Effect of energy level of pullet diet and age on laying performance and expression of hypothalamus-pituitary-gonadal related genes in laying hens.

Dietary energy density influences feed intake (FI) and development of layer-type pullets. A total of 384 nine-wk-old Hy-Line Brown pullets were randomly assigned to one of 3 dietary treatments: fed a diet with 2,600, 2,750, and 2,900 Kcal metabolizable energy/kg (ME/kg) from 10 to 21 wk of age. The results showed that the 2,900 and 2,600 ME groups had lower feed and ME intake (P < 0.01) from 10 to 21 wk of age. The 2,600 ME pullets had heavier body weight (BW) and longer shank length (P < 0.05) at 21 wk of age than the 2,750 ME group. The eggshell percentage was increased by the 2,600 and 2,900 kcal/kg treatments (P = 0.002). Serum concentration of 17-ß-estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) decreased at 70 wk of age (P < 0.05). Pullet diet and its interaction with age had a significant influence (P < 0.001) on the expression of gonadotropin-releasing hormone 1 (GnRH-1) and gonadotropin-inhibitory hormone (GnIH) in the hypothalamus and of gonadotropin releasing hormone 1 receptor (GnRH-1R) and gonadotropin-inhibitory hormone receptor (GnIHR) in the pituitary. In the hypothalamus, GnRH-1 expression increased from 9 to 40 wk of age and then decreased; however, GnIH expression was highest at 70 wk of age. Follicle-stimulating hormone receptor (FSHR) expression increased (P < 0.001) at wk 40 and decreased at wk 70 compared to wk 21 at various follicular stages. In conclusion, the energy level of pullet diet had no unfavorable influence on feed intake, laying rate, egg mass, and FCR, whereas change egg weight and mortality during the laying period from 21 to 70 wk of age. during the laying period. These results suggest that pullet dietary energy can activate the expression of genes related to reproduction in the hypothalamus, whereas it plays a minor role in the regulation of genes in the pituitary and ovary. Age-induced gene expression in the hypothalamus-pituitary-gonadal (HPG) axis is associated with laying performance in hens.

Protein succinylation, hepatic metabolism, and liver diseases.

Succinylation is a highly conserved post-translational modification that is processed via enzymatic and non-enzymatic mechanisms. Succinylation exhibits strong effects on protein stability, enzyme activity, and transcriptional regulation. Protein succinylation is extensively present in the liver, and increasing evidence has demonstrated that succinylation is closely related to hepatic metabolism. For instance, histone acetyltransferase 1 promotes liver glycolysis, and the sirtuin 5-induced desuccinylation is involved in the regulation of the hepatic urea cycle and lipid metabolism. Therefore, the effects of succinylation on hepatic glucose, amino acid, and lipid metabolism under the action of various enzymes will be discussed in this work. In addition, how succinylases regulate the progression of different liver diseases will be reviewed, including the desuccinylation activity of sirtuin 7, which is closely associated with fatty liver disease and hepatitis, and the actions of lysine acetyltransferase 2A and histone acetyltransferase 1 that act as succinyltransferases to regulate the succinylation of target genes that influence the development of hepatocellular carcinoma. In view of the diversity and significance of protein succinylation, targeting the succinylation pathway may serve as an attractive direction for the treatment of liver diseases.

An electrochemiluminescence microsensor based on DNA-silver nanoclusters amplification for detecting cellular adenosine triphosphate.

Adenosine triphosphate (ATP), as the primary energy source, plays vital roles in many cellular events. Developing an efficient assay is crucial to rapidly evaluate the level of cellular ATP. A portable and integrated electrochemiluminescence (ECL) microsensor array based on a closed bipolar electrode (BPE) was presented. In the BPE unit, the ECL chemicals and oxidation/reduction were separated from the sensing chamber. The ATP aptamer was assembled with single-stranded DNA (ssDNA) in the sensing chamber. ATP capture made the aptamer disassemble from the ssDNA and facilitated DNA-templated silver nanocluster (Ag NC) generation by the target-rolling circle amplification (RCA) reaction. The guanine-rich padlock sequence produced tandem periodic cytosine-rich sequences by the RCA, inducing Ag NC generation in the cytosine-rich region of the produced DNA strands through Ag+ reduction. The in situ Ag NC generation enhanced the circuit conductivity of the BPE and promoted the ECL reaction of [Ru(bpy)2dppz]2+/tripropylamine in the anodic reservoir. On this ECL microsensor, a good linear relationship of ATP was achieved ranging from 30 to 1000 nM. The ATP content in HepG2 cells was selectively and sensitively determined without complex pretreatment. The ATP amount of 25 cells could be successfully detected when a sub-microliter sample was loaded.

