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Yang Liu,1,* Chunan Wang,1,* Sitong Liu,1,* Hangzhan - Ma,2 Jiayun Xu,3 Kai Jiang,1 Ruitao Lu,4 Xintao Shuai,5 Jinming Wang,3 Zhong Cao1 1School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Oral Implantology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People’s Republic of China; 4Shenzhen International Institute for Biomedical Research, Shenzhen, Guangdong, People’s Republic of China; 5Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhong Cao; Jinming Wang, Email caozhong@mail.sysu.edu.cn; wjinm@mail.sysu.edu.cnBackground: As a burgeoning cancer treatment modality, photothermal therapy (PTT) has shown robust anti-tumor effects. However, it still faces numerous challenges, such as triggering an inflammatory response and potentially increasing the risk of cancer recurrence. To address these concerns, integration of PTT with anti-inflammatory therapies presents a promising approach to enhance the efficacy of cancer treatment and meanwhile reduce the risk of recurrence.Methods: In this study, Gd3+ was first chelated with dopamine to create Gd-DA chelates, and then the mesoporous dopamine nanoparticles MX@Arg-Gd-MPDA (MAGM NPs) were synthesized by combining arginine (Arg) and the anti-inflammatory medication meloxicam (MX). The photothermal properties of MAGM NPs were then defined and examined; the in vivo MRI imaging effect, as well as MAGM NPs’ anti-cancer and anti-inflammatory efficiency, were tested in a mouse model of breast cancer.Results: The incorporation of Arg doping into MAGM NPs was intended to boost its photothermal conversion efficiency and reactive oxygen species (ROS) scavenging ability. Additionally, synergizing with the anti-inflammatory agent meloxicam (MX) within the nanoparticles aimed to enhance the anti-inflammatory effect following photothermal therapy. Furthermore, gadolinium ions (Gd3+) were chelated into the nanostructure to enable precise T1-T2 dual-mode magnetic resonance imaging (MRI) of the intratumor accumulation profile. This imaging capability was leveraged to guide the implementation of photothermal therapy. Animal experiments demonstrated that MAGM NPs exerted a notable anticancer effect in a 4T1 breast cancer mouse model, under the precise guidance of MRI.Keywords: magnetic resonance imaging, photothermal therapy, anti-inflammatory therapy, mesoporous polydopamine, cancer therapy

Duan X, Lu L, Wang Y, et al. Int J Nanomedicine. 2017;12:6705–6719. The authors have advised that Figures 6, 8 and 9 on pages 6713, 6715 and 6716, respectively, of the published paper are incorrect. The errors were introduced by the Editorial staff during the publication process. The correct figures are shown in Download Article. Read the original article

Nickel-based super alloys are the main candidate materials for aero-engines, gas turbine blades etc. This paper focuses on the simulation of nucleation and growth kinetics of γ' phase, and stress response mechanism of γ’ phase particles during their preferential coarsening (rafting) in elastic inhomogeneous system. A phase-field model is employed in the present study, which incorporates chemical, interfacial, and elastic energies, and it couples essentially to externally imposed mechanical field. Due to the limitations of the 2D model on analyzing the shape and size of the precipitate particles, the process of γ' phase particles growing and coarsening is further modeled by performing 3D simulation. The results show that the average particle size is linearly related to the evolution time and satisfies the Lifshitz-Slyozov-Wagner (LSW) classical coarsening theory when the external stress is not applied. Particles exhibit a strong special orientation under tensile stress, and the orientation is in excellent agreement with previous studies. In the nucleation stage, the collision and coalescence between particles promote rafting significantly, and the number of soft particles is obviously larger than that of hard particles. In the coarsening stage, the growth rate of soft particles is higher than that of hard particles. Three-dimensional simulation results show that the effect of final characteristic size of precipitated particles is not significant by external loads. The morphology evolution and coarsening mechanism of the precipitated particles are of great significance for studying the strengthening mechanism of super-alloy.

Yuan Peng,1,2 Jinsheng Huang,2 Hong Xiao,2 Teng Wu,1 Xintao Shuai1,2 1Center of Biomedical Engineering, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; 2Key Laboratory for Polymeric Composite & Functional Materials of Ministry of Education, Department of Polymer Science, School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China Background: The treatment of glioma remains a challenge because conventional chemotherapy is often ineffective by drug resistance. Combinative therapy using chemotherapeutic agents and siRNA has demonstrated potential to improve anticancer outcome through a synergistic effect in various cancers. The current study aims to achieve better glioma treatment through a combinative therapy based on a folate-targeted nanocarrier carrying both temozolomide (TMZ) and anti-BCL-2 siRNA.Methods: A polymeric micelle (TMZ-FaPEC@siRNA) incorporating TMZ and anti-BCL-2 siRNA was prepared based on folate-conjugated triblock copolymer (Fa-PEG-PEI-PCL, Fa-PEC) of poly(ε-caprolactone) (PCL), poly(ethylenimine) (PEI) and poly(ethylene glycol) (PEG). The physicochemical properties and drug release profile of TMZ-FaPEC@siRNA were tested. The Fa-targeted drug delivery and joint effect of siRNA and TMZ to induce glioma apoptosis and tumor growth inhibition were evaluated both in vitro and in vivo.Results: In vitro cell study demonstrated that the nanocarrier effectively facilitates codelivery of siRNA and TMZ into C6 cells, resulting in a strong apoptotic response of cancer cells by silencing the antiapoptosis BCL-2 gene and activating the proapoptotic Bax gene simultaneously. In vivo study in rat bearing orthotropic glioma showed that tumor growth was inhibited and meanwhile animal survival was prolonged remarkably through intracranial injection of TMZ-FaPEC@siRNA.Conclusion: Our results evidence the strong efficacy of the folate-targeted nanomedicine carrying TMZ and BCL-2 siRNA in treating glioma. Keywords: polymeric nanocarrier, temozolomide, siRNA targeting BCL-2 gene, glioma treatment, drug resistance

