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Abstract Utilizing ultrafast light-matter interaction to manipulate electronic states of quantum materials is an emerging area of research in condensed matter physics. It has significant implications for the development of future ultrafast electronic devices. However, the ability to induce long-lasting metastable electronic states in a fully reversible manner is a long-standing challenge. Here, by using ultrafast laser excitations, we demonstrate the capability to manipulate the electronic polar states in the charge-density-wave material EuTe4 in a non-volatile manner. The process is completely reversible and is achieved at room temperature with an all-optical approach. Each induced non-volatile state brings about modifications to the electrical resistance and second harmonic generation intensity. The results point to layer-specific phase inversion dynamics by which photoexcitation mediates the stacking polar order of the system. Our findings extend the scope of non-volatile all-optical control of electronic states to ambient conditions, and highlight a distinct role of layer-dependent phase manipulation in quasi-two-dimensional systems with inherent sublayer stacking orders.

Abstract Objective This study aims to investigate how the impact of preoperative sarcopenia and inflammatory markers for laryngeal cancer patients and develop a new scoring system to predict their prognosis. Materials and methods Patients who underwent laryngectomy for laryngeal cancer (LC) from December 2015 to December 2020 at the Second Affiliated Hospital of Fujian Medical University were included. Independent prognostic factors were determined using univariate and multivariate analyses. A new scoring system (SFAR) was established based on FAR and preoperative sarcopenia, and statistically analyzed. Results 198 cases included in this study that met the admission criteria. Multivariate analysis shown that preoperative sarcopenia, pTNM stage, and FAR were independent prognostic factors for laryngeal cancer. Based on these three indicators, we developed the SFAR scoring system. Multivariate analysis showed that SFAR was an independent predictor of laryngeal cancer (p

Abstract Background Chondroitin polymerizing factor (CHPF) has been found to be involved in the development of numerous cancers and correlated with poor prognosis. However, its role in the tumorigenesis and development of colorectal cancer (CRC) remains unknown. Methods In our research, we explored CHPF expression and clinicopathological characteristics using The Cancer Genome Atlas Program (TCGA), UALCAN, GSE9348, TIMER2.0 and The Human Protein Atlas (HPA) database, in addition, we validated CHPF expression in CRC cell lines by Real-Time Quantitative PCR (qRT-PCR) and Western blot (WB). KM-Plotter, PrognoScan and TCGA were also utilized to verify its prognosis value in CRC. Small-interfer RNA (Si-RNA) was used to perform Cell Counting Kit-8 (CCK8), colony formation, 5-ethynyl-2′-deoxyuridine (EDU), transwell and wound healing assays to testify its function on the tumor progression. Based on TCGA database, we probed potential biological mechanism by which CHPF play its role via clusterProfiler package and GEPIA database and we validated their correlation by WB assay. Moreover, we explored its potential association with the tumor microenvironment (TME), immune infiltrated cells, immune checkpoints, tumor mutation burden (TMB) as well as microsatellite instability (MSI), and investigated immunotherapy sensitivity via Tumor Immune Dysfunction and Exclusion (TIDE) algorithm as well as potentially effective therapeutic drugs via pRRophetic algorithm. Results CHPF was identified upregulated in CRC tissues and cells, correlated with poor prognosis, and nodal metastasis status, stage and histological subtype. Down-regulation of CHPF inhibited CRC cell proliferation, migration and its expression correlated with wnt pathway key molecules. In addition, high expression of CHPF was positively correlated with TME scores, Regulatory T cells (Tregs) cell infiltration degree, Programmed death-1 (PD-1), MSI-high (MSI-H), and TIDE scores, however, not with TMB. Targeted drug analysis showed that patients with high CHPF expression were more sensitive to telatinib, recaparib, serdemetan, and trametinib. Conclusion CHPF could promote the proliferation and migration of CRC cells and lead to poor prognosis, possibly through wnt pathways as well as changes in TME. Patients with high expression of CHPF had poor efficacy in immunotherapy, which might be related to Tregs cell infiltration. Above all, it might offer more reliable guidance for future immunotherapy.

Measuring pore-water pressure (PWP) in frozen soils poses significant challenges in geotechnical testing experiments, and understanding PWP is crucial for unraveling the mechanism of frost heave generation in cold regions. This paper aims to clarify the development pattern of PWP in frozen soil through laboratory tests, specifically focusing on excess PWP generated under dynamic loading. Seven sets of triaxial tests were conducted to investigate the variations in excess PWP and deformation influenced by temperature, dynamic stress amplitude, and dry density. The results reveal that excess PWP in warm saturated frozen soil undergoes two stages: pore pressure increase and dissipation. The change of external factors mainly affects the peak value of excess PWP and the change rate of excess PWP. Unlike unfrozen soil, excess PWP has a small dissipation rate after the peak and may remain dynamically stable in the later stage of loading. In addition, two empirical models of excess PWP applicable to saturated frozen soils were proposed based on the developmental patterns of excess PWP in frozen soils, and the feasibility was validated using the results obtained from laboratory tests. The model is of great significance for predicting the development of excess PWP in frozen soil under dynamic load.

Abstract Background Woven coronary artery (WCA) is a rare and underdiagnosed congenital anomaly that involves multiple thin and tortuous epicardial arterial conduits reassembling distally into a single lumen. Recanalized thrombus may present as woven-like coronary arteries, appearing similar to WCA on angiographic images. Case presentation A 58-year-old female patient with intermittent chest pain for 5 years and polycythaemia vera (PV) for 8 years. The left anterior descending artery was presented like WCA on coronary angiography and finally confirmed as recanalized thrombus by optical coherence tomography(OCT), which might have been caused by PV. Given the patient’s high thrombotic risk of PV and thrombotic changes in the left circumflex artery (LCX), we ultimately chose a conservative treatment without stenting. Conclusions OCT would be needed for the diagnosis and differential diagnosis of woven-like coronary arteries. And physicians should take an appropriate treatment in a personalized way in patients with PV.

Heat-resistant energetic materials refer to a type of energetic materials that possess a high melting point, high stability and operational safety. By studying the structures of these energetic materials has showed that the thermal stability can be enhanced by introducing amino groups to form intra/inter-molecular hydrogen bonds, constructing conjugate systems and designing symmetrical structures. This article aims to review the physical and chemical properties of ultra-high temperature heat-resistant energetic compounds and provide valuable theoretical insights for the preparation of ultra-high temperature heat-resistant energetic materials. We also analyze the selected 20 heat-resistant energetic materials with decomposition temperatures higher than 350 °C, serving as templates for the synthesis of various high-performance heat-resistant energetic materials.

Highlights By introducing fluorine modulation into MXene, a new MXene-derived material TiOF/Ti3C2 was successfully synthesized with a distinctive three-dimensional structure and a tailored F distribution. In situ characterizations and electrochemical analyses demonstrate that TiOF/Ti3C2 catalysts effectively coupled the multiphase sulfur species conversion processes. The investigations reveal that the theoretical basis of the fluorine catalysis in Li–S batteries originated from Lewis acid–base mechanisms and charge compensation mechanisms.

