A crucial role of adenosine deaminase in regulating gluconeogenesis in mice.

Adenosine deaminase (ADA) catalyzes the irreversible deamination of adenosine (ADO) to inosine and regulates ADO concentration. ADA ubiquitously expresses in various tissues to mediate ADO-receptor signaling. A significant increase in plasma ADA activity has been shown to be associated with the pathogenesis of type 2 diabetes mellitus. Here, we show that elevated plasma ADA activity is a compensated response to high level of ADO in type 2 diabetes mellitus and plays an essential role in the regulation of glucose homeostasis. Supplementing with more ADA, instead of inhibiting ADA, can reduce ADO levels and decrease hepatic gluconeogenesis. ADA restores a euglycemic state and recovers functional islets in db/db and high-fat streptozotocin diabetic mice. Mechanistically, ADA catabolizes ADO and increases Akt and FoxO1 phosphorylation independent of insulin action. ADA lowers blood glucose at a slower rate and longer duration compared to insulin, delaying or blocking the incidence of insulinogenic hypoglycemia shock. Finally, ADA suppresses gluconeogenesis in fasted mice and insulin-deficient diabetic mice, indicating the ADA regulating gluconeogenesis is a universal biological mechanism. Overall, these results suggest that ADA is expected to be a new therapeutic target for diabetes.

PER2/P65-driven glycogen synthase 1 transcription in macrophages modulates gut inflammation and pathogenesis of rectal prolapse.

Rectal prolapse in serious inflammatory bowel disease is caused by abnormal reactions of the intestinal mucosal immune system. The circadian clock has been implicated in immune defense and inflammatory responses, but the mechanisms by which it regulates gut inflammation remain unclear. In this study, we investigate the role of the rhythmic gene Period2 (Per2) in triggering inflammation in the rectum and its contribution to the pathogenesis of rectal prolapse. We report that Per2 deficiency in mice increased susceptibility to intestinal inflammation and resulted in spontaneous rectal prolapse. We further demonstrated that PER2 was essential for the transcription of glycogen synthase 1 by interacting with the NF-κB p65. We show that the inhibition of Per2 reduced the levels of glycogen synthase 1 and glycogen synthesis in macrophages, impairing the capacity of pathogen clearance and disrupting the composition of gut microbes. Taken together, our findings identify a novel role for Per2 in regulating the capacity of pathogen clearance in macrophages and gut inflammation and suggest a potential animal model that more closely resembles human rectal prolapse.

Magneto-chiral backscatterings by rotationally symmetric nonreciprocal structures.

It was proved that the joint operation of electromagnetic reciprocity and n-fold (n ≥ 3) rotational symmetry would secure arbitrary polarization-independent backscattering efficiency [Phys. Rev. B103(4), 045422 (2021)10.1103/PhysRevB.103.045422]. Here we remove the restriction of reciprocity and study the backscatterings of plane waves by rotationally symmetric magneto-optical structures, with collinear incident wavevector, rotational axis and externally applied magnetic field. It is revealed that though nonreciprocity removes the degeneracy of backscattering efficiencies for circularly-polarized incident waves of opposite handedness, the remaining rotational symmetry is sufficient to guarantee that the efficiency is related to the polarization ellipticity only, having nothing to do with the orientations of the polarization ellipses. Moreover, the backscattering efficiency reaches its extremes (maximum or minimum values) always for circularly-polarized incident waves, and for other polarizations the efficiency is their ellipticity-weighted arithmetic average. The principles we have revealed are dictated by rotational symmetries only, which are irrelevant to specific geometric or optical parameters and are intrinsically robust against any rotational-symmetry preserving perturbations. The correlations we have discovered could be further exploited for fundamental explorations in nonreciprocal photonics and practical applications including polarimetry and ellipsometry.

Multifunctional metalens optical tweezers for optical information recognition.