Xiaohui Duan,1,* Liejing Lu,1,* Yong Wang,2 Fang Zhang,1 Jiaji Mao,1 Minghui Cao,1 Bingling Lin,1 Xiang Zhang,1 Xintao Shuai,2,3 Jun Shen1 1Department of Radiology, Sun Yat-Sen Memorial Hospital, 2PCFM Lab of Ministry of Education, School of Materials Science and Engineering, 3BME Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Understanding the long-term fate and potential mechanisms of mesenchymal stem cells (MSCs) after transplantation is essential for improving functional benefits of stem cell-based stroke treatment. Magnetic resonance imaging (MRI) is considered an attractive and clinically translatable tool for longitudinal tracking of stem cells, but certain controversies have arisen in this regard. In this study, we used SPION-loaded cationic polymersomes to label green fluorescent protein (GFP)-expressing MSCs to determine whether MRI can accurately reflect survival, long-term fate, and potential mechanisms of MSCs in ischemic stroke therapy. Our results showed that MSCs could improve the functional outcome and reduce the infarct volume of stroke in the brain. In vivo MRI can verify the biodistribution and migration of grafted cells when pre-labeled with SPION-loaded polymersome. The dynamic change of low signal volume on MRI can reflect the tendency of cell survival and apoptosis, but may overestimate long-term survival owing to the presence of iron-laden macrophages around cell graft. Only a small fraction of grafted cells survived up to 8 weeks after transplantation. A minority of these surviving cells were differentiated into astrocytes, but not into neurons. MSCs might exert their therapeutic effect via secreting paracrine factors rather than directing cell replacement through differentiation into neuronal and/or glial phenotypes. Keywords: mesenchymal stem cells, magnetic resonance imaging, superparamagnetic iron oxide nanoparticles, polymersome, ischemic stroke, green fluorescence protein

Based on the two-mode phase field crystal (PFC) model and the principle of the common tangent, a two-dimensional PFC phase diagram is established. According to the phase diagram, the parameters for a steady growth of the hexagonal and the square phase are found. Moreover, the nucleation and growth characteristics of the square phase from hexagonal phase under different pressures are simulated by using these parameters. The movements of dislocation core under pressure at different transformation stages are revealed and compared with each other. Finally, by changing the grain orientation, the formation and disappearance of grain boundaries at different angles are simulated and analyzed.

Seyin Zou,1,3,† Nuo Cao,1,† Du Cheng,2 Rongqin Zheng,4 Jin Wang,4 Kangshun Zhu,4 Xintao Shuai1,2 1Center of Biomedical Engineering, Zhongshan School of Medicine, 2PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, 3Department of Laboratory Medicine,The Third Affiliated Hospital, Guangzhou Medical University, 4The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China †These authors contributed equally to this workAbstract: A folate conjugated ternary copolymer, FA–PEG–PEI–PCL, of poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and poly(ε-caprolactone) (PCL) was synthesized. The copolymer self-assembled into cationic micelles capable of co-delivering siRNA and the anticancer drug doxorubicin (DOX). This dual functional nanocarrier demonstrated low cytotoxicity and high performance in drug/siRNA delivery. Upon the codelivery of siRNA, targeting the Bcl-2 gene, and DOX, using the folate-targeted nanocarrier, DOX-induced apoptosis in the skov-3 cells overexpressing folate receptor was significantly enhanced through a mechanism of downregulating the antiapoptotic protein Bcl-2, while simultaneously upregulating the proapoptotic protein Bax. This work suggested that the combination of Bcl-2 siRNA and DOX therapies is feasible, based on our dual functional nanocarrier, which set up a good basis for a future in vivo test.Keywords: codelivery, gene silencing, chemotherapy, apoptosis, tumor targeting

Tinghui Yin1*, Ping Wang1*, Rongqin Zheng1, Bowen Zheng1, Du Cheng2, Xinling Zhang1, Xintao Shuai21Department of Medical Ultrasonic, Third Affiliated Hospital, 2PCFM Laboratory of the Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China*These authors contributed equally to this workAbstract: The fabrication and initial applications of nanobubbles (NBs) have shown promising results in recent years. A small particle size is a basic requirement for ultrasound contrast-enhanced agents that penetrate tumor blood vessel pores to allow for targeted imaging and therapy. However, the nanoscale size of the particles used has the disadvantage of weakening the imaging ability of clinical diagnostic ultrasound. In this work, we fabricated a lipid NBs contrast-enhanced ultrasound agent and evaluated its passive targeting ability in vivo. The results showed that the NBs were small (436.8 ± 5.7 nm), and in vitro ultrasound imaging suggested that the ultrasonic imaging ability is comparable to that of microbubbles (MBs). In vivo experiments confirmed the ability of NBs to passively target tumor tissues. The NBs remained in the tumor area for a longer period because they exhibited enhanced permeability and retention. Direct evidence was obtained by direct observation of red fluorescence-dyed NBs in tumor tissue using confocal laser scanning microscopy. We have demonstrated the ability to fabricate NBs that can be used for the in vivo contrast-enhanced imaging of tumor tissue and that have potential for drug/gene delivery.Keywords: phospholipids, ultrasound, contrast agent, tumor-targeted

Yinting Chen1, Weiwei Wang2, Guoda Lian1, Chenchen Qian1, Lingyun Wang1, Linjuan Zeng1, Chengde Liao3, Biling Liang4, Bing Huang5, Kaihong Huang1, Xintao Shuai21Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, 2Center of Biomedical Engineering, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, 3Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Kunming, 4Department of Radiology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, 5Center of Animal Research, Zhongshan Ophthalmic Center Hospital of Sun Yat-sen University, Guangzhou, ChinaAbstract: An antibody-directed nonviral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles and a gastric cancer-associated CD44v6 single-chain variable fragment (scFvCD44v6,-PEG-g-PEI-SPION), was constructed as a gastric cancer-targeting and magnetic resonance imaging (MRI)-visible nanocarrier for small interfering RNA (siRNA) delivery. Biophysical characterization of PEG-g-PEI-SPION and scFvCD44v6-PEG-g-PEI-SPION was carried out, including siRNA condensation capacity, cell viability, and transfection efficiency. Both the targeting and nontargeting nanocarriers were effective for transferring siRNA in vitro. The cellular uptake and distribution of nanoparticles complexed with siRNA was analyzed by fluorescence imaging and immunofluorescent staining. Moreover, the gastric cancer-targeting effect was verified in vivo by MRI and histology analysis. These results indicate that scFvCD44v6-PEG-g-PEI-SPION is a promising nonviral vector for gastric cancer gene therapy and diagnosis.Keywords: tumor targeting, CD44 variant 6, nonviral vector, small interfering RNA, magnetic resonance imaging

