Developing a practical neurodevelopmental prediction model for targeting high-risk very preterm infants during visit after NICU: a retrospective national longitudinal cohort study.

BACKGROUND: Follow-up visits for very preterm infants (VPI) after hospital discharge is crucial for their neurodevelopmental trajectories, but ensuring their attendance before 12 months corrected age (CA) remains a challenge. Current prediction models focus on future outcomes at discharge, but post-discharge data may enhance predictions of neurodevelopmental trajectories due to brain plasticity. Few studies in this field have utilized machine learning models to achieve this potential benefit with transparency, explainability, and transportability. METHODS: We developed four prediction models for cognitive or motor function at 24 months CA separately at each follow-up visits, two for the 6-month and two for the 12-month CA visits, using hospitalized and follow-up data of VPI from the Taiwan Premature Infant Follow-up Network from 2010 to 2017. Regression models were employed at 6 months CA, defined as a decline in The Bayley Scales of Infant Development 3rd edition (BSIDIII) composite score > 1 SD between 6- and 24-month CA. The delay models were developed at 12 months CA, defined as a BSIDIII composite score < 85 at 24 months CA. We used an evolutionary-derived machine learning method (EL-NDI) to develop models and compared them to those built by lasso regression, random forest, and support vector machine. RESULTS: One thousand two hundred forty-four VPI were in the developmental set and the two validation cohorts had 763 and 1347 VPI, respectively. EL-NDI used only 4-10 variables, while the others required 29 or more variables to achieve similar performance. For models at 6 months CA, the area under the receiver operating curve (AUC) of EL-NDI were 0.76-0.81(95% CI, 0.73-0.83) for cognitive regress with 4 variables and 0.79-0.83 (95% CI, 0.76-0.86) for motor regress with 4 variables. For models at 12 months CA, the AUC of EL-NDI were 0.75-0.78 (95% CI, 0.72-0.82) for cognitive delay with 10 variables and 0.73-0.82 (95% CI, 0.72-0.85) for motor delay with 4 variables. CONCLUSIONS: Our EL-NDI demonstrated good performance using simpler, transparent, explainable models for clinical purpose. Implementing these models for VPI during follow-up visits may facilitate more informed discussions between parents and physicians and identify high-risk infants more effectively for early intervention.

Cytosolic phosphoglucose isomerase is essential for microsporogenesis and embryogenesis in Arabidopsis.

Phosphoglucose isomerase (PGI) catalyzes the interconversion of fructose-6-phosphate and glucose-6-phosphate, which impacts cell carbon metabolic flow. Arabidopsis (Arabidopsis thaliana) contains two nuclear PGI genes respectively encoding plastidial PGI1 and cytosolic PGI (cPGI). The loss of PGI1 impairs the conversion of F6P of the Calvin-Benson cycle to G6P for the synthesis of transitory starch in leaf chloroplasts. Since cpgi knockout mutants have not yet been obtained, they are thought to be lethal. The cpgi lethality can be rescued by expressing CaMV 35S promoter (p35S)-driven cPGI; however, the complemented line is completely sterile due to pollen degeneration. Here, we generated a cpgi mutant expressing p35S::cPGI-YFP in which YFP fluorescence in developing anthers was undetectable specifically in the tapetum and in pollen, which could be associated with male sterility. We also generated RNAi-cPGI knockdown lines with strong cPGI repression in floral buds that exhibited reduced male fertility due to the degeneration of most pollen. Histological analyses indicated that the synthesis of intersporal callose walls was impaired, causing microsporocytes to fail to separate haploid daughter nuclei to form tetrads, which might be responsible for subsequent pollen degeneration. We successfully isolated cpgi knockout mutants in the progeny of a heterozygous cpgi mutant floral-dipped with sugar solutions. The rescued cpgi mutants exhibited diminished young vegetative growth, reduced female fertility, and impaired intersporal callose wall formation in a meiocyte, and, thus, male sterility. Collectively, our data suggest that cPGI plays a vital role in carbohydrate partitioning, which is indispensable for microsporogenesis and early embryogenesis.