Traditional optical information recognition (OIR), particle capture and manipulation require many optical devices or mechanical moving system components to achieve a specific function, which is difficult to achieve integration. This paper proposes a new method to realize these functions by using multi-focus metalens combining spectrum and polarization selection. The design incorporates three spectral bands, namely 500 nm, 580 nm, and 660 nm, within the visible light range. Additionally, it utilizes either left-handed or right-handed circularly polarized (LCP/RCP) light, resulting in six distinct focus focusing effects on a single focal plane. By analyzing the normalized light intensity (NLI) at the corresponding focus position, the OIR of any wavelength and polarization detection in the design can be realized, and the particle capture at different focusing positions can be realized. Our work can provide a new idea for the high integration of on-chip light recognition and operation and inspire the design of a highly integrated optical system with a smaller size and more substantial function.

Plasticizer acetyl triethyl citrate (ATEC) induces lipogenesis and obesity.

Environmental chemicals, such as plasticizers, have been linked to increased rates of obesity, according to epidemiological studies. Acetyl triethyl citrate (ATEC) is a plasticizer that is commonly utilized in pharmaceutical products and food packaging as a non-phthalate alternative. Due to its direct contact with the human body and high leakage rate from the polymers, assessment of the potential risk of ATEC exposure at environmentally relevant low doses to human health is needed. Male C57BL/6 J mice were fed diets containing ATEC at doses of either 0.1 or 10 µg/kg per day in a period of 12 weeks to mimic the real exposure environment. The findings suggest that in C57BL/6 J mice, ATEC exposure resulted in increased body weight gain, body fat percentage, and benign hepatocytes, as well as adipocyte size. Consistent with in vivo models, ATEC treatment obviously stimulated the increase of intracellular lipid load in both mouse and human hepatocytes. Mechanically, ATEC induced the transcriptional expression of genes involved in de novo lipogenesis and lipid uptake. Using both enzyme inhibitor and small interfering RNA (siRNA) transfection, we found that stearoyl-coenzyme A desaturase 1 (SCD1) played a significant role in ATEC-induced intracellular lipid accumulation. This study for the first time provided initial evidence suggesting the obesogenic and fatty liver-inducing effect of ATEC at low doses near human exposure levels, and ATEC might be a potential environmental obesogen and its effect on human health need to be further evaluated.

Hydrogel Based on Riclin Cross-Linked with Polyethylene Glycol Diglycidyl Ether as a Soft Filler for Tissue Engineering.

Hydrogels composed of natural polysaccharides have been widely used as filling materials, with a growing interest in medical cosmetology and skin care. However, conventional commercial dermal fillers still have limitations, particularly in terms of mechanical performance and durability in vivo. In this study, a novel injectable and implantable hydrogel with adjustable characteristics was prepared from succinoglycan riclin by introducing PEG diglycidyl ether as a cross-linker. FTIR spectra confirmed the cross-linking reaction. The riclin hydrogels exhibited shear-thinning behavior, excellent mechanical properties, and cytocompatibility through in vitro experiments. Furthermore, when compared with subcutaneous injection of a commercial hyaluronic acid hydrogel, the riclin hydrogels showed enhanced persistence and biocompatibility in Balb/c mice after 16 weeks. These results demonstrate the great potential of the riclin-based hydrogel as an alternative to conventional commercial soft tissue fillers.

High Q lithium niobate metasurfaces with transparent electrodes for efficient amplitude and phase modulation.

Lithium niobate (LN)-based metasurfaces have demonstrated remarkable potential in integrated electro-optically adjustable metadevices with the maturation of thin film LN on insulator (LNOI) technology. Here, we proposed a type of high Q factor tunable metasurface with etchless LN, which is electrically driven in the vertical direction by using transparent conductive film. A transmission amplitude modulation of over 60 dB at a voltage of 20 V is realized through guided mode resonances created at the LN layer with a Q factor of 1320. Meanwhile, phase modulation is also realized with a reflective design by adding a gold layer at the bottom of the metasurface. With a gate voltage of 80 V, about 1.75π phase modulation is achieved while keeping reflection over 92%. Our proposed device achieves effective modulation of optical amplitude and phase in the near-infrared band, which lays a good foundation for the development of high performance LN-based active nanophotonic devices.

Circadian PER1 controls daily fat absorption with the regulation of PER1-PKA on phosphorylation of bile acid synthetase.

