Hydroxychloroquine loaded hollow apoferritin nanocages for cancer drug repurposing and autophagy inhibition.

Hydroxychloroquine sulfate (HCQ) is currently being repurposed for cancer treatment. The antitumor mechanism of HCQ is inhibition of cellular autophagy, but its therapeutic potential is severely limited by poor solubility, lack of tumor targeting and lower cellular uptake. Therefore, utilization of human H-chain apoferritin (HFn) composed only of heavy subunits is an attractive approach for tumor targeting drug delivery. This study focused on pH-triggered encapsulation of HCQ within the inner cavity of HFn to form HFn@HCQ nanoparticles for tumor-targeted drug delivery. Characterization using a range of techniques has been used to confirm the successful establishment of HFn@HCQ. HFn@HCQ exhibited pH-responsive release behavior, with almost no drug release at pH 7.4, but 80% release at pH 5.0. Owing to its intrinsic binding to transferrin receptor 1 (TfR1), HFn@HCQ was significantly internalized through TfR1-mediated endocytosis, with a 4.4-fold difference of internalization amount across cell lines. Additionally, HFn@HCQ enhanced the antitumor effect against four different cancer cell lines when compared against HCQ alone, especially in TfR1 high-expressing cells, where the inhibitory effect was 3-fold higher than free HCQ. The autophagy inhibition of HFn@HCQ has been demonstrated, which is a major pathway to induce cancer cell death. According to current findings, HFn based drug delivery is a promising strategy to target and kill TfR1 overexpressing tumor cells.

A copper missile-triggered power coalescence and death vortex within tumor cell mitochondria for synergistic cuproptosis/phototherapy/chemotherapy.

The importance of copper homeostasis in mitochondria and copper-triggered modality of mitochondrial cell death have been confirmed. However, the existing copper-based nanoplatforms are focused on synergistic therapies while the intracellular therapeutic targets are relatively scattered. Effective integration of all targets within mitochondria to generate power coalescence remains a challenge. Herein, we developed a novel copper-based delivery system to trigger power coalescence and death vortex within tumor cell mitochondria. Specifically, a mitochondrial targeting "copper missile" loaded with curcumin (termed as Cur@CuS-TPP-HA, CCTH) was designed for cuproptosis/phototherapy/chemotherapy synergistic anti-tumor therapy. Once the CCTH NPs are shuttled to the mitochondria, near-infrared (NIR) irradiation initiates the release of copper ions and curcumin for in situ drug accumulation in cancer cell mitochondria. An excess of copper ions and curcumin can activate cuproptosis and mitochondrial apoptosis pathways, respectively. When combined, they can cause an increase in reactive oxygen species (ROS), damage to mitochondrial DNA (mt-DNA), and a decrease in energy supply, thereby leading to a "vicious circle" of mitochondrial damage that further enhances the tumor-killing efficacy. As a consequence, this "copper missile" exhibits advanced anti-tumor effects as verified through in vitro assessments and in vivo evaluations using the 4T1 breast tumor model, providing a promising approach for cuproptosis-based synergistic anti-tumor therapy.

Dental cementum anchored microspheres embedded in a self-healing hydrogel for the antibacterial, anti-inflammation, osteogenic, and anti-osteoclastic management of periodontitis disease.

Periodontitis, a prevalent chronic oral disease, poses a significant threat to periodontal tissues, often resulting in substantial attachment loss and tooth shedding. Leveraging the principles of bone affinity and the mechanism underlying tetracycline pigmentation of teeth, this study strategically employed tetracycline (TC) as a bone-affinity group. We modified TC on the surface of polylactic-co-glycolic acid copolymer (PLGA) microspheres (MSs) through covalent binding, and then loaded berberine (BBR) MSs into a thermosensitive self-healing hydrogel delivery system (BBR/TC-MS). It was verified that the BBR/TC-MS gel rapidly formed an in situ reservoir in the periodontal pocket upon injection, and the chelation between TC and cementum in the periodontal pocket enhanced the anchoring effect of the TC-modified microspheres on cementum, preventing their loss through gingival crevicular fluid. Subsequently, we proved in vitro and in vivo that the BBR/TC-MS gel has excellent bacteriostatic effects against the periodontal pathogenic bacteria Fusobacterium necrophorum (Fn), anti-inflammation property in periodontal and gingival tissues, and osteogenic effect by regulating the RANKL-RANK-OPG pathway to diminish osteoclast activity, thus continuously exerting antibacterial, anti-inflammatory, osteogenic, and anti-osteoclastic effects. This innovative approach holds promise as a targeted and effective strategy for combating multifaceted challenges posed by periodontitis.

