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Abstract Studies of laminopathy-based progeria offer insights into aging-associated diseases and highlight the role of LMNA in chromatin organization. Mandibuloacral dysplasia type A (MAD) is a largely unexplored form of atypical progeria that lacks lamin A post-translational processing defects. Using iPSCs derived from a male MAD patient carrying homozygous LMNA p.R527C, premature aging phenotypes are recapitulated in multiple mesenchymal lineages, including mesenchymal stem cells (MSCs). Comparison with 26 human aging MSC expression datasets reveals that MAD-MSCs exhibit the highest similarity to senescent primary human MSCs. Lamina-chromatin interaction analysis reveals reorganization of lamina-associating domains (LADs) and repositioning of non-LAD binding peaks may contribute to the observed accelerated senescence. Additionally, 3D genome organization further supports hierarchical chromatin disorganization in MAD stem cells, alongside dysregulation of genes involved in epigenetic modification, stem cell fate maintenance, senescence, and geroprotection. Together, these findings suggest LMNA missense mutation is linked to chromatin alterations in an atypical progeroid syndrome.

Abstract Background The mitochondrial dysfunction and oxidative stress imbalance caused by macrophage polarization play a role in the progression of COPD, with CDGSH iron–sulfur domain-containing protein 1 (CISD1) playing a key role. This study revealed the role and mechanism of CISD1 in smoke-induced macrophages. Methods Using a pure cigarette smoke exposure-induced COPD mouse model, stimulation of Raw264.7 macrophages with cigarette smoke extract mimics the COPD environment. Knocking down CISD1 expression in macrophages and combining it with high-throughput sequencing to obtain subsequent differentially expressed genes and pathways. Macrophage polarization tendency under different treatments was determined using flow cytometry. Meanwhile, Mitosox, JC-1, DCFH-DA fluorescence intensity was measured to detect mitochondrial function and cellular oxidative stress levels. Western Blot technique was employed to validate autophagy (mitochondrial autophagy) pathway-related proteins. In addition, Elisa technique was used to measure inflammatory factors (IL-6, TNF-a) in the cell supernatant after co-culturing macrophages (Raw264.7) with epithelial cells (MLE12). Results CISD1 is underexpressed in peripheral blood monocytes of COPD patients. Under in vitro conditions, we verified that cigarette smoke (smoke extract) indeed inhibits CISD1 expression in macrophages. Subsequently, we found that macrophages with knocked-down CISD1 tend to polarize towards M1 phenotype, and exhibit signs of mitochondrial dysfunction and oxidative stress imbalance. In addition, we observed significant activation of the autophagy pathway in CISD1-inhibited macrophages, with upregulation of LC3A/B and downregulation of p62 protein, as well as increased expression of mitochondrial autophagy-related proteins (PINK1, PARKN). Furthermore, co-culturing CISD1-knockdown macrophages (Raw264.7) with epithelial cells (MLE12) resulted in upregulation of inflammatory factors in the supernatant. Conclusions Smoke-induced reduction of CISD1 in macrophages promotes M1 polarization and mitochondrial dysfunction by activating the autophagy pathway, thereby promoting the occurrence and development of COPD.

Abstract In the process of preserving historical buildings in southern Fujian, China, it is crucial to provide timely and accurate statistical data to classify the damage of traditional buildings. In this study, a method based on the improved YOLOv8 neural network is proposed to select aerial photographs of six villages in Xiamen and Quanzhou cities in Fujian Province as the dataset, which contains a total of 3124 photographs. Based on the high-resolution orthophotographs obtained from UAV tilt photography, the YOLOv8 model was used to make predictions. The main task in the first stage is to select the buildings with historical value in the area, and the model's mAP (Mean Accuracy Rate) can reach 97.2% in the first stage task. The second stage uses the YOLOv8 model to segment the images selected in the first stage, detecting possible defects on the roofs, including collapses, missing tiles, unsuitable architectural additions, and vegetation encroachment. In the second stage of the segmentation task, the mAP reaches 89.4%, which is a 1.5% improvement in mAP50 (mean accuracy) compared to the original YOLOv8 model, and the number of parameters and GFLOPs are reduced by 22% and 15%, respectively. This method can effectively improve the disease detection efficiency of historical built heritage in southern Fujian under complex terrain and ground conditions.

Coating modification is an important way to enhance the reactivity of aluminum powder. In this paper, ammonium perchlorate and aluminum powder were assembled into energetic microunits by liquid deposition method. Spherical particles with AP as shell and ultrafine aluminum powder as the core (Al@AP) were gained. The micromorphology results show that the coated particles are about 5 μm, and the coating layer is evenly distributed on the outer surface of aluminum powder, indicating a complete coating. The energetic microunits were implanted into the nitrate ester plasticizing adhesive system (NEPE) as solid phase fillers. The effect of filler on the rheological properties, safety, mechanical properties, thermal reaction and energy properties of the system was analyzed by comparing with the raw aluminum filler. The test results show that the rheological properties, mechanical properties and pressure index of NEPE containing system Al@AP meets the requirements of solid propellant charging. Compared with Al based propellant, the mechanical sensitivity and thermal sensitivity are decreased, the safety is better, and the explosion heat of the propellant is increased by 7.8%. The engine test shows that the specific impulse is increased by 1.2 s. Al@AP can improve the energy output and safety of NEPE propellant, and has potential application prospects in high-energy propellants.

A nanocrystalline alloy, with an iron-based composition (Fe58.5Si16.7B6.5Nb5.1Cu13.2) and a Curie temperature of 570 °C, was investigated for its effectiveness as magnetic shielding films in an induction heating system. The primary focus of the research was to evaluate the shielding performance of the 3-turned (9-layered) shielding films with dimensions of 135 mm × 17 mm × 0.15 mm. Upon winding, these films formed a cylindrical structure that enveloped the coil, with a diameter of 13.9 mm and a height of 17 mm. The results showed that increasing the degree of fragmentation within the nanocrystalline shielding films significantly reduced the magnetic permeability by decreasing the real component from 11,500 to 400 and the imaginary part from 2800 to 20. However, a lower degree of fragmentation led to a 10 % increase in the resistance (Rs) of the heating module, although this effect was less pronounced as the relative permeability continued to increase. Furthermore, observations on preheating time to a set temperature of 400 °C and total energy consumption over a duration of 250s revealed an initial downward trend, followed by a rapid increase that even exceeded the initial values as the magnetic permeability of the nanocrystalline shielding films augmented. Notably, the study emphasized that nanocrystalline shielding films with a relative permeability value of 1000 demonstrated exceptional magnetic shielding performance, resulting in a 12.5 % reduction in preheat time and 7 % less energy consumption during preheating. In addition to empirical findings, the study developed a theoretical model elucidating the shielding mechanism inherent in induction heating systems. This model serves as a robust framework for the application of nanocrystalline shielding materials in such systems, laying the groundwork for enhanced magnetic shielding capabilities in future applications.

