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BackgroundAlthough breakthroughs have been achieved in gastric cancer (GC) therapy with immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), the acquisition of high response rate remains a huge challenge for clinicians. It is imperative to identify novel biomarkers for predicting response to immunotherapy and explore alternative therapeutic strategy for GC.MethodsThe transcriptomic profiles and clinical information of GC patients from The Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD) database was used to screen differentially expressed lncRNAs between the tumor specimens and the paracancerous tissues. The TargetScan, miRDB and miRcode database were then utilized to construct competing endogenous RNA (ceRNA) networks and identify pivotal lncRNAs. An independent dataset from GEO (GSE70880) and 23 pairs of GC specimens of our cohort were subsequently performed for external validity. The relationship between clinical variables and gene expression were evaluated by Kruskal–wallis test and Wilcoxon signed-rank. The prognostic value of the candidate genes was assessed using Kaplan-Meier analysis and Cox regression models. CIBERSORT and Gene set enrichment analysis (GSEA) were used to determine immune cell infiltration. Gastric adenocarcinoma AGS cells and human embryonic kidney 293T (HEK293T) cells with knockdown of LINC01094 were generated by siRNA transfection, followed by detecting the alteration of the target miRNA and PD-L1/PD-L2 by RT-qPCR. Besides, the interaction between lncRNA and the miRNA–PD-L1/PD-L2 axis were verified by dual luciferase reporter assay.ResultsTwenty-two intersecting lncRNAs were identified to be PD-L1/PD-L2-related lncRNAs and LINC01094–miR-17-5p–PD-L1/PD-L2 was constructed as a potential ceRNA network. LINC01094 was increased in tumor specimens than adjacent normal samples and was positively associated with advanced tumor stages and EBV and MSI status. Furthermore, LINC01094 expression was an independent risk factor for poor overall survival (OS) in GC patients. CD8+ T cell exhaustion-related genes were enriched in high-LINC01094 tissues and high-PD-L2 group. A strong positive association of LINC01094 expression was established with M2 macrophages, IL-10+ TAM, as well as PD-L1 and PD-L2 levels, therefore a LINC01094–miR-17-5p–IL-10 network was proposed in macrophages. Using the exoRBase database, LINC01094 was assumed in blood exosomes of GC patients The results of knockdown experiments and luciferase reporter assays revealed that LINC01094 interacted with miR-17-5p and served as a miRNA sponge to regulate the expression of PD-L1 and PD-L2.ConclusionLINC01094 dually regulates the expression of PD-L1 and PD-L2 and shapes the immunosuppressive tumor microenvironment via sponging miR-17-5p. LINC01094 may serve as a potential prognostic predictor and therapeutic target in GC.

Blood has an important role in the healthcare system, particularly in blood transfusions and immunotherapy. However, the occurrence of outbreaks of infectious diseases worldwide and seasonal fluctuations, blood shortages are becoming a major challenge. Moreover, the narrow specificity of immune cells hinders the widespread application of immune cell therapy. To address this issue, researchers are actively developing strategies for differentiating induced pluripotent stem cells (iPSCs) into blood cells in vitro. The establishment of iPSCs from terminally differentiated cells such as fibroblasts and blood cells is a straightforward process. However, there is need for further refinement of the protocols for differentiating iPSCs into immune cells and red blood cells to ensure their clinical applicability. This review aims to provide a comprehensive overview of the strategies and challenges facing the generation of iPSC-derived immune cells and red blood cells.

Abstract Introduction Patent ductus arteriosus (PDA) is one of the most common congenital heart diseases. Once the PDA is diagnosed, it needs to be dealt with in time. At present, main methods include pharmacological treatment, surgical closure, and interventional closure for treatment of PDA. However, the effect of different interventions in PDA management is still controversial. Thus, our study aims to assess the effectiveness of different interventions together and estimate the sequence of these therapies for PDA children. Meanwhile, it is necessary to conduct a Bayesian network meta-analysis to compare the safety of different interventions comprehensively. Methods and analysis To the best of our knowledge, this is the first Bayesian network meta-analysis comparing the efficacy and safety of different interventions for the treatment of PDA. PubMed, Embase, Cochrane Library, Web of Science, gray literature, and trial registry databases were searched from inception to December 2022. We will extract and report data according to methodological guidelines for Bayesian network meta-analysis by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Primary PDA closure, overall PDA closure, technical success, surgical success rate, mortality during hospital stay, operation time, intensive care unit stay, intraoperative radiation dose, radiation exposure time, total postoperative complication rate, and postoperative major complication rate will be defined as the outcomes. The quality of all random studies will be assessed using ROB, and quality of evidence for all outcomes will be judged by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Ethics and dissemination The results will be disseminated through peer-reviewed publication. Since no private and confidential patient data will be contained in the reporting, there are no ethical considerations associated with this protocol. Systematic review registration INPLASY2020110067.

