Hepatotoxicity of oral exposure to 2-methyl-4-nitroaniline: toxicity prediction and in vivo evaluation.

2-Methyl-4-nitroaniline (MNA), an intermediate in the synthesis of azo dyes, is widely distributed in various environmental media and organisms. Although there is speculation regarding MNA's potential to be hepatotoxic, the underlying mechanisms of its hepatotoxicity and its definitive diagnostic process remain largely unexplored. In this research. In the present study, we initially predicted the toxicity and possible toxic effect pathways of MNA using ProTox-II, and found that MNA binds to the PPARγ receptor (binding energy －6.118 kcal/mol) with a potential PPARγ agonist effect. Subsequently, in vivo exposure evaluation was conducted on Wistar rats to assess the impact of MNA after a 90-day exposure period, by detecting serum biochemical indexes, hematological indexes, urinary indexes, inflammatory factors, liver histopathological observations and liver tissue PPARγ mRNA expression. The results showed that MNA causes liver function abnormalities, liver histopathological changes and inflammatory response, along with a pronounced increase in PPARγ mRNA levels. This study suggests that the hepatotoxic mechanism of MNA may be related to its possible upregulation of PPARγ expression, increased liver dysfunction and inflammatory responses. Based on these results, the benchmark dose lower limit (BMDL) of 1.503 mg/kg for male Wistar rats was also established, providing a vital benchmark for determining the safety threshold of MNA. Our data highlight the hepatotoxic mechanism of MNA and contribute to a better understanding of its potential etiological diagnosis.

Lactobacillus rhamnosus NKU FL1-8 Isolated from Infant Feces Ameliorates the Alcoholic Liver Damage by Regulating the Gut Microbiota and Intestinal Barrier in C57BL/6J Mice.

Alcoholic liver damage is caused by long-term or heavy drinking, and it may further progress into alcoholic liver diseases (ALD). Probiotic supplements have been suggested for the prevention or improvement of liver damage. This study was designed to consider the ameliorative effects of Lactobacillus rhamnosus NKU FL1-8 isolated from infant feces against alcoholic liver damage. The mice were gavaged with a 50% ethanol solution and treated with 109 CFU of L. rhamnosus NKU FL1-8 suspension. The factors for liver function, oxidative stress, inflammation, gut microbiota composition, and intestinal barrier integrity were measured. The results showed that L. rhamnosus NKU FL1-8 could decrease the levels of aspartate aminotransferase (AST) to 61% and alanine aminotransferase (ALT) to 50% compared with ethanol given by gavage. It could inhibit the expression level of malondialdehyde (MDA), increase superoxide dismutase (SOD), glutathione (GSH) to relieve oxidative stress, and down-regulate the cytokines to decrease hepatic inflammation. After treatment, the level of triglycerides was reduced, and the expression levels of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and the peroxisome proliferators-activated receptor-α (PPAR-α) pathway were up-regulated. Additionally, the 16S rRNA sequencing analysis showed that L. rhamnosus NKU FL1-8 increased the relative abundance of Lactobacillus, Ruminococcaceae, etc. At the same time, L. rhamnosus NKU FL1-8 could significantly reduce lipopolysaccharides (LPS) and enhance intestinal tight junction proteins. These results demonstrated that L. rhamnosus NKU FL1-8 could reduce the level of oxidative stress, fat accumulation, and liver inflammation caused by alcohol in the host. The underlying mechanism could be that L. rhamnosus NKU FL1-8 inhibits LPS by regulating the gut microbiota and repairing the intestinal barrier. Thereby, these findings support L. rhamnosus NKU FL1-8 as a potential functional food for the relief of ALD.

The residual risk of inflammation and remnant cholesterol in acute coronary syndrome patients on statin treatment undergoing percutaneous coronary intervention.

