Proteomic change in the upper lobe of the left lung of Beagle dogs at the lung migration stage of Toxocara canis infection.

BACKGROUND: Toxocara canis is considered one of the most neglected parasitic zoonoses and threatens the health of millions of people worldwide with a predilection for pediatric and adolescent populations in impoverished communities. Exploring the invasion and developmental mechanisms associated with T. canis infection in its definitive canine hosts will help to better control zoonotic toxocariasis. METHODS: Proteomic changes in samples from the upper lobe of the left lung of Beagle puppies were systematically analyzed by quantitative proteomic technology of data-independent acquisition (DIA) at 96 h post-infection (hpi) with T. canis. Proteins with P-values < 0.05 and fold change > 1.5 or < 0.67 were considered proteins with differential abundance (PDAs). RESULTS: A total of 28 downregulated PDAs and 407 upregulated PDAs were identified at 96 hpi, including RhoC, TM4SFs and LPCAT1, which could be associated with the maintenance and repair of lung homeostasis. GO annotation and KEGG pathway enrichment analyses of all identified proteins and PDAs revealed that many lung proteins have correlation to signal transduction, lipid metabolism and immune system. CONCLUSIONS: The present study revealed lung proteomic alterations in Beagle dogs at the lung migration stage of T. canis infection and identified many PDAs of Beagle dog lung, which may play important roles in the pathogenesis of toxocariasis, warranting further experimental validation.

The Toxoplasma monocarboxylate transporters are involved in the metabolism within the apicoplast and are linked to parasite survival.

The apicoplast is a four-membrane plastid found in the apicomplexans, which harbors biosynthesis and organelle housekeeping activities in the matrix. However, the mechanism driving the flux of metabolites, in and out, remains unknown. Here, we used TurboID and genome engineering to identify apicoplast transporters in Toxoplasma gondii. Among the many novel transporters, we show that one pair of apicomplexan monocarboxylate transporters (AMTs) appears to have evolved from a putative host cell that engulfed a red alga. Protein depletion showed that AMT1 and AMT2 are critical for parasite growth. Metabolite analyses supported the notion that AMT1 and AMT2 are associated with biosynthesis of isoprenoids and fatty acids. However, stronger phenotypic defects were observed for AMT2, including in the inability to establish T. gondii parasite virulence in mice. This study clarifies, significantly, the mystery of apicoplast transporter composition and reveals the importance of the pair of AMTs in maintaining the apicoplast activity in apicomplexans.

The MQRG score: a novel prognostic tool for adrenocortical carcinoma patients based on mitochondrial quality.

Objectives: Adrenal tumors are common, but adrenocortical carcinomas (ACCs) are a rare and challenging form of cancer to diagnose and manage.This study aimed to explore the critical role of mitochondrial quality in maintaining cellular function and the implications of the abnormal expression of mitochondrial metabolism-related proteins observed in ACC patients. We focused on identifying the connection between mitochondrial quality and the development of ACC at molecular and genomic levels. Methods: We compared mitochondrial quality-related genes (MQRGs) across ACC subtypes using overall survival (OS) and disease-free survival (DFS) as evaluation indicators. Furthermore, a novel MQRG score was developed to predict clinical prognosis and guide immunotherapy responses accurately. Results: The majority of MQRGs were upregulated in the ACC samples, correlating to poor prognosis. The MQRG score was confirmed as an independent prognostic factor for ACC, with the high-risk MQRG score group showing a significantly shorter overall survival period. Conclusions: Multilayer alterations in MQRGs are associated with patient prognosis and immune cell infiltration characteristics. This comprehensive analysis of MQRGs can contribute to a deeper understanding of potential differences in ACC patients' tumor microenvironment. This can influence clinical decision-making and advanced prognosis prediction, thereby offering new insights into personalized treatments in ACC.

Expression profiles of host miRNAs and circRNAs and ceRNA network during Toxoplasma gondii lytic cycle.