Hydrostability, mechanical resilience, and biodegradability of paper straws fabricated through lignin-based polyurethane and chitosan binary emulsion bonding.

This study focuses on enhancing the strength and water stability of paper straws through a novel approach involving a binary emulsion of lignin-based polyurethane and chitosan. Kraft lignin serves as the raw material for synthesizing a blocked waterborne polyurethane, subsequently combined with carboxylated chitosan to form a stable binary emulsion. The resulting emulsion, exhibiting remarkable stability over at least 6 months, is applied to the base paper. Following emulsion application, the paper undergoes torrefaction at 155 °C. This process deblocks isocyanate groups, enabling their reaction with hydroxyl groups on chitosan and fibers, ultimately forming ester bonds. This reaction significantly improves the mechanical strength and hydrophobicity of paper straws. The composite paper straws demonstrate exceptional mechanical properties, including a tensile strength of 47.21 MPa, Young's modulus of 4.33 GPa, and flexural strength of 32.38 MPa. Notably, its water stability is greatly enhanced, with a wet tensile strength of 40.66 MPa, surpassing commercial paper straws by 8 folds. Furthermore, the composite straw achieves complete biodegradability within 120 days, outperforming conventional paper straws in terms of environmental impact. This innovative solution presents a promising and sustainable alternative to plastic straws, addressing the urgent need for eco-friendly products.

A nomogram to predict severe COVID-19 patients with increased pulmonary lesions in early days.

Objectives: This study aimed to predict severe coronavirus disease 2019 (COVID-19) progression in patients with increased pneumonia lesions in the early days. A simplified nomogram was developed utilizing artificial intelligence (AI)-based quantified computed tomography (CT). Methods: From 17 December 2019 to 20 February 2020, a total of 246 patients were confirmed COVID-19 infected in Jingzhou Central Hospital, Hubei Province, China. Of these patients, 93 were mildly ill and had follow-up examinations in 7 days, and 61 of them had enlarged lesions on CT scans. We collected the neutrophil-to-lymphocyte ratio (NLR) and three quantitative CT features from two examinations within 7 days. The three quantitative CT features of pneumonia lesions, including ground-glass opacity volume (GV), semi-consolidation volume (SV), and consolidation volume (CV), were automatically calculated using AI. Additionally, the variation volumes of the lesions were also computed. Finally, a nomogram was developed using a multivariable logistic regression model. To simplify the model, we classified all the lesion volumes based on quartiles and curve fitting results. Results: Among the 93 patients, 61 patients showed enlarged lesions on CT within 7 days, of whom 19 (31.1%) developed any severe illness. The multivariable logistic regression model included age, NLR on the second time, an increase in lesion volume, and changes in SV and CV in 7 days. The personalized prediction nomogram demonstrated strong discrimination in the sample, with an area under curve (AUC) and the receiver operating characteristic curve (ROC) of 0.961 and a 95% confidence interval (CI) of 0.917-1.000. Decision curve analysis illustrated that a nomogram based on quantitative AI was clinically useful. Conclusion: The integration of CT quantitative changes, NLR, and age in this model exhibits promising performance in predicting the progression to severe illness in COVID-19 patients with early-stage pneumonia lesions. This comprehensive approach holds the potential to assist clinical decision-making.

Elevated INHBA Promotes Tumor Progression of Cervical Cancer.