BACKGROUND: Residual risk assessment for acute coronary syndrome (ACS) patients after sufficient medical management remains challenging. The usefulness of measuring high-sensitivity C-reactive protein (hsCRP) and remnant cholesterol (RC) in assessing the level of residual inflammation risk (RIR) and residual cholesterol risk (RCR) for risk stratification in these patients needs to be evaluated. METHODS: Patients admitted for ACS on statin treatment who underwent percutaneous coronary intervention (PCI) between March 2016 and March 2019 were enrolled in the analysis. The included patients were stratified based on the levels of hsCRP and RC during hospitalization. The primary outcome was ischemic events at 12 months, defined as a composite of cardiac death, myocardial infarction, or stroke. The secondary outcomes included 12-month all-cause death and cardiac death. RESULTS: Among the 5778 patients, the median hsCRP concentration was 2.60 mg/L and the median RC concentration was 24.98 mg/dL. The RIR was significantly associated with ischemic events (highest hsCRP tertile vs. lowest hsCRP tertile, adjusted hazard ratio [aHR]: 1.52, 95% confidence interval [CI]: 1.01-2.30, P = 0.046), cardiac death (aHR: 1.77, 95% CI:1.02-3.07, P = 0.0418) and all-cause death (aHR: 2.00, 95% CI: 1.24-3.24, P = 0.0048). The RCR was also significantly associated with these outcomes, with corresponding values for the highest tertile of RC were 1.81 (1.21-2.73, P = 0.0043), 2.76 (1.57-4.86, P = 0.0004), and 1.72 (1.09-2.73, P = 0.0208), respectively. The risks of ischemic events (aHR: 2.80, 95% CI: 1.75-4.49, P < 0.0001), cardiac death (aHR: 4.10, 95% CI: 2.18-7.70, P < 0.0001), and all-cause death (aHR: 3.00, 95% CI, 1.73-5.19, P < 0.0001) were significantly greater in patients with both RIR and RCR (highest hsCRP and RC tertile) than in patients with neither RIR nor RCR (lowest hsCRP and RC tertile). Notably, the RIR and RCR was associated with an increased risk of ischemic events especially in patients with adequate low-density lipoprotein cholesterol (LDL-C) control (LDL-C < 70 mg/dl) (Pinteraction=0.04). Furthermore, the RIR and RCR provide more accurate evaluations of risk in addition to the GRACE score in these patients [areas under the curve (AUC) for ischemic events: 0.64 vs. 0.66, P = 0.003]. CONCLUSION: Among ACS patients receiving contemporary statin treatment who underwent PCI, high risks of both residual inflammation and cholesterol, as assessed by hsCRP and RC, were strongly associated with increased risks of ischemic events, cardiac death, and all-cause death.

Application Effect of Plan-do-check Action Cycle Nursing Protocol on Improving the Accuracy of Urine Specimen Collection in Newborn Female Infants.

Background: The effect of traditional disposable infant urine collectors is not ideal for female newborns. Due to the poor adhesion of the traditional urine collection bag, it does not meet the physiological and anatomical characteristics of female newborns. Therefore, it is necessary to adopt effective nursing in urine specimen collection in newborn female infants. Objective: To explore the effect of plan-do-check action cycle nursing protocol on improving the accuracy of urine specimen collection in newborn female infants. Design: This was a randomized controlled study. Setting: This study was carried out in the Department of Pediatrics, Strategic Support Force Medical Center. Participants: A total of 120 female newborns admitted to our hospital from January 2021 to June 2022 were selected and divided into a control group and a study group, with 60 cases in each group. Interventions: The control group collected urine samples by routine methods, which used the traditional disposable urine bag collection method. The study group collected urine samples using the plan-do-check action cycle nursing mode. Primary Outcome Measures: (1) success rate of urine collection, collection times, and sample contamination rate (2) cleanliness of the vaginal opening (3) satisfaction of urine collection (4) retention time of urine samples and (5) urine pondus hydrogenii values. Results: Compared to the control group, the success rate of urine collection in the study group was higher, the collection times and specimen contamination rate were significantly lower, the time for collecting urine samples in the study group was shorter, the cleanliness of female vaginal opening in the study group was significantly better, the proportion of female urine pondus hydrogenii 6-7 in the study group was significantly higher (all P < .05). Conclusion: The application of the plan-do-check action cycle management mode in the urine samples of newborn female infants can not only effectively improve the success rate of collection but also improve the cleanliness of the vaginal mouth and make the test results more accurate.

