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Living systems can generate an enormous range of cellular functions, from mechanical infrastructure and signalling networks to enzymatic catalysis and information storage, using a notably limited set of chemical functional groups. This observation is especially notable when compared to the breadth of functional groups used as the basis for similar functions in synthetically derived small molecules and materials. The relatively small cross-section between biological and synthetic reactivity space forms the foundation for the development of bioorthogonal chemistry, in which the absence of a pair of reactive functional groups within the cell allows for a selective in situ reaction 1 – 4 . However, biologically ‘rare’ functional groups, such as the fluoro 5 , chloro 6 , 7 , bromo 7 , 8 , phosphonate 9 , enediyne 10 , 11 , cyano 12 , diazo 13 , alkene 14 and alkyne 15 – 17 groups, continue to be discovered in natural products made by plants, fungi and microorganisms, which offers a potential route to genetically encode the endogenous biosynthesis of bioorthogonal reagents within living organisms. In particular, the terminal alkyne has found broad utility via the Cu( i )-catalysed azide-alkyne cycloaddition ‘click’ reaction 18 . Here we report the discovery and characterization of a unique pathway to produce a terminal alkyne-containing amino acid in the bacterium Streptomyces cattleya . We found that l -lysine undergoes an unexpected reaction sequence that includes halogenation, oxidative C–C bond cleavage and triple bond formation through a putative allene intermediate. This pathway offers the potential for de novo cellular production of halo-, alkene- and alkyne-labelled proteins and natural products from glucose for a variety of downstream applications. Microbial generation of a terminal-alkyne-containing amino acid can be encoded into E. coli and provides the potential for in vivo generation of proteins and natural products for click chemistry.

Though the early integration of mesenchymal stem cells (MSCs) into tumor-associated stroma of cancer has been demonstrated, the functional contributions and underlying mechanisms of these cells to tumor growth and angiogenesis remain to be clarified. Using a xenograft model, human colorectal cancer cells, MSCs, and their cell mixture were introduced to a subcutaneous site of immunodeficient mice. The tumor growth rate and angiogenesis of each transplantation was then compared. We demonstrate that a variety of colorectal cancer cells, when mixed with otherwise non-tumorigenic MSCs, increase the tumor growth rate and angiogenesis more than that when mixed with carcinoma-associated fibroblasts or normal colonic fibroblasts. The secretion of interleukin-6 (IL-6) from MSCs increases the secretion of endothelin-1 (ET-1) in cancer cells, which induces the activation of Akt and ERK in endothelial cells, thereby enhancing their capacities for recruitment and angiogenesis to tumor. The IL-6/ET-1/Akt or ERK pathway of tumor-stroma interaction can be targeted by an antibody against IL-6 or Lentiviral-mediated RNAi against IL-6 in MSCs, by inhibition or knockdown of ET-1 in cancer cells, or by inhibition of ERK and Akt in host endothelial cells. These demonstrate that attempts to interrupt the interaction of MSCs and cancer cells help to abrogate angiogenesis and inhibit tumor growth in tumors formed by cancer cells admixed with MSCs. These data demonstrate that the tumor microenvironment, namely, MSCs-secreted IL-6, may enrich the proangiognic factors secreted by cancer cells to increase angiogenesis and tumor growth and that targeting this interaction may lead to novel therapeutic and preventive strategies.

In winter, a branch of the China Coastal Current can turn in the Taiwan Strait to join the poleward-flowing Taiwan Coastal Current. The associated cross-strait flows have been inferred from hydrographic and satellite data, from observed abundances off northwestern Taiwan of cold-water copepod species Calanus sinicus and, in late March of 2012, also from debris found along the northwestern shore of Taiwan of a ship that broke two weeks earlier off the coast of China. The dynamics related to such cross flows have not been previously explained and are the focus of this study using analytical and numerical models. It is shown that the strait’s currents can be classified into three regimes depending on the strength of the winter monsoon: equatorward (poleward) for northeasterly winds stronger (weaker) than an upper (lower) bound and cross-strait flows for relaxing northeasterly winds between the two bounds. These regimes are related to the formation of the stationary Rossby wave over the Changyun Ridge off midwestern Taiwan. In the weak (strong) northeasterly wind regime, a weak (no) wave is produced. In the relaxing wind regime, cross-strait currents are triggered by an imbalance between the pressure gradient and wind and are amplified by the finite-amplitude meander downstream of the ridge where a strong cyclone develops.

