m6A-Dependent ITIH1 Regulated by TGF-ß Acts as a Target for Hepatocellular Carcinoma Progression.

Both the transforming growth factor beta (TGF-ß) signaling pathway and N6-methyladenosine (m6A) modification for mRNA play an important role in hepatocellular carcinoma (HCC) progression. However, the relationship between TGF-ß and m6A in hepatocellular carcinoma (HCC) remains unclear. Here, it is found that TGF-ß can promote the liquid phase separation of METTL3, which further leads to the reduction of mRNA stability of ITIH1. As a secreted protein, ITIH1 can act as a ligand of integrin α5ß1 to antagonize fibronectin, induce the inhibition of focal adhesion kinase signaling pathway, and inhibit the progression of HCC. In the preclinical model (mouse model, patient-derived organoid, patient-derived xenografts), purified recombinant ITIH1 (r-ITIH1) protein can be targeted for HCC. More importantly, r-ITIH1 can play a synergistic role in targeting HCC with TGF-ß inhibitor. The downstream ITIH1 regulatory mechanism of TGF-ß and m6A modification is revealed, and ITIH1 can be translational as a potential target for HCC.

Altered local intrinsic neural activity and molecular architecture in internet use disorders.

BACKGROUND: Internet gaming disorder (IGD) is mainly characterized by its core dysfunction in higher-order brain cortices involved in inhibitory control, whose neurobiological basis remains unclear. Then, we will investigate local intrinsic neural activity (INA) alterations in IGD, ascertain whether these potential alterations are related to clinical characteristics, and further explore the underlying molecular architecture. METHOD: In this study, we performed the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) derived from resting-state functional magnetic resonance imaging (rs-fMRI) to explore the impact of IGD on local INA. Correlation analysis revealed the relationship between ReHo and fALFF in terms of group differences and clinical characteristics. Moreover, correlations between fALFF, ReHo, and PET- and SPECT-driven maps were investigated to elucidate the specific molecular architecture alternations in IGD. Finally, receiver operating characteristic curve (ROC) analysis was used to show the potential abilities of fALFF and ReHo in distinguishing individuals with IGD (IGDs) from healthy controls (HCs). RESULT: Compared with HCs, IGDs revealed increased ReHo and fALFF in the prefrontal cortex. Significantly decreased ReHo was observed in the temporal lobe, occipital lobe, and cerebellum. In addition, the ReHo values in the cerebellum_7b_R were positively correlated with internet addiction severity. ROC curve analysis showed that ReHo and fALFF-altered brain regions could effectively distinguish IGDs from HCs. More importantly, cross-modal correlations revealed local INA changes in brain regions associated with the monoamine neurotransmitter system and the less studied cholinergic/GABAergic system. CONCLUSION: These results suggest that local functional impairments are shown in the audiovisual and inhibitory control circuits in IGDs. This may be associated with underlying neurotransmitter system alterations. Therefore, this study provides the possibility of GABAergic receptor agonists and cholinergic receptor inhibitors for the treatment of IGD.

Multifunctional targeting of docetaxel plus bakuchiol micelles in the treatment of invasion and metastasis of ovarian cancer.

The invasion and metastasis of tumors pose significant challenges in the treatment of ovarian cancer (OC), making it difficult to cure. One potential treatment approach that has gained attention is the use of matrix metalloproteinase reactive controlled release micelle preparations. In this study, we developed a novel PEG5000-PVGLIG-hyaluronic acid docetaxel/bakuchiol (PP-HA-DTX/BAK) micelles formulation with desirable characteristics such as particle size, narrow polydispersity index, and a ZETA potential of approximately -5 mV. The surface modification with HA facilitates tumor penetration into the tumor interior, while the incorporation of DSPE-PEG2000-PVGLIG-PEG5000helps conceal DSPE-PEG2000-HA, reducing off-target effects and prolonging drug circulation timein vivo. Bothin vitroandin vivoexperiments demonstrated that these micelles effectively inhibit proliferation, invasion, and metastasis of OC cells while promoting apoptosis. Therefore, our findings suggest that PP-HA-DTX/BAK micelles represent a safe and effective therapeutic strategy for treating OC.

