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Translation of mRNA to protein is tightly regulated by tRNAs, which are subject to various chemical modifications that maintain the structure, stability and function. Deficiency of tRNA N7-methylguanosine (m7G) modification in patients causes a type of primordial dwarfism, but the underlying mechanism remains unknown. Here we report the loss of m7G rewires cellular metabolism, leading to the pathogenesis of primordial dwarfism. Conditional deletion of the catalytic enzyme Mettl1 or missense mutation of the scaffold protein Wdr4 severely impaired endochondral bone formation and bone mass accrual. Mechanistically, Mettl1 knockout decreased abundance of m7G-modified tRNAs and inhibited translation of mRNAs relating to cytoskeleton and Rho GTPase signaling. Meanwhile, Mettl1 knockout enhanced cellular energy metabolism despite of incompetent proliferation and osteogenic commitment. Further exploration revealed that impaired Rho GTPase signaling upregulated branched-chain amino acid transaminase 1 (BCAT1) level that rewired cell metabolism and restricted intracellular α-ketoglutarate (αKG). Supplementation of αKG ameliorated the skeletal defect of Mettl1-deficient mice. In addition to the selective translation of metabolism-related mRNAs, we further revealed that Mettl1 knockout globally regulated translation via integrated stress response (ISR) and mammalian target of rapamycin complex 1 (mTORC1) signaling. Restoring translation either by targeting ISR or mTORC1 aggravated bone defects of Mettl1-deficient mice. Overall, our study unveils a critical role of m7G tRNA modification in bone development by regulating cellular metabolism, and indicates that suspension of translation initiation as quality control mechanism in response to tRNA dysregulation.

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Sleep is essential for overall health, and its disruption is linked to increased risks of metabolic, cognitive, and cardiovascular dysfunctions; however, the molecular mechanisms remain poorly understood. This study investigated how sleep disturbances contribute to metabolic imbalance and cognition impairment using a chronic sleep fragmentation (SF) mouse model. SF mice exhibited impaired cognition, glucose metabolism, and insulin sensitivity compared with controls. We identified increased acetate levels in hypothalamic astrocytes as a defensive response in SF mice. Through acetate infusion or astrocyte-specific Acss1 deletion to elevate acetate levels, we observed mitigated metabolic and cognitive impairments in SF mice. Mechanistically, acetate binds and activates pyruvate carboxylase, thereby restoring glycolysis and the tricarboxylic acid cycle. Among individuals most commonly affected by SF, patients with obstructive sleep apnea exhibited elevated acetate levels when coupled with type 2 diabetes. Our study uncovers the protective effect of acetate against sleep-induced metabolic and cognitive impairments.

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Afterglow materials possess the remarkable capability to harness the energy and subsequently emit light after irradiation is turned off. Owing to their extraordinary ultralong lifetime, afterglow materials have garnered significant interest across various domains such as sensing, optoelectronics, bioimaging, and information encryption. However, these materials typically exhibit temperature sensitivity, rendering their afterglow emission susceptible to efficient quenching at room temperature. Consequently, this study presents herein a straightforward, simple, and universal approach for synthesizing metal-free carbon dots (CDs) endowed with thermally activated delayed fluorescence (TADF) characteristics at room temperature. In this study, TADF-CDs were simply synthesized by pyrolyzing boronic acid (BA) and urea at 500 ℃ for 3 h. Benefiting from the multi-confined effects facilitated by the robust structure of BA matrix, in conjunction with the co-doped heteroatoms of nitrogen and boron, the resultant TADF-CDs manifest remarkably prolonged afterglow TADF emission, characterized by a calculated lifetime of 184.64 ms; moreover, the blue afterglow emission remains perceptible to the naked eye for more than 6 s. The attributes of TADF-CDs were comprehensively elucidated through rigorous characterization, and the universality of the approach was corroborated through experimentation involving fourteen control CDs. Leveraging their distinctive TADF attributes, the prepared TADF-CDs were subsequently employed in advanced applications such as anti-counterfeiting and information encryption.

