Cold exposure alters lipid metabolism of skeletal muscle through HIF-1α-induced mitophagy.

BACKGROUND: In addition to its contractile properties and role in movement, skeletal muscle plays an important function in regulating whole-body glucose and lipid metabolism. A central component of such regulation is mitochondria, whose quality and function are essential in maintaining proper metabolic homeostasis, with defects in processes such as autophagy and mitophagy involved in mitochondria quality control impairing skeletal muscle mass and function, and potentially leading to a number of associated diseases. Cold exposure has been reported to markedly induce metabolic remodeling and enhance insulin sensitivity in the whole body by regulating mitochondrial biogenesis. However, changes in lipid metabolism and lipidomic profiles in skeletal muscle in response to cold exposure are unclear. Here, we generated lipidomic or transcriptome profiles of mouse skeletal muscle following cold induction, to dissect the molecular mechanisms regulating lipid metabolism upon acute cold treatment. RESULTS: Our results indicated that short-term cold exposure (3 days) can lead to a significant increase in intramuscular fat deposition. Lipidomic analyses revealed that a cold challenge altered the overall lipid composition by increasing the content of triglyceride (TG), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE), while decreasing sphingomyelin (SM), validating lipid remodeling during the cold environment. In addition, RNA-seq and qPCR analysis showed that cold exposure promoted the expression of genes related to lipolysis and fatty acid biosynthesis. These marked changes in metabolic effects were associated with mitophagy and muscle signaling pathways, which were accompanied by increased TG deposition and impaired fatty acid oxidation. Mechanistically, HIF-1α signaling was highly activated in response to the cold challenge, which may contribute to intramuscular fat deposition and enhanced mitophagy in a cold environment. CONCLUSIONS: Overall, our data revealed the adaptive changes of skeletal muscle associated with lipidomic and transcriptomic profiles upon cold exposure. We described the significant alterations in the composition of specific lipid species and expression of genes involved in glucose and fatty acid metabolism. Cold-mediated mitophagy may play a critical role in modulating lipid metabolism in skeletal muscle, which is precisely regulated by HIF-1α signaling.

An Ultra-Stable Electrode-Solid Electrolyte Composite for High-Performance All-Solid-State Li-Ion Batteries.

The low ionic and electronic conductivity between current solid electrolytes and high-capacity anodes limits the long-term cycling performance of all-solid-state lithium-ion batteries (ASSLIBs). Herein, this work reports the fabrication of an ultra-stable electrode-solid electrolyte composite for high-performance ASSLIBs enabled by the homogeneous coverage of ultrathin Mg(BH4 )2 layers on the surface of each MgH2 nanoparticle that are uniformly distributed on graphene. The initial discharge process of Mg(BH4 )2 layers results in uniform coverage of MgH2 nanoparticle with both LiBH4 as the solid electrolyte and Li2 B6 with even higher Li ion conductivity than LiBH4 . Consequently, the Li ion conductivity of graphene-supported MgH2 nanoparticles covered with ultrathin Mg(BH4 )2 layers is two orders of magnitude higher than that without Mg(BH4 )2 layers. Moreover, the thus-formed inactive Li2 B6 with strong adsorption capability toward LiBH4 , acts as a stabilizing framework, which, coupled with the structural support role of graphene, alleviates the volume change of MgH2 nanoparticles and facilitates the intimate contact between LiBH4 and individual MgH2 nanoparticles, leading to the formation of uniform stable interfaces with high ionic and electronic conductivity on each MgH2 nanoparticles. Hence, an ultrahigh specific capacity of 800 mAh g-1 is achieved for MgH2 at 2 A g-1 after 350 cycles.

Circ_FOXP1 promotes the growth and survival of high glucose-treated human trophoblast cells through the regulation of miR-508-3p/SMAD family member 2 pathway.

