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Objective To explore the effect of moderate fatty liver on cardiac function in orthotopic autologous liver transplantation model rats. Methods Sixty SPF-grade healthy male SD rats were randomly divided into three groups (20 rats in each group). Group A was fed ordinary diet for 6 weeks and underwent laparotomy followed by separation of the blood vessels and ligaments around the liver and abdominal closure; group B was fed ordinary diet for 6 weeks and underwent orthotopic autologous liver transplantation; group C was fed high-fat diet for 6 weeks and underwent orthotopic autologous liver transplantation. The body mass, liver wet mass, liver index, and serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) after 6 weeks of feeding, as well as intraoperative blood pressure, pulse rate, respiratory rate, proportion of arrhythmia occurring in the new liver stage, and serum levels of lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), and high-sensitivity cardiac troponin (hs-cTn) at 0, 5, 10, and 60 min in the new liver stage were compared. Results The body mass, liver wet mass, liver index, and serum AST and ALT levels, as well as intraoperative systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and proportion of arrhythmia occurring in the new liver stage in group C were significantly higher than those in groups A and B (F=36.40-4 060.54,χ2 =10.91,P0.05). The serum levels of LDH, α-HBDH, CK, CK-MB, and hs-cTn at different time points in the new liver stage were significantly higher in group C than in groups A and B (F=14.11-1 057.08,P

Objective To evaluate the value of N-terminal pro brain natriuretic peptide (NT-proBNP) and hydroxybutyrate dehydrogenase (HBDH) in diagnosing secondary heart failure in elderly patients with sepsis. Methods A case control study was conducted, with 80 elderly patients with sepsis from January 2020 to December 2021 as the study subjects. Patients were divided into a heart failure group (36 cases) and a non heart failure group (44 cases) based on whether they had concurrent heart failure. The echocardiographic indicators, NT-proBNP, HBDH, and levels of inflammatory factors between the two groups were compared. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of echocardiographic indicators, NT-proBNP, and HBDH in sepsis with concurrent heart failure. Results The left ventricular ejection fractions (LVEF), stroke volume variation (SVV), cardiac output (CO), fraction shortening (FS), and mitral early diastolic inflow velocity/mitral late diastolic inflow velocity (E/A) values of the heart failure group were significantly lower than those of the non heart failure group, with statistically significant differences (P<0.05). The NT-proBNP, HBDH, interleukin (IL-6), tumor necrosis factor (TNF-a), procalcitonin (PCT) values, APACHE II scores, and Sofa scores of the heart failure group were significantly higher than those of the non-heart failure group, with statistically significant differences (P<0.05). There was no statistically significant difference in C-reactive protein (CRP) levels between the two groups (P>0.05). For the 36 patients with sepsis and concurrent heart function damage, the NT-proBNP values were negatively correlated with LVEF, SVV, CO, FS, and E/A (P<0.05); and HBDH values were negatively correlated with LVEF and FS (P<0.05). The sensitivities of NT-proBNP, HBDH, and NT-proBNP + HBDH in diagnosing sepsis with concurrent heart failure were 76. 17%, 48.52%, and 92.41%, respectively, and the specificities were 91. 90%, 89. 20%, and 84.58%, respectively. The area under the ROC curve (AUC) were 0.893, 0.757, and 0.944, respectively. Conclusion The diagnostic efficacy of NT-proBNP and HBDH alone for predicting heart failure in patients with sepsis is limited. The combined use of NT proBNP and HBDH has high clinical value in diagnosing sepsis with concurrent heart failure and is significantly correlated with cardiac function indicators. In clinical practice, NT-proBNP and HBDH results may be considered in conjunction with ultrasound diagnosis to determine whether patients with sepsis have concurrent heart failure. [ABSTRACT FROM AUTHOR]

Guhong injection (GHI) has been applied in the therapy of cardio-cerebrovascular disease in clinic, but there is no report about the pharmacokinetic/pharmacodynamic (PK/PD) research on GHI treating myocardial ischemia/reperfusion (MI/R) injury in rats. In this study, eight compounds of GHI in plasma, including N-acetyl-L-glutamine (NAG), chlorogenic acid (CGA), hydroxysafflor yellow A (HSYA), p-coumaric acid ( pCA), rutin, hyperoside, kaempferol-3-Orutinoside, and kaempferol-3-O-glucoside, were quantified by LC-MS/MS. We discovered that the values of t1/2b, k12, V2, and CL2 were larger than those of t1/2a, k21, V1, and CL1 for all compounds. The levels of four biomarkers, creatine kinase-MB (CK-MB), cardiac troponin I (cTn I), ischemia-modified albumin (IMA), and alpha-hydroxybutyrate dehydrogenase (a-HBDH) in plasma were determined by ELISA. The elevated level of these biomarkers induced by MI/R was declined to different degrees via administrating GHI and verapamil hydrochloride (positive control). The weighted regression coefficients of NAG, HSYA, CGA, and pCA in PLSR equations generated from The Unscrambler X software (version 11) were mostly minus, suggesting these four ingredients were positively correlated to the diminution of the level of four biomarkers. Emax and ED50, two parameters in PK/PD equations that were obtained by adopting Drug and Statistics software (version 3.2.6), were almost enlarged with the rise of GHI dosage. Obviously, all analytes were dominantly distributed and eliminated in the peripheral compartment with features of rapid distribution and slow elimination. With the enhancement of GHI dosage, the ingredients only filled in the central compartment if the peripheral compartment was replete. Meanwhile, high-dose of GHI generated the optimum intrinsic activity, but the af- finity of compounds with receptors was the worst, which may be caused by the saturation of receptors. Among the eight analytes, NAG, HSYA, CGA, and pCA exhibited superior cardioprotection, which probably served as the pharmacodynamic substance basis of GHI in treating MI/R injury. [ABSTRACT FROM AUTHOR]

