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Abstract In this paper, we establish a sum rule that connects the pseudoentropy and entanglement entropy of the superposition state. Through analytical continuation of the superposition parameter, we demonstrate that the transition matrix and density matrix of the superposition state can be treated in a unified manner. Within this framework, we naturally derive sum rules for the (reduced) transition matrix, pseudo-Rényi entropy, and pseudoentropy. Furthermore, we demonstrate the close relationship between the sum rule for pseudoentropy and the singularity structure of the entropy function for the superposition state after analytical continuation. We also explore potential applications of the sum rule, including its relevance to understanding the gravity dual of non-Hermitian transition matrices and establishing upper bounds for the absolute value of pseudoentropy.

Abstract Background As the inflorescence of wheat, spike architecture largely determines grain productivity. Dissecting the genetic basis for the spike morphology of wheat can contribute to the designation of ideal spike morphology to improve grain production. Results The present study characterizes a dense spike1 (ds1) mutant, derived from Nongda3753, induced by EMS treatment, which exhibits a dense spike and reduced plant height. Through bulked segregant analysis sequencing (BSA-Seq) of two segregating populations, ds1 was mapped to the short arm of chromosome 7B. Further genotypic and phenotypic analyses of the residual heterozygous lines from F3 to F6 of Yong3002×ds1 revealed that there was a 0-135 Mb deletion in chromosome 7B associated with the dense spike phenotype. The reads count analysis of the two bulks in BSA-Seq, along with the cytological analysis of ds1, ND3753, NIL-ds1 and NIL-Y3002, confirmed that the partial unidirectional translocation of 5AL (543–713 Mb) to 7BS (0-135 Mb) exists in ds1. This translocation led to an increase in both copy number and expression of the Q gene, which is one of the reasons for the dense spike phenotype observed in ds1. Conclusion Partial unidirectional translocation from 5AL to 7BS was identified in the EMS-induced mutant ds1, which exhibits dense spike phenotype. This research illustrates the effect of one chromosome structure variation on wheat spike morphology, and provides new materials with several chromosome structure variations for future wheat breeding.

Abstract Background Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem). Method Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence. Results In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p

Abstract Mitochondria are vital for retinal cell function and survival, and there is growing evidence linking mitochondrial dysfunction to retinal degenerations. Although ARL3 mutations have been linked to multiple forms of retinal degeneration, the relationship between ARL3 and mitochondria remains unexplored. Herein, we investigated the effects of ARL3T31A, ARL3C118F, and ARL3T31A/C118F mutations on mitochondrial function in fibroblasts obtained from patients with ARL3‐related rod‐cone dystrophy. Our findings revealed that these mutations led to a decrease in mitochondrial respiration, an increase in the accumulation mitochondrial reactive oxygen species (ROS), and induction of apoptosis in fibroblasts. Additionally, we conducted a comparative analysis of the effects of ARL3T31A, ARL3C118F, and ARL3T31A/C118F proteins on mitochondria in ARPE‐19 cells. Results showed that ARL3T31A and ARL3T31A/C118F not only affected mitochondrial function but also induced apoptosis in ARPE‐19 cells. Conversely, ARL3C118F primarily influenced cell apoptosis with minimal effects on mitochondrial function in ARPE‐19 cells. Transcriptome analysis further suggested the involvement of respiratory electron transport, response to ROS, and apoptotic signaling pathways in ARL3T31A/C118F cells. Our study demonstrated that ARL3‐related mutations play a significant role in the diversity of mitochondrial function, providing novel insights into the functional analysis of ARL3‐related mutations.

Abstract Accurate and efficient identification of water inrush sources, as one of the three critical elements of mine water hazards, is crucial for mine water management. To identify the sources of mine water inrush effectively, a model named HBA-CatBoost is introduced. This model is established on the hybrid bat algorithm (HBA)-optimized category feature gradient boosting tree (CatBoost), and the shapley additive explanation (SHAP) method is employed to elucidate the model’s decision-making process. Given the prevalent occurrence of water hazards in coal seam roofs and floors in the northern Guizhou coalfield, coupled with the challenges in pinpointing water inrush sources in mines, the HBA-CatBoost model is tested at the Longfeng Coal Mine in northern Guizhou to validate its practicality. Comparative analysis with the HBA-RF, HBA-XGBoost, CatBoost, RF, and XGBoost models demonstrates that the hybrid bat algorithm significantly enhances the classification performance of the CatBoost model, resulting in improved convergence speed and classification accuracy. The HBA-CatBoost model outperforms the aforementioned models in terms of classification effectiveness, achieving accuracy, recall, precision, and F1 scores of 96.43%, 97.22%, 96.43%, and 96.61%, respectively. The SHAP method elucidates the decision mechanism of the optimal HBA-CatBoost model, highlighting the significance of sample features and bolstering the model’s credibility. These outcomes underscore the superior performance of the HBA-CatBoost model and its potential for effectively identifying water inrush sources in mines.

Abstract Brain injury is the leading cause of mortality among patients who survive cardiac arrest (CA). Clinical studies have shown that the presence of post-CA hypoxic hepatitis or pre-CA liver disease is associated with increased mortality and inferior neurological recovery. In our in vivo global cerebral ischemia model, we observed a larger infarct area, elevated tissue injury scores, and increased intravascular CD45+ cell adhesion in reperfused brains with simultaneous hepatic ischemia than in those without it. In the ex vivo brain normothermic machine perfusion (NMP) model, we demonstrated that addition of a functioning liver to the brain NMP circuit significantly reduced post-CA brain injury, increased neuronal viability, and improved electrocortical activity. Furthermore, significant alterations were observed in both the transcriptome and metabolome in the presence or absence of hepatic ischemia. Our study highlights the crucial role of the liver in the pathogenesis of post-CA brain injury.

With the continuous advancement in socioeconomic development and transportation infrastructure, the daily traffic volume on highways has been steadily increasing, resulting in the growing frequency of traffic congestion incidents. Thus, the accurate prediction of highway traffic flow is of great significance for implementing traffic congestion warnings, guiding traffic diversion, and developing the concept of intelligent highways. Traffic flow exhibits intricate spatial and temporal dependencies: in the spatial dimension, the relationships between various traffic nodes are not fixed, changing dynamically over time; in the temporal dimension, multiple temporal patterns of traffic flow sequences are entangled with each other. In addition, an efficient method for fusing spatiotemporal relationships is lacking, making the accurate prediction of traffic flow a challenging endeavor. In this regard, a methodology for forecasting highway traffic flow is proposed based on dynamic graph convolutional networks and spatiotemporal feature extraction modules. Given the challenge posed by the static nature of predefined graph structures in capturing dynamic spatial relationships among traffic nodes, a dynamic graph adjustment module is introduced. Initially, the spatial features of each traffic node are extracted. Subsequently, utilizing these extracted spatial features, spatial similarity scores between traffic nodes are computed. Based on these scores, a traffic network graph structure is adapted: connections between nodes with high similarity scores, previously unlinked, are established with a certain probability, while connections between nodes with low similarity scores, previously linked, are severed with a certain probability. Furthermore, by employing the spatiotemporal feature extraction module and leveraging the updated graph structure, spatial relationships are extracted through graph convolution. This is complemented by integrating a patch concept from temporal processing methodologies. Herein, a one-dimensional traffic flow sequence is decomposed and transformed into two-dimensional data. Through convolutional operations, temporal features within and between periods are simultaneously extracted before reverting the data back to its original dimensionality. This comprehensive approach enables the modeling of spatiotemporal dependencies within the traffic flow data. To validate the effectiveness of the proposed model, experiments were conducted on four highway traffic datasets, contrasting its performance with baseline models. The proposed model achieved the mean absolute error (MAE) values of 15.6, 19.7, 16.8, and 5.21 on the PeMS03, PeMS04, PeMS08, and Fuzhou Jingtai highway datasets, respectively. These results show that the proposed method reaches an advanced level in traffic flow forecasting. Lastly, to assess the efficacy of individual model components, ablative experiments were conducted, and their results were compared. These experiments validate the effectiveness of each component, thereby affirming the efficacy of the proposed model in highway traffic flow forecasting.

