Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke.

JOURNAL/nrgr/04.03/01300535-202503000-00029/figure1/v/2024-06-17T092413Z/r/image-tiff It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 µM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 µM) promoted nuclear translocation of ß-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the ß-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Injectable Hydrogel With Glycyrrhizic Acid and Asiaticoside-Loaded Liposomes for Wound Healing.

BACKGROUND: Open skin wounds increase the risk of infections and can compromise health. Therefore, applying medications to promote healing at the injury site is crucial. In practice, direct drug delivery is often difficult to maintain for a long time due to rapid absorption or wiping off, which reduces the efficiency of wound healing. Consequently, the development of bioactive materials with both antibacterial and wound-healing properties is highly desirable. METHODS: This study synthesized liposomes loaded with glycyrrhizic acid (GA) and asiaticoside (AS) by film dispersion-ultrasonication method, which were then incorporated into a GelMA solution and cross-linked by ultraviolet light to form a bioactive composite hydrogel for wound dressings. RESULTS: This hydrogel is conducive to the transport of nutrients and gas exchange. Compared with GelMA hydrogel (swelling rate 69.8% ± 5.7%), the swelling rate of GelMA/Lip@GA@AS is lower, at 52.1% ± 1.0%. GelMA/Lip@GA@AS also has better compression and rheological properties, and the in vitro biodegradability is not significantly different from that of the collagenase-treated group. In addition, the hydrogel polymer has a stable drug release rate, good biocompatibility, and an angiogenic promoting effect. In vitro experiments prove that, at concentrations of 0.5, 1, 2, and 3 mg/mL, GelMA/Lip@GA@AS can inhibit the growth of Staphylococcus aureus. CONCLUSION: We synthesized GelMA/Lip@GA@AS hydrogel and found it possesses advantageous mechanical properties, rheology, and biodegradability. Experimental results in vitro showed that the bioactive hydrogel could efficiently release drugs, exhibit biocompatibility, and enhance angiogenesis and antimicrobial effects. These results suggest the promising application of GelMA/Lip@GA@AS hydrogel in wound-dressing materials.

Assessing the accuracy of CMRtools software for diagnosing liver iron overload in thalassemia patients: influencing factors and optimisation strategies.

Background: CMRtools is a software package that can be used to measure T2* values to diagnose liver iron overload, however, its accuracy in terms is affected by multiple factors, including goodness-of-fit (R2 value), the number of echo time (TE) images, and the liver iron concentration (LIC). To investigate the effects of the R2 value, the number of TE images, and the LIC on the accuracy of CMRtools software for measuring T2* values to diagnose liver iron overload (LIO). Materials and methods: CMRtools software was used to measure liver T2* values among 108 thalassemia patients via the truncation method, and the R2 values, the number of TE images, and T2* values were recorded. These values were subsequently converted into liver iron concentration (LICT) values. The LICF (derived from MRI-R2/FerriScan) was used as a reference, and the diagnostic accordance rate (DAR) was compared between R2 value subgroups, between TE image number subgroups, and between LIC subgroups. Results: The greater the R2 value was, the greater the standardized DAR (SDAR) was (p < 0.05). The SDAR are not identical between each TE image number subgroup (p > 0.05). However, the relationship between TE image number subgroups and SDAR was analysed using Spearman's correlation, and it was found to be positively correlated (rs = 0.729, p = 0.017). The SDAR are not identical between each LIC subgroup (p > 0.05), furthermore, the relationship between LIC subgroup and SDAR was found irrelevant (p = 0.747). Conclusion: The accuracy of CMRtools software for diagnosing LIO in patients with thalassemia can be improved by artificially controlling the number of TE images to be fitted and selecting higher R2 values.

Visual assessment and quantitative analysis of dual-energy CT virtual non-calcium in imaging diagnosis of multiple myeloma.

