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Haopeng Wang,1,* Hua Zhao,1,* Zheng Chen,1,* Xiaomin Cai,1 Xuhui Wang,1 Ping Zhou,1 Yinda Tang,1 Tingting Ying,1 Xin Zhang,1 Yiman Shen,1 Baimiao Wang,1 Wanchun Zhu,1 Jin Zhu,1 Xinjun Wang,2 Shiting Li1 1Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, 200092, People’s Republic of China; 2Department of Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shiting Li, Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, 200092, People’s Republic of China, Email lishiting@xinhuamed.com.cn Xinjun Wang, Department of Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China, Email wangxj@zzu.edu.cnBackground: Facial nerves have the potential for regeneration following injury, but this process is often challenging and slow. Schwann cells (SCs) are pivotal in this process. Bone mesenchymal stem cells (BMSC)-derived exosomes promote tissue repair through paracrine action, with hypoxic preconditioning enhancing their effects. The main purpose of this study was to determine whether hypoxia-preconditioned BMSC-derived exosomes (Hypo-Exos) exhibit a greater therapeutic effect on facial nerve repair/regeneration and reveal the mechanism.Methods: CCK-8, EdU, Transwell, and ELISA assays were used to evaluate the functions of Hypo-Exos in SCs. Histological analysis and Vibrissae Movements (VMs) recovery were used to evaluate the therapeutic effects of Hypo-Exos in rat model. circRNA array was used to identify the significantly differentially expressed exosomal circRNAs between normoxia-preconditioned BMSC-derived exosomes (Nor-Exos) and Hypo-Exos. miRDB, TargetScan, double luciferase assay, qRT-PCR and WB were used to predict and identify potential exosomal cirRNA_Nkd2-complementary miRNAs and its target gene. The function of exosomal circRNA_Nkd2 in facial nerve repair/regeneration was evaluated by cell and animal experiments.Results: This study confirmed that Hypo-Exos more effectively promote SCs proliferation, migration, and paracrine function, accelerating facial nerve repair following facial nerve injury (FNI) compared with Nor-Exos. Furthermore, circRNA analysis identified significant enrichment of circRNA_Nkd2 in Hypo-Exos compared with Nor-Exos. Exosomal circRNA_Nkd2 positively regulates mediator complex subunit 19 (MED19) expression by sponging rno-miR-214-3p.Conclusion: Our results demonstrated a mechanism by which Hypo-Exos enhanced SCs proliferation, migration, and paracrine function and facial nerve repair and regeneration following FNI through the circRNA_Nkd2/miR-214-3p/Med19 axis. Hypoxic preconditioning is an effective and promising method for optimizing the therapeutic action of BMSC-derived exosomes in FNI. Keywords: hypoxic, BMSCs, exosomes, Schwann cells, facial nerve injury

The present work aims to research the treatment processing of magnesium reinforced with 1 μmsilicon carbide particle (SiCp) using stir casting combined by ultrasonic vibration. Present studies have been done on six different materials: (a) AZ31B alloy without particles, (b) 5 vol.% SiCp/AZ31B composites fabricated with different semi-solid stirring time (5 min, 10 min, 15 min and 20 min), (c) composite with 20 vol.% SiCp. The effects of 1 μm/SiCp pretreatment and stirring time on microstructure and interfacial wettability as well as mechanical properties of the materials were confirmed. Both short and long stirring time for the particle dispersion brought particle agglomeration. Results of SEM microstructure and tensile properties exhibited that the optimal stirring parameters of 625 °C/1500 rpm/15 min are exploited, and 20 vol.% SiCp/AZ31B composite was fabricated by the optimal stirring parameters. The application of optimal stirring parameters for the treatment resulted in homogeneous particle distribution. The addition of SiCp leads to a reduced matrix grain, and 20 vol.% SiCp/AZ31B composite showed smaller grain size than. 5 vol.% SiCp/AZ31B composite. The interface between SiCp and matrix is clear and interfacial wettability well. Tensile test results show that with increasing SiCp content, strengths increase while ductility decreases.