Objectives: This study aimed to explore the role of inhibin subunit beta A (INHBA) in the progression of cervical cancer (CCa) and investigate its potential as a therapeutic target. Specifically, the objectives were to assess the expression levels of INHBA in CCa, examine its correlation with patient survival, and elucidate its impact on CCa cell proliferation, cell cycle regulation, migration, invasion, and in vivo tumor growth and metastasis. Methods: To achieve the objectives, we conducted a comprehensive set of experimental methods. INHBA expression in CCa was analyzed, and its association with patient survival was assessed using clinical data. In vitro experiments involved the investigation of INHBA's effects on CCa cell proliferation, cell cycle dynamics, migration, and invasion through the epithelial-mesenchymal transition (EMT) process. Additionally, in vivo experiments were performed to evaluate the influence of INHBA on CCa growth and lung metastasis. Results: The results of this study revealed upregulated expression of INHBA in CCa, with a significant association between high INHBA expression and poor patient survival. Functionally, INHBA was found to promote the proliferation of CCa cells, regulate the cell cycle, and enhance migration and invasion through the EMT process in vitro. Moreover, in vivo experiments demonstrated that INHBA facilitated the growth and lung metastasis of CCa. Conclusion: In conclusion, our findings suggest that INHBA plays a crucial role in the progression of cervical cancer. The upregulation of INHBA is associated with poor patient survival, and its involvement in promoting key aspects of cancer progression makes it a potential therapeutic target for CCa treatment. These results provide valuable insights into the molecular mechanisms underlying CCa and offer a foundation for further exploration of targeted therapeutic interventions.

Advanced strategies for CRISPR/Cas9 delivery and applications in gene editing, therapy, and cancer detection using nanoparticles and nanocarriers.

Cancer remains one of the deadliest diseases, and is characterised by the uncontrolled growth of modified human cells. Unlike infectious diseases, cancer does not originate from foreign agents. Though a variety of diagnostic procedures are available; their cost-effectiveness and accessibility create significant hurdles. Non-specific cancer symptoms further complicate early detection, leading to belated recognition of certain cancer. The lack of reliable biomarkers hampers effective treatment, as chemotherapy, radiation therapy, and surgery often result in poor outcomes and high recurrence rates. Genetic and epigenetic mutations play a crucial role in cancer pathogenesis, necessitating the development of alternate treatment methods. The advent of CRISPR/Cas9 technology has transformed molecular biology and exhibits potential for gene modification and therapy in various cancer types. Nonetheless, obstacles such as safe transport, off-target consequences, and potency must be overcome before widespread clinical use. Notably, this review delves into the multifaceted landscape of cancer research, highlighting the pivotal role of nanoparticles in advancing CRISPR/Cas9-based cancer interventions. By addressing the challenges associated with cancer diagnosis and treatment, this integrated approach paves the way for innovative solutions and improved patient outcomes.

Urease catalyzed high-density sodium alginate microspheres enable high oral bioavailability of macromolecular drugs.

Destruction of insulin caused by the gastric microenvironment and rapid deactivation pose inevitable barriers to oral macromolecular absorption, especially for most peptide and protein drugs. In this study, we developed high-density sodium alginate microspheres composed of magnesium oxide and urease to address these challenges. These microspheres aim to anchor the gastric mucus layer and induce microenvironmental liquefaction, thereby enhancing gastric retention and the protection of insulin. The sedimentation test confirmed the capability of the Ins/Ur/MgO@SA microsphere to rapidly traverse the gastric juice under the influence of gravity. Additionally, the urease immobilized on the Ins/Ur/MgO@SA microspheres catalyzes the hydrolysis of urea in the gastric mucus and promotes the liquefaction of mucus, which is beneficial for microsphere retention. The inclusion of MgO particles and urease, acting as pHM modifiers, helps in adjusting the local pH to avoid gastric acid-induced damage. Subsequently, an in vivo pharmacokinetic experiment verified that the relative bioavailability of the p.o. Ins/Ur/MgO@SA treated group was 15-fold higher than that of the p.o.insulin treated group. Meanwhile, satisfactory blood glucose level (BGL) reduction was observed in diabetic animals. In conclusion, Ins/Ur/MgO@SA microspheres demonstrate high biocompatibility as insulin carriers with prolonged drug release time and increased gastric retention properties, showing a far-reaching strategy for oral macromolecular drug delivery.

