Tuning optical properties of π-conjugated double nanohoops under external electric field stimuli-responsiveness.

Carbon nanorings have attracted substantial interest from synthetic chemists due to their unique topological structures and distinct physical properties. An intriguing π-conjugated double-nanoring structure, denoted as [8]CPP-[10]cyclacene, was constructed via the integration of [8]cycloparaphenylene ([8]CPP) into [10]cyclacene. Using the external electric field stimuli-responsiveness of [8]CPP-[10]cyclacene, directional charge transfer can be induced, resulting in the emergence of intriguing properties. The effects of the external electric field in three specific directions were explored, vertically in the [8]CPP unit (Fy), vertically in the [10]cyclacene unit (Fz), and horizontally along the double nanorings diameter (Fx). Interestingly, the external electric field vertically to the [10]cyclacene unit significantly enhanced the first hyperpolarizability (ßtot) compared to that vertically to the [8]CPP unit. Notably, [8]CPP-[10]cyclacene under Fx exhibited significantly larger the ßtot values (1.48 × 105 a.u.) than those of vertical Fy and Fz. This work opens up a wide range of nonlinear optics, making it a compelling area to explore in the field of carbon nanomaterials.

Efficacy of a membrane concentration method combined with real-time PCR for detection of Giardia and Cryptosporidium in drinking water.

The occurrence of Giardia and Cryptosporidium (oo)cysts in drinking source water poses a serious public health risk. Here, we established a method that combines membrane concentration and real-time polymerase chain reaction (PCR) to quantify Giardia and Cryptosporidium in drinking water. The water samples were filtered through a cellulose membrane to collect Giardia and Cryptosporidium, and then nucleic acids were extracted. Specific primers and probes were designed and synthesized according to the gph gene sequence of Giardia and 18S rRNA gene sequence of Cryptosporidium. The concentrations of the two targets were determined using real-time PCR technology. The sensitivity, specificity, and stability of the method were evaluated. Our findings revealed that the detection limits of real-time PCR method for detecting Giardia and Cryptosporidium were 0.926 and 0.65 copy/µL, respectively; the spiked recovery rates were above 60% and 38%, respectively, and relative standard deviations were under 0.95% and 2.26%, respectively. Therefore, this effective procedure based on the membrane concentration method and real-time PCR will be useful for detecting Giardia and Cryptosporidium in drinking water for purpose of continuous environmental monitoring.

Triclosan exposure induced disturbance of gut microbiota and exaggerated experimental colitis in mice.

BACKGROUND: Triclosan, an antimicrobial agent in personal care products, could be absorbed into the human body through the digestive tract. This animal experiment aimed to clarify the effects of triclosan exposure on the microbiome and intestinal immune functions in healthy and ulcerative colitis models. METHODS: Balb/c mice were maintained on an AIN-93G diet containing 80ppm triclosan dissolved in polyethylene as vehicle or vehicle alone for 1 week or 4 weeks. In the end, the mice were sacrificed, blood samples and colon tissues were collected for analysis of inflammation, and fecal samples were collected for 16 S rRNA sequencing of gut microbiota. To establish ulcerative colitis mice model, at the beginning of the 4th week, mice maintained on the diet with or without triclosan were treated with 2% Dextran sulfate sodium(DSS) in drinking water for 1 week. Then mice were sacrificed for analysis of colitis and gut microbiota. RESULTS: Triclosan exposure to common mice enhanced the levels of p-NF-κb and Toll-like receptor 4 (TLR4), and decreased the Occludin in the colon. Triclosan exposure to DSS-induced mice increased the level of inflammatory cytokines, reduced the levels of Occludin, and exacerbated the degree of damage to intestinal mucosa and crypt, infiltration of inflammatory cells and atypia of glandular cells. Low-grade intraepithelial neoplasia appeared. Both in common and DSS-induced mice, triclosan exposure changed the diversity and composition of gut microbiota. Fecal samples showed higher enrichment of sulfate-reducing bacteria and Bacteroides, and less butyrate-producing bacteria. CONCLUSION: Triclosan exposure induced disturbance of gut microbiota and exaggerated experimental colitis in mice. And changes in the composition of gut microbiota were characterized by the increase of harmful bacteria, including sulfate-reducing bacteria and Bacteroides, and the reduction of protective probiotics, butyrate-producing bacteria.

