Methionine-choline deficient diet deteriorates DSS-induced murine colitis through disturbance of gut microbes and infiltration of macrophages.

Ulcerative colitis (UC) is associated with changed dietary habits and mainly linked with the gut microbiota dysbiosis, necroptosis of epithelial cells, and mucosal ulcerations. Liver dysfunction and abnormal level of liver metabolism indices were identified in UC patients, suggesting a close interaction between gut and liver disorders. Methionine-choline deficient diet (MCD) has been shown to induce persistent alterations of gut microbiota and metabolome during hepatitis. In this study we further explored the disease phenotypes in UC patients and investigated whether MCD functioned as a trigger for UC susceptibility. After assessing 88 serum specimens from UC patients, we found significant liver dysfunction and dyslipidemia including abnormal ALT, AST, TG, TC, LDL-c and HDL-c. Liver dysfunction and dyslipidemia were confirmed in DSS-induced colitis mice. We fed mice with MCD for 14 days to cause mild liver damage, and then treated with DSS for 7 days. We found that MCD intake significantly exacerbated the pathogenesis of mucosal inflammation in DSS-induced acute, progressive, and chronic colitis, referring to promotion of mucosal ulcers, colon shortening, diarrhea, inflammatory immune cell infiltration, cytokines release, and abnormal activation of inflammatory macrophages in colon and liver specimens. Intraperitoneal injection of clodronate liposomes to globally delete macrophages dramatically compromised the pathogenesis of MCD-triggering colitis. In addition, MCD intake markedly changed the production pattern of short-chain fatty acids (SCFAs) in murine stools, colons, and livers. We demonstrated that MCD-induced colitis pathogenesis largely depended on the gut microbes and the disease phenotypes could be transmissible through fecal microbiota transplantation (FMT). In conclusion, this study supports the concept that intake of MCD predisposes to experimental colitis and enhances its pathogenesis via modulating gut microbes and macrophages in mice.

LTF as a Potential Prognostic and Immunological Biomarker in Glioblastoma.

The lactoferrin (LTF) gene behaves like a tumor suppressor gene in diverse tumors, such as renal cancer, nasopharyngeal carcinoma and gastric cancer. However, the prognostic value of LTF expression in patients with glioblastoma remains unclear. In this study, the expression levels of LTF in patients with GBM were investigated in TCGA, GEPIA, CGGA and GEO database, and a survival analysis of LTF based on TCGA and CGGA was performed. Furthermore, the present study demonstrated the LTF gene co-expression, PPI network, KEGG/GO enrichment and immune cell infiltration analysis on TCGA and TIMER2.0 database. We found that LTF expression was significantly upregulated in GBM samples compared with normal samples and other glioma samples, and Kaplan-Meier analysis demonstrated that the overexpression of LTF were significantly associated with worse overall survival (OS) and 5-year OS in GBM patients (P < 0.05). KEGG/GO enrichment analysis demonstrated that functions of LTF concentrated in immune and inflammatory response and peptidase regulation (P < 0.05). Immune cell infiltration analysis presented that high LTF expression exhibited dysregulated immune infiltration (i.e., CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells and cancer associated fibroblast). LTF was upregulated in tumors and correlated with worse OS in GBM patients, and LTF might function as an oncogene via inducing dysregulated immune infiltration in GBM.

N-Carbamylglutamate in ovo feeding improves carcass yield, muscle fiber development, and meat quality in broiler chickens.