Associations between the artificial intelligence scoring system and live birth outcomes in preimplantation genetic testing for aneuploidy cycles.

BACKGROUND: Several studies have demonstrated that iDAScore is more accurate in predicting pregnancy outcomes in cycles without preimplantation genetic testing for aneuploidy (PGT-A) compared to KIDScore and the Gardner criteria. However, the effectiveness of iDAScore in cycles with PGT-A has not been thoroughly investigated. Therefore, this study aims to assess the association between artificial intelligence (AI)-based iDAScore (version 1.0) and pregnancy outcomes in single-embryo transfer (SET) cycles with PGT-A. METHODS: This retrospective study was approved by the Institutional Review Board of Chung Sun Medical University, Taichung, Taiwan. Patients undergoing SET cycles (n = 482) following PGT-A at a single reproductive center between January 2017 and June 2021. The blastocyst morphology and morphokinetics of all embryos were evaluated using a time-lapse system. The blastocysts were ranked based on the scores generated by iDAScore, which were defined as AI scores, or by KIDScore D5 (version 3.2) following the manufacturer's protocols. A single blastocyst without aneuploidy was transferred after examining the embryonic ploidy status using a next-generation sequencing-based PGT-A platform. Logistic regression analysis with generalized estimating equations was conducted to assess whether AI scores are associated with the probability of live birth (LB) while considering confounding factors. RESULTS: Logistic regression analysis revealed that AI score was significantly associated with LB probability (adjusted odds ratio [OR] = 2.037, 95% confidence interval [CI]: 1.632-2.542) when pulsatility index (PI) level and types of chromosomal abnormalities were controlled. Blastocysts were divided into quartiles in accordance with their AI score (group 1: 3.0-7.8; group 2: 7.9-8.6; group 3: 8.7-8.9; and group 4: 9.0-9.5). Group 1 had a lower LB rate (34.6% vs. 59.8-72.3%) and a higher rate of pregnancy loss (26% vs. 4.7-8.9%) compared with the other groups (p < 0.05). The receiver operating characteristic curve analysis verified that the iDAScore had a significant but limited ability to predict LB (area under the curve [AUC] = 0.64); this ability was significantly weaker than that of the combination of iDAScore, type of chromosomal abnormalities, and PI level (AUC = 0.67). In the comparison of the LB groups with the non-LB groups, the AI scores were significantly lower in the non-LB groups, both for euploid (median: 8.6 vs. 8.8) and mosaic (median: 8.0 vs. 8.6) SETs. CONCLUSIONS: Although its predictive ability can be further enhanced, the AI score was significantly associated with LB probability in SET cycles. Euploid or mosaic blastocysts with low AI scores (≤ 7.8) were associated with a lower LB rate, indicating the potential of this annotation-free AI system as a decision-support tool for deselecting embryos with poor pregnancy outcomes following PGT-A.

Dual-Coating of Fluorinated Polydimethylsiloxane/Fluorinated SiO2 Nanoparticles for Superhydrophobic and High-Efficiency Bacteriostatic Surface.

A simple two-step spray method is used to prepare superhydrophobic and bacteriostatic surfaces, involving dual-coating with polydimethylsiloxane-normal-fluorine (PDMS-NF) or branched-fluorine (PDMS-BF) in combination with fluorinated silica nanoparticles (FSiO2 -NPs) using a spray technique. This approach has the potential to create surfaces with both water-repellent and antimicrobial properties, which could be useful in a variety of applications. It is noteworthy that the dual-coating on cotton fabric exhibited an impressive dual-scale roughness and achieved superhydrophobicity with a water contact angle of 158° and a hysteresis of less than 3°. Additionally, the coating was subjected to an ultra-high concentration of bacteria (109 CFU/mL) and was still able to inhibit more than 80 % of attachment, demonstrating its effectiveness as a bacteriostatic surface.

