SCD1 sustains brown fat sympathetic innervation and thermogenesis during the long-term cold exposure.

Brown fat adipose tissue (BAT) is a therapeutic potential target to improve obesity, diabetes and cold acclimation in mammals. During the long-term cold exposure, the hyperplastic sympathetic network is crucial for BAT the maintain the highly thermogenic status. It has been proved that the sympathetic nervous drives the thermogenic activity of BAT via the release of norepinephrine. However, it is still unclear that how the thermogenic BAT affects the remodeling of the hyperplastic sympathetic network, especially during the long-term cold exposure. Here, we showed that following long-term cold exposure, SCD1-mediated monounsaturated fatty acid biosynthesis pathway was enriched, and the ratios of monounsaturated/saturated fatty acids were significantly up-regulated in BAT. And SCD1-deficiency in BAT decreased the capacity of cold acclimation, and suppressed long-term cold mediated BAT thermogenic activation. Furthermore, by using thermoneutral exposure and sympathetic nerve excision models, we disclosed that SCD1-deficiency in BAT affected the thermogenic activity, depended on sympathetic nerve. In mechanism, SCD1-deficiency resulted in the unbalanced ratio of palmitic acid (PA)/palmitoleic acid (PO), with obviously higher level of PA and lower level of PO. And PO supplement efficiently reversed the inhibitory role of SCD1-deficiency on BAT thermogenesis and the hyperplastic sympathetic network. Thus, our data provided insight into the role of SCD1-mediated monounsaturated fatty acids metabolism to the interaction between thermogenic activity BAT and hyperplastic sympathetic networks, and illustrated the critical role of monounsaturated fatty acids biosynthetic pathway in cold acclimation during the long-term cold exposure.

Mode-Locked Operation of High-Order Transverse Modes in a Vertical-External-Cavity Surface-Emitting Laser.

Understanding the mechanism of mode-locking in a laser with high-order transverse mode is important for achieving an ultrashort pulses train under more complicated conditions. So far, mode-locking with high-order transverse mode has not been reported in other lasers except the multimode fiber laser. This paper demonstrates robust mode-locking with high-order transverse mode in a Kerr-lens mode-locked vertical-external-cavity surface-emitting laser for the first time, to the best of our knowledge. While the longitudinal modes are locked, continuous mode-locking accompanied by high-order transverse mode up to TEM40 is observed. The threshold of the mode-locking is only a little bigger than that of the lasing. After the laser oscillation is built up, the mode-locked pulse train can be obtained almost immediately and maintained until the thermal rollover of the laser. Output powers of 717 mW under fundamental mode and 666 mW under high-order transverse mode are achieved with a 4.3 ps pulse duration and 1.1 GHz pulses repetition rate, and some phenomenological explanations to the related characteristics of the mode-locked operation of high-order transverse mode in the vertical-external-cavity surface-emitting laser are proposed.

108 m Underwater Wireless Optical Communication Using a 490 nm Blue VECSEL and an AOM.

Advanced light sources in the blue-green band are crucial for underwater wireless optical communication (UWOC) systems. Vertical-external-cavity surface-emitting lasers (VECSELs) can produce high output power and good beam quality, making them suitable for UWOC. This paper presents a 108 m distance UWOC based on a 100 mW 490 nm blue VECSEL and an acousto-optic modulator (AOM). The high-quality beam, which is near diffraction-limited, undergoes relatively small optical attenuation when using a conventional avalanche photodiode (APD) as the detector and employing 64-pulse position modulation (PPM). At the time-slot frequency of 50 MHz, the bit error rate (BER) of the UWOC was 2.7 × 10-5. This is the first reported AOM-based UWOC system with a transmission distance over 100 m. The estimated maximum transmission distance may be improved to about 180 m by fully utilizing the detection accuracy of the APD according to the measured attenuation coefficient of the blue VECSEL used. This type of UWOC system, composed of a high-beam-quality light source and a conventional detector, make it more closely suited to practical applications.

ISRIB alleviates aging-associated brown fat UCP1 translational repression and thermogenic deficiency.