BACKGROUND: Insufficient endogenous nutrients in the broiler embryo can lead to muscle gluconeogenesis, which ultimately affects the post-hatching performance of chicks. This study investigated the effects of in ovo feeding (IOF) of N-carbamylglutamate (NCG) on the growth hormones, carcass yield, and meat quality in broilers. Fertile eggs from a 30-week-old Ross 308 breeder flock were divided into three treatment groups: NC (non-injection), SC (100 µL saline-injection), and NCG (2 mg NCG injection). Each group had six replicates, with 70 eggs per replicate during incubation. Injections were administered on the 17.5th day of embryonic development. After hatching, 270 chicks were selected for 42-day rearing for further sampling. RESULTS: Chicks in the NCG group had significantly higher body weight (BW) and average daily gain (ADG) at the growing phase, increased growth and testosterone hormone in both feeding phases (21 and 42 days), and improved average daily gain (ADG) and food conversion ratio (FCR) in both grower and entire feeding phases (P < 0.05). Triiodothyronine (T3) and tetraiodothyronine (T4) levels, carcass yield, dressing, drum weight, breast muscle weight, drumstick weights, thighs, pectoralis major, and their part percentage of carcass were improved in the NCG group (P < 0.05), these effects were varied along feeding phases. Moreover, IOF of the NCG also improved pectoralis breast muscle color values at 24 h post mortem (P < 0.05). CONCLUSION: These results suggest that NCG injection at the late embryonic age of broiler enhances growth performance and meat quality throughout the lifespan and this can probably be attributed to an increase in thyroid and testosterone hormones, indicating potential involvement in metabolic and nutrient partitioning pathway regulation. © 2024 Society of Chemical Industry.

Design and Validation of a Novel Evaluation Scale to Predict Inpatient Large Vessel Occlusion Strokes: Clinical Assessment Stroke Severity for Inpatient Scale.

OBJECTIVES: A large quantity of ischemic stroke events occur in patients hospitalized for non-stroke-related reason. No scale has been developed to identify the large vessel occlusion (LVO) among inpatient stroke alerts. We aimed to develop a novel evaluation scale to predict LVO from in-hospital stroke alerts. METHODS: Data from consecutive in-hospital stroke alerts were analyzed at a single high volume stroke center between January 2016 and October 2020. We developed a predictive scale based on the first half of patients (training group) using multivariate logistic regression and evaluated it in the remaining half of patients (validation group) adopting receiver operating curve. Receiver operating characteristics of the scale were analyzed to evaluate its value for the detection of LVO. RESULTS: A total of 243 patients were enrolled for further study, among them, 94 (38.7%) had confirmed LVO. Three risk factors independently predicted the presence of LVO: recent cardiac or pulmonary procedure (1 point), neurological deficit scale (≥1: 2 points), and history of atrial fibrillation (1 point). The CAPS scale was generated based on predictive factors and demonstrated highly effective discrimination in identifying the presence of LVO in the training group (area under curve = 0.956) and the validation group (area under curve = 0.940). When the score ≥2, CAPS scale showed 97.9% sensitivity, 79.2% specificity, 74.8% positive predictive value, and 98.3% negative predictive value for discriminating LVO. CONCLUSIONS: CAPS scale was developed for identifying LVO among inpatient stroke alerts with high sensitivity and specificity, which may help to quickly prompt responses by appropriate stroke teams.

Immediate postinterventional flat-panel CT: Differentiation of hemorrhagic transformation from contrast exudation of acute ischemic stroke patients after thrombectomy.

BACKGROUND: Flat-panel computed tomography (CT) is an available imaging modality immediately after endovascular thrombectomy without transferring patients to the CT room. PURPOSE: To determine the accuracy of flat-panel CT scans in differentiating hemorrhagic transformation (HT) from contrast exudation after thrombectomy in patients with acute ischemic stroke (AIS). MATERIAL AND METHODS: From January 2019 to December 2021, consecutive patients with AIS who received an immediate flat-panel CT scan and follow-up neuroimaging after thrombectomy were enrolled in our study. The receiver operating characteristic curve was adopted to assess the discriminating accuracy of characteristics of flat-panel CT for HT. RESULTS: A total of 108 patients were enrolled in the study; 58 (53.7%) patients presented with hyperdense lesions on flat-panel CT. Patients with hyperdense lesions experienced a higher proportion of HT than patients without (58.7% vs. 10.0%; P < 0.001). Among all patients with hyperdensity on flat-panel CT, patients who experienced HT had higher average Hounsfield units (HUavg) (125 vs. 93; P = 0.001) and a higher proportion of mass effect (67.6 vs. 12.5; P < 0.001). The flat-panel CT differentiating HT from contrast exudation yielded a sensitivity of 87.2% and a negative predictive value of 90.0%. The area under the curve of HUavg, mass effect, and combination for differentiation of HT were 0.74, 0.78, and 0.83, respectively. CONCLUSION: The hyperdensity on immediately post-thrombectomy flat-panel CT could differentiate HT from contrast exudation with an excellent negative predictive value. The ability of flat-panel CT in differentiating HT from contrast exudation was improved when combined with HUavg and mass effect.