Abstract Background There is growing evidence of bidirectional associations between rheumatoid arthritis and adverse pregnancy outcomes (APOs) in observational studies, but little is known about the causal direction of these associations. Therefore, we explored the potential causal relationships between rheumatoid arthritis and APOs using a bidirectional two-sample Mendelian randomization (MR) in European and Asian populations. Methods We conducted a bidirectional two-sample Mendelian randomization analysis using available summary statistics from released genome-wide association studies. Summary statistics for instrument–outcome associations were retrieved from two separate databases for rheumatoid arthritis and adverse pregnancy outcomes, respectively. The inverse-variance weighted method was used as the primary MR analysis, and cML-MA-BIC was used as the supplementary analysis. MR-Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran Q statistic method were implemented as sensitivity analyses approach to ensure the robustness of the results. Results Our study showed that a higher risk of rheumatoid arthritis in the European population was associated with gestational hypertension (OR: 1.04, 95%CI: 1.02–1.06), pre-eclampsia (OR: 1.06, 95%CI: 1.01–1.11), fetal growth restriction (OR: 1.08, 95%CI: 1.04–1.12), preterm delivery (OR:1.04, 95%CI: 1.01–1.07). Furthermore, we found no evidence that APOs had causal effects on rheumatoid arthritis in the reverse MR analysis. No association between rheumatoid arthritis and APOs was found in East Asian population. There was no heterogeneity or horizontal pleiotropy. Conclusions This MR analysis provides the positive causal association from rheumatoid arthritis to gestational hypertension, pre-eclampsia, fetal growth restriction and preterm delivery genetically. It highlights the importance of more intensive prenatal care and early intervention among pregnant women with rheumatoid arthritis to prevent potential adverse obstetric outcomes.

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. Methods We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. Results A functional assay identified that transforming growth factor-β1 (TGF-β1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. Conclusions These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD.

Abstract The function of Family With Sequence Similarity 83, Member A (FAM83A) in lung squamous cell carcinoma (LUSC) is largely unknown. Here, we detected its prognostic and regulation roles in LUSC. Bioinformatics methods were applied initially to predict the expression level and prognostic value of FAM83A mRNA in LUSC. In vitro experiments, such as western blot, colony formation and cell viability assay, lipid Reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG), and 4-hydroxy-2-nonenal (4-HNE) assay, were used to investigate its mechanism. In vivo experiments were further conducted to validate the mechanism. Results from TCGA and Oncomine databases revealed significantly higher FAM83A mRNA expression levels in LUSC than in normal lung tissue. TCGA and GEO databases and our database revealed that FAM83A expression level was an independent prognostic factor for both overall survival and progression-free survival. Besides, FAM83A was significantly associated with a higher ability of growth and clonogenicity. Mechanistically, in vitro and in vivo experiments revealed that FAM83A could promote LUSC cell growth by inhibiting ferroptosis via activating the Wnt/β-catenin signaling pathway. The rescue experiment demonstrated that inhibition of the Wnt/β-catenin pathway counteracted the function of FAM83A. FAM83A is overexpressed in LUSC and could serve as a prognosis prediction biomarker for LUSC. FAM83A promotes LUSC cell growth by inhibiting ferroptosis via activating the Wnt/β-catenin signaling pathway, which provides a new potential therapeutic target for LUSC treatment.

The deposition area of the hot filament chemical vapor deposition (HFCVD) method can reach 12 inches, which has the potential to produce larger-sized single crystal diamonds. In this study, single crystal diamond with a size of 3 mm × 3 mm × 1 mm and (100) orientation was used as the substrate. Homoepitaxial growth was carried out using the HFCVD method with methane and hydrogen as precursors, and a small amount of nitrogen gas. The results show that under the conditions of a filament temperature of 2200 °C, a carbon source concentration of 4%, and a chamber pressure of 4 kPa, single crystal diamond grows at a rate of 3.41 μm/h. The surface of the diamond exhibits no defects such as polycrystals, cracks, or holes. The full width half maximum (FWHM) of the epitaxial layer’s X-ray diffraction spectrum at the (400) peak is 0.11°, which is lower than that of the substrate at 0.16°, indicating that the crystal quality of the epitaxial layer is higher than that of the substrate. The introduction of nitrogen can increase the growth rate of single crystal diamond, although it reduces the crystal quality of the epitaxial layer. A higher nitrogen concentration can also shift the growth mode of single crystal diamond change to island growth.

Abstract Background Kidney transplant recipients (KTRs) are at an elevated risk of progressing to severe infections upon contracting COVID-19. We conducted a study on risk factors and multi-pathogen infections in KTRs with SARS-CoV-2 Omicron variant. Methods KTRs were subjected to a thorough etiological evaluation. Whenever feasible, they were also provided with bronchoscopy and bronchoalveolar lavage to enable metagenomic next-generation sequencing (mNGS), ideally within a 48-hour window post-admission. We performed a retrospective analysis for pathogens and risk factors of KTRs with the COVID-19 virus variant Omicron. Results We included thirty patients in our study, with sixteen exhibiting single infection of COVID-19 and fourteen experiencing co-infections, predominantly with Pneumocystis jirovecii. Notably, patients with severe cases demonstrated significantly elevated levels of C-reactive protein (CRP) and interleukin-6 compared to those with moderate cases (P

Using fiberglass bolts to reinforce a tunnel face is a practical auxiliary technology for ensuring tunnel face stability in soft ground. The reinforcing effect and the economics of this technology are significantly affected by bolt length. However, to date, the failure mechanism of bolt-reinforced tunnel faces with different bolt lengths has rarely been investigated. To reveal the failure mechanism of bolt-reinforced shallow tunnel faces, in this study, the stability of bolt-reinforced tunnel faces with different bolt lengths was investigated by using laboratory tests and numerical simulations, and a simplified theoretical model for practical engineering was proposed. The face support pressure and failure pattern for different bolt lengths during the face collapse process were obtained, and the influence of bolt length on face stability was clearly revealed. More specifically, the results show that face stability increases with increasing bolt length, and the reinforcing effect of face bolts is governed by the shear failure at the soil-grout interface first in the stable zone of the tunnel face and then in the failure zone. Once the bolt length in the stable zone is larger than that in the failure zone, face stability will not be improved with increasing bolt length; thus, this bolt length is referred to as the optimal bolt length Lopt. The Lopt value is slightly larger than the initial failure range (in the unreinforced condition) and can be approximately calculated by Lopt = (1 − 0.0133φ)D (φ is the friction angle of the soil, and D is the tunnel diameter) in practical engineering. Finally, a simplified theoretical model was established to analyse the stability of reinforced tunnel faces, and the results are in good agreement with both laboratory tests and numerical simulations. The proposed model can be used as an efficient tool for the design of face bolts.