Allicin Promotes Glucose Uptake by Activating AMPK through CSE/H2S-Induced S-Sulfhydration in a Muscle-Fiber Dependent Way in Broiler Chickens.

SCOPE: Allicin, a product of enzymatic reaction when garlic is injured, plays an important role in maintaining glucose homeostasis in mammals. However, the effect of allicin on glucose homeostasis in the state of insulin resistance remains to be elucidated. This study investigates the effect of allicin on glucose metabolism using different muscle fibers in a chicken model. METHODS AND RESULTS: Day-old male Arbor Acres broilers are randomly divided into three groups and fed a basal diet supplemented with 0, 150, or 300 mg kg-1 allicin for 42 days. Results show that allicin improves the zootechnical performance of broilers at the finishing stage. The glucose loading test (2 g kg-1 body mass) indicates the regulatory role of allicin on glucose homeostasis. In vitro results demonstrate allicin increases glutathione (GSH) level and the expression of cystathionine γ lyase (CSE), leading to endogenous hydrogen sulfide (H2S) production in M. pectoralis major (PM) muscle-derived myotubes. Allicin stimulates adenosine monophosphate-activated protein kinase (AMPK) S-sulfhydration and AMPK phosphorylation to promote glucose uptake, which is suppressed in the presence of d,l-propargylglycine (PAG, a CSE inhibitor). CONCLUSION: This study demonstrates that allicin induces AMPK S-sulfhydration and AMPK phosphorylation to promote glucose uptake via the CSE/H2S system in a muscle fiber-dependent manner.

Greenness and chronic respiratory health issues: a systematic review and meta-analysis.

Introduction: The number of chronic respiratory disease (CRD) individuals worldwide has been continuously increasing. Numerous studies have shown that greenness can improve chronic respiratory health issues through different mechanisms, with inconsistent evidence. By quantitatively summarizing existing studies, our purpose is to determine the connection between greenness exposure and various chronic respiratory health. Methods: We conducted a comprehensive search on PubMed, EMBASE, and Web of Science core databases to identify relevant studies on the correlation between greenness exposure and chronic respiratory health issues. Studies published up to January 2023 were included in the search. The study used the most frequent indicator (normalized difference vegetation index [NDVI]) as the definition of greenness exposure. Results: We finally identified 35 studies for meta-analysis. We calculated pooled effects across studies using a random-effects model and conducted a subgroup analysis by age and buffer zones to discuss the effects on chronic respiratory health issues. This study showed that 0.1 increments in NDVI were significantly related to lower rates of asthma incidence, lung cancer incidence, and chronic obstructive pulmonary disease (COPD) mortality risk; the pooled RRs were 0.92 (95% CI: 0.85-0.98), 0.62 (95% CI: 0.40-0.95), and 0.95 (95% CI: 0.92- 0.99), respectively. For the age subgroup, the higher greenness exposure level was related to the incidence rate of asthma among teenagers aged 13-18years (RR: 0.91; 95% CI: 0.83-0.99). For the buffer subgroup, a positive relationship with greenness exposure and asthma incidence/prevalence at 200-300m and 800- 1000m buffers, as well as the COPD mortality at 800-1000m buffer, the pooled RRs were 0.92 (95% CI: 0.86-0.98), 0.87 (95% CI: 0.81-0.93), and 0.93 (95% CI: 0.88- 0.98), respectively. Evidence of publication bias was not detected in this study. Discussion: Our study is the first global meta-analysis between greenness and various CRDs to report an inverse association. Further research is needed in order to determine the effect of greenness exposure on different CRDs. Therefore, when planning for green development, more consideration must be given to public health and green management as intervention measures.https://www.crd.york.ac.uk/PROSPEROFILES/384029_STRATEGY_20230116.pdf.

