Hypomethylation of glycine dehydrogenase promoter in peripheral blood mononuclear cells is a new diagnostic marker of hepatitis B virus-associated hepatocellular carcinoma.

BACKGROUND: Glycine dehydrogenase (GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). METHODS: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B (CHB), and 35 healthy controls (HCs). The methylation status of GLDC promoter in peripheral mononuclear cells (PBMCs) was identified by methylation specific polymerase chain reaction (MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction (qPCR). RESULTS: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients (27.0%) compared to that in CHB patients (68.6%) and HCs (74.3%) (P < 0.001). The methylated group had lower alanine aminotransferase level (P = 0.035) and lower rates of tumor node metastasis (TNM) III/IV (P = 0.043) and T3/T4 (P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients (P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters (P = 0.003). The diagnostic accuracy of alpha-fetoprotein (AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone (AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients (P = 0.038). CONCLUSIONS: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa in children diagnosed by echocardiography: Two case reports.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is rare, particularly in children, and is potentially fatal. This article presents two cases of pediatric mitral-aortic intervalvular fibrosa pseudoaneurysm: one secondary to infective endocarditis and the other confirmed to be congenital in nature. The characteristic echocardiographic manifestations of mitral-aortic intervalvular fibrosa pseudoaneurysm demonstrated in this study will enhance diagnostic efficacy and guide early clinical intervention.

Identification and characterization of a novel hydroxylamine oxidase, DnfA, that catalyzes the oxidation of hydroxylamine to N2.

Nitrogen (N2) gas in the atmosphere is partially replenished by microbial denitrification of ammonia. Recent study has shown that Alcaligenes ammonioxydans oxidizes ammonia to dinitrogen via a process featuring the intermediate hydroxylamine, termed "Dirammox" (direct ammonia oxidation). However, the unique biochemistry of this process remains unknown. Here, we report an enzyme involved in Dirammox that catalyzes the conversion of hydroxylamine to N2. We tested previously annotated proteins involved in redox reactions, DnfA, DnfB, and DnfC, to determine their ability to catalyze the oxidation of ammonia or hydroxylamine. Our results showed that none of these proteins bound to ammonia or catalyzed its oxidation; however, we did find DnfA bound to hydroxylamine. Further experiments demonstrated that, in the presence of NADH and FAD, DnfA catalyzed the conversion of 15N-labeled hydroxylamine to 15N2. This conversion did not happen under oxygen (O2)-free conditions. Thus, we concluded that DnfA encodes a hydroxylamine oxidase. We demonstrate that DnfA is not homologous to any known hydroxylamine oxidoreductases and contains a diiron center, which was shown to be involved in catalysis via electron paramagnetic resonance experiments. Furthermore, enzyme kinetics of DnfA were assayed, revealing a Km of 92.9 ± 3.0 µM for hydroxylamine and a kcat of 0.028 ± 0.001 s-1. Finally, we show that DnfA was localized in the cytoplasm and periplasm as well as in tubular membrane invaginations in HO-1 cells. To the best of our knowledge, we conclude that DnfA is the first enzyme discovered that catalyzes oxidation of hydroxylamine to N2.

Compact nanosecond Yb:YAG/V:YAG solid-state laser generating switchable radially and azimuthally beams.

We demonstrated a compact self-starting nanosecond Yb:YAG/V:YAG solid-state laser with cylindrical vector beams output modulated by the intracavity mode converter S-waveplate experimentally. We can deliver the stable Q-switched pulse with the highest repetition rate 3.61 kHz and minimum pulse width 26 ns at the wavelength of 1030.07 nm with the help of the V:YAG crystal. In addition, the switchable radially and azimuthally polarized beams can be realized with polarization extinction ratios of 92.3% and 89.6%, respectively. The compact laser configuration can provide solutions for generating stable nanosecond structured light, and may benefit the applications like micro/nano material processing.

Dispersion of the third-order optical nonlinearities in 2D (PEA)2PbI4 perovskite film.

We report the wavelength-dependent third-order optical nonlinearity of two-dimensional halide organic-inorganic perovskite (PEA)2PbI4 film experimentally. The high-quality two-dimensional (PEA)2PbI4 film prepared via confinement-assisted drop-casting process exhibits ultrafast optical response and large third-order optical nonlinearities, and the measured nonlinear refractive index is closer to the quantum perturbation model accounting for the excitonic effect. In addition, the wavelength-dependent optical response transition from self-focusing to self-defocusing, saturable absorption to reverse saturable absorption has been observed and investigated. The experimental results confirm the large third-order optical nonlinearities in (PEA)2PbI4 film and may make inroads toward developing cost-effective high-performance optoelectronic devices.

