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Neuroinflammation, characterized by microglial activation and the subsequent secretion of inflammatory cytokines, plays a pivotal role in neurodegenerative diseases and brain injuries, often leading to neuronal damage and death. Alleviating neuroinflammation has thus emerged as a promising strategy to protect neurons and ameliorate neurodegenerative disorders. While peroxisome proliferator-activated receptor gamma (PPARγ) agonists have demonstrated potential therapeutic actions on neuroinflammation, their prolonged use, such as with rosiglitazone, can lead to cardiac risks and lipid differentiation disorders. In this study, we investigated the effects of a newly synthesized PPARγ agonist, VSP-2, on secretion of inflammatory cytokines in BV2 cells. Treatment with VSP-2 significantly reduced the mRNA and protein levels of proinflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Furthermore, VSP-2 attenuated the phosphorylation of nuclear factor kappa B (NF-κB) (65 kD) and IκBα, as well as the nuclear translocation of NF-κB (65 kD). Additionally, the use of PPARγ small interfering RNA was able to attenuate the effects of VSP-2 on proinflammatory cytokines and the NF-κB pathway. In conclusion, our findings suggest that VSP-2 effectively suppressed the expressions of IL-1β, IL-6, and TNF-α via the PPARγ/NF-κB signaling pathway. Given its potential therapeutic benefits, VSP-2 may emerge as a promising candidate for the treatment of neurodegenerative diseases or brain injuries associated with neuroinflammation.

Background: In 2022, our team launched the pioneering national proficiency testing (PT) scheme for the pathological diagnosis of breast cancer, rapidly establishing its credibility throughout China. Aiming to continuously monitor and improve the proficiency of Chinese pathologists in breast pathology, the second round of the PT scheme was initiated in 2023, which will expand the number of participating institutions, and will conduct a nationwide investigation into the interpretation of HER2 0, 1+, and 2+/FISH- categories in China. Methods: The methodology employed in the current round of PT scheme closely mirrors that of the preceding cycle in 2022, which is designed and implemented according to the "Conformity assessment—General requirements for proficiency testing"(GB/T27043—2012/ISO/IEC 17043:2010). More importantly, we utilized a statistics-based method to generate assigned values to enhance their robustness and credibility. Results: The final PT results, published on the website of the National Quality Control Center for Cancer (http://117.133.40.88:3927), showed that all participants passed the testing. However, a few institutions demonstrated systemic biases in scoring HER2 0, 1+, and 2+/FISH- with accuracy levels below 59%, considered unsatisfactory. Especially, the concordance rate for HER2 0 cases was only 78.1%, indicating challenges in distinguishing HER2 0 from low HER2 expression. Meanwhile, areas for histologic type and grade interpretation improvement were also noted. Conclusions: Our PT scheme demonstrated high proficiency in diagnosing breast cancer in China. But it also identified systemic biases in scoring HER2 0, 1+, and 2+/FISH- at some institutions. More importantly, our study highlighted challenges in the evaluation at the extreme lower end of the HER2 staining spectrum, a crucial area for further research. Meanwhile, it also revealed the need for improvements in interpreting histologic types and grades. These findings strengthened the importance of robust quality assurance mechanisms, like the nationwide PT scheme conducted in this study, to maintain high diagnostic standards and identify areas requiring further training and enhancement. [ABSTRACT FROM AUTHOR]