Fibroblast growth factor 23 inhibits osteogenic differentiation and mineralization of chicken bone marrow mesenchymal stem cells.

Fibroblast growth factor 23 (FGF23), a bone-derived hormone, is involved in the reabsorption of phosphate (P) and the production of vitamin D hormones in the kidney. However, whether and how FGF23 regulates chicken bone metabolism remains largely unknown. In the present study, we investigated the effect of FGF23 on osteogenic differentiation and mineralization of chicken bone marrow mesenchymal stem cells (BMSCs). First, we found that the transcription of FGF23 was inhibited by ß-glycerophosphate sodium (GPS, 5 mM, 10 mM, 20 mM) and 10-9 M 1, 25-dihydroxyvitamin D3 (1, 25(OH)2D3), but was stimulated by 10-7 M 1, 25(OH)2D3 and parathyroid hormone (PTH, 10-9 M, 10-8 M, 10-7 M). Second, overexpression of FGF23 by the FGF23 adenovirus (Adv-FGF23) suppressed the formation of mineralized nodules (P < 0.001) and alkaline phosphatase (ALP) activity (P < 0.05) in both differentiated and mineralized osteoblasts. Administration of FGF receptor 3 (FGFR3) inhibitor (50 nM) was sufficient to restore the FGF23-decreased ALP activity (P < 0.05), but not for the formation of mineralized nodules. In addition, the phosphorylation of ERK increased considerably with Adv-FGF23 overexpression (P < 0.05). Administration of an ERK-specific inhibitor (10 µM) could down-regulate the phosphorylation of ERK (P-ERK) (P < 0.05) and slightly restored the Adv-FGF23-reduction of ALP activity (P = 0.08). In summary, our data suggest that GPS, 1, 25(OH)2D3, and PTH could regulate FGF23 mRNA expression in vitro. FGF23 is a negative regulator of bone remodeling. FGF23 not only inhibits BMSCs osteogenesis through the FGFR3-ERK signaling pathway but also suppresses the mineralization of mature osteoblasts.

Improved Cervical Lymph Node Characterization among Patients with Head and Neck Squamous Cell Carcinoma Using MR Texture Analysis Compared to Traditional FDG-PET/MR Features Alone.

Accurate differentiation of benign and malignant cervical lymph nodes is important for prognosis and treatment planning in patients with head and neck squamous cell carcinoma. We evaluated the diagnostic performance of magnetic resonance image (MRI) texture analysis and traditional 18F-deoxyglucose positron emission tomography (FDG-PET) features. This retrospective study included 21 patients with head and neck squamous cell carcinoma. We used texture analysis of MRI and FDG-PET features to evaluate 109 histologically confirmed cervical lymph nodes (41 metastatic, 68 benign). Predictive models were evaluated using area under the curve (AUC). Significant differences were observed between benign and malignant cervical lymph nodes for 36 of 41 texture features (p < 0.05). A combination of 22 MRI texture features discriminated benign and malignant nodal disease with AUC, sensitivity, and specificity of 0.952, 92.7%, and 86.7%, which was comparable to maximum short-axis diameter, lymph node morphology, and maximum standard uptake value (SUVmax). The addition of MRI texture features to traditional FDG-PET features differentiated these groups with the greatest AUC, sensitivity, and specificity (0.989, 97.5%, and 94.1%). The addition of the MRI texture feature to lymph node morphology improved nodal assessment specificity from 70.6% to 88.2% among FDG-PET indeterminate lymph nodes. Texture features are useful for differentiating benign and malignant cervical lymph nodes in patients with head and neck squamous cell carcinoma. Lymph node morphology and SUVmax remain accurate tools. Specificity is improved by the addition of MRI texture features among FDG-PET indeterminate lymph nodes. This approach is useful for differentiating benign and malignant cervical lymph nodes.

The Prevention of Venous Thromboembolism After Gynecological Surgery with Nursing Intervention Based on the G-Caprini Scale.