Pneumatic muscle actuators are newly developed actuators in rotational, non-aligned and specified applications. In this paper, pneumatic muscle actuators are used to set up a two-dimensional pneumatic arm to simulate the excavator's motion. Fuzzy control algorithms are typically applied in pneumatic control systems owing to their non-linearity and ill-defined mathematical models. Two fuzzy controllers, which include the sliding mode fuzzy controller and self-organizing fuzzy controller, are comparatively implemented in this 2D pneumatic arm control system. The present paper provides the comparisons of trajectory tracking performances and adaptations of these two fuzzy controllers via a variety of trajectory tracking experiments.

The 44-item Big Five Personality Inventory (BFI-44) helps in simplify a wide range of complex personality features, including how personality affects breastfeeding. The aim of this study was to examine the reliability of the Malay version of the BFI-44. A cross-sectional study was conducted using the convenience sampling of female respondents. A total of 96 female public university students participated in this study. Cronbach's alpha, intraclass correlation coefficient, limit of agreement, and standard error of measurement (SEM) were used in determining the reliability of the questionnaire. Cronbach's alpha value for Extraversion subscale obtained the highest internal consistency (0.723) and the lowest internal consistency was obtained in the subscale of Openness to Experience (0.543). The intraclass correlation coefficient (ICC) value for all dimensions exceeded 0.70 (ICC= 0.792- 0.883). The Bland-Altman plots showed high reliability in all dimensions except Neuroticism. For SEM, Extraversion scored the lowest (0.773) while Neuroticism scored the highest (1.199). Overall, the BFI-44 in Malay version had moderate to good internal consistency and high test-retest reliability. These findings may give positive implications for the implementation of the questionnaire in future evaluation of Malaysians' personality traits. [ABSTRACT FROM AUTHOR]

Background: Acting as mediators in cell-matrix and cell-cell communication, matricellular proteins play a crucial role in cancer progression. Thrombospondins (TSPs), a type of matricellular glycoproteins, are key regulators in cancer biology with multifaceted roles. Although TSPs have been implicated in anti-tumor immunity and epithelial-mesenchymal transition (EMT) in several malignancies, their specific roles to colon cancer remain elusive. Addressing this knowledge gap is essential, as understanding the function of TSPs in colon cancer could identify new therapeutic targets and prognostic markers. Methods: Analyzing 1981 samples from 10 high-throughput datasets, including six bulk RNA-seq, three scRNA-seq, and one spatial transcriptome dataset, our study investigated the prognostic relevance, risk stratification value, immune heterogeneity, and cellular origin of TSPs, as well as their influence on cancer-associated fibroblasts (CAFs). Utilizing survival analysis, unsupervised clustering, and functional enrichment, along with multiple correlation analyses of the tumor-microenvironment (TME) via Gene Set Variation Analysis (GSVA), spatial localization, Monocle2, and CellPhoneDB, we provided insights into the clinical and cellular implications of TSPs. Results: First, we observed significant upregulation of THBS2 and COMP in colon cancer, both of which displayed significant prognostic value. Additionally, we detected a significant positive correlation between TSPs and immune cells, as well as marker genes of EMT. Second, based on TSPs expression, patients were divided into two clusters with distinct prognoses: the high TSPs expression group (TSPs-H) was characterized by pronounced immune and stromal cell infiltration, and notably elevated T-cell exhaustion scores. Subsequently, we found that THBS2 and COMP may be associated with the differentiation of CAFs into pan-iCAFs and pan-dCAFs, which are known for their heightened matrix remodeling activities. Moreover, THBS2 enhanced CAFs communication with vascular endothelial cells and monocyte-macrophages. CAFs expressing THBS2 (THBS2+ CAFs) demonstrated higher scores across multiple signaling pathways, including angiogenic, EMT, Hedgehog, Notch, Wnt, and TGF-β, when compared to THBS2- CAFs. These observations suggest that THBS2 may be associated with stronger pro-carcinogenic activity in CAFs. Conclusions: This study revealed the crucial role of TSPs and the significant correlation between THBS2 and CAFs interactions in colon cancer progression, providing valuable insights for targeting TSPs to mitigate cancer progression.

