Explore the vast range of titles available.

Glioblastoma (GBM) is the most malignant and highly aggressive brain tumor. In this study, four types of typical GBM cell lines (LN229, SNB19, U87, U251) were cultured in a microfabricated 3-D model to study their in vitro behaviors. The 3-D in vitro model provides hollow micro-chamber arrays containing a natural collagen interface and thus allows the GBM cells to grow in the 3-D chambers. The GBM cells in this model showed specific properties on the aspects of cell morphology, proliferation, migration, and invasion, some of which were rarely observed before. Furthermore, how the cells invaded into the surrounding ECM and the corresponding specific invasion patterns were observed in details, implying that the four types of cells have different features during their development in cancer. This complex in vitro model, if applied to patient derived cells, possesses the potential of becoming a clinically relevant predictive model.

In this work, we constructed a Collagen I–Matrigel composite extracellular matrix (ECM). The composite ECM was used to determine the influence of the local collagen fiber orientation on the collective intravasation ability of tumor cells. We found that the local fiber alignment enhanced cell–ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (∼10 mg/mL protein concentration).

Osteoarthritis (OA) is a common disease that endangers millions of middle‐aged and elderly people worldwide. Researchers from different fields have made great efforts and achieved remarkable progress in the pathogenesis and treatment of OA. However, there is still no cure for OA. In this review, we discuss the pathogenesis of OA and summarize the current clinical therapies. Moreover, we introduce various natural and synthetic biomaterials for drug release, cartilage transplantation, and joint lubricant during the OA treatment. We also present our perspectives and insights on OA treatment in the future. We hope that this review will foster communication and collaboration among biological, clinical, and biomaterial researchers, paving the way for OA therapeutic breakthroughs. Osteoarthritis (OA) pathogenesis, clinical treatment strategies, and functional biomaterials applied in OA therapy.

Regulator of cell death-1 (RCD-1) governs the heteroallelic expression of RCD-1-1 and RCD-1-2, a pair of fungal gasdermin (GSDM)-like proteins, which prevent cytoplasmic mixing during allorecognition and safeguard against mycoparasitism, genome exploitation, and deleterious cytoplasmic elements (e.g., senescence plasmids) by effecting a form of cytolytic cell death. However, the underlying mechanisms by which RCD-1 acts on the cell membrane remain elusive. Here, we demonstrate that RCD-1 binds acidic lipid membranes, forms pores, and induces membrane bending. Using atomic force microscopy (AFM) and AlphaFold, we show that RCD-1-1 and RCD-1-2 form heterodimers that further self-assemble into ~14.5 nm-wide transmembrane pores (~10 heterodimers). Moreover, through AFM force spectroscopy and micropipette aspiration, we reveal that RCD-1 proteins bend membranes with low bending moduli. This combined action of pore formation and membrane deformation may constitute a conserved mechanism within the broader GSDM family. The mechanism of RCD-1 regulated cell death in fungal cells is unknown. Here, the authors use AFM to uncover two mechanisms by which RCD-1 proteins form pores in lipid membranes, and discover a membrane bending activity