Objective: This study aimed to investigate the effect of nursing intervention based on the G-Caprini scale on the incidence of venous thromboembolism (VTE) after gynecological surgery and patients' satisfaction rate for nursing care. Methods: Ninety-eight patients who attended Taizhou People's Hospital and underwent gynecological surgery between January 2021 and December 2021 were selected as subjects and divided into two groups according to a random number table, with 49 cases in each group. The control group was given conventional nursing care, and the experimental group received nursing intervention based on the G-Caprini scale. The rate of postoperative lower-limb deep-vein thrombosis in the two groups was compared, and the incidence of VTE and the level of nursing satisfaction in the two groups were statistically analyzed. Results: The incidence of postoperative VTE in each risk class of the G-Caprini scale was lower in the experimental group than in the control group, and the difference was statistically significant (P < 0.01). In the experimental group, 47 patients were very satisfied with the nursing care, 1 was satisfied, and 1 was dissatisfied, which meant the nursing satisfaction rate in the experimental group was 97.96 (48/49). In the control group, 40 patients were very satisfied with the nursing care, 2 were satisfied, 1 was basically satisfied, and 6 were dissatisfied; thus, the satisfaction rate for nursing care in the control group was 87.75%. The difference between the two groups was statistically significant (χ 2 = 19.657, p < 0.05). Conclusion: Nursing interventions based on the G-Caprini rating scale were significantly effective in preventing VTE in patients after gynecological surgery and resulted in higher levels of patient satisfaction in terms of nursing care.

Insulin-like growth factor-1 is involved in the deteriorated performance of aged laying hens.

The underlying mechanism behind the deteriorated laying performance of aged laying hens remains unclear. In the present study, the laying performance and gene expression along the hypothalamus-pituitary-gonad axis were determined. A total of 300 healthy 90-wk-old ISA hens with similar body weights were classified into three groups according to their laying rate between 90 and 94 wk of age. The experimental groups were the low laying rate (<60%, LLR), high laying rate (>85%, HLR), and intermediate laying rate (60% < laying rate < 85%, MLR) hens. At the end of 94 wk of age, eight hens were randomly selected from each group for tissue collection. The gene expression of hormones and their receptors were determined in the hypothalamus, pituitary, and follicles. The results showed that the serum 17-ß-estradiol had no significant difference among the three groups. However, the level of insulin-like growth factor 1 (IGF1) in LLR hens was significantly decreased in the serum, small white follicles (SWF), and dominant follicles (DF, P < 0.05). Within the hypothalamus and small yellow follicles (SYF), the mRNA expression level of estrogen receptor was higher in the MLR group (P < 0.05). Compared with HLR hens, the steroid hormone-synthesis key gene, CYP19A1 was significantly decreased in the SWF of MLR-hens and DF of MLR- and LLR-hens (P < 0.05). The mRNA expression level of IGF1 receptor was higher in the hypothalamus, pituitary, SWF, large white follicles (LWF), SYF, and DF of LLR hens, compared to the HLR hens (P < 0.05). These results suggest that decreased IGF1 in serum and follicles was associated with the decreased egg production of aged laying hens. The present study provides novel insights into the endocrine changes in aged hens having different egg production.

The level of insulin-like growth factor 1 (IGF1) in low laying rate hens was significantly decreased in the serum, small white follicles, and dominant follicles. In the hypothalamus and small yellow follicles, the mRNA expression level of estrogen receptor in low laying rate hens was higher than in the medium laying rate hens. Compared with the high laying rate hens, the steroid hormone-synthesis gene, CYP19A1 was significantly decreased in the small white and dominant follicles of medium laying rate hens, as well as in the dominant follicles of low laying rate hens. Additionally, the mRNA expression level of IGF1 receptor was increased in the hypothalamus, pituitary, small white follicles, large white follicles, small yellow follicles, and dominant follicles of low laying rate hens compared to the high laying rate hens. These results suggest that decreased IGF1 in the serum and follicles of laying hens was associated with the reduction in the egg production of aged laying hens. The present study provides novel insights into the endocrine changes in aged laying hens having different egg production performances.

Dietary Energy and Protein Levels During the Prelay Period on Production Performance, Egg Quality, Expression of Genes in Hypothalamus-Pituitary-Ovary Axis, and Bone Parameters in Aged Laying Hens.