Summary: Background: Early prediction of lymph node status after neoadjuvant chemotherapy (NAC) facilitates promptly optimization of treatment strategies. This study aimed to develop and validate a deep learning network (DLN) using baseline computed tomography images to predict lymph node metastasis (LNM) after NAC in patients with locally advanced gastric cancer (LAGC). Methods: A total of 1205 LAGC patients were retrospectively recruited from three hospitals between January 2013 and March 2023, constituting a training cohort, an internal validation cohort, and two external validation cohorts. A transformer-based DLN was developed using 3D tumor images to predict LNM after NAC. A clinical model was constructed through multivariate logistic regression analysis as a baseline for subsequent comparisons. The performance of the models was evaluated through discrimination, calibration, and clinical applicability. Furthermore, Kaplan–Meier survival analysis was conducted to assess overall survival (OS) of LAGC patients at two follow-up centers. Findings: The DLN outperformed the clinical model and demonstrated a robust performance for predicting LNM in the training and validation cohorts, with areas under the curve (AUCs) of 0.804 (95% confidence interval [CI], 0.752–0.849), 0.748 (95% CI, 0.660–0.830), 0.788 (95% CI, 0.735–0.835), and 0.766 (95% CI, 0.717–0.814), respectively. Decision curve analysis exhibited a high net clinical benefit of the DLN. Moreover, the DLN was significantly associated with the OS of LAGC patients [Center 1: hazard ratio (HR), 1.789, P

Abstract Probabilistic computing is a computing scheme that offers a more efficient approach than conventional complementary metal-oxide–semiconductor (CMOS)-based logic in a variety of applications ranging from optimization to Bayesian inference, and invertible Boolean logic. The probabilistic bit (or p-bit, the base unit of probabilistic computing) is a naturally fluctuating entity that requires tunable stochasticity; by coupling low-barrier stochastic magnetic tunnel junctions (MTJs) with a transistor circuit, a compact implementation is achieved. In this work, by combining stochastic MTJs with 2D-MoS2 field-effect transistors (FETs), we demonstrate an on-chip realization of a p-bit building block displaying voltage-controllable stochasticity. Supported by circuit simulations, we analyze the three transistor-one magnetic tunnel junction (3T-1MTJ) p-bit design, evaluating how the characteristics of each component influence the overall p-bit output. While the current approach has not reached the level of maturity required to compete with CMOS-compatible MTJ technology, the design rules presented in this work are valuable for future experimental implementations of scaled on-chip p-bit networks with reduced footprint.

Abstract Two-dimensional (2D) materials have garnered significant attention in recent years due to their atomically thin structure and unique electronic and optoelectronic properties. To harness their full potential for applications in next-generation electronics and photonics, precise control over the dielectric environment surrounding the 2D material is critical. The lack of nucleation sites on 2D surfaces to form thin, uniform dielectric layers often leads to interfacial defects that degrade the device performance, posing a major roadblock in the realization of 2D-based devices. Here, we demonstrate a wafer-scale, low-temperature process (

Abstract Accurate multi-organ segmentation in 3D CT images is imperative for enhancing computer-aided diagnosis and radiotherapy planning. However, current deep learning-based methods for 3D multi-organ segmentation face challenges such as the need for labor-intensive manual pixel-level annotations and high hardware resource demands, especially regarding GPU resources. To address these issues, we propose a 3D proxy-bridged region-growing framework specifically designed for the segmentation of the liver and spleen. Specifically, a key slice is selected from each 3D volume according to the corresponding intensity histogram. Subsequently, a deep learning model is employed to pinpoint the semantic central patch on this key slice, to calculate the growing seed. To counteract the impact of noise, segmentation of the liver and spleen is conducted on superpixel images created through proxy-bridging strategy. The segmentation process is then extended to adjacent slices by applying the same methodology iteratively, culminating in the comprehensive segmentation results. Experimental results demonstrate that the proposed framework accomplishes segmentation of the liver and spleen with an average Dice Similarity Coefficient of approximately 0.93 and a Jaccard Similarity Coefficient of around 0.88. These outcomes substantiate the framework's capability to achieve performance on par with that of deep learning methods, albeit requiring less guidance information and lower GPU resources.

Abstract Background Airway bleeding events are a rare incident in SARS-CoV-2-infected patients after tracheostomies. We aimed to explore the correlation between airway bleeding and SARS-CoV-2 infection and evaluate the consistency of SARS-CoV-2 RNA test results in the upper and lower airway samples from patients after tracheostomies. Methods Forty-four patients after temporary or permanent tracheostomy were divided into a positive group (29 patients) and a negative group (15 patients) based on the SARS-CoV-2 RNA test results of their oropharyngeal swabs. The oropharyngeal and tracheal swabs of the positive group were re-collected for SARS-CoV-2 RNA detection. Demographic and clinical characteristics and airway bleeding events were recorded for all enrolled patients. Results Airway bleeding was reported in eleven patients of the positive group (11/29), with seven displaying bloody sputum or hemoptysis, and four featuring massive sputum crust formation in the trachea that resulted in dyspnea, and only one patient in the negative group (1/15), with a significant difference in the airway bleeding rate (37.9% vs. 6.7%, p

Abstract As testicular mesenchymal stromal cells, stem Leydig cells (SLCs) show great promise in the treatment of male hypogonadism. The therapeutic functions of mesenchymal stromal cells are largely determined by their reciprocal regulation by immune responses. However, the immunoregulatory properties of SLCs remain unclear. Here, we observe that SLCs transplantation restore male fertility and testosterone production in an ischemia‒reperfusion injury mouse model. SLCs prevent inflammatory cascades through mitochondrial transfer to macrophages. Reactive oxygen species (ROS) released from activated macrophages inducing mitochondrial transfer from SLCs to macrophages in a transient receptor potential cation channel subfamily member 7 (TRPM7)-mediated manner. Notably, knockdown of TRPM7 in transplanted SLCs compromised therapeutic outcomes in both testicular ischemia‒reperfusion and testicular aging mouse models. These findings reveal a new mechanism of SLCs transplantation that may contribute to preserve testis function in male patients with hypogonadism related to immune disorders.

Abstract Chronic airway obstructive pulmonary disease (COPD) is a preventable and curable disease characterised by persistent airflow limitation. It is characterised by chronic bronchitis and/or emphysema, and its aetiology is related to various factors such as smoking and infectious factors, and so forth. The pathogenesis is complex and prone to frequent exacerbations, and the prognosis of acute exacerbations of COPD is often poor. As a crucial component of the innate immune system, lung macrophages significantly influence the onset and progression of COPD. When macrophage mitochondria become dysfunctional, many macrophage functions (e.g., phagocytosis, cytokine secretion, chemotaxis, etc.) change. The aim of this paper is to describe the three major pathological features of COPD (oxidative stress imbalance, macrophage polarisation and mitochondrial membrane potential [MMP] production and mitochondrial autophagy), to describe in detail the mechanism of mitochondrial autophagy pathway and its association with oxidative stress and macrophage polarisation and to emphasise the role of macrophage mitochondrial reactive oxygen species (mROS) in COPD, with the aim of providing ideas and directions for subsequent studies.