Xiao-Ai Chen1,5*, Li-Jun Zhang2*, Zhi-Jie He3, Wei-Wei Wang4, Bo Xu1, Qian Zhong1, Xin-Tao Shuai4, Li-Qun Yang4, Yu-Bin Deng11Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; 2Futian Affiliated Hospital, Guangdong Medical College, Shenzhen, China; 3Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; 4Institute of Polymer Science, School of Chemistry and Chemical Engineering, BME Center, State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, Guangzhou, China; 5Yunnan Cancer Hospital, The Third Affiliated Hospital, Kunming Medical College, Kunming, China*Both authors contributed equally to this workBackground: Mesenchymal stem cell transplantation is a promising method in regenerative medicine. Gene-modified mesenchymal stem cells possess superior characteristics of specific tissue differentiation, resistance to apoptosis, and directional migration. Viral vectors have the disadvantages of potential immunogenicity, carcinogenicity, and complicated synthetic procedures. Polyethylene glycol-grafted polyethylenimine (PEG-PEI) holds promise in gene delivery because of easy preparation and potentially targeting modification.Methods: A PEG8k-PEI25k graft copolymer was synthesized. Agarose gel retardation assay and dynamic light scattering were used to determine the properties of the nanoparticles. MTT reduction, wound and healing, and differentiation assays were used to test the cytobiological characteristics of rat mesenchymal stem cells, fluorescence microscopy and flow cytometry were used to determine transfection efficiency, and atomic force microscopy was used to evaluate the interaction between PEG-PEI/plasmid nanoparticles and mesenchymal stem cells.Results: After incubation with the copolymer, the bionomics of mesenchymal stem cells showed no significant change. The mesenchymal stem cells still maintained high viability, resettled the wound area, and differentiated into adipocytes and osteoblasts. The PEG-PEI completely packed plasmid and condensed plasmid into stable nanoparticles of 100–150 nm diameter. After optimizing the N/P ratio, the PEG-PEI/plasmid microcapsules delivered plasmid into mesenchymal stem cells and obtained an optimum transfection efficiency of 15%–21%, which was higher than for cationic liposomes.Conclusion: These data indicate that PEG-PEI is a valid gene delivery agent and has better transfection efficiency than cationic liposomes in mesenchymal stem cells.Keywords: stem cells, gene delivery, nanoparticles, atomic force microscopy

Electron beam directed energy deposition (EB-DED) has been successfully employed to additively manufacture and repair Al–Cu alloys, however, the effects of thermal histories on the microstructure and properties have been little investigated. In this study, a specially developed Al–Si–Cu wire (380D) was deposited on the Al–Cu substrates (2A14-T6) via EB-DED to fabricate hybrid components for additive repair purposes. By using both experimental and numerical methods, the effects of substrate thickness on the thermal histories experienced and the microstructures resulted across the structural interfaces, as well as the mechanical properties of the hybrid parts, are comprehensively investigated. Results show that the columnar to equiaxed transition (CET) occurs in the deposits when the temperature gradient G and solidification velocity R satisfy the critical condition of G2/R

Abstract Current small-molecule-regulated synthetic gene switches face clinical limitations such as cytotoxicity, long-term side-effects and metabolic disturbances. Here, we describe an advanced synthetic platform inducible by risk-free input medication (ASPIRIN), which is activated by acetylsalicylic acid (ASA/aspirin), a multifunctional drug with pain-relieving, anti-inflammatory, and cardiovascular benefits. To construct ASPIRIN, we repurpose plant salicylic acid receptors NPR1 and NPR4. Through domain truncations and high-throughput mutant library screening, we enhance their ASA sensitivity. Optimized NPR1 fused with a membrane-tethering myristoylation signal (Myr-NPR1) forms a complex with NPR4, which is fused with a DNA binding domain (VanR) and a transactivation domain (VP16). ASA induces dissociation of the Myr-NPR1/NPR4-VanR-VP16 complex, allowing nuclear translocation of NPR4-VanR-VP16 to activate VanR-operator-controlled gene expression. In male diabetic mice implanted with microencapsulated ASPIRIN-engineered cells, ASA regulates insulin expression, restores normoglycemia, alleviates pain and reduces biomarkers of diabetic neuropathy and inflammation. We envision this system will pave the way for aspirin-based combination gene therapies.

Abstract The influence of tertiary lymphoid structures (TLSs) on disease progression and the response to immunotherapy in head and neck squamous cell carcinoma (HNSCC) is well established, yet the heterogeneity among these structures remains largely unexplored. We utilized digital spatial profiling technology to perform in situ transcriptomic sequencing of TLSs across varying levels of maturation and distinct tumor regions within HNSCC. We assessed the prognostic significance of TLS maturation and spatial distribution in 260 patients with HNSCC through hematoxylin and eosin staining and multiplex immunohistochemistry. Furthermore, we established a TLS scoring system to predict survival in patients with HNSCC. Our study revealed that mature TLSs in the intratumor region (Intra-TLSs) of HNSCC, enriched with memory B cells, plasma cells, and CD4+ T cells, presented increased B-cell activity gene expression. Conversely, early TLSs (E-TLSs), abundant in endothelial cells, fibroblasts, and regulatory T cells, express epithelial‒mesenchymal transition (EMT)-related genes, potentially fostering tumor growth. Compared with mature TLSs within the peritumoral region (Peri-TLSs), mature Intra-TLSs have greater memory B-cell and macrophage densities and upregulate genes involved in B-cell receptor signaling and immune effector processes. Mature Peri-TLSs, characterized by endothelial cell enrichment and EMT receptor interaction genes, may contribute to tumor progression and immune evasion. Patients with mature Intra-TLSs or invasive margin TLSs (Invas-TLSs) have improved 5-year survival, whereas those with mature Peri-TLSs have poorer prognoses. By integrating TLS maturity and distribution in HNSCC, we developed a TLS scoring system to guide personalized treatments, which is crucial for predicting outcomes.

