Search Results (52)

Background: Accumulating evidence indicates that PSAT1 not only reprogrammed metabolic function but also exhibits “moonlighting” functions in promoting tumor malignancy. However, the underlying molecular mechanisms of PSAT1 promoting ER-negative breast cancer cell migration need further investigation. Methods: Briefly, the PSAT1 and ITGA2 expression in cells and tissues was detected using qRT-PCR, immunofluorescence staining and western blot assay. The effect of PSAT1 and ITGA2 was verified both in vitro and in vivo. RNA-seq analysis explored a series of differently expressed genes. The regulation between SP1 and ITGA2 was investigated by ChIP analysis. Results: We reported PSAT1 was highly expressed in ER-breast cancer tissues and tumor cells and positively correlated with metastasis. Moreover, RNA-seq analysis explored a series of differently expressed genes, including ITGA2, in PSAT1 overexpressed cells. Mechanistically, PSAT1 facilitated breast cancer metastasis via the p-AKT/SP1/ITGA2 axis. We further elucidated that PSAT1 promoted the entry of SP1 into the nucleus through the upregulation of p-AKT and confirmed ITGA2 is a target of SP1. In addition, enhanced cell migration was remarkably reversed by ITGA2 depletion or p-AKT inhibitor treatment. Conclusion: This study clarified the mechanism of PSAT1 in promoting ER-negative breast cancer metastasis, which may provide mechanistic clues for attenuating breast cancer metastasis. Full article

Cadmium (Cd) hampers plant growth and harms photosynthesis. Glutamate (Glu) responds to Cd stress and activates the Ca²⁺ signaling pathway in duckweed, emphasizing Glu’s significant role in Cd stress. In this study, we overexpressed phosphoserine aminotransferase (PSAT), a crucial enzyme in Glu metabolism, in duckweed. We investigated the response of PSAT-transgenic duckweed to Cd stress, including growth, Glu metabolism, photosynthesis, antioxidant enzyme activity, Cd²⁺ flux, and gene expression. Remarkably, under Cd stress, PSAT-transgenic duckweed prevented root abscission, upregulated the expression of photosynthesis ability, and increased Chl a, Chl b, and Chl a + b levels by 13.9%, 7%, and 12.6%, respectively. Antioxidant enzyme activity (CAT and SOD) also improved under Cd stress, reducing cell membrane damage in PSAT-transgenic duckweeds. Transcriptomic analysis revealed an upregulation of Glu metabolism-related enzymes in PSAT-transgenic duckweed under Cd stress. Moreover, metabolomic analysis showed a 68.4% increase in Glu content in PSAT duckweed exposed to Cd. This study sheds novel insights into the role of PSAT in enhancing plant resistance to Cd stress, establishing a theoretical basis for the impact of Glu metabolism on heavy metal tolerance in plants. Full article

With the development and popularization of the Beidou-3 navigation satellite system (BDS-3), to ensure its unique short message function, it is necessary to integrate a radio frequency (RF) transmitting circuit with high performance in the BDS-3 terminal. As the key device in an RF transmitting circuit, the RF power amplifier (PA) largely determines the comprehensive performance of the circuit with its transmission power, efficiency, linearity, and integration. Therefore, in this paper, an L-band highly integrated PA chip compatible with 3 W and 5 W output power is designed in InGaP/GaAs heterojunction bipolar transistor (HBT) technology combined with temperature-insensitive adaptive bias technology, class-F harmonic suppression technology, analog pre-distortion technology, temperature-insensitive adaptive power detection technology, and land grid array (LGA) packaging technology. Additionally, three auxiliary platforms are proposed, dedicated to the simulation and optimization of the same type of PA designs. The simulation results show that at the supply voltage of 5 V and 3.5 V, the linear gain of the PA chip reaches 39.4 dB and 38.7 dB, respectively; the output power at 1 dB compression point (P1dB) reaches 37.5 dBm and 35.1 dBm, respectively; the saturated output power (Psat) reaches 38.2 dBm and 36.2 dBm, respectively; the power added efficiency (PAE) reaches 51.7% and 48.2%, respectively; and the higher harmonic suppression ratios are less than −62 dBc and −65 dBc, respectively. The size of the PA chip is only 6 × 4 × 1 mm³. The results also show that the PA chip has high gain, high efficiency, and high linearity under both output power conditions, which has obvious advantages over similar PA chip designs and can meet the short message function of the BDS-3 terminal in various application scenarios. Full article