Summary: Blood microbiome signatures in patients with type 1 diabetes (T1D) remain unclear. We profile blood microbiome using 16S rRNA gene sequencing in 77 controls and 64 children with new-onset T1D, and compared it with the gut and oral microbiomes. The blood microbiome of patients with T1D is characterized by increased diversity and perturbed microbial features, with a significant increase in potentially pathogenic bacteria compared with controls. Thirty-six representative genera of blood microbiome were identified by random forest analysis, providing strong discriminatory power for T1D with an AUC of 0.82. PICRUSt analysis suggested that bacteria capable of inducing inflammation were more likely to enter the bloodstream in T1D. The overlap of the gut and oral microbiome with the blood microbiome implied potential translocation of bacteria from the gut and oral cavity to the bloodstream. Our study raised the necessity of further mechanistic investigations into the roles of blood microbiome in T1D.

Summary: Background: Contrast-enhanced CT scans provide a means to detect unsuspected colorectal cancer. However, colorectal cancers in contrast-enhanced CT without bowel preparation may elude detection by radiologists. We aimed to develop a deep learning (DL) model for accurate detection of colorectal cancer, and evaluate whether it could improve the detection performance of radiologists. Methods: We developed a DL model using a manually annotated dataset (1196 cancer vs 1034 normal). The DL model was tested using an internal test set (98 vs 115), two external test sets (202 vs 265 in 1, and 252 vs 481 in 2), and a real-world test set (53 vs 1524). We compared the detection performance of the DL model with radiologists, and evaluated its capacity to enhance radiologists’ detection performance. Findings: In the four test sets, the DL model had the area under the receiver operating characteristic curves (AUCs) ranging between 0.957 and 0.994. In both the internal test set and external test set 1, the DL model yielded higher accuracy than that of radiologists (97.2% vs 86.0%, p 0.99), and it detected 2 cases that had been missed by radiologists. Interpretation: The developed DL model can accurately detect colorectal cancer and improve radiologists’ detection performance, showing its potential as an effective computer-aided detection tool. Funding: This study was supported by National Science Fund for Distinguished Young Scholars of China (No. 81925023); Regional Innovation and Development Joint Fund of National Natural Science Foundation of China (No. U22A20345); National Natural Science Foundation of China (No. 82072090 and No. 82371954); Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (No. 2022B1212010011); High-level Hospital Construction Project (No. DFJHBF202105).

Abstract Background Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+IFDCS) is a rare disease characterized by mild clinical symptoms and non-specific imaging findings. The diagnosis of the disease depends on pathological diagnosis. However, EBV+IFDCS has a very broad spectrum of histological morphology and immune phenotypes, and its histopathological features have not been fully described by pathologists. Case presentation A 59-year-old female, with no significant discomfort, was found to have a splenic mass during a routine physical examination. Microscopic examination at low magnification revealed numerous epithelioid granulomas, amidst which a substantial inflammatory response was observed. Interspersed among the dense inflammatory cells were spindle or oval-shaped cells, distributed sporadically with indistinct boundaries. Under high magnification, these spindle cells had subtle features: smooth and clear nuclear membranes, inconspicuous small nucleoli, and infrequent mitotic figures. Immunophenotypically, the spindle cells expressed CD21 and CD23, and Epstein-Barr encoding region (EBER) in situ hybridization yielded positive results. The inflammatory milieu predominantly consisted of T cells, with a minority of plasma cells expressing IgG4. The confluence of morphological and immunohistochemical findings led to the final pathological diagnosis of EBV+IFDCS in this case. Conclusions The presentation of EBV+IFDCS with pronounced granulomatous changes is rare. This morphological variant poses a high risk of misdiagnosis, frequently leading to confusion with other granulomatous diseases. Accurate diagnosis necessitates a comprehensive analysis, integrating immunohistochemistry and in situ hybridization. The case presented here is instrumental in raising awareness and understanding of EBV+IFDCS, with the goal of reducing misdiagnoses and unrecognized cases.

Abstract Background Severe asthma places a large burden on patients and society. The characteristics of patients with severe asthma in the Chinese population remain unclear. Methods A retrospective review was conducted in patients with severe asthma. Demographic and clinical data were collected. Patients were grouped according to phenotypes in terms of exacerbations, body mass index (BMI) and fixed airway obstruction (FAO) status, and the characteristics of different groups were compared. Comorbidities, factors that influence asthma phenotypes, were also analyzed in the study. Results A total of 228 patients with severe asthma were included in our study. They were more likely to be overweight or obese. A total of 41.7% of the patients received GINA step 5 therapy, and 43.4% had a history of receiving regular or intermittent oral corticosteroids (OCS). Severe asthmatic patients with comorbidities were prone to have more asthma symptoms and decreased quality of life than patients without comorbidities. Patients with exacerbations were characterized by longer duration of asthma, poorer lung function, and worse asthma control. Overweight or obese patients tended to have more asthma symptoms, poorer lung function and more asthma-related comorbidities. Compared to patients without FAO, those in the FAO group were older, with longer duration of asthma and more exacerbations. Conclusion The existence of comorbidities in patients with severe asthma could result in more asthma symptoms and decreased quality of life. Patients with exacerbations or with overweight or obese phenotypes were characterized by poorer lung function and worse asthma control. Patients with FAO phenotype tended to have more exacerbations.

Abstract Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton’s tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance. HSP90AB1 (Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance. CDK9 (Cyclin-dependent kinase 9), another MYC target, was significantly upregulated in Dual-R samples. Both HSP90AB1 and CDK9 expression were correlated with MYC activity levels. Pharmaceutical co-targeting of HSP90 and CDK9 synergistically diminished MYC activity, leading to potent anti-MCL activity. Collectively, our study revealed that HSP90-MYC-CDK9 network is the primary driving force of therapeutic resistance.

Background : Warm acupuncture (WA) has analgesic and anti-inflammatory effects. However, the underlying mechanism of these effects remain unclear. Objectives: To explore the analgesic and anti-inflammatory effects of WA and the potential underlying mechanism in male Sprague-Dawley rats with non-compressive lumbar disk herniation (LDH) caused by autologous nucleus pulposus (NP) transplantation. Methods : We used low-frequency (2 Hz) electrical stimulation and WA (40℃) to treat GB30 and BL54 acupoints in rats for 30 mins per day. We monitored the paw withdrawal threshold of rats during the experiment and measured serum cytokine levels using commercial kits. Dorsal root ganglion (DRG) tissue pathology was analyzed via H&E staining. We used qRT-PCR to measure the mRNA expression levels of IL-1β, IL-6, and TNF-α genes in DRG. Western blot was used to analyze the expression levels of IL-1β, IL-6, TNFα, P-p38MAPK, p38MAPK, P-IκBα, IκB α, and NF-κB p65 proteins. Results : WA treatment significantly increased the pain threshold of rats, reduced serum IL-6, PEG2, NO, SP, NP-Y, and MMP-3 levels, and effected histopathological improvements in the DRG in rats. Moreover, WA treatment significantly downregulated the expression levels of inflammation-associated genes (Il-1β, Il-6, and Tnf-α) and proteins (IL-1β, IL-6, TNF-α, P-p38MAPK, P-IκBα, and NF-κB p65) in the DRG of non-compressive LDH rats. Conclusion : WA can alleviate pain and inhibit inflammatory response in rats with non-compressive LDH caused by autologous NP transplantation, and these effects are likely associated with the inhibition of the p38MAPK/NF-κB pathway.