Case report: A rare combination of aldosterone-secreting adrenocortical carcinoma and papillary thyroid carcinoma with Graves' disease.

Adrenocortical carcinoma (ACC) is a rare malignancy originating in the adrenal glands, aldosterone-producing ACC, even rarer. Papillary thyroid carcinoma (PTC), by contrast, accounts for the majority of thyroid carcinomas. We herein describe the first reported case of a female with comorbidities of aldosterone-producing ACC, PTC, and Graves' Disease(GD). The patient achieved transient clinical remission following adrenalectomy. However, three months later, aldosterone-producing ACC lung metastases emerged. Subsequently, within another three-month interval, she developed thyroid eye disease(TED). The patient died roughly one year after the adrenal operation. Exome sequencing did not reveal associations between aldosterone-producing ACC, PTC, and GD, and the underlying concurrence mechanism has yet to be elucidated. Further research of similar cases are needed to confirm potential links between the three pathologies.

Molecular data and morphological characters clarify the taxonomic status of Pintara heringi pieridoides (Liu & Gu, 1994) (Hesperiidae, Pyrginae).

We found Albiphasma heringi (Mell, 1922) and A. pieridoides (Liu & Gu, 1994) to be conspecific by the 658 bp COI gene sequences and male genitalia characters. Considering the distinguishable wing patterns and allopatric distribution of the two taxa, we treat pieridoides as a subspecies of heringi. Therefore, the genus Albiphasma Huang, Chiba, Wang and Fan, 2016, which was established for heringi and pieridoides, becomes monotypic, and in light of morphological similarities and close genetic distance between heringi and Pintara bowringi (Joicey & Talbot, 1921), we propose its synonymy with Pintara Evans, 1932. The adults and male genitalia of both P. heringi heringi (Mell, 1922) and P. heringi pieridoides (Liu & Gu, 1994) are illustrated.

A novel fluorescent probe for cascade detection of hydrogen sulfide and hypochlorous acid and its application in bioimaging.

Herein we developed a cascade detection mode for the detection of HS- and ClO- by the novel probe NM-Cl bearing a conjugating naphthalene-dicyanoisophorone unit. The probe displayed sensitive and remarkable fluorescent enhancement in response to HS-, but not to other analytes. The mixture of probe and HS- constructed a specific sensing system for ClO- by fluorescent quenching response. The mechanism studies indicated that the successive reacting of HS- substitution Cl atom in probe and then addition of ClO- facilitation a thiofuran ring-forming induced differentiated fluorescence emission. This study provides a novel mechanism for the detection of HS- and ClO-, the imaging of cell and living animal further indicating the good application prospects of the probe in biosensing and bioimaging.

Differential absorption of cadmium and zinc by tobacco plants: Role of apoplastic pathway.

Cadmium (Cd) contamination presents a significant challenge in global agriculture. This study explores the efficacy of chemical induction, specifically using sodium chloride (NaCl), to limit Cd uptake in tobacco (Nicotiana tabacum) and assesses its impact on essential divalent metal ions (DMIs). We conducted a comprehensive analysis encompassing ion absorption, root histology, and biochemistry to understand the influence of this method. Our results revealed that NaCl induction led to a notable 30 % decrease in Cd absorption, while maintaining minimal impact on zinc (Zn) uptake. Intriguingly, the absence of essential DMIs, such as calcium (Ca), magnesium (Mg), and Zn, was found to diminish the plant's capacity to absorb Cd. Furthermore, moderate NaCl induction resulted in an increased diameter of the root stele and enhanced lignin content, indicating a restriction of Cd absorption through the apoplastic pathway. Conversely, a compensatory absorption mechanism via the symplastic pathway appeared to be activated in the absence of essential elements. These findings highlight the potential of chemical induction as a strategy to mitigate agricultural Cd risks, offering insights into the complex interplay between plant ion transport pathways and metal uptake regulation.