Early plasma D-dimer as a predictor of acute intracranial atherosclerosis-related large vessel occlusion in acute ischemic stroke.

BACKGROUND: Intracranial atherosclerosis-related large vessel occlusion (ICAS+LVO) poses an important technical challenge for endovascular thrombectomy (EVT). PURPOSE: To evaluate the value of D-dimer in predicting ICAS+LVO alone and in combination with other clinical and imaging predictors. MATERIAL AND METHODS: Consecutive patients who underwent EVT at our center between January 2018 and June 2021 were retrospectively reviewed. Patients were classified to the ICAS+LVO or ICAS-LVO group according to angiographic findings. Collateral gradings were evaluated based on computed tomography angiography and categorized as follows: score 0-1 unfavorable collaterals and score 2-3 favorable collaterals. Receiver operating characteristic curve was analyzed to evaluate the predictive value of D-dimer and the combination of other predictors for ICAS+LVO. RESULTS: A total of 374 patients were enrolled, among them, 107 (28.6%) had an ICAS+LVO, while ICAS-LVO was determined in 267 (71.4%) patients. Median D-dimer levels were lower (0.36 vs. 1.18 mg/L; P < 0.001) while the proportion of favorable collaterals was higher (85.0% vs. 22.5%; P < 0.001) in the ICAS+LVO group than the ICAS-LVO group. After multivariable analysis, D-dimer (adjusted odds ratio [OR]=0.32, 95% confidence interval [CI]=0.21-0.50; P < 0.001) and collaterals (adjusted OR=16.25, 95% CI=7.58-34.84; P < 0.001) remained independent predictors of ICAS+LVO. The area under the curve of D-dimer, collaterals, and combination for identification of ICAS+LVO was 0.82, 0.85, and 0.92, respectively. CONCLUSION: Low early plasma D-dimer levels are a significant and independent predictor of ICAS+LVO, and predictive value strengthens when in a combined model using D-dimer and collateral grading.

Perturbing BEAMs: EEG adversarial attack to deep learning models for epilepsy diagnosing.

Deep learning models have been widely used in electroencephalogram (EEG) analysis and obtained excellent performance. But the adversarial attack and defense for them should be thoroughly studied before putting them into safety-sensitive use. This work exposes an important safety issue in deep-learning-based brain disease diagnostic systems by examining the vulnerability of deep learning models for diagnosing epilepsy with brain electrical activity mappings (BEAMs) to white-box attacks. It proposes two methods, Gradient Perturbations of BEAMs (GPBEAM), and Gradient Perturbations of BEAMs with Differential Evolution (GPBEAM-DE), which generate EEG adversarial samples, for the first time by perturbing BEAMs densely and sparsely respectively, and find that these BEAMs-based adversarial samples can easily mislead deep learning models. The experiments use the EEG data from CHB-MIT dataset and two types of victim models each of which has four different deep neural network (DNN) architectures. It is shown that: (1) these BEAM-based adversarial samples produced by the proposed methods in this paper are aggressive to BEAM-related victim models which use BEAMs as the input to internal DNN architectures, but unaggressive to EEG-related victim models which have raw EEG as the input to internal DNN architectures, with the top success rate of attacking BEAM-related models up to 0.8 while the top success rate of attacking EEG-related models only 0.01; (2) GPBEAM-DE outperforms GPBEAM when they are attacking the same victim model under a same distortion constraint, with the top attack success rate 0.8 for the former and 0.59 for the latter; (3) a simple modification to the GPBEAM/GPBEAM-DE will make it have aggressiveness to both BEAMs-related and EEG-related models (with top attack success rate 0.8 and 0.64), and this capacity enhancement is done without any cost of distortion increment. The goal of this study is not to attack any of EEG medical diagnostic systems, but to raise concerns about the safety of deep learning models and hope to lead to a safer design.