Gestational diabetes mellitus (GDM) is a health risk for pregnant women and infants. Emerging evidence suggests that the deregulation of circular RNAs (circRNAs) is associated with the progression of this disorder. The objective of this study was to investigate the role of circ_FOXP1 in GDM. Cell models of GDM were established by treating human trophoblast cells with high glucose (HG). The expression of circ_FOXP1, miR-508-3p and SMAD family member 2 (SMAD2) mRNA was detected by quantitative real-time PCR (qPCR). Cell proliferation was assessed by EdU assay and MTT assay, and cell cycle and cell apoptosis were determined by flow cytometry assay. The protein levels of proliferation- and apoptosis-related markers and SMAD2 were measured by western blot. The relationship between miR-508-3p and circ_FOXP1 or SMAD2 was validated by dual-luciferase reporter assay or pull-down assay. The expression of circ_FOXP1 was downregulated in HG-treated HTR-8/SVneo cells. Circ_FOXP1 overexpression promoted HG-inhibited HTR-8/SVneo cell proliferation and suppressed HG-induced HTR-8/SVneo cell cycle arrest and apoptosis. Circ_FOXP1 positively regulated the expression of SMAD2 by targeting miR-508-3p. MiR-508-3p was overexpressed in HG-treated HTR-8/SVneo cells, and its overexpression reversed the effects of circ_FOXP1 overexpression. MiR-508-3p inhibition also alleviated HG-induced HTR-8/SVneo cell injuries, while the knockdown of SMAD2 abolished these effects. Collectively, circ_FOXP1 promotes the growth and survival of HG-treated human trophoblast cells through the miR-508-3p/SMAD2 pathway, hinting that circ_FOXP1 was involved in GDM progression.

Expression and clinical significance of circular RNA hsa_circ_0003416 in pediatric pulmonary arterial hypertension associated with congenital heart disease.

BACKGROUND: Circular RNAs (circRNAs) have been found to be involved in the development of pulmonary arterial hypertension (PAH). However, their diagnostic value in pediatric PAH remains unclear. This study aimed to examine the characteristic expression of the circRNA hsa_circ_0003416 in the plasma of children with PAH caused by congenital heart disease (CHD); the potential of hsa_circ_0003416 as a diagnostic biomarker was also investigated. METHODS: The plasma expression levels of hsa_circ_0003416 were determined via quantitative reverse transcription-polymerase chain reaction in 50 CHD patients, 50 PAH patients, and 20 healthy subjects; the associations between hsa_circ_0003416 levels and clinical data were analyzed thereafter. Receiver operating characteristic curves were employed to determine the diagnostic capacity of this circRNA. RESULTS: Expression levels of hsa_circ_0003416 in plasma were lower in the PAH-CHD group than in the CHD and healthy control groups (p = 0.009 vs. healthy control group, p = 0.026 vs. CHD group). Moreover, hsa_circ_0003416 was found to be negatively associated with B-type natriuretic peptide (r = -0.342, p = 0.013). In addition, the area under the curve of hsa_circ_0003416 levels in plasma was 0.721 (95% confidence intervals = 0.585-0.857, p = 0.004), suggesting that it has a promising diagnostic value. CONCLUSIONS: Overall, hsa_circ_0003416 was found to be significantly downregulated in children with PAH-CHD and to be potent as a biomarker for PAH-CHD diagnosis.

Effects of YM155 on the proliferation and apoptosis of pulmonary artery smooth muscle cells in a rat model of high pulmonary blood flow-induced pulmonary arterial hypertension.

INTRODUCTION: Proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMCs) play an important role in the occurrence and development of pulmonary arterial hypertension (PAH). The purpose of this study was to investigate the effects of survivin inhibitor YM155 on the proliferation and apoptosis of PASMCs in rats with PAH induced by high pulmonary blood flow. METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into control, model, and YM155 intervention groups. A rat model of PAH induced by high pulmonary blood flow was established, and it was confirmed by assessments of right-ventricular pressure (RVP) and right ventricular hypertrophy index (RVHI). Immunohistochemical staining and western blot analysis were used to detect the expression of survivin, and the proliferation and apoptosis of PASMCs. Lastly, the effects of in vivo treatment of YM155 were tested. RESULTS: The increased expression of survivin mRNA and protein were observed in the model group, accompanied by pulmonary arteriolar wall thickening, lumen stenosis, and perivascular inflammatory cell infiltration. Elevated expression of survivin and pulmonary vascular remodeling were significantly mitigated after YM155 treatment. Specifically, the YM155 intervention group had a significantly lower PASMC proliferation rate and a higher PASMC apoptotic rate. CONCLUSION: YM155 suppressed PASMC proliferation and promoted PASMC apoptosis by inhibiting survivin expression and thereby reducing pulmonary vascular remodeling in high pulmonary blood flow-induced PAH in vivo.

Diagnostic value of 2017 ACR Thyroid Imaging Reporting and Data System (TI-RADS) combined with fine needle aspiration biopsy in thyroid nodules.