Introduction: Available evidence indicates that ketone bodies may improve sleep quality. Therefore, we determined whether ketone ester (KE) intake could counteract sleep disruptions induced by strenuous exercise. Methods: Ten well-trained cyclists with good sleep quality participated in a randomized crossover design consisting of two experimental sessions each involving a morning endurance training and an evening high-intensity interval training ending 1 h before sleep, afterwhich polysomnography was performed overnight. Postexercise and 30 min before sleeping time, subjects received either 25 g of KE (EXKE) or a placebo drink (EXCON). A third session without exercise but with placebo supplements (RCON) was added to evaluate the effect of exercise per se on sleep. Results: Blood D-β-hydroxybutyrate concentrations transiently increased to ~3 mMpostexercise and during the first part of the night in EXKE but not in EXCON or RCON. Exercise significantly reduced rapid eye movement sleep by 26%(P = 0.001 vs RCON) and increased wakefulness after sleep onset by 95% (P = 0.004 vs RCON). Interestingly, KE improved sleep efficiency by 3% (P = 0.040 vs EXCON) and counteracted the exercise-induced decrease in rapid eye movement sleep (P = 0.011 vs EXCON) and the increase in wakefulness after sleep onset (P = 0.009 vs EXCON). This was accompanied by a KE-induced increase in dopamine excretion (P = 0.033 vs EXCON), which plays a pivotal role in sleep regulation. In addition, exercise increased sleep spindle density by 36% (P = 0.005 vs RCON), suggesting an effect on neural plasticity processes during sleep. Conclusions: These data indicate thatKE ingestion improves sleep efficiency and quality after high-intensity exercise. We provide preliminary evidence that this might result from KE-induced increases in dopamine signaling. [ABSTRACT FROM AUTHOR]

Introduction: Thalassemia is a healthcare challenging disease all over the world. It imparts a great burden on patients' families and healthcare institutions. Scientists focus on new aspects to overcome these challenges and increase patient tolerance of disease complications. This study aims to quantify ß-Hydroxybutyrate Dehydrogenase BHBDH activity in thalassemia patients compared to the control group and their correlation with the patient's demographic characteristics. Methods: To do so, serum was collected from patients and the control group and analyzed biochemically for targeted laboratory tests. We determined ß-Hydroxybutyrate Dehydrogenase from normal human serum using biochemical molecular techniques. Results: The results showed that BHBDH activity is significantly higher in the patients compared to the control group regardless of age, sex, or marital status. The results confirmed that enzyme activity and the purification folds were (0.0214 U/ml) and (51.7) respectively for the partially purified enzyme. Furthermore, the proportional molecular weight of the incompletely isolated ß-Hydroxybutyrate Dehydrogenase was (125.8±0.5 kDa) using gel filtration chromatography. The comparative molecular weight of the subunit of partially isolated ß-Hydroxybutyrate Dehydrogenase was (32.1±0.5 kDa) using SDS-PAGE. Conclusion: we demonstrate that BHBDH enzymatic activity is higher than control and this could be a prognostic or diagnostic tool in thalassemia patients. [ABSTRACT FROM AUTHOR]

Alterations in cardiac and renal biomarkers have been reported in coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis to investigate serum concentrations of hydroxybutyrate dehydrogenase (HBDH), a combined marker of myocardial and renal injury, in hospitalized COVID-19 patients with different disease severity and survival status. We searched PubMed, Web of Science and Scopus, between December 2019 and April 2021, for studies reporting HBDH in COVID-19. Risk of bias was assessed using the Newcastle–Ottawa scale, publication bias was assessed with the Begg's and Egger's tests, and certainty of evidence was assessed using GRADE. In 22 studies in 15,019 COVID-19 patients, serum HBDH concentrations on admission were significantly higher in patients with high disease severity or non-survivor status when compared to patients with low severity or survivor status (standardized mean difference, SMD = 0.90, 95% CI 0.74 to 1.07, p < 0.001; moderate certainty of evidence). Extreme between-study heterogeneity was observed (I2 = 93.5%, p < 0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and the direction of the effect size were not substantially modified. A significant publication bias was observed. In meta-regression, the SMD of HBDH concentrations was significantly associated with markers of inflammation, sepsis, liver damage, non-specific tissue damage, myocardial injury, and renal function. Higher HBDH concentrations were significantly associated with higher COVID-19 severity and mortality. This biomarker of cardiac and renal injury might be useful for risk stratification in COVID-19. (PROSPERO registration number: CRD42021258123). [ABSTRACT FROM AUTHOR]

