Identifying and validating the roles of the cuproptosis-related gene DKC1 in cancer with a focus on esophageal carcinoma.

BACKGROUND: Esophageal cancer is a common malignancy of the digestive tract. Despite remarkable advancements in its treatment, the overall prognosis for patients remains poor. Cuproptosis is a form of programmed cell death that affects the malignant progression of tumors. This study aimed to examine the impact of the cuproptosis-associated gene DKC1 on the malignant progression of esophageal cancer. METHODS: Clinical and RNA sequencing data of patients with esophageal cancer were extracted from The Cancer Genome Atlas (TCGA). Univariate Cox regression analysis was used to identify the differentially expressed genes related to cuproptosis that are associated with prognosis. We then validated the difference in the expression of DKC1 between tumor and normal tissues via three-dimensional multiomics difference analysis. Subsequently, we investigated the association between DKC1 expression and the tumor microenvironment by employing the TIMER2.0 algorithm, which was further validated in 96 single-cell datasets obtained from the TISCH database. Additionally, the functional role of DKC1 in pancarcinoma was assessed through GSEA. Furthermore, a comprehensive pancancer survival map was constructed, and the expression of DKC1 was verified in various molecular subtypes. By utilizing the CellMiner, GDSC, and CTRP databases, we successfully established a connection between DKC1 and drug sensitivity. Finally, the involvement of DKC1 in the progression of esophageal cancer was investigated through in vivo and in vitro experiments. RESULTS: In this study, we identified a copper death-related gene, DKC1, in esophageal cancer. Furthermore, we observed varying levels of DKC1 expression across different tumor types. Additionally, we conducted an analysis to determine the correlation between DKC1 expression and clinical features, revealing its association with common cell cycle pathways and multiple metabolic pathways. Notably, high DKC1 expression was found to indicate poor prognosis in patients with various tumors and to influence drug sensitivity. Moreover, our investigation revealed significant associations between DKC1 expression and the expression of molecules involved in immune regulation and infiltration of lymphocyte subtypes. Ultimately, the increased expression of DKC1 in esophageal cancer tissues was verified using clinical tissue samples. Furthermore, DKC1-mediated promotion of esophageal cancer cell proliferation and migration was confirmed through both in vitro and in vivo experiments. Additionally, it is plausible that DKC1 may play a role in the regulation of cuproptosis. CONCLUSION: In this study, we conducted a systematic analysis of DKC1 and its regulatory factors and experimentally validated its excellent diagnostic and prognostic abilities in various cancers. Further research indicated that DKC1 may reshape the tumor microenvironment (TME), highlighting the potential of DKC1-based cancer treatment and its usefulness in predicting the response to chemotherapy.

Circ_0028826 Promotes Growth and Metastasis of NSCLC via Acting as a Sponge of miR-758-3p to Derepress IDH2 Expression.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the cancers with the highest mortality and morbidity in the world. Circular RNAs (circRNAs) are newly identified players in carcinogenesis and development of various cancers. This study is aimed at exploring the functional effects and mechanism of circ_0028826 in the development of NSCLC. METHODS: Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of circ_0028826, IDH2 mRNA, and miR-758-3p. IDH2, Bcl2, Bax, and E-cadherin protein levels were detected using a western blot. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, and transwell assays were used to assess the capacities of proliferation, apoptosis, migration, and invasion. Interaction between miR-758-3p and circ_0028826 or IDH2 was validated using a dual-luciferase reporter assay. The role of circ_0028826 in vivo was checked based on a xenograft tumor model. RESULTS: Circ_0028826 was elevated in NSCLC, and its absence inhibited NSCLC cell proliferation, migration, invasion, and induced apoptosis. In terms of mechanism, circ_0028826 increased IDH2 expression by targeting miR-758-3p. In addition, circ_0028826 knockdown also regulated IDH2 by targeting miR-758-3p to inhibit tumor growth in vivo. CONCLUSION: Circ_0028826 promoted the development of NSCLC via regulation of the miR-758-3p/IDH2 axis, providing a new strategy for NSCLC treatment.