High-damage-threshold mid-infrared saturable absorber enabled by tantalum carbide nanoparticles.

A stable mid-infrared saturable absorber with a high damage threshold is urgently required for high-performance optical modulation in the mid-infrared regime. Here, we demonstrate stable mid-infrared erbium-doped fiber laser generation modulated by tantalum carbide nanoparticles (TaC NPs) experimentally. The TaC NPs show high physicochemical stability, obvious nonlinear optical absorption, and a high damage threshold. By introducing the TaC-based saturable absorber into an erbium-doped fiber laser, stable nanosecond pulses can be successfully delivered with a minimum pulse duration of 575 ns and signal-to-noise ratio of over 40 dB. The experimental results show that TaC NPs can act as a stable mid-infrared pulse modulator, and may make inroads for developing highly stable broadband optoelectronic devices.

Human ß-defensins are correlated with the immune infiltration and regulated by vitamin D3 in periodontitis.

OBJECTIVE: Exploring the correlation between human ß-defensins (HBDs) and immune infiltration in periodontitis, and whether it is regulated by vitamin D3 . BACKGROUND: The human body produces essential antimicrobial peptides called HBDs, which are associated with periodontitis. There is a strong link between periodontal tissue destruction and the immune cell infiltration. Moreover, vitamin D3 has been reported to regulate the expression of immune cell chemokines. However, the relationship between vitamin D3 , HBDs, and immune infiltration in periodontitis remains to be investigated. METHODS: The Gene Expression Omnibus database was accessed to obtain transcriptomic information of gingival samples taken from periodontitis patients. The expression value of HBD-2 and HBD-3 was calculated. Additionally, using the online program ImmuCellAl, 10 immune cells were scored for immune infiltration in the high-HBDs-expression group and the low-HBDs-expression group, separately. After that, transcriptome sequencing was done based on human gingival fibroblasts that had received vitamin D3 treatment. Furthermore, hGFs were treated by vitamin D3 , tumor necrosis factor-α (TNF-α), and Porphyromonas gingivalis lipopolysaccharide (Pg-LPS). The expressions of HBD-2, HBD-3, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) were detected. To seek the potential mechanism, CYP27A1 siRNA was employed to reduce the expression of CYP27A1, and nuclear factor-gene binding protein 65 (NF-κB p65) was examined. RESULTS: In GSE10334, the expressions of HBD-2 and HBD-3 were down-regulated in periodontitis group. Meanwhile, monocyte, macrophage, and CD4_T cell were less infiltrated in low-HBD-2-expression group, while less Gamma-delta T-cell infiltration was found in low-HBD-3-expression group. Transcriptome sequencing found that 21 genes were significantly expressed, of which the function was enriched in response to bacterial origin and TNF signal pathway. Vitamin D3 could significantly up-regulate the expression of HBD-2 and HBD-3, which could be controlled by knocking down CYP27A1 mRNA expression. With prolonged vitamin D3 stimulation, the expression of HBD-2 and HBD-3 increased. TNF-α/Pg-LPS could significantly increase the expression of HBD-2, HBD-3, IL-8, MCP-1, and p65, all of which were reduced by vitamin D3 . CONCLUSION: HBDs are correlated with immune infiltration in periodontitis. Vitamin D3 inhibits the expression of HBDs and chemokines induced by TNF-α/Pg-LPS, possibly through NF-κB pathway, in human gingival fibroblasts.

Genetic Foundations of Direct Ammonia Oxidation (Dirammox) to N2 and MocR-Like Transcriptional Regulator DnfR in Alcaligenes faecalis Strain JQ135.