Abstract Background Coronary artery disease (CAD) is a major global cardiovascular health threat and the leading cause of death in many countries. The disease has a significant impact in China, where it has become the leading cause of death. There is an urgent need to develop non-invasive, rapid, cost-effective, and reliable techniques for the early detection of CAD using machine learning (ML). Methods Six hundred eight participants were divided into three groups: healthy, hypertensive, and CAD. The raw data of pulse wave from those participants was collected. The data were de-noised, normalized, and analyzed using several applications. Seven ML classifiers were used to model the processed data, including Decision Tree (DT), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), Extra Trees (ET), Extreme Gradient Boosting (XGBoost), Light Gradient Boosting (LightGBM), and Unbiased Boosting with Categorical Features (CatBoost). Results The Extra Trees classifier demonstrated the best classification performance. After tunning, the results performance evaluation on test set are: 0.8579 accuracy, 0.9361 AUC, 0.8561 recall, 0.8581 precision, 0.8571 F1 score, 0.7859 kappa coefficient, and 0.7867 MCC. The top 10 feature importances of ET model are w/t 1, t 3/t max , t max , t 3/t 1, As, h f/3, t f/3/t max , t f/5, w and t f/3/t 1. Conclusion Radial artery pulse wave can be used to identify healthy, hypertensive and CAD participants by using Extra Trees Classifier. This method provides a potential pathway to recognize CAD patients by using a simple, non-invasive, and cost-effective technique.

Abstract The hydrogeological conditions of the Qianbei coalfield are complex, and karst water in the roof rock frequently disrupts mining operations, leading to frequent water inrush incidents. Taking the representative Longfeng Coal Mine as a case study, research was conducted on the development pattern of the water-conducting fracture zone and the water inrush mechanisms beneath karst aquifers. On the basis of key stratum theory and calculations of the stratum stretching rate, the karst aquifer in the Changxing Formation was identified as the primary key stratum. It was deduced that the water-conducting fracture zone would develop into the karst aquifer, indicating a risk of roof water inrush at the working face. Numerical simulations were used to study the stress field, displacement field, and plastic zone distribution patterns in the overlying roof strata. Combined with similar simulation tests and digital speckle experiments, the spatiotemporal evolution characteristics of the water-conducting fracture zone were investigated. During the coal mining process, the water-conducting fracture zone will exhibit a "step-type" development characteristic, with the fracture morphology evolving from vertical to horizontal. Near the goaf boundary, the strain gradually decreases, and the instability of the primary key stratum significantly impacts the mining space below, leading to the closure of interlayer voids or the redistribution of water-conducting fissure patterns. Field measurements of the water-conducting fracture zone reveal that postmining roof fractures can be classified into tensile-shear, throughgoing, and discrete types, with decreasing water-conducting capacity in that order, the measured development height of the water-conducting fracture zone (51 m) aligns closely with the theoretical height (51.37 m) and the numerical simulation height (49.17 m). Finally, from the perspective of key stratum instability, the disaster mechanisms of dynamic water inrush and hydrostatic pressure water inrush beneath the karst aquifers in the northern Guizhou coalfield were revealed. The findings provide valuable insights for water prevention and control efforts in the Qianbei coalfield mining area.

Abstract Background Chemotherapy remains the standard first-line treatment for pancreatic adenocarcinoma, but with limited efficacy. We aimed to explore the feasibility of adding the PARP inhibitor fuzuloparib to mFOLFIRINOX in the locally advanced/metastatic (LA/M) setting. Methods This was the dose-escalation and -expansion, phase 1b portion of a phase 1b/2 study. Patients were given oral fuzuloparib at escalating doses starting at 30 mg twice daily (BID) plus intravenous mFOLFIRINOX q2w for 8–12 cycles, followed by maintenance fuzuloparib at 150 mg BID. Cohorts at the maximal tolerated dose (MTD) and lower dose of fuzuloparib were expanded. Primary endpoints were dose-limiting toxicity (DLT), MTD, and recommended phase 2 dose (RP2D). Results As of data cutoff on Jan 15, 2023, 39 patients were recruited. 12 patients were enrolled during dose escalation (30 mg [n = 4]; 60 mg [n = 6]; 100 mg [n = 2]). DLT occurred in 1 patient in 60 mg cohort and 1 patient in 100 mg cohort. 60 mg BID was determined to be the MTD, and then 60 and 30 mg cohorts were expanded to 22 and 15 patients, respectively. The most common grade ≥ 3 treatment-related adverse events were hematologic toxicities. Efficacy in 60 mg cohort seemed to be most favorable, with an objective response rate of 50.0% (95% CI, 26.0–74.0) and disease control rate of 94.4% (95% CI, 72.7–99.9). Conclusions First-line fuzuloparib plus mFOLFIRINOX followed by maintenance fuzuloparib was generally safe and showed encouraging anti-tumor activity in patients with LA/M pancreatic adenocarcinoma. The RP2D of fuzuloparib combination was 60 mg BID. Trial registration ClinicalTrials.gov, NCT04228601.

Abstract Background Machine learning (ML) is extensively employed for forecasting the outcome of various illnesses. The objective of the study was to develop ML based classifiers using a stacking ensemble strategy to predict the Japanese Orthopedic Association (JOA) recovery rate for patients with degenerative cervical myelopathy (DCM). Methods A total of 672 patients with DCM were included in the study and labeled with JOA recovery rate by 1-year follow-up. All data were collected during 2012–2023 and were randomly divided into training and testing (8:2) sub-datasets. A total of 91 initial ML classifiers were developed, and the top 3 initial classifiers with the best performance were further stacked into an ensemble classifier with a supported vector machine (SVM) classifier. The area under the curve (AUC) was the main indicator to assess the prediction performance of all classifiers. The primary predicted outcome was the JOA recovery rate. Results By applying an ensemble learning strategy (e.g., stacking), the accuracy of the ML classifier improved following combining three widely used ML models (e.g., RFE-SVM, EmbeddingLR-LR, and RFE-AdaBoost). Decision curve analysis showed the merits of the ensemble classifiers, as the curves of the top 3 initial classifiers varied a lot in predicting JOA recovery rate in DCM patients. Conclusions The ensemble classifiers successfully predict the JOA recovery rate in DCM patients, which showed a high potential for assisting physicians in managing DCM patients and making full use of medical resources.

Background: Mounting evidence underscores the importance of cell communication within the tumor microenvironment, which is pivotal in tumor proliferation, invasion, and metastasis. Exosomes play a crucial role in cell-to-cell communication. Although single-cell RNA sequencing (scRNA-seq) provides insights into individual cell transcriptional characteristics, it falls short of comprehensively capturing exosome-mediated intercellular communication. Method: We analyzed Pancreatic Ductal Adenocarcinoma (PDAC) tissues, separating supernatant and precipitate for exosome purification and single-cell nucleus suspension. We then constructed Single-nucleus RNA sequencing (snRNA-seq) and small RNA-seq libraries from these components. Our bioinformatic analysis integrated these sequences with ligand-receptor analysis and public miRNA data to map the cell communication network. Results: We established intercellular communication networks using bioinformatic analysis to track exosome miRNA effects and ligand-receptor pairs. Significantly, hsa-miR-1293 emerged as a prognostic biomarker for pancreatic cancer, linked to immune evasion, increased myeloid-derived suppressor cells, and poorer prognosis. Targeting this miRNA may enhance anti-tumor immunity and improve outcomes. Conclusion: Our study offers a novel approach to constructing intercellular communication networks using snRNA-seq and exosome-small RNA sequencing. By integrating miRNA tracing with ligand-receptor analysis, we illuminate the complex interactions in the pancreatic cancer microenvironment, highlighting the pivotal role of miRNAs and identifying potential biomarkers and therapeutic targets.

Abstract Background Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC. Methods Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs’ gene and protein expression was conducted using human colon cancer cells. Results Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines. Conclusion This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.