Background: Severe burns can cause a hypermetabolic response and organ damage. Glutamine is a conditionally essential amino acid with various pharmacological effects. In this study, whether glutamine could alleviate the hypermetabolic response and maintain organ function after burn injury was analyzed.Methods: A multicenter, randomized, single-blind, parallel controlled trial was conducted to evaluate the efficacy of glutamine in decreasing hypermetabolism after burn injury. Physiological and biochemical indexes, such as vital signs, metabolic hormones, metabolic rate, and organ damage, were recorded on the 7th and 14th days after treatment.Results: In total, 55 adult burn patients with a total burn surface area (TBSA) of 30-70% were included in this study and randomly divided into the burn control (B, 28 patients) and burn+glutamine (B+G, 27 patients) groups. Except for the glutamine administration, the groups did not differ in the other treatments and nutrition supplements. The levels of diamine oxidase (DAO), lactulose/mannitol (L/M), β2-microglobulin, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBD) and cardiac troponin l (cTnl) in the B+G group were significantly lower than those in the B group (p < 0.05 or 0.01). The levels of resting energy expenditure (REE), serum catecholamines, glucagon, lactate and Homeostasis model assessment (HOMA) in the B+G group were significantly lower than those in the B group (p < 0.05 or 0.01). No significant difference was found in the length of hospitalization or the mortality rate between the two groups (p > 0.05).Conclusions: Glutamine moderately alleviates the hypermetabolic response and reduces organ damage after severe burns. Therefore, the early application of glutamine, which is effective and safe, should be used as an active intervention as early as possible. [ABSTRACT FROM AUTHOR]

The trace element iron affects immune responses and vaccination, but knowledge of its role in autoimmune diseases is limited. Expansion of pathogenic T cells, especially T follicular helper (Tfh) cells, has great significance to systemic lupus erythematosus (SLE) pathogenesis. Here, we show an important role of iron in regulation of pathogenic T cell differentiation in SLE. We found that iron overload promoted Tfh cell expansion, proinflammatory cytokine secretion, and autoantibody production in lupus-prone mice. Mice treated with a high-iron diet exhibited an increased proportion of Tfh cell and antigen-specific GC response. Iron supplementation contributed to Tfh cell differentiation. In contrast, iron chelation inhibited Tfh cell differentiation. We demonstrated that the miR-21/BDH2 axis drove iron accumulation during Tfh cell differentiation and further promoted Fe2+-dependent TET enzyme activity and BCL6 gene demethylation. Thus, maintaining iron homeostasis might be critical for eliminating pathogenic Th cells and might help improve the management of patients with SLE. [ABSTRACT FROM AUTHOR]

Shen Bai formula (SBF) is a proven effective traditional Chinese medicine for treating viral myocarditis (VMC) sequelae in clinic, and myocardial injury is the pathological basis of VMC sequelae. However, the pharmacological action and mechanism of SBF have not been systematically elucidated. In present research, the doxorubicin-induced myocardial injury rat model was used to evaluate the efficacy of SBF, and energy metabolism and metabolomics approaches were applied to elucidate the effects of SBF on myocardial injury. Through energy metabolism measurement system and UPLC-Q-TOF-MS/MS oriented blood metabolomics, directly reflected the therapeutic effect of SBF at a macro level, and identified biomarkers of myocardial injury in microcosmic, revealing its metabolomic mechanism. Results showed that SBF significantly improved the electrocardiogram (ECG), heart rate (HR), extent of myocardial tissue lesion, and ratio of heart and spleen. In addition, the serum levels of AST, CK, LDH, α-HBDH, cTnI, BNP, and MDA decreased, whereas SOD and ATP activity and content increased. Moreover, SBF increased locomotor activity and basic daily metabolism in rats with myocardial injury, restoring their usual level of energy metabolism. A total of 45 potential metabolomic biomarkers were identified. Among them, 44 biomarkers were significantly recalled by SBF, including representative biomarkers arachidonic acid (AA), 12-HETE, prostaglandin J 2 (PGJ 2), 15-deoxy-Δ-12,14-PGJ 2 , 15-keto-PGE 2 , 15(S)-HPETE, 15(S)-HETE, 8,11,14-eicosatrienoic acid and 9(S)-HODE, which involved AA metabolism, biosynthesis of unsaturated fatty acids and linoleic acid metabolism. We successfully replicated a myocardial injury rat model with the intraperitoneal injection of doxorubicin, and elucidated the mechanism of SBF in treating myocardial injury. This key mechanism may be achieved by targeting action on COX, Alox, CYP, and 15-PGDH to increase or decrease the level of myocardial injury biomarker, and then emphatically interven in AA metabolism, biosynthesis of unsaturated fatty acids and linoleic acid metabolism, and participate in regulating purine metabolism, sphingolipid metabolism, primary bile acid biosynthesis, and steroid hormone synthesis. [Display omitted] • Combine macro energy metabolism with micro serum metabolomics methods to systematically evaluate the efficacy of SBF. • Regulation of arachidonic acid and linoleic acid metabolism are the key pathways of SBF in treating myocardial injury. • COX, Alox, CYP, and 15-PGDH are the key enzymes in the treatment of myocardial injury with SBF. [ABSTRACT FROM AUTHOR]