Abnormalities in static and dynamic intrinsic neural activity and neurotransmitters in first-episode OCD.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling disorder in which the temporal variability of regional brain connectivity is not well understood. The aim of this study was to investigate alterations in static and dynamic intrinsic neural activity (INA) in first-episode OCD and whether these changes have the potential to reflect neurotransmitters. METHODS: A total of 95 first-episode OCD patients and 106 matched healthy controls (HCs) were included in this study. Based on resting-state functional magnetic resonance imaging (rs-fMRI), the static and dynamic local connectivity coherence (calculated by static and dynamic regional homogeneity, sReHo and dReHo) were compared between the two groups. Furthermore, correlations between abnormal INA and PET- and SPECT-derived maps were performed to examine specific neurotransmitter system changes underlying INA abnormalities in OCD. RESULTS: Compared with HCs, OCD showed decreased sReHo and dReHo values in left superior, middle temporal gyrus (STG/MTG), left Heschl gyrus (HES), left putamen, left insula, bilateral paracentral lobular (PCL), right postcentral gyrus (PoCG), right precentral gyrus (PreCG), left precuneus and right supplementary motor area (SMA). Decreased dReHo values were also found in left PoCG, left PreCG, left SMA and left middle cingulate cortex (MCC). Meanwhile, alterations in INA present in brain regions were correlated with dopamine system (D2, FDOPA), norepinephrine transporter (NAT) and the vesicular acetylcholine transporter (VAChT) maps. CONCLUSION: Static and dynamic INA abnormalities exist in first-episode OCD, having the potential to reveal the molecular characteristics. The results help to further understand the pathophysiological mechanism and provide alternative therapeutic targets of OCD.

Evaluation of preoperative magnetic resonance imaging features and diagnostic effectiveness of grades II and III intracranial solitary fibroma.

OBJECTIVES: To explore the value of preoperative magnetic resonance imaging (MRI) characterization of intracranial solitary fibrous tumors (ISFT) and to evaluate the effectiveness of preoperative MRI features in predicting pathological grading. MATERIALS AND METHODS: This retrospective analysis comprised the clinical and preoperative MRI characterization of 55 patients with ISFT in our hospital, including 27 grade II cases and 28 grade III cases confirmed by postoperative pathology. Variables included age, sex, tumor location, cross-midline status, signal characteristics of T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), T2-fluid-attenuated inversion recovery (T2-FLAIR), and diffusion­weighted imaging (DWI), peritumoral edema, intralesional hemorrhage, focal necrosis/cystic degeneration, tumor empty vessel, maximum tumor diameter, maximum, minimum, and average values of apparent diffusion coefficient (ADCmax, ADCmin, and ADCmean), tumors enhancement mode, meningeal tail sign, skull invasion, cerebral parenchymal invasion, and venous sinus involvement. The independent samples t test or Mann-Whitney U test was performed to compare continuous data between the two groups, and the Pearson chi-squared test or Fisher's exact test was used to compare categorical data. In addition, bivariate logistic regression was performed to construct a comprehensive model, and receiver operating characteristic (ROC) curves were generated to calculate the areas under the curve (AUCs), thereby determining the value of each parameter in the differential diagnosis of grades II and III ISFT. RESULTS: The mean age at onset was similar between patients with grades II and III ISFT (46.77 ± 14.66 years and 45.82 ± 12.07 years, respectively). The proportions of men among patients with grades II and III ISFT were slightly higher than those of female patients (male/female: 1.25 [15/12] and 1.33 [16/12], respectively). There were significant differences between grades II and III ISFT in the T2-FLAIR and DWI signal characteristics, maximum, minimum, and average values of the apparent diffusion coefficient (ADCmax, ADCmin, and ADCmean), tumor location, and skull invasion (P = 0.001, P = 0.018, P = 0.000, P = 0.000, P = 0.000, P = 0.010, and P = 0.032, respectively). However, no significant differences were noted between grades II and III ISFT in age, sex, cross-midline status, T1WI and T2WI signal characteristics, peritumoral edema, intralesional hemorrhage, focal necrosis/cystic degeneration, tumor empty vessel shadow, enhancement mode, meningeal tail sign, maximum tumor diameter, brain parenchyma invasion, or venous sinus involvement (all P > 0.05). Moreover, binary logistic regression analysis showed that the model accuracy was 89.1% when ADCmin was included in the regression equation. Moreover, ROC curve analysis showed that the AUC of ADCmin was 0.805 (0.688, 0.922), sensitivity was 74.1%, specificity was 75.0%, and the cutoff value was 672 mm2/s. CONCLUSIONS: Grade III ISFT patients displayed more mixed T2-FLAIR signal characteristics and DWI signal characteristics than grade II patients, as shown by higher skull invasion and tumor mass collapse midline distribution and lower ADCmax, ADCmean, and ADCmin values. The ADCmin value was significant in the preoperative assignment of grades II and III ISFT, thereby contributing to enhanced accuracy in the imaging grading diagnosis of the disease.

