Implantable celecoxib nanofibers made by electrospinning: fabrication and characterization.

Background: Osteoarthritis causes tremendous damage to the joints, reducing the quality of life and imposing significant financial burden. An implantable drug-delivery system can improve the symptomatic manifestations with low doses and frequencies. However, the free drug has short retention in the joint cavity. Materials & methods: This study used electrostatic spinning technology to create an implantable drug-delivery system loaded with celecoxib (celecoxib nanofibers [Cel-NFs]) to improve retention and bioavailability. Results: Cel-NFs exhibited good formability, hydrophilicity and tensile properties. Cel-NFs were able to continuously release drugs for 2 weeks and increase the uptake capacity of Raw 264.7 cells, ultimately ameliorating symptoms in osteoarthritis rats. Conclusion: These results suggest that Cel-NFs can effectively ameliorate cartilage damage, reduce joint pain and alleviate osteoarthritis progression.

Balanced transformer: efficient classification of glioblastoma and primary central nervous system lymphoma.

Objective.Primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) are malignant primary brain tumors with different biological characteristics. Great differences exist between the treatment strategies of PCNSL and GBM. Thus, accurately distinguishing between PCNSL and GBM before surgery is very important for guiding neurosurgery. At present, the spinal fluid of patients is commonly extracted to find tumor markers for diagnosis. However, this method not only causes secondary injury to patients, but also easily delays treatment. Although diagnosis using radiology images is non-invasive, the morphological features and texture features of the two in magnetic resonance imaging (MRI) are quite similar, making distinction with human eyes and image diagnosis very difficult. In order to solve the problem of insufficient number of samples and sample imbalance, we used data augmentation and balanced sample sampling methods. Conventional Transformer networks use patch segmentation operations to divide images into small patches, but the lack of communication between patches leads to unbalanced data layers.Approach.To address this problem, we propose a balanced patch embedding approach that extracts high-level semantic information by reducing the feature dimensionality and maintaining the geometric variation invariance of the features. This approach balances the interactions between the information and improves the representativeness of the data. To further address the imbalance problem, the balanced patch partition method is proposed to increase the receptive field by sampling the four corners of the sliding window and introducing a linear encoding component without increasing the computational effort, and designed a new balanced loss function.Main results.Benefiting from the overall balance design, we conducted an experiment using Balanced Transformer and obtained an accuracy of 99.89%, sensitivity of 99.74%, specificity of 99.73% and AUC of 99.19%, which is far higher than the previous results (accuracy of 89.6% ∼ 96.8%, sensitivity of 74.3% ∼ 91.3%, specificity of 88.9% ∼ 96.02% and AUC of 87.8% ∼ 94.9%).Significance.This study can accurately distinguish PCNSL and GBM before surgery. Because GBM is a common type of malignant tumor, the 1% improvement in accuracy has saved many patients and reduced treatment times considerably. Thus, it can provide doctors with a good basis for auxiliary diagnosis.

The effect of CALIPER-derived parameters for idiopathic pulmonary fibrosis in predicting prognosis, progression, and mortality: a systematic review.

BACKGROUND: High-resolution computed tomography (HRCT), as the main tool for monitoring idiopathic pulmonary fibrosis (IPF), is characterized by subjective variability among radiologists and insensitivity to subtle changes. Recently, a few studies have aimed to decrease subjective bias by assessing the severity of IPF using computer software, i.e., Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER). However, these studies had diverse research directions. In this review, we systematically assess the effect of CALIPER in the management of IPF. METHODS: A systematic review was conducted through a search of published studies in PubMed, Web of Science, Cochrane, Embase, Scopus, and CNKI databases from database inception through February 28, 2022. The methodological quality would be evaluated by using Methodological Index for Non-Randomized Studies (MINORS). Narrative synthesis summarized findings by participant characteristics, study design, and associations with outcomes. RESULTS: Ten studies were included. They evaluated the relationship between CALIPER-derived parameters and pulmonary function test (PFT) and mortality. CALIPER-derived parameters showed a significant correlation with PFT and mortality. Two studies reported that CALIPER could be used to stratify outcomes. CONCLUSION: CALIPER-derived parameters can be used to evaluate prognosis and mortality. CALIPER-derived parameters combined with composite physiologic index (CPI) or Gender-Age-Physiology (GAP) could help clinicians implement targeted management by refining prognostic stratification. However, research has been constrained by small number of retrospective investigations and sample sizes. Therefore, it is essential to design prospective controlled studies and establish the staging system by CALIPER-derived parameters and combining them with CPI, FVC, or GAP. CLINICAL RELEVANCE STATEMENT: It is beneficial for clinic to provide objective, sensitive, and accurate indicators of disease progression. It also helps the clinic to develop individualized treatment plans based on the stage of disease progression and provides evaluation of efficacy in drug trials. KEY POINTS: • Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) is a quantitative CT analysis software that can be used to evaluate the progression of disease on CT. • The CALIPER-derived vessel-related structure shows great performance in the management of idiopathic pulmonary fibrosis. • CALIPER-derived parameters combined with composite physiologic index or Gender-Age-Physiology can be used to refine prognostic stratification.