Abstract To alleviate water resource shortages and tensions and meet the water diversion needs of different river basins, buried (cross-dam) pipelines have become an essential component of water diversion projects. They are installed in levee projects in key river basins such as the Yellow River, Jingjiang River, and Beijiang River. Due to the complex engineering structure and multiple sources of vibration excitation, if vibrations propagate along the pipeline axis towards the surrounding levee, they could have an adverse impact on the stability and safe operation of the levee. To accurately identify the vibration and transmission characteristics of the buried pipeline dikes, determine its primary vibration sources, and clarify the propagation laws of pipeline vibrations within the levee, this study, based on prototype observation data and utilizing signal fusion processing technology, investigates the inherent vibration characteristics of the buried pipeline dikes from the perspectives of excitation, transmission, and response. At the same time, by introducing the “finite element-infinite element” theory, a coupled finite element-infinite element model is established for the pipeline, levee, anchor piers, support piers, foundation, and infinite half-space. This model is then used to analyze the site response induced by flow-induced vibration in buried pipeline levee structures. The results show that the primary vibration frequencies of the buried pipeline dike structure are the unit rotation frequency of 74.4 Hz and the blade vibration frequency of 24.8 Hz. These vibration sources originate from the pump unit and propagate outward along the pipeline axis. Using the transmission range of the vibration source as the basis for determining the vibration impact range, it was established that the horizontal vibration impact of the buried pipeline extends 10 m on either side of the pipeline axis, while the vertical vibration impact extends 7.5 m below the dike crest.

The catenary is an important part of the railway power supply system, and the good health of its key components is an important condition for the operation of high-speed trains. Due to the complex composition of catenary components and the large size difference between components, it is very difficult to implement the locating and detection of all components. It severely limits the subsequent failure analysis of catenary components. Aiming at the problem of the difficult locating of multiple components, this paper proposes a catenary complex component locating method based on the improved YOLO algorithm named CCL-YOLO. Firstly, based on the YOLO baseline method, a framework for locating complex components of railway catenary is proposed, which achieves the accurate locating of 40 catenary components and paves the way for subsequent defect detection. Furthermore, a novel “Gather-and-Distribute” mechanism is introduced, which improves the original feature fusion method and its global feature fusion capability and effectively improves the locating accuracy of complex catenary components. In addition, the Wasserstein distance loss is also applied to improve the detection capability of small objects. Finally, the comprehensive experimental results show that the proposed method for locating complex components of railway catenary can achieve a mean average precision of 94.1% for 40 components of different sizes. Meanwhile, it reduces the number of parameters and the complexity of the algorithm to a certain extent, thus paving the way for subsequent fault detection, which is of important application value.

Abstract Recently, the biologically inspired intelligent artificial visual neural system has aroused enormous interest. However, there are still significant obstacles in pursuing large-scale parallel and efficient visual memory and recognition. In this study, we demonstrate a 28 × 28 synaptic devices array for the artificial visual neuromorphic system, within the size of 0.7 × 0.7 cm2, which integrates sensing, memory, and processing functions. The highly uniform floating-gate synaptic transistors array were constructed by the wafer-scale grown monolayer molybdenum disulfide with Au nanoparticles (NPs) acting as the electrons capture layers. Various synaptic plasticity behaviors have been achieved owing to the switchable electronic storage performance. The excellent optical/electrical coordination capabilities were implemented by paralleled processing both the optical and electrical signals the synaptic array of 784 devices, enabling to realize the badges and letters writing and erasing process. Finally, the established artificial visual convolutional neural network (CNN) through optical/electrical signal modulation can reach the high digit recognition accuracy of 96.5%. Therefore, our results provide a feasible route for future large-scale integrated artificial visual neuromorphic system.

Objective Ankylosing spondylitis (AS) is a debilitating rheumatic condition that significantly impairs mobility and quality of life through chronic inflammation and spinal fusion. The aim of this study is to investigate the optimal sequencing of spinal osteotomy and total hip replacement (THR) as treatment options, a topic that remains a subject of debate among medical professionals. Methods In a retrospective cohort study spanning from 2017 to 2021, we assessed adult patients with AS who underwent both spinal osteotomy and THR, outcome measures involved radiographic assessments like Global Cobb angle, thoracolumbar kyphosis (TLK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS), as well as clinical metrics such as the Harris hip score. For the same surgical group, paired t‐tests were performed for pre‐ and postoperative data, while independent sample t‐tests were used for comparing different surgical groups. The study aims to elucidate the optimal sequencing of these surgical procedures based on these comprehensive metrics. Results Among the 14 patients included, demographic and clinical variables were comparable between the two procedural groups. At the 3‐month follow‐up, all major metrics showed significant postoperative improvements. Specifically, the Global Cobb angle reduced from 98.88 ± 38.54 to 54.48 ± 18.14 (p = 0.018), and the Harris hip scores, evaluated at the 3‐month follow‐up, dramatically increased from 15.14 ± 10.12 to 72.57 ± 14.12 (p = 0.001). Furthermore, the Spine First Group exhibited more pronounced changes in pelvic parameters (p = 0.009), albeit at the expense of longer operation times and increased blood loss. No major complications were encountered. Conclusions Contrary to the prevalent belief that spinal osteotomy should precede THR, our study argues that under certain conditions, opting for hip surgery first can be both viable and advantageous. This approach may mitigate the risk of complications and even facilitate subsequent spinal surgery. Surgical decisions must be highly tailored, focusing on patient‐specific needs and anatomical considerations. The ultimate goal remains consistent: to improve patients' functional abilities in daily activities and thereby enhance their overall quality of life.

The objective of this paper is to examine the vanishing viscosity limit of the nonhomogeneous incompressible NS systerm, subject to the no-slip boundary condition. By adopting Kato's approach of constructing an artificial boundary layer [1], within a smooth and bounded domain designated as $ \Omega\subseteq\mathbb{R}^{2} $, we derive a sufficient condition for the convergence to occur uniformly in time within the energy space $ L^{2}(\Omega) $.

Abstract Hypertrophic cardiomyopathy (HCM) is one of the most common cardiovascular diseases with no effective treatment due to its complex pathogenesis. A novel cell death, disulfidptosis, has been extensively studied in the cancer field but rarely in cardiovascular diseases. This study revealed the potential relationship between disulfidptosis and hypertrophic cardiomyopathy and put forward a predictive model containing disulfidptosis-associated genes (DRGs) of GYS1, MYH10, PDMIL1, SLC3A2, CAPZB, showing excellent performance by SVM machine learning model. The results were further validated by western blot, RNA sequencing and immunohistochemistry in a TAC mice model. In addition, resveratrol was selected as a therapeutic drug targeting core genes using the CTD database. In summary, this study provides new perspectives for exploring disulfidptosis-related biomarkers and potential therapeutic targets for hypertrophic cardiomyopathy.