Assessment of image quality and diagnostic accuracy for cervical spondylosis using T2w-STIR sequence with a deep learning-based reconstruction approach.

OBJECTIVES: To investigate potential of enhancing image quality, maintaining interobserver consensus, and elevating disease diagnostic efficacy through the implementation of deep learning-based reconstruction (DLR) processing in 3.0 T cervical spine fast magnetic resonance imaging (MRI) images, compared with conventional images. METHODS: The 3.0 T cervical spine MRI images of 71 volunteers were categorized into two groups: sagittal T2-weighted short T1 inversion recovery without DLR (Sag T2w-STIR) and with DLR (Sag T2w-STIR-DLR). The assessment covered artifacts, perceptual signal-to-noise ratio, clearness of tissue interfaces, fat suppression, overall image quality, and the delineation of spinal cord, vertebrae, discs, dopamine, and joints. Spanning canal stenosis, neural foraminal stenosis, herniated discs, annular fissures, hypertrophy of the ligamentum flavum or vertebral facet joints, and intervertebral disc degeneration were evaluated by three impartial readers. RESULTS: Sag T2w-STIR-DLR images exhibited markedly superior performance across quality indicators (median = 4 or 5) compared to Sag T2w-STIR sequences (median = 3 or 4) (p < 0.001). No statistically significant differences were observed between the two sequences in terms of diagnosis and grading (p > 0.05). The interobserver agreement for Sag T2w-STIR-DLR images (0.604-0.931) was higher than the other (0.545-0.853), Sag T2w-STIR-DLR (0.747-1.000) demonstrated increased concordance between reader 1 and reader 3 in comparison to Sag T2w-STIR (0.508-1.000). Acquisition time diminished from 364 to 197 s through the DLR scheme. CONCLUSIONS: Our investigation establishes that 3.0 T fast MRI images subjected to DLR processing present heightened image quality, bolstered diagnostic performance, and reduced scanning durations for cervical spine MRI compared with conventional sequences.

Meta-analysis of structural and functional abnormalities in behavioral addictions.

BACKGROUND: The incidence of behavioral addictions (BAs) associated with scientific and technological advances has been increasing steadily. Unfortunately, a large number of studies on the structural and functional abnormalities have shown poor reproducibility, and it remains unclear whether different addictive behaviors share common underlying abnormalities. Therefore, our objective was to conduct a quantitative meta-analysis of different behavioral addictions to provide evidence-based evidence of common structural and functional changes. METHODS: We conducted systematic searches in PubMed, Web of Science and Scopus from January 2010 to December 2023, supplementing reference lists of high-quality relevant meta-analyses and reviews, to identify eligible voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies. Using anisotropic seed-based D-Mapping (AES-SDM) meta-analysis methods, we compared brain abnormalities between BAs and healthy controls (HCs). RESULTS: There were 11 GMV studies (287 BAs and 292 HCs) and 26 fMRI studies (577 BAs and 545 HCs) that met inclusion criteria. Compared with HCs, BAs demonstrated significant reductions in gray matter volume (GMV) in (1) right anterior cingulate gyri extending into the adjacent superior frontal gyrus, as well as in the left inferior frontal gyrus and right striatum. (2) the bilateral precuneus, right supramarginal gyrus, and right fusiform gyrus were hyperfunction; (3) the left medial cingulate gyrus extended to the superior frontal gyrus, the left inferior frontal gyrus, and right middle temporal gyrus had hypofunction. CONCLUSIONS: Our study identified structural and functional impairments in brain regions involved in executive control, cognitive function, visual memory, and reward-driven behavior in BAs. Notably, fronto-cingulate regions may serve as common biomarkers of BAs.

