Accuracy of cone-beam breast computed tomography for assessing breast cancer tumor size-comparison with breast magnetic resonance imaging.

Background: Accurate preoperative assessment of tumor size is important in developing a surgical plan for breast cancer. The purpose of this study was to evaluate the accuracy of cone-beam breast computed tomography (CBBCT) and magnetic resonance imaging (MRI) in the assessment of tumor size and to analyze the factors influencing the discordance. Methods: In this retrospective study, patients with breast cancer who underwent preoperative contrast-enhanced CBBCT (CE-CBBCT) and dynamic contrast-enhanced MRI (DCE-MRI) and received a complete pathologic diagnosis from August 2020 to December 2021 were included, using the pathological result as the gold standard. Two radiologists assessed the CBBCT and MRI features and measured the tumor size with a 2-week washout period. Intraclass correlation coefficient (ICC) and Bland-Altman analyses were used to assess inter-observer reproducibility and agreement based on CBBCT, MRI and pathology. Univariate analyses of differences in clinical, pathological and CBBCT/MRI features between the concordant and discordant groups was performed using the t-test, Mann-Whitney U-test, Chi-squared test and Fisher's exact test. Multivariate analyses were used to identify factors associated with discordance of CBBCT/MRI with pathology. Results: A total of 115 female breast cancer patients (115 lesions) were included. All patients had a single malignant tumor of the unilateral breast. The reproducibility and the agreement ranged from moderate to excellent (ICC =0.607-0.983). Receiver operating characteristic (ROC) analyses showed that the cut-off values of CBBCT-pathology and MRI-pathology discordance were 2.25 and 2.65 cm, respectively. CBBCT/MRI-pathology concordance was significantly associated with the extent of pathology, lesion type, presence of calcification, human epidermal growth factor receptor 2 (HER2) status and fatty infiltration (P<0.05). In lesions containing calcification, the difference of CBBCT-pathology was significantly smaller than MRI-pathology (P=0.021). Non-mass enhancement (NME) was the main predictor of CBBCT- or MRI-pathology discordance [odds ratio (OR) =3.293-6.469, P<0.05], and HER2 positivity was a predictor of CBBCT-pathology discordance (OR =3.514, P=0.019). Conclusions: CBBCT and MRI have comparable accuracy in measurement of tumor size, and CBBCT is advantageous in assessing the size of calcified lesions. NME and HER2 positivity are significant predictors of CBBCT-pathology discordance. This suggests that CBBCT might serve as an alternative imaging technique to assess tumor size when patients do not tolerate MRI.

New anti-inflammatory limonoids from the fruits of Melia azedarach.

The phytochemical study of the fruits of Melia azedarach (Meliaceae) led to the isolation and characterisation of two novel natural limonoids1-deoxy- 3, 20-dicinnamoyl-11-methoxy-meliacarpinin (1) and 12ß- O- methyl nimbolinin A (2), along with twelve known limonoids. Its structure was identified by 1D- and 2D-NMR, HR-ESI-MS and comparison with published data. The anti-inflammatory effect of the compounds was measured in vitro in RAW 264.7 cells by evaluating the production of NO stimulated by LPS. Compounds 1, 8 and 14 indicated significant anti-inflammatory effect with inhibition rate of 11.76, 8.45 and 6.59 µM, respectively. Limonoid 1 significantly inhibited the production of NO, TNF-α and IL-1ß in RAW 264.7 cells. Therefore, limonoid derivative may be a promising source of bioactive metabolite for inflammatory diseases.

Populus euphratica has stronger regrowth ability than Populus pruinosa under salinity stress.