Fast radio bursts (FRBs) are immensely energetic millisecond-duration radio pulses. Observations indicate that nearby FRBs can be produced by old stellar populations, as suggested by the localization of the repeating source FRB 20200120E in a globular cluster of M81. Nevertheless, the burst energies of FRB 20200120E are significantly smaller than those of other cosmological FRBs. Here, we report the detection of a bright burst from FRB 20200120E in 1.1 – 1.7 GHz, with a fluence of approximately 30 Jy ms, which is more than 42 times larger than the previously detected bursts near 1.4 GHz frequency. It reaches one-third of the energy of the weakest burst from FRB 20121102A and is detectable at a distance exceeding 200 Mpc. Our finding bridges the gap between nearby and cosmological FRBs and indicates that FRBs hosted in globular clusters can be bright enough to be observable at cosmological distances. Repeating fast radio burst, FRB 20200120E, has been localized to a globular cluster M81. Here, the authors show detection of a burst from FRB 20200120E that is 42 times stronger than the previously detected bursts.

Electrocaloric effect is presently under active investigation owing to both the recent discoveries of giant electrocaloric effects and its potential for solid state cooling applications. We use first-principles-based direct simulations to predict the electrocaloric temperature change in ferroelectric ultrathin nanowires. Our findings suggest that in nanowires with axial polarization direction the maximum electrocaloric response is reduced when compared to bulk, while the room temperature electrocaloric properties can be enhanced by tuning the ferroelectric transition temperature. The potential of ferroelectric nanowires for electrocaloric cooling applications is discussed.

Recent studies suggest that some serous ovarian carcinomas (SOCs) arise from the fallopian tube (FT) epithelium rather than the ovarian surface epithelium. This hypothesis places emphasis on the FT secretory epithelial cell as a cell-of-origin. Herein, we report the development of a novel ex vivo primary human FT epithelium culture system that faithfully recapitulates the in vivo epithelium, as shown by morphological, ultrastructural and immunophenotypic analyses. Mass spectrometry-based proteomics reveal that these cultures secrete proteins previously identified as biomarkers for ovarian cancer. We also use this culture system to study the response of the FT epithelium to genotoxic stress and find that the secretory cells exhibit a distinct response to DNA damage when compared with neighboring ciliated cells. The secretory cells show a limited ability to resolve the damage over time, potentially leaving them more susceptible to accumulation of additional mutagenic injury. This divergent response is confirmed with in situ studies using tissue samples, further supporting the use of this ex vivo culture system to investigate FT epithelial pathobiology. We anticipate that this novel culture system will facilitate the study of SOC pathogenesis, and propose that similar culture systems could be developed for other organ site-specific epithelia.

Thermally derived carbon fractions including organic carbon (OC) and elemental carbon (EC) have been reported for the U.S. Interagency Monitoring of PROtected Visual Environments (IMPROVE) network since 1987 and have been found useful in source apportionment studies and to evaluate quartz-fiber filter adsorption of organic vapors. The IMPROVE_A temperature protocol defines temperature plateaus for thermally derived carbon fractions of 140 °C for OC1, 280 °C for OC2, 480 °C for OC3, and 580 °C for OC4 in a helium (He) carrier gas and 580 °C for EC1, 740 °C for EC2, and 840 °C for EC3 in a 98% He/2% oxygen (O 2 ) carrier gas. These temperatures differ from those used previously because new hardware used for the IMPROVE thermal/optical reflectance (IMPROVE_TOR) protocol better represents the sample temperature than did the old hardware. A newly developed temperature calibration method demonstrates that these temperatures better represent sample temperatures in the older units used to quantify IMPROVE carbon fractions from 1987 through 2004. Only the thermal fractions are affected by changes in temperature. The OC and EC by TOR are insensitive to the change in temperature protocol, and therefore the long-term consistency of the IMPROVE database is conserved. A method to detect small quantities of O 2 in the pure He carrier gas shows that O 2 levels above 100 ppmv also affect the comparability of thermal carbon fractions but have little effect on the IMPROVE_TOR split between OC and EC.