Abstract Backgrounds Since breast cancer patients respond diversely to immunotherapy, there is an urgent need to explore novel biomarkers to precisely predict clinical responses and enhance therapeutic efficacy. The purpose of our present research was to construct and independently validate a biomarker of tumor microenvironment (TME) phenotypes via a machine learning-based radiomics way. The interrelationship between the biomarker, TME phenotypes and recipients’ clinical response was also revealed. Methods In this retrospective multi-cohort investigation, five separate cohorts of breast cancer patients were recruited to measure breast cancer TME phenotypes via a radiomics signature, which was constructed and validated by integrating RNA-seq data with DCE-MRI images for predicting immunotherapy response. Initially, we constructed TME phenotypes using RNA-seq of 1089 breast cancer patients in the TCGA database. Then, parallel DCE-MRI images and RNA-seq of 94 breast cancer patients obtained from TCIA were applied to develop a radiomics-based TME phenotypes signature using random forest in machine learning. The repeatability of the radiomics signature was then validated in an internal validation set. Two additional independent external validation sets were analyzed to reassess this signature. The Immune phenotype cohort (n = 158) was divided based on CD8 cell infiltration into immune-inflamed and immune-desert phenotypes; these data were utilized to examine the relationship between the immune phenotypes and this signature. Finally, we utilized an Immunotherapy-treated cohort with 77 cases who received anti-PD-1/PD-L1 treatment to evaluate the predictive efficiency of this signature in terms of clinical outcomes. Results The TME phenotypes of breast cancer were separated into two heterogeneous clusters: Cluster A, an "immune-inflamed" cluster, containing substantial innate and adaptive immune cell infiltration, and Cluster B, an "immune-desert" cluster, with modest TME cell infiltration. We constructed a radiomics signature for the TME phenotypes ([AUC] = 0.855; 95% CI 0.777–0.932; p

Cadmium, an environmental toxicant, severely impairs male reproductive functions and currently lacks effective clinical treatments. Mesenchymal stem cell-derived exosomes (MSC-Exos) are increasingly recognized as a potential alternative to whole-cell therapy for tissue injury and regeneration. This study aims to investigate the protective effects of MSC-Exos against cadmium toxicity on male reproduction. Our findings reveal that MSC-Exos treatment significantly promotes spermatogenesis, improves sperm quality, and reduces germ cell apoptosis in cadmium-exposed mice. Mechanistically, MSC-Exos dramatically mitigate cadmium-induced cell apoptosis in a spermatogonia cell line (GC-1 spg) in vitro by reducing DNA damage and promoting autophagic flux. These results suggest that MSC-Exos have a protective effect on cadmium-induced germ cell apoptosis by ameliorating DNA damage and autophagy flux, demonstrating the therapeutic potential of MSC-Exos for cadmium toxicity on male reproduction.

Macrophage/microglia function as immune defense and homeostatic cells that originate from bone marrow progenitor cells. Macrophage/microglia activation is historically divided into proinflammatory M1 or anti-inflammatory M2 states based on intracellular dynamics and protein production. The polarization of macrophages/microglia involves a pivotal impact in modulating the development of inflammatory disorders, namely lung and traumatic brain injuries. Recent evidence indicates shared signaling pathways in lung and traumatic brain injuries, regulated through non-coding RNAs (ncRNAs) loaded into extracellular vesicles (EVs). This packaging protects ncRNAs from degradation. These vesicles are subcellular components released through a paracellular mechanism, constituting a group of nanoparticles that involve exosomes, microvesicles, and apoptotic bodies. EVs are characterized by a double-layered membrane and are abound with proteins, nucleic acids, and other bioactive compounds. ncRNAs are RNA molecules with functional roles, despite their absence of coding capacity. They actively participate in the regulation of mRNA expression and function through various mechanisms. Recent studies pointed out that selective packaging of ncRNAs into EVs plays a role in modulating distinct facets of macrophage/microglia polarization, under conditions of lung and traumatic brain injuries. This study will explore the latest findings regarding the role of EVs in the progression of lung and traumatic brain injuries, with a specific focus on the involvement of ncRNAs within these vesicles. The conclusion of this review will emphasize the clinical opportunities presented by EV-ncRNAs, underscoring their potential functions as both biomarkers and targets for therapeutic interventions.

Single-cell multi-omics technologies have revolutionized cancer research by allowing us to examine individual cells at a molecular level. Unlike traditional bulk omics approaches, which analyze populations of cells together, single-cell multi-omics enables us to uncover the heterogeneity within tumors and understand the unique molecular characteristics of different cell populations. By doing so, we can identify rare subpopulations of cells that are influential in tumor growth, metastasis, and resistance to therapy. Moreover, single-cell multi-omics analysis provides valuable insights into the immune response triggered by various therapeutic interventions, such as immune checkpoint blockade, chemotherapy, and cell therapy. It also helps us better understand the intricate tumor microenvironment and its impact on patient prognosis and response to treatment. This comprehensive review focuses on the recent advancements in single-cell multi-omics methodologies, with an emphasis on single-cell multi-omics technologies. It highlights the important role of these techniques in uncovering the complexity of tumorigenesis and its multiple applications in cancer research, as well as their equally great contributions in other areas such as immunology. Through single-cell multi-omics, we gain a deeper understanding of cancer biology and pave the way for more precise and effective therapeutic strategies. Apart from those above, this paper also aims to introduce the advancements in live cell imaging technology, the latest developments in protein detection techniques, and explore their seamless integration with single-cell multi-omics technology.

Abstract Objective Several research has considered the potential correlation between periodontitis and serum lipids. However, serum lipid profiles correlation with periodontitis remains largely unknown. The investigation objective was to examine periodontitis correlation with serum lipid levels using a bidirectional Mendelian randomization (MR) analysis. Methods The study employed a bidirectional MR analysis with two samples, utilizing a freely accessible genome-wide association study (GWAS). Furthermore, the primary analysis employed the inverse variance weighted (IVW) method. To determine whether the lipid profiles were associated with periodontitis, a variety of sensitivity analyses (including MR-Egger regression, MR-PRESSO, and weighted median), as well as multivariable MR, were employed. Results MR analysis performed by IVW did not reveal any relationship between periodontitis and low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), or total cholesterol (TC). It was also found that LDL, HDL, TG, and TC were not associated to periodontitis. Furthermore, the MR estimations exhibited consistency with other MR sensitivity and multivariate MR (MVMR) analyses. These results show that the correlation between serum lipid levels and periodontitis could not be established. Conclusion The finding indicates a negligible link between periodontitis and serum lipid levels were identified, despite previous observational studies reporting a link between periodontitis and serum lipid levels.