"Pseudo-pseudogenes" in bacterial genomes: Proteogenomics reveals a wide but low protein expression of pseudogenes in Salmonella enterica.

Pseudogenes (genes disrupted by frameshift or in-frame stop codons) are ubiquitously present in the bacterial genome and considered as nonfunctional fossil. Here, we used RNA-seq and mass-spectrometry technologies to measure the transcriptomes and proteomes of Salmonella enterica serovars Paratyphi A and Typhi. All pseudogenes' mRNA sequences remained disrupted, and were present at comparable levels to their intact homologs. At the protein level, however, 101 out of 161 pseudogenes suggested successful translation, with their low expression regardless of growth conditions, genetic background and pseudogenization causes. The majority of frameshifting detected was compensatory for -1 frameshift mutations. Readthrough of in-frame stop codons primarily involved UAG; and cytosine was the most frequent base adjacent to the codon. Using a fluorescence reporter system, fifteen pseudogenes were confirmed to express successfully in vivo in Escherichia coli. Expression of the intact copy of the fifteen pseudogenes in S. Typhi affected bacterial pathogenesis as revealed in human macrophage and epithelial cell infection models. The above findings suggest the need to revisit the nonstandard translation mechanism as well as the biological role of pseudogenes in the bacterial genome.

Suppression of lipopolysaccharide-induced COX-2 expression via p38MAPK, JNK, and C/EBPß phosphorylation inhibition by furomagydarin A, a benzofuran glycoside from Magydaris pastinacea.

The phytochemical investigation of the methanol extract of the seeds of Magydaris pastinacea afforded two undescribed benzofuran glycosides, furomagydarins A-B (1, 2), together with three known coumarins. The structures of the new isolates were elucidated after extensive 1D and 2D NMR experiments as well as HR MS. Compound 1 was able to inhibit the COX-2 expression in RAW264.7 macrophages exposed to lipopolysaccharide, a pro-inflammatory stimulus. RT-qPCR and luciferase reporter assays suggested that compound 1 reduces COX-2 expression at the transcriptional level. Further studies highlighted the capability of compound 1 to suppress the LPS-induced p38MAPK, JNK, and C/EBPß phosphorylation, leading to COX-2 down-regulation in RAW264.7 macrophages.

Advancing screening tool for hospice needs and end-of-life decision-making process in the emergency department.

BACKGROUND: Predicting mortality in the emergency department (ED) is imperative to guide palliative care and end-of-life decisions. However, the clinical usefulness of utilizing the existing screening tools still leaves something to be desired. METHODS: We advanced the screening tool with the A-qCPR (Age, qSOFA (quick sepsis-related organ failure assessment), cancer, Performance Status Scale, and DNR (Do-Not-Resuscitate) risk score model for predicting one-year mortality in the emergency department of Taipei City Hospital of Taiwan with the potential of hospice need and evaluated its performance compared with the existing screening model. We adopted a large retrospective cohort in conjunction with in-time (the trained and the holdout validation cohort) for the development of the A-qCPR model and out-of-time validation sample for external validation and model robustness to variation with the calendar year. RESULTS: A total of 10,474 patients were enrolled in the training cohort and 33,182 patients for external validation. Significant risk scores included age (0.05 per year), qSOFA ≥ 2 (4), Cancer (5), Eastern Cooperative Oncology Group (ECOG) Performance Status score ≥ 2 (2), and DNR status (2). One-year mortality rates were 13.6% for low (score ≦ 3 points), 29.9% for medium (3 < Score ≦ 9 points), and 47.1% for high categories (Score > 9 points). The AUROC curve for the in-time validation sample was 0.76 (0.74-0.78). However, the corresponding figure was slightly shrunk to 0.69 (0.69-0.70) based on out-of-time validation. The accuracy with our newly developed A-qCPR model was better than those existing tools including 0.57 (0.56-0.57) by using SQ (surprise question), 0.54 (0.54-0.54) by using qSOFA, and 0.59 (0.59-0.59) by using ECOG performance status score. Applying the A-qCPR model to emergency departments since 2017 has led to a year-on-year increase in the proportion of patients or their families signing DNR documents, which had not been affected by the COVID-19 pandemic. CONCLUSIONS: The A-qCPR model is not only effective in predicting one-year mortality but also in identifying hospice needs. Advancing the screening tool that has been widely used for hospice in various scenarios is particularly helpful for facilitating the end-of-life decision-making process in the ED.