Nutrition during the pre-lay period takes effect on the production performance in the laying flock. This study evaluated the effects of dietary energy and protein levels in pre-lay diet on performance during the whole laying period and the egg quality, bone quality, and mRNA expression of hypothalamus-pituitary-gonadal (HPG) axis-related genes of hens at the end of the laying cycle. A total of 1,856 15-wk old Hy-Line brown pullets were randomly assigned to one of the four dietary treatments: using a 2 × 2 factorial arrangement with 2 energy levels (2,700 and 2,800 kcal/kg ME, respectively) and 2 protein levels (15 and 16.5% CP, respectively). Pullets were fed ad libitum from 15 to 20 wk and from 20 wk onward, fed with a similar laying diet till 72 wk of age. At 72 wk, the expression of genes in the hypothalamus, pituitary, ovarian, and follicles and bone quality was evaluated. At 72wk, there were no differences in production performance, BW, organ index, and ovarian parameters among the dietary treatments. High-CP diet increased the egg shape index and eggshell thickness (p < 0.05), but the eggshell breaking strength, Haugh unit, and albumen height did not differ among the treatments. Neither dietary energy nor protein level took an effect of bone quality. Low-energy diet increased the mRNA expression of gonadotropin-releasing hormone-1 (GnRH-1) in the hypothalamus (p < 0.05). The mRNA expression level of estrogen receptor-1 (ESR-1) in the hypothalamus and ovary was elevated by the 2,700 ME-15%CP diet (p < 0.05). The expression of cytochrome family 17 subfamily A polypeptide 1 (CYP17A1) in the large white follicle (LWF), small yellow follicles (SYF) and dominant follicle (DF) was decreased by the 2,800 kcal/kg diet (p < 0.05). These results indicate that the prelay diet had no influence on the production performance but had minimal effect on the eggshell characteristics and bone parameters. These results suggest that the energy and protein level of the prelay diet changes the expression of HPG axis-related genes of hens around the end of the laying cycle without changing the circulating sex hormone profile. The effect of prelay diet on the endocrinal adjustment at the end of the laying cycle needs to be investigated further.

Adiponectin Reduces Lipid Content in Chicken Myoblasts by Activating AMPK Signaling Pathway.

Studies in mammals have shown that adiponectin is secreted mainly by adipocytes, and it plays a crucial role in glucose and lipid metabolism in muscles. Clarifying the crosstalk role of adiponectin between adipose tissue and skeletal muscle tissue is very important for internal homeostasis. The glucose and lipid metabolism of chicken is different from that of mammals, and the role of adiponectin in chickens is unclear. Therefore, it is of great significance to study the effect and mechanism of adiponectin on lipid metabolism in chickens. In this study, the regulating effect of adiponectin on lipid metabolism in chicken myoblasts was explored by adding a certain concentration of exogenous recombinant adiponectin. Results showed that adiponectin reduced intracellular lipid content, increasing the mRNA expression of adiponectin receptor and cellular uptake of glucose and fatty acids. In addition, adiponectin activated the 5' adenosine monophosphate activated protein kinase (AMPK) signaling pathway. The above results suggested that adiponectin reduced intracellular lipid content, mainly by binding to adiponectin receptor, activating AMPK pathway, increasing cellular uptake of glucose and fatty acids, and promoting lipid oxidation.

Temporal specificity of IL-6 knockout in enhancing the thermogenic capability of brown adipose tissue.

Although interleukin-6 (IL-6) has been regarded as a homeostatic regulator of fat metabolism, its role in brown adipose thermogenesis remains to be further clarified. By using wild-type (WT) and IL-6-knockout (KO) mice, this study aims to investigate whether IL-6 regulates the thermogenic capability of brown adipose tissue (BAT) at both young and elderly stages. We demonstrated that IL-6 KO enhances BAT thermogenesis at a young age, as evidenced by the increased mRNA and protein expression levels of thermogenic genes, and the elevated interscapular surface temperature. The IL-6-KO enhancement of BAT thermogenesis is associated with improved respiratory exchange ratio (RER) and glucose homeostasis at young stages. However, these improvements disappear in elderly KO mice, which is likely attributable to the highly increased expression of other inflammatory cytokines, such as Tnfα, Il-1ß, and Il-10. Our findings indicate that the lack of IL-6 has a temporal-specific contribution to the promotion of BAT thermogenesis.