[Clinical Characteristics and Risk Factors of ESKAPE Pathogens Bloodstream Infection in Cancer Patients].

OBJECTIVE: To identify the risk factors of ESKAPE pathogens infection and related death in cancer patients, and to supply evidence for clinical precaution and diagnosis. METHODS: A retrospective study of clinical and experimental data of cancer patients with bloodstream infection were carried out in Sichuan Cancer Hospital from 2013 to 2018. The clinical feature, predisposing factors and risk factors of death in ESKAPE group and non-ESKAPE group were analyzed by univariate analysis and multivariate logistic regression. RESULTS: A total of 753 patients were enrolled in the study. Totally 795 pathogenic bacteria strains were isolated from blood culture and there were 278 ESKAPE strains, which took up 34.97% of isolated strains. Univariate analysis and multivariate logistic regression analysis showed that gender of male, multiple pathogens, history of exposure to enzyme inhibitors and agranulocytosis were independent risk factors of ESKAPE pathogens bloodstream infection. Peritoneal infection and combined fungal infection were independent risk factors of ESKAPE bloodstream infection related death. CONCLUSION: The bloodstream infection of ESKAPE pathogens is a problem worthy of clinical attention for cancer patients with neutrophil deficiency, previous antibiotic exposure, and fungal infection and peritoneal infection.

Formal Synthesis of (±)-Pentalenolactone A Methyl Ester.

We report the formal synthesis of (±)-pentalenolactone A methyl ester from simple 2-methoxyphenol. The key features of our route are as follows: a Diels-Alder reaction of masked o-benzoquinone to assemble the functionalized bicyclo[2.2.2]octenone, a continuous-flow oxa-di-π-methane rearrangement for building the diquinane core (AB ring), and an oxidative cleavage/oxidation sequence for annulation of the δ-lactone (C ring).

A vinylogous Michael addition-triggered quadruple cascade reaction for the enantioselective generation of multiple quaternary stereocenters.

An efficient organocatalytic quadruple cascade reaction resulting in spiroxindole scaffolds bearing five quaternary stereocenters is reported. The complex cascade reaction is triggered by the scarcely explored vinylogous Michael addition of 3-alkylidene oxindoles to fully substituted enones and demonstrates the usefulness of the latter as efficient Michael acceptors in generating complex caged products in 26-92% yields, 14-98% ee and up to >25 : 1 d.r. values.

RNA Protection is Effectively Achieved by Pullulan Film Formation.

RNA is a functionally versatile polymer but suffers from susceptibility to spontaneous and RNase-catalyzed degradation. This vulnerability makes it difficult to preserve RNA for extended periods of time, thus limiting its use in various contexts, including practical applications as functional nucleic acids. Here we present a simple method to preserve RNA by pullulan (a complex sugar produced by Aureobasidium pullulans fungus) film formation. This strategy can markedly suppress both spontaneous and RNase degradation. Importantly, the pullulan film readily dissolves in aqueous solution, thus allowing retrieval of fully functional RNA species. In order to illustrate the advantage of this protective method in a practical application, we engineered a simple paper sensor containing a bacteria-detecting RNA-cleaving DNAzyme. This detection capability of the device was unchanged after storage at room temperature for six months.

Investigating the mechanism of hepatocellular carcinoma progression by constructing genetic and epigenetic networks using NGS data identification and big database mining method.

The mechanisms leading to the development and progression of hepatocellular carcinoma (HCC) are complicated and regulated genetically and epigenetically. The recent advancement in high-throughput sequencing has facilitated investigations into the role of genetic and epigenetic regulations in hepatocarcinogenesis. Therefore, we used systems biology and big database mining to construct genetic and epigenetic networks (GENs) using the information about mRNA, miRNA, and methylation profiles of HCC patients. Our approach involves analyzing gene regulatory networks (GRNs), protein-protein networks (PPINs), and epigenetic networks at different stages of hepatocarcinogenesis. The core GENs, influencing each stage of HCC, were extracted via principal network projection (PNP). The pathways during different stages of HCC were compared. We observed that extracellular signals were further transduced to transcription factors (TFs), resulting in the aberrant regulation of their target genes, in turn inducing mechanisms that are responsible for HCC progression, including cell proliferation, anti-apoptosis, aberrant cell cycle, cell survival, and metastasis. We also selected potential multiple drugs specific to prominent epigenetic network markers of each stage of HCC: lestaurtinib, dinaciclib, and perifosine against the NTRK2, MYC, and AKT1 markers influencing HCC progression from stage I to stage II; celecoxib, axitinib, and vinblastine against the DDIT3, PDGFB, and JUN markers influencing HCC progression from stage II to stage III; and atiprimod, celastrol, and bortezomib against STAT3, IL1B, and NFKB1 markers influencing HCC progression from stage III to stage IV.