Introduction: Full-thickness wounds lead to delayed wound healing and scarring. Adipose-derived stem cell (ADSC) grafting promotes wound healing and minimizes scarring, but the low efficiency of grafting has been a challenge. We hypothesized that loading ADSCs onto a clinically widely used dermal regeneration template (DRT) would improve the efficacy of ADSC grafting and promote full-thickness wound healing. Methods: ADSCs from human adipose tissue were isolated, expanded, and labeled with a cell tracker. Labeled ADSCs were loaded onto the DRT. The viability, the location of ADSCs on the DRT, and the abundance of ADSCs in the wound area were confirmed using CCK8 and fluorescence microscopy. Full-thickness wounds were created on Bama minipigs, which were applied with sham, ADSC, DRT, and ADSC-DRT. Wounds from the four groups were collected at the indicated time and histological analysis was performed. RNA-seq analysis was also conducted to identify transcriptional differences among the four groups. The identified genes by RNA-seq were verified by qPCR. Immunohistochemistry and western blotting were used to assess collagen deposition. In vitro, the supernatant of ADSCs was used to culture fibroblasts to investigate the effect of ADSCs on fibroblast transformation into myofibroblasts. Results: ADSCs were successfully isolated, marked, and loaded onto the DRT. The abundance of ADSCs in the wound area was significantly greater in the ADSC-DRT group than in the ADSC group. Moreover, the ADSC-DRT group exhibited better wound healing with improved re-epithelialization and denser collagen deposition than the other three groups. The RNA-seq results suggested that the application of the integrated ADSC-DRT system resulted in the differential expression of genes mainly associated with extracellular matrix remodeling. In vivo, wounds from the ADSC-DRT group exhibited an earlier increase in type III collagen deposition and alleviated scar formation. ADSCs inhibited the transformation of fibroblasts into myofibroblasts, along with increased levels of CTGF, FGF, and HGF in the supernatant of ADSCs. Wounds from the ADSC-DRT group had up-regulated expressions of CTGF, HGF, FGF, and MMP3. Conclusion: The integral of ADSC-DRT increased the efficacy of ADSC grafting, and promoted full-thickness wound healing with better extracellular matrix remodeling and alleviated scar formation.

The World Health Organization (WHO) 2017 classifications for neuroendocrine neoplasms (NENs) subdivided grade 3 pancreatic neuroendocrine neoplasms (pNENs) into G3 well-differentiated pancreatic neuroendocrine tumors (G3 pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs), according to the mitotic count, Ki-67 index, and cell differentiation. As a new category, G3 pNETs remain a challenging group of tumors to manage by lacking large randomized trials and consensus to support its clinical practice. Therefore, the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association gathered experts in this field to formulate this consensus for the diagnosis and treatment of G3 pNETs.

Abstract Organic light-emitting diodes (OLEDs) offer the advantage of flexibility; however, the use of traditional transparent anode ITO limits further extension of their flexible characteristics. In this study, we propose employing an polymer polybenzodifuranedione (PBFDO) as a flexible transparent anode instead of the rigid ITO. To address the issue encountered during the PBFDO solution spin-coating process, we introduced n-butanol into the PBFDO conductive solution to reduce its viscosity and freezing point by modulating intermolecular hydrogen bonding interactions. Consequently, high-quality PBFDO films with high conductivity, superior transmittance, and low surface roughness were successfully obtained via spin-coating. Moreover, due to its proper work function, regular molecular stacking, and low refractive index properties, PBFDO electrode facilitate efficient carrier injection and transport as well as photon extraction. The resulting device utilizing a PBFDO anode combined with Super Yellow as the light-emitting layer exhibited excellent performance characteristics including a normal threshold voltage of 2.6 V and a maximum luminous efficiency of 12.8 cd A−1 comparable to that device based on the ITO electrode. Furthermore, flexible device also achieved satisfactory performance (7.7 cd A−1) when using the PEN substrate.

Influence maximization (IM) algorithms play a significant role in hypergraph analysis tasks, such as epidemic control analysis, viral marketing, and social influence analysis, and various IM algorithms have been proposed. The main challenge lies in IM algorithm evaluation, due to the complexity and diversity of the spreading processes of different IM algorithms in different hypergraphs. Existing evaluation methods mainly leverage statistical metrics, such as influence spread, to quantify overall performance, but do not fully unravel spreading characteristics and patterns. In this paper, we propose an exploratory visual analytics system, IMVis, to assist users in exploring and evaluating IM algorithms at the overview, pattern, and node levels. A spreading pattern mining method is first proposed to characterize spreading processes and extract important spreading patterns to facilitate efficient analysis and comparison of IM algorithms. Novel visualization glyphs are designed to comprehensively reveal both temporal and structural features of IM algorithms’ spreading processes in hypergraphs at multiple levels. The effectiveness and usefulness of IMVis are demonstrated through two case studies and expert interviews.

Introduction Micropapillary serous borderline ovarian tumours (MP-SBOTs) are an aggressive subtype of serous borderline ovarian tumours (SBOTs). Surgery is the mainstay of treatment. Radical surgery (RS, including debulking) is an alternative. However, for patients who are of reproductive age, another treatment option is fertility-sparing surgery (FSS). Up to now, the best surgical approach for MP-SBOTs and whether different procedures will have an impact on postoperative recurrence are still up for debate. This protocol outlines a systematic review and meta-analysis to investigate whether FSS adversely affected outcomes compared with RS in patients with MP-SBOTs. Additionally, we will do a prognosis analysis of BOTs with no microcapillary pattern and MP-SOBTs, if possible.Methods and analysis This protocol will consider non-randomised studies comparing outcomes in patients with MP-SBOTs treated with RS or FSS. The following databases will be searched: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, MEDLINE, Embase Medline, PubMed, Web of Science, China Biological Medicine Database, China National Knowledge Infrastructure and Wan Fang database. We will try our best to search the grey literature to avoid missing crucial research. Data collection and extraction will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Risk of Bias in Non-randomised Studies of intervention will be used to assess non-randomized studies. We will assess the certainty of the evidence using the GRADEpro methodology and describe the degree of certainty of our results using suggested wording based on the GRADEpro assessment. We will conduct a meta-analysis and offer summary statistics for each result if there is enough data available. Instead, we will report the findings narratively where the data do not permit a statistical assessment.Ethics and dissemination Ethics approval was not required for this study. Results will be published through a peer-reviewed publication and communicated at scientific events once complete.PROSPERO registration number CRD42023439136.

Background While the prognostic role of tertiary lymphoid structures (TLS) has been well studied in solid cancers, the prevalence and impact of immature precursor lymphoid structures known as lymphoid aggregates (LA) remain unresolved in relation to the disease process. In this study, we examined characteristics and the prognostic utility of LA and TLS status in histological samples from patients with melanoma.Methods We assessed The Cancer Genomic Atlas-skin cutaneous melanoma digital slides and melanoma specimens from the University of Pittsburgh for the presence of LA and TLS using H&E staining, multiplex immunofluorescence (mIF) and transcriptomic analyses. Cox proportional hazard regression models were used to assess the prognostic value associated with the presence of lymphoid structures in melanomas.Results A total of 278 evaluable samples were analyzed and split into primary melanomas in skin (N=195) and metastatic melanomas involving skin/subcutaneous/soft tissue sites (N=83). 72% of tumor specimens contained histologically defined LA located in peritumoral (34%), intratumoral (5.6%) or stromal (6.1%) locations, with the remaining samples (54.3%) exhibiting LA in multiple locations. In contrast to LA which tended to form more commonly in primary melanoma samples, TLS with germinal centers predominantly formed in peritumoral (45.2%) or stromal (35.5%) locations in metastatic melanomas (p=0.02), with TLS observed in 11% of all melanoma specimens evaluated. mIF analyses revealed cellular heterogeneity of lymphoid structures, with CD20+ (B) cells present in nodule-shaped and stromal locations where they exhibited a high degree of colocalization with CD4+ and CD8+ T cells. A previously defined 12-chemokine gene expression score was significantly higher in samples with evidence of LA versus none (p

