High power optical frequency comb with 10-19 frequency instability.

Optical frequency combs with more than 10 W have paved the way for extreme ultraviolet combs generation by interaction with inert gases, leading to extreme nonlinear spectroscopy and the ultraviolet nuclear clock. Recently, the demand for an ultra-long-distance time and frequency space transfer via optical dual-comb proposes a new challenge for high power frequency comb in respect of power scaling and optical frequency stability. Here we present a frequency comb based on fiber chirped pulse amplification (CPA), which can offer more than 20 W output power. We further characterize the amplifier branch noise contribution by comparing two methods of locking to an optical reference and measure the out-of-loop frequency instability by heterodyning two identical high-power combs. Thanks to the low noise CPA, reasonable locking method, and optical path-controlled amplifiers, the out-of-loop beat note between two combs demonstrates the unprecedented frequency stability of 4.35 × 10-17 at 1s and 6.54 × 10-19 at 1000 s.

Mixed-Valence CuI /CuIII Metal-Organic Frameworks with Non-innocent Ligand for Multielectron Transfer.

We report two novel three-dimensional copper-benzoquinoid metal-organic frameworks (MOFs), [Cu4 L3 ]n and [Cu4 L3 ⋅ Cu(iq)3 ]n (LH4 =1,4-dicyano-2,3,5,6-tetrahydroxybenzene, iq=isoquinoline). Spectroscopic techniques and computational studies reveal the unprecedented mixed valency in MOFs, formal Cu(I)/Cu(III). This is the first time that formally Cu(III) species are witnessed in metal-organic extended solids. The coordination between the mixed-valence metal and redox-non-innocent ligand L, which promotes through-bond charge transfer between Cu metal sites, allows better metal-ligand orbital overlap of the d-π conjugation, leading to strong long-range delocalization and semiconducting behavior. Our findings highlight the significance of the unique mixed valency between formal Cu(I) and highly-covalent Cu(III), non-innocent ligand, and pore environments of these bench stable Cu(III)-containing frameworks on multielectron transfer and electrochemical properties.

Role of Azole Drugs in Promoting Fungal Cell Autophagy Revealed by an NIR Fluorescence-Based Theranostic Probe.

Autophagy, a widespread degradation system in eukaryotes, plays an important role in maintaining the homeostasis of the cellular environment and the recycling of substances. Optical probes for the tracking of autophagy can be used as an effective tool not only to visualize the autophagy process but also to study autophagy-targeted drugs. Various molecule probes for autophagy of cancer cells emerge but are very limited for that of fungal cells, resulting in the lack of research on antifungal drugs targeting autophagy. To address this issue, we report an azole NIR fluorescence-based theranostic probe AF-1 with antifungal activity that is sensitive to autophagy-associated pH. The unique design of this probe lies in the introduction of both the pH-sensitive fluorophore with a detection range matching the pH range of the autophagy process and the conserved core structural fragment of azole drugs, providing a strategy to investigate the relationship between antifungal drug action and autophagy. As such, AF-1 exhibited excellent spectral properties and was found to target and induce the autophagy of the fungal cell membrane while maintaining moderate antifungal activity. Of note, using this theranostic probe as both a dye and drug, the autophagy process of fungi was visualized in a ratiometric manner, revealing the role of azole antifungal drugs in promoting autophagy to induce fungal cell apoptosis.

High energy widely tunable narrow-linewidth Ti:sapphire laser using combined-cavity configuration.

A high-energy narrow-linewidth Ti:sapphire laser with widely tunable wavelength was investigated. The Littman cavity was seeded by an extended prism cavity, and they were coupled together by sharing a partial reflection mirror. The widely wavelength tunability of the prism cavity and the linewidth compression of Littman cavity were incorporated together, which resulted in a significantly increased tunable wavelength range from 720 nm to 884 nm with linewidth of less than 100 MHz. The coupling effect and the synchronization between the two cavities in temporal and spectral domain were discussed. The narrow-linewidth laser centered at 786 nm was further amplified to 36 mJ and frequency-doubled to 393 nm with pulse energy of 18.8 mJ while maintaining the narrow linewidth at a repetition rate of 10 Hz. This widely tunable narrow-linewidth laser is a promising light source for high-resolution fluorescence spectroscopy.

Power-scalable thin-disk Ti:sapphire laser amplifier.

We experimentally demonstrate a 38-fs chirped-pulse amplified (CPA) Ti:sapphire laser system based on the power-scalable thin-disk scheme with an average output power of 1.45 W at a repetition rate of 1 kHz, corresponding to peak power of 38 GW. The beam profile close to the diffraction limit with a measured M2 value of approximately 1.1 is obtained. It demonstrates the potential for an ultra-intense laser with high beam quality compared with the conventional bulk gain amplifier. To the best of our knowledge, this is the first reported Ti:sapphire regenerative amplifier based on the thin-disk approach reaching 1 kHz.