•Using the Royal Free Hospital-Nutrition Prioritizing Tool (RFH-NPT), one in three patients with cirrhosis was at risk of malnutrition (ARMN).•Compared with the Malnutrition Universal Screening Tool (MUST), the RFH-NPT could identify more patients who were at risk of malnutrition, especially among patients with fluid overload.•The incidence of hospital admission was higher in ARMN patients identified by RFH-NPT compared with MUST. [Display omitted] Malnutrition is common among inpatients with cirrhosis. However, data on the prevalence of malnutrition among stable ambulatory patients with cirrhosis is lacking. We sought to investigate the prevalence of patents at risk of malnutrition (ARMN) among ambulatory patients with cirrhosis using the Royal Free Hospital-Nutrition Prioritizing Tool (RFH-NPT) and the Malnutrition Universal Screening Tool (MUST) and compare their correlation to clinical outcomes. Patients attending an outpatient liver cirrhosis clinic at a tertiary hospital were screened for ARMN using both the RFH-NPT and MUST (defined by a score of ≥2 for either tool). Differences in clinical outcomes after 6 mo were compared. There were 134 patients recruited. The RFH-NPT identified more ARMN patients compared with MUST (32.8% versus 8.2%; P < 0.01; Cohen κ, 0.27 [95% CI, 0.12-0.42]; P < 0.001). Fluid overload at recruitment was the only independent predictor of disagreement between the RFH-NPT and MUST (odds ratio [OR], 43.14; 95% CI, 8.70-214.00; P < 0.001). There was a trend toward an increased risk of mortality for ARMN patients by the RFH-NPT (hazard ratio, 3.58; 95% CI, 0.81-15.83; P = 0.06) but not by the MUST (P = 0.62). The incidence of hospital admissions in ARMN patients was higher by the RFH-NPT, with an incidence rate ratio of 13.27 (95% CI, 5.11-43.70; P < 0.001), but not in ARMN patients by the MUST (P = 0.85). Being ARMN by the RFH-NPT was the only independent predictor of hospital admissions (OR, 15.08; 95% CI, 2.47-91.98; P = 0.003). The RFH-NPT identified more ARMN patients when compared with the MUST, especially among patients with fluid overload. Patients at risk of malnutrition were at an increased risk of hospital admissions and possibly death.

AbstractBackgroundThe Physical Resilience Instrument for Older Adults (PRIFOR) is a questionnaire for assessing physical resilience in older adults suffering from acute health stressors. Prior psychometric evidence of the PRIFOR showed that it has good criterion-related validity, known-group validity, predictive validity, and internal consistency. However, it is unclear whether the PRIFOR can be replicated in older adults suffering after surgical treatment. ObjectivesThis study aimed at evaluating whether the three-factor structure of the PRIFOR can be replicated in older adults suffering after surgical treatment. Moreover, the concurrent validity of the PRIFOR was examined using the association between the PRIFOR and measures of depression, cognition, activities of daily living, and frailty. Design and SettingA longitudinal study was adopted in a tertiary-care medical center in Taiwan. ParticipantsA total of 207 patients aged 65 years old and older who underwent surgery and if they were able to communicate independently. Measurements: The PRIFOR, the 5-item Geriatric Depression Scale, the Short Portable Mental Status Questionnaire, the Katz Index of Independence in Activities of Daily Living and Clinical Frailty Scale were all assessed after surgery. ResultsThe three-factor structure (positive thinking, cope and adjust lifestyle, and belief and hopeful mindset) was supported by the CFA results in the present sample. In addition, the PRIFOR showed good concurrent validity with depression (r = −0.470 to −0.542), cognition (r = 0.358 to 0.409), activities of daily living (r = 0.209 to 0.310), and frailty (r =−0.161 to −0.237). ConclusionThe PRIFOR can be recommended to measure physical resilience in older adults suffering after surgical treatment. For the adequate estimation of older adults' level of physical resilience postoperatively and to guide the implementation of individualized interventions, it is important to provide appropriate care for older adults to recover after surgery.

Strong sea surface temperature fronts in open seas are known to affect the atmosphere. Shelf-sea fronts in winter have comparable strengths, yet their impacts on winds have not been studied. In January of 2012, a persistent, narrow band of cloud stretching 600–1,000 km was observed along the front of East China Sea (ECS). Numerical and analytical models show that the cloud was formed atop a recirculating cell induced by the front and, more generally, that β-plumes of low and high pressures emanate and spread far from fronts. Consistent with the theory, observations show that in ECS at inter-annual time scales, strong fronts co-vary with on-shelf convergent wind, strong northeasterly monsoon, and alongshelf alignment of clouds with low clouds near the coast and higher clouds offshore. Our results suggest that shelf-sea fronts are potentially an important dynamic determinant of climate variability of East Asia.