TGF-β1, a key fibrotic cytokine, enhances both the expression and translocation of the activating transcriptional factor 4 (ATF4) and activates the serine/glycine biosynthesis pathway, which is crucial for augmenting collagen production. Targeting the TGF-β1-ATF4-serine/glycine biosynthesis pathway might offer a promising therapeutic approach for fibrotic diseases. In this study, we aimed to identify a proline-containing dipeptide in Hibiscus sabdariffa plant cells that modulates collagen synthesis. We induced Hibiscus sabdariffa plant cells and screened for a proline-containing dipeptide that can suppress TGF-β1-induced collagen synthesis in fibroblasts. Analyses were conducted using LC-MS/MS, RT-qPCR, Western blot analysis, and immunocytochemistry. We identified Gly-Pro (GP) from the extract of Hibiscus sabdariffa plant cells as a dipeptide capable of suppressing TGF-β1-induced collagen production. GP inhibited the phosphorylation of Smad2/3 and reduced the expression of ATF4, which is upregulated by TGF-β1. Notably, GP also decreased the expression of enzymes involved in the serine/glycine biosynthesis and glucose metabolism pathways, such as PHGDH, PSAT1, PSPH, SHMT2, and SLC2A1. Our findings indicate that the peptide GP, derived from Hibiscus sabdariffa plant cells, exhibits potent anti-fibrotic effects, potentially through its regulation of the TGF-β1-ATF4-serine/glycine biosynthesis pathway. Full article

In humans, the phosphorylated pathway (PP) converts the glycolytic intermediate D-3-phosphoglycerate (3-PG) into L-serine through the enzymes 3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase (PSAT) and phosphoserine phosphatase. From the pathogenic point of view, the PP in the brain is particularly relevant, as genetic defects of any of the three enzymes are associated with a group of neurometabolic disorders known as serine deficiency disorders (SDDs). We recombinantly expressed and characterized eight variants of PSAT associated with SDDs and two non-SDD associated variants. We show that the pathogenetic mechanisms in SDDs are extremely diverse, including low affinity of the cofactor pyridoxal 5′-phosphate and thermal instability for S179L and G79W PSAT, loss of activity of the holo form for R342W PSAT, aggregation for D100A PSAT, increased K_m for one of the substrates with invariant k_cats for S43R PSAT, and a combination of increased K_m and decreased k_cat for C245R PSAT. Finally, we show that the flux through the in vitro reconstructed PP at physiological concentrations of substrates and enzymes is extremely sensitive to alterations of the functional properties of PSAT variants, confirming PSAT dysfunctions as a cause of SSDs. Full article

The integrity improvement of receiver autonomous integrity monitoring (RAIM) can benefit from a combination of constellations. With the rapid development of constellation modernization, integrity parameters, including the probability of satellite fault (P_sat) and user range accuracy (URA), have improved. The integrity loss of RAIM needs to be accurately characterized to control the effect of the improved integrity parameters. To reveal the sensitivity of integrity risk with respect to P_sat and URA, a conservative integrity risk estimation method is proposed based on the worst-case protection concept. Acceptable P_sat and URA were derived by comparing the estimated worst-case integrity risk with the required integrity risk. The simulation results showed that RAIM can meet the integrity risk requirement of LPV-200 when P_sat was 10⁻⁴ and URA was smaller than 0.88 m. Full article