Several epidemiological studies suggest a correlation between eating time and obesity. Night eating syndrome characterized by a time-delayed eating pattern is positively associated with obesity in humans as well as in experimental animals. Here, we show that oil intake at night significantly makes more fat than that at day in wild-type mice, and circadian Period 1 (Per1) contributes to this day-night difference. Per1-knockout mice are protected from high-fat diet-induced obesity, which is accompanied by a reduction in the size of the bile acid pool, and the oral administration of bile acids restores fat absorption and accumulation. We identify that PER1 directly binds to the major hepatic enzymes involved in bile acid synthesis such as cholesterol 7alpha-hydroxylase and sterol 12alpha-hydroxylase. A biosynthesis rhythm of bile acids is accompanied by the activity and instability of bile acid synthases with PER1/PKA-mediated phosphorylation pathways. Both fasting and high fat stress enhance Per1 expression, increasing the fat absorption and accumulation. Our findings reveal that Per1 is an energy regulator and controls daily fat absorption and accumulation. Circadian Per1 controls daily fat absorption and accumulation, suggesting Per1 is a potential candidate of a key regulator in stress response and the relevant obesity risk.

Iron accumulation with age alters metabolic pattern and circadian clock gene expression through the reduction of AMP-modulated histone methylation.

Iron accumulates with age in mammals, and its possible implications in altering metabolic responses are not fully understood. Here, we report that both high-iron diet and advanced age in mice consistently altered gene expression of many pathways, including those governing the oxidative stress response and the circadian clock. We used a metabolomic approach to reveal similarities between metabolic profiles and the daily oscillation of clock genes in old and iron-overloaded mouse livers. In addition, we show that phlebotomy decreased iron accumulation in old mice, partially restoring the metabolic patterns and amplitudes of the oscillatory expression of clock genes Per1 and Per2. We further identified that the transcriptional regulation of iron occurred through a reduction in AMP-modulated methylation of histone H3K9 in the Per1 and H3K4 in the Per2 promoters, respectively. Taken together, our results indicate that iron accumulation with age can affect metabolic patterns and the circadian clock.

High quality factor unidirectional guided resonances of a silicon-on-lithium niobate photonic crystal slab for a tunable Gires-Tournois interferometer.

High quality (Q) factor, tunable unidirectional guided resonances (UGRs) based on a silicon-on-lithium niobate (Si-on-LN) photonic crystal (PhC) slab are proposed and numerically investigated. The Q factors of UGRs decay quadratically with respect to the distance from the Γ point to the wave vector along the Γ-X direction, and high Q factor UGRs are obtained by moving UGR close to the Γ point. Also, a Gires-Tournois interferometer (GTI) based on a UGR with a Q factor of 9465 is numerically demonstrated, which produces a maximum group delay of 30 ps around 1.55 µm with unitary reflectance. The group delay and operation wavelengths of the GTI can be adjusted effectively by tuning the refractive index of lithium niobate (LN) and the periods of the silicon bars. Our study may find applications in PhC surface-emitting lasers, dispersion compensation, and compression of light pulses.

Attenuating the triacylglycerol catabolism enhanced lipid production of Rhodotorula strain U13N3.

Enhancing the lipid production of oleaginous yeasts is conducive to cutting the cost of feedstock for biodiesel. To increase the lipid productivity of Rhodotorula sp. U13N3, genes involving lipid degradation were knocked out and fermentation conditions were investigated. Results of transcription analysis demonstrated that genes encoding the ATG15-like lipase (ATG15) and peroxisomal acyl-CoA oxidase (ACOX2) were upregulated significantly at the lipogenesis stage. When ATG15 and ACOX2 were knocked out separately from the genome by the CRISPR/Cas9 method, both ΔATG15 and ΔACOX2 mutants showed better lipid production ability than the parent strain. Flow cytometry and confocal microscopic analyses indicated that simultaneous the knockout of ATG15 and ACOX2 did not impact the cell viability, whereas the lipid production was enhanced markedly as the lipid yield increased by 67.03% in shake flasks. Afterward, the ΔATG15ΔACOX2 transformant (TO2) was cultivated in shake flasks in the fed-batch mode; the highest biomass and lipid yield reached 45.76 g/L and 27.14 g/L at 216 h, respectively. Better performance was achieved when TO2 was cultivated in the 1-L bioreactor. At the end of fermentation (180 h), lipid content, yield, yield coefficient, and productivity reached 65.53%, 27.35 g/L, 0.277 g/g glycerol, and 0.152 g/L/h, respectively. These values were at the high level in comparison with Rhodotorula strains cultivated in glycerol media. Besides, fermentation modes did not affect the fatty acid composition of TO2 significantly. In conclusion, blocking the lipid degradation was an applicable strategy to increase the lipid production of Rhodotorula strains without compromising their cell viability. KEY POINTS: • ATG15-like lipase and acyl-CoA oxidase (ACOX2) participated in lipid degradation. • Knockout of ATG15 and ACOX2 increased lipid productivity, and lipid yield coefficient. • Cell viability maintained at high level in the knockout mutants during fermentation.