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OBJECTIVES: This study aims to evaluate the value of the dynamic and static quantitative metabolic parameters derived from 18F-fluorodeoxyglucose (FDG)-positron emission tomography/CT (PET/CT) in the differential diagnosis of metastatic from non-metastatic lymph nodes (LNs) in lung cancer and to validate them based on the results of a previous study. METHODS: One hundred and twenty-one patients with lung nodules or masses detected on chest CT scan underwent 18F-FDG PET/CT dynamic + static imaging with informed consent. A retrospective collection of 126 LNs in 37 patients with lung cancer was pathologically confirmed. Static image analysis parameters include LN-SUVmax and LN-SUVmax/primary tumor SUVmax (LN-SUVmax/PT-SUVmax). Dynamic metabolic parameters including the net influx rate (Ki) and the surrogate of perfusion (K1) and of each LN were obtained by applying the irreversible two-tissue compartment model using in-house Matlab software. Ki/K1 was then calculated as a separate marker. Based on the pathological findings, we divided into a metastatic group and a non-metastatic group. The χ2 test was used to evaluate the agreement of the individual and combined diagnosis of each metabolic parameter with the gold standard. The receiver-operating characteristic (ROC) analysis was performed for each parameter to determine the diagnostic efficacy in differentiating non-metastatic from metastatic LNs with high FDG-avid. P < 0.05 was considered statistically significant. RESULTS: Among the 126 FDG-avid LNs confirmed by pathology, 70 LNs were metastatic, and 56 LNs were non-metastatic. For ROC analysis, in separate assays, the dynamic metabolic parameter Ki [sensitivity (SEN) of 84.30%, specificity (SPE) of 94.60%, accuracy of 88.89%, and AUC of 0.895] had a better diagnostic value than the static metabolic parameter SUVmax (SEN of 82.90%, SPE of 62.50%, accuracy of 74.60%, and AUC of 0.727) in differentiating between metastatic from non-metastatic LNs groups, respectively. In the combined diagnosis group, the combined SUVmax + Ki diagnosis had a better diagnostic value in the differential diagnosis of metastatic from non-metastatic LNs, with SEN, SPE, accuracy, and AUC of 84.3%, 94.6%, 88.89%, and 0.907, respectively. CONCLUSIONS: When the cutoff value of Ki was 0.022 ml/g/min, it had a high diagnostic value in the differential diagnosis between metastasis and non-metastasis in FDG-avid LNs of lung cancer, especially in improving the specificity. The combination of SUVmax and Ki is expected to be a reliable metabolic parameter for N-staging of lung cancer.

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OBJECTIVES: 18F-fluorodeoxyglucose (FDG) PET/CT has been widely used for the differential diagnosis of cancer. Semi-quantitative standardized uptake value (SUV) is known to be affected by multiple factors and may make it difficult to differentiate between benign and malignant lesions. It is crucial to find reliable quantitative metabolic parameters to further support the diagnosis. This study aims to evaluate the value of the quantitative metabolic parameters derived from dynamic FDG PET/CT in the differential diagnosis of lung cancer and predicting epidermal growth factor receptor (EGFR) mutation status. METHODS: We included 147 patients with lung lesions to perform FDG PET/CT dynamic plus static imaging with informed consent. Based on the results of the postoperative pathology, the patients were divided into benign/malignant groups, adenocarcinoma (AC)/squamous carcinoma (SCC) groups, and EGFR-positive (EGFR+)/EGFR-negative (EGFR-) groups. Quantitative parameters including K1, k2, k3, and Ki of each lesion were obtained by applying the irreversible two-tissue compartmental modeling using an in-house Matlab software. The SUV analysis was performed based on conventional static scan data. Differences in each metabolic parameter among the group were analyzed. Wilcoxon rank-sum test, independent-samples T-test, and receiver-operating characteristic (ROC) analysis were performed to compare the diagnostic effects among the differentiated groups. P < 0.05 were considered statistically significant for all statistical tests. RESULTS: In the malignant group (N = 124), the SUVmax, k2, k3, and Ki were higher than the benign group (N = 23), and all had-better performance in the differential diagnosis (P < 0.05, respectively). In the AC group (N = 88), the SUVmax, k3, and Ki were lower than in the SCC group, and such differences were statistically significant (P < 0.05, respectively). For ROC analysis, Ki with cut-off value of 0.0250 ml/g/min has better diagnostic specificity than SUVmax (AUC = 0.999 vs. 0.70). In AC group, 48 patients further underwent EGFR testing. In the EGFR (+) group (N = 31), the average Ki (0.0279 ± 0.0153 ml/g/min) was lower than EGFR (-) group (N = 17, 0.0405 ± 0.0199 ml/g/min), and the difference was significant (P < 0.05). However, SUVmax and k3 did not show such a difference between EGFR (+) and EGFR (-) groups (P>0.05, respectively). For ROC analysis, the Ki had a cut-off value of 0.0350 ml/g/min when predicting EGFR status, with a sensitivity of 0.710, a specificity of 0.588, and an AUC of 0.674 [0.523-0.802]. CONCLUSION: Although both techniques were specific, Ki had a greater specificity than SUVmax when the cut-off value was set at 0.0250 ml/g/min for the differential diagnosis of lung cancer. At a cut-off value of 0.0350 ml/g/min, there was a 0.710 sensitivity for EGFR status prediction. If EGFR testing is not available for a patient, dynamic imaging could be a valuable non-invasive screening method.

