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Detection of small molecule metabolites (SMM), particularly those involved in energy metabolism using MALDI-mass spectrometry imaging (MSI), is challenging due to factors including ion suppression from other analytes present (e.g., proteins and lipids). One potential solution to enhance SMM detection is to remove analytes that cause ion suppression from tissue sections before matrix deposition through solvent washes. Here, we systematically investigated solvent treatment conditions to improve SMM signal and preserve metabolite localization. Washing with acidic methanol significantly enhances the detection of phosphate-containing metabolites involved in energy metabolism. The improved detection is due to removing lipids and highly polar metabolites that cause ion suppression and denaturing proteins that release bound phosphate-containing metabolites. Stable isotope infusions of [13C6]nicotinamide coupled to MALDI-MSI (Iso-imaging) in the kidney reveal patterns that indicate blood vessels, medulla, outer stripe, and cortex. We also observed different ATP:ADP raw signals across mouse kidney regions, consistent with regional differences in glucose metabolism favoring either gluconeogenesis or glycolysis. In mouse muscle, Iso-imaging using [13C6]glucose shows high glycolytic flux from infused circulating glucose in type 1 and 2a fibers (soleus) and relatively lower glycolytic flux in type 2b fiber type (gastrocnemius). Thus, improved detection of phosphate-containing metabolites due to acidic methanol treatment combined with isotope tracing provides an improved way to probe energy metabolism with spatial resolution in vivo.

Tissues derive ATP from two pathways-glycolysis and the tricarboxylic acid (TCA) cycle coupled to the electron transport chain. Most energy in mammals is produced via TCA metabolism1. In tumours, however, the absolute rates of these pathways remain unclear. Here we optimize tracer infusion approaches to measure the rates of glycolysis and the TCA cycle in healthy mouse tissues, Kras-mutant solid tumours, metastases and leukaemia. Then, given the rates of these two pathways, we calculate total ATP synthesis rates. We find that TCA cycle flux is suppressed in all five primary solid tumour models examined and is increased in lung metastases of breast cancer relative to primary orthotopic tumours. As expected, glycolysis flux is increased in tumours compared with healthy tissues (the Warburg effect2,3), but this increase is insufficient to compensate for low TCA flux in terms of ATP production. Thus, instead of being hypermetabolic, as commonly assumed, solid tumours generally produce ATP at a slower than normal rate. In mouse pancreatic cancer, this is accommodated by the downregulation of protein synthesis, one of this tissue's major energy costs. We propose that, as solid tumours develop, cancer cells shed energetically expensive tissue-specific functions, enabling uncontrolled growth despite a limited ability to produce ATP.

Great progress has been made in understanding gut microbiomes products and their effects on health and disease. Less attention, however, has been given to the inputs that gut bacteria consume. Here, we quantitatively examine inputs and outputs of the mouse gut microbiome, using isotope tracing. The main input to microbial carbohydrate fermentation is dietary fiber and to branched-chain fatty acids and aromatic metabolites is dietary protein. In addition, circulating host lactate, 3-hydroxybutyrate, and urea (but not glucose or amino acids) feed the gut microbiome. To determine the nutrient preferences across bacteria, we traced into genus-specific bacterial protein sequences. We found systematic differences in nutrient use: most genera in the phylum Firmicutes prefer dietary protein, Bacteroides dietary fiber, and Akkermansia circulating host lactate. Such preferences correlate with microbiome composition changes in response to dietary modifications. Thus, diet shapes the microbiome by promoting the growth of bacteria that preferentially use the ingested nutrients.

Background Different treatment methods have been developed for acute Achilles tendon rupture (ATR), including conservative treatment, minimally invasive or transdermal surgery, and open surgery, and there is no consensus about which method is superior. It is important to clarify the presence of Achilles tendon (AT) degeneration, the rupture site, and the rupture shape before surgery to determine whether minimally invasive or open surgery should be selected, thereby reducing the re‐rupture rate following acute ATR. The aim of this study was to investigate the diagnostic value of MRI in identifying the presence of AT degeneration, the rupture site, and the rupture shape for acute closed ATR. Methods From January 2016 to December 2019, patients with acute closed ATR who had undergone repair surgery were retrospectively enrolled. All patients received MRI examination, and the distance between the insertion site and broken end and the rupture shape (types I, II, and III) were independently determined by two observers. Then, the stump of the AT was exposed during the operation. The rupture site and rupture shape were recorded and compared and analyzed with the MRI results. Consistency analyses (using Cohen's kappa coefficient or intraclass correlation coefficient‐ICC) and calculation of diagnostic performance indexes were, respectively, conducted to evaluate the diagnostic value of the MRI. Results This study included 47 consecutive patients with acute ATR, with an average age of 38.4 years. Among them, 40 were male, and seven were female. The intraoperative exploration demonstrated a total of 34 (72.3%), 10 (21.3%), and three (6.4%) patients with type I, II, and III ruptures, respectively. The average distance between the insertion site and the proximal broken end measured intraoperatively was 4.07 ± 1.57 cm. High or excellent consistencies were found for ATR classifications (kappa: 0.739–0.770, p