Global, interhemispheric and intrahemispheric functional connection patterns in male adults with alcohol use disorder.

A growing body of evidence indicates the existence of abnormal local and long-range functional connection patterns in patients with alcohol use disorder (AUD). However, it has yet to be established whether AUD is associated with abnormal interhemispheric and intrahemispheric functional connection patterns. In the present study, we analysed resting-state functional magnetic resonance imaging data from 55 individuals with AUD and 32 healthy nonalcohol users. For each subject, whole-brain functional connectivity density (FCD) was decomposed into ipsilateral and contralateral parts. Correlation analysis was performed between abnormal FCD and a range of clinical measurements in the AUD group. Compared with healthy controls, the AUD group exhibited a reduced global FCD in the anterior and middle cingulate gyri, prefrontal cortex and thalamus, along with an enhanced global FCD in the temporal, parietal and occipital cortices. Abnormal interhemispheric and intrahemispheric FCD patterns were also detected in the AUD group. Furthermore, abnormal global, contralateral and ipsilateral FCD data were correlated with the mean amount of pure alcohol and the severity of alcohol addiction in the AUD group. Collectively, our findings indicate that global, interhemispheric and intrahemispheric FCD may represent a robust method to detect abnormal functional connection patterns in AUD; this may help us to identify the neural substrates and therapeutic targets of AUD.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Decomposing Socioeconomic Inequality in Early Childhood Caries Among 3 to 5-Year-Old Children in China.

INTRODUCTION AND AIMS: Early childhood caries (ECC) is a widespread oral disease that harms children's health in China. Although previous studies have linked ECC prevalence to socioeconomic status, few have measured the degree of socioeconomic inequality. This study aimed to evaluate the socioeconomic inequality of ECC in children aged 3 to 5 years in China and identify the contributor to the inequality. METHODS: We extracted data on 3 to 5-year-old children from the fourth National Oral Health Survey. We measured the inequality of ECC by the average household income per capita. We used the average household income per capita to measure the inequality of ECC. To describe inequality both qualitatively and quantitatively, we used the following methods: concentration curve, Erreygers-corrected concentration index, relative index of inequality and slope index of inequality. We also applied a decomposition based on the probit model to identify the factors that contributed to inequality. RESULTS: The prevalence of ECC in Chinese preschool children was 63.11% (95% CIs: 60.54%, 65.61%). The negative value of the Erreygers-corrected concentration index (-0.0459; 95% CIs: -0.0594, -0.0324), slope index of inequality (-0.0674; 95% CIs: -0.0876, -0.0471) and the positive value of relative index of inequality (0.7484; 95% CIs: 0.6856, 0.8169) all indicated that ECC prevalence was higher among children from low-income families. The main factors contributing to inequality were average household income, parents' educational level and living areas. CONCLUSION: There is a pro-poor inequality in ECC among 3 to 5-year-old children in China. CLINICAL RELEVANCE: To improve oral health equality, policymakers should focus more on children from low-income families, with less educated parents and living in rural areas.

Altered intrinsic neural timescales and neurotransmitter activity in males with tobacco use disorder.