OBJECTIVE: To evaluate the reliability and diagnostic performance of dual-energy CT virtual non-calcium imaging in diagnosing bone marrow infiltration in multiple myeloma. MATERIALS AND METHODS: Seventy-two patients with multiple myeloma and ten controls were recruited. Patients received dual-energy CT and MRI while controls underwent dual-energy CT only, covering the cervical, thoracic, and lumbar spine and the pelvis. Virtual non-calcium images were compared with magnetic resonance images for confirmation and pattern classification. Fleiss Kappa analysis assessed consistency between virtual non-calcium and MRI classifications. Inter-observer agreement for virtual non-calcium and CT attenuation values was evaluated using Bland-Altman analysis. Diagnostic performances across various sites were evaluated using analysis of variance and receiver operating characteristic curve analysis. RESULTS: Dual-energy CT achieved higher consistency in classifying bone marrow infiltration in multiple myeloma than did MRI (kappa = 0.944). In the overall analysis, the mean virtual non-calcium attenuation values in the bone marrow infiltration group (- 28.3 HU; 95% confidence interval (CI), - 32.1, - 24.6) were higher than those in the non-bone marrow infiltration (- 97.5 HU; 95% CI, - 104.7, - 90.3) and control (- 89.1 HU; 95% CI, - 95.1, - 83.1; F = 172.027, P < 0.001) groups. The optimal cutoff values for virtual non-calcium attenuation varied across the overall (- 42.2 HU), cervical spine (- 21.9 HU), thoracic spine (- 42.8 HU), lumbar spine (- 56.9 HU), and pelvis (- 66.3 HU). CONCLUSION: Dual-energy CT virtual non-calcium imaging and MRI exhibited good consistency in categorising bone marrow infiltration patterns in multiple myeloma. Different virtual non-calcium attenuation value cutoffs should be used to diagnose bone marrow infiltration in various body regions.

Edaravone Dexborneol provides neuroprotective effect by inhibiting neurotoxic activation of astrocytes through inhibiting NF-κB signaling in cortical ischemia.

Edaravone Dexborneol (EDB), comprised of edaravone and (+)- bornel, has been demonstrated to have synergistic effects of antioxidant and anti-inflammatory, which makes it to be applied for stroke as a protectant. However, the underlying mechanism of neuroprotection of EDB has not been fully elucidated. Increasing evidence has shown that neurotoxic A1 astrocytes were closely related to neuronal death after cerebral ischemia. However, whether EDB could provide neuroprotection by modulating the activation of astrocytes has not yet been elucidated. The present study aimed to explore whether EDB afforded neuroprotection by modulating A1 polarization of astrocytes and the down-stream signaling after cerebral ischemia. We first validated the neuroprotective effects of EDB in mice suffering focal cerebral ischemia via evaluating behavioral test, infarct volumes and neuronal survival. As for the down-stream signaling, our data further showed that EDB alleviated neuronal death by suppressing activation of neurotoxic A1 astrocytes via inhibition of NF-κB signaling pathway in vitro. Additionally, administration of EDB reduced the number of A1 reactive astrocytes in mice of focal cerebral ischemia. The above findings demonstrated that EDB provided neuroprotective effect by inhibiting neurotoxic activation of A1 astrocytes in animal model of cerebral ischemia, which indicated that EDB-mediated phenotypic regulation of astrocytes is a potential research direction to promote neurological recovery in central nervous system (CNS) diseases.

Attract and kill trees? No simple solution for Anoplophora glabripennis (Coleoptera: Cerambycidae) control.