IntroductionNumerous studies have reported alterations in the composition of gut microbiota in patients with acute ischemic stroke (AIS), with changes becoming more pronounced as the disease progresses. However, the association between the progression of transient ischemic attack (TIA) and AIS remains unclear. This study aims to elucidate the microbial differences among TIA, AIS, and healthy controls (HC) while exploring the associations between disease progression and gut microbiota.MethodsFecal samples were collected from acute TIA patients (n = 28), AIS patients (n = 235), and healthy controls (n = 75) and analyzed using 16 s rRNA gene sequencing. We determined characteristic microbiota through linear discriminant analysis effect size and used the receiver operating characteristic (ROC) curve to assess their predictive value as diagnostic biomarkers.ResultsOur results showed significant gut microbial differences among the TIA, AIS, and HC groups. Patients with AIS exhibited higher abundances of Lactobacillus and Streptococcus, along with lower abundances of Butyricicoccaceae and Lachnospiraceae_UCG-004. Further analysis revealed that the abundance of characteristic bacteria, such as Lactobacillus and Streptococcus, was negatively correlated with HDL levels, while Lactobacillus was positively correlated with risk factors such as homocysteine (Hcy). In contrast, the abundance of Lachnospiraceae_UCG-004 was negatively correlated with both Hcy and D-dimer levels. ROC models based on the characteristic bacteria Streptococcus and Lactobacillus effectively distinguished TIA from AIS, yielding areas under the curve of 0.699 and 0.626, respectively.ConclusionWe identified distinct changes in gut bacteria associated with the progression from TIA to AIS and highlighted specific characteristic bacteria as predictive biomarkers. Overall, our findings may promote the development of microbiome-oriented diagnostic methods for the early detection of AIS.

ObjectiveOur study was conducted to explore the link between oxidative balance score (OBS) and rheumatoid arthritis (RA).MethodsA total of 21,415 participants were included in our research from five cycles (2011–2012, 2013–2014, 2015–2016, 2017–2018, and 2017–2020) of the National Health and Nutrition Examination Survey (NHANES). Moreover, 20 elements related to diet as well as lifestyle were combined to calculate OBS. The relationship between OBS and RA was assessed by employing multivariable regression analysis, and further exploration was carried out through subgroup analysis, restricted cubic spline analysis, and sensitivity analysis. Multiple covariates were selected to adjust the model for more robust results.ResultsIn our cross-sectional study, a higher OBS has a protective effect on the development of RA (OR = 0.98, 95% CI: 0.97 to 0.99). In contrast to individuals aged ≥60, the result is more prominent in the population aged 20–60 (OR = 0.97, 95% CI: 0.96 to 0.98). Marital status appears to introduce interference in the relationship between OBS and RA, and unmarried individuals exhibited different outcomes (OR = 1.02, 95% CI: 0.99 to 1.04) compared to others. The positive influence of OBS was more evident in patients with chronic kidney disease and cardiovascular disease, while it was stronger in individuals without diabetes and liver disease.ConclusionA higher OBS correlates with a reduced odd of RA. Further studies are needed to shoot more sights on improving dietary habits and lifestyles to gain proper OBS and explore whether OBS can be one of the measurements utilized to measure the risk of RA.

Prolonged exposure to volatile anesthetics may raise the risk of developing cognitive impairment by acting on gamma-a Aminobutyric acid A receptors (GABAAR). The dentate gyrus plays an important role in the hippocampus and has a high potential for neural plasticity. However, it is unknown whether prolonged anesthesia induces a change in acute phasic or tonic inhibition in dentate gyrus granule cells (DGGCs) by acting on GABAAR. In order to verify the effects of volatile anesthetics on the current in DGGCs, a whole-cell patch was applied to record acute brain slices, and this study indicated that 4 h but not 2 h of isoflurane (ISO) exposure induced significantly larger tonic currents in DGGCs other than hippocampal CA1 pyramidal and thalamic relay neurons. Furthermore, this study demonstrated that the increased tonic current in DGGCs was dependent on the δ subunit-containing GABAARs by using transgenic δ subunit knockout mice. In conclusion, the δ subunit specific GABAAR is the key element that increased acute tonic inhibition in DGGCs of mice after prolonged ISO exposure, which may be one of the mechanisms of ISO neurotoxicity to the developing brain.

IntroductionNAC (NAM, ATAF, and CUC) transcription factor family, one of the important switches of transcription networks in plants, functions in plant growth, development, and stress resistance. Night lily (Hemerocallis citrina) is an important horticultural perennial monocot plant that has edible, medicinal, and ornamental values. However, the NAC gene family of night lily has not yet been analyzed systematically to date.MethodsTherefore, we conducted a genome-wide study of the HcNAC gene family and identified a total of 113 HcNAC members from the Hemerocallis citrina genome.ResultsWe found that 113 HcNAC genes were unevenly distributed on 11 chromosomes. Phylogenetic analysis showed that they could be categorized into 16 instinct subgroups. Proteins clustering together exhibited similar conserved motifs and intron–exon structures. Collinearity analysis indicated that segmental and tandem duplication might contribute to the great expansion of the NAC gene family in night lily, whose relationship was closer with rice than Arabidopsis. Additionally, tissue-specific pattern analysis indicated that most HcNAC genes had relatively higher expression abundances in roots. RNA-Seq along with RT-qPCR results jointly showed HcNAC genes expressed differently under drought and salinity stresses. Interestingly, HcNAC35 was overexpressed in watermelon, and the stress resilience of transgenic lines was much higher than that of wild-type watermelon, which revealed its wide participation in abiotic stress response.ConclusionIn conclusion, our findings provide a new prospect for investigating the biological roles of NAC genes in night lily.

Bisphenol S (BPS) is widely presented and affects aging with unclear mechanisms. Here, we applied C. elegans to evaluate the effects of BPS on lifespan and healthspan and to investigate the underlying mechanisms. Both early-life and whole-life exposure to BPS at environmentally relevant doses (0.6, 6, 60 μg/L) significantly decreased lifespan, and healthspan (body bend, pharyngeal pumping, and lipofuscin accumulation). BPS exposure impaired mitochondrial structure and function, which promoted ROS production to induce oxidative stress. Furthermore, BPS increased expressions of the insulin/IGF-like signaling (IIS). Also, BPS inhibited expression of the IIS transcription factor daf-16 and its downstream anti-oxidative genes. Quercetin effectively improved BPS-induced oxidative stress byreversing BPS-regulated IIS/daf-16 pathway and anti-oxidative gene expressions. In daf-2 and daf-16 mutants, the effects of BPS and quercetin on lifespan, healthspan, oxidative stress, and anti-oxidative genes expressions were reversed, demonstrating the requirement of IIS/daf-16 for aging regulation. Molecular docking and molecular dynamics simulations confirmed the stable interaction between DAF-2 and BPS mainly via three residues (VAL1260, GLU1329, and MET1395), which was attenuated by quercetin. Our results highlighted that adverse effects of BPS on impairing lifespan and healthspan by affecting IIS/daf-16 function against mitochondrial stress, which could be inhibited by quercetin treatment. Thus, we first revealed the underlying mechanisms of BPS-induced aging and the potential treatment.

Hypobaric hypoxia causes altitude sickness and significantly affects human health. As of now, focusing on rats different proteomic and metabolic changes exposed to different hypoxic times at extreme altitude is blank. Our study integrated in vivo experiments with tandem mass tag (TMT)- and gas chromatography time-of-flight (GC-TOF)-based proteomic and metabolomic assessments, respectively. Male Sprague-Dawley rats were exposed to long-term constant hypoxia for 40 days or short-term constant hypoxia for three days, and their responses were compared with those of a normal control group. Post-hypoxia, serum marker assays related to lipid metabolism revealed significant increases in the levels of low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) in the liver. In contrast, high-density lipoprotein (HDL) levels were upregulated in the long-term constant hypoxia cohorts and were significantly reduced in the short-term constant hypoxia cohorts. Furthermore, metabolic pathway analysis indicated that glycerolipid and glycerophospholipid metabolisms were the most significantly affected pathways in long-term hypoxia group. Subsequently, RT-qPCR analyses were performed to corroborate the key regulatory elements, including macrophage galactose-type lectin (MGL) and Fatty Acid Desaturase 2 (FADS2). The results of this study provide new information for understanding the effects of different hypobaric hypoxia exposure protocols on protein expression and metabolism in low-altitude animals.