Geospatial artificial intelligence for estimating daytime and nighttime nitrogen dioxide concentration variations in Taiwan: A spatial prediction model.

Nitrogen dioxide (NO2) is a major air pollutant primarily emitted from traffic and industrial activities, posing health risks. However, current air pollution models often underestimate exposure risks by neglecting the bimodal pattern of NO2 levels throughout the day. This study aimed to address this gap by developing ensemble mixed spatial models (EMSM) using geo-artificial intelligence (Geo-AI) to examine the spatial and temporal variations of NO2 concentrations at a high resolution of 50m. These EMSMs integrated spatial modelling methods, including kriging, land use regression, machine learning, and ensemble learning. The models utilized 26 years of observed NO2 measurements, meteorological parameters, geospatial layers, and social and season-dependent variables as representative of emission sources. Separate models were developed for daytime and nighttime periods, which achieved high reliability with adjusted R2 values of 0.92 and 0.93, respectively. The study revealed that mean NO2 concentrations were significantly higher at nighttime (9.60 ppb) compared to daytime (5.61 ppb). Additionally, winter exhibited the highest NO2 levels regardless of time period. The developed EMSMs were utilized to generate maps illustrating NO2 levels pre and during COVID restrictions in Taiwan. These findings could aid epidemiological research on exposure risks and support policy-making and environmental planning initiatives.

Team interaction behaviors correlates with team creativity among nursing students: Canonical correlation and moderation analyses.

BACKGROUND: Prior studies have indicated team members' interaction behaviors may predict creativity among nursing students. METHODS: This study investigated the correlation between interaction behaviors and creativity, both individual- and team-level, among nursing students. In this cross-sectional quantitative study, data were obtained from self-reported questionnaires. Individual creativity was assessed using the Torrance Tests of Creative Thinking scale; the perceived team interaction behavior and team creativity were assessed using validated instruments. Canonical correlation analysis was conducted to determine the overall correlation between interaction behaviors, and creativity, and the moderating effect of female proportion dominance was also examined. RESULTS: A total of 164 nursing students (84.1% female) arranged into 14 teams were included in this study. Canonical correlation analysis showed a positive correlation between interaction behaviors and creativity (correlation = 0.88). All dimensions of interactive behaviors were positively related to creativity dimensions. A stronger correlation to team creativity (correlation = 1) was found compared to individual creativity (correlation = 0.07). This study demonstrated that individual interactive behaviors including spontaneous communication and helping behavior predicted high team creativity. CONCLUSIONS: This insight may be valuable for nursing education programs seeking to foster creativity and effective teamwork. The potential moderating effect of female proportions on team interaction behaviors and creativity should be investigated further.

Unveiling the Future of Human and Machine Coding: A Survey of End-to-End Learned Image Compression.

End-to-end learned image compression codecs have notably emerged in recent years. These codecs have demonstrated superiority over conventional methods, showcasing remarkable flexibility and adaptability across diverse data domains while supporting new distortion losses. Despite challenges such as computational complexity, learned image compression methods inherently align with learning-based data processing and analytic pipelines due to their well-suited internal representations. The concept of Video Coding for Machines has garnered significant attention from both academic researchers and industry practitioners. This concept reflects the growing need to integrate data compression with computer vision applications. In light of these developments, we present a comprehensive survey and review of lossy image compression methods. Additionally, we provide a concise overview of two prominent international standards, MPEG Video Coding for Machines and JPEG AI. These standards are designed to bridge the gap between data compression and computer vision, catering to practical industry use cases.

