Light-driven nanoscale vectorial currents.

Controlled charge flows are fundamental to many areas of science and technology, serving as carriers of energy and information, as probes of material properties and dynamics1 and as a means of revealing2,3 or even inducing4,5 broken symmetries. Emerging methods for light-based current control5-16 offer particularly promising routes beyond the speed and adaptability limitations of conventional voltage-driven systems. However, optical generation and manipulation of currents at nanometre spatial scales remains a basic challenge and a crucial step towards scalable optoelectronic systems for microelectronics and information science. Here we introduce vectorial optoelectronic metasurfaces in which ultrafast light pulses induce local directional charge flows around symmetry-broken plasmonic nanostructures, with tunable responses and arbitrary patterning down to subdiffractive nanometre scales. Local symmetries and vectorial currents are revealed by polarization-dependent and wavelength-sensitive electrical readout and terahertz (THz) emission, whereas spatially tailored global currents are demonstrated in the direct generation of elusive broadband THz vector beams17. We show that, in graphene, a detailed interplay between electrodynamic, thermodynamic and hydrodynamic degrees of freedom gives rise to rapidly evolving nanoscale driving forces and charge flows under the extremely spatially and temporally localized excitation. These results set the stage for versatile patterning and optical control over nanoscale currents in materials diagnostics, THz spectroscopies, nanomagnetism and ultrafast information processing.

A novel mechanism of major ginsenosides from Panax ginseng against multiple organ aging in middle-aged mice: Phosphatidylcholine-myo-inositol metabolism based on metabolomic analysis.

Aging is a complex, degenerative process associated with various metabolic abnormalities. Ginsenosides (GS) is the main active components of Panax ginseng, which has anti-aging effects and improves metabolism. However, the anti-aging effect and the mechanism of GS in middle-aged mice has not been elucidated. In this study, GS after 3-month treatment significantly improved the grip strength, fatigue resistance, cognitive indices, and cardiac function of 15-month-old mice. Meanwhile, GS treatment reduced the fat content and obviously inhibited histone H2AX phosphorylation at Ser 139 (γ-H2AX), a marker of DNA damage in major organs, especially in the heart and liver. Further, the correlation analysis of serum metabolomics combined with aging phenotype suggested that myo-inositol (MI) upregulated by GS was positively correlated with left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), the main indicators of cardiac function. More importantly, liver tissue metabolomic analysis showed that GS increased MI content by promoting the synthesis pathway from phosphatidylcholine (PC) to MI for the inhibition of liver aging. Finally, we proved that MI reduced the percentage of senescence-associated ß-galactosidase staining, γ-H2AX immunofluorescence staining, p21 expression, and the production of reactive oxygen species in H2O2-induced cardiomyocytes. These results suggest that GS can enhance multiple organ functions, especially cardiac function for promoting the healthspan of aging mice, which is mediated by the conversion of PC to MI in the liver and the increase of MI level in the serum. Our study might provide new insights into the potential mechanisms of ginsenosides for prolonging the healthspan of natural aging mice.

Metasurface-based varifocal Alvarez lens at microwave frequencies.

Lenses with a tunable focus are highly desirable but remain a challenge. Here, we demonstrate a microwave varifocal meta-lens based on the Alvarez lens principle, consisting of two mechanically movable tri-layer metasurface phase plates with reversed cubic spatial profiles. The manufactured multilayer Alvarez meta-lens enables microwave beam collimation/focusing at frequencies centered at 7.5 GHz, and shows one octave focal length tunability when transversely translating the phase plates by 8 cm. The measurements reveal a gain enhancement up to 15 dB, 3-dB beam width down to 3.5∘, and relatively broad 3-dB bandwidth of 3 GHz. These advantageous characteristics, along with its simplicity, compactness, and lightweightness, make the demonstrated flat Alvarez meta-lens suitable for deployment in many microwave systems.

Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence.