Formation of Hydrophilic Nanofibers from Nanostructural Design in the Co-Encapsulation of Celecoxib through Electrospinning.

This study presents a method for a one-step co-encapsulation of PLGA nanoparticles in hydrophilic nanofibers. The aim is to effectively deliver the drug to the lesion site and achieve a longer release time. The celecoxib nanofiber membrane (Cel-NPs-NFs) was prepared by emulsion solvent evaporation and electrospinning with celecoxib as a model drug. By this method, nanodroplets of celecoxib PLGA are entrapped within polymer nanofibers during an electrospinning process. Moreover, Cel-NPs-NFs exhibited good mechanical strength and hydrophilicity, with a cumulative release of 67.74% for seven days, and the cell uptake at 0.5 h was 2.7 times higher than that of pure nanoparticles. Furthermore, pathological sections of the joint exhibited an apparent therapeutic effect on rat OA, and the drug was delivered effectively. According to the results, this solid matrix containing nanodroplets or nanoparticles could use hydrophilic materials as carriers to prolong drug release time.

Erratum: Long-term and potent IOP-lowering effect of IκBα-siRNA in a nonhuman primate model of chronic ocular hypertension.

[This corrects the article DOI: 10.1016/j.isci.2022.104149.].

Quaternary PdCuNiP Porous Nanosheets with Enhanced Electrochemical Performance in the Ethanol Oxidation Reaction.

The ability to manipulate metal electrocatalysts with satisfactory performance for the ethanol oxidation reaction (EOR) is promising but still unsatisfactory for practical application in direct ethanol fuel cells. Beyond traditional metal-metal alloys, we herein report a novel metal-nonmetal alloy electrocatalyst that takes advantage of quaternary PdCuNiP alloy composition and the ultrathin/porous nanosheet (NS) structure. The optimized PdCuNiP porous NSs feature more undercoordinated active sites and modified electron/function structures, enabling better antipoisoning ability. Under alkaline conditions, this electrocatalyst shows excellent electrochemical EOR performance with a high EOR activity of 4.05 A mgPd-1 and a low activation energy of 21.2 kJ mol-1, comparable to the state-of-the-art electrocatalysts reported in the literature. Meanwhile, PdCuNiP porous NSs are electrocatalytically active for electrochemical oxidation of other fuels (methanol, glycerol, and glucose), highlighting their great potential for various direct alcohol fuel cells. The findings reported here may put forward some insights into designing new functional electrocatalysts for various fuel cell electrocatalysis and beyond.

Long-term and potent IOP-lowering effect of IκBα-siRNA in a nonhuman primate model of chronic ocular hypertension.

Glaucoma is one of the most common causes of irreversible blindness. It is acknowledged that lowering intraocular pressure (IOP) is the effective treatment to slow glaucoma disease progression. The main obstacle of existing drugs is that the effect of reducing IOP does not last long. Degradation of IκB stimulates the transcription of NF-κB, which could upregulate the expression of matrix metalloproteinases (MMPs). Whether a IκB-targeted gene therapy works in glaucoma is unclear. Here, we established a chronic ocular hypertension (COHT) model in rhesus monkey by laser photocoagulation and verified that intracameral delivery of IκBα-siRNA showed long-lasting and potent effects of reducing IOP without obvious inflammation in monkeys with COHT. We also verified that IκBα-siRNA could increase the expressions of MMP2 and MMP9 by knocking down IκBα in vitro and in vivo. Our results in nonhuman primates indicated that IκBα-siRNA may become a promising therapeutic approach for the treatment of glaucoma.

Evaluation of white sandstone mechanical behaviour and the energy evolution of prepeak unloading damage.

Deep high-stress roadway excavation under unloading disturbance inevitably leads to damage deterioration of the surrounding rock, which poses a serious threat to its stability. To explore the energy characteristics of white sandstone damaged by peak front unloading, uniaxial compression tests were conducted on damaged rock samples. The results show that the peak strength and modulus of elasticity of the rock sample gradually decrease with increasing damage degrees. The external work input energy, releasable elastic strain energy and dissipation energy all decreased with increasing damage. Damage evolution curves and equations of the rock samples were obtained based on the damage instantiation model established by the principle of energy dissipation and release. The effects of unloading damage on the fracture characteristics of the rock samples were analysed from both macro and microscopic viewpoints, and the results showed that a micro fracture in the rock is transformed from brittle-ductile damage, while macroscopic damage occurs in the form of a "shear"-"splitting"-"mixed shear-splitting" damage process. This paper has certain research and reference value for understanding the damage evolution characteristics of rocks with peak front unloading damage.