Pest infestation and soil salinization levels are increasing due to climate change. Comprehending plant regrowth after insect damage and salinity stress is crucial to understanding climate change's multifactorial impacts on forest ecosystems. This study examined Populus euphratica and P. pruinosa regrowth after different defoliation levels combined with salinity stress. Specifically, the biomass and regrowth ability, non-structural carbohydrate (NSC) and nitrogen (N) pools in different organs and the whole plant, and the leaf Cl- concentration of both poplars were analyzed. Our results showed that after 50% defoliation and no salt addition, the regrowth of both species recovered similarly to the control level, while their regrowth was about 70% after 90% defoliation. However, under salinity stress, the regrowth (% leaf biomass) of P. euphratica was significantly higher than P. pruinose at either the 50% or 90% defoliation levels. Additionally, P. euphratica had more soluble sugar, starch, NSC and N pools in leaf, stem, root and whole plant than P. pruinose under salinity stress. The regrowth based on leaf biomass increased linearly with soluble sugar, starch, NSC and N pools, and decreased linearly with leaf Cl- concentration across different salinity and defoliation levels. These results indicated that defoliation significantly decreased NSC and N pools, limiting the growth of both poplars, and salinity stress exacerbated the negative effect. Furthermore, when suffering from salinity stress, P. euphratica with higher NSC and N pools exhibited stronger regrowth ability than P. pruinose.

Synthesis and Evaluation of [64Cu]Cu-NOTA-HFn for PET Imaging of Transferrin Receptor 1 Expression in Nasopharyngeal Carcinoma.

As recurrent and metastatic nasopharyngeal carcinoma (NPC) is the most common cause of death among patients with NPC, there is an urgent clinical need for the development of precision diagnosis to guide personalized treatment. Recent emerging evidence substantiates the increased expression of transferrin receptor 1 (also known as cluster of differentiation 71, CD71) within tumor tissues and the inherent targeting capability of natural heavy-chain ferritin (HFn) toward CD71. This study aimed to synthesize and assess a radiotracer ([64Cu]Cu-NOTA-HFn) designed to target CD71 for positron emission tomography (PET) imaging in an NPC tumor-bearing mouse model. The entire radiolabeling process of [64Cu]Cu-NOTA-HFn was completed within 15 min with high yield (>98.5%) and high molar activity (72.96 ± 21.33 GBq/µmol). The in vitro solubility and stability experiments indicated that [64Cu]Cu-NOTA-HFn had a high water solubility (log P = -2.42 ± 0.52, n = 6) and good stability in phosphate-buffered saline (PBS) for up to 48 h. The cell saturation binding assay indicated that [64Cu]Cu-NOTA-HFn had a nanomolar affinity (Kd = 10.9 ± 6.1 nM) for CD71-overexpressing C666-1 cells. To test the target engagement in vivo, prolonged-time PET imaging was performed at 1, 6, 12, 24, and 36 h postinjection (p.i.) of [64Cu]Cu-NOTA-HFn to C666-1 NPC tumor-bearing mice. The C666-1 tumors could be visualized by [64Cu]Cu-NOTA-HFn and blocked by nonradiolabeled HFn. PET imaging quantitative analysis demonstrated that the uptake of [64Cu]Cu-NOTA-HFn in C666-1 tumors peaked at 6 h p.i. and the best radioactive tumor-to-muscle ratio was 10.53 ± 3.11 (n = 3). Ex vivo biodistribution assay at 6 h p.i. showed that the tumor uptakes were 1.43 ± 0.23%ID/g in the nonblock group and 0.92 ± 0.2%ID/g in the block group (n = 3, p < 0.05). Immunohistochemistry and immunofluorescence staining confirmed positive expression of CD71 and the uptake of HFn in C666-1 tumor tissues. In conclusion, our experiments demonstrated that [64Cu]Cu-NOTA-HFn possesses a very high target engagement for CD71-positive NPC tumors and provided a fundamental basis for further clinical translation.

Solvent-free selective hydrogenation of nitroaromatics to azoxy compounds over Co single atoms decorated on Nb2O5 nanomeshes.