ATP-induced hypothermia improves burn injury and relieves burn pain in mice.

Thermal burn injury is a severe and life-threatening form of trauma that presents a significant challenge to clinical therapy. Therapeutic hypothermia has been shown to be beneficial in various human pathologies. Adenosine triphosphate (ATP) induces a hypothermic state that resembles hibernation-like suspended animation in mammals. This study investigates the potential protective role of ATP-induced hypothermia in thermal burn injury. Male C57BL/6 mice underwent a sham procedure or third-degree burn, and ATP-induced hypothermia was applied immediately or 1 h after burn injury. Our results show that ATP-induced hypothermia significantly improved burn depth progression and reduced collagen degradation. Moreover, hypothermia induced by ATP alleviated burn-induced hyperinflammatory responses and oxidative stress. Metabolomic profiling revealed that ATP-induced hypothermia reversed the shifts of metabolic profiles of the skin in burn mice. In addition, ATP-induced hypothermia relieved nociceptive and inflammatory pain, as observed in the antinociceptive test. Our findings suggest that ATP-induced hypothermia attenuates burn injury and provides new insights into first-aid therapy after thermal burn injury.

An insulin-independent mechanism for transcriptional regulation of Foxo1 in type 2 diabetic mice.

Hepatic gluconeogenesis is the major contributor to the hyperglycemia observed in both patients and animals with type 2 diabetes. The transcription factor FOXO1 plays a dominant role in stimulating hepatic gluconeogenesis. FOXO1 is mainly regulated by insulin under physiological conditions, but liver-specific disruption of Foxo1 transcription restores normal gluconeogenesis in mice in which insulin signaling has been blocked, suggesting that additional regulatory mechanisms exist. Understanding the transcriptional regulation of Foxo1 may be conducive to the development of insulin-independent strategies for the control of hepatic gluconeogenesis. Here, we found that elevated plasma levels of adenine nucleotide in type 2 diabetes are the major regulators of Foxo1 transcription. We treated lean mice with 5'-AMP and examined their transcriptional profiles using RNA-seq. KEGG analysis revealed that the 5'-AMP treatment led to shifted profiles that were similar to db/db mice. Many of the upregulated genes were in pathways associated with the pathology of type 2 diabetes including Foxo1 signaling. As observed in diabetic db/db mice, lean mice treated with 5'-AMP displayed enhanced Foxo1 transcription, involving an increase in cellular adenosine levels and a decrease in the S-adenosylmethionine to S-adenosylhomocysteine ratio. This reduced methylation potential resulted in declining histone H3K9 methylation in the promoters of Foxo1, G6Pc, and Pepck. In mouse livers and cultured cells, 5'-AMP induced expression of more FOXO1 protein, which was found to be localized in the nucleus, where it could promote gluconeogenesis. Our results revealed that adenine nucleotide-driven Foxo1 transcription is crucial for excessive glucose production in type 2 diabetic mice.

Type 2 diabetic mice enter a state of spontaneous hibernation-like suspended animation following accumulation of uric acid.