OBJECTIVE: To evaluate diagnostic value of Thyroid Imaging Reporting and Data System published by American College of Radiology (ACR TI-RADS) in 2017, ultrasound-guided fine-needle aspiration (US-FNA), and the combination of both methods in differentiation between benign and malignant thyroid nodules. METHODS: The data of US-FNA and ACR TI-RADS are collected from 159 patients underwent thyroid surgery in our hospital, which include a total of 178 thyroid nodules. A Bethesda System for Reporting Thyroid Cytopathology category of ≥IV and an ACR TI-RADS category ≥4 are regarded as diagnosis standards for malignancy in US-FNA and ACR TI-RADS, respectively. The pathological results after surgery are considered as the gold standard. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the ACR TI-RADS, US-FNA and the combination of both methods for the differential diagnosis of thyroid nodules are calculated, respectively. RESULTS: The sensitivity, specificity and accuracy of ACR TI-RADS are 85.4%, 37.5%and 72.5%, respectively. The sensitivity, specificity and accuracy of US-FNA are 70.0%, 100%and 78.1%, respectively. After combining these two methods, the sensitivity, specificity and accuracy increase to 99.23%, 37.50%and 82.58%, respectively. The sensitivity of ACR TI-RADS is higher than that of US-FAN, and the sensitivity of combining these two methods is also higher than that of using ACR TI-RADS and US-FNA alone. CONCLUSION: The established ACR TI-RADS can help in selecting the target during nodule puncture, while the combination of ACR TI-RADS and US-FAN can further improve diagnostic ability for detecting malignant thyroid nodules.

Early Monitoring Drug Resistant Mutation T790M with a Two-Dimensional Simultaneous Discrimination Nanopore Strategy.

With the aim of detecting low frequency of drug resistant mutation T790M against wild-type sequences, we reported a two-dimensional signal analysis strategy by combining a three locked nucleic acids (LNAs)-modified probe (LP15-3t) and an α-HL nanopore. The specific hybridization of the LP15-3t probe with the T790M generated unique long two-level signals, including characteristic blocking current and characteristic dwell time. Due to the significant dwell time difference (114.2-fold) and the blocking current difference ranging from 81% to 96%, this two-dimensional signal analysis strategy can simultaneously distinguish T790M sequences with a sensitivity of 0.0001% against wild-type sequences. The LOD of T790M was 0.1 pM. This high discrimination capability would have great potential in the detection of rare mutation sequences and the early monitoring of clinical outcome of NSCLC patients with TKI drug resistance.

Visit-to-Visit Variability in Total Cholesterol Correlates with the Progression of Renal Function Decline in a Chinese Community-Based Hypertensive Population.

BACKGROUND: Studies have demonstrated that cholesterol variability is an independent predictor of cerebrovascular and cardiovascular events. OBJECTIVE: This study aimed to investigate the association of visit-to-visit variability in total cholesterol (TC) with kidney decline in a Chinese community-based population. METHODS: We assessed intraindividual variability in TC among 6,465 hypertensive participants and correlated the results with endpoints. TC variability was measured using standard deviation (SD), average successive variability (ASV), coefficient of variation (CV), and variability independent of the mean (VIM). The endpoint of this study was progression of renal function decline defined as a decrease in estimated glomerular filtration rate (eGFR) ≥30% and to a level <60 mL/min/1.73 m2 during follow-up if the baseline eGFR was ≥60 mL/min/1.73 m2, or a decrease in eGFR ≥50% during follow up if the baseline eGFR was <60 mL/min/1.73 m2. RESULTS: After a median follow-up of 27 months, 13.5% (n = 877) of the participants experienced progression of renal function decline. In the multivariable-adjusted Cox model, each 1-SD increase in TC variability (by SD) increased the risk of renal function decline by 11% (HR = 1.11; 95% CI 1.034-1.197; p = 0.004); this was independent of the baseline eGFR, mean follow-up TC levels, and the lipid-lowering therapy. Similar results were found for the 3 other measures of variability, i.e., ASV, CV, and VIM. CONCLUSION: In subjects with hypertension, visit-to-visit variability in TC is an independent predictor of renal function decline.

Simultaneous Discrimination of Single-Base Mismatch and Full Match Using a Label-Free Single-Molecule Strategy.