High glucose environment induces NEDD4 deficiency that impairs angiogenesis and diabetic wound healing.

BACKGROUND: Healing of diabetic wounds, characterized by impaired angiogenesis, remains a clinical challenge. E3 ligase have been identified as potential therapeutic targets of wound healing. OBJECTIVE: We assessed the role of E3 ligase NEDD4 in the context of angiogenesis and diabetic wound healing. METHODS: The mRNA expression levels of NEDD4, TSP1 and VEGF were determined by real-time PCR. Western blotting was used to evaluate the protein expression of NEDD4, TSP1 and VEGF. The ubiquitination of TSP1 was evaluated by immunoprecipitation. MTT assay, wound healing assay and tube formation assay were performed to assess the proliferation, migration and angiogenic functions of endothelial cells. The epigenetic modification in the promoter of NEDD4 was confirmed using BSP assay and ChIP-qPCR assay. The role of NEDD4 in wound healing was further verified in diabetic mouse model. RESULTS: NEDD4 promotes proliferation, migration and tube formation of endothelial cells. It binds to and ubiquitinates TSP1, which lead to TSP1 degradation and thus increased VEGF expression. The inhibitory effect of NEDD4 silencing on the angiogenesis ability of endothelial cells can be restored by TSP1 knockdown. NEDD4 is reduced in diabetic patients, which may due to hypermethylation of NEDD4 promoter mediated via DNMT1 under high glucose condition. Furthermore, inhibition of NEDD4 represses wound healing in diabetic mouse model. CONCLUSION: NEDD4 might promote angiogenesis and wound healing by inhibiting TSP1 via ubiquitination in diabetic patients.

Dual-layer spectral computed tomography aortography using a seventy-five-percent-reduced iodine dose protocol and multiparameter spectral imaging: comparison with conventional computed tomography imaging.

Background: Computed tomography angiography (CTA) is the recommended diagnostic and follow-up imaging modality for acute aortic dissection (AD). However, the high-contrast medium burden associated with repeated CT aortography follow-ups remains a significant concern. This prospective study aimed to assess whether an ultra-low contrast dose (75% cutoff) aortic CTA protocol on dual-layer spectral CT could achieve comparable image quality with the full dose protocol. We also investigated the image quality of the virtual noncontrast (VNC) images derived from the ultra-low dose protocol. Methods: This study included 37 consecutive patients who were referred to aortic CTA from May 2022 to August 2022. The enrolled patients underwent full-dose contrast CTA and ultra-low dose (reduced to 25% of conventional) contrast CTA on dual-layer spectral CT in 1 day. Virtual monochromatic images (VMIs) were reconstructed with 40 and 70 keV. The VNC images were reconstructed for both protocols. Objective image quality evaluation, recorded as signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs), was compared between the groups using 1-way analysis of variance and post hoc analysis with Bonferroni correction. Subjective image quality was also compared between the groups. Finally, VNC images derived from the low-dose (VNClow) and full-dose (VNCfull) protocols were compared to the true noncontrast (TNC) images. Results: Neither CNR nor SNR was lower for the 40-keV images reconstructed from the ultra-low dose group compared to the conventional images. Both were significantly higher than those of the 70-keV images. Regarding subjective image quality, vessel enhancement was not significantly different between the 40-keV VMI and full-dose images [ascending aorta (AAO): 4.37±0.46 vs. 4.57±0.48, P=0.096; brachiocephalic arteries: 4.34±0.45 vs. 4.51±0.49, P=0.152; abdominal aortic side branch: 4.42±0.48 vs. 4.51±0.49, P=0.480]. The VNClow images were similar to the TNC images but significantly different from the VNCfull images (P<0.001). Conclusions: Ultra-low contrast aortic CTA with a 75%-reduced iodine dose using dual-layer spectral CT and the derived VNC achieved image quality comparable to that of conventional CTA and TNC images.

One-year clinical outcomes of bivalirudin versus unfractionated heparin in patients with type 2 diabetes undergoing elective percutaneous coronary intervention.