Ammonia oxidation is an important process in both the natural nitrogen cycle and nitrogen removal from engineered ecosystems. Recently, a new ammonia oxidation pathway termed Dirammox (direct ammonia oxidation, NH3→NH2OH→N2) has been identified in Alcaligenes ammonioxydans. However, whether Dirammox is present in other microbes, as well as its genetic regulation, remains unknown. In this study, it was found that the metabolically versatile bacterium Alcaligenes faecalis strain JQ135 could efficiently convert ammonia into N2 via NH2OH under aerobic conditions. Genetic deletion and complementation results suggest that dnfABC is responsible for the ammonia oxidation to N2 in this strain. Strain JQ135 also employs aerobic denitrification, mainly producing N2O and trace amounts of N2, with nitrite as the sole nitrogen source. Deletion of the nirK and nosZ genes, which are essential for denitrification, did not impair the capability of JQ135 to oxidize ammonia to N2 (i.e., Dirammox is independent of denitrification). Furthermore, it was also demonstrated that pod (which encodes pyruvic oxime dioxygenase) was not involved in Dirammox and that AFA_16745 (which was previously annotated as ammonia monooxygenase and is widespread in heterotrophic bacteria) was not an ammonia monooxygenase. The MocR-family transcriptional regulator DnfR was characterized as an activator of the dnfABC operon with the binding motif 5'-TGGTCTGT-3' in the promoter region. A bioinformatic survey showed that homologs of dnf genes are widely distributed in heterotrophic bacteria. In conclusion, this work demonstrates that, besides A. ammonioxydans, Dirammox occurs in other bacteria and is regulated by the MocR-family transcriptional regulator DnfR. IMPORTANCE Microbial ammonia oxidation is a key and rate-limiting step of the nitrogen cycle. Three previously known ammonia oxidation pathways (i.e., nitrification, anaerobic ammonia oxidation [Anammox], and complete ammonia oxidation [Comammox]) are mediated by autotrophic microbes. However, the genetic foundations of ammonia oxidation by heterotrophic microorganisms have not been investigated in depth. Recently, a previously unknown pathway, termed direct ammonia oxidation to N2 (Dirammox), has been identified in the heterotrophic bacterium Alcaligenes ammonioxydans HO-1. This paper shows that, in the metabolically versatile bacterium Alcaligenes faecalis JQ135, the Dirammox pathway is mediated by dnf genes, which are independent of the denitrification pathway. A bioinformatic survey suggests that homologs of dnf genes are widely distributed in bacteria. These findings enhance the understanding of the molecular mechanisms of heterotrophic ammonia oxidation to N2.

Highly stable soliton and bound soliton generation from a fiber laser mode-locked by VSe2 nanosheets.

We demonstrate the highly stable soliton generation from a fiber laser mode-locked by the VSe2 nanosheets experimentally. The VSe2 nanosheets prepared via the liquid phase exfoliation method exhibit ultrafast relaxation time and excellent nonlinear optical behavior with saturation intensity and modulation depth of 14.28 MW/cm2 and 19.11%, respectively. A highly stable mode-locked Er3+-doped fiber laser with pulse duration of 714 fs and signal-to-noise ratio of 78.44 dB has been delivered successfully based on the VSe2 nanosheets saturable absorber. In addition, the transition from the conventional soliton to bound-state soliton has been observed experimentally. Our results reveal that VSe2 nanosheets possess excellent nonlinear optical performance and can act as a robust optical platform for versatile optical applications.

Realization of all-optical higher-order spatial differentiators based on cascaded operations.

Cascaded operations play an important role in traditional electronic computing systems for the realization of advanced strategies. Here, we introduce the idea of cascaded operations into all-optical spatial analog computing. The single function of the first-order operation has difficulty meeting the requirements of practical applications in image recognition. The all-optical second-order spatial differentiators are implemented by cascading two first-order differential operation units, and the image edge detection of amplitude and phase objects are demonstrated. Our scheme provides a possible pathway toward the development of compact multifunctional differentiators and advanced optical analog computing networks.

Broadband saturable absorption of indium tin oxide nanocrystals toward mid-infrared regime.

We experimentally demonstrate the ultrabroadband optical nonlinearity of indium tin oxide nanocrystals (ITO NCs) in the mid-infrared regime. Especially, the ITO NCs show considerable saturation absorption behavior with large modulation depth covering the spectral range from 2-µm to 10-µm wavelength. We also demonstrate the application of the optical nonlinearity to successfully modulate the erbium-doped fluoride fiber laser to deliver a nanosecond pulse with a signal-to-noise ratio over 43 dB at 2.8-µm wavelength. The results provide a promising platform for the development of ITO-based broadband and robust optoelectronic devices toward the deep mid-infrared spectral range.

How Does C-V2X Help Autonomous Driving to Avoid Accidents?