Pakchoi seedlings (Brassica chinensis L.) is susceptible to damage and spoilage during harvest and transport, leading to significant quality deterioration and financial losses. This study explored the use of ammonium glycyrrhizinate (AG) to address these issues. AG self-assembles into macromolecules at room temperature, blocking stomata and regulating respiration rates in Pakchoi seedlings. Additionally, it disrupts bacterial cell biofilm and inhibits its synthesis. While AG has been used in medicine, its application in the food industry remains limited. The study found that incorporating AG in Pakchoi seedlings preserves water content and total soluble solids (TSS), while preventing declines in catalase (CAT), Vitamin C (VC), and chlorophyll during storage. AG also reduced malondialdehyde (MDA) levels and maintained peroxidase (POD) and superoxide dismutase (SOD) activities. At a concentration of 4.25 g L−1, AG enhanced radical scavenging ability and extended the shelf life of Pakchoi seedlings by inhibiting bacteria and postponing senescence.

To explore the effect of interchange spacing on drivers' visual characteristics in the merging areas of interchange, a high-density group of five interchanges on the expressway of Chongqing, China, was selected as the test site. An naturalistic driving test was conducted with 47 participants, and the Tobii Glasses II portable eye tracker was used to collect gaze data during driving. The drivers' fixation field was divided into six areas by applying a K-means dynamic clustering algorithm combined with the actual scenario. Markov chains were used to calculate the drivers' gaze transition probability matrices under different driving conditions, and the analysis of gaze transition behaviors was directed at common spacing interchanges, small spacing interchanges, and composite interchanges. Under the ramp-mainline condition, drivers’ fixations were primarily concentrated on the near ahead and the left side areas, with higher rates of repeated fixations on the left rearview mirror and left-side line areas. The average value of fixation duration, saccade distance, and saccade speed of small spacing interchange is higher than common spacing interchange. Additionally, under the mainline condition, the probability of one-step transition and repeated fixation rates significantly increased for the right-side lane areas, and the average values of fixation index and saccade index of small spacing interchange are lower than those of common spacing interchange. The results show that the highest probabilities of repeated fixation by drivers occurred in the near ahead and far ahead areas in the interchange merging areas. Insufficient spacing resulted in more frequent occurrences of zero values in one-step transition probability matrices. The research conclusions provide theoretical support for the optimal design and safe operation of the merging area of high-density interchange group of urban expressway.

Abstract Background The immature and suppressed immune response makes transplanted children a special susceptible group to Parvovirus B19 (PVB19). However, the clinical features of transplanted children with PVB19 infection haven’t been comprehensively described. Methods We searched the medical records of all the transplant recipients who attended the Children’s Hospital of Fudan University from 1 Oct 2020 to 31 May 2023, and reviewed the medical literature for PVB19 infection cases among transplanted children. Results A total of 10 cases of PVB19 infection were identified in 201 transplanted children at our hospital, and the medical records of each of these cases were shown. Also, we retrieved 40 cases of PVB19 infection among transplanted children from the literature, thus summarizing a total of 50 unique cases of PVB19 infection. The median time to the first positive PVB19 DNA detection was 14 weeks post-transplantation. PVB19 IgM and IgG were detected in merely 26% and 24% of the children, respectively. The incidence of graft loss/dysfunction was as high as 36%. Hematopoietic stem cell transplant (HSCT) recipients showed higher PVB19 load, lower HGB level, greater platelet damage, lower PVB19 IgM/IgG positive rates, and more graft dysfunction than solid-organ transplant (SOT) recipients, indicating a more incompetent immune system. Conclusions Compared with the published data of transplanted adults, transplanted children displayed distinct clinical features upon PVB19 infection, including lower PVB19 IgM/IgG positive rates, more graft dysfunction, and broader damage on hematopoietic cell lines, which was even more prominent in HSCT recipients, thus should be of greater concern.

Abstract Nickel (Ni), a component of urease, is a micronutrient essential for plant growth and development, but excess Ni is toxic to plants. Tomato (Solanum lycopersicum L.) is one of the important vegetables worldwide. Excessive use of fertilizers and pesticides led to Ni contamination in agricultural soils, thus reducing yield and quality of tomatoes. However, the molecular regulatory mechanisms of Ni toxicity responses in tomato plants have largely not been elucidated. Here, we investigated the molecular mechanisms underlying the Ni toxicity response in tomato plants by physio-biochemical, transcriptomic and molecular regulatory network analyses. Ni toxicity repressed photosynthesis, induced the formation of brush-like lateral roots and interfered with micronutrient accumulation in tomato seedlings. Ni toxicity also induced reactive oxygen species accumulation and oxidative stress responses in plants. Furthermore, Ni toxicity reduced the phytohormone concentrations, including auxin, cytokinin and gibberellic acid, thereby retarding plant growth. Transcriptome analysis revealed that Ni toxicity altered the expression of genes involved in carbon/nitrogen metabolism pathways. Taken together, these results provide a theoretical basis for identifying key genes that could reduce excess Ni accumulation in tomato plants and are helpful for ensuring food safety and sustainable agricultural development.

In order to solve the problem of roof water inrush risk during the mining of No. 9 coal seam in Longfeng Coal Mine, an LDA-RBF neural network model for predicting the development height of water-conduction fracture zone was constructed by linear discriminant analysis (LDA), and a CRITIC-AHP comprehensive weighting method was established based on the improved CRITIC evaluation method combined with analytic hierarchy method (AHP) to evaluate the risk of roof cracking and the water richness level of the aquifer in the mining area. Through ArcGis geographic information processing technology, the cracking risk zone and the water-rich zone are superimposed to obtain a comprehensive zoning map of the water inrush risk of the roof of No.9 coal seam. The results show that the LDA-RBF neural network prediction model has a simple structure and higher fitting accuracy, and the development prediction height of the No.9 coal seam water-conducting fracture zone is 50.4 m, which has exceeded the bottom boundary level of most aquifers in the area, indicating that there is a high risk of cracking in most areas. The improved comprehensive weighting method avoids the problem of excessive subjectivity and objectivity of the evaluation results, and the water-rich zoning results are consistent with the actual water inflow of the borehole. Finally, the water inrush danger zone is mainly distributed in strips in the central and northern parts of the mining area, which is the result of the combined effect of strong water richness and high cracking risk of the aquifer in this area, indicating that the above areas should be paid attention to in actual mining.

Abstract During the development of the vertebrate nervous system, 50% of the nerve cells undergo apoptosis shortly after formation. This process is important for sculpting tissue during morphogenesis and removing transiently functional cells that are no longer needed, ensuring the appropriate number of neurons in each region. Dysregulation of neuronal apoptosis can lead to neurodegenerative diseases. However, the molecular events involved in activating and regulating the neuronal apoptosis program are not fully understood. In this study, we identified several RB1 mutations in patients with neurodegenerative diseases. Then, we used a zebrafish model to investigate the role of Rb1 in neuronal apoptosis. We showed that Rb1-deficient mutants exhibit a significant hindbrain neuronal apoptosis, resulting in increased microglia infiltration. We further revealed that the apoptotic neurons in Rb1-deficient zebrafish were post-mitotic neurons, and Rb1 inhibits the apoptosis of these neurons by regulating bcl2/caspase through binding to Kmt5b. Moreover, using this zebrafish mutant, we verified the pathogenicity of the R621S and L819V mutations of human RB1 in neuronal apoptosis. Collectively, our data indicate that the Rb1-Kmt5b-caspase/bcl2 axis is crucial for protecting post-mitotic neurons from apoptosis and provides an explanation for the pathogenesis of clinically relevant mutations.