Rapid urbanization has had a segmented effect on the ecological land and natural environment in cities. Constructing an ecological network is of vital importance to protect ecological resources and maintain regional ecological security. However, ecological spaces at different administrative scales have their own ecological functions and elemental characteristics. Therefore, we formed the ecological network sequence to present the integrative connection of multi-scale with municipal area (MA), main urban area (MUA) and central urban area (CUA) in Nanjing. Ecological sources were identified through “landscape—function—structure” framework, and ecosystem services value (ESV) was used as an auxiliary method to identify supplementary sources. Ecological corridors and some key points were identified through circuit theory. The results show that the area of ecological sources in MA, MUA and CUA was 427.3 km2, 62.5 km2 and 16.2 km2, respectively. By integrating sources of three scales, we got 14 sources (442.7 km2) in the first sequence and 10 sources (7.7 km2) in the second sequence. Apart from that, we also got 4 new supplementary sources with area of 13.5 km2. The length of ecological corridors in MA, MUA and CUA was 252.5 km, 263.9 km and 22.7 km, respectively. By integrating corridors of three scales, we found that the western corridors between the ecological sources had a higher gravitation. The ecological nodes are generally distributed in the landscape heterogeneity transition zone, ecological resource fringe zone and ecological spatial contiguous zone. The ecological pinch points are generally distributed along the water system. The ecological barrier points are generally distributed in the combination area among the urban block, village and road. In conclusion, this study made up for the research gap of finding the nesting and integration relationship among ecological networks at multi-scale.

This paper proposes a streamlined approach to addressing the problem of allocating finite crew resources to concurrent jobs in the context of municipal drainage infrastructure maintenance. The problem was defined from the perspective of a project manager involved in planning such operations on a day-by-day basis. The problem statement was then transformed into a simplified Integer Linear Programming optimization model. Performance metrics were devised to evaluate the optimization model’s effectiveness. A heuristic algorithm representing the decision-making process by a seasoned planner in the partner company was also developed. Both methods were applied to a case study and contrasted based on the same performance metrics. The findings underscored substantial optimization benefits in rendering decision support in resource-constrained drainage construction operations planning. In conclusion, this research presents an alternative strategy for navigating the complexities inherent in finite crew resource allocation on multiple concurrent drainage projects; lends a cost-effective optimization solution to improving the utilization of finite available crews while satisfying service demands from multiple clients to the largest extent possible.

Accumulating observational studies have linked particulate air pollutants to neurodegenerative diseases (NDDs). However, the causal links and the direction of their associations remain unclear. Therefore, we adopted a two-sample Mendelian randomization (TSMR) design using the GWAS-based genetic instruments of particulate air pollutants (PM2.5 and PM10) from the UK Biobank to explore their causal influence on four common neurodegenerative diseases. Estimates of causative relationships were generated by the Inverse variance weighted (IVW) method with multiple sensitive analyses. The heterogeneity and pleiotropy tests were additionally performed to verify whether our findings were robust. Genetically predicted PM2.5 and PM10 could elevate the occurrence of AD (odds ratio [OR] = 2.22, 95 % confidence interval [CI] 1.53–3.22, PIVW = 2.85×10−5, PFalse discovery rate [FDR] = 2.85×10−4 and OR = 2.41, 95 % CI: 1.26–4.60, PIVW = 0.008, PFDR =0.039, respectively). The results were robust in sensitive analysis. However, no evidence of causality was found for other NDDs. Our present study suggests that PM2.5 and PM10 have a detrimental effect on AD, which indicates that improving air quality to prevent AD may have pivotal public health implications.

BackgroundPulmonary Artery in situ Thrombosis (PAIST) refers to a thrombus forming within the pulmonary arterial system, distinct from an embolus originating from elsewhere in the body (e.g., the deep veins of the lower extremities) and traveling to the lungs where it lodges and forms.Case presentationWe present a case of PAIST caused by the arterial ductus arteriosus. The patient primarily presented with dyspnea, and the chest pain dichotomy Computed Tomography Angiography(CTA) suggested that a nodular low-density filling defect was seen in the lumen of the left pulmonary artery trunk. Initially, pulmonary embolism (PE) was suspected. However, upon reevaluation of the imaging, it became apparent that the patient's pulmonary artery obstruction was closely associated with the ductus arteriosus. After admission, the patient was treated with sodium ampicillin (2.0 g Q12H) for infection, heparin sodium (5,000 IU Q12H) for anticoagulation, and metoprolol succinate extended-release tablets (23.75 mg QD) to correct cardiac remodeling, among other treatments. Subsequently, the patient underwent a cardiac surgery involving the ligation of the arterial duct, resection of pulmonary artery lesions, and open-heart surgery with extracorporeal circulation support. Postoperative examination of the pulmonary artery mass indicated coagulation tissue. The final diagnosis was “PAIST”.ConclusionBoth PAIST and PE manifest as low-density filling defects in the pulmonary arteries. However, due to the relative unfamiliarity with PAIST, such findings are often initially attributed to PE.

BackgroundNeutrophil plays a pivotal role in the management of Klebsiella pneumoniae infection. Delineate the clinical characteristics and prognostic utility of neutrophil in severe patients with K. pneumoniae infection are crucial for clinical management and prognostic assessment.MethodsK. pneumoniae patients with different infection sites were enrolled from Medical Information Mart for Intensive Care IV and eICU Collaborative Research Database. Temporal variations of neutrophil counts within 30 days of clinical onset were examined using locally weighted scatterplot smoothing curves. Logistic regression analysis was performed to assess the relationship between neutrophil counts and hospital mortality.ResultsA total of 1,705 patients caused by K. pneumonia were included in the study. The non-survivor group exhibited a comparatively older age and a higher proportion of K. pneumoniae infections originating from respiratory and bloodstream sources compared to the survivor group (38.4% vs 21.1%, p

Abstract Osteosarcoma is a malignant bone tumor that primarily inflicts the youth. It often metastasizes to the lungs after chemotherapy failure, which eventually shortens patients’ lives. Thus, there is a dire clinical need to develop a novel therapy to tackle osteosarcoma metastasis. Methionine dependence is a special metabolic characteristic of most malignant tumor cells that may offer a target pathway for such therapy. Herein, we demonstrated that methionine deficiency restricted the growth and metastasis of cultured human osteosarcoma cells. A genetically engineered Salmonella, SGN1, capable of overexpressing an L-methioninase and hydrolyzing methionine led to significant reduction of methionine and S-adenosyl-methionine (SAM) specifically in tumor tissues, drastically restricted the growth and metastasis in subcutaneous xenograft, orthotopic, and tail vein-injected metastatic models, and prolonged the survival of the model animals. SGN1 also sharply suppressed the growth of patient-derived organoid and xenograft. Methionine restriction in the osteosarcoma cells initiated severe mitochondrial dysfunction, as evident in the dysregulated gene expression of respiratory chains, increased mitochondrial ROS generation, reduced ATP production, decreased basal and maximum respiration, and damaged mitochondrial membrane potential. Transcriptomic and molecular analysis revealed the reduction of C1orf112 expression as a primary mechanism underlies methionine deprivation-initiated suppression on the growth and metastasis as well as mitochondrial functions. Collectively, our findings unraveled a molecular linkage between methionine restriction, mitochondrial function, and osteosarcoma growth and metastasis. A pharmacological agent, such as SGN1, that can achieve tumor specific deprivation of methionine may represent a promising modality against the metastasis of osteosarcoma and potentially other types of sarcomas as well.