Lightweight, Low-Cost Co2SiO4@diatomite Core-Shell Composite Material for High-Efficiency Microwave Absorption.

The porous and biomimetic cobalt silicate@diatomite (Co2SiO4@diatomite) was successfully synthesized by a two-step method, including the hydrothermal method and calcination to improve the electromagnetic wave absorption property. Different hydrothermal times were well-tuned for Co2SiO4@diatomite composites with different loadings of Co2SiO4. Interestingly, the Co2SiO4@diatomite composites (6 h, 25 wt%) had a smaller minimum reflection loss. Moreover, the minimum reflection loss (RLmin) could reach -12.03 dB at 16.64 GHz and the matched absorber thickness was 10 mm, while the effective absorption bandwidth (EAB, RL ≤ -10 dB) could be 1.92 GHz. In principle, such findings indicate that Co2SiO4@diatomite nanocomposites could be a promising candidate for high-efficiency microwave absorption capability.

The efficacy of anti-EGFR therapy in treating metastatic colorectal cancer differs between the middle/low rectum and the left-sided colon.

BACKGROUND: Clinically, metastatic rectal cancer has been considered a subset of left-sided colon cancer. However, heterogeneity has been proposed to exist between high and middle/low rectal cancers. We aimed to examine the efficacy of anti-epidermal growth factor receptor (EGFR) treatment for middle/low rectal and left-sided colon cancers. METHODS: This study enrolled 609 patients with metastatic colorectal cancer who were treated with anti-EGFR therapy. They were divided into groups based on primary tumour locations: the right-sided colon, the left-sided colon or the middle/low rectum. The efficacy of first-line and non-first-line anti-EGFR treatment was analysed. Genomic differences in colorectal cancer data from The Cancer Genome Atlas (TCGA) were investigated and visualised with OncoPrint and a clustered heatmap. RESULTS: On first-line anti-EGFR treatment, patients with middle/low rectal tumours had significantly lower progression-free survival, overall survival, and overall response rates (6.8 months, 27.8 months and 43%, respectively) than those with left-sided colon cancer (10.1 months, 38.3 months and 66%, respectively). Similar outcomes were also identified on non-first-line anti-EGFR treatment. In TCGA analysis, rectal tumours displayed genetic heterogeneity and shared features with both left- and right-sided colon cancer. CONCLUSIONS: Anti-EGFR treatment has lower efficacy in metastatic middle/low rectal cancer than in left-sided colon cancer.

Double-pass pre-chirp managed amplification with high gain and high average power.

We demonstrate, to the best of our knowledge, the first double-pass pre-chirp managed fiber amplifier. The double-pass fiber amplifier exhibits high gain allowing us to amplify chirped picosecond pulses from 20 mW to 113 W in a rod-type Yb-fiber corresponding to 38 dB gain. We study the dependence of static mode degradation (SMD) on the nonlinear phase shift (NPS) accumulated by the amplified pulse. Our results indicate that a larger nonlinear phase shift results in stronger nonlinear polarization evolution of the fundamental mode and leads to a lower threshold for SMD. After optimization, our pre-chirp managed amplifier seeded by 80 mW pulses delivers 102 W amplified power from the main output. The amplified pulses are compressed to 37 (55) fs with 90 (100) W average power by a grating pair (chirped mirrors). The double-pass configuration significantly simplifies the implementation of pre-chirp managed fiber amplifiers leading to an extremely compact system.

Screening silica-confined single-atom catalysts for nonoxidative conversion of methane.

The development of a single-atom iron catalyst (Fe©SiO2) for the direct conversion of methane to olefins, aromatics, and hydrogen is a breakthrough in the field of nonoxidative conversion of methane (NCM). However, the optimization of the catalyst remains desirable for industrial applications. Herein, 25 transition metals, including Sc, Ti, V, Cr, Mn, Co, Ni, Cu, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Hf, Ta, W, Re, Os, Ir, Pt, and Au, are selected to replace the central Fe atom for screening out better single-atom catalysts for the NCM. Using the performance on the activation of methane, such as the adsorption energy of methane, the dissociation energy, and the barrier of methane as the screening descriptors, Mn©SiO2, Fe©SiO2, W©SiO2, and Re©SiO2 are first screened out. The remarkable performance of the four catalysts on methane activation is attributed to the unique geometric structure and the dz 2 orbitals of the central metal crossing over the Fermi level, which can benefit the interaction between methane and the catalysts. By considering the catalytic performance on the whole pathway of methane to ethylene, W©SiO2 is finally selected as the most active catalyst for the NCM, which has the lowest rate-determining barrier of 1.62 eV and the smallest free energy span (1.06 eV) of the overall catalytic cycle.