Background. MicroRNAs (miRNAs) play an important role in the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH). However, the potential correlation between miRNA expression and the severity of CTEPH remains unclear. Our previous study indicated that miRNAs hsa-let-7b-3p, hsa-miR-17-5p, hsa-miR-106b-5p, hsa-miR-3202, hsa-miR-665, and hsa-miR-93-5p are closely involved in CTEPH. This study assessed the associations between the expression levels of these miRNAs and clinical parameters in CTEPH patients. Methods. A total of eight CTEPH patients and eight healthy adults as a reference group were included, and clinical data including total protein (TP), albumin (Alb), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), uric acid (UA), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were collected. Right heart catheterization was conducted to obtain hemodynamic data including cardiac index (CI). The expression levels of let-7b-3p, miR-17-5p, miR-106b-5p, miR-3202, miR-665, and miR-93-5p were measured by quantitative real-time PCR (qPCR). Correlation analysis was applied to estimate the associations between miRNA expression levels and clinical parameters in CTEPH patients. Results. Serum TP and Alb levels were decreased, while LDH, HBDH, and UA levels were increased in CTEPH patients compared with the reference group (P < 0.05). miR-3202 and miR-665 were upregulated, whereas let-7b-3p, miR-17-5p, miR-106b-5p, and miR-93-5p were downregulated in CTEPH patients relative to the reference group (P < 0.05). miR-93-5p expression was positively correlated with NT-proBNP level and negatively correlated with CI (P < 0.05). Moreover, let-7b-3p tended to be positively correlated with mean pulmonary arterial pressure. Conclusions. miR-93-5p expression was associated with the severity of CTEPH and could act as a potential predictor of high-risk CTEPH. [ABSTRACT FROM AUTHOR]

Aims: Many studies have explored the clinical characteristics of patients with coronavirus disease (COVID‐19), especially patients with cardiovascular disease. However, associated mechanisms and markers remain to be further investigated. This study aimed to investigate the effect of α‐hydroxybutyrate dehydrogenase (α‐HBDH) levels on disease progression and prognosis of patients with COVID‐19. Methods and results: One thousand seven hundred and fifty‐one patients from the Leishenshan hospital in Wuhan were divided into elevated and normal groups by α‐HBDH level, and the clinical information between the two groups was compared retrospectively. The main outcome evaluation criteria included in‐hospital death and disease severity. Univariate and multivariate regression analyses, survival curves, logistic regression, and receiver operating characteristic curve models were performed to explore the relationship between elevated α‐HBDH and the two outcomes. Besides, curve fitting analyses were conducted to analyse the relationship between computed tomography score and survival. Among 1751 patients with confirmed COVID‐19, 15 patients (0.87%) died. The mean (SD) age of patients was 58 years in normal α‐HBDH group and 66 years in elevated α‐HBDH group (P < 0.001). The mortality during hospitalization was 0.26% (4 of 1559) for patients with normal α‐HBDH levels and 5.73% (11 of 192) for those with elevated α‐HBDH levels (P < 0.001). Multivariate Cox analysis confirmed an association between elevated α‐HBDH levels and higher risk of in‐hospital mortality [hazard ratio: 4.411, 95% confidence interval (95% CI), 1.127–17.260; P = 0.033]. Multivariate logistic regression for disease severity and α‐HBDH levels showed significant difference between both groups (odds ratio = 3.759; 95% CI, 1.895–7.455; P < 0.001). Kaplan–Meier curves also illustrated the survival difference between normal and elevated α‐HBDH patients (P < 0.001). Conclusions: Our study found that serum α‐HBDH is an independent risk factor for in‐hospital mortality and disease severity among COVID‐19 patients. α‐HBDH assessment may aid clinicians in identifying high‐risk individuals among COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1–3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods: The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects' clinical manifestations and laboratory tests were analyzed retrospectively. Results: Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3+, CD4+, CD8+, NK, and CD3-CD19+ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 μg/L, the sensitivity and specificity of D-Dimer was 88.90 and 90.20%, respectively. Conclusion: The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to determine the prognostic value of α-hydroxybutyrate dehydrogenase (α-HBDH) in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU)., Materials and Methods: We retrospectively enrolled the data of 544 UTUC patients at West China Hospital from May 2003 to June 2019. Cancer-specific survival (CSS) was the endpoint of interest. The optimal cutoff value of α-HBDH was identified by X-Tile program. After propensity score matching (PSM), we utilized Kaplan‒Meier curves to estimate survival and Cox proportional hazard model for risk assessment. A nomogram was built based on the results of multivariate analysis, and calibration curve, time-dependent receiver operating characteristic (ROC) curves and decision curve analysis were also performed to evaluate the predictive accuracy., Results: Overall, 394 and 150 patients were divided into the α-HBDH-low group and α-HBDH -high group at the cutoff value of 158 U/L, respectively. After PSM, the two groups were well matched for all confounding factors. High α-HBDH was associated with inferior CSS (P = 0.006), and preoperative α-HBDH was an independent predictor for CSS (HR: 1.36; 95% CI:1.08, 1.80), especially in localized UTUC patients (HR: 2.04; 95% CI:1.11, 3.74). Furthermore, the nomogram based on α-HBDH achieved great predictive ability for CSS with areas under the curves of 0.800 and 0.778 for 3-year and 5-year CSS, respectively., Conclusion: Serum α-HBDH was a novel and reliable biomarker for predicting survival outcomes in UTUC patients after RNU but should be further explored., (© 2024. The Author(s).)