Anoplophora glabripennis (Motschulsky), the Asian longhorned beetle, is a serious wood-boring pest of hardwood trees. There have been records that suggest Elaeagnus angustifolia L. (Elaeagnaceae) might be an "attract and kill" tree species for A. glabripennis, i.e., a tree that is attractive to A. glabripennis adults but kills their oviposited eggs. To evaluate the possibility of E. angustifolia as a control measure for A. glabripennis, we carried out a series of behavioral experiments in the laboratory and in the field. Results showed that: (i) A. glabripennis females preferred E. angustifolia branches and leaves over poplar tree species evaluated; the weight of feces from both female and male A. glabripennis feeding on E. angustifolia was significantly higher than from those feeding on Populus deltoides 'Shalinyang' or Populus alba. L. var. pyramidalis; (ii) the average lifespan of females and males feeding on E. angustifolia was significantly longer than those feeding on other host trees evaluated; (iii) in the laboratory oviposition choice experiment, there were significantly fewer egg notch grooves on E. angustifolia than on P. deltoides 'Shalinyang', and those made in E. angustifolia were without eggs; (iv) in the field, the number of egg notch grooves on E. angustifolia was 43.6 ±â€…18.1 per stem, but the number of eggs laid was only 14.4 ±â€…6.4 per stem; and (v) Field surveys of existing mixed forests showed that when E. angustifolia was planted with P. alba. var. pyramidalis or Populus simonii × (Populus pyramidalis + Salix matsudana) 'Poparis' in the mixed forest, both poplar varieties suffered greater infestation than E. angustifolia. Therefore, E. angustifolia is not a suitable attract and kill tree to be extensively planted in mixed forests for control of A. glabripennis.

Effects of nutrient ratios on a newly harmful dinoflagellate Heterocapsa bohaiensis: Evidence from growth, toxicity and transcriptome analyses.

Heterocapsa bohaiensis is a newly identified dinoflagellate species that causes harmful blooms in coastal areas in China, Malaysian, and New Caledonian. These blooms have led to substantial economic losses for local aquaculture. Previous studies have mainly focused on understanding the toxicity of H. bohaiensis. However, the causes of H. bohaiensis blooms remain unknown. In this study, we aimed to ascertain nitrogen (N) and phosphorus (P) requirements for the growth and reproduction of H. bohaiensis. Additionally, we sought to understand the functional mechanisms by comparing the transcriptomes of H. bohaiensis under nutrient-limited conditions and control conditions. The results revealed a wide range of acceptable N:P ratios for H. bohainensis, attributed to a mechanism involving nutrient storage, which allowed H. bohainensis to sustain its growth even when either nitrate or phosphate was depleted. Higher N:P ratios (>27.5) were more conducive to the growth of H. bohainensis than f/2 medium or low ratios, which is related to the N:P ratios absorbed by H. bohainensis. The toxicity of H. bohainensis was significantly enhanced in N-limited or P-limited states. These findings underscore the significance of the physiological metabolism of H. bohainensis in adapting to environmental stresses induced by human activities and establishing the dominance of blooms.

Cross-layer importance evaluation for neural network pruning.

Filter pruning has achieved remarkable success in reducing memory consumption and speeding up inference for convolutional neural networks (CNNs). Some prior works, such as heuristic methods, attempted to search for suitable sparse structures during the pruning process, which may be expensive and time-consuming. In this paper, an efficient cross-layer importance evaluation (CIE) method is proposed to automatically calculate proportional relationships among convolutional layers. Firstly, every layer is pruned separately by grid sampling way to obtain the accuracy of the model for all sampling points. And then, contribution matrices are built to describe the importance of each layer to model accuracy. Finally, the binary search algorithm is used to search the optimal sparse structure under a target pruned value. Extensive experiments on multiple representative image classification tasks demonstrate that proposed method acquires better compression performance under a little time cost compared to existing pruning algorithms. For instance, it reduces more than 50% FLOPs with only a small loss of 0.93% and 0.43% in the top-1 and top-5 accuracy for ResNet50, respectively. At the cost of only 0.24% accuracy loss, the pruned VGG19 model parameters are successfully compressed by 27.23× and the throughput has increased by 2.46×. On the whole, CIE has an excellent effect on the deployment and application of the CNNs model in edge device in terms of efficiency and accuracy.

18F-FDG PET/CT metrics-based stratification of large B-cell lymphoma receiving CAR-T cell therapy: immunosuppressive tumor microenvironment as a negative prognostic indicator in patients with high tumor burden.

