Obesity, a multifactorial disease with many complications, has become a global epidemic. Weight management, including dietary supplementation, has been confirmed to provide relevant health benefits. ...However, experimental evidence and mechanistic elucidation of dietary supplements in this regard are limited. Here, the weight loss efficacy of MHP, a commercial solid beverage consisting of mulberry leaf aqueous extract and
protein peptides, was evaluated in a high-fat high-fructose (HFF) diet-induced rat model of obesity. Body component analysis and histopathologic examination confirmed that MHP was effective to facilitate weight loss and adiposity decrease. Pathway enrichment analysis with differential metabolites generated by serum metabolomic profiling suggests that PPAR signal pathway was significantly altered when the rats were challenged by HFF diet but it was rectified after MHP intervention. RNA-Seq based transcriptome data also indicates that MHP intervention rectified the alterations of white adipose tissue mRNA expressions in HFF-induced obese rats. Integrated omics reveals that the efficacy of MHP against obesogenic adipogenesis was potentially associated with its regulation of PPARγ and FGFR1 signaling pathway. Collectively, our findings suggest that MHP could improve obesity, providing an insight into the use of MHP in body weight management.
Background
It is highly controversial that how to deal with the lateral lymph-node metastasis in patients with rectal cancer. Although lateral lymph node can be detected by preoperative MRI, the ...metastasis status cannot be accurately determined following standard total mesorectal excision (TME) in low-risk patients. This study was to assess the correlation between preoperative MRI detected lateral lymph-node (LLN) features and prognosis in patients with non-preradiated low recurrence risk rectal cancers.
Materials and methods
This retrospective study included 593 low-risk rectal cancers underwent TME without neoadjuvant chemo-radiotherapy from January 2013 to December 2015. The features of the largest LLN were retrospectively reviewed on preoperative MRI. The relationship of MR-LLN features with overall survival, metastasis-free survival, and local relapse-free survival was analyzed.
Results
A total of 593 patients including 415 cases of pN0, 86 cases of pN1, and 92 cases of pN2 were enrolled in this study. In pN0 patients, at least one visible LLN was detected in 104 patients on primary MRI. The MR-T staging, postoperative therapy status, the presence of MR-LLN, and short axis (SA) of MR-LLN were significantly correlated with the recurrence in pN0 patients (all
p
< 0.05). The OS and MFS were significantly lower in patients with MR-LLN SA ≥ 8 mm than SA < 8 mm (
p
< 0.01, HR = 4.35, 95% CI = 1.48–12.77). The OS and MFS of patients with pN0-LLN(+) and SA ≥ 8 mm were similar to pN2-LLN(−) patients. The location of MR-LLN showed no significant impact on prognosis.
Conclusion
For low-risk rectal cancers without neoadjuvant chemo-radiotherapy, the presence of MR-LLN is associated with poor prognosis. The pN0-LLN(+) SA ≥ 8 mm patients might be concerned as pN2 patients and receive more intensive neoadjuvant or adjuvant treatment.
The Belief Rule-Based (BRB) system faces the rule combination explosion issue, making it challenging to construct the rule base efficiently. The Extended Belief Rule-Based (EBRB) system offers a ...solution to this problem by using data-driven methods. However, using EBRB system requires the traversal of the entire rule base, which can be time-consuming and result in the activation of many irrelevant rules, leading to an incorrect decision. Existing search optimization methods can somewhat solve this issue, but they have limitations. Moreover, the calculation of the rule activation weight only considers the similarity between input data and a single rule, ignoring the influence of the rule linkage. To address these problems, we propose a new EBRB system based on the K-Nearest Neighbor graph index (Graph-EBRB). We introduce the Hierarchical Navigable Small World (HNSW) algorithm to create the K-Nearest Neighbor graph index of the EBRB system. This index allows us to efficiently search and activate a set of key rules. We also propose a new activation weight calculation method based on the Graph Convolution Neural Network (GCN), and we optimize the system performance using a parameter learning strategy. We conduct a comprehensive experiment on 14 commonly used public data sets, and the results show that Graph-EBRB system significantly improves the reasoning efficiency and accuracy of the EBRB system. Finally, we apply the Graph-EBRB system to tree disease identification and achieve excellent classification performance, identifying over 90% of the diseased trees on the complete dataset.
