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.

Endoluminal rescue of false lumen graft deployment in TEVAR for type B aortic dissection: a case report and literature review.

Background: Thoracic endovascular aortic repair (TEVAR) has increasingly become the preferred surgical intervention for Stanford type B aortic dissection (TBAD). The primary objective of this procedure is to seal the primary entry tear to promote positive aortic remodeling. However, the increased use of TEVAR has also led to a rise in surgical complications. Among these, the accidental deployment of the stent into the false lumen is a rare but serious complication that can result in aortic false lumen rupture and inadequate perfusion of abdominal organs. Case summary: This case report described a 78-year-old man who presented to our hospital with sudden onset chest and back pain and was subsequently diagnosed with TBAD via aortic CTA. As conventional medical therapy failed to alleviate his chest pain, the patient underwent TEVAR. During the procedure, a complication arose when the distal end of the endograft was mistakenly deployed into the false lumen, leading to insufficient perfusion of the abdominal organs. Recognizing this issue intraoperatively, an additional endograft was promptly inserted at the distal end to reroute blood flow back to the true lumen of the aorta, thereby restoring visceral perfusion. Post-intervention, the patient's chest pain improved, and he was successfully discharged from the hospital. Conclusion: Accidental deployment of a endograft into the false lumen during TEVAR is a rare but serious complication. Intraoperative angiography plays a crucial role in rapidly and accurately identifying this issue by detecting insufficient perfusion of abdominal organs. The use of intravascular ultrasound may help reduce the incidence of this complication. Endovascular repair is an effective emergency strategy to quickly redirect blood flow back to the true lumen, making it the preferred method for managing such emergencies.

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.

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.

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.

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.

Lysosomal transmembrane protein 5: Impact on immune cell function and implications for immune-related deficiencies.

Lysosomal transmembrane protein 5 (LAPTM5) is a lysosomal-associated protein that interacts with surface receptors on various immune cells, including B cells, T cells, macrophages and dendritic cells. Dysregulated expression of LAPTM5 is implicated in the development of multiple immune system-related diseases. In the context of tumors, elevated LAPTM5 levels in immune cells are associated with decreased cell membrane levels of T cell receptors (TCR) or B cell receptors (BCR), leading to impaired antigen presentation and immune escape, thereby promoting tumor progression. Besides, LAPTM5 is critical for inducing non-apoptotic cell death in tumor parenchymal cells since its downregulation leads to inhibition of the cell death pathway in the tumor parenchyma and subsequent enhanced tumorigenesis. LAPTM5 also affects the cell cycle as the elevated LAPTM5 expression in solid tumors causes its inability to block the G0/G1 stage. In non-solid tumors, abnormal LAPTM5 expression disrupts blood cell development and causes irregular proliferation. Furthermore, in the nervous system, aberrant LAPTM5 expression in microglia is correlated with Alzheimer's disease severity. In this context, further preclinical research is essential to validate LAPTM5 as a potential target for diagnosis, therapy, and prognosis in immune-related disorders and tumors. This review summarized the current insights into LAPTM5's role in tumors and immune-related deficits, highlighting its potential as a valuable biomarker and therapeutic target.

Early peripheral perfusion index predicts 28-day outcome in patients with septic shock.

BACKGROUND: To investigate the prognostic value of the peripheral perfusion index (PPI) in patients with septic shock. METHODS: This prospective cohort study, conducted at the emergency intensive care unit of Peking University People's Hospital, recruited 200 patients with septic shock between January 2023 and August 2023. These patients were divided into survival (n=84) and death (n=116) groups based on 28-day outcomes. Clinical evaluations included laboratory tests and clinical scores, with lactate and PPI values assessed upon admission to the emergency room and at 6 h and 12 h after admission. Risk factors associated with mortality were analyzed using univariate and multivariate Cox regression analyses. Receiver operator characteristic (ROC) curve was used to assess predictive performance. Mortality rates were compared, and Kaplan-Meier survival plots were created. RESULTS: Compared to the survival group, patients in the death group were older and had more severe liver damage and coagulation dysfunction, necessitating higher norepinephrine doses and increased fluid replacement. Higher lactate levels and lower PPI levels at 0 h, 6 h, and 12 h were observed in the death group. Multivariate Cox regression identified prolonged prothrombin time (PT), decreased 6-h PPI and 12-h PPI as independent risk factors for death. The area under the curves for 6-h PPI and 12-h PPI were 0.802 (95% CI 0.742-0.863, P<0.001) and 0.945 (95% CI 0.915-0.974, P<0.001), respectively, which were superior to Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment (SOFA) scores (0.864 and 0.928). Cumulative mortality in the low PPI groups at 6 h and 12 h was significantly higher than in the high PPI groups (6-h PPI: 77.52% vs. 22.54%; 12-h PPI: 92.04% vs. 13.79%, P<0.001). CONCLUSION: PPI may have value in predicting 28-day mortality in patients with septic shock.