Abstract Aim To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). Methods The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. Results Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493–0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482–0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. Conclusions Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

Abstract Background There have been no reports on the successful implementation of stellate ganglion block (SGB) in mice. Objectives This study aims to investigate a new method for implementing SGB in mice by placing them in a supine position with abducted upper limbs and touching the trachea and sternoclavicular joint with the hand. Methods Fifty BABL/C mice, 8–10 weeks, were selected and randomly divided into four groups: control group (n = 5); SGB-R group (n = 15); SGB-L group (n = 15); and SGB-L + R (group n = 15). SGB was administered with 0.15% ropivacaine solution in a volume of 0.1 mL. The control group received equal volumes of saline. Horner's syndrome, heart rate, and complications such as brachial plexus block, vascular injury, pneumothorax, local anesthetic toxicity, and death were observed. Results Horner's syndrome developed in 100% of SGB surviving mice; no difference was seen in the time to onset (100.4 ± 13.4 vs 96.7 ± 12.4, mean ± SD, seconds) and duration (264.1 ± 40.5 vs 296.3 ± 48.0, mean ± SD, min) of Horner's syndrome in the left and right SGB (P > 0.05). Compared with the control group (722 [708–726], median [IQR], bpm), the heart rate was significantly slowed down in the right SGB (475 [451.5–491], median [IQR], bpm) (P 0.05). The overall complication rate was 18.4%, with a brachial plexus block rate of 12.3%, a vascular injury rate of 4.6%, and a mortality rate of 1.5%, as well as no local anesthetic toxicity (includes bilateral implementation of SGB) or pneumothorax manifestations were found. Conclusions This method allows for the successful implementation of SGB in a mouse model.

Introduction Our goal was to systematically review the current evidence comparing the relative effectiveness of two maxillary sinus floor elevation (MSFE) approaches (internal and external) without bone grafts with that of conventional/grafted MSFE in patients undergoing implantation in the posterior maxilla. Material and Methods Medical databases (PubMed/Medline, Embase, Web of Science, and Cochrane Library) were searched for randomised controlled trials published between January 1980 and May 2023. A manual search of implant-related journals was also performed. Studies published in English that reported the clinical outcomes of MSFE with or without bone material were included. The risk of bias was assessed using the Cochrane Handbook Risk Assessment Tool. Meta-analyses and trial sequence analyses were performed on the included trials. Meta-regression analysis was performed using pre-selected covariates to account for substantial heterogeneity. The certainty of evidence for clinical outcomes was assessed using GRADEpro GDT online (Guideline Development Tool). Results Seventeen studies, including 547 sinuses and 696 implants, were pooled for the meta-analysis. The meta-analysis showed no statistically significant difference between MSFE without bone grafts and conventional MSFE in terms of the implant survival rate in the short term (n = 11, I2 = 0%, risk difference (RD): 0.03, 95% confidence intervals (CI): –0.01–0.07, p = 0.17, required information size (RIS) = 307). Although conventional MSFE had a higher endo-sinus bone gain (n = 13, I2 = 89%, weighted mean difference (WMD): –1.24, 95% CI: –1.91– –0.57, p = 0.0003, RIS = 461), this was not a determining factor in implant survival. No difference in perforation (n = 13, I2 = 0%, RD = 0.03, 95% CI: –0.02–0.09, p = 0.99, RIS = 223) and marginal bone loss (n = 4, I2 = 0%, WMD = 0.05, 95% CI: –0.14–0.23, p = 0.62, no RIS) was detected between the two groups using meta-analysis. The pooled results of the implant stability quotient between the two groups were not robust on sensitivity analysis. Because of the limited studies reporting on the visual analogue scale, surgical time, treatment costs, and bone density, qualitative analysis was conducted for these outcomes. Conclusions This systematic review revealed that both non-graft and grafted MSFE had high implant survival rates. Owing to the moderate strength of the evidence and short-term follow-up, the results should be interpreted with caution.

Abstract Charging behaviours of electric vehicles (EVs) exhibit substantial randomness, making accurate prediction or modelling challenging. Furthermore, as the number of EVs continues to increase, charging stations are diversifying their offerings to accommodate distinct charging characteristics, addressing a wide spectrum of EV charging needs. Previous research mostly focused on the randomness of EVs while neglecting the heterogeneity in charging infrastructure. Therefore, this paper introduces a decentralized collaborative optimal method for EV charging stations, taking into account the varying facility types and the power limitations. First, a decentralized collaborative framework is proposed. The energy boundary model and the average laxity of EVs contribute to transforming the optimization problem into a Markov Decision Process (MDP) with uncertain transitions. Then, multi‐agent deep deterministic policy gradient multi‐individuals (MADDPG‐MI) algorithm is developed to train several heterogeneous agents presenting different types of charging facilities. Each agent makes decisions for multiple homogenous charging piles. Numerous simulation studies validate that the proposed method can effectively reduce charging costs and manages in scenarios involving either homogeneous or multiple heterogeneous charging facilities. Moreover, the MADDPG‐MI algorithm demonstrates performance consistency among multiple decision‐making units while consuming lower training resources offering enhanced scalability.

Abstract Tumor cells must rewire nucleotide synthesis to satisfy the demands of unbridled proliferation. Meanwhile, they exhibit augmented reactive oxygen species (ROS) production which paradoxically damages DNA and free deoxy-ribonucleoside triphosphates (dNTPs). How these metabolic processes are integrated to fuel tumorigenesis remains to be investigated. MYC family oncoproteins coordinate nucleotide synthesis and ROS generation to drive the development of numerous cancers. We herein perform a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based functional screen targeting metabolic genes and identified nudix hydrolase 1 (NUDT1) as a MYC-driven dependency. Mechanistically, MYC orchestrates the balance of two metabolic pathways that act in parallel, the NADPH oxidase 4 (NOX4)-ROS pathway and the Polo like kinase 1 (PLK1)-NUDT1 nucleotide-sanitizing pathway. We describe LC-1-40 as a potent, on-target degrader that depletes NUDT1 in vivo. Administration of LC-1-40 elicits excessive nucleotide oxidation, cytotoxicity and therapeutic responses in patient-derived xenografts. Thus, pharmacological targeting of NUDT1 represents an actionable MYC-driven metabolic liability.

Microorganisms play an important role in multi-factor synergistic corrosion. The synergistic effects of which are greatly stronger than elastic stress and alternative current. Changes of alternative current directly dominate the effect of microbial synergy. With increasing AC current density, corrosion rate of pipeline steel X80 increased first and then decreased, reaching a peak at 100 A m−2. Number of SRB cells vaired as a function of AC current density. Lower current density promoted SRB growth while high current density inhibited SRB growth. When sessile cells are more than 105 cell cm−2, the dominant role of microorganisms is strong, and corrosion rate increases with current density. The maximum value is reached at 100 A m−2. However, when the cells are less than 103 cell cm−2, the dominant effect is greatly reduced, leading to a reduction in the synergistic effect of the multi-factor, and finally reduced corrosion rate to 200 A m−2.

Background Abdominal aortic aneurysm (AAA) is highly lethal upon onset of acute aortic diseases (AAD) or rupture. Dyslipidaemia and hyperuricaemia are important risk factors for the development of AAA and AAD as well as aortic disease-related death. The aim of this study was to explore whether uric acid (UA) to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) can be used as an independent predictor of the presence of AAA or AAD.Methods Three hundred subjects, including 100 AAA patients (AAA group), 100 AAD patients (AAD group) and 100 controls (CON group), were recruited in this study. UHR and other serum samples were obtained upon the patients’ admission before any medical treatment. The optimal cut-off points of UHR were determined using receiver operating characteristic (ROC) curve analysis.Results The UHR in AAA group was significantly higher than that in CON group, but there was no significant difference between AAD group and CON group. The optimal cut-off point of UHR for AAA was 7.78 (sensitivity 84.7%, specificity 62.4%, and AUC 0.811; p

BackgroundDuring the coronavirus disease 2019 (COVID-19) pandemic, the infection of Mycoplasma pneumoniae (MP) decreased significantly. At the beginning of the summer of 2023, there was an increasing trend of MP infection in China and the MP pneumonia (MPP) is surging when it comes to the school season and lasts for several months which has attracted widespread attention.ObjectiveThis study aims to investigate the prevalent characteristics of the MP and the difference between the COVID-19 pandemic and the post in Shanghai, China.MethodsThe demographic information and the results of laboratory pathogen detection from July 2021 to May 2024 were collected and analyzed to find out the prevalent characteristics of MP. Two periods, during the COVID-19 pandemic and the post-pandemic, were divided and compared. The P1 genotyping and macrolide resistance-associated gene of 23 s rRNA were detected using the remaining MP-positive samples.ResultsDuring the COVID-19 pandemic, the prevalence of the MP has significantly decreased. Female children are more susceptible to MP infection than the male. The school-aged group (>6 years) had the highest infection rate. The rate of MP P1 genotype during post panel is higher than that during COVID-19 pandemic, which is dominant from July 2021 to May 2024, while the macrolide-resistant associated mutations (A2063G) keep high percentage during or post pandemic.ConclusionAfter the COVID-19 pandemic, an outbreak of MP infection occurred from summer onwards in 2023 with children in Shanghai, China. Immunity debt and high rate of macrolide-resistance may take effects in this MP epidemic. Continuous surveillance of MP is necessary to help to alert the prevalence of MPP.