Previous researches of tobacco use disorder (TUD) has overlooked the hierarchy of cortical functions and single modality design separated the relationship between macroscopic neuroimaging aberrance and microscopic molecular basis. At present, intrinsic timescale gradient of TUD and its molecular features are not fully understood. Our study recruited 146 male subjects, including 44 heavy smokers, 50 light smokers and 52 non-smokers, then obtained their rs-fMRI data and clinical scales related to smoking. Intrinsic neural timescale (INT) method was performed to describe how long neural information was stored in a brain region by calculating the autocorrelation function (ACF) of each voxel to examine the difference in the ability of information integration among the three groups. Then, correlation analyses were conducted to explore the relationship between INT abnormalities and clinical scales of smokers. Finally, cross-modal JuSpace toolbox was used to investigate the association between INT aberrance and the expression of specific receptor/transporters. Compared to healthy controls, TUD subjects displayed decreased INT in control network (CN), default mode network (DMN), sensorimotor areas and visual cortex, and such trend of decreasing INT was more pronounced in heavy smokers. Moreover, various neurotransmitters (including dopaminergic, acetylcholine and µ-opioid receptors) were involved in the molecular mechanism of timescale decreasing and differed in heavy and light smokers. These findings supplied novel insights into the brain functional aberrance in TUD from an intrinsic neural dynamic perspective and confirm INT was a potential neurobiological marker. And also established the connection between macroscopic imaging aberrance and microscopic molecular changes in TUD.

scCDC: a computational method for gene-specific contamination detection and correction in single-cell and single-nucleus RNA-seq data.

In droplet-based single-cell and single-nucleus RNA-seq assays, systematic contamination of ambient RNA molecules biases the quantification of gene expression levels. Existing methods correct the contamination for all genes globally. However, there lacks specific evaluation of correction efficacy for varying contamination levels. Here, we show that DecontX and CellBender under-correct highly contaminating genes, while SoupX and scAR over-correct lowly/non-contaminating genes. Here, we develop scCDC as the first method to detect the contamination-causing genes and only correct expression levels of these genes, some of which are cell-type markers. Compared with existing decontamination methods, scCDC excels in decontaminating highly contaminating genes while avoiding over-correction of other genes.

Deep learning-based reconstruction enhances image quality and improves diagnosis in magnetic resonance imaging of the shoulder joint.

Background: Accelerated magnetic resonance imaging sequences reconstructed using the vendor-provided Recon deep learning algorithm (DL-MRI) were found to be more likely than conventional magnetic resonance imaging (MRI) sequences to detect subacromial (SbA) bursal thickening. However, the extent of this thickening was not extensively explored. This study aimed to compare the image quality of DL-MRI with conventional MRI sequences reconstructed via conventional pipelines (Conventional-MRI) for shoulder examinations and evaluate the effectiveness of DL-MRI in accurately demonstrating the degree of SbA bursal and subcoracoid (SC) bursal thickening. Methods: This prospective cross-sectional study enrolled 41 patients with chronic shoulder pain who underwent 3-T MRI (including both Conventional-MRI and accelerated MRI sequences) of the shoulder between December 2022 and April 2023. Each protocol consisted of oblique axial, coronal, and sagittal images, including proton density-weighted imaging (PDWI) with fat suppression (FS) and oblique coronal T1-weighted imaging (T1WI) with FS. The image quality and degree of artifacts were assessed using a 5-point Likert scale for both Conventional-MRI and DL-MRI. Additionally, the degree of SbA and SC bursal thickening, as well as the relative signal-to-noise ratio (rSNR) and relative contrast-to-noise ratio (rCNR) were analyzed using the paired Wilcoxon test. Statistical significance was defined as P<0.05. Results: The utilization of accelerated sequences resulted in a remarkable 54.7% reduction in total scan time. Overall, DL-MRI exhibited superior image quality scores and fewer artifacts compared to Conventional-MRI. Specifically, DL-MRI demonstrated significantly higher measurements of SC bursal thickenings in the oblique sagittal PDWI sequence compared to Conventional-MRI [3.92 (2.83, 5.82) vs. 3.74 (2.92, 5.96) mm, P=0.028]. Moreover, DL-MRI exhibited higher detection of SbA bursal thickenings in the oblique coronal PDWI sequence [2.61 (1.85, 3.46) vs. 2.48 (1.84, 3.25) mm], with a notable trend towards significant differences (P=0.071). Furthermore, the rSNRs of the muscle in DL-MRI images were significantly higher than those in Conventional-MRI images across most sequences (P<0.001). However, the rSNRs of bone on Conventional-MRI of oblique axial and oblique coronal PDWI sequences showed adverse results [oblique axial: 1.000 (1.000, 1.000) vs. 0.444 (0.367, 0.523); and oblique coronal: 1.000 (1.000, 1.000) vs. 0.460 (0.387, 0.631); all P<0.001]. Additionally, all DL-MRI images exhibited significantly greater rSNRs and rCNRs compared to accelerated MRI sequences reconstructed using traditional pipelines (P<0.001). Conclusions: In conclusion, the utilization of DL-MRI enhances image quality and improves diagnostic capabilities, making it a promising alternative to Conventional-MRI for shoulder imaging.