Toxoplasma gondii is an opportunistic protozoan parasite that is highly prevalent in the human population and can lead to adverse health consequences in immunocompromised patients and pregnant women. Noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), play important regulatory roles in the pathogenesis of many infections. However, the differentially expressed (DE) miRNAs and circRNAs implicated in the host cell response during the lytic cycle of T. gondii are unknown. In this study, we profiled the expression of miRNAs and circRNAs in human foreskin fibroblasts (HFFs) at different time points after T. gondii infection using RNA sequencing (RNA-seq). We identified a total of 7, 7, 27, 45, 70, 148, 203, and 217 DEmiRNAs and 276, 355, 782, 1863, 1738, 6336, 1229, and 1680 DEcircRNAs at 1.5, 3, 6, 9, 12, 24, 36, and 48 h post infection (hpi), respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the DE transcripts were enriched in immune response, apoptosis, signal transduction, and metabolism-related pathways. These findings provide new insight into the involvement of miRNAs and circRNAs in the host response to T. gondii infection.

LncRNA CHROMR/miR-27b-3p/MET axis promotes the proliferation, invasion, and contributes to rituximab resistance in diffuse large B-cell lymphoma.

Long non-coding RNAs (LncRNAs) could regulate chemoresistance through sponging microRNAs (miRNAs) and sequestering RNA binding proteins. However, the mechanism of lncRNAs in rituximab resistance in diffuse large B-cell lymphoma (DLBCL) is largely unknown. Here, we investigated the functions and molecular mechanisms of lncRNA CHROMR in DLBCL tumorigenesis and chemoresistance. LncRNA CHROMR is highly expressed in DLBCL tissues and cells. We examined the oncogenic functions of lncRNA CHROMR in DLBCL by a panel of gain-or-loss-of-function assays and in vitro experiments. LncRNA CHROMR suppression promotes CD20 transcription in DLBCL cells and inhibits rituximab resistance. RNA immunoprecipitation, RNA pull-down, and dual luciferase reporter assay reveal that lncRNA CHROMR sponges with miR-27b-3p to regulate mesenchymal-epithelial transition factor (MET) levels and Akt signaling in DLBCL cells. Targeting the lncRNA CHROMR/miR-27b-3p/MET axis reduces DLBCL tumorigenesis. Altogether, these findings provide a new regulatory model, lncRNA CHROMR/miR-27b-3p/MET, which can serve as a potential therapeutic target for DLBCL.

Dynamic Dysregulation of the Triple Network of the Brain in Mild Traumatic Brain Injury and Its Relationship With Cognitive Performance.

A triple network model consisting of a default network, a salience network, and a central executive network has recently been used to understand connectivity patterns in cognitively normal versus dysfunctional brains. This study aimed to explore changes in the dynamic connectivity of triplet network in mild traumatic brain injury (mTBI) and its relationship to cognitive performance. In this work, we acquired resting-state functional magnetic resonance imaging (fMRI) data from 30 mTBI patients and 30 healthy controls (HCs). Independent component analysis, sliding time window correlation, and k-means clustering were applied to resting-state fMRI data. Further, we analyzed the relationship between changes in dynamic functional connectivity (FC) parameters and clinical variables in mTBI patients. The results showed that the dynamic functional connectivity of the brain triple network was clustered into five states. Compared with HC, mTBI patients spent longer in state 1, which is characterized by weakened dorsal default mode network (DMN) and anterior salience network (SN) connectivity, and state 3, which is characterized by a positive correlation between DMN and SN internal connectivity. Mild TBI patients had fewer metastases in different states than HC patients. In addition, the mean residence time in state 1 correlated with Montreal Cognitive Assessment scores in mTBI patients; the number of transitions between states correlated with Glasgow Coma Score in mTBI patients. Taken together, our findings suggest that the dynamic properties of FC in the triple network of mTBI patients are abnormal, and provide a new perspective on the pathophysiological mechanism of cognitive impairment from the perspective of dynamic FC.

Prevalence and Genetic Characterization of Blastocystis in Sheep and Pigs in Shanxi Province, North China: From a Public Health Perspective.

