Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established ...intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase 'WalK' (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resulted in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. The molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.
A custom single‐wall carbon nanotube (SWCNT)‐modulated separator is employed to directly suppress the polysulfide migration and indirectly protect the lithium‐metal anode from severe polysulfide ...contamination. The conductive sp2‐carbon scaffold continuously reactivates and reutilizes the trapped active material, so the SWCNT‐modulated separator provides a facile way to facilitate the implementation of pure sulfur cathodes with high sulfur contents and loadings.
A novel approach to the measurement of microwave frequency based on optical power monitoring is proposed and demonstrated. The microwave signal with its frequency to be measured is modulated on two ...optical carriers with their wavelengths set at one peak and one valley of the spectral response of a sinusoidal filter. The modulation is performed by a Mach-Zehnder modulator that is biased to suppress the optical carriers. A mathematical expression relating the optical powers from the two wavelength channels and the microwave frequency to be measured is developed. By simply monitoring the optical powers at the outputs of the two wavelength channels, the microwave frequency can be evaluated. A proof-of-concept experiment is implemented. Frequency measurement with good accuracy for microwave signals at different power levels is realized.
Apramycin is a clinically promising aminoglycoside antibiotic (AGA). To date, mechanisms underlying the biosynthesis and self‐resistance of apramycin remain largely unknown. Here we report that ...apramycin biosynthesis proceeds through unexpected phosphorylation, deacetylation, and dephosphorylation steps, in which a novel aminoglycoside phosphotransferase (AprU), a putative creatinine amidohydrolase (AprP), and an alkaline phosphatase (AprZ) are involved. Biochemical characterization revealed that AprU specifically phosphorylates 5‐OH of a pseudotrisaccharide intermediate, whose N‐7′ acetyl group is subsequently hydrolyzed by AprP. AprZ is located extracellularly where it removes the phosphate group from a pseudotetrasaccharide intermediate, leading to the maturation of apramycin. Intriguingly, 7′‐N‐acetylated and 5‐O‐phosphorylated apramycin that were accumulated in ΔaprU and ΔaprZ respectively exhibited significantly reduced antibacterial activities, implying Streptomyces tenebrarius employs C‐5 phosphorylation and N‐7′ acetylation as two strategies to avoid auto‐toxicity. Significantly, this study provides insight into the design of new generation AGAs to circumvent the emergence of drug‐resistant pathogens.
Two cryptic self‐resistance mechanisms involving C‐5 phosphorylation and N‐7′ acetylation were discovered in Streptomyces tenebrarius to avoid auto‐toxicity during apramycin biosynthesis. Characterization of the corresponding enzymes revealed the apramycin's assembly line at the pseudotrisaccharide stage.
After a violent earthquake, the supply of medical services may fall short of the rising demand, leading to overcrowding in hospitals, and, consequently, a collapse in the healthcare system. This ...paper takes the emergency care system in Taiwan as the research context, where first-aid hospitals are ranked to three levels, advanced, intermediate, and general, and, currently, emphasizes on a general emergency responsibility hospital. Having limited capacity and capability, a general emergency responsibility hospital treats minor and moderate injuries, from which the majority of earthquake-induced casualties suffer. The purpose of this study is to analyze the impact of this group of earthquake-induced non-urgent patients on the performance of a hospital. A patient flow model was built to represent patients' paths throughout emergency care. Based on the model, discrete event simulation was applied to simulate patients' trajectories and states of a hospital under four seismic scenarios, where patient visits are 1.4, 1.6, 1.9, and 2.3 times the normal number. A healthcare performance index, Crowdedness Index (CI), is proposed to measure crowdedness on a daily basis, which is defined as the ratio of the average waiting time for treatment to the recommended maximal waiting time. Results of simulations rendered the establishment of empirical equations, describing the relation between the maximum CIs and the patient growth ratios. In the most severe case in this study, the maximum CI exceeds 92 and it takes 10 days to recover from the quality drop. This highlights the problem a general emergency responsibility hospital may encounter if no emergency response measure is implemented. Findings are provided pertaining to the predication of a recovery curve and the alarming level of patient increase, which are supportive information for preparedness planning as well as response measure formulation to improve resilience.
Licorice is an herbal plant named for its unique sweet flavor. It is widely used in the food and tobacco industries as a sweetener. Licorice is also used in traditional Chinese medicine (TCM) and ...complementary medicine. Because the use of licorice has long been a part of TCM, the details of its therapeutic applications have been thoroughly established. In modern science, licorice is of interest because of its broad range of applications. Extracts of and compounds isolated from licorice have been well studied and biologically characterized. In this review, we discuss the nutraceutical and functional activities of licorice as well as those of the extracts of and the isolated compounds from licorice, including agents with anti-inflammatory activity, cell-protective abilities, and chemopreventive effects. The side effects of licorice are also enumerated. A comparison of the activities of licorice described by modern science and TCM is also presented, revealing the correspondence of certain characteristics.
In recent years, glycative stress from exogenous or endogenous advanced glycation end products (AGEs) and highly reactive dicarbonyls has gained great attention for its putative effects on cancer ...development. AGEs are a group of compounds formed from the complex chemical reaction of reducing sugars with compounds containing an amino group. AGEs bind to and activate the receptor for AGEs (RAGE), which is a predominant modulator of inflammation‐associated cancer, and AGEs induce reactive oxygen species that are an important regulator of the hallmarks of cancer. Dicarbonyls, which are formed during glycolysis, lipid oxidation, or protein degradation, include glyoxal, methylglyoxal, and 3‐deoxyglucosone and are regarded as major precursors of AGEs. These dicarbonyls not only fuel the AGE pool in living organisms but also evoke carbonyl stress, which may contribute to the carbonylative damage of carbohydrates, lipids, proteins, or DNA. Carbonylative damage then leads to many lesions, some of which are implicated in the pathogenesis of cancer. In this review, studies regarding the effects of AGEs and dicarbonyls on cancer onset or progression are systematically discussed, and the utilization of AGE inhibitors and dicarbonyl scavengers in cancer therapy are noted.
The scheme of AGEs, dicarbonyls, ROS, and inflammation in cancer onset and progression. Exogenous and endogenous AGEs/dicarbonyls induce bursts of ROS and create a chronic inflammatory state. In such conditions, AGEs, dicarbonyls, ROS and pro‐inflammatory mediators interact in a positive feedback loop, leading to cancer onset or the enhancement of cancer progression.
In this paper, a novel technique to realize frequency quadrupling and upconversion in a radio over fiber (RoF) link is proposed and experimentally demonstrated. The frequency quadrupling is achieved ...by using two cascaded Mach-Zehnder modulators (MZMs) that are biased at the minimum transmission point, with a tunable optical delay line placed between the MZMs. By properly adjusting the time delay between the two MZMs, a pair of optical wavelengths with a wavelength spacing corresponding to four times the frequency of the microwave drive signal is generated. The two wavelengths are then sent to a third MZM to which an intermediate-frequency (IF) signal is applied. At the output of the third MZM, a frequency-upconverted signal at the millimeter-wave (mm-wave) band is obtained. The advantages of the technique are that a relatively low-frequency local oscillator (LO) signal is used to generate a high-frequency LO signal and the upconverted signal is more tolerant to the dispersion-induced power fading compared with a conventional RoF link based on double-sideband (DSB) modulation. Experiments are performed to verify the technique.
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