Eradicating Helicobacter pylori via 13C-urea breath screening to prevent gastric cancer in indigenous communities: a population-based study and development of a family index-case method.

OBJECTIVE: Screening and eradication of Helicobacter pylori help reduce disparities in the incidence of gastric cancer. We aimed to evaluate its acceptability and feasibility in the indigenous communities and develop a family index-case method to roll out this programme. DESIGN: We enrolled residents aged 20-60 years from Taiwanese indigenous communities to receive a course of test, treat, retest and re-treat initial treatment failures with the 13C-urea breath tests and four-drug antibiotic treatments. We also invited the family members of a participant (constituting an index case) to join the programme and evaluated whether the infection rate would be higher in the positive index cases. RESULTS: Between 24 September 2018 and 31 December 2021, 15 057 participants (8852 indigenous and 6205 non-indigenous) were enrolled, with a participation rate of 80.0% (15 057 of 18 821 invitees). The positivity rate was 44.1% (95% CI 43.3% to 44.9%). In the proof-of-concept study with 72 indigenous families (258 participants), family members of a positive index case had 1.98 times (95% CI 1.03 to 3.80) higher prevalence of H. pylori than those of a negative index case. The results were replicated in the mass screening setting (1.95 times, 95% CI 1.61 to 2.36) when 1115 indigenous and 555 non-indigenous families were included (4157 participants). Of the 6643 testing positive, 5493 (82.6%) received treatment. According to intention-to-treat and per-protocol analyses, the eradication rates were 91.7% (89.1% to 94.3%) and 92.1% (89.2% to 95.0%), respectively, after one to two courses of treatment. The rate of adverse effects leading to treatment discontinuation was low at 1.2% (0.9% to 1.5%). CONCLUSION: A high participation rate, a high eradication rate of H. pylori and an efficient rollout method indicate that a primary prevention strategy is acceptable and feasible in indigenous communities. TRIAL REGISTRATION NUMBER: NCT03900910.

Associations of prognostic-awareness-transition patterns with emotional distress and quality of life during terminally ill cancer patients' last 6 months of life.

OBJECTIVE: Unprecedently investigate associations of prognostic-awareness-transition patterns with (changes in) depressive symptoms, anxiety symptoms, and quality of life (QOL) during cancer patients' last 6 months. METHODS: In this secondary analysis study, 334 cancer patients in their last 6 months transitioned between four prognostic-awareness states (unknown and not wanting to know, unknown but wanting to know, inaccurate awareness, and accurate awareness), thus constituting three transition patterns: maintaining-accurate-, gaining-accurate-, and maintaining-inaccurate/unknown prognostic awareness. A multivariate hierarchical linear model evaluated associations of the transition patterns with depressive symptoms, anxiety symptoms, and QOL determined at final assessment and by mean difference between the first and last assessment. RESULTS: At the last assessment before death, the gaining-accurate-prognostic-awareness group reported higher levels of depressive symptoms (estimate [95% confidence interval] = 1.59 [0.35-2.84]) and the maintaining- and gaining-accurate-prognostic-awareness groups suffered more anxiety symptoms (1.50 [0.44-2.56]; 1.42 [0.13-2.71], respectively) and poorer QOL (-7.07 [-12.61 to 1.54]; -11.06 [-17.76 to -4.35], respectively) than the maintaining-inaccurate/unknown-prognostic-awareness group. Between the first and last assessment, the maintaining- and gaining-accurate-prognostic-awareness groups' depressive symptoms (1.59 [0.33-2.85]; 3.30 [1.78-4.82], respectively) and QOL (-5.04 [-9.89 to -0.19]; -8.86 [-14.74 to -2.98], respectively) worsened more than the maintaining-inaccurate/unknown-prognostic-awareness group, and the gaining-accurate-prognostic-awareness group's depressive symptoms increased more than the maintaining-accurate-prognostic-awareness group (1.71 [0.42-3.00]). CONCLUSIONS: Unexpectedly, patients who maintained/gained accurate prognostic awareness suffered more depression, anxiety, and poorer QOL at end of life. Promoting accurate prognostic awareness earlier in the terminal-cancer trajectory should be supplemented with adequate psychological care to alleviate patients' emotional distress and enhance QOL. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01912846.