Fertility-sparing treatment in MSI-H/MMRd endometrial carcinoma or atypical endometrial hyperplasia: A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to describe the oncological and reproductive outcomes of patients with MSI-H/MMRd endometrial carcinoma (EC) or atypical endometrial hyperplasia (AEH) undergoing fertility-sparing treatment. METHODS: The study protocol was registered with the PROSPERO database (No: CRD42024530406). A systematic literature search in major electronic databases (PubMed, Embase, and Cochrane Library) was conducted from January 1, 2013 to August 10, 2024. The primary outcomes were complete remission (CR) rate and recurrence rate. Other outcomes included oncological outcomes in patients with Lynch syndrome and overall patient fertility status. RESULTS: The study included ten retrospective studies summarizing 66 patients with MSI-H/MMRd undergoing fertility-sparing treatment. The publication bias analysis was low. The length of follow-up varied from 3 to 164 months according to the different studies analyzed. After fertility-sparing treatment, 61.8 % of patients achieved CR, and 41.2 % of patients relapsed. Twelve patients were identified with germline mutations in Lynch syndrome, nine (75 %) achieved CR, and seven (77.8 %) relapsed. Only one study with active use of assisted reproductive technology reported a 1-year cumulative pregnancy rate of more than 60 % and more than half live births, while the remaining five studies assessed fertility outcomes and reported only one live birth. CONCLUSION: EC and AEH patients with the MSI-H/MMRd subtype had a low remission rate and high recurrence rate compared to conservative treatment. Caution is recommended when evaluating fertility-sparing therapy for patients with the MSI-H/MMRd subtype.

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.

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.

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.

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.

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.

Pharmacokinetics, Mass Balance, and Biotransformation of [14C]tinengotinib, A Novel Multi-target Kinase Inhibitor, in Healthy Subjects.

BACKGROUND AND OBJECTIVE: Tinengotinib, a novel multi-target small molecule kinase inhibitor, is currently undergoing phase II clinical trial in the USA and China. The purpose of this open-label study was to investigate the absorption, metabolism, and excretion of [14C]tinengotinib following a single oral dose in healthy subjects. METHODS: Six healthy male subjects received a single oral dose of [14C]tinengotinib capsules at 10 mg/100 µCi, and blood, urine, and feces samples were collected. Phenotyping experiments were further conducted to confirm the enzymes involved in its metabolism. RESULTS: Tinengotinib was rapidly absorbed in plasma with a time to peak drug concentration (Tmax) of 1.0-4.0 h post-dose and a long terminal half-life (t½) of 23.7 h. Blood-to-plasma radioactivity concentration ratios across timepoints ranged from 0.780 to 0.827, which indicated minimal association of radioactivity with blood cells. The mean cumulative excreted radioactivity was 99.57% of the dose, including 92.46% (68.65% as unchanged) in feces and 7.11% (0.28% as unchanged) in urine. In addition to unchanged tinengotinib, a total of 11 radioactive metabolites were identified in plasma, urine, and feces. The most abundant circulating radioactivity was the parent drug in plasma, which comprised 88.23% of the total radioactivity area under the concentration-time curve (AUC). Metabolite M410-3 was a major circulating metabolite, accounting for 5.38% of the parent drug exposure and 4.75% of the total drug-related exposure, respectively. All excreted metabolites accounted for less than 5.10% and 1.82% of the dose in feces and urine, respectively. In addition, no unique metabolites were observed in humans. Tinengotinib was metabolized mainly via CYP3A4. CONCLUSIONS: Overall, tinengotinib demonstrated a complete mass balance with limited renal excretion, no disproportionate blood metabolism, and slow elimination, primarily through the fecal route. The results of this study provide evidence to support the rational use of tinengotinib as a pharmacotherapeutic agent. REGISTRATION: ChinadrugTrials.org.cn identifier: CTR20212852.

