Anti-Bladder-Tumor Effect of Baicalein from Scutellaria baicalensis Georgi and Its Application In Vivo

Some phytochemicals with the characteristics of cytotoxicity and/or antimetastasis have generated intense interest among the anticancer studies. In this study, a natural flavonoid baicalein was evaluated in bladder cancer in vitro and in vivo. Baicalein inhibits 5637 cell proliferation. It arrests cells in G1 phase at 100 μM and in S phase below 75 μM. The protein expression of cyclin B1 and cyclin D1 is reduced by baicalein. Baicalein-induced p-ERK plays a minor role in cyclin B1 reduction. Baicalein-inhibited p65NF-κB results in reduction of cell growth. Baicalein-induced pGSK(ser9) has a little effect in increasing cyclin B1/D1 expression instead. The translation inhibitor cycloheximide blocks baicalein-reduced cyclin B1, suggesting that the reduction is caused by protein synthesis inhibition. On the other hand, neither cycloheximide nor proteasome inhibitor MG132 completely blocks baicalein-reduced cyclin D1, suggesting that baicalein reduces cyclin D1 through protein synthesis inhibition and proteasomal degradation activation. In addition, baicalein also inhibits cell invasion by inhibiting MMP-2 and MMP-9 mRNA expression and activity. In mouse orthotopic bladder tumor model, baicalein slightly reduces tumor size but with some hepatic toxicity. In summary, these results demonstrate the anti-bladder-tumor properties of the natural compound baicalein which shows a slight anti-bladder-tumor effect in vivo

Intergeneration Transfer of Human Capital: Results from a Natural Experiment in Taiwan

We exploit a natural experiment to estimate the causal impact of parental education on educational outcomes of their children when they are high school seniors. In 1968, the Taiwanese government extended compulsory education from 6 to 9 years and opened over 150 new junior high schools at a differential rate among regions. We form treatment and control groups of women or men who were age 12 or under on the one hand and between the ages of 13 and 25 on the other hand in 1968. Within each region, we exploit variations across cohorts in new junior high school openings to construct an instrument for schooling. We employ this instrument to estimate the causal effects of mother’s and father’s schooling on their child’s college entrance examination test scores in the years 2000-2003, on the probability that the child attended college and on the rank of the college attended. The schooling of each parent does cause their child to experience better educational outcomes. A one-year increase in the schooling of either parent raises the probability that the child attends one of the top six colleges in Taiwan by approximately 10 percent.

Model-Free Adaptive Sensing and Control for a Piezoelectrically Actuated System

Since the piezoelectrically actuated system has nonlinear and time-varying behavior, it is difficult to establish an accurate dynamic model for a model-based sensing and control design. Here, a model-free adaptive sliding controller is proposed to improve the small travel and hysteresis defects of piezoelectrically actuated systems. This sensing and control strategy employs the functional approximation technique (FAT) to establish the unknown function for eliminating the model-based requirement of the sliding-mode control. The piezoelectrically actuated system’s nonlinear functions can be approximated by using the combination of a finite number of weighted Fourier series basis functions. The unknown weighted vector can be estimated by an updating rule. The important advantage of this approach is to achieve the sliding-mode controller design without the system dynamic model requirement. The update laws for the coefficients of the Fourier series functions are derived from a Lyapunov function to guarantee the control system stability. This proposed controller is implemented on a piezoelectrically actuated X-Y table. The dynamic experimental result of this proposed FAT controller is compared with that of a traditional model-based sliding-mode controller to show the performance improvement for the motion tracking performance

Genomic diversity of citrate fermentation in Klebsiella pneumoniae

<p>Abstract</p> <p>Background</p> <p>It has long been recognized that <it>Klebsiella pneumoniae </it>can grow anaerobically on citrate. Genes responsible for citrate fermentation of <it>K. pneumoniae </it>were known to be located in a 13-kb gene cluster on the chromosome. By whole genome comparison of the available <it>K. pneumoniae </it>sequences (MGH 78578, 342, and NTUH-K2044), however, we discovered that the fermentation gene cluster was present in MGH 78578 and 342, but absent in NTUH-K2044. In the present study, the previously unknown genome diversity of citrate fermentation among <it>K. pneumoniae </it>clinical isolates was investigated.</p> <p>Results</p> <p>Using a genomic microarray containing probe sequences from multiple <it>K. pneumoniae </it>strains, we investigated genetic diversity among <it>K. pneumoniae </it>clinical isolates and found that a genomic region containing the citrate fermentation genes was not universally present in all strains. We confirmed by PCR analysis that the gene cluster was detectable in about half of the strains tested. To demonstrate the metabolic function of the genomic region, anaerobic growth of <it>K. pneumoniae </it>in artificial urine medium (AUM) was examined for ten strains with different clinical histories and genomic backgrounds, and the citrate fermentation potential was found correlated with the genomic region. PCR detection of the genomic region yielded high positive rates among a variety of clinical isolates collected from urine, blood, wound infection, and pneumonia. Conserved genetic organizations in the vicinity of the citrate fermentation gene clusters among <it>K. pneumoniae</it>, <it>Salmonella enterica</it>, and <it>Escherichia coli </it>suggest that the13-kb genomic region were not independently acquired.</p> <p>Conclusion</p> <p>Not all, but nearly half of the <it>K. pneumoniae </it>clinical isolates carry the genes responsible for anaerobic growth on citrate. Genomic variation of citrate fermentation genes in <it>K. pneumoniae </it>may contribute to metabolic diversity and adaptation to variable nutrient conditions in different environments.</p