The solvent-free selective hydrogenation of nitroaromatics to azoxy compounds is highly important, yet challenging. Herein, we report an efficient strategy to construct individually dispersed Co atoms decorated on niobium pentaoxide nanomeshes with unique geometric and electronic properties. The use of this supported Co single atom catalysts in the selective hydrogenation of nitrobenzene to azoxybenzene results in high catalytic activity and selectivity, with 99% selectivity and 99% conversion within 0.5 h. Remarkably, it delivers an exceptionally high turnover frequency of 40377 h-1, which is amongst similar state-of-the-art catalysts. In addition, it demonstrates remarkable recyclability, reaction scalability, and wide substrate scope. Density functional theory calculations reveal that the catalytic activity and selectivity are significantly promoted by the unique electronic properties and strong electronic metal-support interaction in Co1/Nb2O5. The absence of precious metals, toxic solvents, and reagents makes this catalyst more appealing for synthesizing azoxy compounds from nitroaromatics. Our findings suggest the great potential of this strategy to access single atom catalysts with boosted activity and selectivity, thus offering blueprints for the design of nanomaterials for organocatalysis.

Eligibility for knee arthroplasty is associated with increased risk of acquired hallux valgus - a Mendelian randomized study.

OBJECTIVE: Clinically, it has been found that patients undergoing knee replacement have a high incidence of concomitant hallux valgus. In this study, we analyzed whether patients with osteoarthritis who underwent surgery and those patient who did not have surgery had an increased risk of hallux valgus by Mendelian randomization and performed reverse causal analysis. DESIGN: Genomewide association study (GWAS) data for osteoarthritis, categorized by knee arthritis with joint replacement, knee arthritis without joint replacement, hip arthritis with joint replacement, and hip arthritis without joint replacement.And acquired hallux valgus were downloaded for Mendelian randomized studies. MR analysis was performed using inverse variance-weighted (IVW), weighted median, and MR-Egger methods. MR-egger regression, MR pleiotropic residuals and outliers (MR-presso), and Cochran's Q statistical methods were used to evaluate heterogeneity and pleiotropy. RESULTS: The IVW results indicate that, compared to healthy individuals, patients who meet the criteria for knee osteoarthritis joint replacement surgery have a significantly higher risk of acquired hallux valgus. There were no significant causal relationships found for the remaining results. No significant heterogeneity or multiplicity was observed in all the Mr analyses. CONCLUSION: Our study supports the increased risk of acquired hallux valgus in patients eligible for knee replacement. There is necessary for clinicians to be concerned about the hallux valgus status of patients undergoing knee arthroplasty.

The chromosome-scale genome and population genomics reveal the adaptative evolution of Populus pruinosa to desertification environment.

The Populus pruinosa is a relic plant that has managed to survive in extremely harsh desert environments. Owing to intensifying global warming and desertification, research into ecological adaptation and speciation of P. pruinosa has attracted considerable interest, but the lack of a chromosome-scale genome has limited adaptive evolution research. Here, a 521.09 Mb chromosome-level reference genome of P. pruinosa was reported. Genome evolution and comparative genomic analysis revealed that tandemly duplicated genes and expanded gene families in P. pruinosa contributed to adaptability to extreme desert environments (especially high salinity and drought). The long terminal repeat retrotransposons (LTR-RTs) inserted genes in the gene body region might drive the adaptive evolution of P. pruinosa and species differentiation in saline-alkali desert environments. We recovered genetic differentiation in the populations of the northern Tianshan Mountain and southern Tianshan Mountain through whole-genome resequencing of 156 P. pruinosa individuals from 25 populations in China. Further analyses revealed that precipitation drove the local adaptation of P. pruinosa populations via some genetic sites, such as MAG2-interacting protein 2 (MIP2) and SET domain protein 25 (SDG25). This study will provide broad implications for adaptative evolution and population studies by integrating internal genetic and external environmental factors in P. pruinosa.