Upon cold exposure, aged people with lower metabolic rate cannot rapidly increase the higher levels of heat production, and are seriously threatened by the hypothermia, extensive cold stress responses and risk of mortality. Here, we show that brown fat thermogenic activity is obviously deficient in aged mice, associating with reduction of UCP1 expression and inhibition of its mRNA translation. As we considered, aging aggravates brown fat oxidative stress and activates the integrated stress response (ISR), inducing the phosphorylation of eIF2α to block the global mRNA translation. Therefore, small-molecule ISR inhibitor (ISRIB) treatment attenuates the higher level of eIF2α phosphorylation, restores the repression of Ucp1 mRNA translation and improves UCP1-mediated thermogenic function to defend cold stress in aged mice. Furthermore, ISRIB treatment increases the relative lower metabolic rates, and alleviates glucose intolerance and insulin resistance in aged mice. Thus, we have uncovered a promising drug that reverses the aged-related the deficiency of UCP1-mediated thermogenesis to combat cold stress and associated metabolic diseases.

QKI regulates adipose tissue metabolism by acting as a brake on thermogenesis and promoting obesity.

Adipose tissue controls numerous physiological processes, and its dysfunction has a causative role in the development of systemic metabolic disorders. The role of posttranscriptional regulation in adipose metabolism has yet to be fully understood. Here, we show that the RNA-binding protein quaking (QKI) plays an important role in controlling metabolic homeostasis of the adipose tissue. QKI-deficient mice are resistant to high-fat-diet (HFD)-induced obesity. Additionally, QKI depletion increased brown fat energy dissipation and browning of subcutaneous white fat. Adipose tissue-specific depletion of QKI in mice enhances cold-induced thermogenesis, thereby preventing hypothermia in response to cold stimulus. Further mechanistic analysis reveals that QKI is transcriptionally induced by the cAMP-cAMP response element-binding protein (CREB) axis and restricts adipose tissue energy consumption by decreasing stability, nuclear export, and translation of mRNAs encoding UCP1 and PGC1α. These findings extend our knowledge of the significance of posttranscriptional regulation in adipose metabolic homeostasis and provide a potential therapeutic target to defend against obesity and its related metabolic diseases.

Boosting Perovskite Photodetector Performance in NIR Using Plasmonic Bowtie Nanoantenna Arrays.

Triple-cation mixed metal halide perovskites are important optoelectronic materials due to their high photon to electron conversion efficiency, low exciton binding energy, and good thermal stability. However, the perovskites have low photon to electron conversion efficiency in near-infrared (NIR) due to their weak intrinsic absorption at longer wavelength, especially near the band edge and over the bandgap wavelength. A plasmonic functionalized perovskite photodetector (PD) is designed and fabricated in this study, in which the perovskite ((Cs0.06 FA0.79 MA0.15 )Pb(I0.85 Br0.15 )3 ) active materials are spin-coated on the surface of Au bowtie nanoantenna (BNA) arrays substrate. Under 785 nm laser illumination, near the bandedge of perovskite, the fabricated BNA-based plasmonic PD exhibits ≈2962% enhancement in the photoresponse over the Si/SiO2 -based normal PD. Moreover, the detectivity of the plasmonic PD has a value of 1.5 × 1012 with external quantum efficiency as high as 188.8%, more than 30 times over the normal PD. The strong boosting in the plasmonic PD performance is attributed to the enhanced electric field around BNA arrays through the coupling of localized surface plasmon resonance. The demonstrated BNA-perovskite design can also be used to enhance performance of other optoelectronic devices, and the concept can be extended to other spectral regions with different active materials.

Beam waist shrinkage of high-power broad-area diode lasers by mode tailoring.

A new approach was proposed and its role in improvement of the beam quality of high-power broad-area diode lasers was demonstrated, in which a composite arrow array and trench microstructure was used to suppress the beam waist and tailor the high order lateral modes. The beam waist shows a special shrinkage with increasing injection current resulting from the combined effect of mode tailoring and the thermal lens effect. A 58% improvement in lateral beam parameter product was realized compared with conventional broad-area diode lasers.

Earlier changes in mice after D-galactose treatment were improved by mitochondria derived small peptide MOTS-c.

MOTS-c, as a mitochondria derived peptide, exerts benefits for insulin resistance in HFD mice and against various stresses in an AMPK dependent way. Here, in the D-galactose chronic injection models, exogenous MOTS-c was given to determine its direct anti-aging effects. The body weight, insulin sensitivity and blood glucose were determined with mild differences. Tissue morphology analyses disclosed that liver, visceral fat and dermal skin, all displayed aberrant lipid depositions in the D-galactose mice. MOTS-c treatment largely alleviated the lipid accumulations, corresponding with positive changes in mitochondria dynamics, observed in liver transmission electron microscopy and in altered mRNA levels of Drp1 and mitofusins. Notably, the aging phenotypes of small intestine tract were more obvious, including histological defects and lower Ki67 levels, plus with the higher levels of DNA stress, such as P21 and P16, as well as mitochondria dynamics. Collectively, these data provided the direct evidence to support that exogenous givings of MOTS-c prevented abnormal fat accumulations in D-gal mice, putatively via improvement of mitochondria dynamic related pathways.