Abstract Background This study aimed to elucidate the safety and intra-articular elution profiles of vancomycin and gentamicin bone cement in patients undergoing primary total knee arthroplasty (TKA), with a focus on serum safety thresholds and therapeutic efficacy. Methods Consecutive patients who underwent unilateral primary TKA were prospectively enrolled. The implants were fixed using gentamicin-impregnated bone cement, and after arthrotomy closure, 1000 mg of vancomycin suspended in 25 mL of normal saline was directly injected into the joint. Peripheral venous blood and drain fluid samples were collected 2, 8, and 24 h postoperatively. The serum and intra-articular concentrations of vancomycin and gentamicin were analyzed using liquid chromatography-tandem mass spectrometry within 24 h. Results Clinical data reflecting renal and liver function were recorded preoperatively, and at 24 and 72 h postoperatively. A total of 100 patients were included. At 2, 8, and 24 h postoperatively, the serum vancomycin concentration was 7.0 ± 2.0, 5.7 ± 1.8, and 3.6 ± 1.4 µg/mL, respectively, while the intra-articular concentration was 468.5 (interquartile range [IQR] 286.0 to 774.8), 139.5 (IQR 52.0 to 295.3), and 34.4 (IQR 22.2 to 56.8) µg/mL, respectively; 33.2 (IQR 19.5 to 80.5) mg vancomycin was lost in drainage fluid at 24 h postoperatively. For gentamicin, the overall intra-articular concentration was 70.4 (IQR 35.4 to 109.2), 33.8 (IQR 17.8 to 73.9), and 21.1 (IQR 12.2 to 36.0) µg/mL at 2, 8, and 24 h postoperatively, respectively, with an undetectable serum concentration. No cases of acute renal injury, liver injury, ototoxicity, or anaphylaxis were observed. Conclusions Intra-articular injection of 1000 mg vancomycin after arthrotomy closure combined with gentamicin-impregnated bone cement provided a therapeutic intra-articular concentration while avoiding systemic toxicity over the initial 24 h after primary TKA. Therefore, intra-articular vancomycin administration may offer a safer alternative to intravenous antibiotics, reducing systemic toxicity; however, further large-scale studies are necessary. Trial registration ClinicalTrials. Gov (registration number: NCT05338021).

Abstract Background Venous thromboembolism (VTE) is a common complication after hip arthroplasty. Here, we investigated the clinical efficacy and safety of prophylactic aspirin vs. conventional therapy in hip arthroplasty for femoral neck fracture. Methods Patients who underwent total hip arthroplasty and hemiarthroplasty for femoral neck fractures between April 2021 and April 2024 were prospectively enrolled. Group A received oral aspirin (100 mg, once daily) as VTE prophylaxis; Group LR received low-molecular-weight heparin (4,250 U, once daily) sequentially followed by rivaroxaban (10 mg, once daily). The patients were followed up for 90 days postoperatively. Safety and efficacy were comprehensively evaluated based on postoperative VTE incidence, laboratory blood tests, bleeding events, and other complications. Results Group A was noninferior to Group LR in preventing VTE (incidence rates of 11.6% and 10.1%, respectively, with a rate difference of 1.5%, 95% CI: 0.7–2.3%, P for non-inferiority test = 0.017). There was no significant difference between the groups in the incidence of bleeding events (3.3 vs. 8.4%; P = 0.092). Furthermore, the rates of other complications did not differ significantly between groups. Conclusion In patients undergoing hip arthroplasty for femoral neck fractures, the efficacy and safety of oral aspirin for preventing VTE was similar to that of low-molecular-weight heparin followed by rivaroxaban.

Abstract Background and objectives Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder that mostly affects the central nervous system and skeletal muscle. This study provides a comprehensive summary of the clinical symptoms, multisystemic pathogenesis, and genetic characteristics of MELAS syndrome. The aim was to improve comprehension of clinical practice and gain a deeper understanding of the latest pathophysiological theories. Methods The present investigation involved a cohort of patients diagnosed with MELAS at Nanjing Drum Tower Hospital between January 2014 and December 2022. Multisystem symptoms, magnetic resonance imaging/spectroscopy (MRI/MRS), muscle biopsy, and mitochondrial DNA (mtDNA) data were summarized and subsequently analysed. Results This retrospective study included a cohort of 29 MELAS patients who predominantly presented symptoms such as stroke-like episodes, proximal muscle weakness, and exercise intolerance. MRI scans revealed very small infarcts beneath the deep cortex during stroke-like episodes, indicating nonvascular brain damage. Pathology analyses of the brain also showed neuronal degeneration and glial cell proliferation in the cerebral parenchyma. Proton magnetic resonance spectroscopy (1H-MRS) analysis revealed an increase in the lactate peak and a reduction in the N-acetylaspartate (NAA) level. Similarly, the phosphorus magnetic resonance spectroscopy (31P-MRS) analysis revealed an abnormal ratio of inorganic phosphate (Pi) to phosphocreatine (PCr). Muscle biopsy revealed the presence of ragged red fibres (RRFs) and cytochrome c oxidase (COX) enzyme-defective cells. These abnormalities indicate structural abnormalities in the mitochondria and deficiencies in oxidative phosphorylation, respectively. In addition to the common m.3243A > G variant, other prevalent variants, including m.5628 T > C, m.6352-13952del, and a 9-bp small deletion combined with m.3243A > G, exist. Conclusions MELAS is a rare mitochondrial syndrome characterized by clinical heterogeneity and genetic heteroplasmy. Abnormalities in mitochondrial metabolic function and impairments in enzyme activity are the pathogenic processes underlying MELAS. Mitochondrial vasculopathy and mitochondrial neuropathy may provide a partial explanation for the unique aetiology of stroke-like episodes.