Identification of single-base mismatches has found wide applications in disease diagnosis, pharmacogenetics, and population genetics. However, there is still a great challenge in the simultaneous discrimination of single-base mismatch and full match. Combined with a nanopore electrochemical sensor, a shared-stem structure of molecular beacon was designed that did not need the labeling, but achieved an enhanced signal-to-background ratio of ∼104, high thermodynamic stability to bind with target sequences, and a fast hybridization rate. Fully matched and single-base mismatched sequences were simultaneously discriminated at the single-molecule level, which is expected to have potential applications ranging from the quick detection, early clinical diagnostics to point-of-care research.

Cancer-associated fibroblasts promote angiogenesis in gastric cancer through galectin-1 expression.

BACKGROUND: Galectin-1, an evolutionarily conserved glycan-binding protein with angiogenic potential, was recently identified as being overexpressed in cancer-associated fibroblasts (CAFs) of gastric cancer. The role of endogenous CAF-derived galectin-1 on angiogenesis in gastric cancer and the mechanism involved remain unknown. METHODS: Immunohistochemical staining was used to investigate the correlation between galectin-1 and vascular endothelial growth factor (VEGF) and CD31 expression in gastric cancer tissues and normal gastric tissues. Galectin-1 was knocked down in CAFs isolated from gastric cancer using small interfering ribonucleic acid (RNA), or overexpressed using recombinant lentiviruses, and the CAFs were co-cultured with human umbilical vein endothelial cells (HUVECs) or cancer cells. Subsequently, proliferation, migration, tube formation, and VEGF/VEGF receptor (VEGFR) 2 expression were detected. The role of CAF-derived galectin-1 in tumor angiogenesis in vivo was studied using the chick chorioallantoic membrane (CAM) assay. RESULTS: Galectin-1 was highly expressed in the CAFs and was positively associated with VEGF and CD31 expression. In the co-culture, high expression of galectin-1 in the CAFs increased HUVEC proliferation, migration, tube formation, and VEGFR2 phosphorylation and enhanced VEGF expression in gastric cancer cells. The CAM assay indicated that high expression of galectin-1 in the CAFs accelerated tumor growth and promoted angiogenesis. In contrast, galectin-1 knockdown in the CAFs significantly inhibited this effect. CONCLUSION: CAF-derived galectin-1 significantly promotes angiogenesis in gastric cancer and may be a target for angiostatic therapy.

Comprehensive analysis based on glycolytic and glutaminolytic pathways signature for predicting prognosis and immunotherapy in ovarian cancer.

Background: Our study attempts to develop and identify an aerobic glycolysis and glutamine-related genes (AGGRGs) signature for estimating prognostic effectively of ovarian cancer (OV) patients. Materials & methods: OV related data were extracted from the multiple public databases, including TCGA-OV, GSE26193, GSE63885, and ICGC-OV. A consistent clustering approach was used to characterize the subtypes associated with AGGRGs. LASSO Cox regressions was utilized to construct the prognosis signatures of AGGRGs. In addition, GSE26193, GSE63885 and ICGC-OV served as independent external cohorts to assess the reliability of the model. In vitro and in vivo experiments were conducted to study the role of AAK1 in the malignant progression and glutamine metabolism of OV, and assessed its therapeutic potential for treating OV patients. Results: OV patients could be separated into four subtypes (quiescent, glycolysis, glutaminolytic, and mixed subtypes). The survival outcome of glutaminolytic subtype was notably worse than the glycolytic subtype. Besides, we identified eight AGGRGs (AAK1, GJB6, HMGN5, LPIN3, INTS6L, PPOX, SPAG4, and ZNF316) to establish a prognostic signature for OV patients. Comprehensive analysis revealed that the signature risk score served as an independent prognostic factor for OV. Additionally, high-risk OV patients were less sensitive to platinum and, conversely, were proved to be more responsive to immunotherapy than low-risk score. In cytological experiments, we found that AAK1 could promote cancer progression and glutamine metabolism via activating the Notch3 pathway in OV cells. Furthermore, knockdown of AAK1 significantly inhibited tumor growth and weight, decreased lung metastases, and ultimately extended the survival time of the nude mice. Conclusions: The prognostic signature of AGGRGs constructed could efficiently estimate the prognosis and immunotherapy effectiveness of OV patients. In addition, AAK1 may represent a promising therapeutic target for OV.

Relationship between Baseline Serum Potassium and 1-Year Readmission in Pediatric Patients with Heart Failure: A Retrospective Cohort Study.