Cellular therapeutic neovascularization has been successfully performed in clinical trials for patients with ischaemia diseases. Despite the vast knowledge of cardiovascular disease and circadian ...biology, the role of the circadian clock in regulating angiogenesis in myocardial infarction (MI) remains poorly understood. In this study, we aimed to investigate the role and underlying mechanisms of Period 2 (Per2) in endothelial progenitor cell (EPC) function. Flow cytometry revealed lower circulating EPC proportion in per2−/− than in wild‐type (WT) mice. PER2 was abundantly expressed in early EPCs in mice. In vitro, EPCs from per2−/− mice showed impaired proliferation, migration, tube formation and adhesion. Western blot analysis demonstrated inhibited PI3k/Akt/FoxO signalling and reduced C‐X‐C chemokine receptor type 4 (CXCR4) protein level in EPCs of per2−/− mice. The impaired proliferation was blocked by activated PI3K/Akt/FoxO signalling. Direct interaction of CXCR4 and PER2 was detected in WT EPCs. To further study the effect of per2 on in vivo EPC survival and angiogenesis, we injected saline or DiI‐labelled WT or per2−/− EPC intramyocardially into mice with induced MI. Per2−/− reduced the retention of transplanted EPCs in the myocardium, which was associated with significantly reduced DiI expression in the myocardium of MI mice. Decreased angiogenesis in the myocardium of per2−/− EPC‐treated mice coincided with decreased LV function and increased infarct size in the myocardium. Per2 may be a key factor in maintaining EPC function in vitro and in therapeutic angiogenesis in vivo.
The study sought to assess the detrimental effects of isoproterenol (ISO) on major organs and investigate the potential reversibility of these adverse reactions in mice. Male mice were divided into ...normal control, 0.2 mg/kg.d and 3.0 mg/kg.d ISO groups, and were subcutaneously administered of the respective doses for 14 consecutive days. Subsequently, a recovery period experiment was conducted, replicating the aforementioned procedure, followed by an additional 2-week recovery period for the mice. Following 14 consecutive days of administration, mice treated with ISO exhibited notable cardiac damage manifested by abnormal ECG patterns, dysregulated energy metabolism, elevated cardiac hypertrophy, and increased heart pathological score. Additionally, the administration of ISO resulted in liver and kidney damage, as evidenced by increased pathological score, serum albumin level, and urea level. Lung damage was also observed, indicated by an increase in lung pathological score. Furthermore, the administration of ISO at a dosage of 3.0 mg/kg.d resulted in a decrease in liver mass index, serum iron content, and an increase in lung mass index. After a 2-week recovery period, mice treated with ISO showed abnormalities in ECG patterns and dysregulated myocardial energy metabolism, accompanied by a decrease in serum iron content. Histopathological examinations revealed continued pathological changes in the heart and lung, as well as significant hemosiderin deposition in the spleen. Furthermore, the group treated with ISO at a dosage of 3.0 mg/kg.d showed an increase in serum AST and TP levels. In summary, the study demonstrates that both 0.2 mg/kg.d and 3.0 mg/kg.d doses of ISO can induce damage to the heart, liver, lung, kidney, and spleen, with the higher dose causing more severe injuries. After a 2-week withdrawal period, the liver, kidney, and thymus injuries caused by 0.2 mg/kg ISO shows signs of recovery, while damage to the heart, lung, and spleen persists. The thymus injury mostly recovers, with minimal kidney pathology, but significant damage to the heart, liver, and lung remains even after the withdrawal period for the 3.0 mg/kg ISO dose.