ABSTRACT Staphylococcus aureus often leads to severe skin infections. However, S. aureus is facing a crisis of antibiotic resistance. The combination of phage and antibiotics is effective for drug-resistant S. aureus infections. Therefore, it is worth exploiting novel antibacterial agents to cooperate with antibiotics against S. aureus infections. Herein, a novel chimeric lysin ClyQ was constructed, which was composed of a cysteine- and histidine-dependent amidohydrolase/peptidase (CHAP) catalytic domain from S. aureus phage lysin LysGH15 and cell wall-binding domain (CBD) from Enterococcus faecalis phage lysin PlyV12. ClyQ had an exceptionally broad host range targeting streptococci, staphylococci, E. faecalis, and E. rhusiopathiae. ClyQ combined with mupirocin (2.64 log reduction) was more effective at treating S. aureus skin infections than ClyQ (0.46 log reduction) and mupirocin (2.23 log reduction) alone. Of equal importance, none of S. aureus ATCC 29213 or S3 exposed to ClyQ developed resistance, and the combination of ClyQ and mupirocin delayed the development of mupirocin resistance. Collectively, chimeric lysin ClyQ enriches the reservoirs for treating S. aureus infections. Our findings may provide a way to alleviate the current antibiotic resistance crisis. IMPORTANCE Staphylococcus aureus, as an Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogen, can escape the elimination of existing antibiotics. At present, phages and phage lysins against S. aureus infections are considered alternative antibacterial agents. However, the development of broad-spectrum chimeric phage lysins to cooperate with antibiotics against S. aureus infections remains at its initial stage. In this study, we found that the broad-host-range chimeric lysin ClyQ can synergize with mupirocin to treat S. aureus skin infections. Furthermore, the development of S. aureus resistance to mupirocin is delayed by the combination of ClyQ and mupirocin in vitro. Our results bring research attention toward the development of chimeric lysin that cooperates with antibiotics to overcome bacterial infections.

Hydrochlorofluorocarbons (HCFCs) are important greenhouse gases and ozone-depleting substances. Thus, a thorough understanding of their atmospheric fate is essential for preventing and controlling atmospheric pollution. Herein, the atmospheric transformation mechanism of CF3CH2CClF2 (HCFC-235fa) by the OH radical and the Cl atom was carried out at the dual-level of CCSD(T)/aug-cc-pVTZ//M06-2X/6-311+G(d,p). The reaction rate coefficients were calculated using the multistructural canonical variational transition state theory with small curvature tunneling (MS-CVT/SCT) at 200–1000 K. The kMS-CVT/SCT(CF3CH2CClF2 + OH) and kMS-CVT/SCT(CF3CH2CClF2 + Cl) values are 9.05 × 10−15 and 1.95 × 10−17 cm³ molecule−1 s−1 at 297 K, respectively. The results show that the role of OH is more important than Cl in the degradation of CF3CH2CClF2. The atmospheric lifetimes (83 days–77.93 years), ozone destruction potential (0.001–0.023), and global warming potentials (GWP100 = 21.06–5157.35) of CF3CH2CClF2 were assessed, and these results indicate that CF3CH2CClF2 is atmospherically persistent and environmentally unfriendly. The evolution mechanisms of CF3C·HCClF2, CF3C(OO˙)HCClF2, and CF3C(O˙)HCClF2 in the presence of O2, HO2˙, and NO were investigated and discussed. The resulting products of CF3CH2CClF2 are mostly highly oxidized multi-functional compounds in the forms of aldehydes, ketones, and organic nitrates. A computational assessment of acute and chronic toxicities was performed at three levels of nutrition in order to improve the understanding of the potential toxicity of CF3CH2CClF2 and its degradation products to the aquatic environment. The acidification potential of CF3CH2CClF2 was calculated to be 1.141 and presumed to contribute to the formation of acid rain. The results may contribute to describing HCFCs' atmospheric fate, persistence, and environmental risks. [ABSTRACT FROM AUTHOR]