Histidine-rich glycoprotein modulates neutrophils and thrombolysis-associated hemorrhagic transformation.

Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood-brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.

Exploring the Mechanism of H2S Synthesis in Male Bactrian Camel Poll Glands Based on Data Independent Acquisition Proteomics and Non-Targeted Metabolomics.

During estrus, the poll glands of male Bactrian Camels (Camelus Bactrianus) become slightly raised, exuding a large amount of pale yellow watery secretion with a characteristic odor that may contain hydrogen sulfide (H2S). However, whether H2S can be synthesized in the poll glands of male Bactrian Camels and its role in inducing camel estrus remains unclear. This study aimed to identify differentially expressed proteins (DEPs) and signaling pathways in the poll gland tissues of male Bactrian Camels using data independent acquisition (DIA) proteomics. Additionally, gas chromatography-mass spectrometry (GC-MS) was performed to identify differentially expressed metabolites (DEMs) in the neck hair containing secretions during estrus in male Bactrian Camels, to explore the specific expression patterns and mechanisms in the poll glands of camels during estrus. The results showed that cystathionine-γ-lyase (CTH) and cystathionine-ß-synthase (CBS), which are closely related to H2S synthesis in camel poll glands during estrus, were mainly enriched in glycine, serine, and threonine metabolism, amino acid biosynthesis, and metabolic pathways. In addition, both enzymes were widely distributed and highly expressed in the acinar cells of poll gland tissues in camels during estrus. Meanwhile, the neck hair secretion contains high levels of amino acids, especially glycine, serine, threonine, and cystathionine, which are precursors for H2S biosynthesis. These results demonstrate that the poll glands of male Bactrian Camels can synthesize and secrete H2S during estrus. This study provides a basis for exploring the function and mechanism of H2S in the estrus of Bactrian Camels.

Associations between diffusion kurtosis imaging metrics and neurodevelopmental outcomes in neonates with low-grade germinal matrix and intraventricular hemorrhage.

Diffusion Kurtosis Imaging (DKI)-derived metrics are recognized as indicators of maturation in neonates with low-grade germinal matrix and intraventricular hemorrhage (GMH-IVH). However, it is not yet known if these factors are associated with neurodevelopmental outcomes. The objective of this study was to acquire DKI-derived metrics in neonates with low-grade GMH-IVH, and to demonstrate their association with later neurodevelopmental outcomes. In this prospective study, neonates with low-grade GMH-IVH and control neonates were recruited, and DKI were performed between January 2020 and March 2021. These neonates underwent the Bayley Scales of Infant Development test at 18 months of age. Mean kurtosis (MK), radial kurtosis (RK) and gray matter values were measured. Spearman correlation analyses were conducted for the measured values and neurodevelopmental outcome scores. Forty controls (18 males, average gestational age (GA) 30 weeks ± 1.3, corrected GA at MRI scan 38 weeks ± 1) and thirty neonates with low-grade GMH-IVH (13 males, average GA 30 weeks ± 1.5, corrected GA at MRI scan 38 weeks ± 1). Neonates with low-grade GMH-IVH exhibited lower MK and RK values in the PLIC and the thalamus (P < 0.05). The MK value in the thalamus was associated with Mental Development Index (MDI) (r = 0.810, 95% CI 0.695-0.13; P < 0.001) and Psychomotor Development Index (PDI) (r = 0.852, 95% CI 0.722-0.912; P < 0.001) scores. RK value in the caudate nucleus significantly and positively correlated with MDI (r = 0.496, 95% CI 0.657-0.933; P < 0.001) and PDI (r = 0.545, 95% CI 0.712-0.942; P < 0.001) scores. The area under the curve (AUC) were used to assess diagnostic performance of MK and RK in thalamus (AUC = 0.866, 0.787) and caudate nucleus (AUC = 0.833, 0.671) for predicting neurodevelopmental outcomes. As quantitative neuroimaging markers, MK in thalamus and RK in caudate nucleus may help predict neurodevelopmental outcomes in neonates with low-grade GMH-IVH.