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).

Quantification of Cardiac Iron Overload at 3 T MRI in a Rabbit Model Utilizing ME-GRE T2* Sequence.

BACKGROUND: Myocardial iron overload can lead to myocardial dysfunction, muscle cell injury, and end-stage heart failure. The enhanced signal-to-noise ratio and technical advancements have made 3 T magnetic resonance imaging (MRI) more accessible in clinical settings. However, 3 T assessments for early diagnosis of myocardial iron overload are scarce. PURPOSE: To evaluate the feasibility of myocardial iron quantification using 3 T MRI in a rabbit model of iron overload. STUDY TYPE: Animal model. ANIMAL MODEL: Overall, 40 male New Zealand white rabbits were categorized into control (N = 8; no treatment) and experimental (N = 32; weekly 200 mg/kg iron dextran injections) groups. SEQUENCE: 3 T MRI with multi-echo gradient echo (ME-GRE) T2* sequence. ASSESSMENT: Each week, two experimental rabbits were randomly selected for blood collection to determine serum iron (SI) levels; their tissue was harvested to assess myocardial and hepatic iron deposition. STATISTICAL TESTS: Spearman's rank correlation tests were used to evaluate the correlations among R2*, cardiac iron concentration (CIC), liver iron concentration (LIC), total amount of iron injected, and SI levels. P ≤ 0.05 was considered statistically significant. RESULTS: The myocardial T2* value in the experimental group was significantly lower than that of the control group. An excellent correlation was observed between R2* values and CIC (r = 0.854). CIC moderately correlated with LIC (r = 0.712) and the total amount of iron injected (r = 0.698). A strong correlation was observed between the total amount of iron injected and LIC (r = 0.866). SI levels poorly correlated with the total amount of iron injected (r = 0.205, P = 0.277) and LIC (r = 0.170, P = 0.370) but fairly correlated with CIC (r = 0.415, P = 0.022). DATA CONCLUSION: A 3 T MRI with an ME-GRE sequence may serve as a noninvasive method for evaluating cardiac iron content. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 1.

First Report on the Trophic Transfer and Priority List of Liquid Crystal Monomers in the Pearl River Estuary.

Liquid crystal monomers (LCMs) are emerging organic pollutants due to their potential persistence, toxicity, and bioaccumulation. This study first characterized the levels and compositions of 19 LCMs in organisms in the Pearl River Estuary (PRE), estimated their bioaccumulation and trophic transfer potential, and identified priority contaminants. LCMs were generally accumulated in organisms from sediment, and the LCM concentrations in all organisms ranged from 32.35 to 1367 ng/g lipid weight. The main LCMs in organisms were biphenyls and analogues (BAs) (76.6%), followed by cyanobiphenyls and analogues (CBAs) (15.1%), and the least were fluorinated biphenyls and analogues (FBAs) (11.2%). The most abundant LCM monomers of BAs, FBAs, and CBAs in LCMs in organisms were 1-(4-propylcyclohexyl)-4-vinylcyclohexane (15.1%), 1-ethoxy-2,3-difluoro-4-(4-(4-propylcyclohexyl) cyclohexyl) benzene (EDPBB, 10.1%), and 4'-propoxy-4-biphenylcarbonitrile (5.1%), respectively. The niche studies indicated that the PRE food web was composed of terrestrial-based diet and marine food chains. Most LCMs exhibited biodilution in the terrestrial-based diet and marine food chains, except for EDPBB and 4,4'-bis(4-propylcyclohexyl) biphenyl (BPCHB). The hydrophobicity, position of fluorine substitution of LCMs, and biological habits may be important factors affecting the bioaccumulation and trophic transfer of LCMs. BPCHB, 1-(prop-1-enyl)-4-(4-propylcyclohexyl) cyclohexane, and EDPBB were characterized as priority contaminants. This study first reports the trophic transfer processes and mechanisms of LCMs and the biomonitoring in PRE.