Objective: The objective was to evaluate the feasibility and safety of computed tomography (CT)-guided percutaneous irreversible electroporation (IRE) in porcine kidneys.Materials and Methods: Under CT guidance, two monopole probes were used to precisely puncture through the renal parenchyma into the renal hilum in nine anesthetized adult Bama miniature pigs. After which, IRE ablation was performed. Biochemical and pathological examinations were carried out 2 h, 2, 7, and 14 days after the procedure.Results: All procedures were performed successfully without any serious complications such as bleeding, infection, or death. All pigs survived until the end of the study. Pathological examinations showed that cells in the ablation area were dead within 2 days after the procedure, whereas the vascular endothelium showed only slight damage. After 2 days, endothelialization ensued and regrowth of smooth muscle cells was observed after 14 days. Hemogram tests indicated a transient increase but gradually returned to baseline levels 14 days after the procedure.Conclusion: IRE was essentially safe, however further studies on tumor ablation using several different animal models are needed. [ABSTRACT FROM AUTHOR]

Background A novel coronavirus (COVID-19) has raised world concern since it emerged in Wuhan, China in December 2019. The infection may result in severe pneumonia with clusters of illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias. Methods Nineteen COVID-19 and 15 other patients with pneumonia (non-COVID-19) in areas outside of Hubei were involved in this study. Both COVID-19 and non-COVID-19 patients were confirmed to be infected using throat swabs and/or sputa with/without COVID-2019 by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the differences between COVID-19 and non-COVID-19. Results All patients had a history of exposure to confirmed cases of COVID-19 or travel to Hubei before illness. The median (IQR) duration was 8 (6–11) and 5 (4–11) days from exposure to onset in COVID-19 and non-COVID-19 cases, respectively. The clinical symptoms were similar between COVID-19 and non-COVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) COVID-19 but 4 (26.67%) non-COVID-19 patients had bilateral involvement while 17 COVID-19 patients (89.47%) but 1 non-COVID-19 patient (6.67%) had multiple mottling and ground-glass opacity on chest CT images. Compared with non-COVID-19, COVID-19 presents remarkably more abnormal laboratory tests, including AST, ALT, γ-GT, LDH, and α-HBDH. Conclusions The COVID-19 infection has onsets similar to other pneumonias. CT scan may be a reliable test for screening COVID-19 cases. Liver function damage is more frequent in COVID-19 than non-COVID-19 patients. LDH and α-HBDH may be considerable markers for evaluation of COVID-19. [ABSTRACT FROM AUTHOR]

The ketone body D-β-hydroxybutyrate (DBHB) has gained attention owing to its cellular signalling function; however, its effect on the human colonic microbiota remains unclear. Here, DBHB dynamics in the human colon were investigated using an in vitro colonic microbiota model, which maintained most of the operational taxonomic units detected in the original faeces. Over 54% of 0.41% (w/v) DBHB was metabolised by microbiota models originating from seven faecal samples after 30 h of fermentation (regarded as DBHB utilisers); however, <19% of DBHB was metabolised by microbiota models from five faecal samples (regarded as non-utilisers of DBHB). In utilisers, DBHB administration increased the relative abundance of the genus Coprococcus, correlated with increased butyrogenesis. Increased butyrogenesis was not observed in DBHB non-utilisers. Based on PICRUSt analysis, the relative abundance of β-hydroxybutyrate dehydrogenase was maintained in microbiota models from DBHB utilisers following DBHB administration; however, it decreased in microbiota models from non-utilisers. After 21 h of fermentation, the intracellular glutamate concentration, which is indicative of growth, showed a positive correlation with DBHB utilisation (R2 = 0.70). Human colonic microbiotas with high growth activity demonstrate efficient utilisation of DBHB for increased butyrate production, which affords health benefits. [ABSTRACT FROM AUTHOR]

AIMS: To compare the effect of two partial mixed ration diets containing either sulfate or chloride-based anionic salts, fed to grazing prepartum dairy cows, on concentrations of Ca, Mg, P and beta-hydroxybutyrate (BHB) in plasma, disease incidence and milk yield during the early postpartum period. METHODS: The study was conducted on a seasonal-calving grazing dairy farm located in Benton (MO, USA). In August 2016, two groups of 200 cows were randomly assigned at 30 days before expected parturition to receive either a sulfate or chloride-based anionic diet, to achieve a dietary cation-anion difference (DCAD) of −25 mEq/kg DM. Cows were fed partial mixed rations to provide 50% of their DM intake, with 50% provided by grazing fescue pasture. Urine samples were collected from 20 cows from each group once a week for 5 weeks until calving for pH assessment. At parturition, 42 cows per group were selected at random and blood samples collected on Days 1, 2, 3 and 7 postpartum. The study continued until 100 cows per group calved. Health events and cumulative milk yield until 30 days postpartum were recorded. Concentrations of Ca, P, and Mg in plasma at Days 1, 2, 3, and 7, and BHB in plasma at Day 7 postpartum were assessed. RESULTS: Mean urine pH was lower in cows in the chloride than sulfate group (p≤0.06) on four of five sampling occasions. Mean concentrations of Ca in plasma on Day 1 were 2.00 (95% CI=1.94-2.05) and 1.91 (95% CI=1.88-1.97) mmol/L for the chloride and sulfate groups, respectively (p=0.15), and on Day 3 were 2.03 (95% CI=1.97-2.08) and 1.90 (95% CI=1.84-1.96) mmol/L, respectively (p=0.038). Concentrations of Mg, P and BHB in plasma and incidence of diseases postpartum were similar in both groups (p>0.05). There were no cases of clinical hypocalcaemia in either group. CONCLUSIONS AND CLINICAL RELEVANCE: Prepartum cows fed a partial mixed ration with a negative DCAD containing chloride-based anionic salts and free access to a fescue pasture had lower prepartum urine pH, and higher concentrations of total Ca in plasma during the first week postpartum, than cows receiving a partial mixed ration containing sulfate-based anionic salts. [ABSTRACT FROM AUTHOR]

