. A DNA fragment of 1,119 bp upstream of the start codon of the TaCCaMK gene (p TaCCaMK) was isolated by thermal asymmetric interlaced PCR (TAIL-PCR), on which six ABA-responsive cis-elements were predicted. p TaCCaMK can drive GUS reporter gene expression in the root and stem stalk of the transgenic Arabidopsis plants which can be repressed by ABA treatments, consistent with the observation in the qRT-PCR assay in wheat. Overexpressing TaCCaMK in Arabidopsis plants reduced their sensitivity to ABA treatment during seed germination and root elongation. Under high-salt conditions, the transgenic plants also conferred enhanced seed germination rate and became hypersensitive with increased chlorosis. Therefore, our data suggest that TaCCaMK is a negative regulator for ABA signaling which may participate in abiotic stress responses in wheat. [ABSTRACT FROM AUTHOR]

Telomerase activity was examined in invasive cervical carcinoma to assess whether it is activated during cervical malignant transformation and to look for its possible association with human papillomavirus (HPV) infection. Histologically confirmed invasive cervical carcinomas and benign cervices were assayed for telomerase activity by using a modified telomere repeat amplification protocol (TRAP). The same cases were subjected to polymerase chain reaction (PCR) detection of HPV by using consensus primers and type-specific (HPV types 16 and 18) primers. Telomerase activity was detected in 40 of 45 (88.9%) invasive cervical carcinomas and 2 (all chronic cervicitis) of 50 (4%) benign cervical lesions. HPV was detected in 36 (24 HPV-16 and 4 HPV-18 cases) of 45 (80%) invasive cervical carcinomas and 20 (11 HPV-16 and 1 HPV-18 cases) of 50 (40%) benign cervical changes. There was a significant correlation between the expression of telomerase with histological grade (ω=0.44, P<0.005), but no correlation was found between telomerase expression and HPV-18 ( P>0.05). Although larger sample studies are needed, there seems to be a clear association between telomerase upregulation and HPV status, mainly HPV-16 infection. [ABSTRACT FROM AUTHOR]

Background: Early life microflora is an important determinant of immune and metabolic development and may have lasting consequences. However, the mode of delivery and the effect of povidone iodine disinfection on neonatal oral microflora colonization are still unclear. The objective of the study was to understand the effects of the use of polyvidone iodine on infant's oral microflora after transvaginal examination during delivery, provided data support for the establishment of neonatal oral microflora health.Methods: A total of 20 cases of full-term neonatal delivered in October 2017 in Shenzhen Bao'an Maternity and Child Health Hospital through vaginal delivery. These neonates were randomly divided into two groups, the conventional disinfection group and the non-disinfection group. Simultaneously, 10 infants with elective cesarean section were taken as comparison. With Illumina MiSeq platform, 16S rRNA V3-V4 sequencing method was used to analyze bacterial DNA of oral secretions.Results: At the phylum level, compared to the non-disinfection group, higher relative abundance of Bacteroidetes and Proteobacteria, and lower proportion of Firmicutes were observed in the cesarean section group and the disinfection group. As main composition of phylum Firmicutes, genus Lactobacillus presented extremely low in the cesarean section group and the disinfection group, whereas it was the absolute dominant bacteria in the non-disinfection group. Compared with the caesarean section group, only Lactobacillus increased in majority of the non-disinfection group. There was no increase in Lactobacillus in the disinfection group, but Prevotella, Escherichia-Shigella, Staphyloccus, and Klebsiella increased significantly. Through KEGG pathway analysis, we found that there were more harmful pathways such as staphylococcus aureus infection, viral myocarditis and sporulation in the disinfection group.Conclusions: The mode of delivery affects the infant's Lactobacillus obtained from the mother. Moreover, vulvar disinfection played an important part in the colonization of neonatal oral microbiota. And the impact of the first oral colonizers on infant health needs further follow-up investigations. [ABSTRACT FROM AUTHOR]