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BACKGROUND: Alzheimer's disease (AD) is a neurological disorder. There is a considerable unmet medical need among those suffering from it. HYPOTHESIS AND PURPOSE: Given the link between type-2 diabetes mellitus (T2DM) and AD, hypoglycemic traditional Chinese medicine formulas (TCMFs) may be a treatment for AD. We investigated the possibility of identifying anti-AD medicines in hypoglycemic TCMFs and presented another option for the screening of AD medications. STUDY DESIGN AND METHODS: Paralysis of the transgenic Caenorhabditis elegans (C. elegans) strain CL4176 (caused by amyloid beta (Aß)1-42 aggregates) was used to evaluate the anti-AD effect. The toxicity and neurodegeneration induced by neuronal expression of Aß in the transgenic C. elegans strain CL2355 were determined using a 5-hydroxytryptamine (5-HT) assay. The transgenic Aß-expressing strain CL 2006 and transgenic tau-expressing strain BR5270 were used to explore the effect of TCMFs on protein expression in C. elegans using ELISAs. Then, network pharmacology was used to determine the mechanism of action. The Traditional Chinese Medicine Inheritance Support System platform was used to investigate prescription patterns, core drugs, and optimum combinations of hypoglycemic TCMFs for AD. RESULTS: Sixteen hypoglycemic TCMFs prolonged the PT50 (half paralysis time) of the CL4176 strain of C. elegans, reduced the percentage of worms paralyzed. The results of network pharmacology showed that prostaglandin-endoperoxide synthase 2 (PTGS2) and acetylcholine esterase (AChE) are main targets of hypoglycemic TCMFs. Enriched pathway analysis showed that the cholinergic receptor-related pathway was the core pathway of hypoglycemic TCMFs. According to the "four qi and five flavors" system of TCM theory, the main pharmacological qualities were "cold" and "sweet." Through the analysis by TCMISS, we found that Huangqi-Gegen drug pair as the significant Chinese herbs of hypoglycemic TCMFs. The Huangqi-Gegen pairing had the most robust therapeutic effect when delivered at a 2:1 (v/v) ratio. It reduced the paralysis caused by 5-HT, decreased protein expression of AChE and PTGS2, and reduced Aß deposition in the brain of the CL2006 strain of C. elegans. CONCLUSIONS: Huangqi-Gegen is a promising treatment of AD, and its mechanism may be induced by suppressing the protein production of AChE and PTGS2, reducing 5-HT intake, and then decreasing Aß deposition.

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PURPOSE: This study aimed to evaluate the clinical feasibility of early 30-minute dynamic 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) positron emission tomography (PET) scanning protocol for patients with lung lesions in comparison to the standard 65-minute dynamic FDG-PET scanning as a reference. METHODS: Dynamic 18F-FDG PET images of 146 patients with 181 lung lesions (including 146 lesions confirmed by histology) were analyzed in this prospective study. Dynamic images were reconstructed into 28 frames with a specific temporal division protocol for the scan data acquired 65 min post-injection. Ki images and quantitative parameters Ki based on two different acquisition durations [the first 30 min (Ki-30 min) and 65 min (Ki-65 min)] were obtained by applying the irreversible two-tissue compartment model using in-house Matlab software. The two acquisition durations were compared for Ki image quality (including visual score analysis and number of lesions detected) and Ki value (including accuracy of Ki, the value of differential diagnosis of lung lesions and prediction of PD-L1 status) by Wilcoxon's rank sum test, Spearman's rank correlation analysis, receiver operating characteristic (ROC) curve, and the DeLong test. The significant testing level (alpha) was set to 0.05. RESULTS: The quality of the Ki-30 min images was not significantly different from the Ki-65 min images based on visual score analysis (P > 0.05). In terms of Ki value, among 181 lesions, Ki-65 min was statistically higher than Ki-30 min (0.027 ± 0.017 ml/g/min vs. 0.026 ± 0.018 ml/g/min, P < 0.05), while a very high correlation was obtained between Ki-65 min and Ki-30 min (r = 0.977, P < 0.05). In the differential diagnosis of lung lesions, ROC analysis was performed on 146 histologically confirmed lesions, the area under the curve (AUC) of Ki-65 min, Ki-30 min, and SUVmax was 0.816, 0.816, and 0.709, respectively. According to the Delong test, no significant differences in the diagnostic accuracies were found between Ki-65 min and Ki-30 min (P > 0.05), while the diagnostic accuracies of Ki-65 min and Ki-30 min were both significantly higher than that of SUVmax (P < 0.05). In 73 (NSCLC) lesions with definite PD-L1 expression results, the Ki-65 min, Ki-30 min, and SUVmax in PD-L1 positivity were significantly higher than that in PD-L1 negativity (P < 0.05). And no significant differences in predicting PD-L1 positivity were found among Ki-65 min, Ki-30 min, and SUVmax (AUC = 0.704, 0.695, and 0.737, respectively, P > 0.05), according to the results of ROC analysis and Delong test. CONCLUSIONS: This study indicates that an early 30-minute dynamic FDG-PET acquisition appears to be sufficient to provide quantitative images with good-quality and accurate Ki values for the assessment of lung lesions and prediction of PD-L1 expression. Protocols with a shortened early 30-minute acquisition time may be considered for patients who have difficulty with prolonged acquisitions to improve the efficiency of clinical acquisitions.