Real-time monitoring the efficacy of 7-hydroxycoumarin to cells cultured on microfluidics in different extracellular pH environments by chip-mass spectrometry.

The extracellular microenvironments play a key role in tumor metabolism. To online dynamic monitoring the efficacy of 7-hydroxycoumarin (7-OHC) to cells cultured on microfluidics in acidic microenvironment, we developed an integrated multi-channel chip-mass spectrometry system. This system has six drug-loading units, cell culture chamber, metabolite collection, filtration, HPLC separation and MS detection. The cells in each microchannel will be incubated with continuous flow of culture medium, metabolites will be collected by the fixed card slot, automatic sampling needle will be precise positioned and sampled. Through this new system, the 7-hydroxycoumarin-sulfonate (7-OHC-sulfonate) and 7-hydroxycoumarin-glucuronide (7-OHC-glucuronide) can be determined in real-time. The results revealed that the addition of lactic acid promoted the formation of inactive 7-OHC-sulfonate and 7-OHC-glucuronide metabolites. Besides, acidic extracellular environment amplified cancer cell proliferation, indicating the anticancer effect of 7-OHC was weakened by low extracellular pH.

Biomimetic multifactor stimulation method for analyzing the synergism of matrix stiffness and inorganic polyphosphates on cellular behaviors.

In the process of tumorigenesis and development, cancer cells must integrate and respond to complex and dynamic signals in the tumor microenvironment. Nevertheless, simulating the original biomechanical and biochemical microenvironment of different cells in vitro is a fundamental challenge in studying synergistic effects. To address this issue, we have proposed a biomimetic multi-factor stimulation platform, which conveniently creates a two-dimensional matrix environment with controllable stiffness as biomechanical factor and can smoothly introduce biochemical cue. Our results indicated that the extracellular matrix (ECM) stiffness could enhance the cell stretching, which further lead to the amplification of cell-matrix adhesion and proliferation. And there existed obvious differences of endocytosis efficiency response of cells on matrix stiffness. Nanoparticles (NPs) with the same size and shape, but differs in electrical charges showed more uptake on harder matrix. Besides, the inorganic polyphosphates (polyP), which acts as energy storage and producer in the in-extracellular space, was proven to synergistically promote aforementioned cell biomechanical behaviors by increasing ATP metabolism for the first time. These results explored the impact of microenvironmental performance on the glioma mechanoresponses, and we believe this biomimetic multifactor stimulation method would exhibit a profound impact on researches of in vitro biomimetic cell culture and NPs-like drug phagocytosis.

Matrix-assisted laser desorption ionization mass spectrometry based quantitative analysis of cordycepin from Cordyceps militaris.

Cordycepin, which has great immunomodulatory activities such as anticancer, antifungal, antivirus, antileukemia and lipid-lowering ones, is the secondary metabolite of Cordyceps militaris (C. militaris). Liquid submerged fermentation is the common cultivation process to produce cordycepin. To optimize the fermentation process and improve production, monitoring the cordycepin secretion in the fermentation is essential. The measurement based on chromatography-mass spectrometry methods is generally involved in the complex sample pretreatments and time-consuming separation, so more rapid and convenient methods are required. Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) is more attractive for faster and direct detection. Therefore, MALDI-MS detection combined with isotope-labeled internal standard was applied to the measurement of cordycepin content in the fermentation broth and mycelium. This method made accurate quantification of cordycepin in the range of 5-400 µg/mL with a relative standard deviation of 5.6%. The recovery rates of fermentation samples after the 1, 13, and 25 days were 90.15%, 94.27%, and 95.06%, respectively. The contents of cordycepin in the mycelium and fermentation broth were 136 mg/g and 148.39 mg/mL on the 20th culture day, respectively. The cordycepin secretion curve of the liquid fermentation of C. militaris was real-time traced over 25 days.

Survival of COVID-19 Patients With Respiratory Failure is Related to Temporal Changes in Gas Exchange and Mechanical Ventilation.