(S)‐3‐Hydroxybutyryl‐CoA dehydrogenase (HBD) has been gaining increased attention recently as it is a key enzyme in the enantiomeric formation of (S)‐3‐hydroxybutyryl‐CoA [(S)‐3HB‐CoA]. It converts acetoacetyl‐CoA to (S)‐3HB‐CoA in the synthetic metabolic pathway. (S)‐3HB‐CoA is further modified to form (S)‐3‐hydroxybutyrate, which is a source of biodegradable polymers. During the course of a study to develop biodegradable polymers, attempts were made to determine the crystal structure of HBD from Clostridium acetobutylicum (CacHBD), and the crystal structures of both apo and NAD+‐bound forms of CacHBD were determined. The crystals belonged to different space groups: P212121 and P21. However, both structures adopted a hexamer composed of three dimers in the asymmetric unit, and this oligomerization was additionally confirmed by gel‐filtration column chromatography. Furthermore, to investigate the catalytic residues of CacHBD, the enzymatic activities of the wild type and of three single‐amino‐acid mutants were analyzed, in which the Ser, His and Asn residues that are conserved in the HBDs from C. acetobutylicum, C. butyricum and Ralstonia eutropha, as well as in the l‐3‐hydroxyacyl‐CoA dehydrogenases from Homo sapiens and Escherichia coli, were substituted by alanines. The S117A and N188A mutants abolished the activity, while the H138A mutant showed a slightly lower Km value and a significantly lower kcat value than the wild type. Therefore, in combination with the crystal structures, it was shown that His138 is involved in catalysis and that Ser117 and Asn188 may be important for substrate recognition to place the keto group of the substrate in the correct position for reaction. Crystal structures of (S)‐3‐hydroxybutyryl‐CoA dehydrogenase from Clostridium acetobutylicum have been determined in apo and NAD+‐bound forms. The structures, together with kinetic analyses using single‐amino‐acid substituted mutants, revealed the catalytically important residues in the enzyme. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the protective effect of citrulline (Cit) on the hearts of rats with sepsis. Methods. Wistar rats were divided into the normal, sham-operated, CLP, Cit, and CLP+Cit groups. Routine blood tests were performed, and the blood biochemical indexes were measured. Pathological changes in the cardiac tissues were observed. The levels of NO and iNOS in blood and SOD activity and MDA levels in the heart were measured. Results. Less inflammatory cell infiltration of the myocardial fibers and significantly decreased white blood cell count, absolute neutrophil count, neutrophil percentage, CK, HBDH, and NO (all P<0.05) were detected in the CLP+Cit group compared with the CLP group. In addition, SOD activity and MDA levels in heart tissues were, respectively, higher and lower in the CLP+Cit group than in the CLP group (both P<0.05). Conclusions. Cit reduces pathological damage in the heart and enhances the heart’s antioxidant capacity, thereby protecting cardiomyocytes. [ABSTRACT FROM AUTHOR]

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ABSTRACT: Poly(3hydroxybutyrate‐co‐4hydroxybutyrate) [P(3HB‐co‐4HB)]/graphite oxide (GO) composites were fabricated using a solution mixing method. The GO structures in the composites were analyzed by using transmission electron microscopy, Raman spectroscopy, and X‐ray diffraction. The fracture morphology of the samples was evaluated by the multifractal, and the effect of GO dispersion on the mechanical properties and the thermal stability were discussed for the P(3HB‐co‐4HB) and the composites. It was found that the interlayer spacing of the GO increased due to the intercalation of the polymer into the GO platelets. As the GO content increased, the relative multifractal spectrum increased, but the mechanical properties declined for the composites, indicating that the filler agglomeration effect overcame the reinforcement benefits for the high loadings of the GO. Moreover, both good dispersion and high content of the GO platelets increased the thermal stability of the composites. Therefore, the relative multifractal spectrum width of the fracture morphology was related to the mechanical properties and the thermal stability of the composites. [ABSTRACT FROM AUTHOR]

Assays for the rapid detection and accurate differentiation of Burkholderia pseudomallei from near-neighbor species are urgently needed in melioidosis endemic regions due to the high associated mortality and biowarfare importance of the pathogen. PCR-based methods have revolutionized this field due to the accuracy, sensitivity, and specificity that are achievable in a rapid way. In this study, a compound molecular detection system, consisting of a duplex PCR assay, was developed for the specific identification of Burkholderia pseudomallei and differentiation from other Burkholderia species. For accurate identification of B. pseudomallei , we deciphered and adopted a novel gene termed putative fimbrial chaperone ( fimC ). d -beta hydroxybutyrate dehydrogenase ( bdha ), reported previously by our group for sequence-based differentiation of B. pseudomallei from other Burkholderia species, was employed as a genus-specific target. Enforcement of an internal amplification control in the PCR format ruled out possible false negative results in the assay. Thus, the developed PCR assay was highly specific (100%) in its detection features, and a clear detection sensitivity of 10 pg/μl for purified gDNA and 3 × 10 3  CFU/ml for B. pseudomallei spiked urine was recorded. Successful identification of B. pseudomallei from an experimental mouse model at both the genus and species level revealed the accurate diagnostic efficiency of the duplex PCR method. [ABSTRACT FROM AUTHOR]