Knowledge correlation graph-guided multi-source interaction domain adaptation network for rotating machinery fault diagnosis.

Leveraging generalized knowledge from multiple source domains with rich labels to the target domain without labeled data is a more realistic and challenging issue compared with single-source domain adaptation. Furthermore, the distribution discrepancies between each source domain and the expansion of data categories increase the difficulty of aligning each source domain with the target domain. To alleviate these issues, a knowledge correlation graph-guided multi-source interaction domain adaptation network (KCGMIDAN) is developed for rotating machinery fault diagnosis. Firstly, a random mini-batch is randomly selected to update comprehensive feature representations (CFR) extracted from each data category across all domains, thus promoting the knowledge interaction of acquired CFR between the current and the next epochs. Then, a knowledge correlation graph (KCG) is established on all CFR to boost knowledge propagation among various domains. To improve the compactness of characteristics within the same category and the separation of various categories, two losses are designed in this procedure to place constraints on the relationships between categories. Finally, query samples are added into KCG to construct the extended KCG, and the recognition of samples is completed by using built deep graph network based on the extended KCG. Extensive experimental results verify that KCGMIDAN can achieve better recognition performance than existing methods.

Characterization and anti-aging effects of polysaccharide from Gomphus clavatus Gray.

In this study, a highly branched polysaccharide (GPF, 112.0 kDa) was isolated and purified from Gomphus clavatus Gray fruiting bodies. GPF was primarily composed of mannose, galactose, arabinose, xylose, and glucose at a molar ratio of 3.2:1.9:1.6:1.2:1.0. GPF was a highly branched heteropolysaccharide composed of 13 glucosidic bonds, with a degree of branching (DB) of 48.85 %. GPF exhibited anti-aging activity in vivo, significantly increased antioxidant enzymes activities (SOD, CAT and GSH-Px), improved total antioxidant capability (T-AOC) and decreased MDA level in the serum and brain of d-Gal induced aging mice. Behavioral experiments showed that GPF effectively improved learning and memory deficits in d-Gal induced aging mice. Mechanistic studies indicated that GPF could activate AMPK by increasing AMPK phosphorylation and upregulating SIRT1 and PGC-1α expression. These findings suggest that GPF has significant potential as a natural candidate to slow down aging and prevent aging-related diseases.

Liquid-like Oral Sustained-Release System Based on Acid-Sensitive in situ Hydrogel for Alleviate Gastrointestinal Side Effects of Indobufen.

Commonly, most oral non-steroidal anti-inflammatory drugs (NSAIDs) have known gastric adverse reactions due to their long-term and high dose administration. In this study, a novel liquid sustained-release system based on multiple-unit in situ hydrogel beads was designed to address this issue. The system is composed of sodium alginate (SA), gellan gum (GG), zinc oxide (ZnO), and magnesium oxide (MgO). Furthermore, indobufen was loaded into the system to evaluate its gastric mucosal protection effect. This effect can be attributed to the topical antacid, pepsin inhibition, and sustained drug release properties of the system. It was proven that the stored solid gel system could undergo a "solid to liquid" transition after shaking. Once swallowed, the liquid gel could disperse well in the stomach as hydrogel beads. Then, the "liquid to solid" gelation occurred from the exterior to interior of each multiple-unit gel bead, triggered by the release of Zn2+ and Mg2+ from neutralization reactions. The formed gel demonstrated mild antacid effect that lasted for 3 hours and 66.3% pepsin inhibition in vivo. Moreover, the rats treated with the indobufen gel system showed a drug plasma concentration versus time curve with less fluctuation compared to the rats treated with the marketed preparation (YinDuo®) group. The gel system also exhibited an extended Tmax (6.50 hours) and reduced Cmax (52.87 µg/mL). Additionally, the gastric mucosal protection of the gel system was verified using three types of peptic gastric ulcer models. These findings suggested that this multiple-unit in situ gel could be a potential oral liquid sustained release delivery system for NSAIDs.