Blastocystis is a common zoonotic intestinal protozoan and causes a series of gastrointestinal symptoms in humans and animals via the fecal-oral route, causing economic losses and posing public health problems. At present, the prevalence and genetic structure of Blastocystis in sheep and pigs in Shanxi province remains unknown. Thus, the present study collected 492 sheep fecal samples and 362 pig fecal samples from three representative counties in northern, central and southern Shanxi province for the detection of Blastocystis based on its SSU rRNA gene. The results showed that the overall prevalence of Blastocystis in the examined sheep and pigs were 16.26% and 14.09%, respectively. Sequences analyses showed that four known subtypes (ST5, ST10, ST14 and ST30) in sheep and two subtypes (ST1 and ST5) in pigs were detected in this study, with ST5 being the predominate subtype among the study areas. Phylogenetic analysis showed that the same subtypes were clustered into the same branch. This study reveals that sheep and pigs in Shanxi province are hosts for multiple Blastocystis subtypes, including the zoonotic subtypes (ST1 and ST5), posing a risk to public health. Baseline epidemiological data are provided that help in improving our understanding of the role of zoonotic subtypes in Blastocystis transmission.

Molecular Identification and Genotyping of Cryptosporidium spp. and Blastocystis sp. in Cattle in Representative Areas of Shanxi Province, North China.

Both Cryptosporidium spp. and Blastocystis sp. are common intestinal protozoa, which can cause zoonotic diseases and economic losses to livestock industry. To evaluate the prevalence and genetic population structure of Cryptosporidium spp. and Blastocystis sp. in beef and dairy cattle in Shanxi Province, north China, a total of 795 fecal samples were collected from beef and dairy cattle in three representative counties in Shanxi Province, and these fecal samples were examined using molecular approaches based on 18S small-subunit ribosomal RNA (SSU rRNA) of Cryptosporidium spp. and Blastocystis sp., respectively. Among 795 cattle fecal samples, 23 were detected as Cryptosporidium-positive and 103 were detected as Blastocystis-positive, and the overall prevalence of Cryptosporidium spp. and Blastocystis sp. in cattle in Shanxi Province was 2.9% and 13.0%, respectively. For Cryptosporidium spp., DNA sequence analysis indicated that all 23 positive samples were identified as C. andersoni. Furthermore, five known subtypes (ST1, ST10, ST14, ST21 and ST26) and three unknown subtypes of Blastocystis sp. were detected among 103 positive samples using DNA sequence analysis. This study reported the occurrence and prevalence of Cryptosporidium spp. and Blastocystis sp. in cattle in Shanxi Province for the first time, which extends the geographical distribution of these two zoonotic parasites and provides baseline data for the prevention and control of these two important zoonotic parasites in cattle in Shanxi Province.

Effects of physical activity combined with different visual target presentation durations of ciliary-muscle training on visual acuity in children.

Purpose: This study aimed to identify the effect of different durations of visual target presentation during ciliary-muscle training on children's kinetic visual acuity (KVA), uncorrected distance visual acuity (UDVA), axial length, and accommodative facility. Methods: Based on the ciliary-muscle regulation mechanism, an intervention program involving ciliary-muscle training with different durations of visual target presentation combined with physical education classes was designed. The intervention aimed to determine the effect of different ciliary-muscle training durations on children's visual acuity. A total of 153 children aged 10-11 years from a school in Suzhou (a major city located in southeastern Jiangsu Province, East China) were enrolled as participants in this 32-week intervention study. This study measured the participants' UDVA and KVA before, during (after the 16th week), and after (after the 32nd week) the experimental intervention. The accommodative facility was measured during and after the intervention. Results: After 32 weeks of the intervention, the KVA and UDVA of each experimental group were significantly improved (p < 0.05). A high percentage in the improvement of KVA was observed in the 3-s and 1-s groups (25.53%, 21.74%), and the highest percentage in the improvement of UDVA was observed in the 3-s group (2.96%). Axial length increased significantly in all groups (p < 0.05), and there was a low percentage increase in the 1-s and 3-s groups (0.82%). The accommodative facility was significantly improved in all experimental groups, with a higher improvement percentage in the 3-s and 1-s groups (3.01% and 2.61%, respectively). After dividing the children in each group according to their visual acuity, the KVA of children in the 1-s group was significantly improved, the UDVA of children with myopia was significantly increased, and the accommodative facility of children with mild and moderate myopia was significantly improved. Moreover, the KVA, UDVA, and accommodative facility of children with mild and moderate myopia in the 3-s group were significantly improved. The KVA of children with emmetropia and the accommodative facility of children with mild and moderate myopia in the 5-s group were also significantly increased. Conclusion: In school physical education classes, the 1-s, 3-s, and 5-s ciliary-muscle regulating exercise could effectively improve the kinetic visual acuity, uncorrected distance visual acuity, and accommodative facility of children aged 10-11 years. Among them, the effects of the 1-s and 3-s durations are better than that of the 5-s duration, as it can reduce the growth rate of axial length and achieve better effects among children with mild and moderate myopia.