Poly(hydroxybutyrate-co-hydroxyvalerate) (PHB-co-HV) is a sustainable and biodegradable polymer, but as a potential packaging material, it suffers from a narrow processing window and embrittlement over time due to secondary crystallisation. This study aims to extend previous research by exploring the effect of the addition of poly(ethylene glycol) (PEG), in a range of molecular weights and compositions, on the rate of embrittlement. On blending, it was apparent that there was a reduction in both the melting point (of up to 7 °C) and the melt viscosity. Furthermore, there was a reduction in both the modulus and tensile strength indicating that PEG acts as an effective plasticiser in PHB-co-HV. In terms of the secondary crystallisation process, the addition of PEG could not prevent the process from occurring, only hinder it. PEG 600 in relatively high concentrations was found to be the most effective in this regard with a 53% reduction in the change in Young's modulus compared to pure PHB-co-HV. This observation, together with the melting point reduction which extends the processing window for PHB-co-HV, makes PEG a worthwhile additive to an otherwise fundamentally brittle polymer. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this paper is to describe the fabrication and characterization of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyexanoate] (PHBHHx) tissue engineering scaffolds with anatomical shape and customized porous structure.Design/methodology/approach Scaffolds with external shape and size modeled on a critical size segment of a rabbit’s radius model and an internal macrochanneled porous structure were designed and fabricated by means of a computer-aided wet-spinning (CAWS) technique. Morphological, thermal and mechanical characterization were carried out to assess the effect of the fabrication process on material properties and the potential of the PHBHHx scaffolds in comparison with anatomical star poly(e-caprolactone) (*PCL) scaffolds previously validated in vivo.Findings The CAWS technique is well suited for the layered manufacturing of anatomical PHBHHx scaffolds with a tailored porous architecture characterized by a longitudinal macrochannel. Morphological analysis showed that the scaffolds were composed by overlapping layers of microfibers with a spongy morphology, forming a 3D interconnected network of pores. Physical-chemical characterization indicated that the used technique did not affect the molecular structure of the processed polymer. Analysis of the compressive and tensile mechanical properties of the scaffolds highlighted the anisotropic behavior of the porous structure and the effect of the macrochannel in enhancing scaffold compressive stiffness. In comparison to the *PCL scaffolds, PHBHHx scaffolds showed higher compressive stiffness and tensile deformability.Originality/value This study shows the possibility of using renewable microbial polyester for the fabrication of scaffolds with anatomical shape and internal architecture tailored for in vivo bone regeneration studies. [ABSTRACT FROM AUTHOR]

The current commercial production of polyhydroxyalkanoates (PHA) is based on heterotrophic bacteria, using organic carbon sources from crops. To avoid the competition with food and feed production, cyanobacteria, metabolising PHA from carbon dioxide can be used. This research focuses on the investigation of the thermal and rheological properties of PHA polymers accumulated by Synechocystis salina , which had been cultivated in digestate supernatant and a mineral medium. The dried bacterial cells had a polymer content of 5.5-6.6%. The relevance of the derived PHA polymers for the common melt polymer processing was correlated with their molecular mass distribution as well as with their thermal and rheological properties. The determined thermal and rheological properties showed that PHA polymers accumulated by S. salina on digestate supernatant or mineral medium are comparable with the commercial available poly(3-hydroxybutyrate). However, the results showed that PHA polymers in general require modification before melt processing to increase their stability in the molten state. [ABSTRACT FROM AUTHOR]

Poly(3-hydroxybutyrate) (PHB) is a microbially synthesized polymer, which is often purified by alkaline treatment. The effect of microstructure on alkaline hydrolysis has been studied by varying concentration of base and the temperature. The morphologies of PHB films before and after degradation were evaluated using DSC and FTIR spectroscopy. The hydrolytic degradation study by weight loss measurement revealed that the crystallinity of PHB greatly decreased the hydrolytic ability of PHB. The crystallization of PHB and the effect of base on hydrolysis was investigated by time dependent FTIR spectroscopy. The normalized absorbance of 3010 cm −1 and 1183 cm −1 were used to characterize the crystalline and the amorphous phases of PHB. FTIR spectroscopy reveal that the extent of hydrolysis decreased with increasing crystallinity. The crotonic acid was detected as a major product after hydrolysis, confirmed by UV/Visible and proton NMR spectroscopy. The normalized absorbance of the crystalline band at 3010 cm −1 band remained constant, suggesting that there is no significant change in crystallinity with degradation. The normalized amorphous band at 1183 cm −1 showed a decrease in absorbance ratio, suggesting degradation of the amorphous phase. Our data suggests that alkaline hydrolysis depends on concentration of base and the crystallinity of PHB. [ABSTRACT FROM AUTHOR]