It is well known that extreme heat events happen frequently due to climate change. However, studies examining the direct health impacts of increased temperature and heat waves are lacking. Previous reports revealed that heatstroke induced acute lung injury and pulmonary dysfunction. This study aimed to investigate whether heat exposure induced lung fibrosis and to explore the underlying mechanisms. Male C57BL/6 mice were exposed to an ambient temperature of 39.5 ± 0.5 °C until their core temperature reached the maximum or heat exhaustion state. Lung fibrosis was observed in the lungs of heat-exposed mice, with extensive collagen deposition and the elevated expression of fibrosis molecules, including transforming growth factor-ß1 (TGF-ß1) and Fibronectin (Fn1) (p < 0.05). Moreover, epithelial-mesenchymal transition (EMT) occurred in response to heat exposure, evidenced by E-cadherin, an epithelial marker, which was downregulated, whereas markers of EMT, such as connective tissue growth factor (CTGF) and the zinc finger transcriptional repressor protein Slug, were upregulated in the heat-exposed lung tissues of mice (p < 0.05). Subsequently, cell senescence examination revealed that the levels of both senescence-associated ß-galactosidase (SA-ß-gal) staining and the cell cycle protein kinase inhibitor p21 were significantly elevated (p < 0.05). Mechanistically, the cGAS-STING signaling pathway evoked by DNA damage was activated in response to heat exposure (p < 0.05). In summary, we reported a new finding that heat exposure contributed to the development of early pulmonary fibrosis-like changes through the DNA damage-activated cGAS-STING pathway followed by cellular senescence.

Near-Infrared-Driven Nanorocket for Rapid and Ultrasensitive Detection of MicroRNA.

Herein, by introducing gold nanostars (AuNSs) as fuel core, a near-infrared-driven nanorocket (NIDNR) with pretty fast walking was exploited for ultrasensitive miRNA detection. Compared with traditional nanomaterials-comprised nanomachines (NMs), the NIDNR possesses much better kinetic and thermodynamic performance owing to the extra photothermal driving force from localized surface plasmon (LSP). Impressively, the whole reaction time of NIDNR down to 15 min was realized, which is almost more than 8 times beyond those of conventional DNA-based NMs. This way, the inherent obstacle of traditional NMs, including long reaction time and low efficiency, could be easily addressed. As a proof of concept, the NIDNR was successfully applied to develop an electrochemical biosensing platform for rapid and sensitive detection of miRNA with an LOD down to 2.95 aM and achieved the real-time assay of real biological samples from human hepatocellular carcinoma cells (MHCC97L) and HeLa, thus providing an innovative insight to design more versatile DNA nanomachines for ultimate application in biosensing platform construction and clinical sample detection.

scSSA: A clustering method for single cell RNA-seq data based on semi-supervised autoencoder.

BACKGROUND: Single cell sequencing is a technology for high-throughput sequencing analysis of genome, transcriptome and epigenome at the single cell level. It can improve the shortcomings of traditional methods, reveal the gene structure and gene expression state of a single cell, and reflect the heterogeneity between cells. Among them, the clustering analysis of single-cell RNA data is a very important step, but the clustering of single-cell RNA data is faced with two difficulties, dropout events and dimension curse. At present, many methods are only driven by data, and do not make full use of the existing biological information. RESULTS: In this work, we propose scSSA, a clustering model based on semi-supervised autoencoder, fast independent component analysis (FastICA) and Gaussian mixture clustering. Firstly, the semi-supervised autoencoder imputes and denoises the scRNA-seq data, and then get the low-dimensional latent representation. Secondly, the low-dimensional representation is reduced the dimension and clustered by FastICA and Gaussian mixture model respectively. Finally, scSSA is compared with Seurat, CIDR and other methods on 10 public scRNA-seq datasets. CONCLUSION: The results show that scSSA has superior performance in cell clustering on 10 public datasets. In conclusion, scSSA can accurately identify the cell types and is generally applicable to all kinds of single cell datasets. scSSA has great application potential in the field of scRNA-seq data analysis. Details in the code have been uploaded to the website https://github.com/houtongshuai123/scSSA/.

Multiregion Linear DNA Walker-Mediated Ultrasensitive Electrochemical Biosensor for miRNA Detection.