Chimeric antigen receptor T (CAR-T) cell therapy has greatly improved the prognosis of relapsed and refractory patients with large B-cell lymphoma (LBCL). Early identification and intervention of patients who may respond poorly to CAR-T cell therapy will help to improve the efficacy. Ninety patients from a Chinese cohort who received CAR-T cell therapy and underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans at the screening stage (median time to infusion 53.5 days, range 27-176 days), 1 month and 3 months after CAR-T cell infusion were analyzed, with RNA-sequencing conducted on 47 patients at the screening stage. Patients with maximum diameter of the largest lesion (Dmax) < 6 cm (N = 60) at screening stage showed significantly higher 3-month complete response rate (85.0% vs. 33.3%, P < 0.001), progression-free survival (HR 0.17; 95% CI 0.08-0.35, P < 0.001) and overall survival (HR 0.18; 95% CI 0.08-0.40, P < 0.001) than those with Dmax ≥ 6 cm (N = 30). Besides, at the screening stage, Dmax combined with extranodal involvement was more efficient in distinguishing patient outcomes. The best cut-off values for total metabolic tumor volume (tMTV) and total lesion glycolysis (tTLG) at the screening stage were 50cm3 and 500 g, respectively. A prediction model combining maximum standardized uptake value (SUVmax) at 1 month after CAR-T cell therapy (M1) and tTLG clearance rate was established to predict early progression for partial response/stable disease patients evaluated at M1 after CAR-T cell therapy and validated in Lyon cohort. Relevant association of the distance separating the two farthest lesions, standardized by body surface area to the severity of neurotoxicity (AUC = 0.74; P = 0.034; 95% CI, 0.578-0.899) after CAR-T cell therapy was found in patients received axicabtagene ciloleucel. In patients with Dmax ≥ 6 cm, RNA-sequencing analysis conducted at the screening stage showed enrichment of immunosuppressive-related biological processes, as well as increased M2 macrophages, cancer-associated fibroblasts, myeloid-derived suppressor cells, and intermediate exhausted T cells. Collectively, immunosuppressive tumor microenvironment may serve as a negative prognostic indicator in patients with high tumor burden who respond poorly to CAR-T cell therapy.

Precise Determination of Cd Isotope Ratios at 3-10 ng Level by Thermal Ionization Mass Spectrometry Using a Molybdenum Silicide Emitter.

Thermal ionization mass spectrometry (TIMS) combined with the double spike technique has excellent analytical precision for Cd isotopic ratio analysis. However, because of the low ionization efficiency of Cd by TIMS, it is still not possible to obtain high precision Cd isotope ratios for small sample size (<100 ng) due to the lack of a highly sensitive emitter for Cd. A new loading method using molybdenum silicide (MoSi2) emitter has been developed for Cd isotope ratio measurements. This emitter produces a significant enhancement in the ionization efficiency of Cd and thus significantly reduces the required sample size to the 3-10 ng level. Analyses of δ114/110Cd for the NIST SRM 3108 using 108Cd-116Cd double spike method show excellent reproducibility (2 SD) that reaches ±0.032‰, ±0.042‰, and ±0.051‰ for 10, 5, and 3 ng of Cd, respectively. This method was further verified with a suite of geological reference materials. Replicate digestions and analyses (n = 8, 2 SD) of δ114/110Cd for NIST SRM 2711a, NOD A-1, and GBW08401 demonstrated good external reproducibility with results of 0.596 ± 0.024‰ for NIST SRM 2711a, 0.150 ± 0.036‰ for NOD A-1, and -0.665 ± 0.084‰ for GBW08401. These data clearly indicate that MoSi2 is an excellent alternative for traditional silica gel to Cd isotopic measurements, especially for samples with a low content of Cd.

Overall survival prediction of gastric cancer using the gene signature of CT-detected extramural venous invasion combined with M2 macrophages infiltration.