BACKGROUND: Patients with diabetes and coronary artery disease have a higher risk of bleeding and thrombotic events. However, data on the safety and efficacy of bivalirudin in these patients undergoing elective percutaneous coronary intervention (PCI) are lacking. METHODS: 1152 patients undergoing elective PCI anticoagulated with bivalirudin and 10,250 patients anticoagulated with unfractionated heparin (UFH) (with or without glycoprotein IIb/IIIa inhibitors [GPI]) were performed propensity-score matching method. The thrombotic endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). The bleeding endpoint was according to the Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding. RESULTS: Finally, 376 (bivalirudin group) and 878 (UFH group) patients with type 2 diabetes (T2D) were enrolled. After one-year follow-up, there were 130 (10.4%) MACCE and 27 (2.2%) bleeding events occurred. Multivariate COX regression analysis showed no significant difference for MACCE between bivalirudin group and UFH group (P > 0.05). Further analysis showed that there was a reduction in the risk of myocardial infarction (MI) between two groups (Hazard ratio [HR] = 0.199, 95% confidence interval [CI]: 0.047-0.845, P = 0.029), but not in the risk of death, revascularization, stent thrombosis or stroke (all P > 0.05). As for BARC 2, 3 or 5 bleeding, no significant difference was found between two groups (P > 0.05). CONCLUSIONS: Although diabetes is considered a high-risk factor for poor prognosis, compared with UFH (with or without GPI), bivalirudin did not increase the risk of MACCE and even decreased the risk of MI in patients with T2D undergoing elective PCI, while the risk of bleeding was similar between two groups.

Contemporary Use of Ticagrelor vs Clopidogrel in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A GRACE Risk Score Stratification-Based Analysis in a Large-Scale, Real-World Study From China.

OBJECTIVE: To evaluate potential gains in outcomes from ticagrelor-based strategy according to risk stratification by Global Registry of Acute Coronary Events (GRACE) score. METHODS: A total of 19,704 patients discharged alive post-acute coronary syndrome who underwent percutaneous coronary intervention and received ticagrelor or clopidogrel between March 2016 and March 2019 were included in the study. The primary endpoint was ischemic events at 12 months, composed of cardiac death, myocardial infarction, and/or stroke. Secondary outcomes included all-cause mortality and Bleeding Academic Research Consortium type 2 to 5 and 3 to 5 bleeding. RESULTS: The ticagrelor group comprised 6432 (32.6%) patients and the clopidogrel group comprised 13,272 (67.4%) patients. During the follow-up period, there was a significant reduction in the incidence of ischemic events in patients treated using ticagrelor who had excessive risk of bleeding. According to the GRACE score, among low-risk patients, ticagrelor use compared with clopidogrel was not associated with decreased ischemic events (HR, 0.82; 95% CI, 0.57 to 1.17; P=.27) with excessive risk of Bleeding Academic Research Consortium type 3 to 5 bleeding (HR, 1.59; 95% CI, 1.16 to 2.17; P=.004). The risk of ischemic events (HR, 0.60; 95% CI, 0.41 to 0.89; P=.01) were lower in the intermediate- to high-risk patients treated with ticagrelor without significant difference in BARC type 3 to 5 bleeding risk (HR, 1.11; 95% CI, 0.75 to 1.65; P=.61). CONCLUSION: There was still a gap between guideline-indicated therapy and the clinical practice in a sizable subset of patients with acute coronary syndrome who underwent percutaneous coronary intervention. The GRACE risk score could identify patients who would derive benefit from the ticagrelor-based antiplatelet strategy.

The Value of the Apolipoprotein B/Apolipoprotein A1 Ratio in Predicting the Rapid Progression of Non-Culprit Coronary Lesions in Acute Coronary Syndrome in Patients with Diabetes Mellitus after Percutaneous Coronary Intervention.