Abstract From social and economic perspectives, compositional data represent the proportions of various components within a whole, carrying non-negative values and providing only relative information. However, in many circumstances, there are often a significant number of missing values in datasets. Due to the complexity caused by these missing values, traditional estimation methods are ineffective. In this paper, an adaptive group LASSO-based imputation method is proposed for compositional data, consolidating the advantages of group LASSO and adaptive LASSO analysis techniques. Considering the impact of outliers on the accuracy of estimation, both simulation and case analysis are conducted to compare the proposed algorithm against four existing methods. The experimental results demonstrate that the proposed adaptive group LASSO method produces a better imputation performance at comparable missing rates.

Abstract Background Lung adenocarcinoma (LUAD) is one of the most common malignant tumors. Although several treatments have been proposed, the long-term prognosis of this cancer is poor. Lipid droplets and mitochondria are important organelles that regulate energy metabolism in cells and are postulated to promote the occurrence and progression of tumors. However, few risk prediction models have been constructed based on lipid drop-mitochondria-related genes (LMRGs). Methods In this study, we constructed a lipid drop-mitochondrial (LD-M) risk score model based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Biological functions and clinical benefits associated with the various risk scores were analyzed using R software, GraphPad Prism 9, and the online database system. Results An LD-M risk score model comprising ABLIM3, AK4, CAV2, CPS1, CYP24A1, DLGAP5, FGR, and SH3BP5, was developed and its predictive power was validated. The risk score was closely associated with the cell cycle. Immunophenoscore (IPS) and Tumor immune dysfunction and exclusion (TIDE) results demonstrated that the low-risk group was more sensitive to immunotherapy. Drug sensitivity analysis indicated that BMS-754807, ZM447439, SB216763, and other drugs had lower IC50 values in the low-risk group. Conclusion Our results suggest that the LD-M risk score is an effective prognostic indicator for individualized treatment of LUAD.

Abstract Background Uveal melanoma (UM) is a rare and deadly eye cancer with high metastatic potential. Despite the predominance of malignant cells within the tumor microenvironment, the heterogeneity and underlying molecular features remain to be fully characterized. Methods We analyzed single-cell transcriptomic profiling of 37,660 malignant cells from 17 UM tumors. A consensus non-negative factorization algorithm was used to decipher transcriptional programs underlying tumor cell-intrinsic heterogeneity. Tumor-infiltrated immune cells were computationally estimated from bulk transcriptomes and bioinformatics methods. A gene signature was derived for subtyping and prognostic stratification and validated in multicenter cohorts. Results ScRNA-seq analysis revealed the existence of diverse subpopulations and transcriptional variability among malignant cells within and between tumors. Furthermore, we observed that the heterogeneity of malignant cell states and compositions correlated with genomic, immunological, and clinical characteristics. By identifying gene expression programs associated with malignant cell heterogeneity at the single cell level, UM samples were classified into two distinct intra-tumoral subtypes (ITMHlo and ITMHhi) with different prognoses and immune microenvironments. Finally, a machine learning-derived 9-gene signature was developed to translate single-cell information into bulk tissue transcriptomes for patient stratification and was validated in multicenter cohorts. Conclusions Our study provides insight into understanding the intra-tumoral heterogeneity of UM and its potential impact on patient stratification.