Altered sensory nerve excitability in fibromyalgia.

BACKGROUND/PURPOSE: To investigate nerve excitability changes in patients with fibromyalgia and the correlation with clinical severity. METHODS: We enrolled 20 subjects with fibromyalgia and 22 sex and age-matched healthy subjects to receive nerve excitability test and nerve conduction study to evaluate the peripheral axonal function. RESULTS: In the fibromyalgia cohort, the sensory axonal excitability test revealed increased superexcitability (%) (P = 0.029) compared to healthy control. Correlational study showed a negative correlation between increased subexcitability (%) (r = -0.534, P = 0.022) with fibromyalgia impact questionnaire (FIQ) score. Computer modeling confirmed that the sensory axon excitability pattern we observed in fibromyalgia cohort was best explained by increased Barrett-Barrett conductance, which was thought to be attributed to paranodal fast K+ channel dysfunction. CONCLUSION: The present study revealed that paranodal sensory K+ conductance was altered in patients with fibromyalgia. The altered conductance indicated dysfunction of paranodal fast K+ channels, which is known to be associated with the generation of pain.

Real-world evidence of the safety and effectiveness of regorafenib in Taiwanese patients with metastatic colorectal cancer: CORRELATE Taiwan.

BACKGROUND/PURPOSE: This analysis reports safety and effectiveness data from the Taiwanese cohort of the CORRELATE study. METHODS: CORRELATE was a prospective, observational study to assess the safety and effectiveness of regorafenib for the treatment of metastatic colorectal cancer (CRC) in real-world clinical practice that was conducted in 13 different countries in Asia, Europe and Latin America. The primary endpoint of the study was incidence of all treatment-emergent AEs (TEAEs), and secondary endpoints included overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). RESULTS: The global study population (N = 1037) included 128 Taiwanese patients with a median age of 64 years, median weight of 62.02 kg and 66.41% were male. Reduced initiating doses of regorafenib and dose interruptions were common in Taiwanese patients (71.87% and 50.00%, respectively). The safety profile of regorafenib was consistent with that seen in Asian patients in the clinical development trials, including the CORRECT and CONCUR studies, with hand-foot-skin reactions (HFSR) of any grade occurring in 33.59% of patients. Median OS was 11.64 months in the Taiwanese patients (95% confidence interval [CI], 8.36-13.82) and median PFS was 2.17 months (95% CI, 1.97-2.89). CONCLUSION: The safety and effectiveness of regorafenib in this real-world study was generally consistent with the known efficacy and safety profile in Asian patients in clinical trials. TRIAL REGISTRATION: NCT02042144.

Insulin-Like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1) Is a Prognostic Biomarker and Associated with Chemotherapy Responsiveness in Colorectal Cancer.

Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an RNA-binding protein and serves as a post-transcriptional fine-tuner regulating the expression of mRNA targets. However, the clinicopathological roles of IGF2BP1 in colorectal cancer (CRC) remains limited. Thus, we aimed to elucidate the clinical significance and biomarker potentials of IGF2BP1 in CRC. A total of 266 specimens from two sets of CRC patients were collected. IGF2BP1 expression was studied by immunohistochemical (IHC) staining. The Kaplan-Meier survival plot and a log-rank test were used for survival analysis. The Cox proportional hazards model was applied to determine the survival impact of IGF2BP1. Public datasets sets from The Cancer Genome Atlas (TCGA) and Human Cancer Metastasis Database (HCMDB), receiver operating characteristic (ROC) plotter, and two CRC cell lines, HCT-116 and DLD-1, were used for validating our findings. We showed that IGF2BP1 was overexpressed in tumor specimens compared to 13 paired normal parts by examining the immunoreactivity of IGF2BP1 (p = 0.045). The increased expression of IGF2BP1 in primary tumor parts was observed regardless of metastatic status (p < 0.001) in HCMDB analysis. IGF2BP1 expression was significantly associated with young age (59.6% vs. 46.7%, p-value = 0.043) and advanced stage (61.3% vs. 40.0%, p-value = 0.001). After controlling for confounding factors, IGF2BP1 remained an independent prognostic factor (HR = 1.705, p-value = 0.005). TCGA datasets analysis indicated that high IGF2BP1 expression showed a lower 5-year survival rate (58% vs. 65%) in CRC patients. The increased expression of IGF2BP1 in chemotherapy non-responder rectal cancer patients was observed using a ROC plotter. Overexpression of IGF2BP1 promoted the colony-forming capacity and 5-fluorouracil and etoposide resistance in CRC cells. Here, IGF2BP1 was an independent poor prognostic marker in CRC patients and contributed to aggressive phenotypes in CRC cell lines.