Abstract Background The incidence of neuroendocrine neoplasms (NENs) is rising rapidly worldwide. However, there are few reports on these heterogeneous diseases in China. Our study aimed to explore the epidemiological characteristics of NENs in Beijing. Methods We conducted a retrospective cohort study using population-based cancer surveillance data in Beijing, China. All data were extracted from the Beijing Cancer Registry with incidence dates from 1 January 1998 to 31 December 2018; the follow-up period was through 31 December 2021. Segi’s world standard population was used to estimate the age-standardized rate. Survival was estimated using the Kaplan–Meier method. Results From 1998 to 2018, the incidence of NENs in Beijing initially showed a significant increasing trend, from 1.07/100,000 to 3.53/100,000; this began to plateau after 2013. The age-specific incidence rate increased with age and peaked in the age group 70–74 years. The incidence in men was significantly higher than that in women (4.41/100,000 vs. 1.69/100,000). The most common sites of NENs were the lung (2.38/100,000) and rectum (0.14/100,000). Most NENs were diagnosed at a late stage. We found that NENs originating from the lung had worse overall survival than extrapulmonary NENs, and male patients had worse survival than female patients. Conclusions This study retrospectively analyzed the epidemiological characteristics of NENs in Beijing from 1998 to 2018. Our findings provide a reference regarding the epidemiological statistics of NENs in Beijing to contribute to the prevention, diagnosis, and treatment of these specific tumors.

Abstract In this work, we realized the detection of diamino-pentazolium cation (DAPZ+) in the reaction solution experimentally and proved it to be meta-diamino-pentazole based on the transition state theory. Quantum chemical methods were used to predict its spectral properties, charge distribution, stability and aromaticity. Considering that DAPZ+ has excellent detonation properties, it was further explored by assembling it with N5 −, N3 − and C(NO2)3 − anions, respectively. The results show a strong interaction between DAPZ+ and the three anions, which will have a positive effect on its stability. Thanks to the high enthalpy of formation and density, the calculated detonation properties of the three systems are exciting, especially [DAPZ+][N5 −] (D: 10,016 m·s−1; P: 37.94 GPa), whose actual detonation velocity may very likely exceed CL-20 (D: 9773 m·s−1). There is no doubt that this work will become the precursor for the theoretical exploration of new polynitrogen ionic compounds.

Abstract Mitochondria have multiple functions such as supplying energy, regulating the redox status, and producing proteins encoded by an independent genome. They are closely related to the physiology and pathology of many organs and tissues, among which the brain is particularly prominent. The brain demands 20% of the resting metabolic rate and holds highly active mitochondrial activities. Considerable research shows that mitochondria are closely related to brain function, while mitochondrial defects induce or exacerbate pathology in the brain. In this review, we provide comprehensive research advances of mitochondrial biology involved in brain functions, as well as the mitochondria-dependent cellular events in brain physiology and pathology. Furthermore, various perspectives are explored to better identify the mitochondrial roles in neurological diseases and the neurophenotypes of mitochondrial diseases. Finally, mitochondrial therapies are discussed. Mitochondrial-targeting therapeutics are showing great potentials in the treatment of brain diseases.

Abstract Background To analyze the impact of the time of natural cessation of the umbilical cord on maternal and infant outcomes in order to explore the time of clamping that would be beneficial to maternal and infant outcomes. Methods The study was a cohort study and pregnant women who met the inclusion and exclusion criteria at the Obstetrics and Gynecology Department of Qilu Hospital of Shandong University from September 2020 to September 2021. Analysis using Kruskal-Wallis rank sum test, Pearson’s Chi-squared test, generalized linear mixed model (GLMM) and repeated measures ANOVA. If the difference between groups was statistically significant, the Bonferroni test was then performed. A two-sided test of P 0.05). The weight of the newborns in the three groups was (3316.27 ± 356.70) g, (3387.26 ± 379.20) g, and (3455.52 ± 363.78) g, respectively, and the number of days of cord detachment was 12.00 (8.00, 15.75) days, 10.00 (7.00, 15.00) days and 9.00 (7.00, 13.00) days, respectively, as the time of natural cessation of the cord increased. The neonatal lymphocyte ratio, erythrocyte pressure, and hemoglobin reached a maximum in the 61–89 s group at (7.41 ± 2.16) %, (61.77 ± 8.17) % and (194.52 ± 25.84) g/L, respectively. Lower incidence of neonatal hyperbilirubinemia in the 61–89 s group compared to the ≥90s group 0 vs 4.8 (P

Abstract We aimed to identify the key potential insulin resistance (IR)-related genes and investigate their correlation with immune cell infiltration in type 2 diabetes (T2D). The GSE78721 dataset (68 diabetic patients and 62 controls) was downloaded from the Gene Expression Omnibus database and utilized for single-sample gene set enrichment analysis. IR-related genes were obtained from the Comparative Toxicology Genetics Database, and the final IR-differentially expressed genes (DEGs) were screened by intersecting with the DEGs obtained from the GSE78721 datasets. Functional enrichment analysis was performed, and the networks of the target gene with microRNA, transcription factor, and drug were constructed. Hub genes were identified based on a protein–protein interaction network. Least absolute shrinkage and selection operator regression and Random Forest and Boruta analysis were combined to screen diagnostic biomarkers in T2D, which were validated using the GSE76894 (19 diabetic patients and 84 controls) and GSE9006 (12 diabetic patients and 24 controls) datasets. Quantitative real-time polymerase chain reaction was performed to validate the biomarker expression in IR mice and control mice. In addition, infiltration of immune cells in T2D and their correlation with the identified markers were computed using CIBERSORT. We identified differential immune gene set regulatory T-cells in the GSE78721 dataset, and T2D samples were assigned into three clusters based on immune infiltration. A total of 2094 IR-DEGs were primarily enriched in response to endoplasmic reticulum stress. Importantly, HDAC9 and ARRDC4 were identified as markers of T2D and associated with different levels of immune cell infiltration. HDAC9 mRNA level were higher in the IR mice than in control mice, while ARRDC4 showed the opposite trend. In summary, we discovered potential vital biomarkers that contribute to immune cell infiltration associated with IR, which offers a new sight of immunotherapy for T2D.

Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of squamous cell carcinoma and represents a significant proportion of esophageal cancer. Metabolic reprogramming plays a key role in the occurrence and development of ESCC. Unsupervised clustering analysis was employed to stratify ESCC samples into three clusters: MPC1-lipid type, MPC2-amino acid type, and MPC3-energy type, based on the enrichment scores of metabolic pathways extracted from the Reactome database. The MPC3 cluster exhibited characteristics of energy metabolism, with heightened glycolysis, cofactors, and nucleotide metabolism, showing a trend toward increased aggressiveness and poorer survival rates. On the other hand, MPC1 and MPC2 primarily involved lipid and amino acid metabolism, respectively. In addition, liquid chromatography‒mass spectrometry-based metabolite profiles and potential therapeutic agents were explored and compared among ESCC cell lines with different MPCs. MPC3 amplified energy metabolism markers, especially carnitines. In contrast, MPC1 and MPC2 predominantly had elevated levels of lipids (primarily triacylglycerol) and amino acids, respectively. Furthermore, MPC3 demonstrated a suboptimal clinical response to PD-L1 immunotherapy but showed increased sensitivity to the doramapimod chemotherapy regimen, as evident from drug sensitivity evaluations. These insights pave the way for a more personalized therapeutic approach, potentially enhancing treatment precision for ESCC patients.

Abstract Because of its high energy, aromaticity, and carbon- and hydrogen-free structure, the cyclo-pentazolate anion (c-N5 -) has attracted increased attention as a potential polynitrogen structural unit for the research of next-generation high energy density materials. However, the poor thermal stability of c-N5 --based compounds has become an important factor restricting their development. Here, we show that a hydrogen-bonded organic framework (HOF) self-assembles with and stabilizes c-N5 -, with c-N5 - situated in the pores of the resulting framework through the formation of symmetrical c-N5 - hydrogen bonds as the main stabilizing factors. These factors result in an onset decomposition temperature of 153 °C for the c-N5 -@HOF portion, which exceeds the thermal stabilities generally observed for c-N5 --based derivatives of below 135 °C. We envisage that further c-N5 --based materials with enhanced stabilities and better performance will be developed in the future.

Background: The real-world clinical impact of mNGS on BALF in the respiratory intensive care unit (RICU) is not yet fully understood. Methods: We investigated the clinical impact of mNGS on BALF samples obtained from 92 patients admitted to the RICU over a 2-year period. We utilized both mNGS and culture methods to evaluate the effectiveness of mNGS in diagnosing pulmonary infections. The clinical impact of mNGS were evaluated by the clinician committees. Results: Among the 92 diagnosed patients, 78 cases (84.7 %) were determined to have infectious diseases caused by pathogenic microorganisms, and the bacterial infections constituted the most prevalent diagnostic category. For mixed infection, the most common type was the Pneumocystis jironecii and cytomegalovirus co-infection. The mNGS results had a positive impact on the clinical management of 43 cases (46.7 %). Moreover, 19 cases (44.2 %) of positive clinical impacts were solely based on new diagnoses made possible by mNGS results. These new diagnoses were particularly helpful for identifying rare pathogens, which could not be detected by conventional diagnostic methods. Conclusions: The BALF mNGS has a positive real-world impact in RICU. Clinician committee play a critical role in ensuring the appropriate use of mNGS.

BackgroundThis study aimed to construct a clinical prediction model and nomogram to differentiate invasive from non-invasive pulmonary adenocarcinoma in solitary pulmonary nodules (SPNs).MethodWe analyzed computed tomography and clinical features as well as preoperative biomarkers in 1,106 patients with SPN who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University between January 2020 and December 2021. Clinical parameters and imaging characteristics were analyzed using univariate and multivariate logistic regression analyses. Predictive models and nomograms were developed and their recognition abilities were evaluated using receiver operating characteristic (ROC) curves. The clinical utility of the nomogram was evaluated using decision curve analysis (DCA).ResultThe final regression analysis selected age, carcinoembryonic antigen, bronchus sign, lobulation, pleural adhesion, maximum diameter, and the consolidation-to-tumor ratio as associated factors. The areas under the ROC curves were 0.844 (95% confidence interval [CI], 0.817–0.871) and 0.812 (95% CI, 0.766–0.857) for patients in the training and validation cohorts, respectively. The predictive model calibration curve revealed good calibration for both cohorts. The DCA results confirmed that the clinical prediction model was useful in clinical practice. Bias-corrected C-indices for the training and validation cohorts were 0.844 and 0.814, respectively.ConclusionOur predictive model and nomogram might be useful for guiding clinical decisions regarding personalized surgical intervention and treatment options.

Parkinson's disease (PD) poses a significant challenge in neurodegenerative disorders, characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). The intricate mechanisms orchestrating DA neurodegeneration in PD are not fully understood, necessitating the exploration of innovative therapeutic approaches. Recent studies have implicated ferroptosis as a major contributor to the loss of DA neurons, revealing a complex interplay between iron accumulation and neurodegeneration. However, the sophisticated nature of this process challenges the conventional belief that mere iron removal could effectively prevent DA neuronal ferroptosis. Here, we report JWA, alternatively referred to as ARL6IP5, as a negative regulator of ferroptosis, capable of ameliorating DA neuronal loss in the context of PD. In this study, synchronized expression patterns of JWA and tyrosine hydroxylase (TH) in PD patients and mice were observed, underscoring the importance of JWA for DA neuronal survival. Screening of ferroptosis-related genes unraveled the engagement of iron metabolism in the JWA-dependent inhibition of DA neuronal ferroptosis. Genetic manipulation of JWA provided compelling evidence linking its neuroprotective effects to the attenuation of NCOA4-mediated ferritinophagy. Molecular docking, co-immunoprecipitation, and immunofluorescence studies confirmed that JWA mitigated DA neuronal ferroptosis by occupying the ferritin binding site of NCOA4. Moreover, the JWA-activating compound, JAC4, demonstrated promising neuroprotective effects in cellular and animal PD models by elevating JWA expression, offering a potential avenue for neuroprotection in PD. Collectively, our work establishes JWA as a novel regulator of ferritinophagy, presenting a promising therapeutic target for addressing DA neuronal ferroptosis in PD.

Abstract Pneumonia is the most common complication of varicella infections. Although previous studies have tended to focus mainly on immunocompromised patients, varicella pneumonia can also occur in healthy adults. Therefore, in this study, we aimed to assess the progression of varicella pneumonia in immunocompetent hosts. This retrospective study involved immunocompetent adult outpatients with varicella who attended the adult Fever Emergency facility of Peking University Third Hospital from April 1, 2020, to October 31, 2022. Varicella pneumonia was defined as a classic chickenpox-type rash in patients with infiltrates on chest computed tomography. The study included 186 patients, 57 of whom had a contact history of chickenpox exposure. Antiviral pneumonia therapy was administered to 175 patients by treating physicians. Computed tomography identified pneumonia in 132 patients, although no deaths from respiratory failure occurred. Seventy of the discharged patients were subsequently contacted, all of whom reported being well. Follow-up information, including computed tomography findings, was available for 37 patients with pneumonia, among whom 24 reported complete resolution whereas the remaining 13 developed persistent calcifications. Notably, we established that the true incidence of varicella pneumonia is higher than that previously reported, although the prognosis for immunocompetent hosts is generally good.