AIM: To quantitatively analyze the retinal intermediate and deep capillary plexus (ICP and DCP) in patients with retinal deep vascular complex ischemia (RDVCI), using 3D projection artifacts removal (3D PAR) optical coherence tomography angiography (OCTA). METHODS: RDVCI patients and gender- and age-matched healthy controls were assessed and underwent OCTA examinations. The parafoveal vessel density (PFVD) of retinal deep vascular complex (DVC), ICP, and DCP were analyzed, and the percentage of reduction (PR) of PFVD was calculated. RESULTS: Twenty-four eyes in 22 RDVCI patients (20 in acute phase and 4 in chronic phase) and 24 eyes of 22 healthy subjects were enrolled as the control group. Significant reduction of PFVD in DVC, ICP, and DCP was observed in comparison with the controls (DVC: acute: 43.59%±6.58% vs 49.92%±5.49%, PR=12.69%; chronic: 43.50%±3.33% vs 51.20%±3.80%, PR=15.04%. ICP: acute: 40.28%±7.91% vs 46.97%±7.14%, PR=14.23%; chronic: 41.48%±2.87% vs 46.43%±3.29%, PR=10.66%. DCP: acute: 45.44%±8.27% vs 51.51%±9.97%, PR=11.79%; chronic: 37.78%±3.48% vs 51.73%±5.17%, PR=26.97%; all P

Epigenetic regulations on the maintenance of neural stem cells (NSCs) are complicated and far from been fully understood. Our previous findings have shown that after blocking Notch signaling in NSCs in vivo, the stemness of NSCs decreases, accompanied by the downregulated expression of miR-582-5p. In the current study, we further investigated the function and mechanism of miR-582-5p in the maintenance of NSCs in vitro and in vivo. After transfecting a mimic of miR-582-5p, the formation of neurospheres and proliferation of NSCs and intermediate progenitor cells (NS/PCs) were enhanced, and the expression of stemness markers such as Sox2, Nestin, and Pax6 also increased. The results were reversed after transfection of an inhibitor of miR-582-5p. We further generated miR-582 knock-out (KO) mice to investigate its function in vivo, and we found that the number of NSCs in the subventricular zone (SVZ) region decreased and the number of neuroblasts increased in miR-582 deficient mice, indicating reduced stemness and enhanced neurogenesis of NSCs. Moreover, RNA-sequencing and molecular biological analysis revealed that miR-582-5p regulates the stemness and proliferation of NSCs by inhibiting secretory protein FAM19A1. In summary, our research uncovered a new epigenetic mechanism that regulates the maintenance of NSCs, therefore providing novel targets to amplify NSCs in vitro and to promote neurogenesis in vivo during brain pathology and aging.

In this study, the polysaccharide was extracted by subcritical water from Dendrobium huoshanense. A novel polysaccharide (DHPs-1) was obtained through several purification steps and its structure and bioactivity were investigated. Structural analysis indicated that the weight-average molecular weight of DHPs-1 was 5.0 × 104 Da and it was mainly composed of glucose (65.04%), mannose (14.23%), galactose (8.17%), galacturonic acid (6.41%), rhamnose (2.34%), and xylose (1.25%). 1,4-Glcp, and 1,4,6-Galp were existed in the backbone of DHPs-1. The residues of 1,3,4-Galp, 1,4-Manp, 1,4-Galp, and 1,3,4,6-Galp could be in the backbone or the side chains with the non-reducing terminal of α-Manp. Bioactivity tests indicated that DHPs-1 had immunomodulatory activity in that it significantly enhanced transcript levels of cytokines [Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and Interleukin-10 (IL-10)]. DPPH and hydroxyl radical scavenging tests showed that it had good antioxidant activity. These results reveal that DHPs-1 could be developed as a safe immunomodulatory agent and antioxidant for pharmacological or functional food applications.

Exosome, a subpopulation of extracellular vesicles, plays diverse roles in various biological processes. As one of the most abundant components of exosomes, exosomal proteins have been revealed to participate in the development of many diseases, such as carcinoma, sarcoma, melanoma, neurological disorders, immune responses, cardiovascular diseases, and infection. Thus, understanding the functions and mechanisms of exosomal proteins potentially assists clinical diagnosis and targeted delivery of therapies. However, current knowledge about the function and application of exosomal proteins is still limited. In this review, we summarize the classification of exosomal proteins, and the roles of exosomal proteins in exosome biogenesis and disease development, as well as in the clinical applications.