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Alzheimer's disease (AD)-related brain deterioration is linked to the type 2 diabetes mellitus (T2DM) features hyperglycemia, hyperinsulinemia, and insulin resistance. Hypoxia as a common risk factor for both AD and T2DM. Hypoxia-inducible factor-1 alpha (HIF-1α) acts as the main regulator of the hypoxia response and may be a key target in the comorbidity of AD and T2DM. HIF-1α expression is closely related to hyperglycemia, insulin resistance, and inflammation. Tissue oxygen consumption disrupts HIF-1α homeostasis, leading to increased reactive oxygen species levels and the inhibition of insulin receptor pathway activity, causing neuroinflammation, insulin resistance, abnormal Aß deposition, and tau hyperphosphorylation. HIF-1α activation also leads to the deposition of Aß by promoting the abnormal shearing of amyloid precursor protein and inhibiting the degradation of Aß, and it promotes tau hyperphosphorylation by activating oxidative stress and the activation of astrocytes, which further exasperates AD. Therefore, we believe that HIF-α has great potential as a target for the treatment of AD. Importantly, the intracellular homeostasis of HIF-1α is a more crucial factor than its expression level.

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Objective: To investigate the diagnostic value of the maximum standard uptake value (SUVmax) of quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) in solitary undetermined bone lesions. Methods: In Part I, retrospective study, 167 untreated patients with extra-skeletal malignant tumors by pathology were consecutively enrolled for staging with Tc-99m methyl-diphosphonate (99mTc-MDP) whole-body bone scan (WBS) and quantitative SPECT/CT, and a total of 396 bone lesions with abnormal radioactivity concentration in 167 patients were included from April 2019 to September 2020. The differences in SUVmax among the benign bone lesions, malignant bone lesions, and normal vertebrae were analyzed. The receiver operating characteristic (ROC) curve and cutoff value of SUVmax were obtained. Part II, prospective study, 49 solitary undetermined bone lesions in SPECT/CT in 49 untreated patients with extra-skeletal malignant tumors were enrolled from October 2020 to August 2022. The diagnostic efficacy of SUVmax in solitary undetermined bone lesions was assessed. The final diagnosis was based on follow-up imaging (CT, MRI, or 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography/computed tomography) for at least 12 months. Results: In Part I, a total of 156 malignant and 240 benign bone lesions was determined; the SUVmax of malignant lesions (26.49 ± 12.63) was significantly higher than those of benign lesions (13.92 ± 7.16) and normal vertebrae (6.97 ± 1.52) (P = 0.00). The diagnostic efficiency of the SUVmax of quantitative SPECT/CT revealed a sensitivity of 75.00% and a specificity of 81.70% at a cutoff value of 18.07. In Part II, 17 malignant and 32 benign lesions were determined. Using SUVmax ≥18.07 as a diagnostic criterion of malignancy, it has a sensitivity of 82.35%, a specificity of 93.75%, and an accuracy of 89.80%. Conclusion: The SUVmax of quantitative SPECT/CT is valuable in evaluating solitary undetermined bone lesions. Using a cutoff SUVmax value of 18.07, quantitative SPECT/CT demonstrated high sensitivity, specificity, and accuracy in differentiating malignant from benign bone lesions.

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BACKGROUND: Dynamic positron emission tomography (PET) images are useful in clinical practice because they can be used to calculate the metabolic parameters (Ki) of tissues using graphical methods (such as Patlak plots). Ki is more stable than the standard uptake value and has a good reference value for clinical diagnosis. However, the long scanning time required for obtaining dynamic PET images, usually an hour, makes this method less useful in some ways. There is a tradeoff between the scan durations and the signal-to-noise ratios (SNRs) of Ki images. The purpose of our study is to obtain approximately the same image as that produced by scanning for one hour in just half an hour, improving the SNRs of images obtained by scanning for 30 min and reducing the necessary 1-h scanning time for acquiring dynamic PET images. METHODS: In this paper, we use U-Net as a feature extractor to obtain feature vectors with a priori knowledge about the image structure of interest and then utilize a parameter generator to obtain five parameters for a two-tissue, three-compartment model and generate a time activity curve (TAC), which will become close to the original 1-h TAC through training. The above-generated dynamic PET image finally obtains the Ki parameter image. RESULTS: A quantitative analysis showed that the network-generated Ki parameter maps improved the structural similarity index measure and peak SNR by averages of 2.27% and 7.04%, respectively, and decreased the root mean square error (RMSE) by 16.3% compared to those generated with a scan time of 30 min. CONCLUSIONS: The proposed method is feasible, and satisfactory PET quantification accuracy can be achieved using the proposed deep learning method. Further clinical validation is needed before implementing this approach in routine clinical applications.