Abstract Background The occurrence of multidrug-resistant and hypervirulent Klebsiella pneumoniae (MDR-hvKp) worldwide poses a great challenge for public health. Few studies have focused on ST218 MDR-hvKp. Methods Retrospective genomic surveillance was conducted at the Peking University Third Hospital from 2017 and clinical information was obtained. To understand genomic and microbiological characteristics, antimicrobial susceptibility testing, plasmid conjugation and stability, biofilm formation, serum killing, growth curves and whole-genome sequencing were performed. We also assessed the clinical and microbiological characteristics of ST218 compared with ST23. Results A total of eleven ST218 Kp isolates were included. The most common infection type was lower respiratory tract infection (72.7%, 8/11) in our hospital, whereas ST23 hvKp (72.7%, 8/11) was closely associated with bloodstream infection. Notably, nosocomial infections caused by ST218 (54.5%, 6/11) was slightly higher than ST23 (36.4%, 4/11). All of the ST218 and ST23 strains presented with the virulence genes combination of iucA + iroB + peg344 + rmpA + rmpA2. Interestingly, the virulence score of ST218 was lower than ST23, whereas one ST218 strain (pPEKP3107) exhibited resistance to carbapenems, cephalosporins, β-lactamase/inhibitors and quinolones and harbored an ~ 59-kb IncN type MDR plasmid carrying resistance genes including bla NDM-1, dfrA14 and qnrS1. Importantly, bla NDM-1 and qnrS1 were flanked with IS26 located within the plasmid that could successfully transfer into E. coli J53. Additionally, PEKP2044 harbored an ~ 41-kb resistance plasmid located within tetA indicating resistance to doxycycline. Conclusion The emergence of bla NDM-1 revealed that there is great potential for ST218 Kp to become a high-risk clone for MDR-hvKp, indicating the urgent need for enhanced genomic surveillance.

Abstract The cycle of precipitation change is key to understanding the driving mechanism of the East Asian summer monsoon (EASM). However, the dominant cycles of EASM precipitation revealed by different proxy indicators are inconsistent, leading to the “Chinese 100 kyr problem”. In this study, we examine a high-resolution, approximately 350,000-year record from a low-latitude loess profile in China. Our analyses show that variations in the ratio of dithionite−citrate−bicarbonate extractable iron to total iron are dominated by the ~20-kyr cycle, reflecting changes in precipitation. In contrast, magnetic susceptibility varies with the ~100-kyr cycle and may be mainly controlled by temperature-induced redox processes or precipitation-induced signal smoothing. Our results suggest that changes in the EASM, as indicated by precipitation in this region, are mainly forced by precession-dominated insolation variations, and that precipitation and temperature may have varied with different cycles over the past ~350,000 years.

Abstract Background m6A modification is currently recognized as a major driver of RNA function that maintains cancer cell homeostasis. Long non-coding (Lnc) RNAs control cell proliferation and play an important role in the occurrence and progression of colorectal cancer (CRC). ZCCHC4 is a newly discovered m6A methyltransferase whose role and mechanism in tumors have not yet been elucidated. Methods The EpiQuik m6A RNA methylation kit was used to detect the level of total RNA m6A in six types of digestive tract tumors. The Kaplan-Meier method and receiver operating characteristic curve were used to evaluate the prognostic and diagnostic value of the newly discovered m6A methyltransferase, ZCCHC4, in CRC. The effects on CRC growth in vitro and in vivo were studied using gain- and loss-of-function experiments. The epigenetic mechanisms underlying ZCCHC4 upregulation in CRC were studied using RIP, MeRIP-seq, RNA pull-down, and animal experiments. Results We reported that the ZCCHC4-LncRNAGHRLOS-KDM5D axis regulates the growth of CRC in vitro and in vivo. We found that ZCCHC4 was upregulated in primary CRC samples and could predict adverse clinical outcomes in patients with CRC. Mechanistically, ZCCHC4 downregulated LncRNAGHRLOS to promote CRC tumorigenesis. As a downstream molecule of LncRNAGHRLOS, KDM5D directly controls CRC cell proliferation, migration, and invasion. Conclusion This study suggests that the ZCCHC4 axis contributes to the tumorigenesis and progression of CRC and that ZCCHC4 may be a potential biomarker for this malignancy.

Abstract Background Pulmonary fibrosis (PF) is a progressive fibrosing interstitial pneumonia that leads to respiratory failure and other complications, which is ultimately fatal. Mesenchymal stem cells (MSCs) transplant is a promising strategy to solve this problem, while the procurement of MSCs from the patient for autotransplant remains a challenge. Methods Here, we presented olfactory mucosa mesenchymal stem cells (OM-MSCs) from mouse turbinate and determined the preventing efficacy of allotransplant for PF. We demonstrated the antiinflammation and immunomodulatory effects of OM-MSCs. Flow cytometric analysis was used to verify the effect of OM-MSCs on monocyte-derived macrophage populations in the lung. Results Administration of OM-MSCs reduces inflammation, attenuates the matrix metallopeptidase 13 (MMP13) expression level and restores the bleomycin (BLM)-induced pulmonary fibrosis by assessing the architecture of lung, collagen type I; (COL1A1), actin alpha 2, smooth muscle, aorta (ACTA2/α-SMA) and hydroxyproline. This therapeutic effect of OM-MSCs was related to the increase in the ratio of nonclassical monocytes to proinflammatory monocytes in the lung. Conclusions This study suggests that transplant of OM-MSCs represents an effective and safe treatment for PF.

Abstract Background Identifying lymph node metastasis areas during surgery for early invasive lung adenocarcinoma remains challenging. The aim of this study was to develop a nomogram mathematical model before the end of surgery for predicting lymph node metastasis in patients with early invasive lung adenocarcinoma. Methods In this study, we included patients with invasive lung adenocarcinoma measuring ≤ 2 cm who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University from January 2020 to January 2022. Preoperative biomarker results, clinical features, and computed tomography characteristics were collected. The enrolled patients were randomized into a training cohort and a validation cohort in a 7:3 ratio. The training cohort was used to construct the predictive model, while the validation cohort was used to test the model independently. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The prediction model and nomogram were established based on the independent risk factors. Recipient operating characteristic (ROC) curves were used to assess the discrimination ability of the model. Calibration capability was assessed using the Hosmer–Lemeshow test and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). Results The overall incidence of lymph node metastasis was 13.23% (61/461). Six indicators were finally determined to be independently associated with lymph node metastasis. These six indicators were: age (P