BACKGROUND: CT-detected Extramural venous invasion (EMVI) is known as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). However, the molecular basis is not clear. In colorectal cancer, M2 macrophages plays a vital role in determining EMVI. This study aimed to investigate the relationship between CT-detected EMVI and the M2 macrophages as well as prognosis predictionusing a radiogenomic approach. METHOD: We utilized EMVI-related genes (from mRNA sequencing of 13 GC samples correlated with EMVI score by spearman analysis, P < 0.01) to overlap the co-expression genes of WGCNA module and M2 macrophages related genes (from mRNA data of 371 GC patients in TCGA database), generating a total of 136 genes. An EMVI-M2-prognosis-related hub gene signature was constructed by COX and least absolute shrinkage and selection operator (LASSO) analysis from a training cohort TCGA database (n = 371) and validated it in a validation cohort from GEO database (n = 357). High- and low-risk groups were divided by hub gene (EGFLAM and GNG11) signature-derived risk scores. We assessed its predictive ability through Kaplan-Meier (K-M) curve and COX analysis. Furthermore, we utilized ESTIMATE to detect tumor mutation burden (TMB) and evaluate sensitivity to immune checkpoint inhibitors (ICIs). Expression of hub genes was tested using western blotting and immunohistochemistry (IHC) analysis. RESULTS: The overall survival (OS) was significantly reduced in the high-risk group (Training/Validation: AUC = 0.701/0.620; P < 0.001/0.003). Furthermore, the risk score was identified as an independent predictor of OS in multivariate COX regression analyses (Training/Validation: HR = 1.909/1.928; 95% CI: 1.225-2.974/1.308-2.844). The low-risk group exhibited significantly higher TMB levels (P = 1.6e- 07) and greater sensitivity to ICIs. Significant higher expression of hub-genes was identified on multiple GC cell lines and original samples. Hub-genes knockdown in gastric cancer cell lines inhibited their proliferation, metastatic and invasive capacity to varying degrees. In vivo experiments indicate that EGFLAM, as one of the hub genes, its high expression can serve as a biomarker for low response to immunotherapy. CONCLUSION: Our study demonstrated EMVI-M2 gene signature could effectively predict the prognosis of GC tissue, reflecting the relationship between EMVI and M2 macrophages.

Radiomics prediction models of left atrial appendage hypercoagulability based on machine learning algorithms: an exploration about cardiac computed tomography angiography imaging.

Transesophageal echocardiography (TEE) is the standard method for diagnosing left atrial appendage (LAA) hypercoagulability in patients with atrial fibrillation (AF), which means LAA thrombus/sludge, dense spontaneous echo contrast and slow LAA blood flow velocity (< 0.25 m/s). Based on machine learning algorithms, cardiac computed tomography angiography (CCTA) radiomics features were adopted to construct prediction models and explore a suitable approach for diagnosing LAA hypercoagulability and adjusting anticoagulation. This study included 652 patients with non-valvular AF. The univariate analysis were used to select meaningful clinical characteristics to predict LAA hypercoagulability. Then 3D Slicer software was adopted to extract radiomics features from CCTA imaging. The radiomics score was calculated using the least absolute shrinkage and selection operator logistic regression analysis to predict LAA hypercoagulability. We then combined clinical characteristics and radiomics scores to construct a nomogram model. Finally, we got prediction models based on machine learning algorithms and logistic regression separately. The area under the receiver operating characteristic curve of radiomics score was 0.8449 in the training set and 0.7998 in the validation set. The nomogram model had a concordance index of 0.838. The final machine-learning based prediction models had good performances (best f1 score = 0.85). Radiomics features of long maximum diameter and high uniformity of Hounsfield unit in left atrial were significant predictors of the hypercoagulable state in LAA, with better predictive efficacy than clinical characteristics. Our combined models based on machine learning were reliable for hypercoagulable state screening and anticoagulation adjustment.

Impact of psychiatric disorders on the risk of glioma: Mendelian randomization and biological annotation.