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BACKGROUND AND AIMS: Vascular calcification (VC) is regarded as an independent risk factor for cardiovascular events in type 2 diabetic patients. Glucose transporter 1 (GLUT1) involves VC. Intermedin/Adrenomedullin-2 (IMD/ADM2) is a cardiovascular protective peptide that can inhibit multiple disease-associated VC. However, the role and mechanism of IMD in diabetic VC remain unclear. Here, we investigated whether IMD inhibits diabetic VC by inhibiting GLUT1. METHODS AND RESULTS: It was found that plasma IMD concentration was significantly decreased in type 2 diabetic patients and in fructose-induced diabetic rats compared with that in controls. Plasma IMD content was inversely correlated with fasting blood glucose level and VC severity. IMD alleviated VC in fructose-induced diabetic rats. Deficiency of Adm2 aggravated and Adm2 overexpression attenuated VC in high-fat diet-induced diabetic mice. In vitro, IMD mitigated high glucose-induced calcification of vascular smooth muscle cells (VSMCs). Mechanistically, IMD reduced advanced glycation end products (AGEs) content and the level of receptor for AGEs (RAGE). IMD decreased glucose transporter 1 (GLUT1) levels. The inhibitory effect of IMD on RAGE protein level was blocked by GLUT1 knockdown. GLUT1 knockdown abolished the effect of IMD on alleviating VSMC calcification. IMD receptor antagonist IMD17-47 and cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) inhibitor H89 abolished the inhibitory effects of IMD on GLUT1 and VSMC calcification. CONCLUSIONS: These findings revealed that IMD exerted its anti-calcification effect by inhibiting GLUT1, providing a novel therapeutic target for diabetic VC.

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Understanding the responses of soil bacterial community to long-term fertilization in dryland of yellow soil could provide theoretical basis for establishing scientific fertilization system and cultivating healthy soil. Based on a 25-year long-term fertilization experiment on yellow soil, we collected soil samples from 0-20 cm layer under different fertilization treatments: no fertilization (CK), balanced application of N, P and K fertilizers (NPK), single application of organic fertilizer (M), combined application of constant organic and inorganic fertilizer (MNPK), and 1/2 organic fertilizer instead of 1/2 chemical fertilizer (MNP). Illumina MiSeq high-throughput sequencing technology was used to examine the effects of different fertilization patterns on soil bacterial community structure and soil nutrient content. The main driving factors of soil bacterial community were explored. The results showed that soil pH and organic matter content under treatments with organic fertilizer increased by 11.4%-13.5% and 28.8%-52.0%, respectively, compared to that under NPK treatment. Long-term fertilization did not affect soil bacterial α diversity, but significantly affected soil bacterial ß diversity. Compared with CK and NPK treatment, treatments of M, MNP, and MNPK significantly changed soil bacterial community structure, and increased the relative abundance of Fusobacteria and Anaerobes. Four fertilization treatments increased the relative abundance of Bacteroidetes, and decreased the relative abundance of Actinomyces and Campylobacter, compared to CK. Soil pH was the most important factor affecting soil bacterial community structure. Fertilization-stimulated rare microbial taxa (Pumilomyces and Anaerobes) were more sensitive to changes in different environmental factors and were the main drivers of the formation of community versatility. In conclusion, organic fertilizer improved soil properties and fertility and changed soil bacterial community structure, which are conducive to cultivating healthy soil.