Highly efficient fixation of carbon dioxide into 2-oxazolidinones under mild conditions by using a reusable ionic liquid/CuI catalyst system.

A green approach was proposed for fixing CO2 with high efficiency and minimal energy consumption to produce 2-oxazolidinones through a one-pot reaction under mild conditions. A catalytic system composed of CuI and the ionic liquid [BMMIM][PF6] was employed, resulting in excellent yields. The starting materials, amines, aldehydes, and alkynes, with various substituents were investigated. The ionic liquid [BMMIM][PF6] used in this study was easy to prepare and easy to recycle for repeated use.

Can ship travel contain COVID-19 outbreak after re-opening: a Bayesian meta-analysis.

Large gatherings of people on cruise ships and warships are often at high risk of COVID-19 infections. To assess the transmissibility of SARS-CoV-2 on warships and cruise ships and to quantify the effectiveness of the containment measures, the transmission coefficient (ß), basic reproductive number (R0), and time to deploy containment measures were estimated by the Bayesian Susceptible-Exposed-Infected-Recovered model. A meta-analysis was conducted to predict vaccine protection with or without non-pharmaceutical interventions (NPIs). The analysis showed that implementing NPIs during voyages could reduce the transmission coefficients of SARS-CoV-2 by 50%. Two weeks into the voyage of a cruise that begins with 1 infected passenger out of a total of 3,711 passengers, we estimate there would be 45 (95% CI:25-71), 33 (95% CI:20-52), 18 (95% CI:11-26), 9 (95% CI:6-12), 4 (95% CI:3-5), and 2 (95% CI:2-2) final cases under 0%, 10%, 30%, 50%, 70%, and 90% vaccine protection, respectively, without NPIs. The timeliness of strict NPIs along with implementing strict quarantine and isolation measures is imperative to contain COVID-19 cases in cruise ships. The spread of COVID-19 on ships was predicted to be limited in scenarios corresponding to at least 70% protection from prior vaccination, across all passengers and crew.

Double-contrast barium enema is no longer justified as a backup examination for colonoscopy in the population screening program: Population study in an organized fecal immunochemical test-based screening program.

BACKGROUND AND AIM: Currently, some countries still acknowledge double-contrast barium enema (DCBE) as a backup confirmatory examination when colonoscopy is not feasible or incomplete in colorectal cancer (CRC) screening programs. This study aims to compare the performance of colonoscopy and DCBE in terms of the risk of incident CRC after negative results in the fecal immunochemical test (FIT)-based Taiwan Colorectal Cancer Screening Program. METHODS: Subjects who had positive FITs and received confirmatory exams, either colonoscopy or DCBE, without the findings of neoplastic lesions from 2004 to 2013 in the screening program comprised the study cohort. Both the colonoscopy and DCBE subcohorts were followed until the end of 2018 and linked to the Taiwan Cancer Registry to identify incident CRC cases. Multivariate analysis was conducted to compare the risk of incident CRC in both subcohorts after controlling for potential confounders. RESULTS: A total of 102 761 colonoscopies and 5885 DCBEs were performed after positive FITs without neoplastic findings during the study period. By the end of 2018, 2113 CRCs (2.7 per 1000 person-years) and 368 CRCs (7.6 per 1000 person-years) occurred in the colonoscopy and DCBE subcohorts, respectively. After adjusting for major confounders, DCBE had a significantly higher risk of incident CRC than colonoscopy, with an adjusted HR of 2.81 (95% CI = 2.51-3.14). CONCLUSIONS: In the FIT screening program, using DCBE as a backup examination was associated with a nearly threefold risk of incident CRC compared with colonoscopy, demonstrating that it is no longer justified as a backup examination for incomplete colonoscopy.