Bone mesenchymal stem cell-derived exosomes involved co-delivery and synergism effect with icariin via mussel-inspired multifunctional hydrogel for cartilage protection.

Mesenchymal stem cells (MSC) are particularly effective in promoting cartilage regeneration due to their immunomodulatory, anti-inflammatory and regenerative repair functions of tissues and organs. Meanwhile, the intra-articular delivery and synergy with other therapeutic drugs have been the key issues driving their further application. We report a mussel-inspired multifunctional hydrogel system, which could achieve co-delivery and synergism effect of MSC-derived exosomes (Exos) with icariin (ICA). The ICA and Exos co-delivered articular cavity injection system are expected to retain in the joint cavity and promote cartilage regeneration, due to the thermosensitive, self-healing and adhesion properties of the mussel-inspired multifunctional hydrogel. The experimental results proved that Exos enhanced the cellular uptake of ICA by more than 2-fold evenly, and the synergism of Exos and ICA efficiently improve the cell proliferation and migration. After synergic treatment, the content of matrix metalloproteinase 13 in the supernatant and intracellular decreased by 47% and 59%, respectively. In vivo study, ICA-loaded Exos exhibited prolonged retention behavior by multifunctional hydrogel delivery, thus displayed an increased cartilage protection. In the model of osteoarthritis, co-delivery hydrogel system relieved the cartilage recession, ensuring appropriate cartilage thickness.

Morphology-induced differences in adsorption behaviors and strength enhancement performance for fiber networks between quaternized amylose and amylopectin.

Cationic starch is the most widely used paper strength additive for papermaking wet end applications. However, it remains unclear how differently quaternized amylose (QAM) and amylopectin (QAP) are adsorbed on the fiber surface and their relative contribution to the inter-fiber bonding of papers. Herein, separated amylose and amylopectin were quaternized with different degrees of substitution (DS). After that, the adsorption behaviors of QAM and QAP on the fiber surface, the viscoelastic properties of the adlayers and their strength enhancement to fiber networks were comparatively characterized. Based on the results, the morphology visualizations of the starch structure displayed a strong impact on the adsorbed structural distributions of QAM and QAP. QAM adlayer with a helical linear or slightly branched structure was thin and rigid, while the QAP adlayer with a highly branched structure was thick and soft. In addition, the DS, pH and ionic strength had some impacts on the adsorption layer as well. Regarding the paper strength enhancement, the DS of QAM correlated positively to the paper strength, whereas the DS of QAP correlated inversely. The results provide a deep understanding of the impacts of starch morphology on performance and offer us some practical guidelines in starch selection.

Ferroptosis-related metabolic mechanism and nanoparticulate anticancer drug delivery systems based on ferroptosis.

Ferroptosis is a new type of cell death discovered in recent years that distinguishes from apoptosis and necrosis, mainly caused by the imbalance between the production and degradation of lipid reactive oxygen species in cells. Although the mechanism of ferroptosis is not yet clear, the phenomenon of ferroptosis has attracted widespread attention from researchers and has become a new hotspot in anti-tumor research. Studies have shown that ferroptosis is involved in the occurrence and development of a variety of diseases such as nervous system diseases, cardiovascular diseases and cancer. And inhibiting or inducing the occurrence of ferroptosis can effectively intervene in related diseases. At the same time, nanotechnology, by virtue of its distinct advantages, has been widely used in the development of nanodrug delivery systems. This review outlines current the advance on the intersection of ferroptosis and biomedical nanotechnology. In this review, the discovery and characteristics of ferroptosis, the mechanism of occurrence and the relationship with disease are summarized. More importantly, we summarized the strategies for inducing ferroptosis based on nanoparticulate drug delivery systems for cancer treatment.