This paper describes Monolithic Microwave Integrated Circuits (MMICs) for an X-band radar transceiver front-end implemented in 0.25 μm GaN High Electron Mobility Transistor (HEMT) technology. Two versions of single pole double throw (SPDT) T/R switches are introduced to realize a fully GaN-based transmit/receive module (TRM), each of which achieves an insertion loss of 1.21 dB and 0.66 dB at 9 GHz, IP_1dB higher than 46.3 dBm and 44.7 dBm, respectively. Therefore, it can substitute a lossy circulator and limiter used for a conventional GaAs receiver. A driving amplifier (DA), a high-power amplifier (HPA), and a robust low-noise amplifier (LNA) are also designed and verified for a low-cost X-band transmit-receive module (TRM). For the transmitting path, the implemented DA achieves a saturated output power (P_sat) of 38.0 dBm and output 1-dB compression (OP_1dB) of 25.84 dBm. The HPA reaches a P_sat of 43.0 dBm and power-added efficiency (PAE) of 35.6%. For the receiving path, the fabricated LNA measures a small-signal gain of 34.9 dB and a noise figure of 2.56 dB, and it can endure higher than 38 dBm input power in the measurement. The presented GaN MMICs can be useful in implementing a cost-effective TRM for Active Electronically Scanned Array (AESA) radar systems at X-band. Full article

Phosphoserine aminotransferase (PSAT) is a pyridoxal 5′-phosphate-dependent enzyme involved in the second step of the phosphorylated pathway of serine biosynthesis. PSAT catalyzes the transamination of 3-phosphohydroxypyruvate to 3-phosphoserine using L-glutamate as the amino donor. Although structural studies of PSAT have been performed from archaea and humans, no structural information is available from fungi. Therefore, to elucidate the structural features of fungal PSAT, we determined the crystal structure of Saccharomyces cerevisiae PSAT (ScPSAT) at a resolution of 2.8 Å. The results demonstrated that the ScPSAT protein was dimeric in its crystal structure. Moreover, the gate-keeping loop of ScPSAT exhibited a conformation similar to that of other species. Several distinct structural features in the halide-binding and active sites of ScPSAT were compared with its homologs. Overall, this study contributes to our current understanding of PSAT by identifying the structural features of fungal PSAT for the first time. Full article

Due to uncertain photovoltaic (PV) power generation, analyzing the voltage stability of transmission networks with a large PV plant is challenging. The stability of PV output power is a critical factor in establishing PV penetration levels in active transmission networks when assessing loading capabilities. Therefore, this article contributes to enhancing the understanding of how a static synchronous compensator (STATCOM) could be used as part of the power system network. STATCOMs are often used to improve the static and transient voltage, maintain transmission limits, and reduce low-frequency disturbances. With the help of a STATCOM unit, a proper investigation and analysis of dynamic voltage stability in a transmission system are presented. The validity of the study is evaluated by the Saudi Arabia grid code (SAGC). The system being tested is comprised of a 300 MW PV plant in Sakaka, Saudi Arabia, integrated into a 17-bus transmission power network and a STATCOM, which is employed at one of the buses. PSAT software is used to evaluate a number of case studies to determine the transient voltage stability with and without the STATCOM and the PV plant. The simulation findings demonstrate how STATCOM functions to improve the quality of the power system in accordance with the SAGC. In addition, the analysis of voltage stability demonstrates that the power network’s resilience to short circuits at the PV system’s grid connection point significantly impacts the voltage’s dynamic behavior. Full article

Excess iron is known to trigger adipose tissue dysfunction and insulin resistance. Circulating markers of iron status have been associated with obesity and adipose tissue in cross-sectional studies. We aimed to evaluate whether iron status is linked to changes in abdominal adipose tissue longitudinally. Subcutaneous abdominal tissue (SAT) and visceral adipose tissue (VAT) and its quotient (pSAT) were assessed using magnetic resonance imaging (MRI), at baseline and after one year of follow-up, in 131 (79 in follow-up) apparently healthy subjects, with and without obesity. Insulin sensitivity (euglycemic– hyperinsulinemic clamp) and markers of iron status were also evaluated. Baseline serum hepcidin (p = 0.005 and p = 0.002) and ferritin (p = 0.02 and p = 0.01)) were associated with an increase in VAT and SAT over one year in all subjects, while serum transferrin (p = 0.01 and p = 0.03) and total iron-binding capacity (p = 0.02 and p = 0.04) were negatively associated. These associations were mainly observed in women and in subjects without obesity, and were independent of insulin sensitivity. After controlling for age and sex, serum hepcidin was significantly associated with changes in subcutaneous abdominal tissue index (iSAT) (β = 0.406, p = 0.007) and visceral adipose tissue index (iVAT) (β = 0.306, p = 0.04), while changes in insulin sensitivity (β = 0.287, p = 0.03) and fasting triglycerides (β = −0.285, p = 0.03) were associated with changes in pSAT. These data indicated that serum hepcidin are associated with longitudinal changes in SAT and VAT, independently of insulin sensitivity. This would be the first prospective study evaluating the redistribution of fat according to iron status and chronic inflammation. Full article

