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Background Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage destruction and inflammation. CC chemokine receptor 1 (CCR1), a member of the chemokine family and its receptor family, plays a role in the autoimmune response. The impact of BX471, a specific small molecule inhibitor of CCR1, on CCR1 expression in cartilage and its effects on OA remain underexplored. Methods This study used immunohistochemistry (IHC) to assess CCR1 expression in IL-1β-induced mouse chondrocytes and a medial meniscus mouse model of destabilization of the medial meniscus (DMM). Chondrocytes treated with varying concentrations of BX471 for 24 h were subjected to IL-1β (10 ng/ml) treatment. The levels of the aging-related genes P16INK4a and P21CIP1 were analyzed via western blotting, and senescence-associated β-galactosidase (SA-β-gal) activity was measured. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), aggrecan (AGG), and the transcription factor SOX9 were determined through western blotting and RT‒qPCR. Collagen II, matrix metalloproteinase 13 (MMP13), and peroxisome proliferator-activated receptor (PPAR)-γ expression was analyzed via western blot, RT‒qPCR, and immunofluorescence. The impact of BX471 on inflammatory metabolism-related proteins under PPAR-γ inhibition conditions (using GW-9662) was examined through western blotting. The expression of MAPK signaling pathway-related molecules was assessed through western blotting. In vivo, various concentrations of BX471 or an equivalent medium were injected into DMM model joints. Cartilage destruction was evaluated through Safranin O/Fast green and hematoxylin–eosin (H&E) staining. Results This study revealed that inhibiting CCR1 mitigates IL-1β-induced aging, downregulates the expression of iNOS, COX-2, and MMP13, and alleviates the IL-1β-induced decrease in anabolic indices. Mechanistically, the MAPK signaling pathway and PPAR-γ may be involved in inhibiting the protective effect of CCR1 on chondrocytes. In vivo, BX471 protected cartilage in a DMM model. Conclusion This study demonstrated the expression of CCR1 in chondrocytes. Inhibiting CCR1 reduced the inflammatory response, alleviated cartilage aging, and retarded degeneration through the MAPK signaling pathway and PPAR-γ, suggesting its potential therapeutic value for OA. Graphical Abstract

Background Accumulating evidence indicates that intervertebral disc degeneration (IDD) is associated with diabetes mellitus (DM), while the underlying mechanisms still remain elusive. Herein, the current study sought to explore the potential molecular mechanism of IDD in diabetic rats based on transcriptome sequencing data. Methods Streptozotocin (STZ)-induced diabetes mellitus type 1 (T1DM) rats were used to obtain the nucleus pulposus tissues for transcriptome sequencing. Next, differentially expressed genes (DEGs) in transcriptome sequencing data and GSE34000 microarray dataset were obtained and intersected to acquire the candidate genes. Moreover, GO and KEGG enrichment analyses were performed to analyze the cellular functions and molecular signaling pathways primarily regulated by candidate DEGs. Results A total of 35 key genes involved in IDD of T1DM rats were mainly enriched in the extracellular matrix (ECM) and cytokine adhesion binding-related pathways. NLRP3 inflammasome activation promoted the pyroptosis of nucleus pulposus cells (NPCs). Besides, BMP7 could affect the IDD of T1DM rats by regulating the inflammatory responses. Additionally, NPCs were isolated from STZ-induced T1DM rats to illustrate the effects of BMP7 on IDD of T1DM rats using the ectopic expression method. Both in vitro and in vivo experiments validated that BMP7 alleviated IDD of T1DM rats by inhibiting NLRP3 inflammasome activation and pyroptosis of NPCs. Conclusion Collectively, our findings provided novel mechanistic insights for understanding of the role of BMP7 in IDD of T1DM, and further highlighted BMP7 as a potential therapeutic target for preventing IDD in T1DM.