Auricularia auricular-judae polysaccharide attenuates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress and inflammation.

Auricularia auricular-judae polysaccharide (AAP) has shown a variety of pharmacological properties. In the present study, the role of AAP in acute lung injury (ALI) induced by lipopolysaccharide (LPS) was analyzed in rats to further explore the possible underlying mechanisms. Adult Sprague-Dawley rats were randomly assigned into the control, AAP, LPS and LPS plus AAP groups. Rats were injected with LPS (10 mg/kg, intraperitoneal) to induce ALI. Rats in the LPS plus AAP group were treated with AAP for 7 days before the induction of ALI. The protein concentration in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by the wet/dry (W/D) weight ratio. The myeloperoxidase (MPO) activity and malondialdehyde (MDA) level were assayed by MPO and MDA kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, were assayed by the enzyme-linked immunosorbent assay method. Pathological changes of lung tissues were observed by hematoxylin and eosin staining. The data showed that treatment with AAP significantly improved LPS-induced lung pathological changes, attenuated protein concentration in the BALF, inhibited MPO activity and reduced the MDA level and lung W/D weight ratio. AAP also inhibited the release of TNF-α and IL-6 in blood. The results indicated that AAP has a protective effect on LPS-induced ALI in rats.

Analysis of codon usage bias of mitochondrial genome in Bombyx mori and its relation to evolution.

BACKGROUND: Synonymous codon usage bias (SCUB) is an inevitable phenomenon in organismic taxa, generally referring to differences in the occurrence frequency of codons across different species or within the genome of the same species. SCUB happens in various degrees under pressure from nature selection, mutation bias and other factors in different ways. It also attaches great significance to gene expression and species evolution, however, a systematic investigation towards the codon usage in Bombyx mori (B. mori) has not been reported yet. Moreover, it is still indistinct about the reasons contributing to the bias or the relationship between the bias and the evolution of B. mori. RESULTS: The comparison of the codon usage pattern between the genomic DNA (gDNA) and the mitochondrial DNA (mtDNA) from B. mori suggests that mtDNA has a higher level of codon bias. Furthermore, the correspondence analysis suggests that natural selection, such as gene length, gene function and translational selection, dominates the codon preference of mtDNA, while the composition constraints for mutation bias only plays a minor role. Additionally, the clustering results of the silkworm superfamily suggest a lack of explicitness in the relationship between the codon usage of mitogenome and species evolution. CONCLUSIONS: Among the complicated influence factors leading to codon bias, natural selection is found to play a major role in shaping the high bias in the mtDNA of B. mori from our current data. Although the cluster analysis reveals that codon bias correlates little with the species evolution, furthermore, a detailed analysis of codon usage of mitogenome provides better insight into the evolutionary relationships in Lepidoptera. However, more new methods and data are needed to investigate the relationship between the mtDNA bias and evolution.

Pemetrexed is mildly active with good tolerability for treatment of patients with colorectal cancer.

PURPOSE: This systematic analysis was conducted to evaluate the efficacy and safety of pemetrexed based salvage chemotherapy for treatment of patients with metastatic colorectal cancer. METHODS: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with colorectal cancer were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. RESULTS: For pemetrexed based regimens, 4 clinical studies including 201 patients with advanced colorectal cancer were considered eligible for inclusion. The analysis suggested that, in all patients, pooled RR was 20.4% (41/201). Major adverse effects were neutropenia, anorexia, fatigue, and anemia. No treatment related death occurred with pemetrexed based treatment. CONCLUSION: This systematic analysis suggests that pemetrexed based regimens are associated with mild activity with good tolerability in treating patients with metastatic colorectal cancer.

Voice and emotion processing in the human neonatal brain.