(1) Background: The effect of tumor immunotherapy is influenced by the immune microenvironment, and it is unclear how lipid metabolism and ferroptosis regulate the immune microenvironment of uterine corpus endometrial carcinoma (UCEC). (2) Methods: Genes associated with lipid metabolism and ferroptosis (LMRGs-FARs) were extracted from the MSigDB and FerrDb databases, respectively. Five hundred and forty-four UCEC samples were obtained from the TCGA database. The risk prognostic signature was constructed by consensus clustering, univariate cox, and LASSO analyses. The accuracy of the risk modes was assessed through receiver operating characteristic (ROC) curve, nomogram, calibration,, and C-index analyses. The relationship between the risk signature and immune microenvironment was detected by the ESTIMATE, EPIC, TIMER, xCELL, quan-TIseq, and TCIA databases. The function of a potential gene, PSAT1, was measured by in vitro experiments. (3) Results: A six-gene (CDKN1A, ESR1, PGR, CDKN2A, PSAT1, and RSAD2) risk signature based on MRGs-FARs was constructed and evaluated with high accuracy in UCEC. The signature was identified as an independent prognostic parameter and it divided the samples into high- and low-risk groups. The low-risk group was positively associated with good prognosis, high mutational status, upregulated immune infiltration status, high expression of CTLA4, GZMA and PDCD1, anti-PD-1 treatment sensitivity, and chemoresistance. (4) Conclusions: We constructed a risk prognostic model based on both lipid metabolism and ferroptosis and evaluated the relationship between the risk score and tumor immune microenvironment in UCEC. Our study has provided new ideas and potential targets for UCEC individualized diagnosis and immunotherapy. Full article

This paper presents a broadband GaN microwave monolithic integrated circuit driver amplifier (MMIC DA) with compact dimensions of 1.65 mm × 0.78 mm for 5G millimeter-wave communication. The optimal impedance domain satisfying the preset goals was first acquired using the simplified load-pull procedure and small-signal simulations, followed by a weighted average method to determine the reference center matching point from which the optimal intrinsic load can be deduced. By means of de-embedding load-pull contours, modeling based on theoretical analysis, and simulation fitting for parameter identification, the nonlinear output capacitance and a series RLC model circuit approximating the input impedance response of the stabilized transistor were extracted. Under the design principle of fully absorbing the parasitic parameters of the device, explicit formulas and tabulated methods related to the Chebyshev impedance transformer were applied to construct filter-based synthesized matching networks at each stage and finally convert them into an implementable mixed-element form via the single-frequency equivalence technique. Measured on-wafer pulsed results for the proposed two-stage DA across 24–30 GHz demonstrated up to 31.1 dBm of saturated output power (P_sat) with less than 1 dB total fluctuation, 19.3 ± 1 dB of small-signal gain, and 39.8% of peak power-added efficiency (PAE) at the mid-frequency. Full article