Low-Dose X-ray Excited Photodynamic Therapy Based on NaLuF4:Tb3+-Rose Bengal Nanocomposite.

X-ray excited photodynamic therapy (X-PDT), which utilizes X-rays as the energy source and X-ray luminescent nanoparticles (XLNPs) as the transducer to excite photosensitizers (PS), resolves the penetration problem of light in traditional PDT to enable the treatment of deep-seated tumors. Nevertheless, the high X-ray dosage used in X-PDT hampers its potential applications in clinics. In this study, to alleviate the dose problem, ß-NaLuF4:Tb3+ spherical nanoparticles (NPs) with ultrastrong green X-ray excited optical luminescence (XEOL) due to the less nonradiative relaxation probability and high X-ray absorption mass coefficient, which perfectly matches the absorption spectrum of a photosensitizer named rose bengal (RB), were synthesized and employed as the energy transducer for X-PDT. After covalent conjugation of NPs with RB, high Förster resonant energy transfer (FRET) efficiency up to 94.29% was achieved, leading to high production of singlet oxygen. In vivo X-PDT efficacy was evaluated by nude mice with a HepG2 tumor xenograft. With excellent biocompatibility, the synthesized NPs-RB nanocomposite showed significant antitumor efficiency up to 80 ± 12.3% with a total X-ray dose of only 0.19 Gy, demonstrating the feasibility of low-dose X-PDT in vivo for the first time. The present work provides a promising platform for X-PDT in deep-seated tumors.

Quasi-rhombus metasurfaces as multimode interference couplers for controlling the propagation of modes in dielectric-loaded waveguides.

Metasurfaces can control the propagation of free space and guided modes by imparting a phase gradient and modifying the mode propagation properties. Here we propose a design to control optical signals in a dielectric-loaded waveguide using quasi-rhombus gradient plasmonic metasurface structure. The metasurface acts as a multimode interference coupler that can focus, route, and split the propagating field in UV-visible spectral range. The ability to gain full control on waveguided mode with minimal footprint can significantly impact miniaturization of optical devices and photonic integrated circuits.

Loss tailoring of high-power broad-area diode lasers.

Broad-area diode lasers (BALs) with high power are highly desirable for a variety of applications. However, such lasers suffer from strongly deteriorated beam quality due to multimode behavior in the lateral direction. In this Letter, we present an approach to flexibly tailor the optical loss of different-order lateral modes by etching micro-holes on the laser mesa with controlled position and numbers. Through arranging the micro-holes at the peak positions of high-order lateral modes with an increasing number from the mesa center to both edges, high-order modes are suppressed due to a larger propagation loss than the fundamental mode. As a result of enhanced mode discrimination, we demonstrate that this technique provides a greatly improved beam quality and about two times higher brightness for 100 µm wide BAL, while maintaining high power and slope efficiency output.

RNA-binding protein QKI regulates contact inhibition via Yes-associate protein in ccRCC.

Contact inhibition adjusts organ size to the proper size and ensures the cultured cells growing to a monolayer. By regulating the downstream coordinator YAP, the evolutionarily conserved Hippo transduction pathway attunes cell growth and death in response to cell contact inhibition, polarity, self-renewal, and differentiation. Dysregulation of this pathway is involved in various diseases such as cancer. RNA-binding protein QKI regulates cell proliferation, metabolism, division, and immunity in various cancer models, but its role in cancer cell contact inhibition remains unclear. In this study, we aimed to clarify the relationship between QKI and YAP, and the role of their interaction in cell contact inhibition. We found a lower QKI expression level in sparse condition, whereas a higher expression level in confluent condition by western blot analysis and immunofluorescence assay. QKI knockdown elevated cell proliferation and invasion both in vitro and in vivo. Strikingly, the results of CCK-8 assay, colony formation assay, and transwell assay showed that the phenomenon was in accord with the expression level of pYAP and reverse with YAP. Higher levels of Wnt3a and ß-catenin were also found in xenografts of QKI-knockdown clear cell renal cell carcinoma (ccRCC) CAKI-1 cells by western blot analysis and immumohistochemical staining. Finally, a positive correlation between QKI and pYAP was found in clinical specimens by immunohistochemistry. Thus, as a negative regulator of YAP, QKI attuned the cell contact inhibition, leading to inhibition of cancer cell proliferation and invasion through Wnt and GPCR pathway.

