Serum exosomal microRNAs as potential biomarkers for centrally mediated abdominal pain syndrome.

Centrally mediated abdominal pain syndrome (CAPS) has generated a heavy disease burden worldwide. This study aimed to explore the serum exosomal microRNAs as potential diagnostic biomarkers for CAPS. From September 2022 to October 2023, 97 patients with CAPS and 96 healthy subjects were enrolled. Differentially expressed serum exosomal miRNAs between patients with CAPS and healthy controls were identified by high-throughput sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). The Receiver Operating Characteristic (ROC) curves and multivariate logistic regression analysis were used to evaluate the diagnostic value of the serum exosomal miRNAs. MiR-6850-5p, miR-194-5p, miR-199a-3p, miR-4525 which were significantly downregulated in serum exomes of CAPS patients compared to healthy controls which yielded the AUC values of 0.914 (95% CI, 0.873-0.954), 0.767 (95% CI, 0.695-0.839), 0.617 (95% CI, 0.527-0.708) and 0.561 (95% CI, 0.465-0.656), respectively to distinguish CAPS patients from healthy subjects. And AUC of the integration of the above 4 miRNAs was 0.931 (95% CI, 0.896-0.966). Multivariate logistic regression indicated that hsa-miR-6850-5p (OR=0.046; p<0.001), anxiety (OR=7.670; p=0.025) and depression (OR=22.967; p=0.008) were the independent predictors of CAPS. Serum exosomal miR-6850-5p is a promising diagnostic biomarker for CAPS. PERSPECTIVE: This study may be the first to explore serum exosomal miRNAs as a new diagnostic biomarker for CAPS, and the findings may help clinicians to access comprehensive understanding and accurate diagnosis of CAPS.

IRF4-mediated Treg phenotype switching can aggravate hyperoxia-induced alveolar epithelial cell injury.

Bronchopulmonary dysplasia (BPD) is characterized by alveolar dysplasia, and evidence indicates that interferon regulatory factor 4 (IRF4) is involved in the pathogenesis of various inflammatory lung diseases. Nonetheless, the significance and mechanism of IRF4 in BPD remain unelucidated. Consequently, we established a mouse model of BPD through hyperoxia exposure, and ELISA was employed to measure interleukin-17 A (IL-17 A) and interleukin-6 (IL-6) expression levels in lung tissues. Western blotting was adopted to determine the expression of IRF4, surfactant protein C (SP-C), and podoplanin (T1α) in lung tissues. Flow cytometry was utilized for analyzing the percentages of FOXP3+ regulatory T cells (Tregs) and FOXP3+RORγt+ Tregs in CD4+ T cells in lung tissues to clarify the underlying mechanism. Our findings revealed that BPD mice exhibited disordered lung tissue structure, elevated IRF4 expression, decreased SP-C and T1α expression, increased IL-17 A and IL-6 levels, reduced proportion of FOXP3+ Tregs, and increased proportion of FOXP3+RORγt+ Tregs. For the purpose of further elucidating the effect of IRF4 on Treg phenotype switching induced by hyperoxia in lung tissues, we exposed neonatal mice with IRF4 knockout to hyperoxia. These mice exhibited regular lung tissue structure, increased proportion of FOXP3+ Tregs, reduced proportion of FOXP3+RORγt+ Tregs, elevated SP-C and T1α expression, and decreased IL-17 A and IL-6 levels. In conclusion, our findings demonstrate that IRF4-mediated Treg phenotype switching in lung tissues exacerbates alveolar epithelial cell injury under hyperoxia exposure.

Iron Stress Affects the Growth and Differentiation of Toxoplasma gondii.

Iron is an indispensable nutrient for the survival of Toxoplasma gondii; however, excessive amounts can lead to toxicity. The parasite must overcome the host's "nutritional immunity" barrier and compete with the host for iron. Since T. gondii can infect most nucleated cells, it encounters increased iron stress during parasitism. This study assessed the impact of iron stress, encompassing both iron depletion and iron accumulation, on the growth of T. gondii. Iron accumulation disrupted the redox balance of T. gondii while enhancing the parasite's ability to adhere in high-iron environments. Conversely, iron depletion promoted the differentiation of tachyzoites into bradyzoites. Proteomic analysis further revealed proteins affected by iron depletion and identified the involvement of phosphotyrosyl phosphatase activator proteins in bradyzoite formation.