Abstract The transient receptor potential melastatin (TRPM) channel family has been previously implicated in various diseases, including those related to temperature sensing, cardiovascular health, and neurodegeneration. Nowadays, increasing evidence indicates that TRPM family members also play significant roles in various types of cancers, exhibiting both pro- and anti-tumorigenic functions. They are involved in tumor cell proliferation, survival, invasion, and metastasis, serving as potential diagnostic and prognostic biomarkers for cancer. This paper begins by describing the structure and physiological functions of the TRPM family members. It then outlines their roles in several common malignancies, including pancreatic, prostate, colorectal, breast, brain cancer, and melanoma. Subsequently, we focused on investigating the specific mechanisms by which TRPM family members are involved in tumorigenesis and development from both the tumor microenvironment (TME) and intracellular signaling. TRPM channels not only transmit signals from the TME to regulate tumor cell functions, but also mediate extracellular matrix remodeling, which is conducive to the malignant transformation of tumor cells. Importantly, TRPM channels depend on the regulation of the inflow of various ions in cells, and participate in key signaling pathways involved in tumor progression, such as Wnt/β-catenin, MAPK, PI3K/AKT, p53, and autophagy. Finally, we summarize the current strategies and challenges of targeting TRPM channels in tumor treatment, and discuss the feasibility of combining targeted TRPM channel drugs with cancer immunotherapy.

Abstract Background Angiotensin-converting enzyme-2 (ACE2) acts as a key regulatory molecule and important therapeutic target in the pathological remodeling of numerous organs and diseases. In this study, a rapid, simple, and efficient synthetic route with a catalytic, 18F-for-Cl (18F/Cl) exchange scheme was designed for the preparation of 18F-labeled MLN-4760, and its targeting ability was investigated in a humanized ACE2 mouse model. Results A novel 18F-labeled MLN-4760 radioligand, abbreviated as 18F-MLN-4760, was successfully synthesized by the 18F/Cl exchange-labeling, and was purified by SepPak C18 columns with a radiochemical yield of 30% and a radiochemical purity of 29.89%. Target distribution of 18F-MLN-4760 in several organs with high ACE2 expression was observed by PET imaging with good stability over 120 min. The biodistribution data showed that the uptake of 18F-MLN-4760 in ACE2-overexpressing organs and tissues was highly specific, and immunohistochemistry confirmed the same results of ACE2 expression and biodistribution in the major organs (heart, liver, lungs, and kidneys). There was a good correlation between the uptake in the organs with high ACE2 expression and ACE2 expression levels (r = 0.935). Conclusion 18F-MLN-4760 was successfully synthesized via 18F/Cl exchange under phase transfer catalysis, and served as a potential probe for ACE2-targeted PET imaging.

The connection of dissimilar materials has always been a great challenge, especially titanium alloy and aluminum alloy, which have broad application prospects in the aerospace industry. In this work, the Ti6Al4V/AA2024 alloy component was prepared by laser-directed energy deposition (L-DED) technology based on a conventional interweaving structure, and the microstructure of four typical position interfaces was analyzed. Aiming at the problem of poor forming quality of titanium alloy in the second interweaving layer caused by high laser reflectivity of aluminum alloy, a secondary deposition process was proposed. The microstructure and mechanical properties of Ti6Al4V/AA2024 alloy component fabricated by two different processes were characterized and tested. The problems of discontinuity and penetrating cracks at the Ti6Al4V layer in the second interweaving layer are effectively tackled by secondary deposition. As a result, the mechanical property of the deposited structure can be effectively improved, of which the average compressive shear strength is 8% higher than that of the conventional interweaving Ti6Al4V/AA2024 alloy component. The stress at the Ti6Al4V/AA2024 interface presents a zig-zag distribution because of the interweaving structure, which avoids the generation of continuous stress bands and effectively inhibits the interface crack propagation.

Abstract Hematite is a well-known catalyst for the oxygen evolution reaction on photoanodes in photoelectrochemical water-splitting cells. However, the knowledge of hematite-water interfaces and water oxidation mechanisms is still lacking, which limits improvements in photoelectrochemical water-splitting performance. Herein, we use the Fe-terminated hematite (0001) surface as a model and propose a comprehensive mechanism for the oxygen evolution reaction on both non-solvated and solvated surfaces. Key reaction intermediates are identified through ab initio molecular dynamics simulations at the density functional theory level with a Hubbard U correction. Several notable intermediates are proposed, and the effects of water solvent on these intermediates and the overall reaction mechanisms are suggested. The proposed mechanisms align well with experimental observations under photoelectrochemical water oxidation conditions. Additionally, we highlight the potential role of O2 desorption in the oxygen evolution reaction on hematite, as O2 adsorption may block reaction sites and increases surface hydrophobicity, leading to an unfavorable pathway for oxygen evolution.

A coal mine dual prevention construction evaluation model based on association rule mining and combined weighting cloud model is proposed. Firstly, based on association rule mining, the evaluation indicators for the effectiveness evaluation system of the dual prevention mechanism construction in coal mines are determined. Secondly, the analytic hierarchy process and anti entropy weight method are used to obtain the subjective and objective weights of the indicators. Then, the composite normalization method is used to obtain the combined weights of the indicators, and a cloud theory model is introduced to construct an evaluation model for coal mine dual prevention construction based on the cloud model. Finally, by analyzing a coal mine as a sample, the evaluation results of the model are compared with those of the analytic hierarchy process cloud model and the anti entropy weight method cloud model. The results indicate that the evaluation model is more scientific and accurate in the evaluation of dual prevention construction in coal mines, which helps to assist coal mines in establishing a scientific and reasonable “dual prevention” mechanism.

Repair offers significant time—cost savings and durability by reusing existing parts efficiently. Prior to implementation of repaired parts, it is crucial to clarify mechanical properties and deformation mechanisms to ensure proper performance. In this study, a repair deposition was performed on the groove of wrought stainless steel 316L using the same material powder. The repaired sample exhibited an excellent combination of ductility and strength (T.EL: 58%, YS: 407 MPa, UTS: 673 MPa) compared to the wrought counterpart. With heterogeneity in microstructure, the hetero-deformation-induced strengthening of the repaired sample resulted in a synergy of strength-ductility combinations.