Abstract Background Liposarcoma is a malignant mesenchymal tumor that most commonly involves the retroperitoneum and lower extremities. However, liposarcoma of esophagus has been rarely reported in the literature. Case presentation We report a case of a 46-year-old man with complaint of intermittent dysphagia for 6 years, accompanied with paroxysmal vomiting of pedicled tumor to the mouth. Imaging studies showed a huge mixed density lesion in the middle esophageal lumen. Surgical resection of the tumor was performed through an external cervical approach. Microscopically, the tumor was composed of mature adipocytes in normal adipose tissue prominently intersected by sparsely cellular fibrous septa containing atypical, enlarged spindle cells with hyperchromatic nuclei. Immunohistochemically, the tumor cells were positive for Vimentin, S-100, CD34 and MDM2. Besides, fluorescence in situ hybridization (FISH) analysis indicated the presence of amplification involving MDM2 gene. The patient was diagnosed as having esophageal well-differentiated liposarcoma and recovered well after the operation. Conclusions Esophageal liposarcoma is an extremely rare tumor. Due to the nonspecific clinical manifestation and lack of experience, it is challenging to make a clear diagnosis before operation. Definite diagnosis of esophageal liposarcoma depends on histopathology, immunohistochemistry and molecular analysis.

The effects of the following independent variables-micro intensity, extraction time, ethanol concentration, and solvent-to-solid ratio on the extraction yield of paeoniflorin from Paeoniae Radix Rubra were examined by single factor test and Box-Behnken design. The antioxidant activity in vitro of extractions was also assessed. Then, the paeoniflorin extraction process was optimized using the response surface methodology (RSM) and particle swarm optimization-artificial neural network (PSO-ANN). Results showed that the prediction and optimization performance of PSO-ANN was better than RSM, that with the correlation coefficient R2 was 0.9925 and 0.9099, respectively. The optimized extraction conditions by PSO-ANN were as follows: Ethanol concentration (81% v/v), solvent-to-solid ratio (30 mL/g), extraction time (22 s), extractions (5 times), and micro intensity (420 W). Under the optimized parameters, the extraction yield of paeoniflorin was 378.977±1.982 mg PE/g d.w.. The scavenging rates of paeoniflorin extract (100 μg/mL) on DPPH and ABTS+ free radicals were 87.61% and 80.74% respectively, that closed to the positive control. The extract also had a certain reduction ability. The results of this study provide a new method for optimizing the extraction process, as well as provide a theoretical basis for the application of effective components of Paeoniae Radix Rubra as additives.

Abstract Background Drug resistance limits the treatment effect of cisplatin-based chemotherapy in head and neck squamous cell carcinoma (HNSCC), and the underlying mechanism is not fully understood. The aim of this study was to explore the cause of cisplatin resistance in HNSCC. Methods We performed survival and gene set variation analyses based on HNSCC cohorts and identified the critical role of tumor necrosis factor alpha-induced protein 2 (TNFAIP2) in cisplatin-based chemotherapy resistance. Half-maximal inhibitory concentration (IC50) examination, colony formation assays and flow cytometry assays were conducted to examine the role of TNFAIP2 in vitro, while xenograft models in nude mice and 4-nitroquinoline N-oxide (4NQO)-induced HNSCC models in C57BL/6 mice were adopted to verify the effect of TNFAIP2 in vivo. Gene set enrichment analysis (GSEA) and coimmunoprecipitation coupled with mass spectrometry (Co-IP/MS) were performed to determine the mechanism by which TNFAIP2 promotes cisplatin resistance. Results High expression of TNFAIP2 is associated with a poor prognosis, cisplatin resistance, and low reactive oxygen species (ROS) levels in HNSCC. Specifically, it protects cancer cells from cisplatin-induced apoptosis by inhibiting ROS-mediated c-JUN N-terminal kinase (JNK) phosphorylation. Mechanistically, the DLG motif contained in TNFAIP2 competes with nuclear factor-erythroid 2-related factor 2 (NRF2) by directly binding to the Kelch domain of Kelch-like ECH-associated protein 1 (KEAP1), which prevents NRF2 from undergoing ubiquitin proteasome-mediated degradation. This results in the accumulation of NRF2 and confers cisplatin resistance. Positive correlations between TNFAIP2 protein levels and NRF2 as well as its downstream target genes were validated in HNSCC specimens. Moreover, the small interfering RNA (siRNA) targeting TNFAIP2 significantly enhanced the cisplatin treatment effect in a 4NQO-induced HNSCC mouse model. Conclusions Our results reveal the antioxidant and cisplatin resistance-regulating roles of the TNFAIP2/KEAP1/NRF2/JNK axis in HNSCC, suggesting that TNFAIP2 might be a potential target in improving the cisplatin treatment effect, particularly for patients with cisplatin resistance.

MXene has great potential in the application of thermoelectric materials due to its high conductivity, but its application in this field is limited by the low Seebeck coefficient. In this work, a laminated composite film with a regular 2-dimensional heterogeneous interface was constructed by using 2-dimensional MXene and TiS2. The results show that the sandwich structure composite film has a high Seebeck coefficient (−80.4 μV K−1) while maintaining a high electrical conductivity (322.12 S cm−1). The power factor of the sandwich structure film is higher than that of the disordered structure film, which is 22 times that of the Ti3C2Tx film. The simple flexible device prepared by MTM film has an ideal power density (26.6 W m−2) at a temperature difference of 70 K. This work provides strong evidence and feasible reference for optimizing and improving the thermoelectric properties of MXene-based materials by using high-quality heterostructures.

ObjectivesThis study aims to explore the relationship between the severity of asthma and neutrophils and related oxidative stress-associated molecules in peripheral blood and induced sputum.MethodsA total of 67 subjects were included in this study, namely, 25 patients with severe asthma and 42 patients with non-severe asthma. Clinical data, induced sputum and peripheral blood were collected. Lung function and molecules related to oxidative stress in induced sputum and peripheral blood of asthma patients were detected. The relationship between neutrophils and asthma severity was analyzed. HDAC2 mRNA and protein expression levels and HDAC2 activity were also analyzed. Multivariate logistic regression was performed to select statistically significant variables.ResultsThe absolute value of neutrophils and percentage of neutrophils were higher in the severe asthma patients. These two values were used to predict the severity of asthma by ROC analysis, with the best cutoff values being 4.55 × 109/L (sensitivity 83.3%, specificity 64.0%) and 55.15% (sensitivity 54.8%, specificity 88.0%). The ROS concentration of neutrophils in the induced sputum samples and the 8-iso-PGF2α concentration in the peripheral blood samples were higher in the severe asthma group (P = 0.012; P = 0.044), whereas there was reduced HDAC2 protein activity in PBMCs (P < 0.001). A logistic equation and a nomogram were created to give a precise prediction of disease severity.ConclusionOxidative stress is increased in severe asthma patients. Peripheral blood neutrophils and 8-iso-PGF2α can be used as biomarkers to predict the severity of asthma. A prediction model was created for evaluating asthma severity.