The effects of eccentric training on hamstring flexibility and strength in young dance students.

The objective of this research is to examine the impact of eccentric training on hamstring flexibility and strength in young dancers during the concluding stages of their foundational dance training program. A total of 24 female, second-year dance students from Hebei Normal University were selected as participants. They were divided into three distinct groups: Nordic hamstring exercise and single-leg deadlift group (NHE&SLD), forward bending exercises and standing leg lift group (FBE&SLL), and a control group (CG). The study was designed around a 6-week training regimen. An isokinetic dynamometer was used to measure seated knee flexor-extensor strength, while electronic goniometry was employed to measure hamstring flexibility in the supine position. Paired sample t-tests were conducted within each group, and one-way analysis of covariance (ANCOVA) was utilized for comparisons between groups. In the NHE&SLD group, significant disparities were observed in both concentric (T = - 5.687, P = 0.001) and eccentric (T = - 3.626, P = 0.008) hamstring strength pre and post-intervention. The pre-intervention dominant leg concentric strength test values significantly influenced the post-intervention outcomes (F = 5.313, P = 0.001, η2 = 0.840). Similarly, the pre-intervention dominant leg eccentric strength test values impacted the post-intervention results (F = 4.689, P = 0.043, η2 = 0.190). Following the intervention, the NHE&SLD group displayed marked changes in the active straight leg raising angle on both left (T = - 4.171, P = 0.004) and right (T = - 6.328, P = 0.001) sides. The FBE&SLL group also revealed significant changes in the active straight leg raising angle on both left (T = - 4.506, P = 0.003) and right (T = - 4.633, P = 0.002) sides following the intervention. The pre-intervention left leg concentric strength test value significantly influenced the post-intervention outcomes (F = 25.067, P = 0.001, η2 = 0.556). Likewise, the pre-intervention right leg eccentric strength test value significantly influenced the post-intervention results (F = 85.338, P = 0.01, η2 = 0.810). Eccentric training can better enhance the flexibility and strength of hamstring muscles in dance students. Traditional stretching training significantly improves the flexibility of the hamstring muscles. Eccentric training has more training benefits than traditional stretching training. It is recommended for dance students to use eccentric training when increasing hamstring flexibility and strength.

Review and Prospect of Development Status of Traditional Chinese Medicine Processing Technology from 1.0 to 4.0 / 中国实验方剂学杂志

The development and application of processing technology is closely related to the quality of Chinese medicine. Currently， Chinese medicine processing is still in the mechanization stage with limited processing equipment， low levels of automation and intelligence. As a result， the imprecise control of parameters during processing leads to unstable quality of Chinese herbal pieces. However， with the arrival of the big data era and the continuous development of "Internet+"， Chinese medicine processing technology and equipment have been continuously improved and updated， and gradually shifted to the development direction of automation and intelligence. The linkage production technology of Chinese herbal pieces optimizes the separate processing equipment coupling into the production line for continuous manufacture of Chinese herbal pieces， intending to improve production efficiency. The large-scale industrialized production of Chinese herbal pieces tends towards digital technology of processing experience and online inspection technology based on machine vision， electronic nose， and electronic tongue. These technologies are crucial prerequisites for standardizing the parameters of Chinese medicine processing. And further by docking the processing process and equipment with the internet， realizing the intelligent control of the production process is an important process for the transformation and upgrading of Chinese herbal piece industry in the future. In this paper， we summarized the development characteristics of different stages of Chinese medicine processing technology， combed application and development of processing theory， the evolution of processing equipment， and problems in the current industrial development stage of Chinese medicine processing， in order to provide ideas and methods for achieving digital and intelligent innovation of processing technology as well as high-efficient and high-quality production of Chinese herbal pieces.