Accidents are continuously reported for autonomous driving vehicles including those with advanced sensors installed. Some of accidents are usually caused by bad weather, poor lighting conditions and non-line-of-sight obstacles. Cellular Vehicle-to-Everything (C-V2X) radio technology can significantly improve those weak spots for autonomous driving. This paper describes one of the C-V2X system solutions: Vulnerable Road User Collision Warning (VRUCW) for autonomous driving. The paper provides the system architecture, design logic, network topology, message flow, artificial intelligence (AI) and network security feature. As a reference it also includes a commercial project with its test results.

Periodontal soft tissue increase induced by periodontally accelerated osteogenic orthodontics surgery.

OBJECTIVES: To quantitatively assess periodontal soft tissue changes, including gingival thickness and keratinized gingiva width after periodontally accelerated osteogenic orthodontics (PAOO) surgery by digital measurements.  METHODS: This study enrolled 15 maxillaries with 89 anterior teeth and 16 mandibles with 94 anterior teeth from Chinese adult patients with skeletal Angle Class III malocclusion for whom PAOO surgery was proposed during orthodontic treatment. Intraoral scanning and cone beam computed tomography (CBCT) examinations were performed before PAOO surgery and 6 months after the surgery. Keratinized gingiva width was measured on the digital model acquired by intraoral scanning. The gingival thickness was measured using a digital three-dimensional (3D) model based on the combination of digital intraoral scanning and CBCT data. RESULTS: The mean gingival thickness before surgery was 0.91 ± 0.32 mm and 1.21 ± 0.38 mm at 6-month after PAOO. Patients showed periodontal soft tissue increase with a mean gingival tissue gain of 0.30 ± 0.33 mm. At 1 mm, 2 and 3 mm apical to cemento-enamel junction (CEJ) levels, the gingival thickness increase of the mandible was higher than that of the maxilla (0.38 ± 0.30 mm vs. 0.24 ± 0.31 mm, 0.43 ± 0.35 mm vs. 0.26 ± 0.41 mm, 0.36 ± 0.27 vs. 0.25 ± 0.32 mm, respectively, all P < 0.05). Moreover, the sites of gingival thickness ≤ 1 mm before surgery showed more tissue gain than the sites > 1 mm (0.36 ± 0.32 mm vs. 0.18 ± 0.31 mm, P < 0.001). The mean keratinized gingiva width at T0 was 3.88 ± 1.22 mm, and increased 1.05 ± 1.24 mm 6 months after PAOO surgery. Moreover, a digital 3D model for gingival thickness measurement based on the combination of digital intraoral scanning and CBCT displayed high reliability and accuracy with an intra-class correlation coefficient (ICC) of 0.897. CONCLUSION: PAOO could improve an insufficient quantity of periodontal soft and hard tissues in patients with skeletal Angle Class III malocclusion, including the gingival thickness and keratinized gingiva width. A digital 3D model based on the combination of digital intraoral scanning and CBCT data could provide a new digital measurement of gingival thickness with high accuracy and reliability.

Novel Alcaligenes ammonioxydans sp. nov. from wastewater treatment sludge oxidizes ammonia to N2 with a previously unknown pathway.

Heterotrophic nitrifiers are able to oxidize and remove ammonia from nitrogen-rich wastewaters but the genetic elements of heterotrophic ammonia oxidation are poorly understood. Here, we isolated and identified a novel heterotrophic nitrifier, Alcaligenes ammonioxydans sp. nov. strain HO-1, oxidizing ammonia to hydroxylamine and ending in the production of N2 gas. Genome analysis revealed that strain HO-1 encoded a complete denitrification pathway but lacks any genes coding for homologous to known ammonia monooxygenases or hydroxylamine oxidoreductases. Our results demonstrated strain HO-1 denitrified nitrite (not nitrate) to N2 and N2 O at anaerobic and aerobic conditions respectively. Further experiments demonstrated that inhibition of aerobic denitrification did not stop ammonia oxidation and N2 production. A gene cluster (dnfT1RT2ABCD) was cloned from strain HO-1 and enabled E. coli accumulated hydroxylamine. Sub-cloning showed that genetic cluster dnfAB or dnfABC already enabled E. coli cells to produce hydroxylamine and further to 15 N2 from (15 NH4 )2 SO4 . Transcriptome analysis revealed these three genes dnfA, dnfB and dnfC were significantly upregulated in response to ammonia stimulation. Taken together, we concluded that strain HO-1 has a novel dnf genetic cluster for ammonia oxidation and this dnf genetic cluster encoded a previously unknown pathway of direct ammonia oxidation (Dirammox) to N2 .