Multimodal medical image fusion using adaptive co-occurrence filter-based decomposition optimization model.

MOTIVATION: Medical image fusion has developed into an important technology, which can effectively merge the significant information of multiple source images into one image. Fused images with abundant and complementary information are desirable, which contributes to clinical diagnosis and surgical planning. RESULTS: In this article, the concept of the skewness of pixel intensity (SPI) and a novel adaptive co-occurrence filter (ACOF)-based image decomposition optimization model are proposed to improve the quality of fused images. Experimental results demonstrate that the proposed method outperforms 22 state-of-the-art medical image fusion methods in terms of five objective indices and subjective evaluation, and it has higher computational efficiency. AVAILABILITY AND IMPLEMENTATION: First, the concept of SPI is applied to the co-occurrence filter to design ACOF. The initial base layers of source images are obtained using ACOF, which relies on the contents of images rather than fixed scale. Then, the widely used iterative filter framework is replaced with an optimization model to ensure that the base layer and detail layer are sufficiently separated and the image decomposition has higher computational efficiency. The optimization function is constructed based on the characteristics of the ideal base layer. Finally, the fused images are generated by designed fusion rules and linear addition. The code and data can be downloaded at https://github.com/zhunui/acof. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Polydopamine-coated downconversion nanoparticle as an efficient dual-modal near-infrared-II fluorescence and photoacoustic contrast agent for non-invasive visualization of gastrointestinal tract in vivo.

Herein, a multifunctional dual-modal imaging probe is successfully developed to integrate the advantages of second near-infrared window (NIR-II, 1000-1700 nm) fluorescence imaging (FI) and photoacoustic imaging (PAI) with the ultimate goal of improving diseases diagnosis and management. Melanin-inspired polydopamine (PDA) polymer coated NaYF4:Yb3+,Er3+@NaYbF4@NaYF4:Nd3+ down conversion nanoparticles (DCNPs) is designed via water-in-oil microemulsion method, which comprises a DCNP core, acting as the NIR-II optical imaging agent, and a PDA shell, acting as the PA contrast agent. By taking the advantages of high spatial resolution and excellent temporal resolution, the dual-modal contrast agent is capable for high sensitivity real-time visualization of gastrointestinal tract, diagnosis of gastrointestinal peristalsis disorder and NIR-II FI-guided intestinal obstruction surgery. All of the above results demonstrate the great potential of DCNP@PDA NP as an efficient NIR-II/PAI dual-modal contrast agent for precision medicine.

Intensely red-emitting luminescent upconversion nanoparticles for deep-tissue multimodal bioimaging.

Nowadays, in order to improve the diagnostic accuracy of the disease, more and more contrast agents have been applied in the clinical imaging modalities. A combination of nanotechnology with optical, computed X-ray tomography (CT), and magnetic resonance imaging (MRI) has great potential to improve disease diagnosis and therapy. Herein, we developed a novel multimodal contrast agent for deep-tissue bioimaging based on PEGylated Mn2+ doped NaLuF4:Yb/Er nanoparticles (PEG-UCNPs). The multimodal nanoprobes have revealed the intensely red upconversion luminescence emission for deep-tissue upconversion luminescence (UCL) imaging. Moreover, Owing to the high longitudinal relaxivity, the PEG-UCNPs can be used as T1-weighted MRI contrast agents. Additionally, with the high X-ray mass absorption coefficient of Lu3+, the novel nanoprobes are appropriate for CT imaging. With integration the high paramagnetic property, superior X-ray mass absorption coefficient and excellent upconversion luminescence in one system, the multimodal nanoprobes can provide a unique opportunity for MRI, CT and UCL imaging. More importantly, modification with PEG endows the novel nanoprobes with high biocompatibility, which would bring more opportunities for the biomedical applications in clinic.

Facile preparation of rare-earth based fluorescence/MRI dual-modal nanoprobe for targeted cancer cell imaging.

Nowadays, cancer has become a serious threat to public health worldwide. Early and precise diagnosis is critical for the detection, monitoring and management of cancer. Herein, a facile strategy for developing a fluorescence/MRI dual-modal nanoprobe (FA-PEI-NaGdF4:Eu nanoparticles) has been reported for targeted cancer cell imaging. The fluorescence/MRI nanoprobes have strong fluorescence and the high signal-to-noise ratio, which is suitable for the fluorescence imaging. Moreover, the FA-PEI-NaGdF4:Eu nanoprobes have high longitudinal relaxivity, making them suitable for T1-weighted MR imaging. Additionally, due to modification with FA, the fluorescence/MRI nanoprobes could target cancer cells that possessed large numbers of folate receptors. The results of the cytotoxicity assay revealed that the nanoprobes had the excellent biocompatibility. With the high biocompatibility, excellent imaging performance and superior targeting, the FA-PEI-NaGdF4:Eu nanoprobes can be used as a promising candidate for targeted fluorescence/MRI cancer cell imaging and would bring more opportunities for the biomedical applications.