BackgroundNumerous research studies have indicated a possible association between type 2 diabetes (T2DM) and gut microbiota. To explore specific metabolic pathways connecting gut microbiota and T2DM, we employed Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC) techniques.MethodsThis research utilized data from genome-wide association studies (GWAS) that are publicly accessible. We evaluated the genetic correlation between gut microbiota and T2DM using LDSC. Causality was primarily determined through the inverse variance weighted (IVW) method. To verify the robustness of our results, we conducted sensitivity analyses using several approaches, including the weighted median, MR-Egger, and MR-PRESSO. We integrated summary effect estimates from LDSC, along with forward and reverse MR, into a meta-analysis for T2DM using various data sources. Additionally, mediation analysis was performed to explore the impact of plasma metabolites on the relationship between gut microbiota and T2DM.ResultsOur study indicated a significant genetic correlation between genus RuminococcaceaeUCG005 (Rg = −0.26, Rg_P = 2.07×10−4) and T2DM. Moreover, the forward MR analysis identified genus RuminococcaceaeUCG010 (OR = 0.857, 95% CI 0.795, 0.924; P = 6.33×10−5) and order Clostridiales (OR = 0.936, 95% CI 0.878, 0.997; P = 0.039) as being significantly associated with a decreased risk of T2DM. The analysis also highlighted several plasma metabolites as significant mediators in these relationships, with metabolites like octadecadienedioate (C18:2-DC) and branched chain 14:0 dicarboxylic acid being notably involved.ConclusionThe findings demonstrate a significant impact of gut microbiota on T2DM via plasma metabolites, suggesting potential metabolic pathways for therapeutic targeting. This study enhances our understanding of the microbiota’s role in T2DM pathogenesis and supports the development of microbiota-based interventions.

IntroductionCitrus canker, caused by Xanthomonas citri subsp. citri (Xcc), is a devastating disease worldwide. Previously, we successfully generated canker-resistant Citrus sinensis cv. Hamlin lines in the T0 generation. This was achieved through the transformation of embryogenic protoplasts using the ribonucleoprotein (RNP) containing Cas12a and one crRNA to edit the canker susceptibility gene, CsLOB1, which led to small indels.MethodsHere, we transformed embryogenic protoplasts of Hamlin with RNP containing Cas12a and three crRNAs.ResultsAmong the 10 transgene-free genome-edited lines, long deletions were obtained in five lines. Additionally, inversions were observed in three of the five edited lines with long deletions, but not in any edited lines with short indel mutations, suggesting long deletions maybe required for inversions. Biallelic mutations were observed for each of the three target sites in four of the 10 edited lines when three crRNAs were used, demonstrating that transformation of embryogenic citrus protoplasts with Cas12a and three crRNAs RNP can be very efficient for multiplex editing. Our analysis revealed the absence of off-target mutations in the edited lines. These cslob1 mutant lines were canker- resistant and no canker symptoms were observed after inoculation with Xcc and Xcc growth was significantly reduced in the cslob1 mutant lines compared to the wild type plants.DiscussionTaken together, RNP (Cas12a and three crRNAs) transformation of embryogenic protoplasts of citrus provides a promising solution for transgene-free multiplex genome editing with high efficiency and for deletion of long fragments.

IntroductionThe immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet.MethodsHere, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) and compared them to 18 adults (13 with COVID-19).ResultsThe child-adult integrated single cell data indicated that children with the disease presented a restrained response to type I interferon in most of the major immune cell types, along with suppression of upstream interferon regulatory factor and toll-like receptor expression in monocytes, which was confirmed by in vitro interferon stimulation assays. Unlike adult patients, children with COVID-19 showed lower frequencies of activated proinflammatory CD14+ monocytes, possibly explaining the rareness of cytokine storm in them. Notably, natural killer (NK) cells in pediatric patients displayed potent cytotoxicity with a rich expression of cytotoxic molecules and upregulated cytotoxic pathways, whereas the cellular senescence, along with the Notch signaling pathway, was significantly downregulated in NK cells, all suggesting more robust cytotoxicity in NK cells of children than adult patients that was further confirmed by CD107a degranulation assays. Lastly, a modest adaptive immune response was evident with more naïve T cells but less activated and proliferated T cells while less naïve B cells but more activated B cells in children over adult patients.ConclusionConclusively, this preliminary study revealed distinct cell frequency and activation status of major immune cell types, particularly more robust NK cell cytotoxicity in PBMC that might help protect children from severe COVID-19.

Background: Previous studies have shown that pyroptosis in hepatocyte is essential for the development of MAFLD. Growing evidence has shown that exosomal miRNAs-mediated communication between inflammatory cells and hepatocyte is an important link in MAFLD. In the present study, we aim to elucidate whether macrophage-derived exosomal miRNAs contribute to the hepatocyte pyroptosis in the pathophysiological process of MAFLD. Methods: The effects of hepatocyte pyroptosis were investigated in an HFD-induced MAFLD mouse model and in the liver tissues from patients with MAFLD using immunohistochemistry, real-time PCR, Western blotting, and luciferase reporter assay, among other techniques. MiR-155 inhibitor tail injections and AAV-FoxO3a-GFP were also administered to respectively inhibit or overexpress its expression in an HFD-induced MAFLD mouse model. Results: Hepatocyte pyroptosis was heightened in the liver tissue of patients with MAFLD or HFD-induced MAFLD mouse. Importantly, treatment with a caspase-1 inhibitor or overexpression of FoxO3a reversed this trend. Our study also demonstrated that miR-155 expression and the number of infiltrated macrophages were increased, and knockdown of miR-155 attenuated hepotocyte pyroptosis and liver fibrosis in HFD-induced mouse. In addition, we demonstrated that macrophage-derived exosomal miR-155 was transferred to hepatocytes, leading to hepatocyte pyroptosis in MAFLD mouse. Furthermore, blockade of exosome secretion improved hepotocyte pyroptosis and liver fibrosis in HFD-induced mouse. On the contrary, macrophage-derived exosomal miR-155 worsened hepotocyte pyroptosis. Moreover, we found that miR-155 promoted hepatocyte pyroptosis in MAFLD by down-regulating FoxO3a. Conclusions: Taken together, our results demonstrated that macrophage-derived exosomal miR-155 promotes hepatocyte pyroptosis and liver fibrosis in MAFLD.

Similar to the layout of an oscillating heat pipe (OHP), a quartz hybrid heat pipe (HHP) with an inner diameter of 5 mm, exceeding 59.7 % of the capillary threshold of OHP, was designed. The detailed thermal hydraulic behavior of fluid in the HHP has been revealed. It was found that the HHP undergoes a heat transfer mode transition from phase change to pulsating flow. It is also means that the liquid slugs can be dynamically and stably formed if the heat input is sufficient. The single bubble growth and the multi-bubble coalescence are two ways to form the intermittent flow. In addition, as the main flow pattern in low filling ratio (FR), the formation of annular flow is closely concerned in the behaviors of fluid. Moreover, the higher the FR is, the clearer the contour of slug flow is. At the same time, the oscillating motion can be formed easily at a high FR, resulting in a better performance of HHP in lower heat load. However, as the heat input increases, HHP with a 60 % filling ratio exhibits lower thermal resistance, achieving a minimum value of 0.08 °C/W at 100 W.