In this work, an intelligent multiregion linear DNA walker (MLDW) with a high walking rate and a high amplification efficiency was explored for ultrasensitive detection of miRNA. Significantly, amounts of functional domain could be concentrated in a long linear DNA obtained by the target miRNA-mediated rolling-circle amplification to simultaneously increase the local concentration and collision probability, resulting in an obviously improved reaction rate. Impressively, the MLDW can accomplish the reaction within 30 min, which is at least 4 times beyond that of traditional single-leg and multiple-leg DNA walkers. As a proof of concept, the high-efficiency MLDW was used to develop an electrochemical biosensing platform for ultrasensitive detection of target miRNA-21 with a low detection limit down to 36 aM. Therefore, the MLDW we designed puts forward an innovative insight to construct a functional DNA nanodevice and promote the investigation of the inherent performance of nucleic acid signal amplification for ultimate application in the detection of biomolecules and clinical disease diagnosis.

Correcting abnormalities in miR-124/PTPN1 signaling rescues tau pathology in Alzheimer's disease.

MicroRNAs have been implicated in diverse physiological and pathological processes. We previously reported that aberrant microRNA-124 (miR-124)/non-receptor-type protein phosphatase 1 (PTPN1) signaling plays an important role in the synaptic disorders associated with Alzheimer's disease (AD). In this study, we further investigated the potential role of miR-124/PTPN1 in the tau pathology of AD. We first treated the mice with intra-hippocampal stereotactic injections. Then, we used quantitative real-time reverse transcription PCR (qRT-PCR) to detect the expression of microRNAs. Western blotting was used to measure the level of PTPN1, the level of tau protein, the phosphorylation of tau at AD-related sites, and alterations in the activity of glycogen synthase kinase 3ß (GSK-3ß) and protein phosphatase 2 (PP2A). Immunohistochemistry was also used to detect changes in tau phosphorylation levels at AD-related sites and somadendritic aggregation. Soluble and insoluble tau protein was separated by 70% formic acid (FA) extraction to examine tau solubility. Finally, behavioral experiments (including the Morris water maze, fear conditioning, and elevated plus maze) were performed to examine learning and memory ability and emotion-related behavior. We found that artificially replicating the abnormalities in miR-124/PTPN1 signaling induced AD-like tau pathology in the hippocampus of wild-type mice, including hyperphosphorylation at multiple sites, insolubility and somadendritic aggregation, as well as learning/memory deficits. We also found that disruption of miR-124/PTPN1 signaling was caused by the loss of RE1-silencing transcription factor protein, which can be initiated by Aß insults or oxidative stress, as observed in the brains of P301S mice. Correcting the deregulation of miR-124/PTPN1 signaling rescued the tau pathology and learning/memory impairments in the P301S mice. We also found that miR-124/PTPN1 abnormalities induced activation of glycogen synthase kinase 3 (GSK-3) and inactivation of protein phosphatase 2A (PP2A) by promoting tyrosine phosphorylation, implicating an imbalance in tau kinase/phosphatase. Thus, targeting the miR-124/PTPN1 signaling pathway is a promising therapeutic strategy for AD.

Ginsenoside Rg1 promotes lymphatic drainage and improves chronic inflammatory arthritis.

OBJECTIVE: The lymphatic system plays an important role in joint diseases. This study aimed to evaluate the effects of ginsenoside Rg1 on lymphatic drainage and accumulation of inflammatory products in the joints. METHODS: Two-month-old transgenic mice that overexpress tumor necrosis factor alpha (TNF-α; TNF-Tg) were used as the animal models. Ginsenoside Rg1 was administered for 12 weeks and the lymphatic drainage in the mice was evaluated using near infrared-indocyanine green (NIR-ICG) lymphatic imaging system. The clinical symptoms of arthritis were evaluated weekly. The ankle and knee joints were harvested for hematoxylin-eosin (HE), alcian blue/orange G (ABOG), and tartrate-resistant acid phosphatase (TRAP) staining, and the foot dorsal skin was used for whole-mount immuno-staining. Simultaneously, the serum levels of IL-6 and TNF-α were detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: Ginsenoside Rg1 significantly improved the lymphatic drainage function, reduced synovial inflammation and bone erosion, decreased serum IL-6 and TNF-α concentration, and increased smooth muscle coverage on the collecting lymphatic vessels in the foot skin of the TNF-Tg mice. Furthermore, ginsenoside Rg1 treatment for 12 weeks did not cause any damage to the liver and kidney tissues. CONCLUSION: Ginsenoside Rg1 improves lymphatic drainage and joint inflammation in TNF-Tg mice. Therefore, ginsenoside Rg1 has the potential to be a candidate drug for the treatment of inflammatory arthritis.