Facile fabrication of single-phase multifunctional BaGdF5 nanospheres as drug carriers.

Multifunctional BaGdF5 nanospheres with mesoporous, luminescent, and magnetic properties have been successfully synthesized with the assistance of trisodium citrate by a hydrothermal method. The mesoporous structure is revealed by scanning electron microscope and transmission electron microscope images as well as N2 adsorption-desorption isotherm. The as-synthesized BaGdF5 nanospheres exhibit an intense broad bluish emission (centered at 450 nm) under the excitation of 390 nm, which might originate from the CO2·(-) radical-related defect produced by Cit(3-) groups. It is also shown that these BaGdF5 nanospheres brightened the T1-weighted images, suggesting that they could act as T1 contrast agents for magnetic resonance imaging. Using metformin hydrochloride as the model drug, the luminescent porous spheres show good drug storage/release capability. Furthermore, the emission intensity varies as a function of the cumulative drug release, making the drug-carrying system easily trackable and monitorable by detecting the luminescence intensity. Additionally, the paramagnetic property, originating from the unpaired electrons of Gd(3+) ions, opens the possibility of directing the magnetic targeted carrier to the pathological site by magnetic field gradient.

Biocompatible and high-performance amino acids-capped MnWO4 nanocasting as a novel non-lanthanide contrast agent for X-ray computed tomography and T(1)-weighted magnetic resonance imaging.

In the present work, a novel non-lanthanide dual-modality contrast agent, manganese tungstate (MnWO4), has been successfully constructed by a facile and versatile hydrothermal route. With the merits of a high atomic number and a well-positioned K-edge energy of tungsten, our well-prepared non-lanthanide nanoprobes provide a higher contrast efficacy than routine iodine-based agents in clinics. Additionally, the presence of Mn in these nanoparticles endow them with excellent T1-weighted MR imaging capabilities. As an alternative to T2-weighted MRI and CT dual-modality contrast agents, the nanoprobes can provide a positive contrast signal, which prevents confusion with the dark signals from hemorrhage and blood clots. To the best of our knowledge, this is the first report that a non-lanthanide imaging nanoprobe is applied for CT and T1-weighted MRI simultaneously. Moreover, comparing with gadolinium-based T1-weighted MRI and CT dual-modality contrast agents that were associated with nephrogenic systemic fibrosis (NSF), our contrast agents have superior biocompatibility, which is proved by a detailed study of the pharmacokinetics, biodistribution, and in vivo toxicology. Together with excellent dispersibility, high biocompatibility and superior contrast efficacy, these nanoprobes provide detailed and complementary information from dual-modality imaging over traditional single-mode imaging and bring more opportunities to the new generation of non-lanthanide nanoparticulate-based contrast agents.

Lanthanide-based hollow mesoporous nanoparticles: a novel multifunctional platform for simultaneous gene delivery and cell imaging.

GdPO4:Eu hollow spheres (denoted as GdPO4:Eu HMNs) with large pore channels in the shell have been designed as gene carriers while simultaneously acting as dual-mode bio-imaging probes.

Long-circulating Gd(2)O(3):Yb(3+), Er(3+) up-conversion nanoprobes as high-performance contrast agents for multi-modality imaging.

Due to their unique electric, magnetic, and optical properties, engineered nanostructures have been applied to provide diagnostic, therapeutic, as well as prognostic information about the status of disease. In this study, we report a multifunctional nanoprobe based on PEGylated Gd(2)O(3):Yb(3+), Er(3+) nanorods (denoted as PEG-UCNPs) for in vivo up-conversion luminescence (UCL), T(1)-enhanced magnetic resonance (MR), and X-ray computed tomography (CT) multi-modality imaging. A facile and large-scale hydrothermal system combining the merits of an in situ thermal decomposition method and a surface-modified approach is introduced to construct high-quality PEG-UCNPs. By grafting PEG molecules on the surface of PEG-UCNPs, the nanostructures possess excellent stability against in vivo environment and hold long blood circulation time. Cell-cytotoxicity assay, hemolyticity, as well as post-injection histology, hematology, and inflammation analysis further demonstrate their non-cytotoxic character and indicate further in vivo application. In detail, the capability of PEG-UCNPs as high-performance contrast agents for UCL/MR/CT imaging is evaluated successfully through small-animal experiments. Additionally, pharmacokinetics, biodistribution, and clearance route are studied after intravenous injection in a mouse model, reflecting their overall safety.