In response to muscle injury, muscle stem cells are stimulated by environmental signals to integrate into damaged tissue to mediate regeneration. L-leucine (L-leu), a branched-chain amino acid (BCAA) that belongs to the essential amino acids (AAs) of the animal, has gained global interest on account of its muscle-building and regenerating effects. The present study was designed to investigate the impact of L-leu exposure to promote the proliferation of equine skeletal muscle satellite cells (SCs) on the regulation of RNA networks, including mRNA, long non-coding RNA (lncRNA), covalently closed circular RNA (circRNA), and microRNA (miRNA) in skeletal muscles. Equine SCs were used as a cell model and cultured in different concentrations of L-leu medium. The cell proliferation assay found that the optimal concentration of L-leu was 2 mM, so we selected cells cultured with L-leu concentrations of 0 mM and 2 mM for whole-transcriptiome sequencing, respectively. By high-throughput sequencing analysis, 2470 differentially expressed mRNAs (dif-mRNAs), 363 differentially expressed lncRNAs (dif-lncRNAs), 634 differentially expressed circRNAs (dif-circRNAs), and 49 differentially expressed miRNAs (dif-miRNAs) were significantly altered in equine SCs treated with L-leu. To identify the function of autoimmunity and anti-inflammatory responses after L-leu exposure, enrichment analysis was conducted on those differentially expressed genes (DEGs) related to lncRNA, circRNA, and miRNA. The hub genes were selected from PPI Network, including ACACB, HMGCR, IDI1, HAO1, SHMT2, PSPH, PSAT1, ASS1, PHGDH, MTHFD2, and DPYD, and were further identified as candidate biomarkers to regulate the L-leu-induced proliferation of equine SCs. The up-regulated novel 699_star, down-regulated novel 170_star, and novel 360_mature were significantly involved in the competing endogenous RNA (ceRNA) complex network. The hub genes involved in cell metabolism and dif-miRNAs may play fundamental roles in the L-leu-induced proliferation of equine SCs. Our findings suggested that the potential network regulation of miRNAs, circ-RNAs, lncRNAs, and mRNAs plays an important role in the proliferation of equine SCs, so as to build up new perspectives on improving equine performance and treatment strategies for the muscle injuries of horses. Full article

Tumour metabolomics and transcriptomics co-expression network as related to biological folate alteration and cancer malignancy remains unexplored in human non-small cell lung cancers (NSCLC). To probe the diagnostic biomarkers, tumour and pair lung tissue samples (n = 56) from 97 NSCLC patients were profiled for ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS)-analysed metabolomics, targeted transcriptionomics, and clinical folate traits. Weighted Gene Co-expression Network Analysis (WGCNA) was performed. Tumour lactate was identified as the top VIP marker to predict advance NSCLC (AUC = 0.765, Sig = 0.017, CI 0.58–0.95). Low folate (LF)-tumours vs. adjacent lungs displayed higher glycolytic index of lactate and glutamine-associated amino acids in enriched biological pathways of amino sugar and glutathione metabolism specific to advance NSCLCs. WGCNA classified the green module for hub serine-navigated glutamine metabolites inversely associated with tumour and RBC folate, which module metabolites co-expressed with a predominant up-regulation of LF-responsive metabolic genes in glucose transport (GLUT1), de no serine synthesis (PHGDH, PSPH, and PSAT1), folate cycle (SHMT1/2 and PCFR), and down-regulation in glutaminolysis (SLC1A5, SLC7A5, GLS, and GLUD1). The LF-responsive WGCNA markers predicted poor survival rates in lung cancer patients, which could aid in optimizing folate intervention for better prognosis of NSCLCs susceptible to folate malnutrition. Full article

As a typical sequence to sequence task, sign language production (SLP) aims to automatically translate spoken language sentences into the corresponding sign language sequences. The existing SLP methods can be classified into two categories: autoregressive and non-autoregressive SLP. The autoregressive methods suffer from high latency and error accumulation caused by the long-term dependence between current output and the previous poses. And non-autoregressive methods suffer from repetition and omission during the parallel decoding process. To remedy these issues in SLP, we propose a novel method named Pyramid Semi-Autoregressive Transformer with Rich Semantics (PSAT-RS) in this paper. In PSAT-RS, we first introduce a pyramid Semi-Autoregressive mechanism with dividing target sequence into groups in a coarse-to-fine manner, which globally keeps the autoregressive property while locally generating target frames. Meanwhile, the relaxed masked attention mechanism is adopted to make the decoder not only capture the pose sequences in the previous groups, but also pay attention to the current group. Finally, considering the importance of spatial-temporal information, we also design a Rich Semantics embedding (RS) module to encode the sequential information both on time dimension and spatial displacement into the same high-dimensional space. This significantly improves the coordination of joints motion, making the generated sign language videos more natural. Results of our experiments conducted on RWTH-PHOENIX-Weather-2014T and CSL datasets show that the proposed PSAT-RS is competitive to the state-of-the-art autoregressive and non-autoregressive SLP models, achieving a better trade-off between speed and accuracy. Full article