Role of PPARγ in Ulcerative Colitis and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Ulcerative colitis （UC） is a chronic inflammatory bowel disease primarily affecting the colon and rectum， with the typical symptoms such as abdominal pain， bloody diarrhea， and tenesmus. The pathogenesis of UC remains to be fully elucidated. The disease is prone to recurrence， seriously affecting the patients' quality of life. Conventional therapies for UC have limitations， including unsatisfactory clinical efficacy， lengthy courses， and adverse reactions. Therefore， there is an urgent need to explore new therapeutic agents. Peroxisome proliferator-activated receptor gamma （PPARγ）， a ligand-dependent nuclear receptor protein that plays a crucial role in maintaining intestinal homeostasis， is closely associated with the onset and development of UC. Traditional Chinese medicine （TCM） has advantages such as multi-targeting and mild side effects in the treatment of UC. Recent studies have shown that TCM can exert the therapeutic effects on UC by modulating PPARγ. The TCM methods for regulating PPARγ include clearing heat， drying dampness， moving Qi， activating blood， resolving stasis， invigorating the spleen， warming the kidney， and treating with both tonification and elimination. On one hand， TCM directly activates PPARγ or mediates signaling pathways such as nuclear factor-κB （NF-κB）， mitogen-activated protein kinase （MAPK）， Toll-like receptor 4 （TLR4）， and regulates helper T cell 17 （Th17）/regulatory T cell （Treg） balance to promote macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype， thereby inhibiting intestinal inflammation. On the other hand， TCM regulates the intestinal metabolism to activate PPARγ， lower the nitrate level， and maintain local hypoxia. In this way， it can restore the balance between specialized anaerobes and facultative anaerobes， thereby improving the gut microbiota and treating UC. This article summarizes the role of PPARγ in UC and reviews the research progress of TCM in treating UC by intervening in PPARγ in the last five years， aiming to give insights into the treatment and new drug development for UC.

A genetic variant in the immune-related gene ERAP1 affects colorectal cancer prognosis / 中华医学杂志(英文版)

BACKGROUND@#Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.@*METHODS@#We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.@*RESULTS@#The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1 ) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1 . The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes.@*CONCLUSION@#The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1 .@*TRIAL REGISTRATION@#No. NCT00454519 ( https://clinicaltrials.gov/ ).

The number of FOXP3+regulatory T cells (Tregs) decreased and transformed into RORγt+FOXP3+Tregs in lung tissues of mice with bronchopulmonary dysplasia / 细胞与分子免疫学杂志

Objective To explore the phenotypic conversion of regulatory T cells (Tregs) in the lungs of mice with bronchopulmonary dysplasia (BPD)-affected mice. Methods A total of 20 newborn C57BL/6 mice were divided into air group and hyperoxia group, with 10 mice in each group. The BPD model was established by exposing the newborn mice to hyperoxia. Lung tissues from five mice in each group were collected on postnatal days 7 and 14, respectively. Histopathological changes of the lung tissues was detected by HE staining. The expression level of surfactant protein C (SP-C) in the lung tissues was examined by Western blot analysis. Flow cytometry was performed to assess the proportion of FOXP3+ Tregs and RORγt+FOXP3+ Tregs in CD4+ lymphocytes. The concentrations of interleukin-17A (IL-17A) and IL-6 in lung homogenate were measured by using ELISA. Spearman correlation analysis was used to analyze the correlation between FOXP3+Treg and the expression of SP-C and the correlation between RORγt+FOXP3+ Tregs and the content of IL-17A and IL-6. Results The hyperoxia group exhibited significantly decreased levels of SP-C and radical alveolar counts in comparison to the control group. The proportion of FOXP3+Tregs was reduced and that of RORγt+FOXP3+Tregs was increased. IL-17A and IL-6 concentrations were significantly increased. SP-C was positively correlated with the expression level of RORγt+FOXP3+ Tregs. RORγt+FOXP3+ Tregs and IL-17A and IL-6 concentrations were also positively correlated. Conclusion The number of FOXP3+ Tregs in lung tissue of BPD mice is decreased and converted to RORγt+ FOXP3+ Tregs, which may be involved in hyperoxy-induced lung injury.