Fear of falling as a mediator in the association between social frailty and health-related quality of life in community-dwelling older adults.

BACKGROUND: Social frailty is associated with Fear of Falling (FoF) and health-related quality of life (HrQoL). However, how social frailty simultaneously influences FoF and HrQoL remains unclear. The study aims to understand the links between social frailty, FoF, and HrQoL in older adults and the mediating role of FoF in the relations between social frailty and HrQoL. METHODS: In this cross-sectional survey, 1,933 community-dwelling older adults from Changhua County, Taiwan, were interviewed using a self-administrated questionnaire. In total, 1,251 participants with complete data were included for analysis. Data were analyzed using the SPSS PROCESS macro. A simple mediation was employed using social frailty as the independent variable, FoF as the mediator variable, and HrQoL as the outcome variable. RESULTS: Social frailty was associated with HrQoL and indirectly with HrQoL through FoF, and FoF was directly associated with HrQoL. Of the 5-item social frailty index, "going out less frequently" was correlated with HrQoL and indirectly with HrQoL through FoF. Individuals who felt unhelpful toward family or friends had the worst physical HrQoL and did not talk to someone daily had the most negative influence on mental HrQoL. CONCLUSIONS: Social frailty can directly and indirectly, through FoF decrease HrQoL. It also emphasizes the importance of social connectivity in reducing the risk of falls. This study points to the need for social connectivity and fall prevention programs as essential components of strategies to enhance the health and well-being of community-dwelling older adults.

Schisanhenol ameliorates oxLDL-caused endothelial dysfunction by inhibiting LOX-1 signaling.

Atherosclerotic lesions play a critical role in leading cardiovascular diseases. Oxidized low-density lipoprotein (OxLDL) is a vital risk factor for atherosclerosis since it acts a crucial role in endothelial dysfunction and foam cell formation. Schisanhenol, a composition extracted from the fruit of Schisandra rubriflora, has been reported to have antioxidative effects on human LDL oxidation. This study investigates whether Schisanhenol protects against oxLDL-mediated endothelial damage by modulating the lectin-like oxLDL receptor-1 (LOX-1)-mediated inflammatory processes. Human umbilical vein endothelial cells (HUVECs) were pre-treated with 10 or 20 µM Schisanhenol for 2 h and then exposed to 150 µg/mL oxLDL. We revealed that Schisanhenol reduced oxLDL-enhanced LOX-1 expression. We also found that oxLDL down-regulated endothelial nitric oxide synthase (eNOS) as well as activated inducible NOS (iNOS), thereby enhancing the generation of nitric oxide (NO). Moreover, oxLDL elevated the expression levels of phosphorylated-p38MAPK, subsequently promoting NF-κB-modulated inflammatory responses. Pretreatment with Schisanhenol exerted significant cytoprotective function in all the above-mentioned detrimental events. Results from this present study reveal that Schisanhenol has a potential therapeutic effect on preventing oxLDL-induced endothelial injuries.

Small-Molecule Analysis Based on DNA Strand Displacement Using a Bacteriorhodopsin Photoelectric Transducer: Taking ATP as an Example.