Mitochondrial-Derived Peptide MOTS-c Increases Adipose Thermogenic Activation to Promote Cold Adaptation.

Cold exposure stress causes hypothermia, cognitive impairment, liver injury, and cardiovascular diseases, thereby increasing morbidity and mortality. Paradoxically, cold acclimation is believed to confer metabolic improvement to allow individuals to adapt to cold, harsh conditions and to protect them from cold stress-induced diseases. However, the therapeutic strategy to enhance cold acclimation remains less studied. Here, we demonstrate that the mitochondrial-derived peptide MOTS-c efficiently promotes cold adaptation. Following cold exposure, the improvement of adipose non-shivering thermogenesis facilitated cold adaptation. MOTS-c, a newly identified peptide, is secreted by mitochondria. In this study, we observed that the level of MOTS-c in serum decreased after cold stress. MOTS-c treatment enhanced cold tolerance and reduced lipid trafficking to the liver. In addition, MOTS-c dramatically upregulated brown adipose tissue (BAT) thermogenic gene expression and increased white fat "browning". This effect might have been mediated by MOTS-c-activated phosphorylation of the ERK signaling pathway. The inhibition of ERK signaling disturbed the up-regulatory effect of MOTS-c on thermogenesis. In summary, our results indicate that MOTS-c treatment is a potential therapeutic strategy for defending against cold stress by increasing the adipose thermogenesis via the ERK pathway.

High-brightness diode lasers obtained via off-axis spectral beam combining with selective feedback.

We proposed a modified off-axis spectral beam combining method, based on the concept of selective feedback. A high reflectivity mirror with a fixed width was used to select and couple back the optical modes in the external cavity. The emission power exceeding 20 W with M2 factors of 2.7 × 4.4 in the fast and slow axes was demonstrated. The beam quality of the system was improved by a factor of three to four compared with that of a single emitter, and a high brightness of 190 MW cm-2 str-1 was achieved.

Going beyond the beam quality limit of spectral beam combining of diode lasers in a V-shaped external cavity.

A novel spectral beam combining (SBC) approach based on off-axis feedback in a V-shaped external cavity (VSBC) was proposed and demonstrated. A highly reflecting mirror was used to supply the optical feedback by partial overlapping the beam. The advantages of simple setup, output coupler free, tunable beam quality and emission power over traditional SBC were presented. The beam quality exceeds single emitter with the similar energy conversion efficiency to the traditional SBC. The M2 factors of 2.31 × 3.76 in fast and slow axes and a brightness of 122 MWcm-2sr-1 were realized at 30 A based on a commercial broad-area diode laser array.

Trans-Ferulic Acid-4-ß-Glucoside Alleviates Cold-Induced Oxidative Stress and Promotes Cold Tolerance.

Trans-ferulic acid-4-ß-glucoside (C16H20O9, TFA-4ß-G) is a monomer extracted from the Chinese medicine called radix aconiti carmichaeli (Fuzi). To date, research on this substance is lacking. Here, we found that trans-ferulic acid-4-ß-glucoside effectively promoted cold acclimatization in mice via increased heat production and alleviation of oxidative stress in a cold environment. Thus, our work indicates that ferulic acid-4-ß-glucoside is a potential therapeutic candidate for prevention and treatment of cold stress injury.

Cognitive and neuroimaging changes in healthy immigrants upon relocation to a high altitude: A panel study.

BACKGROUND: Cognitive and neuroimaging changes under chronic high-altitude exposure have never been followed up and dynamically assessed. OBJECTIVES: To investigate the cognitive and brain structural/functional alterations associated with chronic high-altitude exposure. METHODS: Sixty-nine college freshmen that were immigrating to Tibet were enrolled and followed up for two years. Neuropsychological tests, including verbal/visual memory and simple/recognition reaction time, were utilized to determine whether the subjects' cognitive function had changed in response to chronic high-altitude exposure. Structural magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) were used to quantify brain gray matter (GM) volumes, regional homogeneity (ReHo) and functional connectivity (FC) alterations before and after exposure. Areas with changes in both GM and ReHo were used as seeds in the inter-regional FC analysis. RESULTS: The subjects showed significantly lower accuracy in memory tests and longer reaction times after exposure, and neuroimaging analysis showed markedly decreased GM volumes and ReHo in the left putamen. FC analysis seeding of the left putamen showed significantly weakened FC with the superior temporal gyrus, anterior/middle cingulate gyrus and other brain regions. In addition, decreased ReHo was found in the superior temporal gyrus, superior parietal lobule, anterior cingulate gyrus and medial frontal gyrus, while increased ReHo was found in the hippocampus. Differences in ReHo/FC before and after high-altitude exposure in multiple regions were significantly correlated with the cognitive changes. CONCLUSION: Cognitive functions such as working memory and psychomotor function are impaired during chronic high-altitude exposure. The putamen may play an important role in chronic hypoxia-induced cognitive impairment. Hum Brain Mapp 38:3865-3877, 2017. © 2017 Wiley Periodicals, Inc.