Jointed tails enhance control of three-dimensional body rotation.

Tails used as inertial appendages induce body rotations of animals and robots-a phenomenon that is governed largely by the ratio of the body and tail moments of inertia. However, vertebrate tails have more degrees of freedom (e.g., number of joints, rotational axes) than most current theoretical models and robotic tails. To understand how morphology affects inertial appendage function, we developed an optimization-based approach that finds the maximally effective tail trajectory and measures error from a target trajectory. For tails of equal total length and mass, increasing the number of equal-length joints increased the complexity of maximally effective tail motions. When we optimized the relative lengths of tail bones while keeping the total tail length, mass, and number of joints the same, this optimization-based approach found that the lengths match the pattern found in the tail bones of mammals specialized for inertial maneuvering. In both experiments, adding joints enhanced the performance of the inertial appendage, but with diminishing returns, largely due to the total control effort constraint. This optimization-based simulation can compare the maximum performance of diverse inertial appendages that dynamically vary in moment of inertia in 3D space, predict inertial capabilities from skeletal data, and inform the design of robotic inertial appendages.

Human bone marrow mesenchymal stem cell-driven LncRNA PTCSC3 upregulation within lung adenocarcinoma cells reduces erlotinib resistance by mitigating Wnt/ß-Catenin pathway.

lncRNA PTCSC3, which stands for Papillary Thyroid Carcinoma Susceptibility Candidate 3, has been found to play a role in various cellular processes, including cell proliferation, apoptosis, and migration, acting as either an oncogene or a tumor suppressor depending on the context. This study investigates the influence of lncRNA PTCSC3, derived from human bone marrow mesenchymal stem cell (hBMSC), on the efficacy of erlotinib (Er)-resistant lung adenocarcinoma (LUAD) cells and elucidates underlying mechanism. The hBMSCs and LUAD (PC9 and A549) cells were employed to establish an Er-resistant LUAD cell model. It was observed that exposure to hBMSCs reduced the viability of A549-Er and PC9-Er cells and increased their rate of apoptosis. Further investigations revealed that in the presence of hBMSCs-containing medium, PTCSC3 expression was significantly upregulated, concomitantly with a suppression of the Wnt/ß-Catenin pathway. Conversely, silencing PTCSC3 led to enhanced A549-Er and PC9-Er activities, reduced cell apoptosis, and activated Wnt/ß-Catenin pathway. The effects of PTCSC3 modulation were also examined by transfecting LUAD cells with different PTCSC3 expression vectors and treating them with XAV939, a Wnt/ß-Catenin pathway inhibitor, which similarly decreased cell viability. In the rescue experiment, the effect of hBMSCs on LUAD cells could be counteracted by down-regulation of PTCSC3, and the effect of PTCSC3 down-regulation on cells was mitigated by XAV939. This study revealed that hBMSCs promote the up-regulation of PTCSC3 in LUAD cells, thus inhibiting Wnt/ß-Catenin pathway and reversing Er resistance, offering a potential novel strategy to enhance the efficacy of chemotherapy in LUAD.

SLC34A2 Targets in Calcium/Phosphorus Homeostasis of Mammary Gland and Involvement in Development of Clinical Mastitis in Dairy Cows.