Severe COVID-19 cases often progress to life-threatening conditions such as acute respiratory distress syndrome (ARDS), sepsis, and multiple organ dysfunction syndrome (MODS). Gelsolin (GSN), an actin-binding protein with anti-inflammatory and immunomodulatory properties, is a promising therapeutic target for severe COVID-19. Plasma GSN levels are significantly decreased in critical illnesses, including COVID-19, correlating with dysregulated immune responses and poor outcomes. GSN supplementation may mitigate acute lung injury, ARDS, and sepsis, which share pathophysiological features with severe COVID-19, by scavenging actin, modulating cytokine production, enhancing macrophage phagocytosis, and stabilizing the alveolar-capillary barrier. Preliminary data indicate that recombinant human plasma GSN improves oxygenation and lung function in severe COVID-19 patients with ARDS. Although further research is needed to optimize GSN therapy, current evidence supports its potential to mitigate severe consequences of COVID-19 and improve patient outcomes. This review provides a comprehensive analysis of the biological characteristics, mechanisms, and therapeutic value of GSN in severe COVID-19.

IntroductionCitrus is one of the most important fruit crops worldwide, and the root-associated microbiota can have a profound impact on tree health and growth.MethodsIn a collaborative effort, the International Citrus Microbiome Consortium investigated the global citrus root microbiota with samples collected from nine citrus-producing countries across six continents. We analyzed 16S rDNA and ITS2 amplicon sequencing data to identify predominant prokaryotic and fungal taxa in citrus root samples. Comparative analyses were conducted between root-associated microbial communities and those from the corresponding rhizosphere and bulk soil samples. Additionally, genotype-based group-wise comparisons were performed to assess the impact of citrus genotype on root microbiota composition.ResultsTen predominant prokaryotic phyla, containing nine bacterial phyla including Proteobacteria, Actinobacteria, Acidobacteria, and Bacteroidetes and one archaeal phylum (Thaumarchaeota), and multiple fungal phyla including Ascomycota and Basidiomycota were identified in the citrus root samples. Compared with the microbial communities from the corresponding rhizosphere and bulk soil samples from the same trees, the prokaryotic and fungal communities in the roots exhibited lower diversity and complexity but greater modularity compared to those in the rhizosphere. In total, 30 root-enriched and 150 root-depleted genera in bacterial community were identified, whereas 21 fungal genera were enriched, and 147 fungal genera were depleted in the root niche compared with the rhizosphere. The citrus genotype significantly affected the root prokaryotic and fungal communities. In addition, we have identified the core root prokaryotic genera comprising Acidibacter, Allorhizobium, Bradyrhizobium, Chitinophaga, Cupriavidus, Devosia, Dongia, Niastella, Pseudomonas, Sphingobium, Steroidobacter and Streptomyces, and the core fungal genera including Acrocalymma, Cladosporium, Fusarium, Gibberella, Mortierella, Neocosmospora and Volutella. The potential functions of these core genera of root microbiota were predicted.ConclusionOverall, this study provides new insights into the assembly of microbial communities and identifies core members of citrus root microbiota across a wide geographic range. The findings offer valuable information for manipulating root microbiota to enhance plant growth and health.

Abstract Surface modification is frequently used to solve the problems of low combustion properties and agglomeration for aluminum‐based fuels. However, due to the intrinsic incompatibility between the aluminum powder and the organic modifiers, the surface coating is usually uneven and disordered, which significantly deteriorates the uniformity and performances of the Al‐based fuels. Herein, a new approach of monolayer nano‐vesicular self‐assembly is proposed to prepare high‐performance Al fuels. Triblock copolymer G‐F‐G is produced by glycidyl azide polymer (GAP) and 2,2′‐(2,2,3,3,4,5,5‐Octafluorohexane‐1,6‐diyl) bis (oxirane) (fluoride) ring‐open addition reaction. By utilizing G‐F‐G vesicular self‐assembly in a special solvent, the nano‐sized vesicles are firmly adhered to the surface of Al powder through the long‐range attraction between the fluorine segments and Al. Meanwhile, the electrostatic repulsion between vesicles ensures an extremely thin coating thickness (≈15 nm), maintaining the monolayer coating structure. Nice ignition, combustion, anti‐agglomeration, and water‐proof properties of Al@G‐F‐G(DMF) are achieved, which are superior among the existing Al‐based fuels. The derived Al‐based fuel has excellent comprehensive properties, which can not only inspire the development of new‐generation energetic materials but also provide facile but exquisite strategies for exquisite surface nanostructure construction via ordered self‐assembly for many other applications.

IntroductionThis study characterized Vibrio alginolyticus isolated from seafood and freshwater products in China (2020).Methods and ResultsIn total, 122 (95.31%) V. alginolyticus isolates were resistant to at least 1 antibiotic category, and 2 (1.56%) isolates were resistant to at least 3 antibiotic categories and belong to multi-drug resistance (MDR) isolates. A high prevalence rate was observed to be blaCARB (98.04%) encoding beta-lactam resistance, followed by tet (97.06%) encoding tetracycline resistance and fos (4.90%) encoding resistance to fosfomycin. Among the 57 V. alginolyticus isolates, the commonest virulence genes were type III secretion system translocated gene vopD, vopB, and vcrH (54.4%, 31/57), type III secretion system regulated gene tyeA (54.39%), followed by vscI and vscF (50.88%) encoded type III secretion system inner rod protein and needle protein, respectively. Multilocus sequence typing (MLST) showed considerable genetic diversity, with 34 distinct sequence types (STs) identified among 55 isolates. ST421 (n = 5), ST166 (n = 4), ST523 (n = 3), ST516 (n = 3), and ST507 (n = 3) were dominant STs among 55 V. alginolyticus isolates.DiscussionThese findings highlight the widespread occurrence of V. alginolyticus in both freshwater and seafood products, underscoring the critical need for vigilant monitoring of these bacteria. Such measures are essential for ensuring effective food safety management and safeguarding public health.

Currently, chemotherapy remains occupying a pivotal place in the treatment of pancreatic ductal adenocarcinoma (PDAC). Nonetheless, the emergence of drug resistance in recent years has limited the clinical efficacy of chemotherapeutic agents, especially gemcitabine (GEM). Through bioinformatics analysis, AT-rich Interactive Domain-containing Protein 3A (ARID3A), one of transcription factors, is discovered to possibly participate in this progress. This study thoroughly investigates the potential role of ARID3A in the malignant progression and GEM chemoresistance of PDAC and explores the underlying mechanisms. The results indicate that ARID3A knockdown suppresses tumor development and enhances the sensitivity of PDAC cells to GEM in vitro and vivo. Mechanically, CUT&Tag profiling sequencing, RNA‐sequencing and functional studies demonstrates that decreased ARID3A expression alleviates the transcriptional inhibition of phosphatase and tensin homolog (PTEN), consequently leading to glutathione peroxidase 4 (GPX4) depletion and increased lipid peroxidation levels. Activated ferroptosis induced by the inhibition of GPX4 subsequently restricts tumor progression and reduces GEM resistance in PDAC. This research identifies the ferroptosis regulatory pathway of ARID3A-PTEN-GPX4 axis and reveals its critical role in driving the progression and chemoresistance of pancreatic cancer. Notably, both inhibition of ARID3A and enhancement of ferroptosis can increase chemosensitivity to GEM, which offers a promising opportunity for developing therapeutic strategies to combat acquired chemotherapy resistance in pancreatic cancer.

A 54-year-old woman was admitted to the hospital with a left neck mass. Enhanced CT and ultrasound examinations revealed a lesion in the left sternocleidomastoid muscle. The patient undergone right thyroid lobe resection 8 years ago. Interestingly, the lesion on the sternocleidomastoid muscle, along with the left lobe of the patient’s thyroid, visually appears to form a displaced and complete thyroid in the early Tc-99m-MIBI parathyroid scintigraphy. Combined with Tc-99m-MIBI scintigraphy and abnormal PTH and blood calcium levels, the consideration was given to the lesion in the sternocleidomastoid muscle as an ectopic parathyroid adenoma. Subsequent surgical pathology confirmed this suspicion.