Comparative genomic analysis of the Growth-Regulating Factors-Interacting Factors (GIFs) in six Salicaceae species and functional analysis of PeGIF3 reveals their regulatory role in Populus heteromorphic leaves.

BACKGROUND: The growth-regulating factor-interacting factor (GIF) gene family plays a vital role in regulating plant growth and development, particularly in controlling leaf, seed, and root meristem homeostasis. However, the regulatory mechanism of heteromorphic leaves by GIF genes in Populus euphratica as an important adaptative trait of heteromorphic leaves in response to desert environment remains unknown. RESULTS: This study aimed to identify and characterize the GIF genes in P. euphratica and other five Salicaceae species to investigate their role in regulating heteromorphic leaf development. A total of 27 GIF genes were identified and characterized across six Salicaceae species (P. euphratica, Populus pruinose, Populus deltoides, Populus trichocarpa, Salix sinopurpurea, and Salix suchowensis) at the genome-wide level. Comparative genomic analysis among these species suggested that the expansion of GIFs may be derived from the specific Salicaceae whole-genome duplication event after their divergence from Arabidopsis thaliana. Furthermore, the expression data of PeGIFs in heteromorphic leaves, combined with functional information on GIF genes in Arabidopsis, indicated the role of PeGIFs in regulating the leaf development of P. euphratica, especially PeGIFs containing several cis-acting elements associated with plant growth and development. By heterologous expression of the PeGIF3 gene in wild-type plants (Col-0) and atgif1 mutant of A. thaliana, a significant difference in leaf expansion along the medial-lateral axis, and an increased number of leaf cells, were observed between the overexpressed plants and the wild type. CONCLUSION: PeGIF3 enhances leaf cell proliferation, thereby resulting in the expansion of the central-lateral region of the leaf. The findings not only provide global insights into the evolutionary features of Salicaceae GIFs but also reveal the regulatory mechanism of PeGIF3 in heteromorphic leaves of P. euphratica.

Therapeutic potential of natural killer cells in neuroimmunological diseases.

Natural killer (NK) cells, a major component of the innate immune system, have prominent immunoregulatory, antitumor proliferation, and antiviral activities. NK cells act as a double-edged sword with therapeutic potential in neurological autoimmunity. Emerging evidence has identified NK cells are involved in the development and progression of neuroimmunological diseases such as multiple sclerosis, neuromyelitis optica spectrum disorders, autoimmune encephalitis, Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, and idiopathic inflammatory myopathy. However, the regulatory mechanisms and functional roles of NK cells are highly variable in different clinical states of neuroimmunological diseases and need to be further determined. In this review, we summarize the evidence for the heterogenic involvement of NK cells in the above conditions. Further, we describe cutting-edge NK-cell-based immunotherapy for neuroimmunological diseases in preclinical and clinical development and highlight challenges that must be overcome to fully realize the therapeutic potential of NK cells.

Clinically relevant stratification of lung squamous carcinoma patients based on ubiquitinated proteasome genes for 3P medical approach.