Antibiotics-induced gut microbiota dysbiosis promotes tumor initiation via affecting APC-Th1 development in mice.

Gut microbiota is critical for maintaining body immune homeostasis and thus affects tumor growth and therapeutic efficiency. Here, we investigated the link between microbiota and tumorgenesis in a mice model of subcutaneous melanoma cell transplantation, and explored the underlying mechanism. We found disruption of gut microbiota by pretreating mice with antibiotics promote tumor growth and remodeling the immune compartment within the primary tumor. Indeed, gut microbial dysbiosis reduced the infiltrated mature antigen-presenting cells of tumor, together with lower levels of co-stimulators, such as CD80, CD86 and MHCII, as well as defective Th1 cytokines, including IFNγ, TNFα, IL12p40, and IL12p35. Meantime, splenic APCs displayed blunted ability in triggering T cell proliferation and IFNγ secretion. However, oral administration of LPS restored the immune surveillance effects and thus inhibited tumor growth in the antibiotics induced gut microbiota dysbiosis group. Taken together, these data highly supported that antibiotics induced gut microbiota dysbiosis promotes tumor initiation, while LPS supplementation would restore the effective immune surveillance and repress tumor initiation.

The mitochondrial genome-encoded peptide MOTS-c interacts with Bcl-2 to alleviate nonalcoholic steatohepatitis progression.

Nonalcoholic steatohepatitis (NASH) is a metabolism-associated fatty liver disease with accumulated mitochondrial stress, and targeting mitochondrial function is a potential therapy. The mitochondrial genome-encoded bioactive peptide MOTS-c plays broad physiological roles, but its effectiveness and direct targets in NASH treatment are still unclear. Here, we show that long-term preventive and short-term therapeutic effects of MOTS-c treatments alleviate NASH-diet-induced liver steatosis, cellular apoptosis, inflammation, and fibrosis. Mitochondrial oxidative capacity and metabolites profiling analysis show that MOTS-c significantly reverses NASH-induced mitochondrial metabolic deficiency. Moreover, we identify that MOTS-c directly interacts with the BH3 domain of antiapoptotic B cell lymphoma-2 (Bcl-2), increases Bcl-2 protein stability, and suppresses Bcl-2 ubiquitination. By using a Bcl-2 inhibitor or adeno-associated virus (AAV)-mediated Bcl-2 knockdown, we further confirm that MOTS-c improves NASH-induced mitochondrial dysfunction, inflammation, and fibrosis, which are dependent on Bcl-2 function. Therefore, our findings show that MOTS-c is a potential therapeutic agent to inhibit the progression of NASH.

Continuous-wave operation of 1550 nm low-threshold triple-lattice photonic-crystal surface-emitting lasers.

Benefitting from narrow beam divergence, photonic crystal surface-emitting lasers are expected to play an essential role in the ever-growing fields of optical communication and light detection and ranging. Lasers operating with 1.55 µm wavelengths have attracted particular attention due to their minimum fiber loss and high eye-safe threshold. However, high interband absorption significantly decreases their performance at this 1.55 µm wavelength. Therefore, stronger optical feedback is needed to reduce their threshold and thus improve the output power. Toward this goal, photonic-crystal resonators with deep holes and high dielectric contrast are often used. Nevertheless, the relevant techniques for high-contrast photonic crystals inevitably complicate fabrication and reduce the final yield. In this paper, we demonstrate the first continuous-wave operation of 1.55 µm photonic-crystal surface-emitting lasers by using a 'triple-lattice photonic-crystal resonator', which superimposes three lattice point groups to increase the strength of in-plane optical feedback. Using this geometry, the in-plane 180° coupling can be enhanced threefold compared to the normal single-lattice structure. Detailed theoretical and experimental investigations demonstrate the much lower threshold current density of this structure compared to 'single-lattice' and 'double-lattice' photonic-crystal resonators, verifying our design principles. Our findings provide a new strategy for photonic crystal laser miniaturization, which is crucial for realizing their use in future high-speed applications.