"Shell-Core" Bilayer Nanoparticle as Chemotherapeutic Drug Co-Delivery Platforms Render Synchronized Microenvironment Respond and Enhanced Antitumor Effects.

Background: Synergistic chemotherapy has been proved as an effective antitumor means in clinical practice. However, most co-administration treatment often lacks simultaneous control over the release of different chemotherapeutic agents. Materials and Methods: ß-cyclodextrin modified hyaluronic acid was the "shell", and the oxidized ferrocene-stearyl alcohol micelles served as the "core", where doxorubicin (DOX) and curcumin (CUR) were loaded in shell and core of the bilayer nanoparticles (BNs), respectively. The pH- and glutathione (GSH)-responsive synchronized release behavior was evaluated in different mediums, and the in vitro and in vivo synergistic antitumor effect and CD44-mediated tumor targeting efficiency were further investigated. Results: These BNs had a spherical structure with the particle size of 299 ± 15.17 nm, while the synchronized release behaviour of those two drugs was proved in the medium with the pH value of 5.5 and 20 mM GSH. The co-delivery of DOX and CUR reduced the IC50 value by 21% compared to DOX alone, with a further 54% reduction after these BNs delivery measurements. In tumor-bearing mouse models, these drug-loaded BNs showed significant tumor targeting, enhanced antitumor activity and reduced systemic toxicity. Conclusion: The designed bilayer nanoparticle could be considered as potential chemotherapeutic co-delivery platform for efficient synchronized microenvironment respond and drug release. Furthermore, the simultaneous and synergistic drug release guaranteed the enhanced antitumor effects during the co-administration treatment.

Risk factors and characteristics of new-onset coronary heart disease in adults with physical disabilities: A retrospective cohort study.

Objectives: There is limited information about coronary heart disease (CHD) in adults with physical disabilities. This study was performed to assess the incidence and predictors of the new development of CHD in adults with physical disabilities. Methods: A retrospective cohort study was performed on 3902 physically disabled people in Shanghai, China. Baseline information was collected in January 2012, and participants were followed-up with for 7.5 years for CHD events. Risk factors for demographic characteristics, disease history, electrocardiography, and blood biochemical indicators were evaluated using a Cox proportional hazard model. Subgroup analyzes were performed according to gender and level of physical disability. Results: Out of the total 3902 adults with physical disabilities (average age 55.9 ± 8.5 years), 468 (12.0%) developed CHD, during a median follow-up period of 7 years. Independent predictors of CHD included the following: age (HR = 1.411, 95% CI = 1.255-1.587, p＜0.001), gender (HR = 0.773, 95% CI = 0.637-0.940, p = 0.010), abnormal electrocardiogram(HR = 1.396, 95% CI = 1.088-1.792, p = 0.009), hypertension (HR = 1.657, 95% CI = 1.369-2.006, p＜0.001), diabetes (HR = 1.649, 95% CI = 1.307-2.081, p＜0.001), serum uric acid (HR = 1.001, 95% CI = 1.000-1.002, p = 0.046), and total cholesterol (HR = 1.416, 95% CI = 1.054-1.902, p = 0.021). In addition to the risk factors of the total population with physical disability, triglyceride was also a significant risk factor for CHD in the subgroup with women and mild disability. Conclusions: During a 7.5 years period, the CHD incidence rate among physically disabled people was 12.0%. We identified the role of CHD risk factors such as age, gender, hypertension, diabetes, serum uric acid, total cholesterol, and abnormal electrocardiogram.

High skin permeation, deposition and whitening activity achieved by xanthan gum string vitamin c flexible liposomes for external application.