Formation of glioma stem cells (GSCs) is considered as one of the main reasons of temozolomide (TMZ) resistance in glioma patients. Recent studies have shown that tumor microenvironment-derived signals could promote GSCs formation. But the critical molecule and underlying mechanism for GSCs formation after TMZ treatment is not entirely identified. Our study showed that TMZ treatment promoted GSCs formation by glioma cells; TMZ treatment of biopsy-derived glioblastoma multiforme cells upregulated HMGB1; HMGB1 altered gene expression profile of glioma cells with respect to mRNA, lncRNA and miRNA. Furthermore, our results showed that TMZ-induced HMGB1 increased the formation of GSCs and when HMGB1 was downregulated, TMZ-mediated GSCs formation was attenuated. Finally, we showed that the effect of HMGB1 on glioma cells was mediated by TLR2, which activated Wnt/β-catenin signaling to promote GSCs. Mechanistically, we found that HMGB1 upregulated NEAT1, which was responsible for Wnt/β-catenin activation. In conclusion, TMZ treatment upregulates HMGB1, which promotes the formation of GSCs via the TLR2/NEAT1/Wnt pathway. Blocking HMGB1-mediated GSCs formation could serve as a potential therapeutic target for preventing TMZ resistance in GBM patients.

Objective: Colorectal cancer is one of the most important malignant cancer in the world with high incidence and mortality. Some studies have found that the expression of low serum L1 cell adhesion molecule is associated with poor prognosis in some malignancies. It is suggested that L1 cell adhesion molecule is a candidate serum marker for certain tumors. However, the relationship between serum L1 cell adhesion molecule and colorectal cancer, especially about the diagnostic value, is rarely reported. Therefore, this study aimed to evaluate the diagnostic potential of serum L1 cell adhesion molecule in patients with colorectal cancer. Methods: Enzyme-linked immunosorbent assay was carried out to detect L1 cell adhesion molecule level in sera of 229 patients with colorectal cancer and 145 normal controls. Receiver operating characteristic curves were employed to calculate the accuracy of diagnosis. Results: The levels of serum L1 cell adhesion molecule in the colorectal cancer group were significantly lower than that in normal controls ( P < .05). In the normal group, the area under the receiver operating characteristic curve (area under the curve) of all colorectal cancer was 0.781 (95% confidence interval: 0.734-0.828) and early-stage colorectal cancer was 0.764 (95% confidence interval: 0.705-0.823). With optimized cutoff of 17.760 ng/mL, L1 cell adhesion molecule showed certain diagnostic value with specificity of 90.3% and sensitivities of 43.2% and 36.2% in colorectal cancer and early-stage colorectal cancer, respectively. Clinical data analysis showed that the levels of L1 cell adhesion molecule were significantly correlated with gender ( P < .05) and early and late stages ( P < .05). Furthermore, when compared with carcinoembryonic antigen, serum L1 cell adhesion molecule had significantly improved diagnostic accuracy for both colorectal cancer and early-stage colorectal cancer. Conclusions: Our study demonstrated that serum L1 cell adhesion molecule might be served as a potential biomarker for the diagnosis of colorectal cancer.

Background: The serotype and antimicrobial resistance of Haemophilus influenzae in adult patients have changed due to the application of antimicrobials and H. influenzae type b (Hib) vaccine worldwide. However, the epidemiologic characteristics of H. influenzae in Shanghai are still unavailable.Objective: To determine the serotype distribution, antimicrobial resistance and multilocus sequence type (MLST) of H. influenzae in adult patients in Shanghai.Methods: A total of 51 clinical isolates from adult patients were consecutively collected. Serotypes were determined according to specific capsule gene, bexA, amplified by PCR. Antimicrobial susceptibility test was carried out by the broth microdilution method. β-lactamase production was detected by cefinase disk and the ftsI gene were amplified and sequenced to determine the penicillin binding protein 3 (PBP3) mutation. Molecular epidemiology was performed by MLST analyses.Results: All isolates studied were nontypeable H. influenzae (NTHi) and three of them (5.88%) caused invasive infection. The resistant rates of ampicillin and trimethoprim/sulfamethoxazole were both 45.10%. One third of these isolates produced TEM-1 type β-lactamase and 11.76% were β-lactamase negative ampicillin resistant strains (BLNAR). The PBP3 mutation was detected in 74.51% of the isolates, of which 12 belonged to group III. A total of 36 sequence types (STs) were identified among all isolates. Four isolates of ST103 (7.84%) all produced β-lactamase without mutation of PBP3.Conclusion:H. influenzae infections among adults in Shanghai are predominately caused by NTHi with genetic diversity among adult patients. The prevalence of both β-lactamase production and PBP3 mutation may contribute to high ampicillin resistance rate in Shanghai.