Observation of Intersubband Polaritons in a Single Nanoantenna Using Nano-FTIR Spectroscopy.

Strong coupling of an intersubband (ISB) electron transition in quantum wells to a subwavelength plasmonic nanoantenna can give rise to intriguing quantum phenomena, such as ISB polariton condensation, and enable practical devices including low threshold lasers. However, experimental observation of ISB polaritons in an isolated subwavelength system has not yet been reported. Here, we use scanning probe near-field microscopy and Fourier-transform infrared (FTIR) spectroscopy to detect formation of ISB polariton states in a single nanoantenna. We excite the nanoantenna by a broadband IR pulse and spectrally analyze evanescent fields on the nanoantenna surface. We observe the distinctive splitting of the nanoantenna resonance peak into two polariton modes and two π-phase steps corresponding to each of the modes. We map ISB polariton dispersion using a set of nanoantennae of different sizes. This nano-FTIR spectroscopy approach opens doors for investigations of ISB polariton physics in the single subwavelength nanoantenna regime.

Broadband Linear-to-Circular Polarization Conversion Enabled by Birefringent Off-Resonance Reflective Metasurfaces.

Due to the scarcity of circular polarization light sources, linear-to-circular polarization conversion is required to generate circularly polarized light for a variety of applications. Despite significant past efforts, broadband linear-to-circular polarization conversion remains elusive particularly in the terahertz and midinfrared frequency ranges. Here we propose a novel mechanism based on coupled mode theory, and experimentally demonstrate at terahertz frequencies that highly efficient (power conversion efficiency approaching unity) and ultrabroadband (fractional bandwidth up to 80%) linear-to-circular polarization conversion can be accomplished by the judicious design of birefringent metasurfaces. The underlying mechanism operates in the frequency range between well separated resonances, and relies upon the phase response of these resonances away from the resonant frequencies, as well as the balance of the resonant and nonresonant channels. This mechanism is applicable for any operating frequencies from microwave to visible. The present Letter potentially opens a wide range of opportunities in wireless communications, spectroscopy, and emergent quantum materials research where circularly polarized light is desired.

High-Temperature Refractory Metasurfaces for Solar Thermophotovoltaic Energy Harvesting.

Solar energy promises a viable solution to meet the ever-increasing power demand by providing a clean, renewable energy alternative to fossil fuels. For solar thermophotovoltaics (STPV), high-temperature absorbers and emitters with strong spectral selectivity are imperative to efficiently couple solar radiation into photovoltaic cells. Here, we demonstrate refractory metasurfaces for STPV with tailored absorptance and emittance characterized by in situ high-temperature measurements, featuring thermal stability up to at least 1200 °C. Our tungsten-based metasurface absorbers have close-to-unity absorption from visible to near-infrared and strongly suppressed emission at longer wavelengths, while our metasurface emitters provide wavelength-selective emission spectrally matched to the band-edge of InGaAsSb photovoltaic cells. The projected overall STPV efficiency is as high as 18% when a fully integrated absorber/emitter metasurface structure is employed, which is comparable to the efficiencies of the best currently available commercial single-junction PV cells and can be further improved to potentially exceed those in mainstream photovoltaic technologies. Our work opens a path forward for high-performance STPV systems based on refractory metasurface structures.

Resonance coupling and polarization conversion in terahertz metasurfaces with twisted split-ring resonator pairs.

We investigate edge-coupling of twisted split-ring resonator (SRR) pairs in the terahertz (THz) frequency range. Using a simple coupled-resonator model we show that such a system exhibits resonance splitting and cross-polarization conversion. Numerical simulations and experimental measurements agree well with theoretical calculations, verifying the resonance splitting as a function of the coupling strength given by the SRR separation. We further show that a metal ground plane can be integrated to significantly enhance the resonance coupling, which enables the effective control of resonance splitting and the efficiency and bandwidth of the cross-polarization conversion. Our findings improve the fundamental understanding of metamaterials with a view of accomplishing metamaterial functionalities with enhanced performance, which is of great interest in realizing THz functional devices required in a variety of applications.

Demonstration of a highly efficient terahertz flat lens employing tri-layer metasurfaces.