Radiomics features on computed tomography reflect thrombus histological age prior to endovascular treatment of acute ischemic stroke.

PURPOSE: To investigate the role of radiomics features in thrombus age identification and establish a CT-based radiomics model for predicting thrombus age of large vessel occlusion stroke patients. METHODS: We retrospectively reviewed patients with middle cerebral artery occlusion receiving mechanical thrombectomy from July 2020 to March 2022 at our center. The retrieved clots were stained with Hematoxylin and Eosin (H&E) and determined as fresh or older thrombi based on coagulation age. Clot-derived radiomics features were selected by least absolute shrinkage and selection operator (LASSO) regression analysis, by which selected radiomics features were integrated into the Rad-score via the corresponding coefficients. The prediction performance of Rad-score in thrombus age was evaluated with the area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 104 patients were included in our analysis, with 52 in training and 52 in validation cohort. Older thrombi were characterized with delayed procedure time, worse functional outcome and marginally associated with more attempts of device. We extracted 982 features from NCCT images. Following T test and LASSO analysis in training cohort, six radiomics features were selected, based on which the Rad-score was generated by the linear combination of features. The Rad-score showed satisfactory performance in distinguishing fresh with older thrombi, with the AUC of 0.873 (95 %CI: 0.777-0.956) and 0.773 (95 %CI: 0.636-0.910) in training and validation cohort, respectively. CONCLUSION: This study established and validated a CT-based radiomics model that could accurately differentiate fresh with older thrombi for stroke patients receiving mechanical thrombectomy.

A propensity score matching investigation of short-term results of single-incision laparoscopic low anterior rectal resection via ileostomy site.

Aims: The study was performed to verify the results of single-incision laparoscopic surgery (SILS) through the ileostomy site for low rectal cancer compared with conventional laparoscopic surgery (CLS). Materials and Methods: From January 2019 to November 2021, 133 patients with low rectal cancer underwent single-incision (n = 27) or conventional (n = 106) methods of low anterior rectal resection surgery with ileostomy. All patients were balanced by propensity score matching for basic information in a ratio of 1:2, resulting in 27 and 54 in SILS and CLS groups, respectively. Results: Relative to the CLS group, the SILS group exhibited fewer leucocyte changes, shorter time to first exhaust and first bowel sounds, shorter length of hospital stay and lower Visual Analogue Score on post-operative days (POD2) and POD3. Intraoperative or post-operative complications or readmissions were comparable between the two groups. The oncologic results remained consistent between the two groups other than the number of lymph nodes dissected in group no. 253. Conclusions: Single-incision laparoscopic low rectal resection surgery through the ileostomy site has advantages in terms of reduced post-operative pain, shorter post-operative exhaust time and length of hospital stay while also achieving oncologic outcomes similar to those of conventional laparoscopy. It can be an alternative procedure for patients with low rectal cancer who require ileostomy.

Dispersionless Coupling among Optical Waveguides by Artificial Gauge Field.

Coupling among closely packed waveguides is a common optical phenomenon, and plays an important role in optical routing and integration. Unfortunately, this coupling property is usually sensitive to the working wavelength and structure features that hinder the broadband and robust functions. Here, we report a new strategy utilizing an artificial gauge field (AGF) to engineer the coupling dispersion and realize a dispersionless coupling among waveguides with periodically bending modulation. The AGF-induced dispersionless coupling is experimentally verified in a silicon waveguide platform, which already has well-established broadband and robust routing functions (directional coupling and splitting), suggesting potential applications in integrated photonics. As examples, we further demonstrate a three-level-cascaded AGF waveguide network to route broadband light to desired ports with an overwhelming advantage over the conventional ones in comparison. Our method provides a new route of coupling dispersion control by AGF and benefits applications that fundamentally rely on waveguide coupling.