Although the voice-sensitive neural system emerges very early in development, it has yet to be demonstrated whether the neonatal brain is sensitive to voice perception. We measured the EEG mismatch response (MMR) elicited by emotionally spoken syllables "dada" along with correspondingly synthesized nonvocal sounds, whose fundamental frequency contours were matched, in 98 full-term newborns aged 1-5 days. In Experiment 1, happy syllables relative to nonvocal sounds elicited an MMR lateralized to the right hemisphere. In Experiment 2, fearful syllables elicited stronger amplitudes than happy or neutral syllables, and this response had no sex differences. In Experiment 3, angry versus happy syllables elicited an MMR, although their corresponding nonvocal sounds did not. Here, we show that affective discrimination is selectively driven by voice processing per se rather than low-level acoustical features and that the cerebral specialization for human voice and emotion processing emerges over the right hemisphere during the first days of life.

Signaling kinase AMPK activates stress-promoted transcription via histone H2B phosphorylation.

The mammalian adenosine monophosphate-activated protein kinase (AMPK) is a serine-threonine kinase protein complex that is a central regulator of cellular energy homeostasis. However, the mechanisms by which AMPK mediates cellular responses to metabolic stress remain unclear. We found that AMPK activates transcription through direct association with chromatin and phosphorylation of histone H2B at serine 36. AMPK recruitment and H2B Ser36 phosphorylation colocalized within genes activated by AMPK-dependent pathways, both in promoters and in transcribed regions. Ectopic expression of H2B in which Ser36 was substituted by alanine reduced transcription and RNA polymerase II association to AMPK-dependent genes, and lowered cell survival in response to stress. Our results place AMPK-dependent H2B Ser36 phosphorylation in a direct transcriptional and chromatin regulatory pathway leading to cellular adaptation to stress.

Newborn screening for methylmalonic aciduria by tandem mass spectrometry: 7 years' experience from two centers in Taiwan.

BACKGROUND: The clinical course of methylmalonic aciduria (MMA) is fulminant in neonates and emergency management is necessary to save lives. It is therefore very important to differentiate affected from unaffected neonates immediately when there are abnormal results regarding MMA in newborn screening. METHODS: Between January 2002 and December 2008, 598,522 newborns were screened for MMA by 2 neonatal screening centers: the Chinese Foundation of Health and the Taipei Institute of Pathology. A total of 22 newborns were referred to confirmatory medical centers, and 7 were confirmed as having MMA. The initial propionylcarnitine (C3) level, C3/acetylcarnitine (C2) ratio, plasma ammonia, liver function tests, blood pH and bicarbonate were compared between the true-positive and false-positive groups. RESULTS: The C3/C2 ratio and plasma ammonia were markedly higher in the true-positive MMA group (p < 0.0001). Blood gas pH (p = 0.029), bicarbonate (p = 0.019), and aspartate aminotransferase (p = 0.005) also significantly differed between these 2 groups. CONCLUSION: Referred newborns with elevated plasma C3/C2 ratios > 0.4 or ammonia levels > 200 mg/dL should be highly suspected of having MMA.

Trans-2-phenylcyclopropylamine induces nerve cells apoptosis in zebrafish mediated by depression of LSD1 activity.

Trans-2-phenylcyclopropylamine (referred to as PCPA hereafter, also known as tranylcypromine and Parnate) is used clinically as an antidepressant. Here, we use a new model-zebrafish (Danio rerio) to study the molecular mechanisms of its adverse reactions in vivo. Following a PCPA exposure (75 microM), embryos showed "sluggish" action (slow swim and slow escape action). Whole mount in situ hybridization showed that sox1a and huc expressions were downregulated in PCPA-treated embryos, which indicated a decrease in the number of nerve cells. TUNEL assay diplayed that the drop of nerve cells number due to excessive apoptosis. Moreover, lysine-specific demethylase 1 morpholino injection (LSD1 MO) also induced increased cellular apoptosis in embryos just as PCPA. RT-PCR at 24hpf evaluated that the absence of LSD1 resulted in increased expression of two p53 target genes (p21 and bax2). These findings demonstrate for the first time that PCPA-induced apoptosis through inhibition of LSD1 demethylase activity and p53-dependent signaling pathway might be required for the maintenance of nerve cell apoptosis.

Three minimum wet thickness regions of slot die coating.