We demonstrate a terahertz flat lens based on tri-layer metasurfaces allowing for broadband linear polarization conversion, where the phase can be tuned through a full 2π range by tailoring the geometry of the subwavelength resonators. The lens functionality is realized by arranging these resonators to create a parabolic spatial phase profile. The fabricated 124-µm-thick device is characterized by scanning the beam profile and cross section, showing diffraction-limited focusing and ∼68% overall efficiency at the operating frequency of 400 GHz. This device has potential for applications in terahertz imaging and communications, as well as beam control in general.

A review of metasurfaces: physics and applications.

Metamaterials are composed of periodic subwavelength metal/dielectric structures that resonantly couple to the electric and/or magnetic components of the incident electromagnetic fields, exhibiting properties that are not found in nature. This class of micro- and nano-structured artificial media have attracted great interest during the past 15 years and yielded ground-breaking electromagnetic and photonic phenomena. However, the high losses and strong dispersion associated with the resonant responses and the use of metallic structures, as well as the difficulty in fabricating the micro- and nanoscale 3D structures, have hindered practical applications of metamaterials. Planar metamaterials with subwavelength thickness, or metasurfaces, consisting of single-layer or few-layer stacks of planar structures, can be readily fabricated using lithography and nanoprinting methods, and the ultrathin thickness in the wave propagation direction can greatly suppress the undesirable losses. Metasurfaces enable a spatially varying optical response (e.g. scattering amplitude, phase, and polarization), mold optical wavefronts into shapes that can be designed at will, and facilitate the integration of functional materials to accomplish active control and greatly enhanced nonlinear response. This paper reviews recent progress in the physics of metasurfaces operating at wavelengths ranging from microwave to visible. We provide an overview of key metasurface concepts such as anomalous reflection and refraction, and introduce metasurfaces based on the Pancharatnam-Berry phase and Huygens' metasurfaces, as well as their use in wavefront shaping and beam forming applications, followed by a discussion of polarization conversion in few-layer metasurfaces and their related properties. An overview of dielectric metasurfaces reveals their ability to realize unique functionalities coupled with Mie resonances and their low ohmic losses. We also describe metasurfaces for wave guidance and radiation control, as well as active and nonlinear metasurfaces. Finally, we conclude by providing our opinions of opportunities and challenges in this rapidly developing research field.

FeCu bimetallic clusters for efficient urea production via coupling reduction of carbon dioxide and nitrate.

Urea electrosynthesis has appeared to meet the nitrogen cycle and carbon neutrality with energy-saving features. Copper can co-electrocatalyze among CO2 and nitrogen species to generate urea, however developing effective electrocatalysts is still an obstacle. Here, we developed a nitrogen-doped porous carbon loaded with FeCu clusters that convert CO2 and NO3- into urea, with the highest Faradaic efficiency of 39.8 % and yield rate of 1024.6 µg h-1 mgcat.-1, under optimized ambient conditions, exceeding that at the Fe or Cu homogeneous sites. Furthermore, a favorable CN coupling pathway originates from *NHCO and *NHCONO two intermediates with lower free energy barriers on FeCu dual active sites are verified through in-situ Fourier transform infrared spectroscopy and theoretical calculations. This research might provide deep insights into coupling mechanisms and investigation of efficient catalysts for green urea production.

Easily constructed porous silver films for efficient catalytic CO2 reduction and Zn-CO2 batteries.

For the electroreduction of carbon dioxide into high value-added chemicals, highly active and selective catalysts are crucial, and metallic silver is one of the most intriguing candidate materials available at a reasonable cost. Herein, through a novel two-step operation of Ag paste/SBA-15 coating and HF etching, porous silver films on a commercial carbon paper with a waterproofer (p-Ag/CP) could be easily fabricated on a large scale as highly efficient carbon dioxide reduction reaction (CO2RR) electrocatalysts with a CO Faraday efficiency (FECO) as high as 96.7% at -1.0 V vs. the reversible hydrogen electrode (RHE), and it still reaches up to 90% FECO over applied potentials ranging from -0.8 to -1.1 V vs. the RHE. Meanwhile, the membrane electrode assembly (MEA) utilizing the p-Ag/CP catalyst has achieved a current density, FECO, and stability of ∼60 mA cm-2, >91%, and 11 h, respectively. Furthermore, the assembled aqueous Zn-CO2 battery using p-Ag/CP cathode yielded a peak power density of 0.34 mW cm-2, 75 charge-discharge cycles for 25 h, and 64% FECO at 2.5 mA cm-2. Compared with flat Ag/CP, the significant enhancement in the CO2RR activity of p-Ag/CP was mainly attributed to the distinctive porous structure and an improved three-phase boundary, which is capable of inducing the stabilization of *COOH intermediates, increased active specific surface areas, fast electron transfer kinetic and mass transportation. Further, theoretical calculations revealed that p-Ag/CP possessed an optimized energy barrier for *COOH intermediates.