Inhibition of PDE4 by apremilast attenuates skin fibrosis through directly suppressing activation of M1 and T cells.

Systemic sclerosis (SSc) is a life-threatening chronic connective tissue disease with the characteristics of skin fibrosis, vascular injury, and inflammatory infiltrations. Though inhibition of phosphodiesterase 4 (PDE4) has been turned out to be an effective strategy in suppressing inflammation through promoting the accumulation of intracellular cyclic adenosine monophosphate (cAMP), little is known about the functional modes of inhibiting PDE4 by apremilast on the process of SSc. The present research aimed to investigate the therapeutic effects and underlying mechanism of apremilast on SSc. Herein, we found that apremilast could markedly ameliorate the pathological manifestations of SSc, including skin dermal thickness, deposition of collagens, and increased expression of α-SMA. Further study demonstrated that apremilast suppressed the recruitment and activation of macrophages and T cells, along with the secretion of inflammatory cytokines, which accounted for the effects of apremilast on modulating the pro-fibrotic processes. Interestingly, apremilast could dose-dependently inhibit the activation of M1 and T cells in vitro through promoting the phosphorylation of CREB. In summary, our research suggested that inhibiting PDE4 by apremilast might provide a novel therapeutic option for clinical treatment of SSc patients.

STING inhibitor ameliorates LPS-induced ALI by preventing vascular endothelial cells-mediated immune cells chemotaxis and adhesion.

Acute lung injury (ALI) is a common and devastating clinical disorder featured by excessive inflammatory responses. Stimulator of interferon genes (STING) is an indispensable molecule for regulating inflammation and immune response in multiple diseases, but the role of STING in the ALI pathogenesis is not well elucidated. In this study, we explored the molecular mechanisms of STING in regulating lipopolysaccharide (LPS)-induced lung injury. Mice were pretreated with a STING inhibitor C-176 (15, 30 mg/kg, i.p.) before LPS inhalation to induce ALI. We showed that LPS inhalation significantly increased STING expression in the lung tissues, whereas C-176 pretreatment dose-dependently suppressed the expression of STING, decreased the production of inflammatory cytokines including TNF-α, IL-6, IL-12, and IL-1ß, and restrained the expression of chemokines and adhesion molecule vascular cell adhesion protein-1 (VCAM-1) in the lung tissues. Consistently, in vitro experiments conducted in TNF-α-stimulated HMEC-1cells (common and classic vascular endothelial cells) revealed that human STING inhibitor H-151 or STING siRNA downregulated the expression levels of adhesion molecule and chemokines in HMEC-1cells, accompanied by decreased adhesive ability and chemotaxis of immunocytes upon TNF-α stimulation. We further revealed that STING inhibitor H-151 or STING knockdown significantly decreased the phosphorylation of transcription factor STAT1, which subsequently influenced its binding to chemokine CCL2 and adhesive molecule VCAM-1 gene promoter. Collectively, STING inhibitor can alleviate LPS-induced ALI in mice by preventing vascular endothelial cells-mediated immune cell chemotaxis and adhesion, suggesting that STING may be a promising therapeutic target for the treatment of ALI.

Impact of Gabapentin on PACU Length of Stay and Perioperative Intravenous Opioid Use for ERAS Hysterectomy Patients.