Background: Respiratory failure due to coronavirus disease of 2019 (COVID-19) often presents with worsening gas exchange over a period of days. Once patients require mechanical ventilation (MV), the temporal change in gas exchange and its relation to clinical outcome is poorly described. We investigated whether gas exchange over the first 5 days of MV is associated with mortality and ventilator-free days at 28 days in COVID-19. Methods: In a cohort of 294 COVID-19 patients, we used data during the first 5 days of MV to calculate 4 daily respiratory scores: PaO2/FiO2 (P/F), oxygenation index (OI), ventilatory ratio (VR), and Murray lung injury score. The association between these scores at early (days 1-3) and late (days 4-5) time points with mortality was evaluated using logistic regression, adjusted for demographics. Correlation with ventilator-free days was assessed (Spearman rank-order coefficients). Results: Overall mortality was 47.6%. Nonsurvivors were older (P < .0001), more male (P = .029), with more preexisting cardiopulmonary disease compared to survivors. Mean PaO2 and PaCO2 were similar during this timeframe. However, by days 4 to 5 values for all airway pressures and FiO2 had diverged, trending lower in survivors and higher in nonsurvivors. The most substantial between-group difference was the temporal change in OI, improving 15% in survivors and worsening 11% in nonsurvivors (P < .05). The adjusted mortality OR was significant for age (1.819, P = .001), OI at days 4 to 5 (2.26, P = .002), and OI percent change (1.90, P = .02). The number of ventilator-free days correlated significantly with late VR (-0.166, P < .05), early and late OI (-0.216, P < .01; -0.278, P < .01, respectively) and early and late P/F (0.158, P < .05; 0.283, P < .01, respectively). Conclusion: Nonsurvivors of COVID-19 needed increasing intensity of MV to sustain gas exchange over the first 5 days, unlike survivors. Temporal change OI, reflecting both PaO2 and the intensity of MV, is a potential marker of outcome in respiratory failure due to COVID-19.

Investigation of the lipidomic changes in differentiated glioblastoma cells after drug treatment using MALDI-MS.

Lipids differences between tumor and normal tissue have been proved to be of diagnostic and therapeutic significance. The research of lipidomics in tumor is more and more important. Mass spectrometry like matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) can be more convenient and informative for lipids researching in biological and clinical researches. Most of malignant tumors like glioblastoma are characterized by incomplete differentiation, so differentiation therapy has made important progress in tumor treatment. Lipid profiles changes after therapy are worthy investigating. In our study, glioblastoma cell line U87-MG cells were treated by inducers of sodium phenylbutyrate (SPB) and all-trans retinoic acid (ATRA). The changes in lipids on cell membrane were profiled by MALDI-MS. The differentiation degree was assessed by cell proliferation, cell cycle, morphology and protein expression before MALDI-MS analysis. Comparing the inducer treated and untreated U87-MG cells, reduced proliferation rate, blocked cell cycle, benign nucleus morphology and changed expression of protein CD133 and glial fibrillary acidic protein (GFAP), were found after drug treatment. Moreover, the lipids of cell membrane presented distinguished differences in the drug treated cells. Most of the glycerophosphocholines (PC) with an increasing abundance are unsaturated PCs (PC (38:1), 816 m/z; PC (36:1), 788 m/z; PC (31:1), 725 m/z), and those decreasing are saturated PCs (PC (32:0), 734 m/z). These results provide the lipidomic differentiation which may be a significant guidance for evaluating the therapeutic effect of tumor therapy.

Machine learning classification of texture features of MRI breast tumor and peri-tumor of combined pre- and early treatment predicts pathologic complete response.