The type II Na/Pi co-transporter (NaPi2b), encoded by the solute carrier (SLC) transporter 34A2 (SLC34A2), is responsible for calcium (Ca) and phosphorus (P) homeostasis. Unbalanced Ca/P metabolism induces mastitis in dairy cows. However, the specific role of SLC34A2 in regulating this imbalance in Holstein cows with clinical mastitis (CM) remains unclear. The aim of this study was to investigate the role of SLC34A2 and identify differentially expressed proteins (DEPs) that interact with SLC34A2 and are associated with Ca/P metabolism in dairy cows with CM. Immunohistochemical and immunofluorescence staining results showed that SLC34A2 was located primarily in the mammary epithelial cells of the mammary alveoli in both the control (healthy cows, Con/C) and CM groups. Compared to the Con/C group, the relative expression of the SLC34A2 gene and protein were significantly downregulated in the CM group. We identified 12 important DEPs included in 11 GO terms and two pathways interacting with SLC34A2 using data-independent acquisition proteomics. The PPI (protein-and-protein interaction) network results suggested that these DEPs were associated with ion metabolism and homeostasis, especially SLC34A2. These results demonstrate that SLC34A2 downregulation is negatively correlated with the occurrence and development of CM in Holstein cows, providing a basis for exploring the function and regulatory mechanism of SLC34A2 in Ca/P metabolism and homeostasis in Holstein cows with CM.

Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy.

Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.

Veliparib exerts protective effects in intracerebral hemorrhage mice by inhibiting the inflammatory response and accelerating hematoma resolution.

Poly (ADP-ribose) polymerase (PARP) inhibitors have potent anti-inflammatory effects, including the suppression of brain microglial activation. Veliparib, a well-known PARP1/2 inhibitor, exhibits particularly high brain penetration, but its effects on stroke outcome is unknown. Here, the effects of veliparib on the short-term outcome of intracerebral hemorrhage (ICH), the most lethal type of stroke, were investigated. Collagenase-induced mice ICH model was applied, and the T2-weighted magnetic resonance imaging was performed to evaluate lesion volume. Motor function and hematoma volume were also measured. We further performed immunofluorescence, enzyme linked immunosorbent assay, flow cytometry, and blood-brain barrier assessment to explore the potential mechanisms. Our results demonstrated veliparib reduced the ICH lesion volume dose-dependently and at a dosage of 5 mg/kg, veliparib significantly improved mouse motor function and promoted hematoma resolution at days 3 and 7 post-ICH. Veliparib inhibited glial activation and downregulated the production of pro-inflammatory cytokines. Veliparib significantly decreased microglia counts and inhibited peripheral immune cell infiltration into the brain on day 3 after ICH. Veliparib improved blood-brain barrier integrity at day 3 after ICH. These findings demonstrate that veliparib improves ICH outcome by inhibiting inflammatory responses and may represent a promising novel therapy for ICH.

CDK1 and CCNA2 play important roles in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a malignant tumor that occurs in oral cavity and is dominated by squamous cells. The relationship between CDK1, CCNA2, and OSCC is still unclear. The OSCC datasets GSE74530 and GSE85195 configuration files were downloaded from the Gene Expression Omnibus (GEO) database and were derived from platforms GPL570 and GPL6480. Differentially expressed genes (DEGs) were screened. The weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, construction and analysis of protein-protein interaction (PPI) network, Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEGs. A total of 1756 DEGs were identified. According to Gene Ontology (GO) analysis, they were predominantly enriched in processes related to organic acid catabolic metabolism, centromeric, and chromosomal region condensation, and oxidoreductase activity. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the DEGs were mainly concentrated in metabolic pathways, P53 signaling pathway, and PPAR signaling pathway. Weighted gene co-expression network analysis was performed with a soft-thresholding power set at 9, leading to the identification of 6 core genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1). The gene expression heatmap revealed that core genes (CDK1, CCNA2) were highly expressed in OSCC samples. Comparative Toxicogenomics Database analysis demonstrated associations between the 6 genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1) and oral tumors, precancerous lesions, inflammation, immune system disorders, and tongue tumors. The associated miRNAs for CDK1 gene were hsa-miR-203a-3p.2, while for CCNA2 gene, they were hsa-miR-6766-3p, hsa-miR-4782-3p, and hsa-miR-219a-5p. CDK1 and CCNA2 are highly expressed in OSCC. The higher the expression of CDK1 and CCNA2, the worse the prognosis.

