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.

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.

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.

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.

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.

Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity.

Autoimmune diseases such as ankylosing spondylitis (AS) can be driven by emerging neoantigens that disrupt immune tolerance. Here, we developed a workflow to profile posttranslational modifications involved in neoantigen formation. Using mass spectrometry, we identified a panel of cysteine residues differentially modified by carboxyethylation that required 3-hydroxypropionic acid to generate neoantigens in patients with AS. The lysosomal degradation of integrin αIIb [ITGA2B (CD41)] carboxyethylated at Cys96 (ITGA2B-ceC96) generated carboxyethylated peptides that were presented by HLA-DRB1*04 to stimulate CD4+ T cell responses and induce autoantibody production. Immunization of HLA-DR4 transgenic mice with the ITGA2B-ceC96 peptide promoted colitis and vertebral bone erosion. Thus, metabolite-induced cysteine carboxyethylation can give rise to pathogenic neoantigens that lead to autoreactive CD4+ T cell responses and autoantibody production in autoimmune diseases.

Efficacious Removal of Trace Mercury from Honeysuckle Water Decoction Using Multifunctional Mesoporous Carbon.

A mesoporous carbon (PC-2) obtained by using sucrose as a carbon source and urea as a nitrogen source has been used to remove trace mercury (Hg) from honeysuckle water decoction with high efficiency. The morphology, chemical composition, and pore structure of PC-2 have been characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and Brunauer-Emmett-Teller (BET). The results show that the specific surface area of PC-2 with the -NH2 functional is 1077.44 m2·g-1, and the mesoporous pore size is mainly around 2.8 nm. The investigation of the relationship between the adsorption performance and the structure of PC-2 indicates that the pore size and the chemical composition of carbons are significantly correlated with adsorption performance of mercury in water and honeysuckle water decoction. PC-2 has high efficiency approximated 100% for mercury from aqueous solutions. The pseudo-second-order kinetic model and the Freundlich model could better fit the adsorption process of Hg(II) onto PC-2. The process was dominated by chemical adsorption. Meanwhile, the adsorption behavior and the influence on the medicinal components (chlorogenic acid) of mercury removal in honeysuckle water decoction were determined by high performance liquid chromatography (HPLC). Results suggest that PC-2 has high efficiency approximated 66% for mercury from honeysuckle water decoction under optimal adsorption conditions, without affecting its active ingredients (chlorogenic acid). Therefore, PC-2 can potentially be used for adsorption of mercury in honeysuckle water decoction.

Gastrointestinal metastatic signet ring cell breast cancer in young females: a case report.

Background: Signet ring cell carcinoma (SRCC) is characterized by strong invasiveness and rapid progression. It occurs mostly in young and middle-aged patients, and early patients may have no clinical symptoms. Gastric SRCC with breast cancer metastasis is relatively rare. It often presents challenges for clinicians and pathologists and may lead to an absolutely different therapeutic strategy. Case Description: In this paper, we report on a 37-year-old woman who was admitted to the hospital with a left breast mass discovered 5 days earlier, the mass was occasionally painful, and there was no skin swelling, skin depression, or other abnormalities. The initial diagnosis considered her to have a left breast tumor. The patient was previously healthy with no family history of tumor. Considering the possibility of malignant lesions, she underwent resection of the left breast tumor and surrounding tissue. Postoperative pathological findings suggested SRCC (left breast mass). Although the patient had no history of gastrointestinal tumors, considering that SRCC can also appear in the gastrointestinal tract and other organs. We performed gastroscopy on the patient, showed an ulcerative mass in the greater curvature of the gastric body, with irregular nodular uplift of the surrounding mucosa. The excised breast lesions were analyzed by immunohistochemistry, and the pathological result showed SRCC (left breast tumor). Combined with the results of immunohistochemistry, it was consistent with gastrointestinal metastasis. Through our multi-faceted differential diagnosis, the final diagnosis of the patient was clear, which not only bought time for the patient's subsequent treatment, but also avoided misdiagnosis and blind treatment due to the particularity and rarity of the case. Conclusions: Gastric cancer should be considered when breast tumors show SRCC without in situ lesion. Signet ring cell gastric cancer (occult) should be excluded even if the patient has no family history of gastric cancer. It is important to distinguish metastatic cancer from primary breast cancer to avoid misdiagnosis and blind treatment due to the particularity of the case, at which point an early recognition can be made and an optimal treatment plan can be chosen.

Hypoxia causes mitochondrial dysfunction and brain memory disorder in a manner mediated by the reduction of Cirbp.

Environmental hypoxic hazard has increasingly become a global public health issue, with impelling evidences supporting the relation between hypoxia and cognitive disorders. As a potent stressor, hypoxia causes mitochondrial dysfunction with insufficient energy production, thus the formation of brain memory disorder. Yet, the underlying molecular mechanism/s against hypoxia induced injury have yet to be identified. Here, we report that cold inducible RNA binding protein (Cirbp) attenuates hypoxia induced insufficient energy production and oxidative stress. Further analyses show that Cirbp sustains protein levels of respiratory chain complexes II (SDHB) and IV (MT-CO1), and directly binds the 3'UTR of Atp5g3 to control mitochondrial homeostasis and ATP biogenesis upon hypoxic stress. Altogether, our data establish Cirbp as a critical protective factor against hypoxic health hazard and provide novel insights into its latent regulation network.