Objective: The early identification and diagnosis of transplant-associated thrombotic microangiopathy (TA-TMA) are essential yet difficult in patients underwent hematopoietic stem cell transplantation (HSCT). To develop an evidence-based, nurse-leading early warning model for TA-TMA, and implement the healthcare quality review and improvement project. Methods: This study was a mixed-methods, before-and-after study. The early warning model was developed based on quality evidence from literature search. The healthcare quality review and improvement project mainly included baseline investigation of nurse, improvement action and effectiveness evaluation. The awareness and knowledge of early parameter of TA-TMA among nurses and the prognosis of patients underwent HSCT were compared before and after the improvement. Results: A total of 1 guideline, 1 evidence synthesis, 4 expert consensuses, 10 literature reviews, 2 diagnostic studies, and 9 case series were included in the best evidence. The early warning model including warning period, high-risk characteristics and early manifestation of TA-TMA was developed. The improvement action, including staff training and assessment, suspected TA-TMA identification and patient education, was implemented. The awareness and knowledge rate of early parameter of TA-TMA among nurses significantly improved after improvement action (100% vs. 26.7%, P < 0.001). The incidence of TA-TMA was similar among patients underwent HSCT before and after improvement action (2.8% vs. 1.2%, P = 0.643), while no fall event occurred after improvement action (0 vs. 1.2%, P < 0.001). Conclusion: The evidence-based early warning model and healthcare quality improvement project could enhance the awareness and knowledge of TA-TMA among healthcare providers and might improve the prognosis of patients diagnosed with TA-TMA. [ABSTRACT FROM AUTHOR]

In this study, we synthesized Fe3O4 nanoparticles (Fe3O4 NPs) of varying sizes and morphologies using the solvothermal method and incorporated them as additives into carbonyl iron magnetorheological fluids (CI-MRFs). We tested the shear stress, yield stress, viscosity and storage modulus of the MRFs using a magnetorheometer to investigate how the size and morphology of Fe3O4 NPs influence the performance of MRFs. Our results indicate that the size of the additive nanoparticles significantly enhances the MR properties of MRFs more than their morphological attributes. This enhancement results from optimizing and stabilizing the CI magnetic chain structure of the nanoparticles in the presence of a magnetic field. Specifically, MRFs with Fe3O4 NPs averaging 250 nm in size exhibit higher yield stress and storage modulus and show increased resistance to shear strains. Although the nanoparticle morphology has a modest effect on the rheological properties of MRFs, hexahedral and octahedral particles can enhance rheological properties through increased internal friction compared to spherical particles. Additionally, Fe3O4 NPs of different sizes and morphologies improve the sedimentation stability of MRFs, with those around 250 nm being particularly effective at slowing down sedimentation. Both hexahedral and octahedral Fe3O4 NPs slow down sedimentation more effectively than spherical Fe3O4 NPs. This paper investigates the rheological properties of CI-MRFs by controlling the additive particle size and morphological features, providing a research foundation for the design and optimization of MRFs. [ABSTRACT FROM AUTHOR]

Four-wheel independently driven electric vehicles (FWID-EV) endow a flexible and scalable control framework to improve vehicle performance. This paper integrates the torque vectoring and active suspension system (ASS) to enhance the vehicle's longitudinal and vertical motion control performance. While the nonlinear characteristic of the tire model leads to a relatively heavier computational burden. To facilitate the controller design and ease the load, a half-vehicle dynamics system is built and simplified to the linear-time-varying (LTV) model. Then a model predictive controller is developed by formulating the objective function by comprehensively considering the safety, energy-saving and comfort requirements. The in-wheel motor efficiency and the power loss of tire slip are treated as optimization indices in this work to reduce energy consumption. Finally, the effectiveness of the proposed controller is verified through the rapid-control-prototype (RCP) test. The results demonstrate the enhancement of the energy-saving as well as comfort on the basis of vehicle stability. [ABSTRACT FROM AUTHOR]

Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single‐cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA‐seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high‐throughput and high‐sensitivity method called snHH‐seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full‐length RNA‐seq data is also established. snHH‐seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan‐cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full‐length RNA at the single‐nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology. [ABSTRACT FROM AUTHOR]