CCNA2 and KIF23 are molecular targets for the prognosis of adenoid cystic carcinoma.

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a tumor type derived from glands. However, relationship between CCNA2 and KIF23, and adenoid cystic carcinoma remains unclear. METHODS: GSE36820 and GSE88804 profiles for ACC were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Weighted Gene Co-expression Network Analysis (WGCNA) was conducted. Subsequently, the construction and analysis of protein-protein interaction (PPI) network, functional enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were performed. A gene expression heat map was generated to visually depict the expression difference of core genes between adenoid cystic carcinoma and normal samples. TargetScan was employed to identify miRNAs that regulated central DEGs. Western blotting (WB) was conducted for cell verification. RESULTS: A total of 885 DEGs were identified. GO and KEGG analyses revealed their main enrichment in responses to chemical stimuli, cell proliferation, tissue development, and regulation of cell proliferation. The GO and KEGG results indicated significant enrichment in aldosterone-regulated sodium reabsorption, the cell cycle, and the PPAR signaling pathway. Notably, core genes (CCNA2 and KIF23) were found to be highly expressed in Adenoid Cystic Carcinoma samples and expressed at low levels in normal samples. WB validated the overexpression of CCNA2 and KIF23 in the Adenoid Cystic Carcinoma group, confirming the protein-level changes associated with cell cycle, metastasis, apoptosis, and inflammatory factors in Adenoid Cystic Carcinoma groups with gene overexpression and knockout. CONCLUSIONS: CCNA2 and KIF23 exhibit high expression levels in ACC, suggesting their potential role as molecular targets for this malignancy.

Assessment of brain structure and volume reveals neurodevelopmental abnormalities in preterm infants with low-grade intraventricular hemorrhage.

There is increasing evidence of abnormal neurodevelopmental outcomes in preterm infants with low-grade intraventricular hemorrhage (IVH). The purpose of the study was to explore whether brain microstructure and volume are associated with neuro-behavioral outcomes at 40 weeks corrected gestational age in preterm infants with low-grade IVH. MR imaging at term-equivalent age (TEA) was performed in 25 preterm infants with mild IVH (Papile grading I/II) and 40 control subjects without IVH. These subjects all had neonatal behavioral neurological assessment (NBNA) at 40 weeks' corrected age. Microstructure and volume evaluation of the brain were performed by using diffusion kurtosis imaging (DKI) and Synthetic MRI. Correlations among microstructure parameters, volume, and developmental outcomes were explored by using Spearman's correlation. In preterm infants with low-grade IVH, the volume of brain parenchymal fraction (BPF) was reduced. In addition, mean kurtosis (MK), fractional anisotropy (FA), radial kurtosis (RK), axial kurtosis (AK) in several major brain regions were reduced, while mean diffusivity (MD) was increased (P < 0.05). BPF, RK in the cerebellum, MK in the genu of the corpus callosum, and MK in the thalamus of preterm infants with low-grade IVH were associated with lower NBNA scores (r = 0.831, 0.836, 0.728, 0.772, P < 0.05). DKI and Synthetic MRI can quantitatively evaluate the microstructure alterations and brain volumes in preterm infants with low-grade IVH, which provides clinicians with a more comprehensive and accurate neurobehavioral assessment of preterm infants with low-grade IVH.

Prognostic Factors and Construction of Nomogram Prediction Model of Lung Cancer Patients Using Clinical and Blood Laboratory Parameters.