Seroprevalence of Toxoplasma gondii infection in sheep and cattle in Shanxi Province, North China.

Toxoplasmosis is a worldwide zoonotic disease caused by infection with the intracellular protozoan parasite Toxoplasma gondii, posing significant economic losses to the livestock industry. As a major livestock province, little is known of the prevalence of T. gondii infection in sheep and cattle in Shanxi Province, North China. In this study, a total of 1962 blood samples from cattle (n = 978) and sheep (n = 984), collected from 11 administrative cities in Shanxi Province, were examined for antibodies against T. gondii by using the indirect enzyme linked immunosorbent assay (ELISA) kits commercially available. The results showed that antibodies to T. gondii were detected in 306 of the 978 cattle serum samples (31.29%, 95% CI 28.38-34.19), ranging from 12.64% to 60.00% among the different cities. The overall seroprevalence of T. gondii in sheep was 17.78% (175/984, 95% CI 15.40-20.17), ranging from 2.22% to 41.11% among the different administrative cities. The T. gondii seroprevalence was associated with the management mode and geographical location. This is the first report of T. gondii seroprevalence in cattle and sheep in Shanxi Province, North China, which provides baseline data to plan future control strategies for T. gondii infection in this province.

Hsa_circ_0057105 modulates a balance of epithelial-mesenchymal transition and ferroptosis vulnerability in renal cell carcinoma.

BACKGROUND: The incidence of renal cell carcinoma (RCC) has increased in recent years. Metastatic RCC is common and remains a major cause of mortality. A regulatory role for circular RNAs (circRNAs) in the occurrence and progression of RCC has been identified, but their function, molecular mechanisms, and potential clinical applications remain poorly understood. METHODS: High-throughput RNA sequencing was used to explore the differential expression of circRNAs and their related pathways in RCC patients. Transwell and CCK-8 assays were used to assess the function of hsa_circ_0057105 in RCC cells. The clinical relevance of hsa_circ_0057105 was evaluated in a cohort of RCC patients. The hsa_circ_0057105 regulatory axis was defined using RNA pull-down, luciferase reporter assays, and fluorescence in situ hybridization assays, and the in vivo effect of hsa_circ_0057105 was validated using animal experiments. RESULTS: Single-sample gene set enrichment analysis and correlation analysis of RNA-seq data showed that hsa_circ_0057105 was potentially oncogenic and may serve to regulate epithelial-mesenchymal transition (EMT) activation in RCC. Hsa_circ_0057105 expression was associated with advanced TNM stages and was an independent prognostic factor for poor RCC patient survival. Phenotypic studies show that hsa_circ_0057105 can enhance the migration and invasion abilities of RCC cells. Further, hsa_circ_0057105 was shown to inhibit the expression of miR-577, a miRNA that regulated the expression of both COL1A1, which induced EMT activation, and VDAC2, which modulated ferroptosis sensitivity. The dual regulatory roles of hsa_circ_0057105 on EMT and ferroptosis sensitivity were verified using rescue experiments. Animal studies confirmed that hsa_circ_0057105 increased the metastatic ability and ferroptosis sensitivity of RCC cells in vivo. CONCLUSIONS: In RCC, hsa_circ_0057105 regulates COL1A1 and VDAC2 expression through its sponge effect on miR-577, acting like a 'double-edged sword'. These findings provide new insight into the relationship between EMT and ferroptosis in RCC and provide potential biomarkers for RCC surveillance and treatment.