Watt-level superfluorescent fiber source near 3 µm.

We report a watt-level mid-infrared (mid-IR) superfluorescent fiber source from ${{\rm Er}^{3 +}}$-doped ZBLAN fiber near 3 µm spectral range. With the power amplifier configuration, the mid-IR superfluorescent fiber source with power up to 1.85 W has been delivered successfully with slope efficiency about 18.6%. The experimental results may pave an avenue toward a high-power, high-temporal-stability superfluorescent source for versatile mid-IR applications.

LncRNA MCM3AP-AS1 sponges miR-148a to enhance cell invasion and migration in small cell lung cancer.

BACKGROUND: MCM3AP-AS1 is a recently characterized lncRNA playing an oncogenic role in several cancers. However, its role in lung cancer remains unknown. Here, we aimed to explore the functions of MCM3AP-AS1 in small cell lung cancer (SCLC) and the possible underlying mechanisms. METHODS: MCM3AP-AS1 and ROCK1 levels in SCLC patients were analyzed by qPCR. RNA pull-down and luciferase assays were performed to analyze the interaction between MCM3AP-AS1 and miR-148a. ROCK1 mRNA and protein levels were detected by qPCR and Western blot, respectively. Cell invasion and migration were analyzed by Transwell assays. RESULTS: MCM3AP-AS1 was upregulated in patients with SCLC, and a high MCM3AP-AS1 level was accompanied by a low survival rate. The binding of MCM3AP-AS1 to miR-148a predicted by bioinformatics analysis was verified by RNA pull-down and luciferase assays. However, MCM3AP-AS1 and miR-148a did not affect each other's expression. ROCK1 was upregulated in SCLC tissues and positively correlated with MCM3AP-AS1. In SCLC cells, MCM3AP-AS1 overexpression increased ROCK1 and promoted cancer cell invasion and migration, while miR-148a overexpression showed the opposite effects and attenuated the effects of MCM3AP-AS1 overexpression on ROCK1 expression and cell behaviors. CONCLUSIONS: MCM3AP-AS1 sponges miR-148a, thereby increasing SCLC cell invasion and migration via upregulating ROCK1 expression.

The damage and tolerance mechanisms of Phaffia rhodozyma mutant strain MK19 grown at 28 °C.

BACKGROUND: Phaffia rhodozyma has many desirable properties for astaxanthin production, including rapid heterotrophic metabolism and high cell densities in fermenter culture. The low optimal temperature range (17-21 °C) for cell growth and astaxanthin synthesis in this species presents an obstacle to efficient industrial-scale astaxanthin production. The inhibition mechanism of cell growth at > 21 °C in P. rhodozyma have not been investigated. RESULTS: MK19, a mutant P. rhodozyma strain grows well at moderate temperatures, its cell growth was also inhibited at 28 °C, but such inhibition was mitigated, and low biomass 6 g/L was obtained after 100 h culture. Transcriptome analysis indicated that low biomass at 28 °C resulted from strong suppression of DNA and RNA synthesis in MK19. Growth inhibition at 28 °C was due to cell membrane damage with a characteristic of low mRNA content of fatty acid (f.a.) pathway transcripts (acc, fas1, fas2), and consequent low f.a. CONTENT: Thinning of cell wall and low mannose content (leading to loss of cell wall integrity) also contributed to reduced cell growth at 28 °C in MK19. Levels of astaxanthin and ergosterol, two end-products of isoprenoid biosynthesis (a shunt pathway of f.a. biosynthesis), reached 2000 µg/g and 7500 µg/g respectively; ~2-fold higher than levels at 21 or 25 °C. Abundance of ergosterol, an important cell membrane component, compensated for lack of f.a., making possible the biomass production of 6 g/L for MK19 at 28 °C. CONCLUSIONS: Inhibition of growth of P. rhodozyma at 28 °C results from blocking of DNA, RNA, f.a., and cell wall biosynthesis. In MK19, abundant ergosterol made possible biomass production 6 g/L at 28 °C. Significant accumulation of astaxanthin and ergosterol indicated an active MVA pathway in MK19 at 28 °C. Strengthening of the MVA pathway can be a feasible metabolic engineering approach for enhancement of astaxanthin synthesis in P. rhodozyma. The present findings provide useful mechanistic insights regarding adaptation of P. rhodozyma to 28 °C, and improved understanding of feasible metabolic engineering techniques for industrial scale astaxanthin production by this economically important yeast species.