Objective: This work aimed to explore the prognostic risk factors of lung cancer (LC) patients and establish a line chart prediction model. Methods: A total of 322 LC patients were taken as the study subjects. They were randomly divided into a training set (n = 202) and a validation set (n = 120). Basic information and laboratory indicators were collected, and the progression-free survival (PFS) and overall survival (OS) were followed up. Single-factor and cyclooxygenase (COX) multivariate analyses were performed on the training set to construct a Nomogram prediction model, which was validated with 120 patients in the validation set, and Harrell's consistency was analyzed. Results: Single-factor analysis revealed significant differences in PFS (P<0.05) between genders, body mass index (BMI), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCCA), treatment methods, treatment response evaluation, smoking status, presence of pericardial effusion, and programmed death ligand 1 (PD-L1) at 0 and 1-50%. Significant differences in OS (P<0.05) were observed for age, tumor location, treatment methods, White blood cells (WBC), uric acid (UA), CA125, pro-gastrin-releasing peptide (ProGRP), SCCA, cytokeratin fragment 21 (CYFRA21), and smoking status. COX analysis identified male gender, progressive disease (PD) as treatment response, and SCCA > 1.6 as risk factors for LC PFS. The consistency indices of the line chart models for predicting PFS and OS were 0.782 and 0.772, respectively. Conclusion: Male gender, treatment response of PD, and SCCA > 1.6 are independent risk factors affecting the survival of LC patients. The PFS line chart model demonstrates good concordance.

Evaluation of white matter microstructural alterations in premature infants with necrotizing enterocolitis.

Background: Preterm infants with necrotizing enterocolitis (NEC) are at high risk of adverse neurodevelopmental outcomes. The aim of this study was to explore the value of diffusion tensor imaging (DTI) combined with serum C-reactive protein (CRP) and procalcitonin (PCT) in evaluating alterations of white matter (WM) microstructure in preterm infants with NEC. Methods: A retrospective cross-sectional study was conducted in which all participants were consecutively enrolled at The Third Affiliated Hospital of Zhengzhou University from June 2017 and October 2021. Data from 30 preterm infants with NEC [mean gestational age at birth 31.41±1.15 weeks; mean age at magnetic resonance imaging (MRI) 37.53±3.08 weeks] and 40 healthy preterm infants with no NEC were recorded (mean gestational age at birth 32.27±2.09 weeks; mean age at MRI 37.15±3.23 weeks). WM was used to obtain the fractional anisotropy (FA) and mean diffusivity (MD) values of the regions of interest (ROIs). Additionally, serum levels of CRP and PCT were determined. Spearman correlation analysis was performed between the WM-derived parameters, CRP level, and the PCT serum index. Results: Preterm infants with NEC had reduced FA values and elevated MD values in WM regions [posterior limbs of the internal capsule (PLIC), lentiform nucleus (LN), frontal white matter (FWM)] compared to the control group (P<0.05). Additionally, the FA of the PLIC was negatively correlated with serum CRP (r=-0.846; P<0.05) and PCT (r=-0.843; P<0.05). Meanwhile, the MD of PLIC was positively correlated with serum CRP (r=0.743; P<0.05) and PCT (r=0.743; P<0.05, respectively). The area under the curve (AUC) of FA and MD combined with CRP and PCT in the diagnosis of WM microstructure alterations with NEC was 0.968, representing a considerable improvement in predicted efficacy over single indicators, including FA [AUC: 0.938; 95% confidence interval (CI): 0.840-0.950], MD (AUC: 0.807; 95% CI: 0.722-0.838), CRP (AUC: 0.867; 95% CI: 0.822-0.889), and PCT (AUC: 0.706; 95% CI: 0.701-0.758). Conclusions: WM can noninvasively and quantitatively assess the WM microstructure alterations in preterm infants with NEC. WM combined with serum CRP and PCT demonstrated superior performance in detecting and evaluating WM microstructure alterations in preterm infants with NEC.

Theoretical Analysis and Numerical Simulation of the Wear of the Sealing Substrate of a High-Pressure, High-Frequency Opening and Closing Hydrogen Ball Valve.