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Current research has long focused on soil organic carbon and soil aggregates stability. However, the effects of different long-term fertilization on the composition of yellow soil aggregates and the characteristics of the occurrence of organic carbon in the karst region of Southwest China are still unclear. Based on a 25-year long-term located experiment on yellow soil, soil samples from the 0-20 cm soil layer were collected and treated with different fertilizers (CK: unfertilized control; NPK: chemical fertilizer; 1/4 M + 3/4 NP: 25% chemical fertilizer replaced by 25% organic fertilizer; 1/2 M + 1/2 NP: 50% chemical fertilizer replaced by organic fertilizer; and M: organic fertilizer). In water-stable aggregates, soil aggregates stability, total organic carbon (TOC), easily oxidized organic carbon (EOC), carbon preservation capacity (CPC), and carbon pool management index (CPMI) were analyzed. The findings demonstrated that the order of the average weight diameter (MWD), geometric mean diameter (GWD), and macro-aggregate content (R0.25) of stable water aggregates was M > CK > 1/2M +1/2NP > 1/4M +3/4NP> NPK. The MWD, GWD, and R0.25 of NPK treatment significantly decreased by 32.6%, 43.2%, and 7.0 percentage points, respectively, compared to CK treatment. The order of TOC and EOC content in aggregates of different particle sizes was M > 1/2M +1/2NP > 1/4M +3/4NP> CK > NPK, and it increased as the rate of organic fertilizer increased. In macro-aggregates and bulk soil, the CPC of TOC (TOPC) and EOC (EOPC), as well as CPMI, were arranged as M > 1/2M +1/2NP > 1/4M +3/4NP> CK > NPK, but the opposite was true for micro-aggregates. In bulk soil treated with organic fertilizer, the TOPC, EOPC, and CPMI significantly increased by 27.4%-53.8%, 29.7%-78.1%, 29.7-82.2 percentage points, respectively, compared to NPK treatment. Redundancy analysis and stepwise regression analysis show that TOC was the main physical and chemical factor affecting the aggregates stability, and the TOPC in micro-aggregates has the most direct impact. In conclusion, the primary cause of the decrease in SOC caused by the long-term application of chemical fertilizer was the loss of organic carbon in macro-aggregates. An essential method to increase soil nutrient supply and improve yellow soil productivity was to apply an organic fertilizer to increase aggregates stability, storage and activity of SOC in macro-aggregates.

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SMARCA4-deficient non-small cell lung cancer (NSCLC) is a more recently recognized subset of NSCLC. We describe the 18F-fluorodeoxyglucose (FDG) PET/CT findings in a rare case of SMARCA4-deficient NSCLC and response to therapy. A 45-year-old male patient with a history of heavy smoking (10 years) underwent an 18F-fluorodeoxyglucose (FDG) PET/CT dynamic (chest) + static (whole-body) scan for diagnosis and pre-treatment staging. 18F-FDG PET/CT showed an FDG-avid mass in the upper lobe of the left lung (SUVmax of 22.4) and FDG-avid lymph nodes (LN) in the left pulmonary hilar region (SUVmax of 5.7). In addition, there were multiple metastases throughout the body, including in the distant LNs, adrenal glands, bone, left subcutaneous lumbar region, and brain. Pathological findings confirmed SMARCA4-deficient NSCLC. After four cycles of chemotherapy and immune checkpoint inhibitors (ICI), the patient underwent again an 18F-FDG PET/CT scan (including a dynamic scan) for efficacy evaluation. We report a case that deepens the understanding of the 18F-FDG PET/CT presentation of SMARCA4-deficient NSCLC as well as dynamic imaging features and parametric characteristics.

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Nowadays, there has been a rapid expansion of tea plantations in the mountainous areas of southwest China. However, little research has focused on the pollution problems caused by the losses of nitrogen and phosphorus from tea plantations in this area. Therefore, a field experiment was conducted using the runoff plots in situ monitoring method following farmers' conventional management from 2018 to 2020 in Guizhou Province, southwest China. The characteristics of nitrogen and phosphorus losses from tea plantation in the mountainous area were clarified, and the effect of rainfall intensity on the nitrogen and phosphorus losses were explored. 298 natural rainfall events with a total rainfall of 2258 mm were observed during the 2-year observation period, and erosive rainfall accounted for 78.1% of the total rainfall. The total surface runoff amount was 72 mm, and the surface runoff coefficient was 3.19%. The total nitrogen (TN) and total phosphorus (TP) concentrations in the surface runoff ranged from 0.68 to 14.86 mg·L-1 and 0.18 to 2.34 mg·L-1, respectively. The TN and TP losses from tea plantations were 1.47 kg N ha-1 yr-1 and 0.210 kg P ha-1 yr-1. Rainfall intensity directly and significantly affected the surface runoff and nitrogen and phosphorus loss. Where 72.6% of the cumulative rainfall, 92.5% of the total surface runoff amounts, 87.4% of total nitrogen loss, and 90.5% of total phosphorus loss were observed in rainfall events above 10 mm. Taken together, the results provide scientific guidance for quantifying the characteristics of nutrient loss in subtropical mountain tea plantations.

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Objective: Central precocious puberty (CPP) is a rare condition that causes early sexual development in children. Although the cure is effective, the etiology of central precocious puberty is unclear. Methods: In total, 10 girls with central precocious puberty and same number of age-matched female controls were enrolled. Plasma samples were collected from each participant and subjected to untargeted metabolomics and lipidomics. Student's t-tests were employed to compare the mean of each metabolite and lipid. Furthermore, orthogonal partial least-squares discriminant analysis was conducted and the variable importance in the projection was calculated to identify differentially expressed metabolites or lipids. Subsequent bioinformatics was conducted to investigate the potential function of differentially expressed metabolites and lipids. Results: Fifty-nine differentially expressed metabolites were identified based on the criteria used (variable importance in the projection >1 and a P value < 0.05). Kyoto Encyclopedia Genes and Genome (KEGG) enrichment analysis showed that differentially expressed metabolites were enriched in four pathways: beta-alanine metabolism, histidine metabolism, bile secretion, and steroid hormone biosynthesis. As for the lipidomics, 41 differentially expressed lipids were observed and chain length analysis and lipid saturation analysis yielded similar results. Significant differences between the two groups were only observed in (O-acyl) ω-hydroxy fatty acids (OAHFA). Conclusion: The present study showed that antibiotic overuse, increased meat consumption, and obesity may have potential roles in the development of central precocious puberty in girls. Several metabolites have diagnostic value but further research is required.