Pediatric heart failure (HF) is associated with high readmission rates, but the optimal serum potassium range for this population remains unclear. In this single-center retrospective cohort study, 180 pediatric patients hospitalized for HF between January 2016 and January 2022 were stratified into low-potassium (<3.7 mmol/L), middle-potassium (3.7-4.7 mmol/L), and high-potassium (≥4.7 mmol/L) groups based on the distribution of potassium levels in the study population. The primary outcome was readmission for HF within 1 year of discharge. Cox regression and restricted cubic spline models were used to assess the association between potassium levels and 1-year HF readmission rates. Notably, 38.9% of patients underwent 1 or more 1-year readmissions for HF within 1 year. The high-potassium group had a significantly higher readmission frequency than the middle-potassium group. In multivariate Cox regression models, potassium levels of ≥4.7 mmol/L were independently associated with increased 1-year readmission risk. A J-shaped relationship was observed between baseline potassium levels and 1-year readmission risk, with the lowest risk at 4.1 mmol/L. In pediatric patients with HF, a serum potassium level ≥ 4.7 mmol/L was independently associated with increased 1-year readmission risk. Maintaining potassium levels within a narrow range may improve outcomes in this population.

Leucine improves the growth performance, carcass traits, and lipid nutritional quality of pork in Shaziling pigs.

Leucine is involved in promoting fatty acid oxidation and lipolysis, mediating lipid metabolism and energy homeostasis, thus it has been widely used in livestock production. However, the effects of leucine on fat deposition and nutrition in Shaziling pigs remain unclear. A total of 72 Shaziling pigs (150 days old, weight 35.00 ± 1.00 kg) were randomly divided into 2 groups and fed with basal diet (control group) or basal diet containing 1% leucine (leucine group) for 60 days. The results showed that leucine significantly increased the average daily feed intake but decreased the ratio of feed to gain (P < 0.05), increased the loin muscle area and serum glucose content (P < 0.05) of Shaziling pigs. Besides, leucine regulated the re-distribution of fatty acids from adipose tissue to muscle as it significantly increased the contents of C18:1n-9 and C22:6n-3 (DHA) in the longissimus thoracis while decreased the contents of C22:5n-3 (DPA), C20:5n-3 (EPA), and DHA in the adipose tissue of Shaziling pigs (P < 0.05). Lipidomic analysis showed that the contents of phosphatidylethanolamines (PEs), cardiolipins (CLs), and phosphatidylglycerols (PGs) in the longissimus thoracis and the contents of lysophosphatidylethanolamines (LPEs), ceramides (Cers), phosphatidylinositols (PIs) in adipose tissue of Shaziling pigs were decreased in leucine group (P < 0.05). Collectively, this study clarified that dietary addition of 1% leucine have a better effect on growth performance and the deposition of beneficial fatty acids in the muscle of Shaziling pigs, which is conductive to the production of high quality and healthy pork. In addition, leucine altered the lipid composition of muscle and fat in Shaziling pigs. The related results provide a theoretical basis and application guidance for regulating fat deposition in Shaziling pigs, which is important for the healthy breeding of Shaziling pigs.

[Observation on the efficacy of continuous veno-venous hemodia-filtration combined with hemoperfusion HA380 in the treatment of 15 cases of heat stroke with multiple organ dysfunction syndrome].