An experimental study was carried out to determine the minimum wet thickness of slot die coating for low-viscosity solutions. There exist three distinct coating regions (I, II, and III), depending on the physical properties of the coating fluid, die geometry, and flow conditions. A critical Reynolds number was found, below which viscous and surface tension effects are important. In Region I, the minimum wet thickness increases with increasing capillary number and becomes independent of capillary number in Region II. Region III exists above the critical Reynolds number where fluid inertia is dominant. In this region, the minimum wet thickness decreases as Reynolds number increases. Flow visualization on the coating bead reveals that the position of the downstream meniscus of the coating bead determines the types of coating region, whereas the shape and position of the upstream meniscus determine the type of coating defects. It was also observed that the downstream meniscus was not located at the die lip corner and both the static and dynamic contact angles varied under different conditions. These findings are critical for realistic theoretical study of slot die coating.

Harlequin ichthyosis: report of one case.

Harlequin ichthyosis (HI) is the most devastating form of skin disorder, which is inherited as autosomal recessive trait related to consanguineous marriage. Although prenatal examination has become scheduled and convenient throughout Taiwan, an unexpected case of HI in a male premature infant born at 32 weeks of gestation was presented. The parents were healthy, neither relatives nor having history of congenital abnormality. We report our management and the massive impact left on both parents. We believe this is an extremely rare case in Taiwan.

LKB1 is recruited to the p21/WAF1 promoter by p53 to mediate transcriptional activation.

The tumor suppressor LKB1 is an evolutionarily conserved serine/threonine kinase. In humans, LKB1 can be inactivated either by germ-line mutations resulting in Peutz-Jeghers syndrome or by somatic mutations causing predisposition to multiple sporadic cancers. LKB1 has wide-ranging functions involved in tumor suppression and cell homeostasis, including establishing cell polarity, setting energy metabolic balance (via phosphorylation of AMP-dependent kinase), regulating the cell cycle, and promoting apoptosis. LKB1 function was previously linked to the tumor suppressor p53 and shown to activate the p53 target gene p21/WAF1. In this study, we further investigated LKB1 activation of the p21/WAF1 gene and addressed whether LKB1 is directly involved at the gene promoter. We find that, consistent with previous studies, LKB1 stabilizes p53 in vivo, correlating with activation of p21/WAF1. We show that LKB1 physically associates with p53 in the nucleus and directly or indirectly phosphorylates p53 Ser15 (previously shown to be phosphorylated by AMP-dependent kinase) and p53 Ser392. Further, these two p53 residues are required for LKB1-dependent cell cycle G(1) arrest. Chromatin immunoprecipitation analyses show that LKB1 is recruited directly to the p21/WAF1 promoter, as well as to other p53 activated promoters, in a p53-dependent fashion. Finally, a genetic fusion of LKB1 to defective p53, deleted for its activation domains, promotes activation of p21/WAF1. These results indicate that LKB1 has a direct role in activation of p21/WAF1 gene.

Effect of a Siraitia grosvenori extract containing mogrosides on the cellular immune system of type 1 diabetes mellitus mice.

The purpose of this study was to observe the islet changes of pancreas in insulin-dependent diabetes mellitus (IDDM) mice in comparison to normal mice after application of an extract from Siraitia grosvenori fruits containing mogrosides, in particular, mogroside V. We hypothesized that mogroside extract (MG) attenuates the severity of alloxan-induced IDDM by effects on the immune system. Our data show that IDDM mice exhibited significant injury to pancreatic islets cells, which were atrophic. In addition, alloxan induced a notable increase in the expression of CD8+ lymphocytes to form a dramatic decrease in CD4+/CD8+ ratio (while CD4+ was unchanged). MG, administered to normal and experimental diabetic mice for 4 wk, effectively attenuated the early clinical symptoms, biochemical abnormalities, and pathological damages in pancreatic islets. Furthermore, at low dose, MG regulated the immune imbalance observed in alloxan-induced IDDM mice by up-regulating the CD4+ T-lymphocyte subsets and CD4/CD8 ratio, and altering the intracellular cytokine profiles. The expression of the pro-inflammatory Th1 cytokines: IFN-gamma, TNF-alpha in splenic lymphocytes was altered toward a beneficial Th2 pattern. MG therapy had no effect on normal mice, except that low dosage MG could up-regulate the IL-4 expression levels. The results revealed that MG exhibited antidiabetic effects presumably due to the presence of mogrosides.