Background Cancer metastasis is the main cause of mortality in cancer patients. However, the drugs targeting metastasis processes are still lacking, which is partially due to the short of effective in vitro model for cell invasion studies. The traditional 2-D culture method cannot reveal the interaction between cells and the surrounding extracellular matrix during invasion process, while the animal models usually are too complex to explain mechanisms in detail. Therefore, a precise and efficient 3-D in vitro model is highly desirable for cell invasion studies and drug screening tests. Methods Precise micro-fabrication techniques are developed and integrated with soft hydrogels for constructing of 3-D lung-cancer micro-environment, mimicking the pulmonary gland or alveoli as in vivo . Results A 3-D in vitro model for cancer cell culture and metastasis studies is developed with advanced micro-fabrication technique, combining microfluidic system with soft hydrogel. The constructed microfluidic platform can provide nutrition and bio-chemical factors in a continuous transportation mode and has the potential to form stable chemical gradient for cancer invasion research. Hundreds of micro-chamber arrays are constructed within the collagen gel, ensuring that all surrounding substrates for tumor cells are composed of natural collagen hydrogel, like the in vivo micro-environment. The 3-D in vitro model can also provide a fully transparent platform for the visual observation of the cell morphology, proliferation, invasion, cell-assembly, and even the protein expression by immune-fluorescent tests if needed. The lung-cancer cells A549 and normal lung epithelial cells (HPAEpiCs) have been seeded into the 3-D system. It is found out that cells can normally proliferate in the microwells for a long period. Moreover, although the cancer cells A549 and alveolar epithelial cells HPAEpiCs have the similar morphology on 2-D solid substrate, in the 3-D system the cancer cells A549 distributed sparsely as single round cells on the extracellular matrix (ECM) when they attached to the substrate, while the normal lung epithelial cells can form cell aggregates, like the structure of normal tissue. Importantly, cancer cells cultured in the 3-D in vitro model can exhibit the interaction between cells and extracellular matrix. As shown in the confocal microscope images, the A549 cells present round and isolated morphology without much invasion into ECM, while starting from around Day 5, cells changed their shape to be spindle-like, as in mesenchymal morphology, and then started to destroy the surrounding ECM and invade out of the micro-chambers. Conclusions A 3-D in vitro model is constructed for cancer cell invasion studies, combining the microfluidic system and micro-chamber structures within hydrogel. To show the invasion process of lung cancer cells, the cell morphology, proliferation, and invasion process are all analyzed. The results confirmed that the micro-environment in the 3-D model is vital for revealing the lung cancer cell invasion as in vivo .

The monitoring of mechanical indexes involved in body movement has attracted immense interest in the diagnosis of neurodegenerative diseases. Here, we present a hybrid flexible conductive structural color (SC) film with the capability of dual‐signal mechanics screening. The film is constructed by oxidatively polymerizing pyrrole on the surface of an inverse opal polyurethane (IPU) membrane, which can be utilized to measure the mechanical indexes through resistance change. Owing to the inverse opal structure, the film shows visual structural color change when stretched and released according to the body movement. Additionally, the highly uniform ordered porous structure endows the conductive film with a lower coefficient of variance on relative resistance change. Benefiting from these features, we have demonstrated that such a flexible conductive SC film could monitor Parkinson's disease (PD) by detecting mechanical indexes simultaneously via dual signals. These features indicate the great value of the stretchable conductive SC films in mechanics sensing applications. A hybrid flexible conductive structural color (SC) film is fabricated for dual‐signal mechanics screening.

The unprecedented demand for variants diagnosis in response to the COVID‐19 epidemic has brought the spotlight onto rapid and accurate detection assays for single nucleotide polymorphisms (SNPs) at multiple locations. However, it is still challenging to ensure simplicity, affordability, and compatibility with multiplexing. Here, a novel technique is presented that combines peptide nucleic acid (PNA) clamps and near‐infrared (NIR)‐driven digital polymerase chain reaction (dPCR) to identify the Omicron and Delta variants. This is achieved by simultaneously identifying highly conserved mutated signatures at codons 19, 614, and 655 of the spike protein gene. By microfluidically introducing graphene‐oxide‐nanocomposite into the assembled gelatin microcarriers, they achieved a rapid temperature ramping‐up rate and switchable gel‐to‐sol phase transformation synchronized with PCR activation under NIR irradiation. Two sets of duplex PCR reactions, each classifying respective PNA probes, are emulsified in parallel and illuminated together using a homemade vacuum‐based droplet generation device and a programmable NIR control module. This allowed for selective amplification of mutant sequences due to single‐base‐pair mismatch with PNA blockers. Sequence‐recognized bioreactions and fluorescent‐color scoring enabled quick identification of variants. This technique achieved a detection limit of 5,100 copies and a 5‐fold quantitative resolution, which is promising to unfold minor differences and dynamic changes. PNA‐assisted NIR photothermal multiplexed dPCR technique recognizes SNPs at codons T19R, O614G, and H655Y of the spike protein gene, thereby discriminating Omicron and Delta variants from the wild‐type of SARS‐CoV‐2. Gelatin microcarriers loaded with GO nanocomposite assist PCR thermocycling under NIR irradiation, where three PNA probes target against SNPs to selectively amplify mutated templates via replication with multi‐color labeling.