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Objectives: 18F-fluorodeoxyglucose (FDG) PET/CT has been widely used in tumor diagnosis, staging, and response evaluation. To determine an optimal therapeutic strategy for lung cancer patients, accurate staging is essential. Semi-quantitative standardized uptake value (SUV) is known to be affected by multiple factors and may fail to differentiate between benign and malignant lesions. Lymph nodes (LNs) in the mediastinal and pulmonary hilar regions with high FDG uptake due to granulomatous lesions such as tuberculosis, which has a high prevalence in China, pose a diagnostic challenge. This study aims to evaluate the diagnostic value of the quantitative metabolic parameters derived from dynamic 18F-FDG PET/CT in differentiating metastatic and non-metastatic LNs in lung cancer. Methods: One hundred and eight patients with pulmonary nodules were enrolled to perform 18F-FDG PET/CT dynamic + static imaging with informed consent. One hundred and thirty-five LNs in 29 lung cancer patients were confirmed by pathology. Static image analysis parameters including LN-SUVmax, LN-SUVmax/primary tumor SUVmax (LN-SUVmax/PT-SUVmax), mediastinal blood pool SUVmax (MBP-SUVmax), LN-SUVmax/MBP-SUVmax, and LN-SUVmax/short diameter. Quantitative parameters including K1, k2, k3 and Ki and of each LN were obtained by applying the irreversible two-tissue compartment model using in-house Matlab software. Ki/K1 was computed subsequently as a separate marker. We further divided the LNs into mediastinal LNs (N=82) and pulmonary hilar LNs (N=53). Wilcoxon rank-sum test or Independent-samples T-test and receiver-operating characteristic (ROC) analysis was performed on each parameter to compare the diagnostic efficacy in differentiating lymph node metastases from inflammatory uptake. P<0.05 were considered statistically significant. Results: Among the 135 FDG-avid LNs confirmed by pathology, 49 LNs were non-metastatic, and 86 LNs were metastatic. LN-SUVmax, MBP-SUVmax, LN-SUVmax/MBP-SUVmax, and LN-SUVmax/short diameter couldn't well differentiate metastatic from non-metastatic LNs (P>0.05). However, LN-SUVmax/PT-SUVmax have good performance in the differential diagnosis of non-metastatic and metastatic LNs (P=0.039). Dynamic metabolic parameters in addition to k3, the parameters including K1, k2, Ki, and Ki/K1, on the other hand, have good performance in the differential diagnosis of metastatic and non-metastatic LNs (P=0.045, P=0.001, P=0.001, P=0.001, respectively). For ROC analysis, the metabolic parameters Ki (AUC of 0.672 [0.579-0.765], sensitivity 0.395, specificity 0.918) and Ki/K1 (AUC of 0.673 [0.580-0.767], sensitivity 0.570, specificity 0.776) have good performance in the differential diagnosis of metastatic from non-metastatic LNs than SUVmax (AUC of 0.596 [0.498-0.696], sensitivity 0.826, specificity 0.388), included the mediastinal region and pulmonary hilar region. Conclusion: Compared with SUVmax, quantitative parameters such as K1, k2, Ki and Ki/K1 showed promising results for differentiation of metastatic and non-metastatic LNs with high uptake. The Ki and Ki/K1 had a high differential diagnostic value both in the mediastinal region and pulmonary hilar region.