Residual stress has significant influence on the performance of mechanical components, and the nondestructive estimation of residual stress is always a difficult problem. This study applies the relative nonlinear coefficient of critical refraction longitudinal (LCR) wave to nondestructively characterize the stress state of materials; the feasibility of residual stress estimation using the nonlinear property of LCR wave is verified. The nonlinear ultrasonic measurements based on LCR wave are conducted on components with known stress state to calculate the relative nonlinear coefficient. Experimental results indicate that the relative nonlinear coefficient monotonically increases with prestress and the increment of relative nonlinear coefficient is about 80%, while the wave velocity only decreases about 0.2%. The sensitivity of the relative nonlinear coefficient for stress is much higher than wave velocity. Furthermore, the dependence between the relative nonlinear coefficient and deformation state of components is found. The stress detection resolution based on the nonlinear property of LCR wave is 10 MPa, which has higher resolution than wave velocity. These results demonstrate that the nonlinear property of LCR wave is more suitable for stress characterization than wave velocity, and this quantitative information could be used for residual stress estimation.

Purpose: This study investigated native Cantonese-speaking preschool children’s diadochokinetic performance, including rate, accuracy, and regularity. The second aim of this study was to examine whether language-specific patterns exist by comparing diadochokinetic rates with the average DKK rate for native English speakers. Method: Sixty-four typically developing preschool children who were native Cantonese speakers participated. The diadochokinetic task administered to the children involved repetitions of monosyllabic, disyllabic, and trisyllabic words and nonsense words. The maximum performance of the children was compared by diadochokinetic rate (number of syllables per second), accuracy (percentage of matched production), and regularity (pairwise variability indexes, known as PVIs). Results: Monosyllabic units were produced faster, more accurately, and more regularly than multisyllabic units. Word repetition showed higher accuracy and generally lower regularity than nonsense words but similar rates. Older children were faster and more regular (higher raw PVI of initial consonants) than younger children, but younger children performed as accurately as them. When compared with data from English speakers, the diadochokinetic rates of Cantonese children were generally lower. Conclusions: Developmental progression was evident in terms of rate and regularity. The distinctive accuracy and regularity patterns between word and nonsense word repetition suggest a clinical value for both stimulus types. Language typology plays a role in diadochokinetic rate, supporting the use of languagespecific reference data in practice. The typical diadochokinetic profile obtained in this study could serve as a clinical reference for speech motor assessments. [ABSTRACT FROM AUTHOR]

Purpose: Research into the phonological development of Chinese children is in its infancy compared with the relatively extensive data available on the English-speaking population. This article provided a comprehensive review of empirical studies on the acquisition of Mandarin phonology. Method: Studies over the past 45 years that describe phonological development in Mandarin-speaking children were located through electronic databases, citation searches, keyword searches through online search engines, and manual searches of libraries. The research design of the studies was reviewed, and findings of acceptable studies were summarized. Results: After reviewing the abstracts of 798 studies, a total of 12 that met the inclusion criteria were retained. These studies are discussed with reference to the demographic background of participants, geographic regions, aspects of speech sounds measured, data collection tools, transcription systems used, reliability, and the main findings. Conclusions: The general developmental patterns reported were consistent. The methodological design varied substantially. These discrepancies, however, provide insights for further systematic investigations into phonological development in Mandarin. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, occurring in the colon or rectum portion of large intestine. With marked antioxidant, anti-inflammation and anti-tumor activities, Camellia nitidissima Chi has been used as an effective treatment of cancer. The azoxymethane/dextran sodium sulfate (AOM/DSS) induced CRC mice model was established and the prevention effect of C. nitidissima Chi extracts on the evolving of CRC was evaluated by examination of neoplastic lesions, histopathological inspection, serum biochemistry analysis, combined with nuclear magnetic resonance (NMR)-based metabolomics and correlation network analysis. C. nitidissima Chi extracts could significantly inhibit AOM/DSS induced CRC, relieve the colonic pathology of inflammation and ameliorate the serum biochemistry, and could significantly reverse the disturbed metabolic profiling toward the normal state. Moreover, the butanol fraction showed a better efficacy than the water-soluble fraction of C. nitidissima Chi. Further development of C. nitidissima Chi extracts as a potent CRC inhibitor was warranted. [ABSTRACT FROM AUTHOR]