BACKGROUND An important line of research is the development of a new generation of formulations with targeted and controlled release of the pesticide, using matrices made from biodegradable materials. In this study, slow-release formulations of the fungicide tebuconazole ( TEB) have been prepared by embedding it into the matrix of poly-3-hydroxybutyrate ( P3HB) in the form of films, microgranules and pellets. RESULTS The average rates of P3HB degradation were determined by the geometry of the formulation, reaching, for 63 days, 0.095-0.116, 0.081-0.083 and 0.030-0.055 mg day−1 for films, microgranules and pellets respectively. The fungicidal activity of P3HB/ TEB against the plant pathogen Fusarium moniliforme was compared with that of the commercial formulation Raxil Ultra. A pronounced fungicidal effect of the experimental P3HB/ TEB formulations was observed in 2-4 weeks after application, and it was retained for 8 weeks, without affecting significantly the development of soil aboriginal microflora. CONCLUSION TEB release can be regulated by the process employed to fabricate the formulation and the fungicide loading, and the TEB accumulates in the soil gradually, as the polymer is degraded. The experimental forms of TEB embedded in the slowly degraded P3HB can be used as a basis for developing slow-release fungicide formulations. © 2016 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the effects of arsenic trioxide (AsO) in the chicken heart, and 72 1-day-old male Hy-line chickens were fed either a commercial diet (C group) or an arsenic supplement diet containing 7.5 mg/kg (L group), 15 mg/kg (M group), or 30 mg/kg (H group) AsO for 90 days. The results showed that exposure to AsO merely lowered ( P < 0.05) the activities of catalase (CAT) and glutathione peroxidase (GSH-Px) in M and H groups at 90 days, significantly downregulated the inhibition ability of hydroxyl radicals (OH·), and upregulated ( P < 0.05) the contents of malondialdehyde (MDA) in AsO exposure groups at 30, 60, and 90 days. Meanwhile, the messenger RNA levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and prostaglandin E synthase (PTGEs)) significantly increased ( P < 0.05) in AsO exposure groups at 30, 60, and 90 days, and histological and ultrastructural damage was observed in AsO exposure groups. Additionally, AsO-induced cardiac enzyme (aspartate transaminase (AST), creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and α-hydroxybutyrate dehydrogenase (α-HBDH)) levels increased ( P < 0.05) at 90 days. These findings suggested that AsO exposure led to oxidative stress, inflammatory response, and histological and ultrastructural damage and altered the levels of cardiac enzymes in chicken heart tissues. This result may be helpful for further studies on the toxicological mechanisms of AsO in the chicken heart. [ABSTRACT FROM AUTHOR]

Alterations in brain metabolism are closely associated with the molecular hallmarks of Parkinson's disease (PD). A clear understanding of the main metabolic perturbations in PD is therefore important. Here, we retrospectively analysed the expression of metabolic genes from 34 PD-control post-mortem human brain transcriptome data comparisons from literature, spanning multiple brain regions. We found high metabolic correlations between the Substantia nigra (SN)- and cerebral cortex-derived tissues. Moreover, three clusters of PD patient cohorts were identified based on perturbed metabolic processes in the SN - each characterised by perturbations in (a) bile acid metabolism (b) omega-3 fatty acid metabolism, and (c) lipoic acid and androgen metabolism - metabolic themes not comprehensively addressed in PD. These perturbations were supported by concurrence between transcriptome and proteome changes in the expression patterns for CBR1, ECI2, BDH2, CYP27A1, ALDH1B1, ALDH9A1, ADH5, ALDH7A1, L1CAM, and PLXNB3 genes, providing a valuable resource for drug targeting and diagnosis. Also, we analysed 58 PD-control transcriptome data comparisons from in vivo / in vitro disease models and identified experimental PD models with significant correlations to matched human brain regions. Collectively, our findings suggest metabolic alterations in several brain regions, heterogeneity in metabolic alterations between study cohorts for the SN tissues and the need to optimize current experimental models to advance research on metabolic aspects of PD.

Within the last decades, environmental pollution with persistent plastics steadily increased; therefore the production of biodegradable materials like poly-ß-hydroxybutyrate (PHB) is essential. Currently, PHB is produced with heterotrophic bacteria from crops. This leads to competition with food and feed production, which can be avoided by using photoautotrophic cyanobacteria, as Synechocystis salina , synthesizing PHB from CO 2 at nutrient limitation. This study aims to increase the economic efficiency of PHB production with cyanobacteria by using nutrients from anaerobic digestate. First, growth and PHB production of S. salina in digestate fractions (supernatant and permeate, with/without precipitating agents) and dilutions thereof and then the scale-up (photobioreactor, 200 L working volume) were evaluated. With precipitated and centrifuged digestate diluted 1/3 the highest biomass (1.55 g L -1 ) and PHB concentrations (95.4 mg L -1 ), being 78% of those in mineral media, were achieved. In the photobioreactor-experiments biomass (1.63 g L -1 ) and PHB concentrations (88.7 mg L -1 ), being 79% and 72% of those in mineral medium, were reached, but in a cultivation time 10 days longer than in mineral medium. The possibility to use digestate as sustainable and low cost nutrient solution for microalgae cultivation and photoautotrophic PHB production, instead of applying it on fields or processing it to achieve discharge limits, makes this application a highly valid option. [ABSTRACT FROM AUTHOR]

Acrylic acid and propionic acid are important chemicals requiring affordable, renewable production solutions. Here, we metabolically engineered Escherichia coli with genes encoding components of the 3-hydroxypropionate/4-hydroxybutyrate cycle from Metallosphaera sedula for conversion of glucose to acrylic and propionic acids. To construct an acrylic acid-producing pathway in E. coli, heterologous expression of malonyl-CoA reductase (MCR), malonate semialdehyde reductase (MSR), 3-hydroxypropionyl-CoA synthetase (3HPCS), and 3-hydroxypropionyl-CoA dehydratase (3HPCD) from M. sedula was accompanied by overexpression of succinyl-CoA synthetase (SCS) from E. coli. The engineered strain produced 13.28 ± 0.12 mg/L of acrylic acid. To construct a propionic acid-producing pathway, the same five genes were expressed, with the addition of M. sedula acryloyl-CoA reductase (ACR). The engineered strain produced 1430 ± 30 mg/L of propionic acid. This approach can be expanded to synthesize many important organic chemicals, creating new opportunities for the production of chemicals by carbon dioxide fixation. [ABSTRACT FROM AUTHOR]