BACKGROUND: The conflicting results about the relationship between certain psychiatric disorders and glioma has been reported in previous studies. Moreover, little is known about the common pathogenic mechanism between psychiatric symptoms and glioma. This study aims to find out mental disorders related etiology of glioma and to interpret the underlying biological mechanisms. METHODS: A panel of SNPs significantly associated with eight psychiatric disorders (ADHD, SCZ, Insomnia, NEU, MDD, MI, BIP, and SWB) were identified as exposure related genetic instruments. Summary GWAS data for glioma comes from eight independent datasets. Two sample Mendelian randomization study was undertaken by IVW, RAPS, MR.Corr, and BWMR methods. This study incorporated the glioma associated CGGA cohort and Rembrandt cohort. ssGSEA, variance expression, and KEGG were conducted to analyze the psychiatric disorders associated genes expression profiling and associated functional enrichment in the glioma patients. RESULTS: ADHD has a suggestive risk effect on all glioma (OR = 1.15, 95%CI = 1.01--1.29, P = 0.028) and a significant causal effect on non-GBM glioma (OR = 1.33, 95%CI = 1.12--1.58, P = 0.001). Similarly, SCZ displayed a causal relationship with all glioma (OR = 1.09, 95%CI = 1.04-1.14, P = 3.47 × 10-4) and non-GBM glioma (OR = 1.14, 95%CI = 1.08-1.21, P = 7.37 × 10-6). Besides, insomnia was correlated with the risk of non-GBM glioma (OR = 1.49, 95%CI = 1.03-2.17, P = 0.036). The ADHD/SCZ/Insomnia associated DEGs of glioma patients were enriched in neurotransmitter signaling pathway, immune reaction, adhesion, invasion, and metastasis, regulating the pluripotency of stem cells, metabolism of glycan, lipid and amino acids. LIMITATIONS: The extensibility of the conclusion to other ethnic and geographical groups should be careful because the data used in this study come from European. CONCLUSIONS: This study provides genetic evidence to suggest ADHD, SCZ, and insomnia as causes of glioma and common pathogenic process between ADHD/Insomnia/SCZ and glioma.

Transport and retention of COVID-19-related antiviral drugs in saturated porous media under various hydrochemical conditions.

Antiviral drugs have garnered considerable attention, particularly in the global battle against the COVID-19 pandemic, amid heightened concerns regarding environmentally acquired antiviral resistance. A comprehensive understanding of their transport in subsurface environments is imperative for accurately predicting their environmental fate and risks. This study investigated the mobility and retention characteristics of six COVID-19 antiviral drugs in saturated quartz sand columns. Results showed that the mobility of the drugs was primarily contingent on their hydrophobicity, with ribavirin and favipiravir exhibiting the highest transportability, while arbidol displaying the greatest retention. The transport characteristics of ribavirin and favipiravir remained largely unaffected by pH, whereas the retention of the other four antivirals remained consistently minimal under alkaline conditions. Elevating ionic strength marginally facilitated the transport of these antivirals, while the presence of Ca2+ notably enhanced their retention in quartz sand compared to Na+. Ribavirin and remdesivir warrant particular attention due to their relatively high transportability and propensity for environmentally acquired antiviral resistance. These findings contribute to an enhanced understanding of the leachate potential and transport of COVID-19-related antivirals in sandy porous media, furnishing fundamental data for predicting their environmental fate and associated risks.

Health economic evaluation of an artificial intelligence (AI)-based rapid nutritional diagnostic system for hospitalised patients: A multicentre, randomised controlled trial.