Comparative genomics analysis reveals sequence characteristics potentially related to host preference in Cryptosporidium xiaoi.

Cryptosporidium spp. are important diarrhea-associated pathogens in humans and livestock. Among the known species, Cryptosporidium xiaoi, which causes cryptosporidiosis in sheep and goats, was previously recognized as a genotype of the bovine-specific Cryptosporidium bovis based on their high sequence identity in the ssrRNA gene. However, the lack of genomic data has limited characterization of the genetic differences between the two closely related species. In this study, we sequenced the genomes of two C. xiaoi isolates and performed comparative genomic analysis to identify the sequence uniqueness of this ovine-adapted species compared with other Cryptosporidium spp. Our results showed that C. xiaoi is genetically related to C. bovis as shown by their 95.8% genomic identity and similar gene content. Consistent with this, both C. xiaoi and C. bovis appear to have fewer genes encoding mitochondrial metabolic enzymes and invasion-related protein families. However, they appear to possess several species-specific genes. Further analysis indicates that the sequence differences between these two Cryptosporidium spp. are mainly in 24 highly polymorphic genes, half of which are located in the subtelomeric regions. Some of these subtelomeric genes encode secretory proteins that have undergone positive selection. In addition, the genomes of two C. xiaoi isolates, identified as subtypes XXIIIf and XXIIIh, share 99.9% nucleotide sequence identity, with six highly divergent genes encoding putative secretory proteins. Therefore, these species-specific genes and sequence polymorphism in subtelomeric genes probably contribute to the different host preference of C. xiaoi and C. bovis.

Autophagy Induced by Low Shear Stress Leads to Endothelial Glycocalyx Disruption.

INTRODUCTION: Previous studies have confirmed that low shear stress (LSS) induces glycocalyx disruption, leading to endothelial dysfunction. However, the role of autophagy in LSS-induced glycocalyx disruption and relevant mechanism are not clear. In this study, we hypothesized that LSS may promote autophagy, disrupting the endothelium glycocalyx. METHODS: Human umbilical vein endothelial cells were subjected to physiological shear stress and LSS treatments, followed by the application of autophagy inducers and inhibitors. Additionally, cells were treated with specific matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) inhibitor. The expression of autophagic markers, glycocalyx, MMP-2, and MMP-9 was measured. RESULTS: LSS impacted the expression of endothelium autophagy markers, increasing the expression of LC3II.LC3I-1 and Beclin-1, and decreasing the levels of p62, accompanied by glycocalyx disturbance. Moreover, LSS upregulated the expression of MMP-2 and MMP-9 and downregulated the levels of syndecan-1 and heparan sulfate (HS). Additionally, expression of MMP-2 and MMP-9 was increased by an autophagy promoter but was decreased by autophagy inhibitor treatment under LSS. Autophagy and MMP-2 and MMP-9 further caused glycocalyx disruption. CONCLUSION: LSS promotes autophagy, leading to glycocalyx disruption. Autophagy increases the expression of MMP-2 and MMP-9, which are correlated with the glycocalyx destruction induced by LSS.

A combined amplicon approach to nematode polyparasitism occurring in captive wild animals in southern China.