Cyclotetrabenzoin Acetate: A Macrocyclic Porous Molecular Crystal for CO2 Separations by Pressure Swing Adsorption*.

A porous molecular crystal (PMC) assembled by macrocyclic cyclotetrabenzoin acetate is an efficient adsorbent for CO2 separations. The 7.1×7.1 Šsquare pore of PMC and its ester C=O groups play important roles in improving its affinity for CO2 molecules. The benzene walls of macrocycle engage in an apparent [π⋅⋅⋅π] interaction with the molecule of CO2 at low pressure. In addition, the polar carbonyl groups pointing inward the square channels reduce the size of aperture to a 5.0×5.0 Šsquare, which offers kinetic selectivity for CO2 capture. The PMC features water tolerance and high structural stability under vacuum and various gas adsorption conditions, which are rare among intrinsically porous organic molecules. Most importantly, the moderate adsorbate-adsorbent interaction allows the PMC to be readily regenerated, and therefore applied to pressure swing adsorption processes. The eluted N2 and CH4 are obtained with over 99.9 % and 99.8 % purity, respectively, and the separation performance is stable for 30 cycles. Coupled with its easy synthesis, cyclotetrabenzoin acetate is a promising adsorbent for CO2 separations from flue and natural gases.

Ammonium nutrition mitigates cadmium toxicity in rice (Oryza sativa L.) through improving antioxidase system and the glutathione-ascorbate cycle efficiency.

Nitrogen (N) forms not only affect cadmium (Cd) accumulation in plants, but also affect plant resistance to Cd toxicity. However, few researches have been reported underlying the mechanism of the relationship between nitrogen forms and plant resistance under Cd exposure. Here, we explored the mechanism on how different NO3-/NH4+ ratios affect antioxidase system and the glutathione-ascorbate cycle under five different ratios of NO3-/NH4+ (1:0, 2:1, 1:1, 1:2, 0:1) and three dosages of Cd exposure (0, 1, 5 µmol L-1 Cd) in rice (Oryza sativa L.). The results showed that high NO3- and high Cd exposure both significantly inhibited tissue growth of rice plants, and this inhibiting trend was mitigated with increasing NH4+ ratios as proved by the increased biomass and the decreased concentrations of malonaldehyde (MDA) and hydrogen peroxide (H2O2), as well as the levels of Cd contents in rice tissues. Additionally, high NH4+ ratios elevated the SOD activities in rice tissues, especially at high Cd treatment. However, other two antioxidases (CAT and APX) were insensitive to changes of NO3-/NH4+ ratios (except the full NO3-). Furthermore, high NH4+ ratios induced increasing of the efficiency of glutathione-ascorbate cycle (GSH-AsA) under two levels of Cd exposure, as evidenced by increasing concentrations of GSH and AsA and the activities of GR and DHAR in rice tissues. Overall, these results revealed that ammonium nutrition caused an enhancement resistance to Cd stress in rice plants was responsible for increasing of partial antioxidase system and the efficiencies of GSH-AsA cycle.

Unravelling the Enigma of Nonoxidative Conversion of Methane on Iron Single-Atom Catalysts.

The direct, nonoxidative conversion of methane on a silica-confined single-atom iron catalyst is a landmark discovery in catalysis, but the proposed gas-phase reaction mechanism is still open to discussion. Here, we report a surface reaction mechanism by computational modeling and simulations. The activation of methane occurs at the single iron site, whereas the dissociated methyl disfavors desorption into gas phase under the reactive conditions. In contrast, the dissociated methyl prefers transferring to adjacent carbon sites of the active center (Fe1 ©SiC2 ), followed by C-C coupling and hydrogen transfer to produce the main product (ethylene) via a key -CH-CH2 intermediate. We find a quasi Mars-van Krevelen (quasi-MvK) surface reaction mechanism involving extracting and refilling the surface carbon atoms for the nonoxidative conversion of methane on Fe1 ©SiO2 and this surface process is identified to be more plausible than the alternative gas-phase reaction mechanism.

RAB27B-activated secretion of stem-like tumor exosomes delivers the biomarker microRNA-146a-5p, which promotes tumorigenesis and associates with an immunosuppressive tumor microenvironment in colorectal cancer.