High-pressure valves are an essential infrastructure for hydrogen refueling stations, and the issue of safety and reliability of their operation affects the efficiency of the entire hydrogen delivery system. Hydrogen ball valves are subjected to high-frequency, rapid reciprocating opening and closing for a long time, and the sealing surface between the valve seat and the ball has an uneven wear distribution problem. In this paper, a theoretical derivation of the seat wear volume and wear depth during the hydrogen ball valve adhesive wear process is presented, and a simulation model based on transient dynamics theory is established to carry out a nonlinear finite element analysis of the dynamic contact and frictional wear of the sealing structure during the opening and closing process of the hydrogen ball valve. In order to effectively reduce the wear unevenness of the sealing surface of the ball valve, a new type of valve seat sealing surface with an unequal-width structure is proposed. Comparing the sealing pressure and seat sealing surface wear depth of the ball valve before and after the improvement, the improved ball valve sealing performance is reliable, while the seat sealing surface wear distribution is more uniform.

Safety and Tolerability of Direct Ischemic Postconditioning Following Thrombectomy for Acute Ischemic Stroke.

BACKGROUND: Experimental studies have demonstrated the neuroprotection of ischemic postconditioning (IPostC) in acute ischemic stroke by attenuating ischemia-reperfusion injury. This study aimed to investigate the safety and tolerability of direct IPostC in both a dog model and patients with acute ischemic stroke treated with thrombectomy. METHODS: The study involved 2 parts. First, IPostC was induced by repeated balloon inflation and deflation in dogs, where a low-pressure balloon was navigated to the anterior spinal artery, and 4 cycles of 5-minute ischemia followed by 5-minute reperfusion were performed. Vascular injuries were assessed using angiography and vascular tissue specimens. Then, a 3+3 dose-escalation trial was conducted in patients with acute ischemic stroke following successful thrombectomy recanalization. Patients received direct IPostC with ischemia and reperfusion durations in progressive increments of 0, 1, 2, 3, 4, and 5 minutes ×4 cycles. Major adverse responses were defined as vessel perforation, rupture, dissection, reocclusion, severe vasospasm, thrombotic events, and rupture of the balloon. RESULTS: IPostC was investigated in 4 dogs. No vessel perforation or rupture, dissection, or vasospasm was observed under the angiography. Only 1 vessel experienced mild injury between the intima and the internal elastic membrane detected on a histopathologic slide. Then, 18 patients were recruited. The duration of IPostC was progressively escalated with no major response happened. No patient experienced agitation, discomfort, or other tolerability issues. Five patients (27.8%) experienced any intracranial hemorrhage after thrombectomy, and 1 (5.6%) was symptomatic. At 3-month follow-up, no patient died, and 9 patients (50%) achieved functional independence. CONCLUSIONS: Direct IPostC inducing by 4 cycles of 5-minute ischemia followed by 5-minute reperfusion is safe, feasible, and tolerable in patients with acute ischemic stroke treated with thrombectomy. Further investigations are needed to determine the safety and preliminary efficacy of direct IPostC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05153655.

Gas/Liquid Chromatography-Mass Spectrometry Analysis of Key Functional Substances Regulating Poll Gland Secretion in Male Camels during Seasonal Estrus.

Increased poll gland secretion is a major characteristic and indicator of estrus in male Bactrian camels; however, research on these poll glands and their secretion is extremely rare. In this study, we determine the chemical composition of poll gland secretions and identify the key functional substances that regulate seasonal estrus in male camels. A GC/LC-MS dual platform was used to analyze ventral hair (control) and neck mane samples containing poll gland secretions from male Bactrian camels during estrus. Multidimensional and single-dimensional analyses were used to screen differentially expressed metabolites (DEMs) between groups. Functional prediction of enriched metabolites was performed using a Human Metabolome Database comparison and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, which were then compared with a behavioral analysis of male Bactrian camels in estrus. A total of 1172 DEMs and 34 differential metabolic pathways were identified. One metabolite group was found to relate to steroid synthesis and metabolism, and another metabolite group was associated with neural metabolism. Therefore, we speculate that steroids and neurochemicals jointly regulate estrous behavior in male Bactrian camels, thus providing theoretical insights into the development and function of poll glands in Bactrian camels.