Molecular dynamics simulation of surfactant reducing MMP between CH4 and n-decane.

Reinjecting produced methane offers cost-efficiency and environmental benefits for enhances oil recovery. High minimum miscibility pressure (MMP) in methane-oil systems poses a challenge. To overcome this, researchers are increasingly focusing on using surfactants to reduce MMP, thus enhancing the effectiveness of methane injections for oil recovery. This study investigated the impact of pressure and temperature on the equilibrium interfacial tension of the CH4+n-decane system using molecular dynamics simulations and the vanishing interfacial tension technique. The primary goal was to assess the potential of surfactants in lowering MMP. Among four tested surfactants, ME-6 exhibited the most promise by reducing MMP by 14.10% at 373 K. Key findings include that the addition of ME-6 enriching CH4 at the interface, enhancing its solubility in n-decane, improving n-decane diffusion capacity, CH4 weakens n-decane interactions and strengthens its own interaction with n-decane. As the difference in interactions of n-decane with ME-6's ends decreases, the system trends towards a mixed phase. This research sets the stage for broader applications of mixed-phase methane injection in reservoirs, with the potential for reduced gas flaring and environmental benefits.

LRRK2 is involved in heat exposure-induced acute lung injury and alveolar type II epithelial cell dysfunction.

Heat exposure induces excessive hyperthermia associated with systemic inflammatory response that leads to multiple organ dysfunction including acute lung injury. However, how heat impairs the lung remains elusive so far. We aimed to explore the underlying mechanism by focusing on leucine-rich repeat kinase 2 (LRRK2), which was associated with lung homeostasis. Both in vivo and in vitro models were induced by heat exposure. Firstly, heat exposure exerted core temperature (Tc) disturbance, pulmonary dysfunction, atelectasis, inflammation, impaired energy metabolism, and reduced surfactant proteins in the lung of mice. In addition, decreased LRRK2 expression and increased heat shock proteins (HSPs) 70 were observed with heat exposure in both the lung of mice and alveolar type II epithelial cells (AT2). Furthermore, LRRK2 inhibition aggravated heat exposure-initiated Tc dysregulation, injury in the lung and AT2 cells, and enhanced HSP70 expression. In conclusion, LRRK2 is involved in heat-induced acute lung injury and AT2 cell dysfunction.

Ginseng polysaccharide components attenuate obesity and liver lipid accumulation by regulating fecal microbiota and hepatic lysine degradation.

The increasing incidence of obesity has led to widespread attention in the exploration of natural ingredients. Ginseng polysaccharides (PGP), the main components from Panax ginseng, have been reported potential effect to attenuate obesity and regulate lipid metabolism. In this study, we found that PGP inhibited the high-fat diet (HFD)-induced weight gain, fat ratio and fat tissue weight after 8-week administration. Serum and liver lipid analysis showed that PGP decreased the levels of triglyceride and total cholesterol, which was mediated by the inhibition of key genes for fatty acid and cholesterol metabolisms. Metabolomics studies showed that the inhibitory effect of PGP on liver lipid accumulation was significantly correlated with its regulation of citric acid cycle and lysine degradation. PGP regulated the expression of genes related to lysine degradation in both liver tissue and hepatocytes. In addition, PGP reshaped the composition of fecal microbiota at the genus and species levels in obese mice. Spearman's correlation analysis demonstrated that Staphylococcus sciuri, Staphylococcus lentus, and Pseudoflavonifractor sp. An85 may be the potential targets that PGP maintains the abundance of l-lysine against obesity. It concluded that PGP can attenuate obesity and liver lipid accumulation by regulating fecal microbiota and hepatic lysine degradation.