BACKGROUND & AIMS: Malnutrition is prevalent among hospitalised patients, and increases the morbidity, mortality, and medical costs; yet nutritional assessments on admission are not routine. This study assessed the clinical and economic benefits of using an artificial intelligence (AI)-based rapid nutritional diagnostic system for routine nutritional screening of hospitalised patients. METHODS: A nationwide multicentre randomised controlled trial was conducted at 11 centres in 10 provinces. Hospitalised patients were randomised to either receive an assessment using an AI-based rapid nutritional diagnostic system as part of routine care (experimental group), or not (control group). The overall medical resource costs were calculated for each participant and a decision-tree was generated based on an intention-to-treat analysis to analyse the cost-effectiveness of various treatment modalities. Subgroup analyses were performed according to clinical characteristics and a probabilistic sensitivity analysis was performed to evaluate the influence of parameter variations on the incremental cost-effectiveness ratio (ICER). RESULTS: In total, 5763 patients participated in the study, 2830 in the experimental arm and 2933 in the control arm. The experimental arm had a significantly higher cure rate than the control arm (23.24% versus 20.18%; p = 0.005). The experimental arm incurred an incremental cost of 276.52 CNY, leading to an additional 3.06 cures, yielding an ICER of 90.37 CNY. Sensitivity analysis revealed that the decision-tree model was relatively stable. CONCLUSION: The integration of the AI-based rapid nutritional diagnostic system into routine inpatient care substantially enhanced the cure rate among hospitalised patients and was cost-effective. REGISTRATION: NCT04776070 (https://clinicaltrials.gov/study/NCT04776070).

Investigating immune dysregulation and hub genes in septic cardiomyopathy development.

Septic cardiomyopathy is a life-threatening heart dysfunction caused by severe infection. Considering the complexity of pathogenesis and high mortality, the identification of efficient biomarkers are needed to guide clinical practice. Based on multimicroarray analysis, this study aimed to explore the pathogenesis of septic cardiomyopathy and the related immune landscape. The results showed that septic cardiomyopathy resulted in organ dysfunction due to extreme pro- and anti-inflammatory effects. In this process, KLRG1, PRF1, BCL6, GAB2, MMP9, IL1R1, JAK3, IL6ST, and SERPINE1 were identified as the hub genes regulating the immune landscape of septic cardiomyopathy. Nine transcription factors regulated the expression of these genes: SRF, STAT1, SP1, RELA, PPARG, NFKB1, PPARA, SMAD3, and STAT3. The hub genes activated the Th17 cell differentiation pathway, JAK-STAT signaling pathway, and cytokine‒cytokine receptor interaction pathway. These pathways were mainly involved in regulating the inflammatory response, adaptive immune response, leukocyte-mediated immunity, cytokine-mediated immunity, immune effector processes, myeloid cell differentiation, and T-helper cell differentiation. These nine hub genes could be considered biomarkers for the early prediction of septic cardiomyopathy.

Isovaleramide attenuates ethylene glycol poisoning-induced acute kidney injury and reduces mortality by inhibiting alcohol dehydrogenase activity in rats.

We explored the potential value of the alcohol dehydrogenase (ADH) inhibitor isovaleramide (ISO) in the treatment of acute ethylene glycol (EG) poisoning-induced acute kidney injury. Sprague-Dawley rats were divided into the control, EG, EG + ISO (10 mg/kg) and EG + ISO (20 mg/kg) groups. It is found that ISO intervention significantly reduced the ADH activity in liver tissue by using visible spectrophotometry, inhibited the in vivo metabolism of EG by using gas chromatography, lowered the levels of toxic metabolites glycolic acid and oxalic acid by using high-performance liquid chromatography and decreased the expression of kidney injury markers serum creatinine (sCr), KIM-1, neutrophil gelatinase-associated lipocalin (NGAL) and liver fatty acid-binding protein (L-FABP) by ELISA. Additionally, Western blotting results showed that ISO down-regulated the expression of apoptotic factors Bax and cleaved caspase-3 in the kidneys and upregulated the expression of antiapoptotic factor Bcl-2. Pizzolato staining and polarized light microscopy results revealed the reduced deposition of calcium oxalate crystals in the kidney tubules. Using haematoxylin and eosin (H&E), periodic acid-Schiff (PAS) and Masson staining, we found attenuated kidney tissue pathological injury. Finally, ISO significantly reduced the mortality rate. In conclusion, ISO has the potential to be a valuable drug for the treatment of EG poisoning-induced acute kidney injury.