A method to protect the endometrium for microwave ablation treating types 1-3 uterine fibroids: a preliminary comparative study.

PURPOSE: To investigate the feasibility of percutaneous intrauterine instillation of chilled saline to protect the endometrium during microwave ablation (MWA) treating types 1-3 uterine fibroids. MATERIALS AND METHODS: Twenty-six patients with types 1-3 uterine fibroids were prospectively enrolled in an intrauterine saline instillation group (study group). The same number of patients with types 1-3 uterine fibroids who previously received MWA without endometrial protection were retrospectively included in a control group. Endometrial impairment was evaluated by hysteroscopy and magnetic resonance imaging (MRI). RESULTS: In the study group, hysteroscopy revealed an intact endometrium in 17 patients, congestion and reddening of the endometrium due to heat in 8 patients, and a burnt necrosis with a size < 1 cm on the functional layer of the endometrium in 1 patient. On MRI, in the study group, there were 17 (65.4%), 6 (23.1%), and 3 (11.5%) patients with grades 0, 1, and 2 endometrial impairment, respectively, but no grade 3 endometrial impairment. In the control group, there were 8 (30.8%), 8 (30.8%), 7 (26.9%), and 3 (11.5%) patients with grades 0, 1, 2, and 3 endometrial impairment, respectively. Endometrial impairment in the study group was significantly better than that in the control group (p = 0.006). One patient had puncture tunnel bleeding and no other complications occurred in the study group. CONCLUSION: Intraoperative percutaneous intrauterine instillation of chilled saline may be effective and safe in reducing the thermal damage to the endometrium caused by MWA for treating types 1-3 uterine fibroids.

Itaconate: A Potent Macrophage Immunomodulator.

With advances in immunometabolic studies, more and more evidence has shown that metabolic changes profoundly affect the immune function of macrophages. The tricarboxylic acid cycle is a central metabolic pathway of cells. Itaconate, a byproduct of the tricarboxylic acid cycle, is an emerging metabolic small molecule that regulates macrophage inflammation and has received much attention for its potent anti-inflammatory effects in recent years. Itaconate regulates macrophage function through multiple mechanisms and has demonstrated promising therapeutic potential in a variety of immune and inflammatory diseases. New progress in the mechanism of itaconate continues to be made, but it also implies complexity in its action and a need for a more comprehensive understanding of its role in macrophages. In this article, we review the primary mechanisms and current research progress of itaconate in regulating macrophage immune metabolism, hoping to provide new insights and directions for future research and disease treatment.

High triglyceride glucose-body mass index correlates with prehypertension and hypertension in east Asian populations: A population-based retrospective study.

Background: There is compelling evidence for an association between triglyceride glucose-body mass index (TyG-BMI) and cardiovascular disease (CVD). However, data on the relationship between TyG-BMI and prehypertension (pre-HTN) or hypertension (HTN) remains scant. The aim of this study was to characterize the association between TyG-BMI and pre-HTN or HTN risk, and to assess the ability of TyG-BMI in predicting pre-HTN and HTN in Chinese and Japanese populations. Methods: A total of 214,493 participants were included in this study. The participants were divided into 5 groups based on quintiles of TyG-BMI index at baseline (Q1, Q2, Q3 Q4 and Q5). Logistic regression analysis was then employed to assess the relationship between TyG-BMI quintiles and pre-HTN or HTN. Results were presented as odds ratios (ORs) and 95% confidence intervals (CIs). Results: Our restricted cubic spline analysis showed that TyG-BMI was linearly correlated with both pre-HTN and HTN. Multivariate logistic regression analysis indicated that TyG-BMI was independently correlated with pre-HTN [ORs and 95% CIs were 1.011 (1.011-1.012), 1.021 (1.02-1.023), 1.012 (1.012-1.012), respectively] and HTN [ORs and 95% CIs were 1.021 (1.02-1.021), 1.031 (1.028-1.033), 1.021 (1.02-1.021), respectively] in Chinese or Japanese individuals or both groups after adjusting for all variates. In addition, subgroup analyses showed that the relationship between TyG-BMI and pre-HTN or HTN was independent of age, sex, BMI, country, smoking and drinking status. Across all study populations, the areas under the TyG-BMI curve predicting pre-HTN and HTN were 0.667 and 0.762, respectively, resulting in cut-off values of 189.7 and 193.7, respectively. Conclusion: Our analyses showed that TyG-BMI was independently correlated with both pre-HTN and HTN. Besides, TyG-BMI showed superior predictive power in predicting pre-HTN and HTN compared to TyG or BMI alone.