ObjectivesPredicting whether axillary lymph nodes could achieve pathologic Complete Response (pCR) after breast cancer patients receive neoadjuvant chemotherapy helps make a quick follow-up treatment plan. This paper presents a novel method to achieve this prediction with the most effective medical imaging method, Dynamic Contrast-enhanced Magnetic Resonance Imaging (DCE-MRI).MethodsIn order to get an accurate prediction, we first proposed a two-step lesion segmentation method to extract the breast cancer lesion region from DCE-MRI images. With the segmented breast cancer lesion region, we then used a multi-modal fusion model to predict the probability of axillary lymph nodes achieving pCR.ResultsWe collected 361 breast cancer samples from two hospitals to train and test the proposed segmentation model and the multi-modal fusion model. Both segmentation and prediction models obtained high accuracy.ConclusionThe results show that our method is effective in both the segmentation task and the pCR prediction task. It suggests that the presented methods, especially the multi-modal fusion model, can be used for the prediction of treatment response in breast cancer, given data from noninvasive methods only.

Regulatory T cells are a subgroup of T cells with immunomodulatory functions. Different from most cytotoxic T cells and helper T cells, they play a supporting role in the immune system. What’s more, regulatory T cells often play an immunosuppressive role, which mainly plays a role in maintaining the stability of the immune system and regulating the immune response in the body. However, recent studies have shown that not only playing a role in autoimmune diseases, organ transplantation, and other aspects, regulatory T cells can also play a role in the immune escape of tumors in the body, through various mechanisms to help tumor cells escape from the demic immune system, weakening the anti-cancer effect in the body. For a better understanding of the role that regulatory T cells can play in cancer, and to be able to use regulatory T cells for tumor immunotherapy more quickly. This review focuses on the research progress of various mechanisms of regulatory T cells in the tumor environment, the related research of tumor cells acting on regulatory T cells, and the existing various therapeutic methods acting on regulatory T cells.

Abstract Background Pyroptosis is closely related to cancer prognosis. In this study, we tried to construct an individualized prognostic risk model for hepatocellular carcinoma (HCC) based on within-sample relative expression orderings (REOs) of pyroptosis-related lncRNAs (PRlncRNAs). Methods RNA-seq data of 343 HCC samples derived from The Cancer Genome Atlas (TCGA) database were analyzed. PRlncRNAs were detected based on differentially expressed lncRNAs between sample groups clustered by 40 reported pyroptosis-related genes (PRGs). Univariate Cox regression was used to screen out prognosis-related PRlncRNA pairs. Then, based on REOs of prognosis-related PRlncRNA pairs, a risk model for HCC was constructed by combining LASSO and stepwise multivariate Cox regression analysis. Finally, a prognosis-related competing endogenous RNA (ceRNA) network was built based on information about lncRNA–miRNA–mRNA interactions derived from the miRNet and TargetScan databases. Results Hierarchical clustering of HCC patients according to the 40 PRGs identified two groups with a significant survival difference (Kaplan–Meier log-rank, p = 0.026). Between the two groups, 104 differentially expressed lncRNAs were identified (|log2(FC)|> 1 and FDR

Myeloid cells are the predominant cell type in the tumor microenvironment of human and murine glioblastoma (GBM). By generating a mouse model deficient for all monocyte chemoattractant proteins, here the authors show that blocking monocyte recruitment promotes a compensatory neutrophil influx and that concomitant neutrophil inhibition is required to improve survival in GBM preclinical models.

Abstract Background Laennec's capsule is a fibrous membrane attached to the surface of the liver, which is independent of the hepatic veins. However, the presence of Laennec's capsule surrounding the peripheral hepatic veins is controversial. This study aims to describe the characteristic of Laennec's capsule around the hepatic veins at all levels. Methods Seventy‐one hepatic surgical specimens were collected along the cross and longitudinal sections of the hepatic vein. Tissue sections of 3–4 mm were cut and stained with hematoxylin and eosin (H&E), resorcinol‐fuchsin (R&F), and Victoria blue (V&B). Elastic fibers were observed around the hepatic veins. They were measured using K‐Viewer software. Results Morphologically, we observed a thin, dense fibrous layer (so‐called Laennec's capsule) around the hepatic veins at all levels, which was different from the thick elastic fibers of the hepatic vein wall. Therefore, there was a potential gap between Laennec's capsule and the hepatic veins. Laennec's capsule was visualized significantly better with R&F and V&B staining compared to H&E staining. The thickness of Laennec's capsule around the main, first, and secondary branches of the hepatic vein were 79.86 ± 24.20 μm, 48.41 ± 18.25 μm, and 23.56 ± 10.03 μm in the R&F staining, and 80.15 ± 21.85 μm, 49.46 ± 17.52 μm, and 25.05 ± 11.03 μm in the V&B staining, respectively. They were significantly different from each other (P

Nanocrystalline carbonyl iron (CI) particles are promising microwave absorbents at elevated temperature, whereas their excessive grain boundary energy leads to the growth of nanograins and a deterioration in permeability. In this work, we report a strategy to enhance the thermal stability of the grains and microwave absorption of CI particles by doping a SiBaFe alloy. Grain growth was effectively inhibited by the pinning effect of SiBaFe alloy nanoparticles at the grain boundaries. After heat treatment at 600 °C, the grain size of CI particles increased from ~10 nm to 85.1 nm, while that of CI/SiBaFe particles was only 32.0 nm; with the temperature rising to 700 °C, the grain size of CI particles sharply increased to 158.1 nm, while that of CI/SiBaFe particles was only 40.8 nm. Excellent stability in saturation magnetization and microwave absorption was also achieved in CI/SiBaFe particles. After heat treatment at 600 °C, the flaky CI/SiBaFe particles exhibited reflection loss below −10 dB over 7.01~10.11 GHz and a minimum of −14.92 dB when the thickness of their paraffin-based composite was 1.5 mm. We provided a low-cost and efficient kinetic strategy to stabilize the grain size in nanoscale and microwave absorption for nanocrystalline magnetic absorbents working at elevated temperature.

Abstract Background Defect in proofreading exonuclease activity of polymerases epsilon and delta (Pols ε and δ) leads to mutagenesis and genomic instability and has been described in several cancer types. Somatic POLE exonuclease domain mutations (EDMs) have been reported in 7–12% endometrial cancers (ECs) and defined a subgroup of endometrial cancers with ultrahigh somatic mutation frequencies, high tumor infiltrated lymphocytes and favorable outcomes. Case presentation Herein, we presented a novel somatic mutation in POLE exonuclease domain associated with ultra-mutational signature and MMR deficiency in endometrial cancer. A novel POLE EDM (p.T278K) was found by a 11-gene NGS panel. The MSS status detected by the MSI test was inconsistent with the dMMR status by IHC. The loss of MSH6 expression in the tumor could be interpreted by the two nonsense mutations (p.E1234* and p.E1322*) of the MSH6 gene which may lead to truncated proteins. The T278K mutation was pathogenic identified by a 602-gene NGS panel with 27.3% of C > A substitution, 0.6% of indels, 0.6% of C > G substitution and a high TMB of 203.8 mut/Mb. Conclusions We report an endometrial cancer patient harbored a novel somatic POLE T278K mutation. This mutation was a novel pathogenic POLE EDM should be considered as “POLE (ultramutated)” in clinical practice for the molecular classification of EC.