Abstract Background Pulmonary hypertension (PH) is marked by elevated pulmonary artery pressures due to various causes, impacting right heart function and survival. Disulfidptosis, a newly recognized cell death mechanism, may play a role in PH, but its associated genes (DiGs) are not well understood in this context. This study aims to define the diagnostic relevance of DiGs in PH. Methods Using GSE11726 data, we analyzed DiGs and their immune characteristics to identify core genes influencing PH progression. Various machine learning models, including RF, SVM, GLM, and XGB, were compared to determine the most effective diagnostic model. Validation used datasets GSE57345 and GSE48166. Additionally, a CeRNA network was established, and a hypoxia-induced PH rat model was used for experimental validation with Western blot analysis. Results 12 DiGs significantly associated with PH were identified. The XGB model excelled in diagnostic accuracy (AUC = 0.958), identifying core genes DSTN, NDUFS1, RPN1, TLN1, and MYH10. Validation datasets confirmed the model’s effectiveness. A CeRNA network involving these genes, 40 miRNAs, and 115 lncRNAs was constructed. Drug prediction suggested therapeutic potential for folic acid, supported by strong molecular docking results. Experimental validation in a rat model aligned with these findings. Conclusion We uncovered the distinct expression patterns of DiGs in PH, identified core genes utilizing an XGB machine-learning model, and established a CeRNA network. Drugs targeting the core genes were predicted and subjected to molecular docking. Experimental validation was also conducted for these core genes.

Abstract Background Halo-pelvic traction (HPT) is acknowledged for enhancing pulmonary function and reducing neurological complications in severe and rigid scoliosis and kyphoscoliosis. While its role in improving coronal balance is established, its impact on sagittal kyphosis remains under-researched. This study aims to assess HPT’s effects on sagittal alignment in these conditions. Methods A retrospective review of 37 patients with severe and rigid scoliosis or kyphoscoliosis was conducted to evaluate HPT’s efficacy. The analysis focused on the impact of HPT on coronal and sagittal parameters, pulmonary function tests (PFTs) and complications. Radiographic assessments included main cobb angle in coronal, sagittal major kyphosis. Results HPT was applied for an average of 2.9 months, significantly reducing the primary coronal curve from 127.7°±30.3° to 74.9°±28.3° (P

Highlights Additive-assisted layer-by-layer (LBL) deposition enables organic solar cells to achieve an unprecedented power conversion efficiency of 20.8%, the highest efficiency to date. The gradient fibrillar morphology enabled by additive-assisted LBL processing promotes the formation of bulk p-i-n structure, improving exciton and carrier diffusion, and reducing recombination losses. The wrinkle pattern morphology achieved by additive-assisted LBL processing is constructed to enhance the light capture capability.

Abstract The COVID-19 pandemic has challenged the current paradigm of clinical and community-based disease detection. We present a multimodal wearable sensor system paired with a two-minute, movement-based activity sequence that successfully captures a snapshot of physiological data (including cardiac, respiratory, temperature, and percent oxygen saturation). We conducted a large, multi-site trial of this technology across India from June 2021 to April 2022 amidst the COVID-19 pandemic (Clinical trial registry name: International Validation of Wearable Sensor to Monitor COVID-19 Like Signs and Symptoms; NCT05334680; initial release: 04/15/2022). An Extreme Gradient Boosting algorithm was trained to discriminate between COVID-19 infected individuals (n = 295) and COVID-19 negative healthy controls (n = 172) and achieved an F1-Score of 0.80 (95% CI = [0.79, 0.81]). SHAP values were mapped to visualize feature importance and directionality, yielding engineered features from core temperature, cough, and lung sounds as highly important. The results demonstrated potential for data-driven wearable sensor technology for remote preliminary screening, highlighting a fundamental pivot from continuous to snapshot monitoring of cardiorespiratory illnesses.

Abstract Post-transcriptional regulation mediated by RNA binding proteins is crucial for male germline development. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), an RNA binding protein, is specifically expressed in human and mouse male gonads and is involved in manifold biological processes and tumorigenesis. However, the function of IGF2BP1 in mammalian spermatogenesis remains poorly understood. Herein, we generated an Igf2bp1 conditional knockout mouse model using Nanos3-Cre. Germ cell deficiency of Igf2bp1 in mice caused spermatogenic defects in an age-dependent manner, resulting in decreased numbers of undifferentiated spermatogonia and increased germ cell apoptosis. Immunoprecipitation-mass spectrometry analysis revealed that ELAV-like RNA binding protein 1, a well-recognized mRNA stabilizer, interacted with IGF2BP1. Single cell RNA-sequencing showed distinct mRNA profiles in spermatogonia from conditional knockout versus wide type mice. Further research showed that IGF2BP1 plays a vital role in the modulation of spermatogenesis by regulating Lin28a mRNA, which is essential for clonal expansion of undifferentiated spermatogonia. Thus, our results highlight the crucial effects of IGF2BP1 on spermatogonia for the long-term maintenance of spermatogenesis.

ObjectiveThis prospective study aimed to analyze the efficacy and safety of fine-needle prick (FNP) in the assessment of parathyroid gland (PG) perfusion during thyroid surgery.MethodsA total of 147 patients with papillary thyroid carcinoma (PTC) who underwent lobectomy with therapeutic unilateral central lymph node dissection (CLND) performed by the same surgeon at the First Hospital of Jilin University between June and September 2024 were included in this prospective study. Following removal of the thyroid and unilateral central lymph nodes, indocyanine green (ICG) was prepared and administered intravenously. Fluorescence signals and images were captured using a near-infrared system to obtain the ICG1 score. Approximately 5–10 min thereafter, the fluorescent signal dissipated, after which the preserved PG was evaluated using FNP. An FNP score was established based on oozing blood from the parathyroid. After hemostasis was achieved by compression with gauze, ICG was reinjected to reassess PG perfusion, which yields the ICG2 score.ResultsIn 13 patients, only one parathyroid was identified, while the other was inadvertently excised during surgery. A total of 269 (95.73%) parathyroids were evaluated, with consistent scores observed between the use of the ICG1 and FNP methods. However, in six congested PGs with a darkened appearance, the FNP method could not accurately assess blood supply due to the slow oozing of accumulated blood following the procedure. The Spearman’s correlation coefficient between the ICG1 and FNP methods was 0.973 (p < 0.001), demonstrating strong concordance in determining PG blood supply. Furthermore, the identical ICG1 and ICG2 scores indicated that FNP did not adversely affect PG perfusion.ConclusionThe FNP test could represent a safer, simpler, and more reliable alternative to ICG for the assessment of PG perfusion. However, further validation in patients undergoing total thyroidectomy and bilateral CLND is warranted.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2400084531.