This study aims to assess the predictive value of the apolipoprotein B (ApoB) /apolipoprotein A1 (ApoA1) ratio in acute coronary syndrome (ACS) in patients with diabetes mellitus (DM) for the rapid progression (RP) of non-culprit coronary lesions (NCCLs) after percutaneous coronary intervention (PCI) and observe the effect of the ApoB/ApoA1 ratio on major adverse cardiac events (MACE).A total of 175 patients with DM presenting with ACS who received a PCI and an average 13-month follow-up coronary angiography (CAG) were enrolled from January 2015 to December 2020. According to the CAG, the patients were divided into the RP group and the non-RP group. MACE was defined as a composite of death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization from unstable or progressive angina at the end of a 24-month follow-up.The low-density lipoprotein cholesterol (LDL-C), ApoB, ApoB/ApoA1 ratio, and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio levels at baseline were significantly higher in the RP group than in the non-RP group. The ApoA1 level at baseline in the non-RP group was significantly higher than in the RP group. The predictive significance of the ApoB/ApoA1 ratio (area under the curve (AUC) = 0.712) for the RP of NCCLs was significantly higher than those of ApoA1, ApoB, LDL-C/HDL-C ratio (AUC = 0.628, AUC = 0.640, and AUC = 0.620, respectively). A higher ApoB/ApoA1 ratio and the RP of NCCLs were significantly associated with the occurrence of MACE.The ApoB/ApoA1 ratio was an effective clinical indicator for the RP of NCCLs after PCI in patients with DM presenting with ACS. The high ApoB/ApoA1 ratio and the RP of NCCLs were two risks for MACE.

Multi-omics analyses reveal relationships among polyphenol-rich oolong tea consumption, gut microbiota, and metabolic profile: A pilot study.

Convincing evidence has suggested the health potentials of oolong tea (OT) on gut microbiota homeostasis; however, limited population-based studies exist regarding the effect of OT consumption on human gut microbial and metabolic profile. This pilot study explored gut microbial and metabolic changes in healthy adults with a 3-week oolong tea intake. Our findings showed that OT treatment significantly altered gut microbial diversity (Shannon index, 5.4±0.1 vs. 5.7±0.1 pre- and post-OT treatment), reorganized gut microbiota composition, enriched Bacteroides and Prevotella, decreased Megamonas, and improved gastrointestinal function. Also, gut microbes from overweight subjects with BMI >23.9 exhibited greater responses to OT treatment compared with normal-weight counterparts. Metabolomic analysis identified OT intake-induced 23 differential metabolites and 10 enriched metabolic pathways. This study may provide new insights into the association among OT intervention, host gut microbiome and metabolic profile, and improve the knowledge of clinical strategies and personalized nutrition.

Duplicated adrenal veins in primary aldosteronism misdiagnosed with ectopic aldosteronoma due to apparent bilateral aldosterone suppression.

BACKGROUND: Primary aldosteronism (PA) is considered the number one aetiology for secondary hypertension. Apart from confirmatory tests and localisation of PA determined by computed tomography (CT), adrenal venous sampling (AVS) is used to define whether aldosterone hypersecretion occurs inside one or both adrenal glands. However, even correctly-performed AVS may lead to undiagnostic results such as apparent bilateral adrenal suppression (apparent bilateral aldosterone suppression), in which the adrenal aldosterone-to-cortisol ratios (AC ratios) are decreased bilaterally compared to the peripheral blood sample, with several causes contributing to it. CASE DESCRIPTION: Here, we describe the case of a 48-year-old man who was referred to our department for further investigation with a history of refractory hypertension, hypokalaemia, and aortic dissection. His hypertension and hypokalaemia were initially attributed to ectopic aldosteronoma due to his adrenal CT scan and AVS results. However, the correct diagnosis of an adenoma with duplicated right adrenal veins (duplicated adrenal veins) due to apparent bilateral aldosterone suppression was confirmed during surgery. CONCLUSION: AVS is the gold standard accepted for PA subtyping, but sometimes when apparent bilateral aldosterone suppression is present, it can give ambiguous results. Duplicated right adrenal veins, may impact results, thus, AVS may not accurately provide evidence of unilateral hypersecretion for all PA patients. Repeat AVS or adrenal surgery can provide worthwhile diagnostic conclusions.