The material considered in this study not only has a functionally graded characteristic but also exhibits different tensile and compressive moduli of elasticity. One-dimensional and two-dimensional ...mechanical models for a functionally graded beam with a bimodular effect were established first. By taking the grade function as an exponential expression, the analytical solutions of a bimodular functionally graded beam under pure bending and lateral-force bending were obtained. The regression from a two-dimensional solution to a one-dimensional solution is verified. The physical quantities in a bimodular functionally graded beam are compared with their counterparts in a classical problem and a functionally graded beam without a bimodular effect. The validity of the plane section assumption under pure bending and lateral-force bending is analyzed. Three typical cases that the tensile modulus is greater than, equal to, or less than the compressive modulus are discussed. The result indicates that due to the introduction of the bimodular functionally graded effect of the materials, the maximum tensile and compressive bending stresses may not take place at the bottom and top of the beam. The real location at which the maximum bending stress takes place is determined via the extreme condition for the analytical solution.
Along with the increasing prevalence of obesity worldwide, the deleterious effects of high-calorie diet are gradually recognized through more and more epidemiological studies. However, the concealed ...and chronic causality whitewashes its unhealthy character. Given an ingenious mechanism orchestrates the metabolic adaptation to high-fat high-fructose (HFF) diet and connive its lipotoxicity, in this study, an experimental rat/mouse model of obesity was induced and a comparative transcriptomic analysis was performed to probe the mystery. Our results demonstrated that HFF diet consumption altered the transcriptomic pattern as well as different high-calorie diet fed rat/mouse manifested distinct hepatic transcriptome. Validation with RT-qPCR and Western blotting confirmed that SREBP1-FASN involved in de novo lipogenesis partly mediated metabolic self-adaption. Moreover, hepatic ACSL1-CPT1A-CPT2 pathway involved in fatty acids β-oxidation, played a key role in the metabolic adaption to HFF. Collectively, our findings enrich the knowledge of the chronic adaptation mechanisms and also shed light on future investigations. Meanwhile, our results also suggest that efforts to restore the fatty acids metabolic fate could be a promising avenue to fight against obesity and associated steatosis and insulin resistance challenged by HFF diet.
Overconsumption of HFF diet unbalances the energy intake and expenditure and usually leads to obesity and associated complications. Different kinds of high-calorie diet fed rats/mice manifest distinct hepatic transcriptome and the underlying ingenious regulatory mechanisms remain unclear. Downregulation of some key proteins (SREBP1, FASN) involved in de novo lipogenesis and ACSL1-CPT1A-CPT2 pathway positively mediate the metabolic adaptation to HFF. Display omitted
The existing data on the degree of pain in patients during CT-guided percutaneous transthoracic needle biopsy (PTNB) of lung lesions are limited and the factors related to pain are unclear. In this ...study, we aimed to evaluate the prevalence and severity of pain reported during PTNB and to identify factors associated with increased reported pain.
Patients who underwent PTNB from April 2022 to November 2022 were prospectively evaluated using the numeric rating scale, which assesses subjective pain based on a 0-10 scoring system (0 = no pain; 10 = the worst pain imaginable). The scale divides the scores into three categories: mild pain (1-3 points), moderate pain (4-6 points), and severe pain (7-10 points). Pain scores from 4 to 10 were considered significant pain. Demographic data of patients, lesion characteristics, biopsy variables, complications, the patient's subjective feelings, and pathological result data were analyzed by multivariable logistic regression analysis to identify variables associated with significant pain.