The Clinical Characteristics and Related Factors of Centrally Mediated Abdominal Pain Syndrome.

INTRODUCTION: The aim of this study was to explore the clinical characteristics and related factors of centrally mediated abdominal pain syndrome (CAPS). METHODS: Our study included 73 patients with CAPS and 132 age-matched and gender-matched healthy controls. The general information of the participants was collected, and the questionnaires were completed including the 7-item Generalized Anxiety Disorder Scale, 9-item Patient Health Questionnaire, Hamilton Anxiety Scale, Hamilton Depression Scale Pittsburgh Sleep Quality Index, Visual Analog Scale, and Short-Form 36. Univariate and forward stepwise regression analyses were performed to explore the influencing factors of CAPS. RESULTS: Nonexercise (adjusted odds ration [AOR] 4.53; confidence interval [CI] 1.602-12.809), mild-to-moderate depression (AOR 7.931; CI 3.236-19.438), married status (AOR 3.656; CI 1.317-10.418), and drinking coffee (AOR 0.199; CI 0.051-0.775) were found to be related with centrally mediated abdominal syndrome. The Hamilton Anxiety Scale score (7-13) was significantly related to moderate-to-severe abdominal pain (AOR 7.043; CI 1.319-37.593). Higher Hamilton Depression Scale score was related to lower mental component scale score (ß = -0.726, P < 0.01) and physical component scale score (ß = -0.706, P < 0.01). DISCUSSION: Depression, married status, and nonexercise were the independent risk factors of CAPS. Conversely, coffee intake was an independent protective factor of CAPS. Anxiety was related to the severity of abdominal pain, while depression was related to low health-related quality of life.

[Effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging mice].

OBJECTIVE: To observe the effects of moxa smoke through olfactory pathway on learning and memory ability in rapid aging (SAMP8) mice, and to explore the action pathway of moxa smoke. METHODS: Forty-eight six-month-old male SAMP8 mice were randomly divided into a model group, an olfactory dysfunction group, a moxa smoke group and an olfactory dysfunction + moxa smoke group, with 12 mice in each group. Twelve age-matched male SAMR1 mice were used as the blank group. The olfactory dysfunction model was induced in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group by intraperitoneal injection of 3-methylindole (3-MI) with 300 mg/kg, and the moxa smoke group and the olfactory dysfunction + moxa smoke group were intervened with moxa smoke at a concentration of 10-15 mg/m3 for 30 min per day, with a total of 6 interventions per week. After 6 weeks, the emotion and cognitive function of mice was tested by open field test and Morris water maze test, and the neuronal morphology in the CAI area of the hippocampus was observed by HE staining. The contents of neurotransmitters (glutamic acid [Glu], gamma-aminobutyric acid [GABA], dopamine [DA], and 5-hydroxytryptamine [5-HT]) in hippocampal tissue of mice were detected by ELISA. RESULTS: The mice in the blank group, the model group and the moxa smoke group could find the buried food pellets within 300 s, while the mice in the olfactory dysfunction group and the olfactory dysfunction + moxa smoke group took more than 300 s to find them. Compared with the blank group, the model group had increased vertical and horizontal movements (P<0.05) and reduced central area residence time (P<0.05) in the open field test, prolonged mean escape latency on days 1-4 (P<0.05), and decreased search time, swimming distance and swimming distance ratio in the target quadrant of the Morris water maze test, and decreased GABA, DA and 5-HT contents (P<0.05, P<0.01) and increased Glu content (P<0.05) in hippocampal tissue. Compared with the model group, the olfactory dysfunction group had increased vertical movements (P<0.05), reduced central area residence time (P<0.05), and increased DA content in hippocampal tissue (P<0.05); the olfactory dysfunction + moxa smoke group had shortened mean escape latency on days 3 and 4 of the Morris water maze test (P<0.05) and increased DA content in hippocampal tissue (P<0.05); the moxa smoke group had prolonged search time in the target quadrant (P<0.05) and increased swimming distance ratio, and increased DA and 5-HT contents in hippocampal tissue (P<0.05, P<0.01) and decreased Glu content in hippocampal tissue (P<0.05). Compared with the olfactory dysfunction group, the olfactory dysfunction + moxa smoke group showed a shortened mean escape latency on day 4 of the Morris water maze test (P<0.05). Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a decreased 5-HT content in the hippocampus (P<0.05). Compared with the blank group, the model group showed a reduced number of neurons in the CA1 area of the hippocampus with a disordered arrangement; the olfactory dysfunction group had similar neuronal morphology in the CA1 area of the hippocampus to the model group. Compared with the model group, the moxa smoke group had an increased number of neurons in the CA1 area of the hippocampus that were more densely packed. Compared with the moxa smoke group, the olfactory dysfunction + moxa smoke group had a reduced number of neurons in the CA1 area of the hippocampus, with the extent between that of the moxa smoke group and the olfactory dysfunction group. CONCLUSION: The moxa smoke could regulate the contents of neurotransmitters Glu, DA and 5-HT in hippocampal tissue through olfactory pathway to improve the learning and memory ability of SAMP8 mice, and the olfactory is not the only effective pathway.