OBJECTIVE: To investigate the clinical efficacy of continuous veno-venous hemodia-filtration (CVVHDF) combined with hemoperfusion (HP) HA380 in the treatment of heat stroke patients with multiple organ dysfunction syndrome (MODS). METHODS: A retrospective and observational study was conducted. A total of 15 patients with heat stroke combined with MODS who were admitted to the department of intensive care unit (ICU) of Suizhou Central Hospital/Hubei University of Medicine from July to September 2022 were selected as the study objects. All 15 patients were treated with CVVHDF combined with HA380 based on the comprehensive management strategy for severe illness. Organ function indicators [including total bilirubin (TBil), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), creatinine (Cr), cardiac troponin T (cTnT), myoglobin (Myo), MB isoenzyme of creatine kinase (CK-MB), sequential organ failure assessment (SOFA)] and inflammatory indicators [including white blood cell count (WBC), neutrophil count (NEU), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6)] were collected. The improvements of the above indexes at admission, after the first HP, after the second HP, after the third HP, and on the 5th day of treatment were compared. Combined with the clinical outcome of patients, the comprehensive efficacy of CVVHDF combined with HA380 in the treatment of severe heat radiation disease was evaluated. RESULTS: There were 10 males and 5 females among the 15 patients. The average age was (64.5±11.5) years old. There were 6 cases of classical heat stroke and 9 cases of exertional heat stroke. Glasgow coma scale (GCS) was 3-8 at admission; SOFA score was 9-17 within 12 hours after admission; acute physiology and chronic health evaluation II (APACHE II) was 25-45 within 24 hours after admission. After treatment, the IL-6 level and SOFA score gradually decreased, and there were significant differences in the decrease after the second HP compared to admission [IL-6 (ng/L): 48.37 (15.36, 113.03) vs. 221.90 (85.87, 425.90), SOFA: 8.3±3.3 vs. 11.1±2.4, both P < 0.05]. The PCT level reached its peak after the first HP [12.51 (6.07, 41.65) µg/L], and then gradually decreased, and the difference was statistically significant after the third HP [1.26 (0.82, 5.40) µg/L, P < 0.05]. Compared those at admission, Cr level significantly improved after the first HP (µmol/L: 66.94±25.57 vs. 110.80±31.13, P < 0.01), Myo significantly decreased after the second HP [µg/L: 490.90 (164.98, 768.05) vs. 3 000.00 (293.00, 3 000.00), P < 0.05], After the third HP, the CK level also showed significant improvement [U/L: 476.0 (413.0, 922.0) vs. 2 107.0 (729.0, 2 449.0), P < 0.05]. After CVVHDF combined with 3 times HP treatment, the patient's inflammatory response was gradually controlled and organ function gradually recovered. On the 5th day of the disease course, WBC, PCT and IL-6 levels were significantly improved compared to admission, and AST, CK, LDH, Cr, Myo, CK-MB, and SOFA score were significantly corrected compared with those on admission. The 24-hour survival rate of 15 patients was 86.67%, and the 24-hour, 7-day and 28-day survival rates were both as high as 73.33%. The average mechanical ventilation time of 11 surviving patients was (101.8±22.0) hours, the average continuous renal replacement therapy (CRRT) time was (58.8±11.0) hours, the average length of ICU stay was (6.3±1.0) days, and the average total hospitalization was (14.6±5.2) days. CONCLUSIONS: CVVHDF combined with HP HA380 in the treatment of heat stroke patients with MODS can effectively improve organ function and alleviate the inflammatory storm, which is an effective means to improve the rescue rate and reduce the mortality of severe heat stroke patients.

CENPA promotes glutamine metabolism and tumor progression by up-regulating SLC38A1 in endometrial cancer.

Glutamine addiction is a significant hallmark of metabolic reprogramming in tumors and is crucial to the progression of cancer. Nevertheless, the regulatory mechanisms of glutamine metabolism in endometrial cancer (EC) remains elusive. In this research, we found that elevated expression of CENPA and solute carrier family 38 member 1 (SLC38A1) were firmly associated with worse clinical stage and unfavorable outcomes in EC patients. In addition, ectopic overexpression or silencing of CENPA could either enhance or diminish glutamine metabolism and tumor progression in EC. Mechanistically, CENPA directly regulated the transcriptional activity of the target gene, SLC38A1, leading to enhanced glutamine uptake and metabolism, thereby promoting EC progression. Notably, a prognostic model utilizing the expression levels of CENPA and SLC38A1 genes independently emerged as a prognostic factor for EC. More importantly, CENPA and SLC38A1 were significantly elevated and positively correlated, as well as indicative of poor prognosis in multiple cancers. In brief, our study confirmed that CENPA is a critical transcription factor involved in glutamine metabolism and tumor progression through modulating SLC38A1. This revelation suggests that targeting CENPA could be an appealing therapeutic approach to address pan-cancer glutamine addiction.

Effects of five carbohydrate sources on cat diet digestibility, postprandial glucose, insulin response, and gut microbiomes.