The recognition and diagnosis of primary aldosteronism (PA) have increased in recent years and clinicians usually require adrenal venous sampling (AVS) to identify the affected side, and it's crucial for further treatments of PA patients (surgery or medicine).We presented an example of unilateral aldosteronoma with duplicated adrenal veins whose AVS results suggested apparent bilateral aldosterone suppression (the adrenal venous aldosterone/cortisol ratios are bilaterally lower than the peripheral ratios). He was misdiagnosed with ectopic aldosteronoma due to computed tomography (CT) features, but surgery findings revealed duplicated adrenal veins.Unclear AVS results such as apparent bilateral aldosterone suppression can lead to a missed diagnosis of unilateral PA, preventing patients from receiving potentially curative adrenal resection.Our case can serve as an example for clinicians that encounter the same condition to provide further investigational clues to ensure the correct aetiological diagnosis for patients with PA.

Non-invasive auditory and visual stimulation attenuates α-Synuclein deposition and improves motor and non-motor symptoms in PD mice.

Parkinson's disease (PD) is characterized by dopaminergic neuron loss and α-synuclein (α-Syn) aggregates, but lacks effective treatments for the disease progression and non-motor symptoms. Recently, combined 40 Hz auditory and visual stimulation is emerging as a promising non-invasive method to decrease amyloid and improve cognition in Alzheimer's disease (AD), but whether this treatment can modify α-Syn-induced PD pathology remains unclear. Here we evaluated the effects of chronic exposure to 40 Hz and 80 Hz auditory and visual stimulation on α-Syn accumulation and the functional effects of 40 Hz stimulation on motor, cognitive and mood dysfunctions in PD mice. We found that 40 Hz and 80 Hz auditory and visual stimulation activated multiple cortical regions, entrained gamma oscillations and markedly attenuated p-α-Syn deposition in neurons, but not astrocytes, microglial cells in the primary and secondary motor cortex (M1, M2), medial prefrontal cortex (mPFC) and the striatum. Moreover, 40 Hz stimulation significantly reduced cell apoptosis in M1, increased the neuromuscular strength selectively in PD mice, which correlated with p-α-Syn reduction in the motor cortex. In addition, 40 Hz stimulation improved spatial working memory and decreased depressive-like behaviors specifically in PD mice, which correlated with p-α-Syn reduction in mPFC, but promoted anxiety-like behaviors and increased stress-related adreno-cortico-tropic-hormone (ACTH), corticosterone levels in the plasma of normal mice. Collectively, we demonstrated that chronic multisensory gamma stimulation (40 Hz and 80 Hz) significantly attenuates α-Syn deposition in neurons of the interconnected cortex and 40 Hz stimulation improved neuromuscular strength, spatial working memory, and reduced depressive behaviors, which support its non-invasive therapeutic potential for modifying PD progression and treating non-motor symptoms.

Periostin Acts as a Bridge between Gestational Diabetes Mellitus (GDM) and Chronic Inflammation to Modulate Insulin Resistance by Modulating PPARα/NF-κB/TNF-α Signaling Pathway.