The prevalence of canine dirofilariasis in China: a systematic review and meta-analysis.

BACKGROUND: Dirofilariasis, the disease caused by Dirofilaria spp., and in particular by Dirofilaria immitis and Dirofilaria repens in canines, occurs frequently in canids and felids, and occasionally in humans, in temperate, sub-tropical and tropical regions globally. Although highly effective, safe and convenient preventive medicines have been available for the treatment of dirofilariasis for the past three decades, the disease remains a major veterinary and public health concern in endemic areas. The insect vectors, host-parasite relationships and interactions of Dirofilaria spp. have received little attention in China, and there is very little information in English regarding the prevalence of dirofilariasis in animals and humans in the country. The aim of this systematic review and meta-analysis is to evaluate the status of canine dirofilariasis in China based on the available literature in English and in Chinese. METHODS: We systematically searched five databases for epidemiologic studies on the prevalence of canine dirofilariasis in China and finally selected 42 studies eligible for inclusion in the systematic review and meta-analysis. The meta-analysis was performed using the random effects model in the meta package in R v4.2.1. RESULTS: The random effects model gave a pooled and weighted prevalence of Dirofilaria infection among dogs in China in the past 100 years of 13.8% (2896/51,313, 95% confidence interval 8.2-20.4%) with a high level of heterogeneity (I2 =  99.5%). CONCLUSIONS: Our analyses indicated that the prevalence of canine dirofilariasis in China has gradually declined, but that the range of Dirofilaria spp. has expanded. Older and outdoor dogs presented a higher rate of positive infection. The findings indicated that more attention should be paid to host factors for the effective control and management of this disease.

Acupuncture Improved the Function of the Lower Esophageal Sphincter and Esophageal Motility in Chinese Patients with Refractory Gastroesophageal Reflux Disease Symptoms: A Randomized Trial.