Hibernation is an example of extreme hypometabolic behavior. How mammals achieve such a state of suspended animation remains unclear. Here we show that several strains of type 2 diabetic mice spontaneously enter into hibernation-like suspended animation (HLSA) in cold temperatures. Nondiabetic mice injected with ATP mimic the severe hypothermia analogous to that observed in diabetic mice. We identified that uric acid, an ATP metabolite, is a key molecular in the entry of HLSA. Uric acid binds to the Na+ binding pocket of the Na+/H+ exchanger protein and inhibits its activity, acidifying the cytoplasm and triggering a drop in metabolic rate. The suppression of uric acid biosynthesis blocks the occurrence of HLSA, and hyperuricemic mice induced by treatment with an uricase inhibitor can spontaneously enter into HLSA similar to that observed in type 2 diabetic mice. In rats and dogs, injection of ATP induces a reversible state of HLSA similar to that seen in mice. However, ATP injection fails to induce HLSA in pigs due to the lack of their ability to accumulate uric acid. Our results raise the possibility that nonhibernating mammals could spontaneously undergo HLSA upon accumulation of ATP metabolite, uric acid.

Phase change metamaterial for tunable infrared stealth and camouflage.

In the paper, a type of phase change metamaterial for tunable infrared stealth and camouflage is proposed and numerically studied. The metamaterial combines high temperature resistant metal Mo with phase-changing material GST and can be switched between the infrared "stealthy" and "non-stealthy" states through the phase change process of the GST. At the amorphous state of GST, there is a high absorption peak at the atmospheric absorption spectral range, which can achieve infrared stealth in the atmospheric window together with good radiative heat dissipation in the non-atmospheric window. While at the crystalline state of GST, the absorption peak becomes broader and exhibits high absorption in the long-wave infrared atmospheric window, leading to a "non-stealthy" state. The relationship between the infrared stealth performance of the structure with the polarization and incident angle of the incident light is also studied in detail. The proposed infrared stealth metamaterial employs a simple multilayer structure and could be fabricated in large scale. Our work will promote the research of dynamically tunable, large scale phase change metamaterials for infrared stealth as well as energy and other applications.

Design of photonic crystal fiber to excite surface plasmon resonance for highly sensitive magnetic field sensing.

To improve the sensing performance of optical fiber magnetic field sensor based on magneto-refractive effect, a D-shaped photonic crystal fiber-surface plasmon resonance (PCF-SPR) sensor based on magneto-refractive effect is proposed and its magnetic field sensing characteristics are investigated. The designed D-shaped PCF has a core-analyte-gold structure. Within the D-shaped PCF, the side polishing surface is coated with the gold film and the special hole is sandwiched between the core and the gold film. To realize the high magnetic field sensitivity for the fiber SPR magnetic field sensor, the special hole is filled with magnetic fluid (MF). In this paper, we analyze the mode transmission characteristics and magnetic field sensing characteristics of this fiber sensor by finite element method. We also obtain a general rule for the optimization of PCF-SPR sensors by analyzing the dispersion curves, the energy of the surface plasmon polariton mode and the core mode on the sensing performance of the designed fiber sensor. The maximum refractive index sensitivity and magnetic field sensitivity of the optimized fiber are 59714.3 nm/RIU and 21750 pm/mT (50-130 Oe), respectively. Compared with optical fiber magnetic field sensors based on magneto-refractive effect reported previously, the magnetic field sensitivity in this paper is nearly two orders of magnitude higher and it can initially achieve nT magnitude magnetic field resolution and testing capability. The proposed fiber sensor has the advantages of simple structure, easy production, high sensitivity, and strong environmental adaptability. It not only improves the sensing performance of optical fiber magnetic field sensors, but also provides an ideal alternative platform for biosensors like microfluidics because of its high refractive index sensitivity and the special structure.

Two-channel photonic crystal fiber based on surface plasmon resonance for magnetic field and temperature dual-parameter sensing.