This study aims to investigate the use of Long Short-Term Memory (LSTM) models for predicting temporal variations in grounding resistance using time series data. This analysis is the first to apply LSTM models to grounding resistance prediction, utilizing experimental data, including soil resistivity and rainfall. The LSTM model is trained, validated, and tested with various parameters, enabling a comparative assessment of its accuracy in capturing grounding resistance variations. Furthermore, the study benchmarks the LSTM model’s performance against traditional Artificial Neural Networks, confirming the LSTM’s superior predictive accuracy regarding time-dependent changes in grounding resistance. The results of the prediction show that LSTM significantly surpasses traditional methods in terms of mean absolute percentage error, with an improvement of 72.73% across various metrics.

BackgroundThe process of aging in Chinese society is accompanied by the concurrent development of the Internet. In recent years, the influence of Internet use on the activities of older adults has attracted growing interest and is now a significant focus of both public health and gerontological research. Nevertheless, there is a need for further empirical research in this area.PurposeThis study aimed to examine the mechanisms and interaction processes, as well as the relationship between Internet use and offline leisure activities among Chinese older adults. Theories of active aging and environmental gerontology guided the construction and assessment of the mediating role of self-perception of aging between Internet use and offline leisure activities. Additionally, the moderating role of community-based leisure places (CBLP) was examined.MethodsA moderated mediation model was constructed using the SPSS 27 PROCESS Macro. This study employs the most recent China Longitudinal Aging Social Survey (CLASS) 2020 cross-sectional data, and the valid sample comprises 8,180 Chinese older adult individuals aged 60 years or older.Results(1) Internet use and offline leisure activities among older adults exhibited a significant positive correlation. (2) Self-perception of aging played a significant positive mediating role between Internet use and offline leisure activities. (3) CBLP significantly and positively moderated the relationship between Internet use and offline leisure activities.ConclusionThe Internet can be an effective tool for addressing the challenges of aging. Active Internet use may lead to more positive age perception and more active offline leisure activities, and efforts should be made to increase the digitization of the aging society. Positive self-perception of aging is an important psychological factor influencing the offline and online activities of older adults. It is imperative that the concept of active aging be vigorously promoted. Concurrently, community infrastructure serves as the foundation for the mutual promotion of online and offline activities. Attention should be given to the development of infrastructure for an age-friendly environment. These findings deepen the understanding of the consequences of interactions between online and offline activities, subjective mindsets, and objective environments for older adults.

Maintaining grassland stock and improving its ecosystem services (ES) are critical yet challenging for ecological and economic sustainability. However, the diversity and spatial heterogeneity of global grasslands pose significant challenges to studying the spatio-temporal coupling characteristics of grassland area and ES changes, especially in the karst desertification control (KDC) regions. This study quantified the grassland area, grassland ES, and the elasticity of grassland ES in response to changes in grassland area within the KDC region of South China. The Moran index was applied to analyze spatio-temporal evolution characteristics, and a quantile regression model was used to explored the segmentation effects of influencing factors. Results showed that: (1) During 2000–2020, despite a 4.36 % decrease in grassland area (399,205 hm2) within the KDC region of South China, the comprehensive index of grassland ES increased from 0.99 to 1.03. Furthermore, counties where the elasticity index of grassland ES exceeded 1 constituted 73.52 %, indicating a general improvement in ES supply capacity. (2) Factors influencing grassland ES in the KDC region demonstrated clear segmentation effects, with the intensity and direction of the same factors varying significantly across different thresholds. The significance of socio-economic factors has been increasing steadily. (3) Within the framework of the UN Decade on Ecosystem Restoration 2021–2030, differentiated ecological engineering measures should be tailored based on the specific constraints of grassland ES in the KDC region. Our research results open a new perspective for the study of the impact mechanism of grassland ES. It can enrich the understanding of grassland ES and offer valuable insights to guide future initiatives for ecosystem restoration and sustainable development in ecologically fragile, particularly karst, areas.

Abstract Background Nocardia, a rare but potentially fatal pathogen, can induce systemic infections with diverse manifestations. This study aimed to investigate the tissue and organ damage caused by Nocardia farcinica (N. farcinica) in mice via different infection routes, evaluate the resulting host immune responses, and assess its invasiveness in brain tissue. Methods BALB/c mice were infected with N. farcinica through intranasal, intraperitoneal, and intravenous routes (doses: 1 × 10^8, 1 × 10^7, 1 × 10^7 CFU in 50 µl PBS). Over a 7-day period, body temperature, weight, and mortality were monitored, and samples were collected for histopathological analysis and bacterial load assessment. Serum was isolated for cytokine detection via ELISA. For RNA-seq analysis, mice were infected with 1 × 107 CFU through three infection routes, after which brain tissue was harvested. Results Intraperitoneal and intravenous N. farcinica infections caused significant clinical symptoms, mortality, and neural disruption in mice, resulting in severe systemic infection. Conversely, intranasal infection primarily affected the lungs without causing significant damage to other organs. Intraperitoneal and intravenous infections significantly increased serum cytokines, particularly TNF-α and IFN-γ. RNA-seq analysis of brains from intravenously infected mice revealed significant differential gene expression, whereas the intranasal and intraperitoneal routes showed limited differences (only three genes). The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the intravenous group were primarily related to immune processes. Conclusion The study demonstrated that intravenous N. farcinica infection induces significant clinical symptoms, triggers an inflammatory response, damages multiple organs, and leads to systemic infections.

Abstract Background Effective response and reducing the burden of family care for children with cancer is critical, and China currently lacks a specific assessment tool. Aims This study aimed to translate and validate the Caregiving Burden Scale for Family Caregivers of Children with Cancer (CBSFC-CC) and then test and implement the tool. Methods According to the Beaton cross-cultural debugging guide, preliminary Chinese version of CBSFC-CC scale was formed, which was suitable for Chinese language environment and clinical context. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were performed to verify structural validity. Convergent validity, discriminant validity and reliability were also conducted. Results A total of 529 family caregivers of children with cancer participated in the survey. EFA extracts and combines four factors and explained 65.80% of the total variation. CFA proved that all the goodness-of-fit indicators were acceptable. The Cronbach’s alpha of the Chinese version of CBSFC-CC was .96, and the test–retest reliability coefficient was .95. Four dimensions and 29 items were identified in the final Chinese version of CBSFC-CC. Conclusion The chinese version CBSFC-CC is scientifically reasonable and has good reliability and validity, which can be applied to the investigation of the nursing burden of family caregivers of children with cancer in China.