We investigated the impact of preoperative gabapentin on perioperative intravenous opioid requirements and post anesthesia care unit length of stay (PACU LOS) for patients undergoing laparoscopic and vaginal hysterectomies within an Enhanced Recovery After Surgery (ERAS) pathway. A multidisciplinary team retrospectively examined 2,015 patients who underwent laparoscopic or vaginal hysterectomies between October 2016 and January 2020 at a single academic institution. The average PACU LOS was 168 min among patients who did not receive gabapentin vs. 180 min both among patients who received ≤ 300 mg of gabapentin and patients who received > 300 mg of gabapentin. After adjusting for demographics and medical comorbidities, PACU LOS for patients given ≤ 300 mg gabapentin was 6% longer (rate ratio (RR) = 1.06, 95% CI = 1.01-1.11) than for patients who were not given gabapentin, and for patients who received > 300 mg of gabapentin was 7% longer (RR = 1.07, 95%CI = 1.01-1.13) than for those who did not receive gabapentin. Patients who received ≤ 300 mg gabapentin received 9% less perioperative intravenous hydromorphone than patients who did not receive gabapentin (RR = 0.91, 95% CI = 0.86 - 0.97); patients who received > 300 mg of gabapentin received 12% less perioperative intravenous hydromorphone than patients who did not receive gabapentin (RR = 0.88, 95% CI = 0.82 - 0.95). These findings represent an absolute difference of 0.09 mg intravenous hydromorphone. There were no statistically significant differences in total intravenous fentanyl received. Preoperative gabapentin given as part of an ERAS pathway is associated with statistically but not clinically significant increases in PACU LOS and decreases in total perioperative intravenous opioid use.

Restoring mitochondrial function and normalizing ROS-JNK/MAPK pathway exert key roles in glutamine ameliorating bisphenol A-induced intestinal injury.

Bisphenol A (BPA) is toxic to the reproductive and nervous system, even carcinogenetic in humans and animals. However, few studies focused on effects of BPA on the intestinal tract. Here, we detected BPA-induced injuries on intestinal mucosa and explored a reliable approach to counteract BPA effects. C57BL/6J mice were gavage BPA or BPA accompanied with ingestion of 4% (w/w) of glutamine for 4-wks. In vitro, IEC-6 cells were treated with 0.4 mmol/L BPA for 6 hours mimicking acute injury and 0.2 mmol/L BPA for 12 hours followed with or without the inclusion of 4 mmol/L glutamine for 12 hours to determine cell renewal, mitochondrial function and ROS-JNK/MAPK pathway upon moderate BPA exposure. As results, BPA exposure caused severe intestinal injury, and disturbed intestinal epithelial cell proliferation and apoptosis, accompanied with mitochondrial malfunction and activated JNK/MAPK pathway as well. Notably, glutathione metabolism was implicated in BPA-induce injury. Glutamine could well rescue cell renewal and mitochondrial function from BPA exposure-induced injuries. In conclusion, we demonstrated impaired effect of BPA exposure on intestinal functions, which could be well counteracted by glutamine partly via restoring mitochondrial function and normalizing ROS-JNK/MAPK pathway. Thereby, we provided a novel application of glutamine to rescue intestinal injury.

Structural transformation and electrochemical properties of a nanosized flower-like R-MnO2 cathode in a sodium battery.

High-energy density and low-cost sodium-ion batteries are being sought to meet increasing energy demand. Here, R-MnO2 is chosen as a cathode material of sodium-ion batteries owing to its low cost and high energy density. The structural transformation from the tunnel R-MnO2 to the layered NaMnO2 and electrochemical properties during the charge/discharge are investigated at the atomic level by combining XRD and related electrochemical experiments. Na≤0.04MnO2 has a tunnel R-MnO2 phase structure, Na≥0.42MnO2 has a layered NaMnO2 phase structure, and Na0.04-0.42MnO2 is their mixed phase. Mn3+ 3d4[t2gß3dz2(1)3dx2-y2(0)] in NaMnO2 loses one 3dz2 electron and the redox couple Mn3+/Mn4+ delivers 206 mA h g-1 during the initial charge. The case that the Fermi energy level difference between R-MnO2 and NaMnO2 is lower than that between the layered Na(12-x)/12MnO2 and NaMnO2 makes the potential plateau of R-MnO2 turning into NaMnO2 lower than that of the layered Na(12-x)/12MnO2 to NaMnO2. This can be confirmed by our experiment from the 1st-2nd voltage capacity profile of R-MnO2 in EC/PC (ethylene carbonate/propylene carbonate) electrolyte. The study would give a new view of the production of sustainable sodium battery cathode materials.