BACKGROUND: Gastrointestinal tract (GIT) nematodes prefer to live in the intestines of wild animals, causing damage and even death, and posing a zoonotic risk. The polyparasitism of GIT nematodes results in the complex dynamics of the nematode communities that occur naturally in wild animals. However, the nematode community in captive wild animals is poorly understood. METHODS: We combined  microscopic examination and amplicon sequencing for community diversity. RESULTS: We characterized GIT nematode assemblages to one order, one family, four genera, and ten species, in 512 fecal samples of 121 species from captive wild animals in southern China. The positive rate of GIT nematodes was 20.7% (106/512), including 42.3% (11/26) in reptiles, 26.5% (39/147) in herbivores, 25.0% (25/100) in non-human primates, 20.0% (5/25) in omnivores, 12.2% (9/74) in carnivores, and 12.1% (17/140) in avians. The dominant nematodes were Haemonchus contortus in herbivores and Trichuris species in primates. The nematode communities of arboreal primates differed from their terrestrial counterparts, reflecting both host phylogeny and ecological constraints. Soil-transmitted Strongyloides species were widespread throughout the herbivore, primate, avian, and carnivore communities, and tended to infect omnivorous primates and terrestrial herbivores. In addition, new Trichuris and Heterakis species were found in the nematode communities of captive porcupines and peafowls. CONCLUSION: This study highlights the variation in the composition of the GIT nematode community and strengthens the attention to the harms induced by zoonotic nematodes and co-infective nematodes with low species richness.

Respiratory syncytial virus subtypes in children with bronchiolitis: does it correlate with clinical severity?

BACKGROUND: In this retrospective study, we aimed to evaluate the factors associated with the severity of respiratory syncytial virus (RSV) bronchiolitis in children aged under 2 years who were admitted to the Children's Hospital of Hebei between June 2018 and January 2019. METHODS: Sputum samples positive for RSV via multiplex PCR were subtyped using real-time PCR. Data collected included risk factors for disease severity, demographics, microbiology, and outcomes. RESULTS: Of the 82 children with RSV bronchiolitis, 79 were treated and discharged with improvement, while 3 died. All three patients had underlying medical conditions, including complex congenital heart disease and severe combined immunodeficiency. Further, disease severity was associated with preexisting underlying disease, fever duration, and bacterial co-infection, but not with the RSV subtype. CONCLUSIONS: Our findings suggest that an appropriate therapeutic regimen should include the detection of bacterial co-infections and the identification of underlying diseases for the effective management of severe RSV bronchiolitis.

Predictive role of glycocalyx components and MMP-9 in cardiopulmonary bypass patients for ICU stay.

Background: Shedding of glycocalyx is relevant to worse prognosis in surgical patients, and elevated levels of serum matrix metalloproteinase-9 (MMP-9) are associated with this phenomenon. This study aimed to investigate the dynamic alterations of serum glycocalyx components and MMP-9 during cardiopulmonary bypass (CPB), and evaluate their predictive capacities for prolonged intensive care unit (ICU) stay, as well as their correlation with coagulation dysfunction. Methods: This retrospective study analyzed serum levels of syndecan-1, heparan sulfate (HS), and MMP-9 at different time points during CPB, and assessed their association with prolonged ICU stay and coagulation dysfunction. Results: Syndecan-1, HS, and MMP-9 exhibited divergent changes during CPB. Serum levels of syndecan-1 (AUC = 78.0 %) and MMP-9 (AUC = 78.4 %) were validated as reliable predictors for prolonged ICU stay, surpassing the predictive value of creatinine (AUC = 70.0 %). Syndecan-1 (rho = 0.566, P < 0.01 at T1 and rho = 0.526, P < 0.01 at T2) and HS (rho = 0.403, P < 0.05 at T4) exhibited correlations with activated partial thromboplastin time (APTT) ratio beyond the normal range. Conclusions: Our findings advocate the potential efficacy of serum glycocalyx components and MMP-9 as early predictive indicators for extended ICU stay following cardiac surgery with CPB. Additionally, we observed a correlation between glycocalyx disruption during CPB and coagulation dysfunction. Further studies with expansive cohorts are warranted to consolidate our findings and explore the predictive potential of other glycocalyx components.