Objective To investigate the levels and clinical significance of serum microRNA (miR)-651 and miR-630 in patients with cervical cancer. Methods From June 2017 to May 2020, 108 cervical cancer patients accepted by our hospital were collected as the cervical cancer group. Meantime, 100 cervical intraepithelial neoplasia (CIN) patients treated in our hospital were regarded as the CIN group, and 110 healthy individuals who underwent physical examination were regarded as the control group. Real-time fluorescence quantitative PCR (qRT-PCR) was applied to detect serum levels of miR-651 and miR-630, while analyzing the relationship between serum miR-651 and miR-630 as well as clinical features and prognosis of patients. Results The serum levels of miR-651 and miR-630 in the cervical cancer group and CIN group were obviously lower than those in the control group (P<0.05), while the serum levels of miR-651 and miR-630 in the cervical cancer group were obviously lower than those in the CIN group (P < 0.05). The expression levels of serum miR-651 and miR-630 were positively correlated (r = 0.542, P < 0.05). The serum levels of miR-651 and miR-630 were related to HPV infection, differentiation, lymph node metastasis, and FIGO staging (P < 0.05). The overall survival rate of patients with low levels of miR-651 and miR-630 was lower than that of patients with high levels. Cox regression analysis showed that, HPV infection, degree of differentiation, lymph node metastasis, FIGO staging, miR-651, and miR-630 were all influencing factors for the prognosis of cervical cancer patients (P < 0.05). Conclusion The serum levels of miR-651 and miR-630 in cervical cancer patients decrease, which are related to HPV infection, differentiation, lymph node metastasis, FIGO staging, and prognosis. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoimmunotherapy has a promising effect on locally advanced esophageal squamous cell carcinoma (ESCC). However, reliable biomarkers robustly predicting therapeutic response are still lacking., Methods: Formalin-fixed and paraffin-embedded pre-neoadjuvant chemoimmunotherapy biopsy samples from locally advanced ESCC patients were collected. Cohort 1 composed of 66 locally advanced ESCC patients from a prospective clinical trial (NCT04506138) received two cycles of camrelizumab in combination with nab-paclitaxel and carboplatin every 3 weeks. Cohort 2 included 48 patients receiving various types of immune checkpoint inhibitors with (nab-)paclitaxel and platinum-based chemotherapy as neoadjuvant therapy. Cohort 3 consisted of 27 ESCC patients receiving neoadjuvant treatment of toripalimab with chemotherapy and was used as the external validation dataset. Targeted RNA sequencing, immunohistochemistry for programmed death ligand 1 (PD-L1), and multiplex immunofluorescence (mIF) imaging were performed., Results: Integration of targeted RNA sequencing, PD-L1 immunohistochemistry, and mIF revealed a significant immune-suppressive microenvironment with higher neutrophil infiltration, enriched TGF-β, and cell cycle pathways in non-pathological complete response (non-pCR) patients. NK, activated CD4 + T cell infiltration, interferon-gamma, antigen processing and presentation, and other immune response signatures were significantly associated with pCR. Based on discovered tumor microenvironmental characteristics and their closely related genes were screened. Consequently, a seven-gene neoadjuvant chemoimmunotherapy risk prediction signature (NCIRPs) model, was constructed. In addition to cohort 1, this model alone or with PD-L1-combined positive score (CPS) demonstrated a higher prediction accuracy of pathological response than PD-L1 CPS or other routinely used immune signatures, such as IFN-γ, in cohorts 2 and 3. Neither prognostic association nor correlation with response to chemoradiotherapy was observed in The Cancer Genome Atlas Program ESCC dataset or in ESCC patients in the neoadjuvant chemoradiotherapy cohort (cohort 4)., Conclusion: The NCIRPs model that was developed and validated using treatment-naïve endoscopic samples from the largest ESCC neoadjuvant chemoimmunotherapy dataset represents a robust and clinically meaningful approach to select a putative responder for neoadjuvant chemoimmunotherapy in locally advanced ESCC patients., Competing Interests: Competing interests: CZ, QL, and XZ were employed by Amoy Diagnostics Co., Ltd. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)