Bisphenol A (BPA) is a prevalent environmental contaminant found in plastics and known for its endocrine-disrupting properties, posing risks to both human health and the environment. Despite its widespread presence, the impact of BPA on papillary thyroid cancer (PTC) progression, especially under realistic environmental conditions, is not well understood. This study examined the effects of BPA on PTC using a 3D thyroid papillary tumor spheroid model, which better mimicked the complex interactions within human tissues compared to traditional 2D models. Our findings demonstrated that BPA, at environmentally relevant concentrations, could induce significant changes in PTC cells, including a decrease in E-cadherin expression, an increase in vimentin expression, and reduced thyroglobulin (TG) secretion. These changes suggest that BPA exposure may promote epithelial–mesenchymal transition (EMT), enhance invasiveness, and reduce cell differentiation, potentially complicating treatment, including by increasing resistance to radioiodine therapy. This research highlights BPA’s hazardous nature as an environmental contaminant and emphasizes the need for advanced in vitro models, like 3D tumor spheroids, to better assess the risks posed by such chemicals. It provides valuable insights into the environmental implications of BPA and its role in thyroid cancer progression, enhancing our understanding of endocrine-disrupting chemicals.

Some unavoidable factors in the process of cold strip shape measurement interfere with the shape meter, so the shape measuring results cannot reflect the true shape of the strip and the measuring precision is low. The influences of the measuring error of the strip edges, the transverse temperature difference of the strip, the deflection of shape detection roller, and the shape of the strip coil on the shape measuring results were analyzed in detail, and the corresponding compensation models were established. The simulation calculation and analysis were carried out on a cold strip mill, and a number of disciplinarian cognitions were obtained.

Entry into cells is necessary for many nanomaterial applications, and a common solution is to functionalize nanoparticles (NPs) with cell-penetrating ligands. Despite intensive studies on these functionalized NPs, little is known about their effect on cellular activities to engulf other cargo from the nearby environment. Here, we use NPs functionalized with TAT (transactivator of transcription) peptide (T-NPs) as an example to investigate their impact on cellular uptake of bystander cargo. We find that T-NP internalization enables cellular uptake of bystander NPs, but not common fluid markers, through a receptor-dependent macropinocytosis pathway. Moreover, the activity of this bystander uptake is stimulated by cysteine presence in the surrounding solution. The cargo selectivity and cysteine regulation are further demonstrated ex vivo and in vivo. These findings reveal another mechanism for NP entry into cells and open up an avenue of studying the interplay among endocytosis, amino acids, and nanomaterial delivery. To enter the cells, nanomaterials often need covalent conjugation with cell-penetrating ligands such as TAT. Here, the authors show that simple mixing with TAT-coupled nanoparticles enables the cellular uptake of unfunctionalized nanoparticles, and its activity is stimulated by cysteine in the medium.

Natural musculoskeletal systems have been widely recognized as an advanced robotic model for designing robust yet flexible microbots. However, the development of artificial musculoskeletal systems at micro-nanoscale currently remains a big challenge, since it requires precise assembly of two or more materials of distinct properties into complex 3D micro/nanostructures. In this study, we report femtosecond laser programmed artificial musculoskeletal systems for prototyping 3D microbots, using relatively stiff SU-8 as the skeleton and pH-responsive protein (bovine serum albumin, BSA) as the smart muscle. To realize the programmable integration of the two materials into a 3D configuration, a successive on-chip two-photon polymerization (TPP) strategy that enables structuring two photosensitive materials sequentially within a predesigned configuration was proposed. As a proof-of-concept, we demonstrate a pH-responsive spider microbot and a 3D smart micro-gripper that enables controllable grabbing and releasing. Our strategy provides a universal protocol for directly printing 3D microbots composed of multiple materials. Musculoskeletal systems are recognized as a model for designing robust yet flexible microbots but the development of artificial musculoskeletal systems at nanoscale currently remains challenging. Here the authors report a laser programmed artificial musculoskeletal systems for prototyping 3D microbots, using relatively stiff SU-8 as the skeleton and pH-responsive proteins as the smart muscle.

The 16S rRNA gene has been a mainstay of sequence-based bacterial analysis for decades. However, high-throughput sequencing of the full gene has only recently become a realistic prospect. Here, we use in silico and sequence-based experiments to critically re-evaluate the potential of the 16S gene to provide taxonomic resolution at species and strain level. We demonstrate that targeting of 16S variable regions with short-read sequencing platforms cannot achieve the taxonomic resolution afforded by sequencing the entire (~1500 bp) gene. We further demonstrate that full-length sequencing platforms are sufficiently accurate to resolve subtle nucleotide substitutions (but not insertions/deletions) that exist between intragenomic copies of the 16S gene. In consequence, we argue that modern analysis approaches must necessarily account for intragenomic variation between 16S gene copies. In particular, we demonstrate that appropriate treatment of full-length 16S intragenomic copy variants has the potential to provide taxonomic resolution of bacterial communities at species and strain level. Here, the authors explore the potential of the 16S gene for discriminating bacterial taxa and show that full-length sequencing combined with appropriate clustering of intragenomic sequence variation can provide accurate representation of bacterial species in microbiome datasets.