Cat obesity has become a serious problem that affects cats' lives and welfare. Knowing how to control obesity in pet cats and its mechanism is urgently needed. Here, by feeding 30 cats different diets for 28 d, we explored the effects of 5 cat foods with potato, sweet potato, cassava, rice, and wheat as the main carbohydrate sources on the glycolipid metabolism of pet cats. The results showed that dietary carbohydrate sources did not affect the normal growth performance and stool scores of cats. Notably, we found that the starch gelatinization degree of sweet potato and cassava cat food were higher than those of other groups, while the rice diets had the highest digestibility, but the difference was not significant (P > 0.05). Furthermore, cats fed cassava diets had lower postprandial glucose responses. The mean glucose value, maximum glucose value, AUC0-360 min, AUC≤30 min, and AUC≥30 min in the cassava group were lower than those in other dietary groups (P > 0.05). In addition, we found that the carbohydrate source had a minimal effect on serum biochemical immune indices, but the blood lipid indices, such as TG, TC, HDL, and LDL of cats fed the cassava diet were maintained at a low level compared with other groups (P > 0.05). In addition, diets with different carbohydrate sources affect the gut microbial composition, and sweet potato and cassava diets tend to increase the diversity of gut microbiota with a higher Shannon index and Simpson index. The abundance of Fusobacterium, Veillonella, and Actinobacillus was significantly higher in sweet potato diet-fed cats (P < 0.05), while the abundance of Delftia, Shinella, Rothia, and Hydrogenophage was highest in cassava diet-fed cats (P < 0.05). Collectively, this study revealed that cassava and sweet potato diets have a better effect on feeding value, controlling blood glucose and blood lipids, and improving the intestinal flora of pet cats, which is worth developing dietary formulations to alleviate pet obesity.

Pet obesity is becoming increasingly common and may have a negative impact on pet health. The exploration of measures to alleviate pet obesity is urgently needed. Carbohydrates are an important component of pet food, and their digestion and absorption affect the levels of blood glucose and blood lipids and the procession of obesity. Therefore, the objective of this study was to evaluate the effects of different sources of carbohydrates on cat digestibility, postprandial glucose response, serum biochemical immune index, and microbiomes. The results showed that cat food with cassava and sweet potato as the main source of carbohydrates has a better effect on controlling blood glucose and blood lipids and improving the intestinal flora of pet cats. This provides a valuable reference for the research and development of pet food.

Conjugated linoleic acids inhibit lipid deposition in subcutaneous adipose tissue and alter lipid profiles in serum of pigs.

Conjugated linoleic acids (CLAs) have served as a nutritional strategy to reduce fat deposition in adipose tissues of pigs. However, the effects of CLAs on lipid profiles in serum and how these lipid molecules regulate fat deposition are still unclear. In this study, we explored the effects of CLAs on regulating lipid deposition in adipose tissues in terms of lipid molecules and microbiota based on a Heigai pig model. A total of 56 Heigai finishing pigs (body weight: 85.58 ±â€…10.39 kg) were randomly divided into two treatments and fed diets containing 1% soyabean oil or 1% CLAs for 40 d. CLAs reduced fat deposition and affected fatty acids composition in adipose tissues of Heigai pigs via upregulating the expression of the lipolytic gene (hormone-sensitive lipase, HSL) in vivo and in vitro. CLAs also altered the biochemical immune indexes including reduced content of total cholesterol (TChol), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) and changed lipids profiles including decreased sphingolipids especially ceramides (Cers) and sphingomyelins (SMs) in serum of Heigai pigs. Mechanically, CLAs may decrease peroxisome proliferator-activated receptorγ (PPARγ) expression and further inhibit adipogenic differentiation in adipose tissues of pigs by suppressing the function of Cers in serum. Furthermore, Pearson's correlation analysis showed HSL expression was positively related to short-chain fatty acids (SCFAs) in the gut (P ≤ 0.05) but the abundance of Cers was negatively related to the production and functions of SCFAs (P ≤ 0.05). CLAs altered the distribution of the lipid in serum and inhibited adipogenic differentiation by suppressing the function of Cers and further decreasing PPARγ expression in adipose tissues of Heigai pigs. Besides, the HSL expression and the abundance of Cers are associated with the production and functions of SCFAs in the gut.

Meat quality is affected by fat deposition and conjugated linoleic acids (CLAs) have served as a nutritional strategy to reduce fat deposition in adipose tissues of pigs. We explored the effects of CLAs on lipid profiles in serum and how these lipid molecules regulate fat deposition based on a Heigai pig model. We found CLAs reduced fat deposition in vivo and in vitro and changed lipids profiles in serum including decreased sphingolipids especially cermides (Cers) and sphingomyelins in the serum of Heigai pigs. We also demonstrated CLAs inhibited adipogenic differentiation by suppressing the function of Cers and further decreasing peroxisome proliferator-activated receptorγ expression in adipose tissues. Furthermore, Pearson's correlation analysis showed hormone-sensitive lipase expression and the abundance of Cers are related to the production and functions of short-chain fatty acids in the gut. Our findings provide useful insights into the role of CLAs in regulating lipid composition in serum and lipid metabolism in adipose tissue and provide a new insight into producing high-quality pork in the pig industry by using nutritional strategies.