PURPOSE: This study used machine learning classification of texture features from MRI of breast tumor and peri-tumor at multiple treatment time points in conjunction with molecular subtypes to predict eventual pathological complete response (PCR) to neoadjuvant chemotherapy. MATERIALS AND METHOD: This study employed a subset of patients (N = 166) with PCR data from the I-SPY-1 TRIAL (2002-2006). This cohort consisted of patients with stage 2 or 3 breast cancer that underwent anthracycline-cyclophosphamide and taxane treatment. Magnetic resonance imaging (MRI) was acquired pre-neoadjuvant chemotherapy, early, and mid-treatment. Texture features were extracted from post-contrast-enhanced MRI, pre- and post-contrast subtraction images, and with morphological dilation to include peri-tumoral tissue. Molecular subtypes and Ki67 were also included in the prediction model. Performance of classification models used the receiver operating characteristics curve analysis including area under the curve (AUC). Statistical analysis was done using unpaired two-tailed t-tests. RESULTS: Molecular subtypes alone yielded moderate prediction performance of PCR (AUC = 0.82, p = 0.07). Pre-, early, and mid-treatment data alone yielded moderate performance (AUC = 0.88, 0.72, and 0.78, p = 0.03, 0.13, 0.44, respectively). The combined pre- and early treatment data markedly improved performance (AUC = 0.96, p = 0.0003). Addition of molecular subtypes improved performance slightly for individual time points but substantially for the combined pre- and early treatment (AUC = 0.98, p = 0.0003). The optimal morphological dilation was 3-5 pixels. Subtraction of post- and pre-contrast MRI further improved performance (AUC = 0.98, p = 0.00003). Finally, among the machine-learning algorithms evaluated, the RUSBoosted Tree machine-learning method yielded the highest performance. CONCLUSION: AI-classification of texture features from MRI of breast tumor at multiple treatment time points accurately predicts eventual PCR. Longitudinal changes in texture features and peri-tumoral features further improve PCR prediction performance. Accurate assessment of treatment efficacy early on could minimize unnecessary toxic chemotherapy and enable mid-treatment modification for patients to achieve better clinical outcomes.

Peripheral IL-6/STAT3 signaling promotes beiging of white fat.

Interleukin-6 (IL-6) can reportedly centrally affect the thermogenesis of brown fat. However, whether the peripheral IL-6 signaling regulates beiging of white fat remains largely unknown. In vitro experiments indicated IL-6-KO-derived white adipocytes exhibited lower thermogenic gene expression compared to the WT, associating with reduced phosphorylation of STAT3 at Tyr705. Mechanistically, exogenous IL-6 application increased the p-STAT3Tyr705 level, thus the phosphorylated STAT3 bound to the promoter regions, and enhanced the transcription of Pparγ and Ucp1. The protein interaction of PGC-1α with PPARγ was increased by IL-6, which also contributed to stimulate Ucp1 expression. In vivo experiments demonstrated that IL-6 KO decreased the beiging potential of white fat with suppressed STAT3 Tyr705 phosphorylation. Accordingly, IL-6-KO mature mice were associated with disrupted glucose homeostasis and accelerated hepatic steatosis. Collectively, we identified a novel function of peripheral IL-6/STAT3 signaling which is essential for beiging of white fat, such ensuring fat and glucose homeostasis.

Cytokines and their relationship with the severity and prognosis of coronavirus disease 2019 (COVID-19): a retrospective cohort study.

OBJECTIVE: To delineate the characteristics and clinical significance of plasma inflammatory cytokines altered in COVID-19. DESIGN: Retrospective, single-centre cohort study. SETTING: Tongji Hospital in Wuhan, China. PARTICIPANTS: Among a cohort of 308 patients with a diagnosis of COVID-19, 138 patients died while 170 patients recovered and were discharged from the hospital. The data were collected until 27 February 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: Clinical characteristics and laboratory findings were obtained from electronic medical records using data collection forms. RESULTS: The percentage of patients with elevated interleukin 2 receptor (IL-2R), IL-6, IL-8, IL-10 and tumour necrosis factor (TNF) increased with severity of disease (p<0.0001 for all). IL-2R (p<0.0001), IL-6 (p<0.0001), IL-8 (p=0.0001), IL-10 (p<0.0001) and TNF (p<0.0001) were also twofold to 20-fold higher in patients who died compared with those who recovered. Also, IL-6 and IL-10 increased in both the progressive patient groups: moderate (p=0.0026) and severe (p<0.0001). In multivariate analysis, higher levels of IL-2R (OR 1.001, 95% CI 1.000 to 1.002, p=0.031) and IL-6 (OR 1.013, 95% CI 1.003 to 1.024, p=0.015) on admission were associated with increasing odds of in-hospital death, independent of other covariates, including severity of disease and lymphocyte count. CONCLUSION: Increased proinflammatory and anti-inflammatory cytokines, including IL-2R, IL-6, IL-8, TNF and IL-10, showed an obvious association with both COVID-19 severity and in-hospital mortality. Thus, our study indicates that cytokines are valuable in predicting the severity of COVID-19 and helps in distinguishing critically ill patients from the less affected ones.