Background: Diazotrophic (nitrogen-fixing) Gram-positive and endospore-formed Paenibacillus spp. have potential uses as a bacterial fertilizer in agriculture. The transcriptional analysis of nitrogen fixation in Paenibacillus is lacking, although regulation mechanisms of nitrogen fixation have been well studied in Gram-negative diazotrophs. Results: Here we report a global transcriptional profiling analysis of nitrogen fixation in Paenibacillus sp. WLY78 cultured under N2-fixing condition (without O2 and NH4+) and non-N2-fixing condition (air and 100 mM NH4+). The nif (nitrogen fixation) gene operon composed of 9 genes (nifBHDKENXhesAnifV) in this bacterium was significantly up-regulated in N2-fixing condition compared to non-N2-fixing condition, indicating that nif gene transcription is strictly controlled by NH4+ and O2. qRT-PCR confirmed that these nif genes were differently expressed. Non-nif genes specifically required in nitrogen fixation, such as mod, feoAB and cys encoding transporters of Mo, Fe and S atoms, were coordinately transcribed with nif genes in N2-fixing condition. The transcript abundance of suf operon specific for synthesis of Fe-S cluster was up-regulated in N2-fixing condition, suggesting that Sul system, which takes place of nifS and nifU, plays important role in the synthesis of nitrogenase. We discover potential specific electron transporters which might provide electron from Fe protein to MoFe protein of nitrogenase. The glnR whose predicted protein might mediate nif transcription regulation by NH4+ is significantly up-regulated in N2-fixing condition. The transcription levels of nitrogen metabolism and anaerobic respiration were also analyzed. Conclusions: The nif gene operon (nifBHDKENXhesAnifV) in Paenibacillus sp. WLY78 is significantly up-regulated in N2-fixing condition compared to non-N2-fixing condition. Non-nif genes specifically required in nitrogen fixation were also significantly up-regulated in N2-fixing condition. Fur and Fnr which are involved in anaerobic regulation and GlnR which might mediate nif gene transcription regulation by NH4+ were significantly up-regulated in N2-fixing condition. This study provides valuable insights into nitrogen fixation process and regulation in Gram-positive firmicutes. [ABSTRACT FROM AUTHOR]

Background: Nitrogen fixation has been established in protokaryotic model Escherichia coli by transferring a minimal nif gene cluster composed of 9 genes (nifB, nifH, nifD, nifK, nifE, nifN, nifX, hesA and nifV) from Paenibacillus sp. WLY78. However, the nitrogenase activity in the recombinant E. coli 78-7 is only 10% of that observed in wild-type Paenibacillus. Thus, it is necessary to increase nitrogenase activity through synthetic biology. Results: In order to increase nitrogenase activity in heterologous host, a total of 28 selected genes from Paenibacillus sp. WLY78 and Klebsiella oxytoca were placed under the control of Paenibacillus nif promoter in two different vectors and then they are separately or combinationally transferred to the recombinant E. coli 78-7. Our results demonstrate that Paenibacillus suf operon (Fe-S cluster assembly) and the potential electron transport genes pfoAB, fldA and fer can increase nitrogenase activity. Also, K. oxytoca nifSU (Fe-S cluster assembly) and nifFJ (electron transport specific for nitrogenase) can increase nitrogenase activity. Especially, the combined assembly of the potential Paenibacillus electron transporter genes (pfoABfldA) with K. oxytoca nifSU recovers 50.1% of wild-type (Paenibacillus) activity. However, K. oxytoca nifWZM and nifQ can not increase activity. Conclusion: The combined assembly of the potential Paenibacillus electron transporter genes (pfoABfldA) with K. oxytoca nifSU recovers 50.1% of wild-type (Paenibacillus) activity in the recombinant E. coli 78-7. Our results will provide valuable insights for the enhancement of nitrogenase activity in heterogeneous host and will provide guidance for engineering cereal plants with minimal nif genes. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we aimed to evaluate the efficacy of sentence-combining (SC) and narrative-based (NAR) intervention approaches to syntax intervention using a randomized-controlled-trial design. Method: Fifty-two Cantonese-speaking, school-age children with language impairment were assigned randomly to either the SC or the NAR treatment arm. Seven children did not receive treatment as assigned. Intervention in both arms targeted the same complex syntactical structures. The SC group focused on sentence combination training, whereas the NAR group made use of narratives in which the target structures were embedded. Pretest and posttest performances measured using a standardized language assessment were subjected to analyses of covariance mixed-effect-model analyses of variance. Results: Children in both treatment arms demonstrated significant growth after 4 months of intervention. The main effect between treatment arms and time was not significant after controlling the pretest performance, suggesting that both treatment approaches showed similar effects. The main effect of time was significant. Conclusions: This study provided evidence to support language intervention in the school years in Cantonese-speaking children. However, neither approach was shown to be more efficacious than the other. Future researchers could examine the effects of a longer treatment period and include functional outcome measures. [ABSTRACT FROM AUTHOR]