The incidence of adverse effects and pathogen resistance encountered with small molecule antibiotics is increasing. As such, there is mounting focus on immunogene therapy to augment the immune system’s response to infection and accelerate healing. A major obstacle to in vivo gene delivery is that the primary uptake pathway, cellular endocytosis, results in extracellular excretion and lysosomal degradation of genetic material. Here we show a nanosystem that bypasses endocytosis and achieves potent gene knockdown efficacy. Porous silicon nanoparticles containing an outer sheath of homing peptides and fusogenic liposome selectively target macrophages and directly introduce an oligonucleotide payload into the cytosol. Highly effective knockdown of the proinflammatory macrophage marker IRF5 enhances the clearance capability of macrophages and improves survival in a mouse model of Staphyloccocus aureus pneumonia. In the context of increasing bacterial antibiotic-resistance, gene therapy that targets the immune system to clear infection is a major goal. Here the authors show a silicon based nanosystem that modulates the macrophage response in an in vivo model of Staphylococcal pneumonia.

Nanoscale surface texturing, drilling, cutting, and spatial sculpturing, which are essential for applications, including thin-film solar cells, photonic chips, antireflection, wettability, and friction drag reduction, require not only high accuracy in material processing, but also the capability of manufacturing in an atmospheric environment. Widely used focused ion beam (FIB) technology offers nanoscale precision, but is limited by the vacuum-working conditions; therefore, it is not applicable to industrial-scale samples such as ship hulls or biomaterials, e.g., cells and tissues. Here, we report an optical far-field-induced near-field breakdown (O-FIB) approach as an optical version of the conventional FIB technique, which allows direct nanowriting in air. The writing is initiated from nanoholes created by femtosecond-laser-induced multiphoton absorption, and its cutting “knife edge” is sharpened by the far-field-regulated enhancement of the optical near field. A spatial resolution of less than 20 nm (λ/40, with λ being the light wavelength) is readily achieved. O-FIB is empowered by the utilization of simple polarization control of the incident light to steer the nanogroove writing along the designed pattern. The universality of near-field enhancement and localization makes O-FIB applicable to various materials, and enables a large-area printing mode that is superior to conventional FIB processing.Nanotechnology: Better writing with lightAn optical version of Focused Ion Beam technology (FIB) allows nanoscale “writing” such as surface texturing, drilling and sculpting of materials to be performed in air, avoiding the need for a vacuum which limits the application of conventional FIB. The “Optical Far-field-Induced near-field Breakdown” (O-FIB) approach has been developed by Hong-Bo Sun of Tsinghua University and colleagues at Jilin University in China and Swinburne University of Technology in Austrilia. It works by creating nanoholes with a femtosecond laser, which is controlled by sophisticated optical effects. The process can cover larger areas than conventional FIB, and with a spatial resolution below 20 nanometres. The ability to be performed in an open atmosphere offers new possibilities for nanoscale writing. These range from working on industrial scale materials such as ship hulls, down to living tissues and cells.

Non-Abelian braiding has attracted substantial attention because of its pivotal role in describing the exchange behaviour of anyons—candidates for realizing quantum logics. The input and outcome of non-Abelian braiding are connected by a unitary matrix that can also physically emerge as a geometric-phase matrix in classical systems. Hence it is predicted that non-Abelian braiding should have analogues in photonics, although a feasible platform and the experimental realization remain out of reach. Here we propose and experimentally realize an on-chip photonic system that achieves the non-Abelian braiding of up to five photonic modes. The braiding is realized by controlling the multi-mode geometric-phase matrix in judiciously designed photonic waveguide arrays. The quintessential effect of braiding—sequence-dependent swapping of photon dwell sites—is observed in both classical-light and single-photon experiments. Our photonic chips are a versatile and expandable platform for studying non-Abelian physics, and we expect the results to motivate next-generation non-Abelian photonic devices.Non-Abelian braiding—a candidate for realizing quantum logics—is demonstrated by controlling the geometric-phase matrix in a photonic chip, and its key characteristics are observed.