ABSTRACT Purpose: Osteoarthritis (OA) is a degenerative joint disease which is categorized via destruction of joint cartilage and it also affects the various joints, especially knees and hips. Sinomenine active phytoconstituents isolated from the stem of Sinomenium acutum and already proof anti-inflammatory effect against the arthritis model of rodent. In this experimental protocol, we scrutinized the anti-osteoarthritis effect of sinomenine against monosodium iodoacetate (MIA) induced OA in rats. Methods: MIA (3 mg/50 μL) was used for inducing the OA in the rats, and rats received the oral administration of sinomenine (2.5, 5 and 7.5 mg/kg body weight) up to the end of the experimental study (four weeks). The body and organs weight were estimated. Aggrecan, C-terminal cross-linked telopeptide of type II collagen (CTX-II), glycosaminoglycans (GCGs), monocyte chemoattractant protein-1 (MCP-1), Interferon gamma (IFN-γ), antioxidant, inflammatory cytokines, inflammatory mediators and matrix metalloproteinases (MMP) were analyzed. Results: Sinomenine significantly (P < 0.001) boosted the body weight and reduced the heart weight, but the weight of spleen and kidney remain unchanged. Sinomenine significantly (P < 0.001) reduced the level of nitric oxide, MCP-1 and improved the level of aggrecan, IFN-γ and GCGs. Sinomenine remarkably upregulated the level of glutathione, superoxide dismutase and suppressed the level of malonaldehyde. It effectually modulated the level of inflammatory cytokines and inflammatory mediators and significantly (P < 0.001) reduced the level of MMPs, like MMP-1, 2, 3, 9 and 13. Conclusions: Sinomenine is a beneficial active agent for the treatment of OA disease.

Abstract Background Aging and diabetes can impair the balance function of the elderly and diabetic patients and increase their fall risk. This study aimed to assess the shaking amplitude of the center-of-pressure (CoP) during static standing, to analyze the effects of aging and diabetes on the balance control. Materials and methods This cross-sectional observational study, compared the balance performance of 20 healthy younger adults (27.65 ± 5.60 years), 16 healthy older adults (58.88 ± 3.54 years) and 15 diabetic patients (58.33 ± 5.33 years) in four static standing conditions on a force plate: horizontal, anteroposterior (AP), left and right slope planes (5° angles on AP, left and right directions, respectively). The trajectory coordinates of the CoP over time were recorded and analyzed by principal components analysis to obtain the 95% confidence ellipse and its parameters: angle, major and minor axes lengths, and area. The balance indicators were compared among the three groups using one-way analysis of variance (ANOVA), Brown–Forsythe test or Kruskal–Wallis H test, depending on the normality and homogeneity of variance assumptions. Results The diabetic group had a significantly larger confidence ellipse area than the healthy younger adults on the horizontal plane (P = 0.032) and than the healthy older adults on the horizontal (P = 0.036), AP slope (P = 0.023), and right ML slope (P = 0.037) planes. There were no significant differences in the major axis length of the confidence ellipse among the three groups. The diabetic group had a significantly longer minor axis length than the healthy younger adults on the AP slope (P = 0.039), left ML slope (P = 0.045) and right ML slope (P = 0.016) planes and than the healthy older adults on the AP slope (P = 0.007), left ML slope (P = 0.035) and right ML slope (P = 0.012) planes. Conclusions The balance control of diabetic patients is decreased compared with healthy younger and older people, and the body swing amplitude increases mainly in the direction of minor axis of confidence ellipse during static standing, while the swing amplitude in the direction of the major axis has no significant change. Evaluating the balance function of diabetic patients can help clinicians identify people with fall risk early and intervene early, thereby reducing the occurrence of fall events in this population.

This protocol describes an adaptation of a classic sequential touching object categorisation task to assess infant attention set-shifting, suitable for ages 12–24 months. The task is conducted in a social interactive context with a parent, who scaffolds their infants’ attention shift from high-salience to low-salience dimensional properties of objects (e.g., shape vs material). This task is adapted from Ellis and Oakes (2006), where 14 month-old infants were able to flexibly attend to both shape and material. In this paper, we present a methodological innovation which permits the direct measurement of the effect of parent-child interactions on an early developing executive function skill. This novel social interactive protocol permits direct assessment of the effect of parent-child interaction on an early executive function skill, attention set-shifting. • The parental role is to scaffold a shift in their child's attention from a high salient (e.g. shape) to a low-salient (e.g. material) dimension of the stimulus set. • The protocol is suitable for infants aged between 12 and 24 months.