Circulating microRNAs (miRNAs) are important in the diagnosis of a number of diseases, since serum or plasma miRNAs are more stable compared with miRNA isolated from blood samples. The aim of the present study was to investigate the association between the expression levels of serum let-7c miRNA and the clinical diagnosis of breast cancer (BC). The circulating let-7c levels of 90 BC patients and 64 healthy controls were determined by performing a reverse transcription-quantitative polymerase chain reaction assay. The results demonstrated that let-7c expression was downregulated in the BC tissues compared with the paracarcinoma control tissues. In addition, the let-7c expression in the serum of BC patients was significantly lower compared with the healthy controls (P<0.01). Using a cutoff value of 0.374x103 copies/ml, the serum expression levels of let-7c exhibited 87.5% sensitivity and 78.9% specificity for distinguishing BC patients from healthy controls (area under the receiver operating characteristic curve, 0.848; 95% confidence interval, 0.785-0.911). Furthermore, the results demonstrated that the serum expression levels of let-7c were significantly higher in premenopausal compared with postmenopausal patients (P<0.05), supporting the hypothesis that postmenopausal status may affect the serum expression levels of let-7c. However, no statistically significant differences were detected in the serum levels of let-7c between ER (or PR)-positive and -negative patients. Therefore, the current study hypothesized that serum let-7c may be used as a novel and valuable biomarker for the diagnosis of BC. [ABSTRACT FROM AUTHOR]

Magnetic-particle-composite-medium-filled stacked-spiral inductors for rf complementary metal oxide semiconductor (CMOS) applications in GHz are demonstrated. The new inductor features a nearly closed magnetic circuit loop, an optimized high-permeability and low-loss sub-1 μm magnetic particles' composite core, and a developed 0.18-μm CMOS-compatible device fabrication process. An equivalent circuit model with structural amplifying factors is proposed and modeled. The prototype of the 6-level stacked inductor with Co2Z magnetic-particles-composite-medium filling increases the inductance L by 50%, and quality factor Q by 37% at frequencies as high as 1 GHz, with high inductance density as 825 nH/mm2 and a reduced size area by 80% compared to the planar spiral inductor. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs), present in the serum in a stable and reproducible manner, may be used as biomarkers for various diseases. Few studies have previously investigated circulating miRNAs in the peripheral blood of breast cancer (BC) patients. To identify the role of serum miR-182 levels in BC, the present study detected miR-182 levels in the serum of 46 BC patients and 58 controls, by quantitative PCR. The results showed that the serum miR-182 levels in BC patients were signiicantly higher compared with the serum of healthy controls (P<0.01). The miR-182 was also overexpressed in the BC tissues compared with the para-carcinoma tissues. Furthermore, the serum levels of miR-182 in the estrogen receptor (ER)-positive patients were considerably lower compared with those in the ER-negative patients. The serum levels of miR-182 in the progesterone receptor (PR)-positive patients were also found to be lower compared with those in the PR-negative patients. The current study highlights results consistent with miR-182 as a novel and valuable biomarker for the diagnosis of BC. [ABSTRACT FROM AUTHOR]

A novel piezoresistive sensing method is presented herein for the detection of nanobeam resonator based on a monolithically integrated MOS (metal-oxide-semiconductor) capacitor structure. The bottom layer of the nanobeam located beneath the MOS capacitor is utilized as a piezoresistor for the detection of internal stress resulting from nanobeam deformation, and therefore the challenging process of ultra-shallow junction doping is avoided. When a bias voltage applied on the MOS gate exceeds the threshold, the depletion layer width is built up to the maximum, and the piezoresistive cancellation effect beside the neutral plane is eliminated. Based on a conventional microelectromechanical (MEMS) process, an MOS capacitor is fabricated at the terminal of a double-clamped nanobeam with dimensions of 46 im x 7 im x 149 nm. The measured R-V curve of this MOS structure presents a 64.7 nm thick piezoresistor which closely agrees with the design. This double-clamped nanobeam is excited into mechanical resonance by mounting it on a piezoelectric ceramic, and the amplitude-frequency response is measured by a network analyzer. The measured resonant frequency is 3.97 MHz and the quality (0-factor is 82 in atmosphere environment. Besides, this piezoresistive sensing method is verified by a laser-Doppler vibrometry. [ABSTRACT FROM AUTHOR]