The first emergence of paramyxovirus type 12 in wild birds in mainland, China.

Avian paramyxoviruses (APMV) belong to the subfamily Avulavirinae of the family Paramyxoviridae and include 22 distinct subtypes or serotypes (1-22). Avian paramyxovirus serotype 12 (APMV-12) is found sporadically in wild birds worldwide, and reports from only Italy and Taiwan have been published to date; information on its genetic variation and biological characteristics is still limited. In this study, 3 APMV-12 strains, designated WB19, LY9, and LY11, were isolated from 8643 wild bird faecal samples during the annual influenza virus surveillance of wild birds in Guangdong, China between 2018 and 2024, which is first reported in mainland China. The complete genomes of the 3 viruses with 6 gene segments, 3'-N-P-M-F-HN-L-5', were 15,231 nt in length. Phylogenetic analysis based on the whole genome showed that the 3 APMV-12 strains had the highest homology with an APMV-12 strain isolated from Taiwan in 2015, followed by the prototype APMV-12 strains isolated from mallard ducks in Italy in 2005. Genetic analysis of the whole gene of each of them indicated that they were derived from a Eurasian lineage. This study provides additional evidence that wild birds transmit viruses between countries, and this should be monitored to understand APMV transmission, evolution and epidemiology.

miR-NPs-RVG promote spinal cord injury repair: implications from spinal cord-derived microvascular endothelial cells.

BACKGROUND: Spinal cord injury (SCI) often leads to a loss of motor and sensory function. Axon regeneration and outgrowth are key events for functional recovery after spinal cord injury. Endogenous growth of axons is associated with a variety of factors. Inspired by the relationship between developing nerves and blood vessels, we believe spinal cord-derived microvascular endothelial cells (SCMECs) play an important role in axon growth. RESULTS: We found SCMECs could promote axon growth when co-cultured with neurons in direct and indirect co-culture systems via downregulating the miR-323-5p expression of neurons. In rats with spinal cord injury, neuron-targeting nanoparticles were employed to regulate miR-323-5p expression in residual neurons and promote function recovery. CONCLUSIONS: Our study suggests that SCMEC can promote axon outgrowth by downregulating miR-323-5p expression within neurons, and miR-323-5p could be selected as a potential target for spinal cord injury repair.

Hypoxia-induced TGFBI maintains glioma stem cells by stabilizing EphA2.

Rationale: Glioma stem cells (GSCs) have emerged as pivotal drivers of tumor malignancy, sustained by various microenvironmental factors, including immune molecules and hypoxia. In our previous study, we elucidated the significant role of transforming growth factor beta-induced protein (TGFBI), a protein secreted by M2-like tumor-associated macrophages, in promoting the malignant behavior of glioblastoma (GBM) under normoxic conditions. Building upon these findings, the objective of this study was to comprehensively explore the crucial role and underlying mechanisms of autocrine TGFBI in GSCs under hypoxic conditions. Methods: We quantified TGFBI expression in glioma specimens and datasets. In vitro and in vivo assays were employed to investigate the effects of TGFBI on sustaining self-renewal and tumorigenesis of GSCs under hypoxia. RNA-seq and LC-MS/MS were conducted to explore TGFBI signaling mechanisms. Results: TGFBI is preferentially expressed in GSCs under hypoxic conditions. Targeting TGFBI impair GSCs self-renewal and tumorigenesis. Mechanistically, TGFBI was upregulated by HIF1α in GSCs and predominantly activates the AKT-c-MYC signaling pathway in GSCs by stabilizing the EphA2 protein through preventing its degradation. Conclusion: TGFBI plays a crucial role in maintaining the stem cell properties of GSCs in the hypoxic microenvironment. Targeting the TGFBI/EphA2 axis emerges as a promising and innovative strategy for GBM treatment, with the potential to improve the clinical outcomes of patients.