A systematic understanding of the evolution and growth dynamics of invasive solid tumors in response to different chemotherapy strategies is crucial for the development of individually optimized oncotherapy. Here, we develop a hybrid three-dimensional (3D) computational model that integrates pharmacokinetic model, continuum diffusion-reaction model and discrete cell automaton model to investigate 3D invasive solid tumor growth in heterogeneous microenvironment under chemotherapy. Specifically, we consider the effects of heterogeneous environment on drug diffusion, tumor growth, invasion and the drug-tumor interaction on individual cell level. We employ the hybrid model to investigate the evolution and growth dynamics of avascular invasive solid tumors under different chemotherapy strategies. Our simulations indicate that constant dosing is generally more effective in suppressing primary tumor growth than periodic dosing, due to the resulting continuous high drug concentration. In highly heterogeneous microenvironment, the malignancy of the tumor is significantly enhanced, leading to inefficiency of chemotherapies. The effects of geometrically-confined microenvironment and non-uniform drug dosing are also investigated. Our computational model, when supplemented with sufficient clinical data, could eventually lead to the development of efficient in silico tools for prognosis and treatment strategy optimization.

Adsorbents with high adsorption efficiency and excellent biosafety for biomedical applications are highly required. MXene is a promising candidate owning these advantages, yet pristine MXene faces dilemmas including insufficient utility of surface site as well as limited processibility. Here, we develop MXene‐encapsulated porous microcapsules via microfluidics. The microcapsules have a biomass hydrogel shell that provides robust support for MXene in the core, by which the microcapsules are endowed with high MXene dosage and remarkable biosafety. Additionally, the MXene nanoflakes assemble into a three‐dimensional network via metal ion‐induced gelation, thereby avoiding restacking and significantly improving surface utilization. Moreover, a freeze‐pretreatment of the microcapsules during preparation results in the formation of a macroporous structure in the shell, which can facilitate the diffusion of the target molecules. These features, combined with additional magneto‐responsiveness rendered by the incorporation of magnetic nanoparticles, contribute to prominent performances of the microcapsules in cleaning uremia toxins including creatinine, urea, and uric acid. Thus, it is anticipated that the MXene‐encapsulated microcapsules will be promising adsorbents in dialysis‐related applications, and the combination of microfluidic encapsulation with metal ion gelation will provide a novel approach for construction of hybrid MXene materials with desired functions. MXene‐confined porous microcapsules are successfully developed through microfluidics. Such microcapsules own a 3D‐crosslinked MXene core and a macroporous biomass shell. Inspiringly, the microcapsules possess both high efficiency and excellent biosafety when adsorbing biomolecules. Besides, the microcapsules show magneto‐responsiveness, rendered by the incorporation of magnetic nanoparticles, thereby achieving flexible separation.

IntroductionThe current pharmacological management of type 2 diabetes mellitus (T2DM) faces challenges such as low rates of optimal glycaemic control, high incidences of adverse drug reactions and suboptimal treatment compliance. Pueraria lobata radix (PLR), a medicinal and edible herb, has shown hypoglycaemic effects in animal models. However, existing clinical studies have only assessed the hypoglycaemic effect of PLR-containing herb formulas or PLR extract preparations. The aim of this study is to investigate the efficacy and safety of using PLR solely as an adjuvant therapy for T2DM.Methods and analysisThis study is a multicentre, randomised, double-blind, placebo-controlled trial. 200 patients with T2DM will be randomly allocated to either the PLR group or the placebo group for a consecutive 12-week intervention. Regular visits will be conducted at weeks 4, 8 and 12, following the initiation of the study to evaluate the efficacy and safety of PLR. The primary outcome is the change in haemoglobin A1c (HbA1c) from baseline at week 12. Secondary outcomes include changes in HbA1c from baseline at weeks 4 and 8; the HbA1c response rate (< 7%), changes in fasting blood glucose, 2-hour blood glucose, fasting C-peptide, body mass index, severity of diabetes symptoms, quality of life from baseline at weeks 4, 8 and 12; and changes in blood lipid indicators at week 12. Safety outcomes include the incidences of total adverse events (AEs), serious AEs and PLR-related AEs.Ethics and disseminationThe protocol has been approved by the Ethics Committees of the First Affiliated Hospital of Nanchang University (approval number: IIT[2024]LLS No.303) and the Affiliated Hospital of Jiangxi University of Chinese Medicine (approval number: JZFYLL2024006200087). We will disseminate the study findings through publications in peer-reviewed journals and conference presentations.Trial registration numberClinicalTrials.gov NCT06494683.