Abstract Background Acute kidney injury (AKI) is a common complication after cardiac surgery, and preoperative renal dysfunction is an important risk factor. Proteinuria indicates renal structural damage, but there are few studies on proteinuria and the risk of AKI after cardiac surgery in patients with renal dysfunction. This study aimed to elucidate whether proteinuria can predict AKI after cardiac surgery in patients with renal dysfunction. Methods Patients with stages 3–4 chronic kidney disease (CKD) who underwent cardiac surgery were included in this retrospective study. AKI was defined according to the KDIGO criteria. The association between proteinuria and AKI in patients with CKD stages 3–4 was investigated. Results The incidence of AKI in the entire cohort (n = 1546) was 53.55%. The in-hospital mortality of patients with was higher than patients without AKI (AKI vs. no AKI, 4.7 vs. 0.8%, P

Triggering receptor expressed on myeloid cell-2 (TRE M2) is a transmembrane receptor which is specifically expressed on myeloid cells. To date, TRE M2 has been confirmed as a key factor in many pathologies, such as Alzheimer’s disease, obesity-related metabolic syndrome, fatty liver and atherosclerosis. However, the role of TRE M2 in tumors remains poorly understood. TRE M2 is highly expressed in more than 200 primary and metastatic tumors, a feature that makes TRE M2 a potential clinical target for tumor immunotherapy. The tumor microenvironment (TME) is the “soil” which tumors survive on and exhibits immunosuppressive characteristics. During the development of a tumor, TME will secrete various chemotactic factors to recruit myeloid cells. It is clear now that cancer progression and metastasis depend on the interactions between cancer cells and myeloid cell infiltration in TME. As an important receptor involved in inflammatory suppression signaling pathways, TRE M2 may play an important role in immune escape by the tumor. Recently, several studies have illustrated that TRE M2 expressed on tumor infiltrated myeloid cells acts as a crucial regulator of the antitumor immune response. In this review, we systematically summarize recent publications about the latest advances in knowledge of TRE M2 in cancer, especially focusing on its role in tumor associated myeloid cells and tumor immunotherapy.

Abstract Background Hepatocellular carcinoma (HCC) is an aggressive malignancy with high morbidity and mortality. Conversion therapy can improve surgical resection rate and prolong survival time for patients with advanced HCC. We show that combination therapy with lenvatinib and camrelizumab is a novel approach to downstage unresectable HCC. Case presentation A 49-year-old man was diagnosed with massive HCC with hilar lymph node and lung metastases. Since radical resection was not feasible, lenvatinib and camrelizumab were administered as first-line therapy. After 10 cycles of camrelizumab and continuous oral administration of lenvatinib, the tumor exhibited striking shrinkage in volume indicating a partial radiological response, accompanied by a reduction in the alpha-fetoprotein levels, followed by salvage resection. Intriguingly, an improvement in predictive biomarkers, like lactate dehydrogenase (LDH) and neutrophil-to-lymphocyte ratio (NLR), was observed. Notably, the pathological examination found high levels of necrosis in the resected tumor, and flow cytometry analysis indicated a significant increase in the ratio of CD5+ and CD5− B lymphocytes in the peripheral blood. After the treatment, the overall survival period was over 24 months, and no recurrence was observed 17-month post-surgery. Conclusions A combination of lenvatinib and camrelizumab may be a new conversion therapy for initially unresectable HCC to resectable HCC, thus contributing to improve the disease prognosis. In addition, the combination regimen could cause an activated immune response, and LDH, NLR, and CD5+ B-cell levels might be predictors for immunotherapy efficacy.

Abstract Purpose To investigate the prognostic value of quantitative analysis of CT among patients with idiopathic pulmonary fibrosis (IPF) by quantifying the fibrosis extent and to attempt to provide precise medium-long term prognostic predictions for individual patients. Methods This was a retrospective cohort study that included 95 IPF patients in Zhongshan Hospital, Fudan University. 64 patients firstly diagnosed with IPF from 2009 to 2015 was included as the derivation cohort. Information regarding sex, age, the Gender-Age-Physiology (GAP) index, high-resolution computed tomography (HRCT) images, survival status, and pulmonary function parameters including forced vital capacity (FVC), FVC percent predicted (FVC%pred), diffusing capacity of carbon monoxide (DLCO), DLCO percent predicted (DLCO%pred), carbon monoxide transfer coefficient (KCO), KCO percent predicted (KCO%pred) were collected. 31 patients were included in the validation cohort. The Synapse 3D software was used to quantify the fibrotic lung volume (FLV) and total lung volume (TLV). The ratio of FLV to TLV was calculated and labeled CTFLV/TLV%, reflecting the extent of fibrosis. All the physiological variants and CTFLV/TLV% were analyzed for the dimension of survival through both univariate analysis and multivariate analysis. Formulas for predicting the probability of death based on the baseline CTFLV/TLV% were calculated by logistic regression, and validated by the validation cohort. Results The univariate analysis indicated that CTFLV/TLV% along with DLCO%pred, KCO%pred and GAP index were significantly correlated with survival. However, only CTFLV/TLV% was meaningful in the multivariate analysis for prognostic prediction (HR 1.114, 95% CI 1.047–1.184, P = 0.0006), and the best cutoff was 11%, based on receiver operating characteristic (ROC) curve analysis. The survival times for the CTFLV/TLV% ≤ 11% and CTFLV/TLV% > 11% groups were significantly different. Given the CTFLV/TLV% data, the death probability of a patient at 1 year, 3 years and 5 years could be calculated by using a particular formula. The formulas were tested by the validation cohort, showed high sensitivity (88.2%), specificity (92.8%) and accuracy (90.3%). Conclusion Quantitative volume analysis of CT might be useful for evaluating the extent of fibrosis in the lung. The CTFLV/TLV% could be a valuable biomarker for precisely predicting the medium-long term prognosis of individual patients with IPF.

Mesenchymal stem cells (MSCs) show high expression of PD-L1. Exosomes can transmit signals between tumor cells and stromal cells; however, the effect of tumor-derived exosomes on stromal cell signaling pathways is unclear. The expression of PD-L1 in bone marrow mesenchymal stem cells (BMMSCs) was detected by western blot and RT-PCR. The effects of gastric cancer cell line-derived exosomes on BMMSC migration and the effects of conditioned medium from educated BMMSCs on tumor cell migration were analyzed. Our results demonstrate that exosomes derived from gastric cancer cell lines activate the AKT/c-Myc pathway of BMMSCs and upregulate PD-L1 expression on BMMSCs. Moreover, the pro-migration effect of exosomes from gastric cancer cell lines on BMMSCs is dependent on PD-L1. The upregulation of PD-L1 on BMMSCs promoted the migration of gastric cancer cells. In conclusion, tumor-derived exosomes could upregulate the expression of PD-L1 on BMMSCs to promote tumor migration. Our results provide a new therapeutic avenue in gastric cancer.