The dynamic cell-cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are extracellular vesicles that actively participate in cell-cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the ß-catenin/Tcf-4-activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA-146a-5p (miR-146a) is the major miRNA in CRCSC exosomes and exosomal miR-146a promotes stem-like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR-146a expression in serum exhibits higher miR-146aHigh /NumbLow CRCSC traits, an increased number of tumor-filtrating CD66(+) neutrophils and a decreased number of tumor-infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome-mediated stemness expansion.

Subjective sleep quality as a mediator in the relationship between pain severity and sustained attention performance in patients with fibromyalgia.

Pain severity and sleep are associated with cognitive performance in patients with fibromyalgia. This study examined whether sleep mediates the relationships of pain severity with psychomotor vigilance and attention in patients with fibromyalgia by analysing 80 patients with fibromyalgia. Cognitive performance, pain severity and sleep parameters were determined using the Psychomotor Vigilance Task, Brief Pain Inventory-Short Form and sleep diaries of seven consecutive nights, respectively. The patients' demographic data were analysed for potential confounding factors. After adjustment for these confounders, a series of regression analyses was performed to examine the mediating role of sleep. The results indicated that higher pain severity was strongly associated with poorer sustained attention and lower sleep quality, the total effects of pain severity on psychomotor vigilance and attention were significant (c path: ß = 0.23, p = 0.04), and pain severity was a significant sleep quality predictor (a path: ß = -0.33, p < 0.01). When sleep quality was entered into the regression model (a × b path), the effects of pain severity on psychomotor vigilance and attention became non-significant (c' path: ß = 0.15, p = 0.20) after adjustment of age, indicating a complete mediating effect of sleep quality in the pain severity-cognitive performance relationship. In conclusion, sleep quality mediates the pain severity-cognitive performance relationship: pain affects sleep quality, which in turn impairs sustained attention. Our findings provide further insight into the processes underlying the relationship between pain and poor cognitive function. Improved sleep quality may offset the detrimental effects of pain on sustained attention.

Dissecting Porosity in Molecular Crystals: Influence of Geometry, Hydrogen Bonding, and [π···π] Stacking on the Solid-State Packing of Fluorinated Aromatics.

Porous molecular crystals are an emerging class of porous materials that is unique in being built from discrete molecules rather than being polymeric in nature. In this study, we examined the effects of molecular structure of the precursors on the formation of porous solid-state structures with a series of 16 rigid aromatics. The majority of these precursors possess pyrazole groups capable of hydrogen bonding, as well as electron-rich aromatics and electron-poor tetrafluorobenzene rings. These precursors were prepared using a combination of Pd- and Cu-catalyzed cross-couplings, careful manipulations of protecting groups on the nitrogen atoms, and solvothermal syntheses. Our study varied the geometry and dimensions of precursors, as well as the presence of groups capable of hydrogen bonding and [π···π] stacking. Thirteen derivatives were crystallographically characterized, and four of them were found to be porous with surface areas between 283 and 1821 m2 g-1. Common to these four porous structures were (a) rigid trigonal geometry, (b) [π···π] stacking of electron-poor tetrafluorobenzenes with electron-rich pyrazoles or tetrazoles, and

Highly-stable mode-locked PM Yb-fiber laser with 10 nJ in 93-fs at 6 MHz using NALM.

We demonstrate highly stable mode-locked Yb-doped fiber oscillators using a nonlinear amplifying loop mirror, delivering linearly polarized laser pulses with high energy at a low repetition rate of several MHz. These lasers are composed of polarization-maintaining fibers and fiber-based components without intra-cavity dispersion compensation. The spectral and temporal characteristics are systematically investigated at different repetition rates. Spectral bandwidth of 31 nm is realized in the case of 6 MHz repetition rate, and the pulse energy reaches 10 nJ. A pair of gratings compresses the output pulse to 93 fs. RMS power stability is as low as 0.04% in 10 hours, which shows excellent stability. We believe that this type of fiber oscillator is an ideal seed for further high power amplification.

65-fs Yb-doped all-fiber laser using tapered fiber for nonlinearity and dispersion management.

We implement an ultrafast Yb-doped all-fiber laser which incorporates tapered single-mode fibers for managing nonlinearity and dispersion. The tapered fiber placed in the oscillator cavity aims to broaden the optical spectrum of the intracavity pulse. At the oscillator output, we use another tapered fiber to perform pulse compression. The resulting 66.1-MHz Yb-doped all-fiber oscillator self-starts and generates 0.4-nJ, 65-fs pulses, which can serve as a compact and robust seed source for subsequent high-power, high-energy amplifiers.