Caffeic acid phenethyl amide ameliorates ischemia/reperfusion injury and cardiac dysfunction in streptozotocin-induced diabetic rats

BACKGROUND: Caffeic acid phenethyl ester (CAPE) has been shown to protect the heart against ischemia/reperfusion (I/R) injury by various mechanisms including its antioxidant effect. In this study, we evaluated the protective effects of a CAPE analog with more structural stability in plasma, caffeic acid phenethyl amide (CAPA), on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats. METHODS: Type 1 diabetes mellitus was induced in Sprague–Dawley rats by a single intravenous injection of 60 mg/kg STZ. To produce the I/R injury, the left anterior descending coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. CAPA was pretreated intraperitoneally 30 minutes before reperfusion. An analog devoid of the antioxidant property of CAPA, dimethoxyl CAPA (dmCAPA), and a nitric oxide synthase (NOS) inhibitor (Nω-nitro-l-arginine methyl ester [l-NAME]) were used to evaluate the mechanism involved in the reduction of the infarct size following CAPA-treatment. Finally, the cardioprotective effect of chronic treatment of CAPA was analyzed in diabetic rats. RESULTS: Compared to the control group, CAPA administration (3 and 15 mg/kg) significantly reduced the myocardial infarct size after I/R, while dmCAPA (15 mg/kg) had no cardioprotective effect. Interestingly, pretreatment with a NOS inhibitor, (l-NAME, 3 mg/kg) eliminated the effect of CAPA on myocardial infarction. Additionally, a 4-week CAPA treatment (1 mg/kg, orally, once daily) started 4 weeks after STZ-induction could effectively decrease the infarct size and ameliorate the cardiac dysfunction by pressure-volume loop analysis in STZ-induced diabetic animals. CONCLUSIONS: CAPA, which is structurally similar to CAPE, exerts cardioprotective activity in I/R injury through its antioxidant property and by preserving nitric oxide levels. On the other hand, chronic CAPA treatment could also ameliorate cardiac dysfunction in diabetic animals

Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake

Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist

Ligand-Activated Peroxisome Proliferator-Activated Receptor- Protects Against Ischemic Cerebral Infarction and Neuronal Apoptosis by 14-3-3 Upregulation

Thiazolidinediones (TZD) were reported to protect against ischemia-reperfusion (I/R) injury. Their protective actions are considered to be PPAR-γ (peroxisome proliferator-activated receptor γ)-dependent. However, it is unclear how PPAR-γ activation confers resistance to I/R

FAST observations of an extremely active episode of FRB 20201124A: II. Energy Distribution

We report the properties of more than 800 bursts detected from the repeating fast radio burst (FRB) source FRB 20201124A with the Five-hundred-meter Aperture Spherical radio Telescope (FAST) during an extremely active episode on UTC September 25-28, 2021 in a series of four papers. In this second paper of the series, we mainly focus on the energy distribution of the detected bursts. The event rate initially increased exponentially but the source activity stopped within 24 hours after the 4th day. The detection of 542 bursts in one hour during the fourth day marked the highest event rate detected from one single FRB source so far. The bursts have complex structures in the time-frequency space. We find a double-peak distribution of the waiting time, which can be modeled with two log-normal functions peaking at 51.22 ms and 10.05 s, respectively. Compared with the emission from a previous active episode of the source detected with FAST, the second distribution peak time is smaller, suggesting that this peak is defined by the activity level of the source. We calculate the isotropic energy of the bursts using both a partial bandwidth and a full bandwidth and find that the energy distribution is not significantly changed. We find that an exponentially connected broken-power-law function can fit the cumulative burst energy distribution well, with the lower and higher-energy indices being $-1.22\pm0.01$ and $-4.27\pm0.23$, respectively. Assuming a radio radiative efficiency of $\eta_r = 10^{-4}$, the total isotropic energy of the bursts released during the four days when the source was active is already $3.9\times10^{46}$ erg, exceeding $\sim 23\%$ of the available magnetar dipolar magnetic energy. This challenges the magnetar models invoking an inefficient radio emission (e.g. synchrotron maser models).Comment: 26 pages, 7 figures, accepted for publication in Research in Astronomy and Astrophysic

The Apostasia genome and the evolution of orchids

Constituting approximately 10% of flowering plant species, orchids (Orchidaceae) display unique flower morphologies, possess an extraordinary diversity in lifestyle, and have successfully colonized almost every habitat on Earth(1-3). Here we report the draft genome sequence of Apostasia shenzhenica(4), a representative of one of two genera that form a sister lineage to the rest of the Orchidaceae, providing a reference for inferring the genome content and structure of the most recent common ancestor of all extant orchids and improving our understanding of their origins and evolution. In addition, we present transcriptome data for representatives of Vanilloideae, Cypripedioideae and Orchidoideae, and novel third-generation genome data for two species of Epidendroideae, covering all five orchid subfamilies. A. shenzhenica shows clear evidence of a whole-genome duplication, which is shared by all orchids and occurred shortly before their divergence. Comparisons between A. shenzhenica and other orchids and angiosperms also permitted the reconstruction of an ancestral orchid gene toolkit. We identify new gene families, gene family expansions and contractions, and changes within MADS-box gene classes, which control a diverse suite of developmental processes, during orchid evolution. This study sheds new light on the genetic mechanisms underpinning key orchid innovations, including the development of the labellum and gynostemium, pollinia, and seeds without endosperm, as well as the evolution of epiphytism; reveals relationships between the Orchidaceae subfamilies; and helps clarify the evolutionary history of orchids within the angiosperms