Abstract Despite the significant frequency of autonomic dysfunction (AutD) in Parkinson’s disease (PD) patients, its pathogenesis and diagnosis are challenging. Here, we aimed to further explore the mechanism of phosphorylated α-synuclein (p-α-syn) deposited in vagus nerve Schwann cells (SCs) causing SCs damage and PD AutD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) was administrated to C57BL/6 mice twice a week for 35 days. Following the final injection, locomotor functions, gastrointestinal symptoms, urine functions, and cardiovascular system functions were evaluated. Meanwhile, we examined p-α-syn deposited in vagus nerve SCs, Toll-like receptor 2 (TLR2) activation, and SCs loss using immunofluorescence, western blot, and Luxol fast blue staining. In vitro, the rat SCs line RSC96 cells were exposed to α-synuclein preformed fibril (α-syn PFF), and cell viability was detected by CCK8. Co-IP was used to identify the interaction between p-α-syn and TLR2. Furthermore, the role of TLR2 in p-α-syn-mediated SCs damage was confirmed by the administration of CU-CPT22, a specific blocker of TLR2. In vivo, apart from dyskinesia, MPTP mice exhibited constipation, urinary dysfunction, and cardiovascular failure, which were associated with the deposition of p-α-syn in vagus nerve SCs, TLR2 activation, and vagus nerve demyelination. In vitro, stimulation of α-syn PFF induced a time-dependent loss of viability, and p-α-syn deposited in RSC96 cells induced a cellular inflammatory response by interacting with TLR2, resulting in cell dysfunction and apoptosis. However, both SCs inflammatory response and cell viability were alleviated after inhibition of TLR2. Furthermore, 1 h fecal pellets and water content, the frequency of 1 h urine, blood pressure, heart rate, and heart rate variability of mice in the MPTP + CU-CPT22 group were also improved. Our results support the perspective that p-α-syn interacts with TLR2 induced SCs damage and is involved in PD AutD, which sheds fresh light on the mechanism of PD AutD and indicates a promising treatment for PD AutD targeting SCs p-α-syn/ TLR2 signaling pathway.

Abstract Background Osteoarthritis (OA) is a chronic and low-grade inflammatory disease associated with metabolism disorder and multiple cell death types in the synovial tissues. Sulfur metabolism has not been studied in OA. Methods First, we calculated the single sample gene set enrichment analysis score of sulfur metabolism-associated annotations (i.e., cysteine metabolism process, regulation of sulfur metabolism process, and disulfidptosis) between healthy and synovial samples from patients with OA. Sulfur metabolism-related differentially expressed genes (DEGs) were analyzed in OA. Least absolute shrinkage and selection operator COX regression were used to identify the sulfur metabolism-associated gene signature for diagnosing OA. Correlation and immune cell deconvolution analyses were used to explore the correlated functions and cell specificity of the signature gene, TM9SF2. TM9SF2’s effect on the phagocytosis of macrophages M2 was analyzed by coculturing macrophages with IgG-coated beads or apoptotic Jurkat cells. Results A diagnostic six gene signature (i.e., MTHFD1, PDK4, TM9SF2, POU4F1, HOXA2, NCKAP1) was identified based on the ten DEGs, validated using GSE12021 and GSE1919 datasets. TM9SF2 was upregulated in the synovial tissues of OA at both mRNA and protein levels. The relationship between TM9SF2 and several functional annotations, such as antigen processing and presentation, lysosome, phagosome, Fcγ-mediated phagocytosis, and tyrosine metabolism, was identified. TM9SF2 and macrophages M2 were significantly correlated. After silencing TM9SF2 in THP-1-derived macrophages M2, a significantly reduced phagocytosis and attenuated activation of PLC-γ1 were observed. Conclusion A sulfur metabolism-associated six-gene signature for OA diagnosis was constructed and upregulation of the phagocytosis-associated gene, TM9SF2, was identified. The findings are expected to deepen our understanding of the molecular mechanism underlying OA development and be used as potential therapeutic targets.

Abstract Background Markers that can be used to evaluate the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) remain undefined. Objective This study aimed to investigate the prognostic impact of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in patients with HNSCC who underwent surgery-based treatment for the first time. Methods This retrospective study included patients HNSCC who underwent surgery-based treatment at our institution between January 2018 and December 2020. Specificity and sensitivity were analyzed using receiver operating characteristic (ROC) curves and the critical value was determined. Patients were divided into low and high groups according to NLR, PLR, and LMR the critical value. Log-rank and Cox proportional hazards models were used to evaluate the associations between preoperative NLR, PLR, LMR, and overall survival (OS). Results A total of 304 patients with HNSCC were included, of whom 190 (62.5%) and 114 (37.5%), 203 (66.8%) and 101 (33.2%), 98 (32.2%), and 206 (67.8%) cases were classified as low NLR and high NLR groups, low PLR and high PLR groups, and low LMR and high LMR groups, respectively. Univariate analysis showed that white blood cell count (WBC), neutrophil count (NEU), platelet count (PLT), NLR, pathologic N stage (pN stage), TNM stage and postoperative complications were significantly associated with OS (p

As an important intermediate in the synthesis of most energetic pentazole compounds, the reaction system of sodium pentazole is complex and has many by-products, but there is no suitable HPLC analysis method. Based on the study of ultraviolet absorption peak of sodium pentazole aqueous solution, the HPLC purity analysis method of sodium pentazole was successfully established and its sensitivity, accuracy and repeatability were verified. When the detection wavelength was 192 nm, the chromatographic column was Agilent WondaSil C18 Superb (4.6 × 250 mm, 5 μm), the mobile phase was 95% water and 5% acetonitrile mixed solution, the flow rate was 0.8 ml/min, the analysis time was 8 min, the sample size was 1 μL and the column temperature was 40 °C, a liquid phase map of sodium pentazole was obtained. The analysis results showed that the retention time of pentazole sodium was 3.76 min, and showed a good linear relationship in the range of 0.3068–0.3288 g/L. The linear equation is y = -217447.64+835837.85x, the correlation coefficient R2 is 0.99997, and it has good sensitivity, accuracy and repeatability. In addition, three by-products from the synthesis of sodium pentazole were simply separated.

Integrating multi-modal data in natural language processing has opened new pathways for the enhancement of dialogue summarization. However, existing models often struggle to effectively synthesize textual, auditory, and visual inputs. This paper introduces a Modality-Enhanced Multi-Channel Attention Network (MEMA), a novel approach designed to optimize the integration and interaction of diverse modalities for dialogue summarization. MEMA leverages symmetrical embedding strategies to balance the integrity and distinctiveness of each modality, ensuring a harmonious interaction within the unified architecture. By maintaining symmetry in the processing flow, MEMA enhances the contextual richness and coherence of the generated summaries. Our model demonstrates superior performance on the Multi-modal Dialogue Summarization (MDS) dataset, particularly in generating contextually enriched abstract summaries. The results underscore MEMA’s potential to transform dialogue summarization by providing a more symmetrical and integrated understanding of multi-modal interactions, bridging the gap in multi-modal data processing, and setting a new standard for future summarization tasks.

Multimodal summarization, a rapidly evolving field within multimodal learning, focuses on generating cohesive summaries by integrating information from diverse modalities, such as text and images. Unlike traditional unimodal summarization, multimodal summarization presents unique challenges, particularly in capturing fine-grained interactions between modalities. Current models often fail to account for complex cross-modal interactions, leading to suboptimal performance and an over-reliance on one modality. To address these issues, we propose a novel framework, hypergraph transformer-based multimodal summarization (HGTMFS), designed to model high-order relationships across modalities. HGTMFS constructs a hypergraph that incorporates both textual and visual nodes and leverages transformer mechanisms to propagate information within the hypergraph. This approach enables the efficient exchange of multimodal data and improves the integration of fine-grained semantic relationships. Experimental results on several benchmark datasets demonstrate that HGTMFS outperforms state-of-the-art methods in multimodal summarization.