Relevance: The proteasome is a crucial mechanism that regulates protein fate and eliminates misfolded proteins, playing a significant role in cellular processes. In the context of lung cancer, the proteasome's regulatory function is closely associated with the disease's pathophysiology, revealing multiple connections within the cell. Therefore, studying proteasome inhibitors as a means to identify potential pathways in carcinogenesis and metastatic progression is crucial in in-depth insight into its molecular mechanism and discovery of new therapeutic target to improve its therapy, and establishing effective biomarkers for patient stratification, predictive diagnosis, prognostic assessment, and personalized treatment for lung squamous carcinoma in the framework of predictive, preventive, and personalized medicine (PPPM; 3P medicine). Methods: This study identified differentially expressed proteasome genes (DEPGs) in lung squamous carcinoma (LUSC) and developed a gene signature validated through Kaplan-Meier analysis and ROC curves. The study used WGCNA analysis to identify proteasome co-expression gene modules and their interactions with the immune system. NMF analysis delineated distinct LUSC subtypes based on proteasome gene expression patterns, while ssGSEA analysis quantified immune gene-set abundance and classified immune subtypes within LUSC samples. Furthermore, the study examined correlations between clinicopathological attributes, immune checkpoints, immune scores, immune cell composition, and mutation status across different risk score groups, NMF clusters, and immunity clusters. Results: This study utilized DEPGs to develop an eleven-proteasome gene-signature prognostic model for LUSC, which divided samples into high-risk and low-risk groups with significant overall survival differences. NMF analysis identified six distinct LUSC clusters associated with overall survival. Additionally, ssGSEA analysis classified LUSC samples into four immune subtypes based on the abundance of immune cell infiltration with clinical relevance. A total of 145 DEGs were identified between high-risk and low-risk score groups, which had significant biological effects. Moreover, PSMD11 was found to promote LUSC progression by depending on the ubiquitin-proteasome system for degradation. Conclusions: Ubiquitinated proteasome genes were effective in developing a prognostic model for LUSC patients. The study emphasized the critical role of proteasomes in LUSC processes, such as drug sensitivity, immune microenvironment, and mutation status. These data will contribute to the clinically relevant stratification of LUSC patients for personalized 3P medical approach. Further, we also recommend the application of the ubiquitinated proteasome system in multi-level diagnostics including multi-omics, liquid biopsy, prediction and targeted prevention of chronic inflammation and metastatic disease, and mitochondrial health-related biomarkers, for LUSC 3PM practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00352-w.

Non-cytopathic bovine viral diarrhea virus (BVDV) inhibits innate immune responses via induction of mitophagy.

Bovine viral diarrhea virus (BVDV) belongs to the genus Pestivirus within the family Flaviviridae. Mitophagy plays important roles in virus-host interactions. Here, we provide evidence that non-cytopathic (NCP) BVDV shifts the balance of mitochondrial dynamics toward fission and induces mitophagy to inhibit innate immune responses. Mechanistically, NCP BVDV triggers the translocation of dynamin-related protein (Drp1) to mitochondria and stimulates its phosphorylation at Ser616, leading to mitochondrial fission. In parallel, NCP BVDV-induced complete mitophagy via Parkin-dependent pathway contributes to eliminating damaged mitochondria to inhibit MAVS- and mtDNA-cGAS-mediated innate immunity responses, mtROS-mediated inflammatory responses and apoptosis initiation. Importantly, we demonstrate that the LIR motif of ERNS is essential for mitophagy induction. In conclusion, this study is the first to show that NCP BVDV-induced mitophagy plays a central role in promoting cell survival and inhibiting innate immune responses in vitro.

Elevated expression of Toll-like receptor 7 and its correlation with clinical features in patients with primary Sjögren's syndrome.

BACKGROUND: The labial salivary glands (LSGs) are important for the diagnosis, evaluation of therapeutic efficacy, and genetic analyses of primary Sjögren's syndrome (pSS). In autoimmune diseases, the recognition of self nucleic acids and viral RNA and DNA through endogenous Toll-like receptor(TLR) triggers the production of type I IFN and pro-inflammatory cytokines, leading to the occurrence and progression of the disease. Here, we detected the expression of TLR7 in LSGs and analyse its correlation with clinical features and serum cytokines in pSS patients. METHODS: LSGs and serum samples were obtained from 56 pSS patients and 19 non-SS patients (non-pSS patients). The expression of TLR7 in the LSGs was evaluated with immunohistochemistry. The serum levels of interferon-α (IFN-α) and interleukin-6 (IL-6) were quantified by ELISA. Laboratory parameters were measured by clinical standard laboratory techniques. RESULTS: TLR7-positive cells in pSS were localized in the ductal epithelial cells and lymphocytes of LSGs. The expression of TLR7 was upregulated in pSS patients compared with controls. Patients with anti-Ro52 antibody positivity showed higher TLR7 levels than those who were negative but not those with anti-Ro60 and anti-SSB. TLR7 levels were positively associated with the levels of IgG, IgA, ANA, IL-6, IFN-α and serum globulin but were not associated with IgM, C3, C4, or rheumatoid factor (RF) in serum. CONCLUSION: TLR7 may be involved in the inflammatory response and the production of antibodies in pSS and plays an important role in local and systemic pSS manifestations. This research showed that TLR7 is involved in pSS pathogenesis.