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Enhancing maize lodging resistance with plant growth retardants (PGRs) is common in maize production. However, the underlying mechanisms of yield formation as affected by PGRs are still poorly understood. A field experiment contained PGR application (a mixture of ethephon and cycocel, EC) with normal (T1) and double (T2) doses and water control (CK) was conducted at four maize plant densities (4.5, 6.0, 7.5, and 9.0 plants m-2) in 2020 and 2021. In this two-year study, the grain yield and kernel number per ear (KNE) of EC treatments were reduced by 4.8-9.0% and 3.3-12.2%, respectively, compared with CK under densities of 4.5, 6.0, and 7.5 plants m-2 without lodging. However, under the density of 9.0 plants m-2, EC treatments had no pronounced effects on grain yield and yield components. Across all densities, EC significantly decreased the leaf area index (LAI), and the lowest LAI was recorded in T2. The concentrations of nonstructural carbohydrates (NSCs; starch and soluble sugar) in the stem were significantly decreased by 9.9-10.2% in T2 averaged all densities. The sucrose and starch concentrations in grains also declined in the EC treatments. The key enzymes (cell wall acid invertase, sucrose synthase, and adenosine diphosphate pyrophosphorylase) and grain polyamine concentrations showed a slight downward trend under EC treatments compared to CK. NSCs in stems and grains, kernel enzyme activities, and polyamines in grains presented significant positive correlations with KNE. Additionally, structural carbohydrate (SC; including cellulose, hemicellulose, and lignin) concentrations in stems were improved with enhanced lodging resistance by spraying EC. Significant negative relationships were observed between SC with kernel number m-2 (KNM) and yield, suggesting that improved SC in stems might affect the availability of NSCs for kernel set. Although the lowest kernel weight and KNE were obtained at 9.0 plant m-2, relatively high LAI still ensured high KNM and high yield. Collectively, EC treatment increased SC in stems, enhanced lodging resistance of maize and reduced NSC availability for kernels, ultimately presenting adverse effects on maize kernel number and yield under relative low density.

RESUMEN

Vascular calcification (VC) is a common pathophysiological process of chronic kidney disease (CKD). Sirtuin 3 (Sirt3), a major NAD+-dependent protein deacetylase predominantly in mitochondria, is involved in the pathogenesis of VC. We previously reported that intermedin (IMD) could protect against VC. In this study, we investigated whether IMD attenuates VC by Sirt3-mediated inhibition of mitochondrial oxidative stress. A rat VC with CKD model was induced by the 5/6 nephrectomy plus vitamin D3. Vascular smooth muscle cell (VSMC) calcification was induced by CaCl2 and ß-glycerophosphate. IMD1-53 treatment attenuated VC in vitro and in vivo, rescued the depressed mitochondrial membrane potential (MMP) level and decreased mitochondrial ROS levels in calcified VSMCs. IMD1-53 treatment recovered the reduced protein level of Sirt3 in calcified rat aortas and VSMCs. Inhibition of VSMC calcification by IMD1-53 disappeared when the cells were Sirt3 absent or pretreated with the Sirt3 inhibitor 3-TYP. Furthermore, 3-TYP pretreatment blocked IMD1-53-mediated restoration of the MMP level and inhibition of mitochondrial oxidative stress in calcified VSMCs. The attenuation of VSMC calcification by IMD1-53 through upregulation of Sirt3 might be achieved through activation of the IMD receptor and post-receptor signaling pathway AMPK, as indicated by pretreatment with an IMD receptor antagonist or AMPK inhibitor blocking the inhibition of VSMC calcification and upregulation of Sirt3 by IMD1-53. AMPK inhibitor treatment reversed the effects of IMD1-53 on restoring the MMP level and inhibiting mitochondrial oxidative stress in calcified VSMCs. In conclusion, IMD attenuates VC by improving mitochondrial function and inhibiting mitochondrial oxidative stress through upregulating Sirt3.

RESUMEN

Global warming has increased the occurrence of high temperature stress in plants, including maize, resulting in decreased the grain number and yield. Previous studies indicate that heat stress mainly damages the pollen grains and thus lowered maize grain number. Other field studies have shown that heat stress after pollination results in kernel abortion. However, the mechanism by which high temperature affect grain abortion following pollination remains unclear. Hence, this study investigated the field grown heat-resistant maize variety "Zhengdan 958" (ZD958) and heat-sensitive variety "Xianyu 335" (XY335) under a seven-day heat stress treatment (HT) after pollination. Under HT, the grain numbers of XY335 and ZD958 were reduced by 10.9% (p = 0.006) and 5.3% (p = 0.129), respectively. The RNA sequencing analysis showed a higher number of differentially expressed genes (DEGs) between HT and the control in XY335 compared to ZD958. Ribulose diphosphate carboxylase (RuBPCase) genes were downregulated by heat stress, and RuBPCase activity was significantly lowered by 14.1% (p = 0.020) in XY335 and 5.3% (p = 0.436) in ZD958 in comparison to CK. The soluble sugar and starch contents in the grains of XY335 were obviously reduced by 26.1 and 58.5%, respectively, with no distinct change observed in ZD958. Heat stress also inhibited the synthesis of grain starch, as shown by the low activities of metabolism-related enzymes. Under HT, the expression of trehalose metabolism genes in XY335 were upregulated, and these genes may be involved in kernel abortion at high temperature. In conclusion, this study revealed that post-pollination heat stress in maize mainly resulted in reduced carbohydrate availability for grain development, though the heat-resistant ZD958 was nevertheless able to maintain growth.