Abstract Locus coeruleus (LC) dysfunction is involved in the pathophysiology of depression; however, the neural circuits and specific molecular mechanisms responsible for this dysfunction remain unclear. Here, it is shown that activation of tyrosine hydroxylase (TH) neurons in the LC alleviates depression‐like behaviors in susceptible mice. The dorsolateral septum (dLS) is the most physiologically relevant output from the LC under stress. Stimulation of the LCTH‐dLSSST innervation with optogenetic and chemogenetic tools bidirectionally can regulate depression‐like behaviors in both male and female mice. Mechanistically, it is found that brain‐derived neurotrophic factor (BDNF), but not norepinephrine, is required for the circuit to produce antidepressant‐like effects. Genetic overexpression of BDNF in the circuit or supplementation with BDNF protein in the dLS is sufficient to produce antidepressant‐like effects. Furthermore, viral knockdown of BDNF in this circuit abolishes the antidepressant‐like effect of ketamine, but not fluoxetine. Collectively, these findings underscore the notable antidepressant‐like role of the LCTH‐dLSSST pathway in depression via BDNF‐TrkB signaling.

Minocycline is a tetracycline commonly used for several dermatological diseases. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but severe adverse event which can be caused by minocycline. An 18-year-old male patient developed fever, acute rash, pharyngeal pain, lymphadenopathy, hematologic abnormalities, increased creatinine level, elevated liver enzyme levels, and splenomegaly 4 weeks after the oral treatment of minocycline, 100 mg daily, for acne. Once diagnosed with DRESS syndrome, intravenous methylprednisolone was applied and his clinical manifestations and laboratory results remarkably improved. Then, a total of 13 DRESS syndrome cases induced by minocycline were reviewed and their clinical characteristics were summarized. In these cases, only two patient (15.4%) was present with pharynx involved. In conclusion, we reported a rare minocycline-induced DRESS syndrome who developed fever, eosinophilia, acute rash, pharyngitis, lymphadenopathy, acute kidney injury, hepatitis, and splenomegaly. Our report provides detailed clinical features of minocycline-induced DRESS syndrome, which helps us further understand this severe adverse event.

Background: Necroptosis could regulate immunity in cancers, and stratification of colorectal cancer (CRC) subtypes based on key genes related to necroptosis might be a novel strategy for CRC treatment. Method: The RNA-sequencing data of CRC and other 31 types of cancers were obtained from The Cancer Genome Atlas (TCGA) database. Consensus clustering was performed based on protein-coding genes (PCGs) related to necroptosis score calculated by single sample gene set enrichment analysis (ssGSEA). Module genes showing a significant positive correlation with the necroptosis score were identified by weighted correlation network analysis (WGCNA) and further used to develop a risk stratification model applying least absolute shrinkage and selection operator (LASSO) and Cox regression analysis. The risks score for each sample in CRC cohorts, immunotherapy cohorts and pan-cancer study cohorts was calculated. Result: Two subgroups (C1 cluster and C2 cluster) of CRC were identified based on the necroptosis score. Compared with C1 cluster, the survival possibility of C2 cluster was greatly reduced, the levels of necroptosis score, immune cell infiltration, immune score and expression of immune checkpoint molecules were significantly increased and immunotherapy response was less active. Low-risk patients defined by the risk model had a significant survival advantage than high-risk counterparts in both CRC and the other 31 cancer types. Furthermore, the risk model was also more efficient than the Tumor Immune Dysfunction and Exclusion (TIDE) tool in predicting OS and immunotherapy response for the samples in the immunotherapy cohort. Conclusion: CRC patients were classified by necroptosis score-related PCGs, and a risk model was designed to evaluate the immunotherapy and prognosis of patients with CRC. The current molecular subtype and prognostic model could help stratify patients with different risks and predict their prognosis and immunotherapy sensitivity.

X-ray structural science is undergoing a revolution driven by the emergence of X-ray Free-electron Laser (XFEL) facilities. The structures of crystalline solids can now be studied on the picosecond time scale relevant to phonons, atomic vibrations which travel at acoustic velocities. In the work presented here, X-ray diffuse scattering is employed to characterize the time dependence of the liquid phase emerging from femtosecond laser-induced melting of polycrystalline gold thin films using an XFEL. In a previous analysis of Bragg peak profiles, we showed the supersonic disappearance of the solid phase and presented a model of pumped hot electrons carrying energy from the gold surface to scatter at internal grain boundaries. This generates melt fronts propagating relatively slowly into the crystal grains. By conversion of diffuse scattering to a partial X-ray pair distribution function, we demonstrate that it has the characteristic shape obtained by Fourier transformation of the measured F(Q). The diffuse signal fraction increases with a characteristic rise-time of 13 ps, roughly independent of the incident pump fluence and consequent final liquid fraction. This suggests the role of further melt-front nucleation processes beyond grain boundaries.

To quickly break through a reinforced concrete wall and meet the damage range requirements of rescuers entering the building, the combined damage characteristics of the reinforced concrete wall caused by EFP penetration and explosion shock wave were studied. Based on LS-DYNA finite element software and RHT model with modified parameters, a 3D large-scale numerical model was established for simulation analysis, and the rationality of the material model parameters and numerical simulation algorithm were verified. On this basis, the combined damage effect of EFP penetration and explosion shock wave on reinforced concrete wall was studied, the effect of steel bars on the penetration of EFP was highlighted, and the effect of impact positions on the damage of the reinforced concrete wall was also examined. The results reveal that the designed shaped charge can form a crater with a large diameter and high depth on the reinforced concrete wall. The average crater diameter is greater than 67 cm (5.58 times of charge diameter), and crater depth is greater than 22 cm (1.83 times of charge diameter). The failure of the reinforced concrete wall is mainly caused by EFP penetration. When only EFP penetration is considered, the average diameter and depth of the crater are 54.0 cm (4.50 times of charge diameter) and 23.7 cm (1.98 times of charge diameter), respectively. The effect of explosion shock wave on crater depth is not significant, resulting in a slight increase in crater depth. The average crater depth is 24.5 cm (2.04 times of charge diameter) when the explosion shock wave is considered. The effect of explosion shock wave on the crater diameter is obvious, which can aggravate the damage range of the crater, and the effect gradually decreases with the increase of standoff distance. Compared with the results for a plain concrete wall, the crater diameter and crater depth of the reinforced concrete wall are reduced by 5.94% and 9.96%, respectively. Compared to the case in which the steel bar is not hit, when the EFP hit one steel bar and the intersection of two steel bars, the crater diameter decreases by 1.36% and 5.45% respectively, the crater depth decreases by 4.92% and 14.02% respectively. The EFP will be split by steel bar during the penetration process, resulting in an irregular trajectory.