Cirbp-PSD95 axis protects against hypobaric hypoxia-induced aberrant morphology of hippocampal dendritic spines and cognitive deficits.

Hypobaric hypoxia (HH) is a typical characteristic of high altitude environment and causes a spectrum of pathophysiological effects, including headaches, gliovascular dysfunction and cognitive retardation. Here, we sought to understand the mechanisms underlying cognitive deficits under HH exposure. Our results showed that hypobaric hypoxia exposure impaired cognitive function and suppressed dendritic spine density accompanied with increased neck length in both basal and apical hippocampal CA1 region neurons in mice. The expression of PSD95, a vital synaptic scaffolding molecule, is down-regulated by hypobaric hypoxia exposure and post-transcriptionally regulated by cold-inducible RNA-binding protein (Cirbp) through 3'-UTR region binding. PSD95 expressing alleviates hypoxia-induced dendritic spine morphology changes of hippocampal neurons and memory deterioration. Moreover, overexpressed Cirbp in hippocampus rescues HH-induced abnormal expression of PSD95 and attenuates hypoxia-induced dendritic spine injury and cognitive retardation. Thus, our findings reveal a novel mechanism that Cirbp-PSD-95 axis appears to play an essential role in HH-induced cognitive dysfunction in mice.

Experimental Investigation of the Pressure Decay Characteristics of Oil Reservoirs after Fracturing Operations.

Field experience shows that extending shut-in periods are conducive to increasing tight oil production after fracturing operations. Understanding the regularity of pressure decay is helpful to establish an appropriate shut-in time. However, the characteristics and influencing factors of pressure decay are unclear. This paper studies the porosity, permeability, mineral composition, and pore structure of samples in six different blocks. The pressure decay regularity is tested according to an independently designed indoor shut-in experimental device, and the oil distribution of experimental samples is monitored using nuclear magnetic resonance technology. The results show that the fracturing fluid enters the matrix pores under the action of percolation to slowly drive out the oil, causing the well pressure to decay over time. There are three types of pressure decay characteristics: concave type, fluctuation type, and quadratic type. Compared with conventional sandstone, the pressure decay rate of tight reservoirs is slower, and the pressure decay characteristics are more complicated. Clay mineral-rich reservoirs will swell when exposed to water. As a result, the strength of the framework will be weakened and collapsed. What's more, it will cause blockage of the throat, blocking the flow of oil and the decay of pressure. In addition, the rate of pressure decay is also related to the volume of fracturing fluid, initial borehole pressure, and formation closure stress. At a certain proppant thickness (fracture width), the larger the fracturing fluid volume, the larger the fracture surface area and the faster the pressure decay rate; Moreover, the greater the initial shut-in pressure, the greater the pressure difference and the faster the decay rate; the formation closure stress causes the core porosity and the permeability to decrease, resulting in a decrease in the decay rate. The experimental results are of great significance for establishing a proper shut-in time and enhancing the oil recovery of tight reservoirs.

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.

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.

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.

Extracting more light for vertical emission: high power continuous wave operation of 1.3-µm quantum-dot photonic-crystal surface-emitting laser based on a flat band.

For long distance optical interconnects, 1.3-µm surface-emitting lasers are key devices. However, the low output power of several milliwatts limits their application. In this study, by introducing a two-dimensional photonic-crystal and using InAs quantum dots as active materials, a continuous-wave, 13.3-mW output power, 1.3-µm wavelength, room-temperature surface-emitting laser is achieved. In addition, such a device can be operated at high temperatures of up to 90 °C. The enhanced output power results from the flat band structure of the photonic crystal and an extra feedback mechanism. Surface emission is realized by photonic crystal diffraction and thus the distributed Bragg reflector is eliminated. The proposed device provides a means to overcome the limitations of low-power 1.3-µm surface-emitting lasers and increase the number of applications thereof.

Pueraria lobata for Diabetes Mellitus: Past, Present and Future.

Gegen (Radix Puerariae Lobatae), the root of Pueraria lobata, is an edible and medicinal herb which has been used in treating diabetic symptoms in the orient for thousands of years. We present an evidence map of the efficacy and safety of Gegen and Gegen formulas (GGFs) that use Gegen as an essential herb for diabetes, and also its mechanism of actions. We comprehensively searched the ancient medical records to identify empirical evidence; conducted a systematic review (SR) based on moderate- to high-quality randomized controlled trials (RCTs) to synthesize the clinical evidence; and reviewed the possible mechanisms of its antidiabetic effects. Empirical application of Gegen in treating diabetic symptoms dated back to more than 2000 years ago. Common herbs used in RCTs that accompany with Gegen included Radix et Rhizoma Glycyrrhizae, Radix et Rhizoma Ginseng, Rhizoma Dioscoreae, Poria, and Radix Ophiopogonis. The combinations used today are consistent with their usage in ancient times. Results of the SR showed that GGFs could benefit patients with type 2 diabetes for blood glucose control. When in combination with hypoglycemic agents or insulin, GGFs enhanced the glucose-lowering effect as well as the lipid-lowering effects. Also, the incidence and the risk of adverse events (AE), especially the hypoglycemic episodes, were lower in the combination group. No serious or life-threatening AE was reported. The experimental evidence presented that Gegen and GGFs might exert and enhance the anti-diabetic effects through activation of multiple mechanisms, such as reducing insulin resistance, increasing insulin release, inhibiting glucose absorption and reabsorption, and improving insulin sensitivity, glucose uptake, and metabolism.

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.

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.