PC5-Based Cellular-V2X Evolution and Deployment.

C-V2X (Cellular Vehicle-to-Everything) is a state-of-the-art wireless technology used in autonomous driving and intelligent transportation systems (ITS). This technology has extended the coverage and blind-spot detection of autonomous driving vehicles. Economically, C-V2X is much more cost-effective than the traditional sensors that are commonly used by autonomous driving vehicles. This cost-benefit makes it more practical in a large scale deployment. PC5-based C-V2X uses an RF (Radio Frequency) sidelink direct communication for low latency mission-critical vehicle sensor connectivity. Over the C-V2X radio communications, the autonomous driving vehicle's sensor ability can now be largely enhanced to the distances as far as the network covers. In 2020, 5G is commercialized worldwide, and Taiwan is at the forefront. Operators and governments are keen to see its implications in people's daily life brought by its low latency, high reliability, and high throughput. Autonomous driving class L3 (Conditional Automation) or L4 (Highly Automation) are good examples of 5G's advanced applications. In these applications, the mobile networks with URLLC (Ultra-Reliable Low-Latency Communication) are perfectly demonstrated. Therefore, C-V2X evolution and 5G NR (New Radio) deployment coincide and form a new ecosystem. This ecosystem will change how people will drive and how transportation will be managed in the future. In this paper, the following topics are covered. Firstly, the benefits of C-V2X communication technology. Secondly, the standards of C-V2X and C-V2X applications for automotive road safety system which includes V2P/V2I/V2V/V2N, and artificial intelligence in VRU (Vulnerable Road User) detection, object recognition and movement prediction for collision warning and prevention. Thirdly, PC5-based C-V2X deployment status in global, especially in Taiwan. Lastly, current challenges and conclusions of C-V2X development.

The Sucrose Non-Fermenting 1-Related Protein Kinase 2 (SnRK2) Genes Are Multifaceted Players in Plant Growth, Development and Response to Environmental Stimuli.

Reversible protein phosphorylation orchestrated by protein kinases and phosphatases is a major regulatory event in plants and animals. The SnRK2 subfamily consists of plant-specific protein kinases in the Ser/Thr protein kinase superfamily. Early observations indicated that SnRK2s are mainly involved in response to abiotic stress. Recent evidence shows that SnRK2s are multifarious players in a variety of biological processes. Here, we summarize the considerable knowledge of SnRK2s, including evolution, classification, biological functions and regulatory mechanisms at the epigenetic, post-transcriptional and post-translation levels.

Glycerol kinase enhances hepatic lipid metabolism by repressing nuclear receptor subfamily 4 group A1 in the nucleus.

Glycerol kinase (GYK) plays a critical role in hepatic metabolism by converting glycerol to glycerol 3-phosphate in an ATP-dependent reaction. GYK isoform b is the only glycerol kinase present in whole cells, and has a non-enzymatic moonlighting function in the nucleus. GYK isoform b acts as a co-regulator of nuclear receptor subfamily 4 group A1 (NR4A1) and participates in the regulation of hepatic glucose metabolism by protein-protein interaction with NR4A1. Herein, GYK expression was found to upregulate the expression of NR4A1-mediated lipid metabolism-related genes (SREBP1C, FASN, ACACA, and GPAM) in HEK293T and L02 cells, and in mouse in vivo studies. GYK expression increased blood levels of cholesterol, triglyceride, and high-density lipoprotein cholesterol, but not low-density lipoprotein cholesterol levels. It enhanced the transcriptional activity of Nr4a1 target genes by negatively cooperating with NR4A1 and its enzymatic activity or by other undefined moonlighting functions. This enhancement was observed in both normal and diabetic mice. We also found a feed-forward regulation loop between GYK and NR4A1, serving as part of a GYK-NR4A1 regulatory mechanism in hepatic metabolism. Thus, GYK regulates the effect of NR4A1 on hepatic lipid metabolism in normal and diabetic mice, partially through the cooperation of GYK and NR4A1.