We enrolled 215 participants who underwent 215 biopsy procedures (mean age: 64.5 ± 9.3 years, 123 were men). The mean procedure-related pain score was 2 ± 2. Overall, 20% (43/215) of participants reported no pain (score of 0), 67.9% (146/215) reported pain scores of 1-3, 11.2% (24/215) reported scores of 4-6, and 0.9% (2/215) reported scores of 7 or higher. Furthermore, non-significant pain (scores of 0-3) was reported during 87.9% (189/215) of the procedures. In the adjusted model, significant pain was positively associated with lesions ≥ 34 mm (p = 0.001, odds ratio OR = 6.90; 95% confidence interval CI: 2.18, 21.85), a needle-pleural angle ≥ 77° (p = 0.047, OR = 2.44; 95% CI: 1.01, 5.89), and a procedure time ≥ 26.5 min (p = 0.031, OR = 3.11; 95% CI: 1.11, 8.73).
Most participants reported no pain or mild pain from CT-guided percutaneous transthoracic needle biopsies of lung lesions. However, those with a larger lesion, a greater needle-pleural angle, and a longer procedure time reported greater pain.
Purpose
The primary objective was to demonstrate the relationship between lung ultrasound (LUS) manifestations and the outcomes of intensive care unit (ICU) patients. The secondary objective was to ...determine the characteristics of LUS manifestations in different subgroups of ICU patients.
Methods
This prospective multi‐center cohort study was conducted in 17 ICUs. A total of 1702 patients admitted between August 31, 2017 and February 16, 2019 were included. LUS was performed according to the bedside lung ultrasound in emergency (BLUE)‐plus protocol, and LUS scores were calculated. Data on the outcomes and oxygenation indices were analyzed and compared between different primary indication groups.
Results
The LUS scores were significantly higher for non‐survivors than for survivors and were significantly different between the oxygenation index groups, with higher scores in the lower oxygenation index groups. The LUS score was an independent risk factor for the 28‐day mortality. The area under the receiver operating characteristic curve was 0.663 for prediction of the 28‐day mortality and 0.748 for prediction of an oxygenation index ≤100.
Conclusions
The LUS score based on the BLUE‐plus protocol was an independent risk factor for the 28‐day mortality and was important for the prediction of an oxygenation index ≤100. An early LUS score within 24 hours of ICU admission helps predicting the outcome of ICU patients.
•Porcine epidemic diarrhea virus (PEDV) is economically important to pig production.•Spray-dried pig plasma has been implicated in PEDV transmission.•PEDV-positive pig plasma and PEDV-spiked plasma ...were tested in a swine bioassay.•The spray-drying process effectively inactivated PEDV.•The risk of transmitting PEDV through spray-dried pig plasma is minimal.
Porcine epidemic diarrhea virus (PEDV) is considered an emergent pathogen associated with high economic losses in many pig rearing areas. Recently it has been suggested that PEDV could be transmitted to naïve pig populations through inclusion of spray-dried porcine plasma (SDPP) into the nursery diet which led to a ban of SDPP in several areas in North America and Europe. To determine the effect of spray-drying on PEDV infectivity, 3-week-old pigs were intragastrically inoculated with (1) raw porcine plasma spiked with PEDV (RAW-PEDV-CONTROL), (2) porcine plasma spiked with PEDV and then spray dried (SD-PEDV-CONTROL), (3) raw plasma from PEDV infected pigs (RAW-SICK), (4) spray-dried plasma from PEDV infected pigs (SD-SICK), or (5) spray-dried plasma from PEDV negative pigs (SD-NEG-CONTROL). For the spray-drying process, a tabletop spray-dryer with industry-like settings for inlet and outlet temperatures was used. In the RAW-PEDV-CONTROL group, PEDV RNA was present in feces at day post infection (dpi) 3 and the pigs seroconverted by dpi 14. In contrast, PEDV RNA in feces was not detected in any of the pigs in the other groups including the SD-PEDV-CONTROL group and none of the pigs had seroconverted by termination of the project at dpi 28. This work provides direct evidence that the experimental spray-drying process used in this study was effective in inactivating infectious PEDV in the plasma. Additionally, plasma collected from PEDV infected pigs at peak disease did not contain infectious PEDV. These findings suggest that the risk for PEDV transmission through commercially produced SDPP is minimal.
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