BackgroundDiabetic foot ulcerations (DFUs) are a common but highly morbid complication of long-standing diabetes, carrying high rates of associated major amputation and mortality. Transverse tibial bone transport (TTT) has recently been applied for treatment of DFUs with the aim of accelerating wound healing. This study was performed to evaluate the effectiveness and safety of TTT in patients with DFUs.MethodsTwo authors independently retrieved the platforms of PubMed, Embase and CENTRAL, to identify studies associated with treatment of DFUs with TTT. Quantitative meta-analyses were performed to pool all available outcomes about the effectiveness and complications of TTT operation, with fixed- (I250%) model according to I2.ResultsA total of 7 studies, involving 818 participants, were included, with 661 participants treated with TTT operation. The pooled healing rate and limb salvage rate were 0.96 (95%CI: 0.93~0.98) and 0.98 (95%CI: 0.95~1.00) respectively after treatment with TTT. The pooled mean healing time was 15.03 (95%CI: 9.05~21.00) months. When compared with the pre-operative baseline values, the ankle-brachial index (ABI, MD: 0.23; 95%CI: 0.03~0.44; p

The photo-induced dissociative ionization of lanthanide complexes Ln(hfac)3 (Ln = Pr, Er, Yb) is studied using ultrafast shaped laser pulses in a time-of-flight (TOF) mass spectrometry setup. Various fluorine and Ln-containing mass fragments were observed, which can be interpreted by the photo-fragmentation mechanistic pathway involving C–C bond rotation processes proposed previously. A set of experiments used pulse shaping guided by closed-loop feedback control to identify pulses that optimize the ratio of LnF+/LnO+. In agreement with previous studies in which very little LnO+ was observed, broad pulses were found to maximize the LnF+/LnO+ ratio, which involves metal–ligand bond-breaking followed by bond rotation and bond rearrangement. In contrast, a transform limited (TL) pulse favored the formation of LnO+. Finally, the recently developed experimental control pulse slicing (CPS) technique was applied to elucidate the dynamics induced by fields that either maximize or minimize the LnF+/LnO+ ratio, which also indicates that longer laser pulses facilitate LnF+ formation during the C–C bond rotation dissociative-ionization process. [ABSTRACT FROM AUTHOR]

Objective: About 10% of patients after cardiopulmonary bypass (CPB) would undergo acute liver injury, which aggravated the mortality of patients. Ac2-26 has been demonstrated to ameliorate organic injury by inhibiting inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 on acute liver injury after CPB. Methods: A total of 32 SD rats were randomized into sham, CPB, Ac, and Ac/AKT1 groups. The rats only received anesthesia, and rats in other groups received CPB. The rats in Ac/AKT1 were pre-injected with the shRNA to interfere with the expression of AKT1. The rats in CPB were injected with saline, and rats in Ac and Ac/AKT1 groups were injected with Ac2-26. After 12 h of CPB, all the rats were sacrificed and the peripheral blood and liver samples were collected to analyze. The inflammatory factors in serum and liver were detected. The liver function was tested, and the pathological injury of liver tissue was evaluated. Results: Compared with the sham group, the inflammatory factors, liver function, and pathological injury were worsened after CPB. Compared with the CPB group, the Ac2-26 significantly decreased the pro-inflammatory factors and increased the anti-inflammatory factor, improved liver function, and ameliorated the pathological injury. All the therapeutic effects of Ac2-26 were notably attenuated by the shRNA of AKT1. The Ac2-26 increased the GSK3β and eNOS, and this promotion was inhibited by the shRNA. Conclusion: The Ac2-26 significantly treated the liver injury, inhibited inflammation, and improved liver function. The effect of Ac2-26 on liver injury induced by CPB was partly associated with the promotion of AKT1/GSK3β/eNOS. Key points: Question: The effect and mechanism of Ac2-26 on acute liver injury following CPB were unknown. Findings: The Ac2-26 significantly ameliorated the liver injury, inhibited the inflammation, and improved liver function. Meaning: This research furthered our understanding of the therapeutic effect of Ac2-26 on liver injury induced by CPB was positively associated with AKT1. [ABSTRACT FROM AUTHOR]

Significance: Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective, portable, and quantitative evaluation of foot microcirculation. Aim: We aim to use a wearable device laser Doppler flowmetry (LDF) to evaluate the foot microcirculation of T2DM patients at rest. Approach: Eleven T2DM patients and twelve healthy subjects participated in this study. The wearable LDF was used to measure the blood flows (BFs) for regions of the first metatarsal head (M1), fifth metatarsal head (M5), heel, and dorsal foot. Typical wavelet analysis was used to decompose the five individual control mechanisms: endothelial, neurogenic, myogenic, respiratory, and heart components. The mean BF and sample entropy (SE) were calculated, and the differences between diabetic patients and healthy adults and among the four regions were compared. Results: Diabetic patients showed significantly reduced mean BF in the neurogenic (p = 0.044) and heart (p = 0.001) components at theM1 and M5 regions (p = 0.025) compared with healthy adults. Diabetic patients had significantly lower SE in the neurogenic (p = 0.049) and myogenic (p = 0.032) components at the M1 region, as well as in the endothelial (p < 0.001) component at the M5 region and in the myogenic component at the dorsal foot (p = 0.007), compared with healthy adults. The SE in the myogenic component at the dorsal foot was lower than at theM5 region (p = 0.050) and heel area (p = 0.041). Similarly, the SE in the heart component at the dorsal foot was lower than at the M5 region (p = 0.017) and heel area (p = 0.028) in diabetic patients. Conclusions: This study indicated the potential of using the novel wearable LDF device for tracking vascular complications and implementing targeted interventions in T2DM patients. [ABSTRACT FROM AUTHOR]