INTRODUCTION: Gestational diabetes mellitus (GDM) is considered an imbalance of glucose metabolism and insulin resistance during pregnancy. AIMS/OBJECTIVE: To evaluate the levels of periostin (POSTN) in patients with GDM and investigate the association between POSTN and GDM. MATERIALS AND METHODS: A total of 30 pregnant women (NC group) and 30 pregnant women with GDM (GDM group) were involved. The GDM mouse model was established by intraperitoneally injecting streptozotocin. The oral glucose tolerance test (OGTT), insulin, and insulin resistance indices were tested. An immunohistochemical and Western blot assay was conducted to determine the expression of POSTN, PPARα, TNF-α, and NF-κB. HE staining was performed to evaluate inflammation in the placental tissues of women with GDM and GDM mice. POSTN-siRNA was transfected into glucose-pretreated HTR8 cells, and pAdEasy-m-POSTN shRNA was infected in GDM mice. The RT-PCR assay determined the gene transcription of POSTN, TNF-α, NF-κB, and PPARα. RESULTS: Pregnantwomen in theGDMgroup demonstrated significantly higherOGTT (p < 0.05), insulin levels (p < 0.05) and insulin resistance (p < 0.05) compared to those of the NC group. The serum levels of POSTN in pregnantwomen of theGDMgroup were significantly higher than that of theNC group (p < 0.05). The obvious inflammation was activated in pregnant women in the GDMgroup. POSTN-siRNAsignificantly enhanced the cell viability of glucose-treated HTR8 cells compared to that without glucose treatment (p < 0.05). POSTNsiRNA (pAdEasy-m-POSTN shRNA) markedly reduced the glucose level of glucose-treated HTR8 cells (GDM mice) compared to that without treatment (p < 0.05). POSTN-siRNA (pAdEasy-m-POSTN shRNA) promoted PPARα gene transcription (p < 0.05) and inhibited NF-κB/TNF-α gene transcription (p < 0.05) in glucose-treated HTR8 cells (GDMmice) compared to thosewithout treatment. POSTN-siRNAmodulated NF- κB/TNF-α pathway mediated inflammation by regulating PPARα in HTR8 cells and GDMmice. PPARα participated in POSTN-associated inflammation. pAdEasy-m-POSTN shRNA inhibited T-CHO/TG levels in GDM mice compared to those without treatment (p < 0.05). All the effects of POSTN-siRNA (pAdEasy-m- POSTN shRNA) were obviously blocked by PPARα inhibitor treatment. CONCLUSION: POSTN levels were significantly higher in pregnant women with GDM and were associated with chronic inflammation and PPARα expression. POSTN may act as a bridge between GDM and chronic inflammation to modulate insulin resistance by modulating PPARα/NF-κB/TNF-α signaling pathway.

Comparing cadmium uptake kinetics, xylem translocation, chemical forms, and subcellular distribution of two tobacco (Nicotiana tabacum L.) cultivars.

Tobacco (Nicotiana tabacum L.) is a potential phytoremediator that can reduce soil cadmium (Cd) contamination. Pot and hydroponic experiments were conducted to investigate the difference in absorption kinetics, translocation patterns, accumulation capacity, and extraction amounts between two leading tobacco cultivars in China. We studied the chemical forms and subcellular distribution of Cd in the plants to understand the diversity of the detoxification mechanism of the cultivars. The concentration-dependent kinetics of Cd accumulation in leaves, stems, roots, and xylem sap for cultivars Zhongyan 100 (ZY100) and K326, fitted well with the Michaelis-Menten equation. K326 exhibited high biomass, Cd tolerance, Cd translocation, and phytoextraction abilities. The acetic acid, sodium chloride, and water-extractable fractions accounted for > 90% of Cd in all ZY100 tissues but only in K326 roots and stems. Moreover, the acetic acid and NaCl fractions were the predominant storage forms, while the water fraction was the transport form. The ethanol fraction also contributed significantly to Cd storage in K326 leaves. As the Cd treatment increased, more NaCl and water fractions were found in K326 leaves, while only NaCl fractions increased in ZY100 leaves. For subcellular distribution, > 93% Cd proportions were primarily stored in both cultivars' soluble or cell wall fraction. The proportion of Cd in the cell wall fraction of ZY100 roots was less than that of K326, while that proportion in the soluble fraction in ZY100 leaves was higher than in K326 leaves. These findings demonstrate that Cd accumulation patterns, detoxification, and storage strategies differ between the cultivars, providing a deeper understanding of Cd tolerance and accumulation mechanism in tobacco plants. It also guides the screening of germplasm resources or gene modification to improve the Cd phytoextraction efficiency of tobacco.

Corrigendum: Untargeted metabolomics identified kynurenine as a predictive prognostic biomarker in acute myocardial infarction.

[This corrects the article DOI: 10.3389/fimmu.2022.950441.].