C-type lectin 2D (CLEC2D) is upregulated in clear cell renal cell carcinoma (ccRCC) tissues and predicts poor prognosis.

Clear cell renal cell carcinoma (ccRCC) is known as the most common type of renal cancer. Recently, a series of advances have been made in targeted therapy for ccRCC. To combat this highly metastatic tumor, novel therapeutic targets still need to be developed. C-type lectins (CLECs) contain a characteristic C-type lectin-like domain and affect several physiological functions. The effects of C-type lectin 2D (CLEC2D) on cancer progression have been revealed in several types of cancers; however, its expression in ccRCC tissues, and the possible effects on the progression and metastasis of ccRCC, are still unclear. Herein, we found the high mRNA and protein levels of CLEC2D in ccRCC tissues. We further found that CLEC2D expression was correlated with the prognosis of ccRCC patients and correlated with the tumor size (p = 0.019*) of patients. In addition, CLEC2D affected tumor immune infiltration, confirmed by the further analysis. CLEC2D knockdown suppressed the proliferation of ccRCC cells in vitro and restrained ccRCC tumor growth and immune infiltration in mice. Therefore, we believe that CLEC2D has the potential to serve as a promising ccRCC therapeutic target.

Identification of ferroptosis-related diagnostic markers in primary Sjögren's syndrome based on machine learning / Identificación de marcadores diagnósticos relacionados con la ferroptosis en el síndrome de Sjögren primario basado en aprendizaje automático

Background: Primary Sjogren's syndrome (pSS) is a common autoimmune disorder that affects up to 0.3-3% of the global population. Ferroptosis has recently been identified to play a significant role in autoimmune diseases. However, the molecular mechanisms of ferroptosis in the initiation and progression of pSS remains unclear. Material and Methods: To investigate the molecular mechanisms underlying the occurrence and progression of pSS, we utilized a comprehensive approach by integrating data obtained from the Gene Expression Omnibus (GEO) database with data from the FerrDb database to identify the ferroptosis-related differentially expressed genes (DEGs). Furthermore, we implemented an innovative transcriptomic analysis method utilizing a computer-aided algorithm to establish a network between hub genes associated with ferroptosis and the immune microenvironment in pSS patients. Results: Our results revealed significant differences in the gene expression profiles of pSS samples compared to normal tissues, with 1,830 significantly up-regulated genes and 1,310 significantly down-regulated genes. In addition, our results showed a significant increase in the proportions of B cells and CD4+ T cells in pSS samples compared to normal tissues. AND then, our analysis revealed that a combination of six ferroptosis-related genes, including TBK1, SLC1A4, PIK3CA, ENO3, EGR1, and ATG5, could serve as optimal markers for the diagnosis of pSS. The combined analysis of these six genes accurately diagnosed the occurrence of pSS. Conclusions: This study offers valuable insights into the pathogenesis of pSS and highlights the importance of targeting ferroptosis-related DEGs, which suggests a novel treatment strategy for pSS.(AU)

The Mechanical Properties and Microstructure of Tailing Recycled Aggregate Concrete.