Here, by performing multi-omics microbiome analyses in a cohort of children with new-onset T1D, the authors characterize altered microbial functional and metabolic traits involved in T1D, which they validate in animal experiments, together providing potential avenues for microbiome-based interventions.

Abstract Objective To analyze the genotypes and phenotypes of a child with developmental dysplasia of the hip (DDH), developmental delays, recurrent fever, hypothyroidism and cleft palate. Methods G-banding karyotyping analysis and next-generation sequencing (NGS) were performed for the patient. The genotypes of the parents of the patient were verified by copy number variation analysis and Sanger sequencing to determine the source of variations. Results The karyotype of the patient was 46, XX. A 10.44 Mb deletion (chr18:67562936-78005270del) at 18q22.2q23 was found by NGS. We identified 2 HSPG2 mutations (chr1: 22206699, c.2244C > A, exon 17, p.H748Q; chr1: 22157321–22157321, c.11671 + 154insA, intron). One mutation was inherited from the father, and the other was inherited from the mother. Conclusion This is the first 18q deletion syndrome case accompanied by DDH. Most phenotypes of this patient, such as developmental delays and cleft palate, may be related to the 18q22.2q23 deletion, but no variants in genes related to DDH were found in this deletion region. DDH may be related to mutations of HSPG2.

BackgroundEBV-associated smooth muscle tumours (EBV-SMTs) are uncommon neoplasms associated with immunodeficiency. The pathogenesis of EBV-SMTs is poorly understood. IL-2-inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, is the predominant Tec kinase in T cells. Researchers have shown that ITK is involved in the pathogenesis of autoimmune diseases and carcinogenesis, and the loss of ITK function due to mutation in patients can lead to EBV-associated lymphoproliferation. Multiple Epstein-Barr virus–associated smooth muscle tumours with ITK mutation have rarely been reported.Case presentationA 6-year-old female child was admitted to the hospital due to recurrent bilateral hip pain for more than one year. Tumours were found in the lung, near the intracranial cavernous sinus and in the lumbar spine and paraspinal soft tissues by CT and MRI. The patient underwent vertebral tumour biopsy, which suggested low-grade myogenic or inflammatory myofibroblastic tumours, so the patient was given three courses of chemotherapy without symptom relief or mass reduction. The patient underwent lumbar mass resection, the pathological results indicated EBV-SMT, and a novel germline homozygous deletion mutation in the ITK gene was detected. The deletion mutation in this gene has not yet been reported and the clinical significance of the pathogenicity of the variant is unknown. Intrabronchial mass resection was performed under fibre bronchoscopy, and the pathological results indicated EBV-SMT. No significant recurrence or progression was observed after more than 2 years of follow-up.ConclusionsWe present a rare case of multiple EBV-SMTs combined with ITK gene mutation. Some of the tumours were removed, and some were treated conservatively. There was no significant recurrence or progression after more than two years of follow-up. The optimal treatment regimen still needs to be further explored, and the relationship between ITK gene mutation at this locus and immunodeficiency and EBV-SMT warrants further investigation.

Abstract Background The fundamental initial step in the metabolic process of fatty acids (FA) is facilitated by Acyl‐coenzyme A synthetase (ACS). ACS enables FAs to engage in both anabolic and catabolic pathways by creating thioester bonds with CoA, thus triggering their activation. This paper demonstrated the effect of in vitro cells on the ACS family of key enzymes in FA metabolism in response to inflammatory or lipid stimulating factors and provided insight into the relevant metabolic mechanisms. Methods The expression levels of 27 ACS family members were assessed across various lung epithelial cell lines, such as HBE, SPC‐1A, or NCI‐H460, in response to external challenges including lipopolysaccharide (LPS), lysophosphatidylcholine (lysoPC), cigarette smoking extract (CSE), cholesterol, and interference with the ACSL5 gene in response to FASN, CPT1A inhibitors. Results Our data showed that ACSF2 was highly expressed in SPC‐A1 and NCI‐H460 cells compared with HBE cell, while ACSL4 and ACSVL4 were lower expressed. The 27 ACS family genes associated with FA metabolism varied under several different exogenous stimuli.

This study focuses on the cultural heritage of Xiamen and uses the spatial analysis method of ArcGIS to analyze the spatiotemporal evolution and distribution characteristics of cultural heritage. Through analysis, we aim to optimize the structure of cultural heritage protection areas and tourism routes in urban planning by analyzing the spatial structure characteristics of Xiamen’s cultural heritage types in various historical periods. The results show that in terms of the time dimension, the existing cultural heritage in Xiamen was mainly built between 1840 and 1949, and the center of cultural heritage shows an overall trend of a “north-south direction”. In terms of spatial dimension, the existing cultural height in Xiamen shows a clustering distribution pattern, with clusters located in the Gulangyu and Xiagang areas of Siming District. According to the period, there is a clear spatial correlation pattern, showing a spatial clustering trend of “strong first and then weak”.

Fuzhou is an important city on the southeast coast of China with rich cultural heritage resources, and it is a national historical and cultural city in China. The main purposes of this study are the following: 1. To study the current situation and spatial distribution of cultural heritage; 2. To study the construction of cultural heritage corridors; 3. To utilize the holistic characteristics of heritage corridors to integrate the cultural heritage elements along the corridors and achieve the optimal allocation of resources. This study collects data from 605 cultural heritage sites in Fuzhou City and establishes a GIS database. The spatial distribution characteristics of cultural heritage in Fuzhou City are studied using aggregation analysis, nearest neighbor analysis, and buffer analysis in GIS technology. The following results were obtained: there is a cultural heritage corridor in Fuzhou City with the Minjiang River serving as the main land and water transportation line, and the closer one is to the water transportation line, the more intensive the distribution of cultural heritage points; and there are three cultural heritage node areas and one special cultural heritage node area. The study of Fuzhou’s heritage corridor system has important reference significance for the protection of cultural heritage in coastal historical cities in China and even in East Asia and has exploratory value for the holistic protection of cultural heritage and for the planning and development of tourism.

Abstract The growing demand for sustained self‐powered devices with multifunctional sensing networks is one of the main challenges for smart textiles, which are the critical elements for the future Internet of Things (IoT) and Point of Care (POC). Here, cellulose‐based smart textile is integrated with dynamic Schottky diode (DSD) to generate sustained power source (current density of 8.9 mA m⁻2) for self‐powered built‐in sensing network. In response to normal and shear motions, a pressure sensor with a sensitivity of 0.12 KPa⁻1 and an impact sensor are demonstrated, respectively. The woven structure of the textile contributes to signal amplification, which can also form a matrix of sensing elements for distributed sensing. The proposed strategy of fabricating self‐powered and multifunctional sensing networks with smart textiles shows tremendous potential for future intelligent society.