A uniformly oriented purple membrane (PM) monolayer containing photoactive bacteriorhodopsin has recently been applied as a sensitive photoelectric transducer to assay color proteins and microbes quantitatively. This study extends its application to detecting small molecules, using adenosine triphosphate (ATP) as an example. A reverse detection method is used, which employs AuNPs labeling and specific DNA strand displacement. A PM monolayer-coated electrode is first covalently conjugated with an ATP-specific nucleic acid aptamer and then hybridized with another gold nanoparticle-labeled nucleic acid strand with a sequence that is partially complementary to the ATP aptamer, in order to significantly minimize the photocurrent that is generated by the PM. The resulting ATP-sensing chip restores its photocurrent production in the presence of ATP, and the photocurrent recovers more effectively as the ATP concentration increases. Direct and single-step ATP detection is achieved in 15 min, with detection limits of 5 nM and a dynamic range of 5 nM-0.1 mM. The sensing chip exhibits high selectivity against other ATP analogs and is satisfactorily stable in storage. The ATP-sensing chip is used to assay bacterial populations and achieves a detection limit for Bacillus subtilis and Escherichia coli of 102 and 103 CFU/mL, respectively. The demonstration shows that a variety of small molecules can be simultaneously quantified using PM-based biosensors.

Src-FAK Signaling Mediates Interleukin 6-Induced HCT116 Colorectal Cancer Epithelial-Mesenchymal Transition.

Colorectal cancer is one of the most prevalent and lethal malignancies, affecting approximately 900,000 individuals each year worldwide. Patients with colorectal cancer are found with elevated serum interleukin-6 (IL-6), which is associated with advanced tumor grades and is related to their poor survival outcomes. Although IL-6 is recognized as a potent inducer of colorectal cancer progression, the detail mechanisms underlying IL-6-induced colorectal cancer epithelial-mesenchymal transition (EMT), one of the major process of tumor metastasis, remain unclear. In the present study, we investigated the regulatory role of IL-6 signaling in colorectal cancer EMT using HCT116 human colorectal cancer cells. We noted that the expression of epithelial marker E-cadherin was reduced in HCT116 cells exposed to IL-6, along with the increase in a set of mesenchymal cell markers including vimentin and α-smooth muscle actin (α-SMA), as well as EMT transcription regulators-twist, snail and slug. The changes of EMT phenotype were related to the activation of Src, FAK, ERK1/2, p38 mitogen-activated protein kinase (p38MAPK), as well as transcription factors STAT3, κB and C/EBPß. IL-6 treatment has promoted the recruitment of STAT3, κB and C/EBPß toward the Twist promoter region. Furthermore, the Src-FAK signaling blockade resulted in the decline of IL-6 induced activation of ERK1/2, p38MAPK, κB, C/EBPß and STAT3, as well as the decreasing mesenchymal state of HCT116 cells. These results suggested that IL-6 activates the Src-FAK-ERK/p38MAPK signaling cascade to cause the EMT of colorectal cancer cells. Pharmacological approaches targeting Src-FAK signaling may provide potential therapeutic strategies for rescuing colorectal cancer progression.

Does Diffusely Infiltrating Lobular Carcinoma of the Breast Arise from Epithelial-Mesenchymal Hybrid Cells?

Classic diffusely infiltrating lobular carcinoma has imaging features divergent from the breast cancers originating from the terminal ductal lobular units and from the major lactiferous ducts. Although the term "invasive lobular carcinoma" implies a site of origin within the breast lobular epithelium, we were unable to find evidence supporting this assumption. Exceptional excess of fibrous connective tissue and the unique cell architecture combined with the aberrant features at breast imaging suggest that this breast malignancy has not originated from cells lining the breast ducts and lobules. The only remaining relevant component of the fibroglandular tissue is the mesenchyme. The cells freshly isolated and cultured from diffusely infiltrating lobular carcinoma cases contained epithelial-mesenchymal hybrid cells with both epithelial and mesenchymal properties. The radiologic and histopathologic features of the tumours and expression of the mesenchymal stem cell positive markers CD73, CD90, and CD105 all suggest development in the direction of mesenchymal transition. These hybrid cells have tumour-initiating potential and have been shown to have poor prognosis and resistance to therapy targeted for malignancies of breast epithelial origin. Our work emphasizes the need for new approaches to the diagnosis and therapy of this highly fatal breast cancer subtype.