The aim of this study was to develop sustainable concrete by recycling concrete aggregates from steel waste and construction waste (iron ore tailings (IOTs) and recycled coarse aggregates (RCAs)) to replace silica sand and natural coarse aggregates. In experimental testing, the compressive strength, peak strain, elastic modulus, energy dissipated under compression, and compressive stress-strain curve were analyzed. Microscopically, scanning electron microscopy and energy-dispersive spectrometry were employed to investigate the microstructural characteristics of the interfacial transition zone (ITZ), and the results were compared with the ITZs of natural aggregate concrete and recycled aggregate concrete (RAC). In addition, the pore structure of concrete was determined by nuclear magnetic resonance. The results revealed that an appropriate IOT content can improve the ITZ and compactness of RAC, as well as optimize the mechanical and deformation properties of RAC. However, due to the presence of a smaller number of microcracks on the surface of IOT particles, excessive IOTs could reduce the integrity of the matrix structure and weaken the strength of concrete. According to the research, replacing silica sand with 30% IOTs led to a reduction in the porosity and microcracking which resulted in a much denser microstructure.

The H9N2 avian influenza virus increases APEC adhesion to oviduct epithelia by viral NS1 protein-mediated activation of the TGF-ß pathway.

H9N2 avian influenza is a low-pathogenic avian influenza circulating in poultry and wild birds worldwide and frequently contributes to chicken salpingitis that is caused by avian pathogenic Escherichia coli (APEC), leading to huge economic losses and risks for food safety. Currently, how the H9N2 virus contributes to APEC infection and facilitates salpingitis remains elusive. In this study, in vitro chicken oviduct epithelial cell (COEC) model and in vivo studies were performed to investigate the role of H9N2 viruses on secondary APEC infection, and we identified that H9N2 virus enhances APEC infection both in vitro and in vivo. To understand the mechanisms behind this phenomenon, adhesive molecules on the cell surface facilitating APEC adhesion were checked, and we found that H9N2 virus could upregulate the expression of fibronectin, which promotes APEC adhesion onto COECs. We further investigated how fibronectin expression is regulated by H9N2 virus infection and revealed that transforming growth factor beta (TGF-ß) signaling pathway is activated by the NS1 protein of the virus, thus regulating the expression of adhesive molecules. These new findings revealed the role of H9N2 virus in salpingitis co-infected with APEC and discovered the molecular mechanisms by which the H9N2 virus facilitates APEC infection, offering new insights to the etiology of salpingitis with viral-bacterial co-infections.IMPORTANCEH9N2 avian influenza virus (AIV) widely infects poultry and is sporadically reported in human infections. The infection in birds frequently causes secondary bacterial infections, resulting in severe symptoms like pneumonia and salpingitis. Currently, the mechanism that influenza A virus contributes to secondary bacterial infection remains elusive. Here we discovered that H9N2 virus infection promotes APEC infection and further explored the underlying molecular mechanisms. We found that fibronectin protein on the cell surface is vital for APEC adhesion and also showed that H9N2 viral protein NS1 increased the expression of fibronectin by activating the TGF-ß signaling pathway. Our findings offer new information on how AIV infection promotes APEC secondary infection, providing potential targets for mitigating severe APEC infections induced by H9N2 avian influenza, and also give new insights on the mechanisms on how viruses promote secondary bacterial infections in animal and human diseases.

Shaping high-performance wearable robots for human motor and sensory reconstruction and enhancement.

Most wearable robots such as exoskeletons and prostheses can operate with dexterity, while wearers do not perceive them as part of their bodies. In this perspective, we contend that integrating environmental, physiological, and physical information through multi-modal fusion, incorporating human-in-the-loop control, utilizing neuromuscular interface, employing flexible electronics, and acquiring and processing human-robot information with biomechatronic chips, should all be leveraged towards building the next generation of wearable robots. These technologies could improve the embodiment of wearable robots. With optimizations in mechanical structure and clinical training, the next generation of wearable robots should better facilitate human motor and sensory reconstruction and enhancement.

Monocytes Release Pro-Cathepsin D to Drive Blood-to-Brain Transcytosis in Diabetes.