Efficiency Improvements of Nonoperating Room Cardiac Anesthesia Services.

OBJECTIVE: Scheduling and staffing nonoperating room anesthesia (NORA) cases often require cross-service coordination and can result in significant delays in patient care, resource inefficiencies, and provider dissatisfaction. The objective of the present study was to reduce these delays and case cancellations for patients requiring cardiac anesthesia for their transesophageal echocardiography procedure. DESIGN: Preintervention and postintervention analysis of prospectively collected observational data. SETTING: Single institution, quaternary care hospital. PARTICIPANTS: Patients requiring cardiac anesthesia for transesophageal echocardiography. INTERVENTIONS: The study included the following three interventions: outpatient transesophageal echocardiography order screening, identifying the daily NORA cardiac anesthesia attending, and centralizing the scheduling process among all cardiac NORA locations. MEASUREMENTS AND MAIN RESULTS: Before the interventions, the average delay time for echocardiography laboratory cases was 34.9 minutes (n = 38, standard deviation 30.6). In the two months after the aforementioned interventions were performed, the average delay time was 20.2 minutes (n = 50, standard deviation 10.0), representing a decrease in the wait time of 42%. In the preintervention period, two cases had delays of 60 minutes or more; in the postintervention group, there were zero cases with delays of 60 minutes or more. During the postintervention period, zero cases were rescheduled or cancelled because of lack of availability or scheduling conflicts by the cardiac anesthesia team as opposed to three cases that were rescheduled or cancelled in the preintervention period. CONCLUSION: In the two months after implementing changes to the scheduling process for NORA cases in the echocardiography laboratory, a substantial reduction in average case delay, elimination of long delays lasting more than one hour, and avoidance of case cancellations were observed.

Effects of Pyrroloquinoline Quinone on Lipid Metabolism and Anti-Oxidative Capacity in a High-Fat-Diet Metabolic Dysfunction-Associated Fatty Liver Disease Chick Model.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and its interaction with many metabolic pathways raises global public health concerns. This study aimed to determine the therapeutic effects of Pyrroloquinoline quinone (PQQ, provided by PQQ.Na2) on MAFLD in a chick model and primary chicken hepatocytes with a focus on lipid metabolism, anti-oxidative capacity, and mitochondrial biogenesis. The MAFLD chick model was established on laying hens by feeding them a high-energy low-protein (HELP) diet. Primary hepatocytes isolated from the liver of laying hens were induced for steatosis by free fatty acids (FFA) and for oxidative stress by hydrogen peroxide (H2O2). In the MAFLD chick model, the dietary supplementation of PQQ conspicuously ameliorated the negative effects of the HELP diet on liver biological functions, suppressed the progression of MAFLD mainly through enhanced lipid metabolism and protection of liver from oxidative injury. In the steatosis and oxidative stress cell models, PQQ functions in the improvement of the lipid metabolism and hepatocytes tolerance to fatty degradation and oxidative damage by enhancing mitochondrial biogenesis and then increasing the anti-oxidative activity and anti-apoptosis capacity. At both the cellular and individual levels, PQQ was demonstrated to exert protective effects of hepatocyte and liver from fat accumulation through the improvement of mitochondrial biogenesis and maintenance of redox homeostasis. The key findings of the present study provide an in-depth knowledge on the ameliorative effects of PQQ on the progression of fatty liver and its mechanism of action, thus providing a theoretical basis for the application of PQQ, as an effective nutrient, into the prevention of MAFLD.

The transcription factor ZmNAC126 accelerates leaf senescence downstream of the ethylene signalling pathway in maize.