Objectives: Acupuncture is therapeutic for refractory gastroesophageal reflux disease by an unclear mechanism. This study was aimed at investigating the effect of acupuncture on esophageal motility in patients with symptoms of refractory gastroesophageal reflux disease. Methods: Sixty-eight patients with refractory gastroesophageal reflux disease symptoms were prospectively enrolled from August 2014 to December 2018 and randomized into acupuncture and control groups (n = 33 and 35, respectively). The acupuncture group received acupuncture, and the control group received sham acupuncture. Pre- and post-acupuncture high-resolution manometry was performed to evaluate the effect of acupuncture on esophageal motility. The GerdQ questionnaire was used to evaluate the pre- and post-intervention symptoms. Results: After acupuncture, there was a significant increase in the length of lower esophageal sphincter (3.10 ± 1.08 cm vs. 3.78 ± 1.01 cm), length of intra-abdominal lower esophageal sphincter (2.14 ± 1.05 cm vs. 2.75 ± 1.16 cm), and mean basal pressure of lower esophageal sphincter (22.02 ± 10.03 mmHg vs. 25.06 ± 11.48 mmHg) in the acupuncture group (P = 0.014); moreover, the numbers of fragmented contraction and ineffective contraction decreased from 36 to 12 (P < 0.001) and 43 to 18 (P = 0.001), respectively, in the acupuncture group. However, no significant difference was observed in the control group. The GerdQ score decreased significantly from 9.45 ± 2.44 to 7.82 ± 2.21 points in the first week after acupuncture (P < 0.001). Conclusions: Acupuncture, which improves esophageal motility, has short-term efficacy in patients with symptoms of refractory gastroesophageal reflux disease. This trial is registered with Chinese Clinical Trial Registry (ChiCTR1800019646).

Radiomics nomogram for the prediction of microvascular invasion of HCC and patients' benefit from postoperative adjuvant TACE: a multi-center study.

OBJECTIVES: To evaluate the performance of a radiomics nomogram developed based on gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) MRI for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS: A total of 260 eligible patients were retrospectively enrolled from three hospitals (140, 65, and 55 in training, standardized external, and non-standardized external validation cohort). Radiomics features and image characteristics were extracted from Gd-EOB-DTPA MRI image before hepatectomy for each lesion. In the training cohort, a radiomics nomogram which incorporated the radiomics signature and radiological predictors was developed. The performance of the radiomics nomogram was assessed with respect to discrimination calibration, and clinical usefulness with external validation. A score (m-score) was constructed to stratify the patients and explored whether it could accurately predict patient who benefit from PA-TACE. RESULTS: A radiomics nomogram integrated with the radiomics signature, max-D(iameter) > 5.1 cm, peritumoral low intensity (PTLI), incomplete capsule, and irregular morphology had favorable discrimination in the training cohort (AUC = 0.982), the standardized external validation cohort (AUC = 0.969), and the non-standardized external validation cohort (AUC = 0.981). Decision curve analysis confirmed the clinical usefulness of the novel radiomics nomogram. The log-rank test revealed that PA-TACE significantly decreased the early recurrence in the high-risk group (p = 0.006) with no significant effect in the low-risk group (p = 0.270). CONCLUSIONS: The novel radiomics nomogram combining the radiomics signature and clinical radiological features achieved preoperative non-invasive MVI risk prediction and patient benefit assessment after PA-TACE, which may help clinicians implement more appropriate interventions. CLINICAL RELEVANCE STATEMENT: Our radiomics nomogram could represent a novel biomarker to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization, which may help clinicians to implement more appropriate interventions and perform individualized precision therapies. KEY POINTS: • The novel radiomics nomogram developed based on Gd-EOB-DTPA MRI achieved preoperative non-invasive MVI risk prediction. • An m-score based on the radiomics nomogram could stratify HCC patients and further identify individuals who may benefit from the PA-TACE. • The radiomics nomogram could help clinicians to implement more appropriate interventions and perform individualized precision therapies.

High Fischer ratio peptide of hemp seed: Preparation and anti-fatigue evaluation in vivo and in vitro.

The high Fischer (F) ratio hemp peptide (HFHP) was prepared by enrichment using activated carbon adsorption, ultrafiltration, and Sephadex G-25 gel filtration chromatography. The OD220/OD280 ratio reached 47.1 with a molecular weight distribution from 180 to 980 Da, a peptide yield up to 21.7 %, and the F value was 31.5. HFHP had high scavenging ability of DPPH, hydroxyl free radicals, and superoxide. Mice experiments showed that the HFHP increased the activity of superoxide dismutase and glutathione peroxidase. The HFHP had no effect on the body weight of mice, but prolonged their weight-bearing swimming time. The lactic acid, serum urea nitrogen, and malondialdehyde of the mice after swimming was reduced, and the liver glycogen increased. The correlation analysis indicated that the HFHP had significant anti-oxidation and anti-fatigue properties.