T1 mapping as a quantitative imaging biomarker for diagnosing cervical cancer: a comparison with diffusion kurtosis imaging.

BACKGROUND: T1 mapping can potentially quantitatively assess the intrinsic properties of tumors. This study was conducted to explore the ability of T1 mapping in distinguishing cervical cancer type, grade, and stage and compare the diagnostic performance of T1 mapping with diffusion kurtosis imaging (DKI). METHODS: One hundred fifty-seven patients with pathologically confirmed cervical cancer were enrolled in this prospectively study. T1 mapping and DKI were performed. The native T1, difference between native and postcontrast T1 (T1diff), mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) were calculated. Cervical squamous cell carcinoma (CSCC) and adenocarcinoma (CAC), low- and high-grade carcinomas, and early- and advanced-stage groups were compared using area under the receiver operating characteristic (AUROC) curves. RESULTS: The native T1 and MK were higher, and the MD and ADC were lower for CSCC than for CAC (all p < 0.05). Compared with low-grade CSCC, high-grade CSCC had decreased T1diff, MD, ADC, and increased MK (p < 0.05). Compared with low-grade CAC, high-grade CAC had decreased T1diff and increased MK (p < 0.05). Native T1 was significantly higher in the advanced-stage group than in the early-stage group (p < 0.05). The AUROC curves of native T1, MK, ADC and MD were 0,772, 0.731, 0.715, and 0.627, respectively, for distinguishing CSCC from CAC. The AUROC values were 0.762 between high- and low-grade CSCC and 0.835 between high- and low-grade CAC, with T1diff and MK showing the best discriminative values, respectively. For distinguishing between advanced-stage and early-stage cervical cancer, only the AUROC of native T1 was statistically significant (AUROC = 0.651, p = 0.002). CONCLUSIONS: Compared with DKI-derived parameters, native T1 exhibits better efficacy for identifying cervical cancer subtype and stage, and T1diff exhibits comparable discriminative value for cervical cancer grade.

Long-term exposure to ambient fine particulate matter and periodontitis: An observational study using nationally representative survey data.

AIM: The rising prevalence of periodontitis imposes substantial burdens on individuals and society. Identifying environmental risk factors for periodontitis may contribute to tackling the global public health burden of it. This study aimed to assess the association between long-term exposure to PM2.5 and periodontitis in a nationally representative population from China. MATERIALS AND METHODS: In this multi-centre cross-sectional study of 372 communities in 31 provinces of Mainland China, we used data from the Fourth National Oral Health Survey of China in 2015-2016, in combination with high-resolution gridded concentrations of fine particulate matter (PM2.5). Logistic regression was applied to assess the relationship between long-term PM2.5 exposure and the risk of periodontitis. In addition, we examined whether the association varied by individual characteristics, and estimated the exposure-response relationship and the risk of damaged tooth in each tooth quadrant. RESULTS: A total of 8391 participants from 96 cities were diagnosed with periodontitis, accounting for 60.04% (8391/13,459) of the participants. For each 10 µg/m3 increment in 1-, 3- and 5-year average concentrations of PM2.5, the risk of total periodontitis increased by 9.0% (95% confidence interval: 6.0%, 12.0%), 8.0% (6.0, 11·0) and 7.0% (5.0, 10.0), respectively. Mild periodontitis was more strongly associated with PM2.5 exposure than moderate and severe periodontitis. The teeth in the lower anterior, lower posterior or upper anterior are more susceptible to the effect of PM2.5 on the periodontal pocket, calculus and bleeding gums. CONCLUSIONS: Long-term exposure to PM2.5 is significantly associated with an increased risk of periodontitis in the nationally representative Chinese population. Considering the rising prevalence of periodontitis, considerable costs of treatment, and substantially adverse effects on individuals and society, these findings suggest that stricter air quality regulations may help ease the burden of periodontal disease.