Leaf senescence is an integral part of plant development, during which, nutrients are remobilized from senescent leaves to fast-growing organs. The initiation and progression dynamics of leaf senescence is therefore vital not only to the maximal accumulation of assimilates but also to the efficient remobilization of nutrients. Senescence is a finely tuned process that involves the action of a large number of transcription factors (TFs). The NAC TFs play critical roles in regulating leaf senescence in Arabidopsis, wheat, rice and tomato. Here, we identified a NAC TF, ZmNAC126 that is responsive to leaf senescence in maize. Ectopic overexpression of ZmNAC126 in Arabidopsis and maize enhanced chlorophyll degradation and promoted leaf senescence. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that ZmNAC126 could directly bind to the promoters of major chlorophyll catabolic genes in maize. Dual-luciferase assay in maize protoplasts indicated that ZmNAC126 positively regulates these chlorophyll catabolic genes in maize. Moreover, ZmNAC126 could be induced by ethylene, and ZmEIN3, a major TF of ethylene signalling, could bind to its promoter to transactivate its expression. Taken together, ZmNAC126 may play a pivotal role in regulating natural and ethylene-triggered leaf senescence in maize.

Dynamic membrane proteome of adipogenic and myogenic precursors in skeletal muscle highlights EPHA2 may promote myogenic differentiation through ERK signaling.

The balance of myogenic and adipogenic differentiation is crucial for skeletal muscle homeostasis. Given the vital role of membrane proteins (MBPs) in cell signal perception, membrane proteomics was conducted to delineate mechanisms regulating differentiation of adipogenic and myogenic precursors in skeletal muscle. Adipogenic and myogenic precursors with divergent differentiation potential were isolated from the longissimus dorsi muscle of neonatal pigs by the preplate method. A total of 85 differentially expressed MBPs ( P < 0.05 and fold change ≥1.2 or ≤0.83) between 2 precursors were detected via isobaric tags for relative and absolute quantitation (iTRAQ) assay, including 67 up-regulated and 18 down-regulated in myogenic precursors. Functional enrichment analysis uncovered that myogenic and adipogenic precursors showed significant differences in cytoskeleton organization, syncytium formation, environmental information processing, and organismal systems. Furthermore, key MBPs in regulating cell differentiation were also characterized, including ITGB3, ITGAV, ITPR3, and EPHA2. Noteworthily, EPHA2 was required for myogenic differentiation, and it may promote myogenic differentiation through ERK signaling. Collectively, our study provided an insight into the distinct MBP profile between myogenic and adipogenic precursors in skeletal muscle and served as a solid basis for supporting the role of MBPs in regulating differentiation.-Zhang, X., Wang, L., Qiu, K., Xu, D., Yin, J. Dynamic membrane proteome of adipogenic and myogenic precursors in skeletal muscle highlights EPHA2 may promote myogenic differentiation through ERK signaling.

miR-98-5p promotes apoptosis and inhibits migration and cell growth in papillary thyroid carcinoma through Bax/Caspase-3 by HMGA2.

BACKGROUND: The aims of this study were to investigate the function and mechanism of miRNA-98-5p in papillary thyroid carcinoma. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of miRNA-98-5p in papillary thyroid carcinoma. Western blotting and caspase-3/9 activity levels, flow cytometric analysis, cell migration assays, DAPI assay, cell proliferation assay, and LDH activity levels were used in this study. RESULTS: In patient with papillary thyroid carcinoma, miRNA-98-5p was reduced, and HMGA2 was increased. Downregulation of miRNA-98-5p promoted the cell growth, inhibited apoptosis, and induced HMGA2 protein expression in papillary thyroid carcinoma cell via activation of HMGA2. Overexpression of miRNA-98-5p inhibited the cell growth, induced apoptosis, and suppressed HMGA2 protein expression in papillary thyroid carcinoma cell through the suppression of HMGA2. Si-HMGA2 inhibited the effects of anti-miRNA-98-5p on cell growth of papillary thyroid carcinoma. CONCLUSION: Therefore, these results suggested the regulation of HMGA2 suppresses proliferation of papillary thyroid carcinoma through miRNA-98-5p.