In this paper, a dual-parameter sensor based on surface plasmon resonance (SPR)-photonic crystal fiber (PCF) is proposed, which can be applied in detecting the magnetic field and temperature. In this sensor, two elliptical channels are designed on both sides of the fiber core. The left channel (Ch 1) is coated with gold film and filled with magnetic fluid (MF) to achieve a response to the magnetic field and temperature using SPR. The right channel (Ch 2) is coated with gold film as well as Ta2O5 film to improve the SPR sensing performance. Finally, Ch 2 is filled with polydimethylsiloxane (PDMS) to achieve a response to the temperature. The mode characteristics, structural parameters and sensing performance are investigated by the finite element method. The results show that when the magnetic field is in the range of 50-130 Oe, the magnetic field sensitivities of Ch 1 and Ch 2 are 65 pm Oe-1 and 0 pm Oe-1, respectively. When the temperature is in the range of 17.5-27.5 °C, the temperature sensitivities of Ch 1 and Ch 2 are 520 pm °C-1 and 2360 pm °C-1, respectively. By establishing and demodulating a sensing matrix, the sensor can not only measure the temperature and magnetic field simultaneously but also solve the temperature cross-sensitivity problem. In addition, when the temperature exceeds a certain value, the proposed sensor is expected to achieve dual-parameter sensing without a matrix. The proposed dual-parameter SPR-PCF sensor has a unique structure and excellent sensing performance, which are important for the simultaneous sensing of multiple basic physical parameters.

Efficient coupling between an integrated photonic waveguide and an optical fiber.

Because on-chip integration of light sources cannot be realized effectively now, integrated nanophotonic chips must couple external light to the integrated photonic waveguide with high efficiency. Realizing high efficiency coupling requires a low-loss coupling structure. In this paper, the factors allowing high efficiency coupling to be realized are analyzed theoretically and the coupling between a lensed fiber and a tapered silicon nitride (Si3N4) waveguide is realized experimentally. Because the coupling efficiency of this structure is not ideal in the experiment, a scheme of direct alignment between the lensed fiber and a cantilever waveguide is proposed. Although the scheme offers a very high coupling efficiency in theory, because of the warpage of the waveguide they cannot be directly aligned experimentally. Finally, this paper advances a scheme for the tapered fiber to be directly overlapped onto the Si3N4/SiO2 cantilever. It is found that the coupler maintains an ideal coupling efficiency for wavelength from 1530 nm to 1600 nm, laying a foundation for the integration of nano-photonic devices and optical fibers.

Electrically tunable absorber based on a graphene integrated lithium niobate resonant metasurface.

Perfect absorbers are of great importance in various applications such as photodetectors, optical sensors and optical modulators. Recently, perfect absorption metasurface based on monolayer graphene has attracted lots of research interest. In this paper, a graphene-lithium niobate (LN) perfect absorption metasurface is constructed, where graphene works as a thin absorptive layer as well as a conductive electrode. The proposed device achieves 99.99% absorption at 798.42 nm and 1.14 nm redshift of the absorption peak is realized at 300 V(from -150 V to 150 V) external bias voltage through the electro-optical effect of LN, which enables the proposed device work as a electrically tunable absorber in the visible and near infrared range. The switching ratio of reflected light R/R0 could reach -44.08 dB with an applied voltage tuning from -150 V to 0 V at 798.42 nm. Our work demonstrates the potential of LN integrated high-Q resonant metasurface in realizing electro-optic tunable nanophotonic devices in the visible and near infrared band. It will promote the research of graphene integrated optoelectronic devices as well as LN based tunable nanophotonic devices which have widespread applications such as modulators and optical phase arrays.

Fabrication of a honeycomb-like bimetallic SERS substrate for the detection of triphenyltin chloride.

Triphenyltin chloride (TPhT) is an organotin compound that causes intensive toxicological risk to the environment and humans. A detection method with high sensitivity and stability is therefore desired to better detect TPhT. In this study, a novel SERS substrate was prepared by sputtering an ultra-thin Au layer on a honeycomb-like silver nanoarray fabricated via the nanosphere lithography method. The ultra-thin Au layer was formed by sputtering the intermittent Au nanoparticles on the silver nanoarray, resulting in bimetallic coupling with dramatically increased hotspots and extremely high SERS enhancement with an analytical enhancement factor (AEF) of 6.08 × 109 using Rhodamine 6G (R6G) as the probe molecule. Based on density functional theory (DFT) simulations, the Raman characteristic peaks of TPhT at 999 cm-1 and 655 cm-1 were selected for TPhT detection. The AEF of the SERS substrate HC5-AgAu was calculated to be 3.38 × 106 with the detection concentration of TPhT down to 10-10 M. The as-prepared honeycomb-like silver-gold bimetallic SERS substrate demonstrated great stability and sensitivity for TPhT detection, which might also be applied in monitoring many other environmental pollutants.