Separation and determination of triadimefon and its metabolites triadimenol enantiomers in fruit puree by supercritical fluid chromatography.

A method was established for the separation and determination of triadimefon and its metabolite triadimenol enantiomer residues in major complementary fruit puree for infants and young children (banana puree, pineapple puree, and grape puree) by supercritical fluid chromatography. After the samples were extracted with acetonitrile and purified with a solid phase extraction cartridge, Acquity Trefoil CEL2 chiral chromatographic column was adopted for separation, and gradient elution was conducted at the flow rate of 1.0 ml/min under the mobile phase of supercritical carbon dioxide - 0.5% ammonia methanol, the detection wavelength was 220 nm and quantification was conducted with the external standard method. The limits of quantitation of triadimefon and triadimenol enantiomers were both 0.05 mg/kg, the linear ranges were 0.5-50 mg/L, and the linear correlation coefficients were greater than 0.9993. The recoveries in the spiked samples at 0.05, 0.2, and 3.0 mg/kg were from 80.1 to 106%, and the relative standard deviation reached 3.3-7.6%. The method is efficient, rapid, reproducible, and environmentally friendly, enabling accurate analysis of pesticide enantiomers, which can detect the enantiomer residues of triadimefon and its metabolite triadimenol in major complementary fruit puree for infants and young children.

The association between urinary polycyclic aromatic hydrocarbon metabolites and liver function among US population: a cross-sectional study.

Most studies have focused on the pulmonary toxicity of inhaled PAHs to date; therefore, their hepatotoxic consequences are yet unknown. The main aim of this study is to examine the association between urinary polycyclic aromatic hydrocarbons (PAHs) and liver function parameters among the US population. The data included in this study were from the National Health and Nutritional Examination Survey (NHANES) 2003-2016. Finally, we included 2515 participants from seven cycles of the NHANES. Logistic regression was performed to calculate the association between each PAH and liver function parameters (elevated vs. normal) with odds ratio (OR) and 95% confidence intervals (CIs), along with adjustment for confounding variables. P < 0.05 was considered to indicate a statistically significant difference. All analyses were performed using R software 4.0.1. In the present study, all 2515 individuals were aged ≥ 18 years, 1211 males, and 1304 females. The average age normal was 45.56 ± 20.20, and the elevated was 46.04 ± 19.73 years, respectively. The results of logistic regression indicated that increased 9-hydroxyfluorene (OR = 2.11, 95% CI = [1.52, 2.95], P < 0.001), 2-hydroxyfluorene (OR = 1.61, 95% CI = [1.23, 2.11], P < 0.001), and 3-hydroxyfluorene (OR = 1.54, 95% CI = [1.21, 1.95], P < 0.001) were associated with elevated GGT. In conclusion, 9-hydroxyfluorene is associated with elevated GGT level, and the effect of 9-hydroxyfluorene on GGT is modified by other PAHs, which means that 9-hydroxyfluorene has a greater influence on GGT when other PAHs are increased.

Regulation of Mitochondrial Energy Metabolism by Glutaredoxin 5 in the Apicomplexan Parasite Neospora caninum.