C-myc is a proto-oncogene that plays an important role in a variety of diseases. There were a lot of research on the correlation between C-myc and human viruses. However, the study about C-myc related to aquatic species virus is very limited. In the present study, the qRT-PCR, cellular immunofluorescence and western blotting determination data reported that C-myc and glutaminase (GLS) genes were significantly upregulated when grouper fin cells (GF-1) were infected with red grouper nervous necrosis virus (RGNNV). After knocking down the C-myc gene, the mRNA and protein levels of GLS, capsid protein (CP) and RNA polymerase (RdRp) of RGNNV were significantly reduced in RGNNV-infected GF-1 cells and the overexpression of the C-myc gene remarkably promoted these genes, which indicated that the replication of the virus and GLS gene were positively regulated by C-myc in RGNNV-infected GF-1 cells. In addition, supplementation of exogenous ATP can partially restore viral replication when RGNNV-infected GF-1 cells were cultured in glutamine-free medium, which confirmed that the glutamine was decomposed into ATP to provide energy for viral replication. Further studies confirmed that overexpression of C-myc can increase the content of ATP in normal cells. To sum up, these data suggested that activation of C-myc gene affected viral replication by regulating GLS expression to drive glutamine dissolution.

Periodontitis is an inflammatory disease caused by bacterial biofilms, which leads to the destruction of periodontal tissue. Current treatments, such as mechanical cleaning and antibiotics, struggle to effectively address the persistent biofilms, inflammation, and tissue damage. A new approach involves developing a Janus nanomotor (J-CeM@Au) by coating cerium dioxide-doped mesoporous silica (CeM) with gold nanoparticles (AuNPs). This nanomotor exhibits thermophoretic motion when exposed to near-infrared (NIR) laser light due to the temperature gradient produced by the photothermal effects of asymmetrically distributed AuNPs. The NIR laser provides the energy for propulsion and activates the nanomotor's antibacterial properties, allowing it to penetrate biofilms and kill bacteria. Additionally, the nanomotor's ability to scavenge reactive oxygen species (ROS) can modulate the immune response and create a regenerative environment, promoting the healing of periodontal tissue. Overall, this multifunctional nanomotor offers a promising new approach for treating periodontitis by simultaneously addressing biofilm management and immune modulation with autonomous movement.

Abstract Background Balance dysfunction affects 70% of stroke patients. Emerging neurophysiological approaches, such as virtual reality therapy (VRT) and repetitive transcranial magnetic stimulation (rTMS), have been proven by clinical studies that the balance function of stroke patients can be improved when applied alone, but there are relatively few studies on the combined treatment of balance dysfunction after stroke. This study aimed to evaluate the impact of a 4-week intensive intervention combining VRT and rTMS on both balance function and brain plasticity among stroke patients. Methods This single-blind, randomized controlled trial was conducted at the Rehabilitation Medical Center of the Rehabilitation General Hospital of Ningxia Medical University. A cohort of 136 stroke patients, with durations of 2 to 24 weeks post-stroke, were enrolled in the study. Participants were randomly allocated in a 1:1:1:1 ratio to four groups: the VR group (n = 34), the rTMS group (n = 34), the combined treatment group receiving both VR and rTMS (n = 34), and the control group undergoing traditional balance training (n = 34). All patients underwent a standardized inpatient rehabilitation program over 4 weeks. The VR group received daily 30-min sessions of VR therapy for 20 days. The rTMS group underwent daily sessions of rTMS stimulation for 20 min, targeting the motor imagery region in the affected hemisphere. The combination group received VR therapy after completing their rTMS treatment. The control group received conventional balance training, with each session lasting 30 min. Additionally, all patients received an extra 60 min of standard rehabilitation therapy twice daily. Assessments were conducted at baseline, 2 weeks, and 4 weeks post-treatment, using the Berg Balance Scale (BBS) as the primary measure, and secondary measures including the Timed Up-and-Go Test (TUGT), Fugl-Meyer Assessment-Lower Extremity (FMA-LE), and 6-m walking test (6MWT), as well as assessments for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VGEF), tyrosine receptor kinase (TrκB), motor-evoked potential latency (PL), central motor conduction time (CMCT), and amplitude. Discussion The widespread application of VR technology and rTMS in clinical settings is well-established. However, the potential synergistic effects of combining these modalities on balance function and neuroplasticity in stroke patients remain uncertain. Our hypothesis suggests that the integration of VR with rTMS may result in more pronounced improvements in both balance function and neuroplasticity among stroke patients, surpassing the outcomes achievable with VR alone, rTMS alone, or traditional therapy. The possible mechanism is that VR-based training combined with rTMS plays a superimposed effect, promoting better repair of damaged neurons and ultimately improving balance function in stroke patients. The positive results anticipated from this trial could provide objective evidence advocating for the concurrent use of VR and rTMS in clinical interventions. Trial registration The study protocol underwent review and approval by the Medical Research Ethics Committee of the General Hospital of Ningxia Medical University on January 26, 2024 (No. KYLL-2024–0162). Subsequently, it was registered in the Chinese Clinical Trial Registry on March 11, 2024 (registration number: ChiCTR2400081775). Currently, the study is still ongoing.