For most external applied antioxidant whitening ingredients, effective stratum corneum breakthrough, epidermal penetration and dermal deposition are necessary premises for inhibition of melanin production and transfer occurring in stratum basale. Herein, xanthan gum was added into vitamin C-containing flexible liposome (Vc-L) suspension. The long polymer chain of xanthan gum string dispersed Vc-L together to gain a lotion (Vc-LX) for external application. In this study, the storage stability experiments demonstrated that the additional xanthan gum could improve the storage stability of Vc liposome suspension. The cumulative in vitro skin penetration and deposition of Vc-LX was found to significantly increase within 24 h in mouse skin, compared with those of the Vc aqueous solution and Vc conventional liposomes treated groups (***p < 0.001). Most importantly, in vivo skin whitening experiments gave that Vc-LX has better skin whitening activity (ΔL*) than marketed products (GARNIER® Vc377), Vc flexible liposomes, and Vc conventional liposomes. Moreover, in vitro cytotoxicity experiments and skin irritation experiments demonstrated that Vc-LX has good biosafety. Therefore, this study suggested that Vc-LX may be a promising local skin delivery system for water-soluble antioxidant ingredients.

Traumatic Brain Magnetic Resonance Imaging Feature Extraction Based on Variable Model Algorithm in Stroke Examination.

The purpose of this study was to explore the diagnostic value of different sequence scanning of nonparametric variable model-based cranial magnetic resonance imaging (MRI) for ischemic stroke. A histogram analysis-based nonparametric variable model was proposed first, which was compared with the parametric deformation (PD) model and geometric deformation (GD) model. Then, 116 patients with acute ischemic stroke were selected as the research subjects. Routine MRI (T2WI, T1WI, FLAIR, DWI, SWI, and 3D TOF MRA) and MR SCALE-PWI were performed. The results showed that the nonparametric variable model algorithm was relatively complete in the actual segmentation results of MRI images, and the display clarity of lesions was better than PD and GD algorithms. The diagnostic sensitivity, specificity, and overall performance of the variable model algorithm were significantly higher than those of the other two algorithms (P < 0.05). According to ROC curve analysis, the AUC areas of DWI, SWI, 3D TOF MRA, and MR SCALE-PWI for the diagnosis of ischemic penumbra were 0.793, 0.825, 0.871, and 0.933, respectively. In summary, the segmentation results of MRI images by the nonparametric variable model based on histogram analysis were relatively complete, and the clarity of lesions was better than that of the traditional model. MRI images can effectively identify the occurrence of ischemic stroke. Moreover, MR SCALE-PWI had a good early identification effect on ischemic penumbra, which can reduce unnecessary treatment for patients.

A deep reinforcement transfer convolutional neural network for rolling bearing fault diagnosis.

Deep neural networks highly depend on substantial labeled samples when identifying bearing fault. However, in some practical situations, it is very difficult to collect sufficient labeled samples, which limits the application of deep neural networks in practical engineering. Therefore, how to use limited labeled samples to complete fault diagnosis tasks is an urgent problem. In this paper, a deep reinforcement transfer convolutional neural network (DRTCNN) is developed to tackle the problem. Firstly, an intelligent diagnosis agent constructed by a convolutional neural network is trained to obtain maximum long-term cumulative rewards, which is characterized by the ability to autonomously learn the latent relationship between fault samples and corresponding labels. Secondly, the parameter transfer learning method is utilized to establish a target task agent of DRTCNN. Finally, limited labeled target domain fault samples and the training mechanism of deep Q-network are employed to train the target task agent for performing target diagnosis tasks. Two diagnosis cases are conducted to verify the effectiveness of the proposed method when only limited labeled target domain fault samples are available.

Copper-induced tumor cell death mechanisms and antitumor theragnostic applications of copper complexes.

Recent studies found that unbalanced copper homeostasis affect tumor growth, causing irreversible damage. Copper can induce multiple forms of cell death, including apoptosis and autophagy, through various mechanisms, including reactive oxygen species accumulation, proteasome inhibition, and antiangiogenesis. Hence, copper in vivo has attracted tremendous attention and is in the research spotlight in the field of tumor treatment. This review first highlights three typical forms of copper's antitumor mechanisms. Then, the development of diverse biomaterials and nanotechnology allowing copper to be fabricated into diverse structures to realize its theragnostic action is discussed. Novel copper complexes and their clinical applications are subsequently described.