Iron-sulfur [Fe-S] clusters are one of the most ancient and functionally versatile natural biosynthetic prosthetic groups required by various proteins involved in important metabolic processes, including the oxidative phosphorylation of proteins, electron transfer, energy metabolism, DNA/RNA metabolism, and protein translation. Apicomplexan parasites harbor two possible [Fe-S] cluster assembly pathways: the iron-sulfur cluster (ISC) pathway in the mitochondria and the sulfur formation (SUF) pathway in the apicoplast. Glutaredoxin 5 (GRX5) is involved in the ISC pathway in many eukaryotes. However, the cellular roles of GRX5 in apicomplexan parasites remain to be explored. Here, we showed that Neospora caninum mitochondrial GRX5 (NcGRX5) deficiency resulted in aberrant mitochondrial ultrastructure and led to a significant reduction in parasite proliferation and virulence in mice, suggesting that NcGRX5 is important for parasite growth in vitro and in vivo. Comparative proteomics and energy metabolomics were used to investigate the effects of NcGRX5 on parasite growth and mitochondrial metabolism. The data showed that disruption of NcGRX5 downregulated the expression of mitochondrial electron transport chain (ETC) and tricarboxylic acid cycle (TCA) cycle proteins and reduced the corresponding metabolic fluxes. Subsequently, we identified 23 proteins that might be adjacent to or interact with NcGRX5 by proximity-based protein labeling techniques and proteomics. The interactions between NcGRX5 and two iron-sulfur cluster synthesis proteins (ISCS and ISCU1) were further confirmed by coimmunoprecipitation assays. In conclusion, NcGRX5 is important for parasite growth and may regulate mitochondrial energy metabolism by mediating the biosynthesis of iron-sulfur clusters. IMPORTANCE Iron-sulfur [Fe-S] clusters are among the oldest and most ubiquitous prosthetic groups, and they are required for a variety of proteins involved in important metabolic processes. The intracellular parasites in the phylum Apicomplexa, including Plasmodium, Toxoplasma gondii, and Neospora caninum, harbor the ISC pathway involved in the biosynthesis of [Fe-S] clusters in mitochondria. These cofactors are required for a variety of important biological processes. However, little is known about the role of oxidoreductase glutaredoxins in these parasites. Our data indicate that NcGRX5 is an essential protein that plays multiple roles in several biological processes of N. caninum. NcGRX5 interacts with the mitochondrial iron-sulfur cluster synthesis proteins ISCS and ISCU1 and also regulates parasite energy metabolism. These data provide an insider's view of the metabolic regulation and iron-sulfur cluster assembly processes in the apicomplexan parasites.

Pharmacology of orange-spotted grouper (Epinephelus coioides) melanocortin-5 receptor and its modulation by Mrap2.

The mammalian melanocortin-5 receptors (MC5Rs) are involved in various functions, including exocrine gland secretion, glucose uptake, adipocyte lipolysis, and immunity. However, the physiological role of fish Mc5r is rarely studied. Melanocortin-2 receptor accessory protein 2 (MRAP2) modulates pharmacological properties of melanocortin receptors. Herein, to lay the foundation for future physiological studies, we cloned the orange-spotted grouper (Epinephelus coioides) mc5r, with a 1008 bp open reading frame and a predicted protein of 334 amino acids. Grouper mc5r had abundant expression in the brain, skin, and kidney. Four ligands could bind to grouper Mc5r and dose-dependently increase intracellular cAMP levels. Grouper Mrap2 did not affect binding affinity or potency of Mc5r; however, grouper Mrap2 decreased cell surface expression and maximal binding of Mc5r. Mrap2 also significantly decreased the maximal response to a superpotent agonist but not the endogenous agonist. This study provided new data on fish Mc5r pharmacology and its regulation by Mrap2.

Tissue distribution of Qingfei Paidu Decoction based on HPLC-MS/MS / 中国中药杂志

The tissue distribution of Qingfei Paidu Decoction was studied by HPLC-MS/MS in vivo. Hypersil GOLD C_(18) column(2.1 mm×50 mm, 1.9 μm) was used for gradient elution with acetonitrile as the mobile phase A and 0.1% formic acid solution as the mobile phase B. High-resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning mode and multiple response monitoring(MRM) mode was employed to analyze the behaviors of the active components of Qingfei Paidu Decoction in diffe-rent tissues. The results showed that 19, 9, 17, 14, 22, 19, 24, and 2 compounds were detected in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. The compounds belonged to 8 groups, covering 14 herbs in the prescription. After administration with Qingfei Paidu Decoction, the compounds were rapidly distributed in various tissues, especially in the lung, liver, large intestine, and kidney. The majority of the compounds displayed secondary distribution. This study comprehensively analyzed the distribution rules of the main active components in Qingfei Paidu Decoction and provided a basis for the clinical application.