Imaging of nerve injury in neonatal acute bilirubin encephalopathy using 1H-MRS and Glu-CEST techniques.

Objectives: To investigate the significance of proton magnetic resonance spectroscopy (1H-MRS) and glutamate chemical exchange saturation transfer (Glu-CEST) techniques in assessing the condition and prognosis of acute bilirubin encephalopathy patients and to understand the mechanism of nerve injury in this disease. Materials and methods: From September 2019 to February 2021, 31 neonates with acute bilirubin encephalopathy and 16 healthy neonates were enrolled in this study. All the quantitative results of 1H-MRS, Glu-CEST, and conventional magnetic resonance imaging (MRI) of all neonates were analyzed. The associations between statistically significant indicators of imaging and developmental quotients (DQ) were analyzed. Results: The 31 cases were assigned to the mild subgroup (n = 21) and moderate and severe subgroup (n = 10) according to the bilirubin-induced neurologic dysfunction (BIND) scores. The case group had elevated Cho and GABA absolute concentrations compared to the normal control group (all p < 0.05). Compared with the normal control group, the absolute concentration of GABA of the moderate and severe subgroup was significantly larger (p < 0.05). Compared with the normal control group, the Glu-CEST% values in the left basal ganglia, right thalamus, left frontal cortex and bilateral medial geniculate body of the case group was significantly larger (all p < 0.05). The moderate and severe subgroup had higher Glu-CEST% values in the left basal ganglia, right thalamus, and bilateral medial geniculate body than the normal control group (all p < 0.05). A negative association was revealed between the DQ scores and the Glu-CEST% values in the left basal ganglia (r = -0.888, p < 0.05). Conclusion: The combination of 1H-MRS and Glu-CEST techniques can monitor the intracerebral metabolite level of acute bilirubin encephalopathy and evaluate the illness severity.

J-shape relationship between normal fasting plasma glucose and risk of type 2 diabetes in the general population: results from two cohort studies.

BACKGROUND: Previous studies have reported that high fasting plasma glucose (FPG), even that within the normal range, is associated with the risk of type 2 diabetes (T2D). Nevertheless, these findings are limited to specific populations. Thus, studies in the general population are imperative. METHODS: This study included two cohorts comprising 204 640 individuals who underwent physical examinations at the Rich Healthcare Group present at 32 locations in 11 cities of China from 2010 to 2016 and 15 464 individuals who underwent physical tests at the Murakami Memorial Hospital in Japan. Cox regression, restricted cubic spline (RCS), Kaplan-Meier (KM) curves, and subgroup analysis were used to determine the relationship between FPG and T2D. Receiver operating characteristic (ROC) curves were used to evaluate the predictive power of FPG for T2D. RESULTS: The mean age of the 220 104 participants (204 640 Chinese and 15 464 Japanese participants) was 41.8 years (41.7 years for the Chinese and 43.7 years for the Japanese participants). During follow-up, 2611 individuals developed T2D (2238 Chinese and 373 Japanese participants). The RCS demonstrated a J-shaped relationship between FPG and T2D risk, with inflexion points of 4.5 and 5.2 for the Chinese and Japanese populations, respectively. Multivariate-adjusted hazard ratio (HR) was 7.75 for FPG and T2D risk after the inflexion point (7.3 for Chinese and 21.13 for Japanese participants). CONCLUSIONS: In general Chinese and Japanese populations, the normal baseline FPG range showed a J-shaped relationship with the risk of T2D. Baseline FPG levels help identify individuals at high risk of T2D and may enable early primary prevention to improve their outcomes.