BACKGROUND: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined. METHODS: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral tests, immunofluorescence, transmission electron microscopy, Western blot analysis, vascular leakage assay, and single-cell RNA sequencing were performed to clarify the phenotype and elucidate the molecular mechanism. RESULTS: Monocytes expressed high-level CTSD in patients with type 2 diabetes. The transgenic mice expressing human CTSD in the monocytes showed increased brain microvascular permeability resembling the diabetic microvascular phenotype, accompanied by cognitive deficit. Mechanistically, the monocytes release nonenzymatic pro-CTSD to upregulate caveolin expression in brain endothelium triggering caveolae-mediated transcytosis, without affecting the paracellular route of brain microvasculature. The circulating pro-CTSD activated the caveolae-mediated transcytosis in brain endothelial cells via its binding with low-density LRP1 (lipoprotein receptor-related protein 1). Importantly, genetic ablation of CTSD in the monocytes exhibited a protective effect against the diabetes-enhanced brain microvascular transcytosis and the diabetes-induced cognitive impairment. CONCLUSIONS: These findings uncover the novel role of circulatory pro-CTSD from monocytes in the pathogenesis of cerebral microvascular lesions in diabetes. The circulatory pro-CTSD is a potential target for the intervention of microvascular complications in diabetes.

3D Carbon-Based Conductive Network Printed for Glucose Sensors on Curved and Flexible Substrates.

The rising prevalence of diabetes has led to an increased focus on real-time glucose monitoring. Wearable glucose sensor patches allow noninvasive, real-time monitoring, reducing patient discomfort compared to invasive sensors. However, most existing glucose sensor patches rely on complex and contaminating metal vapor deposition technologies, which pose limitations in practical production. In this study, we propose a novel approach for preparing graphite/multiwall carbon nanotubes (MWCNT)/reduced graphene oxide (rGO) using a high-viscosity ink, which can be easily obtained through simple mechanical stirring. To create intricate patterns and enable printing on curved substrates, we employed a 3D printer equipped with an infrared laser ranging system. The ink served as a working electrode, and we developed a three-electrode system patch with a concentric circle structure. Subsequently, the working electrode underwent enzymatic modification with glucose dehydrogenase with flavin adenine dinucleotide (GDH-FAD) using a polymer embedding method. The resulting wearable glucose sensor exhibited a sensitivity of 2.42 µA mM-1 and a linear detection range of 1-12 mM. In addition, the glucose sensor has excellent anti-interference capability and demonstrates good repeatability in simulated real human wear scenarios, which meets the requirements for accurate human detection. These findings provide valuable insights into the development of human health monitoring technologies.

Sustainable assessment and synergism of ceramic powder and steel slag in iron ore tailings-based concrete.

Solid waste management is a critical issue worldwide. Effectively utilizing these solid waste resources presents a viable solution. This study focuses on Iron ore tailings (IOTs), a solid waste generated during iron ore processing, which can be used as supplementary cementitious materials (SCMs) but have low reactivity, hindering their large-scale application in concrete production. To address this, ternary SCMs were prepared using ceramic powder (CP) and steel slag (SS) to enhance the performance of concrete incorporating IOTs. The study found that the synergistic effect of CP and SS significantly improved the compressive strength of concrete, with a notable increase of up to 21% compared to concrete with IOTs alone. Mercury intrusion porosimetry (MIP) and backscattering electron (BSE) analyses revealed that the ternary SCMs significantly optimized the characteristics of the interfacial transition zone (ITZ), which in turn enhanced the compressive properties of the concrete. This contributed to maintaining the structural integrity of the concrete, even amidst variations in the pore structure. Importantly, the incorporation of ternary SCMs led to a 23% reduction in carbon emissions, from 400.01 kg CO2/m3 to 307.48 kg CO2/m3, and elevated eco-strength efficiency from 0.1 to 0.14. The study highlights the role of multi-material synergy in developing composite SCMs systems, fostering the sustainable advancement of green building materials.