Green Nanopesticide: pH-Responsive Eco-Friendly Pillar[5]arene-Modified Selenium Nanoparticles for Smart Delivery of Carbendazim to Suppress Sclerotinia Diseases.

Controlled-release delivery systems have been widely used to improve the efficacy and bioavailability of pesticides and minimize environmental risks. Herein, a fungicide carbendazim (CBZ)-loaded, a kind of nanovalve including trimethylammoniumpillar[5]arene (AP5), and methyl orange (MO)-functionalized mesoporous selenium (MSe) nanopesticides (CBZ@AP5/MSe⊃MO) were prepared. The nanovalve endowed CBZ@AP5/MSe⊃MO with a pH-responsive property, so the CBZ@AP5/MSe⊃MO can respond to the microenvironment of the pathogen Sclerotinia sclerotiorum (S. sclerotiorum). First, MO was shed due to protonation, and AP5-functionalized MSe gradually dissolved in an acid environment. Finally, CBZ was released rapidly. It is reported that AP5 and MO as the host and guest functionalized mesoporous selenium (MSe) have never been applied to agriculture. In vitro release experiments showed that the cumulative release rate of CBZ at pH 4.5 was 1.74 times higher than that in a neutral environment. In addition, we found that the contact angle of the CBZ@AP5/MSe⊃MO in maize and rape leaves was effectively decreased, which could retain more in the leaves after washout. It can also decrease the dry biomass and the reducing sugar of S.sclerotiorum. The CBZ@AP5/MSe⊃MO holds a good safety profile for plants, animal cells, and the environment owing to the targeted release properties. These results suggest that CBZ@AP5/MSe⊃MO is an environmentally friendly and effective drug-loaded system against S. sclerotiorum. It provides a new strategy for the design and development of nanopesticides and the control of S. sclerotiorum.

Prognostic nutritional index value in the prognosis of Kawasaki disease with coronary artery lesions.

Objectives: The prognostic nutritional index (PNI) is a purported predictor of intravenous immunoglobulin (IVIG) resistance and coronary artery aneurysm (CAA) development in patients with Kawasaki disease (KD). However, limited data exist on CAA regression. This study aimed to confirm whether the PNI is a predictor for CAA persistency in patients with KD. Methods: This retrospective study grouped 341 patients with KD based on the coronary artery status and time of aneurysm persistence. The clinical and laboratory parameters were compared, and multivariate logistic regression analysis was performed to identify the independent risk factors for persistent CAA. The receiver operating characteristic (ROC) curve was further used to assess the predictive values of the PNI in persistent CAA. Results: Among the study patients, 80 (23.5%) presented with CAA, including CAA persisting for 2 years in 17 patients (5.0%). Patients with CAA were more frequently treated with corticosteroids (p < 0.016). No statistically significant differences were found in the nutritional status and PNI among patients with or without coronary artery lesions, regardless of injury severity. Patients in the persistent CAA group presented with higher rates of overnutrition and showed lower PNI values and a higher incidence of thrombosis than those in the normal group (p < 0.05). The PNI and the maximum Z-score at 1 month of onset were significantly associated with CAA persisting for 2 years and may be used as predictors of persistent CAA. The area under the ROC curve was 0.708 (95% confidence interval, 0.569-0.847), and a 40.2 PNI cutoff yielded a sensitivity and specificity of 41 and 92%, respectively, for predicting CAA persisting for 2 years. Kaplan-Meier survival analysis revealed that the estimated median time of aneurysm persistence was significantly higher in patients with PNI values of ≤40 than in those with PNI values of >40 (hazard ratio, 2.958; 95% confidence interval, 1.601-5.464; p = 0.007). After sampling-time stratification, the PNI differed significantly between patients with and without persistent CAA when sampled on the second (p = 0.040), third (p = 0.028), and fourth days (p = 0.041) following disease onset. Conclusion: A lower PNI value is an independent risk factor for CAA persisting for 2 years in patients with KD, besides the maximum Z-score at 1 month after onset. Furthermore, the PNI obtained within 4 days from fever onset may possess greater predictive power for patients with persistent CAA.