Improved Differential Diagnosis Based on BI-RADS Descriptors and Apparent Diffusion Coefficient for Breast Lesions: A Multiparametric MRI Analysis as Compared to Kaiser Score.

RATIONALE AND OBJECTIVES: To develop the nomogram utilizing the American College of Radiology BI-RADS descriptors, clinical features, and apparent diffusion coefficient (ADC) to differentiate benign from malignant breast lesions. MATERIALS AND METHODS: A total of 341 lesions (161 malignant and 180 benign) were included. Clinical data and imaging features were reviewed. Univariable and multivariable logistic regression analyses were performed to determine the independent variables. ADC as a continuous or classified into binary form with a cutoff value of 1.30 × 10-3 mm2/s, incorporated other independent predictors to construct two nomograms, respectively. Receiver operating curve and calibration plot was employed to test the models' discriminative ability. The diagnostic performance between the developed model and the Kaiser score (KS) was also compared. RESULTS: In both models, high patient age, the presence of root sign, time-intensity curves (TICs) types (plateau and washout), heterogenous internal enhancement, the presence of peritumoral edema, and ADC were independently associated with malignancy. The AUCs of two multivariable models (AUC, 0.957; 95% CI: 0.929-0.976 and AUC, 0.958; 95% CI: 0.931-0.976) were significantly higher than that of the KS (AUC, 0.919, 95% CI: 0.885-0.946; both P < 0.001). At the same sensitivity of 95.7%, our models showed an increase in specificity by 5.56% (P = 0.076) and 6.11% (P = 0.035), respectively, as compared to the KS. CONCLUSION: The models incorporating MRI features (root sign, TIC, margins, internal enhancement, and presence of edema), quantitative ADC value, and patient age showed improved diagnostic performance and might have avoided more unnecessary biopsies in comparison with the KS, although further external validation is required.

Group 2 innate lymphoid cells resolve neuroinflammation following cerebral ischaemia.

BACKGROUND: Acute brain ischaemia elicits pronounced inflammation, which aggravates neural injury. However, the mechanisms governing the resolution of acute neuroinflammation remain poorly understood. In contrast to regulatory T and B cells, group 2 innate lymphoid cells (ILC2s) are immunoregulatory cells that can be swiftly mobilised without antigen presentation; whether and how these ILC2s participate in central nervous system inflammation following brain ischaemia is still unknown. METHODS: Leveraging brain tissues from patients who had an ischaemic stroke and a mouse model of focal ischaemia, we characterised the presence and cytokine release of brain-infiltrating ILC2s. The impact of ILC2s on neural injury was evaluated through antibody depletion and ILC2 adoptive transfer experiments. Using Rag2-/-γc-/- mice receiving passive transfer of IL-4-/- ILC2s, we further assessed the contribution of interleukin (IL)-4, produced by ILC2s, in ischaemic brain injury. RESULTS: We demonstrate that ILC2s accumulate in the areas surrounding the infarct in brain tissues of patients with cerebral ischaemia, as well as in mice subjected to focal cerebral ischaemia. Oligodendrocytes were a major source of IL-33, which contributed to ILC2s mobilisation. Adoptive transfer and expansion of ILC2s reduced brain infarction. Importantly, brain-infiltrating ILC2s reduced the magnitude of stroke injury severity through the production of IL-4. CONCLUSIONS: Our findings revealed that brain ischaemia mobilises ILC2s to curb neuroinflammation and brain injury, expanding the current understanding of inflammatory networks following stroke.