Background: In mammals, hair cells do not undergo spontaneous regeneration when they are damaged and result in permanent hearing loss. Previous studies in cultured Organ of Corti dissected from neonatal animals have shown that both DAPT (r-secretase inhibitor in the Notch signal pathway) treatment and Atoh1 overexpression can induce supernumerary hair cells. The effects of simultaneous DAPT treatment and Atoh1 over expression in the cells of cultured Organ of Corti from neonatal rats are still obscure. Principal Findings: In this study, we set out to investigate the interaction of DAPT treatment and Atoh1 overexpression as well as culture time and the location of basilar fragment isolated form neonatal rat inner ear. Our results showed that DAPT treatment induced more hair cells in the apical turn, while Atoh1 overexpression induced more extra hair cells in the middle turn of the cultured Organ of Corti. When used together, their effects are additive but not synergistic. In addition, the induction of supernumerary hair cells by both DAPT and Atoh1 overexpression is dependent on the treatment time and the location of the cochlear tissue. Moreover, DAPT treatment causes dramatic changes in the orientation of the stereociliary bundles of hair cells, whereas Atoh1 overexpression didn't induce drastic change of the polarity of stereociliary bundles. Conclusions/Significance: Taken together, these results suggest that DAPT treatment are much more potent in inducing supernumerary hair cells than Atoh1 overexpression and that the new hair cells mainly come from the trans-differentiation of supporting cells around hair cells. The orientation change of stereociliary bundle of hair cells may be attributed to the insertion of the newly formed hair cells. The immature hair bundles on the newly formed hair cells may also contribute to the overall chaos of the stereociliary bundle of the sensory epithelia. [ABSTRACT FROM AUTHOR]

In this study, a triblock copolymer PDMAEMA-b-poly(PEGMA)-b-PDMAEMA (DED) and a diblock copolymer PDMAEMA-b-poly(PEGMA) (DE) were synthesized by atom transfer radical polymerization (ATRP) with the initiators bis(2-bromoisobutyryl) hexanediamide (BiBH) and ethyl 2-bromoisobutyrate (EBiB), respectively. Their molecular weights and chemical compositions were almost the same with only difference being in the block sequences. The influence of the block copolymer structures on the gene transfection results was investigated systematically. Gel retardation assay, atomic force microscopy (AFM) observation, particle size and zeta potential measurements with dynamic light scattering (DLS) were used to characterize the properties of the polymer/pDNA complexes. DED showed moderate aggregation behavior with far less cytotoxicity to in vitroand in vivoto zebrafish than DE, which indicates that DED would be a promising vector for gene therapeutic applications. [ABSTRACT FROM AUTHOR]

The growing volume of vague information poses interesting challenges and calls for new theories, techniques and tools for analysis of vague data sets. In this paper, we study how to extract knowledge from vague objective information systems (VOISs) based on rough sets theory. We first introduce the basic notion termed rough vague sets by combining rough sets theory and vague sets theory. By using the rough vague lower approximation distribution in the VOIS, the concept of attribute reduction is introduced. Then, we develop an algorithm based on a discernibility matrix to compute all the attribute reductions. Finally, a viable approach for extracting decision rules from the VOIS is proposed. An example is also presented to illustrate the application of the proposed theories and approaches in handling medical diagnosis problems. [ABSTRACT FROM AUTHOR]

Controllable cell growth on the defined areas of surfaces is important for potential applications in biosensor fabrication and tissue engineering. In this study, controllable cell growth was achieved by culturing 293 T fibroblast cells on a mica surface which had been patterned with collagen strips by a microcontact printing (μCP) technique. The collagen area was designed to support cell adhesion and the native mica surface was designed to repel cell adhesion. Consequently, the resulting cell patterns should follow the micro-patterns of the collagen. X-ray photoelectron spectroscopy (XPS), water contact angle (WCA) measurement, atomic-force microscope (AFM) observation, and force-curve measurement were used to monitor property changes before and after the collagen adsorption process. Further data showed that the patterned cells were of good viability and able to perform a gene-transfection experiment in vitro. This technique should be of potential applications in the fields of biosensor fabrication and tissue engineering. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The sorption behavior of sodium dodecylbenzene sulfonate (SDBS), an anionic surfactant, on marine sediments was systematically investigated. The experimental results showed that 100 min was required for the adsorption equilibrium. For the sediments treated by HCl and H2O, sorption behavior of SDBS was fit with linear isotherm very well over the concentration range studied at 298 K. The sorption occurred primarily due to partition function of hydrophobic chains into organic carbon of sediments. Sorption of SDBS on H2O2-treated sediments was satisfactorily fit with Freundlich isotherm model and mainly through surface function of clay minerals in the sediment. The sorption was favorably influenced by the increased salinity, deceased pH and decreased temperature of seawater. [ABSTRACT FROM AUTHOR]