Abstract Vector beams have attracted widespread attention because of their unique optical properties; in particular, their combination with tight focusing can produce many interesting phenomena. The rise of 3D printing technology provides more possibilities for exploration. In this work, a cascading method involving a metamaterial and a metalens is used to generate a tightly focused field of vector beams in the terahertz band, which is prepared via 3D printing. As a proof-of-concept demonstration, a series of metamaterial modules capable of generating states of different orbital angular momentum are proposed by cascading with a metalens. The experimental results are in good agreement with the simulation results, fully verifying the feasibility of the scheme. The proposed design and fabrication strategy provides a new idea for the tight focusing of terahertz vector beams.

Abstract Background Knee osteoarthritis (KOA) was characterized by pain and limited joint function, which seriously affected the quality of life of patients. The vast majority of KOA was closely related to degeneration of the patellofemoral joint and abnormal patellar movement trajectory. Tissue-bone homeostasis manipulation (TBHM) could correct abnormal patellar movement trajectory on the basis of loosening soft tissue. However, there was little strong evidence to verify its efficacy on the patients with KOA. The study objective was to explore the efficacy of the TBHM on gait and knee function in the patients with KOA. Methods Sixty KOA patients were randomly assigned to either the joint mobilization (n = 30) or TBHM (n = 30) group. The joint mobilization group received joint mobilization, while the TBHM group received TBHM. For two groups, the patients participated in 30 min rehabilitation sessions thrice per week for 12 weeks. The primary outcome was biomechanical gait outcomes during walking, including step length, step velocity, double support, knee range of motion (ROM), and knee adduction moment (KAM). The secondary outcomes were the Western Ontario and McMaster Index (WOMAC) and 36-Item short- form health survey (SF-36), which reflected improvements in knee function and quality of life, respectively. At baseline and 12 weeks, evaluations were conducted and compared between groups. Results After a 12-week intervention, significant group differences were observed in KAM (p = 0.018), WOMAC-Pain (p = 0.043) and WOMAC-Stiffness (p = 0.026). A noteworthy finding was the presence of a significant interaction effect between group and time specifically observed in step velocity during gait (p = 0.046), WOMAC-Function (p = 0.013) and SF-36 (p = 0.027). Further analysis revealed a significant difference in step velocity (p = 0.034), WOMAC-Function (p = 0.025) and SF-36 (p = 0.042) during post-assessment between the two groups. Moreover, a significant time effect was observed across all outcomes of the two groups (p

Abstract Influenza viruses cause substantial morbidity and mortality every year despite seasonal vaccination. mRNA-based vaccines have the potential to elicit more protective immune responses, but for maximal breadth and durability, it is desirable to deliver both the viral hemagglutinin and neuraminidase glycoproteins. Delivering multiple antigens individually, however, complicates manufacturing and increases cost, thus it would be beneficial to express both proteins from a single mRNA. Here, we develop an mRNA genetic configuration that allows the simultaneous expression of unmodified, full-length NA and HA proteins from a single open reading frame. We apply this approach to glycoproteins from contemporary influenza A and B viruses and, after vaccination, observe high levels of functional antibodies and protection from disease in female mouse and male ferret challenge models. This approach may further efforts to utilize mRNA technology to improve seasonal vaccine efficacy by efficiently delivering multiple viral antigens simultaneously and in their native state.