One-stop detection of anterior cruciate ligament injuries on magnetic resonance imaging using deep learning with multicenter validation.

Background: Anterior cruciate ligament (ACL) injuries are closely associated with knee osteoarthritis (OA). However, diagnosing ACL injuries based on knee magnetic resonance imaging (MRI) has been subjective and time-consuming for clinical doctors. Therefore, we aimed to devise a deep learning (DL) model leveraging MRI to enable a comprehensive and automated approach for the detection of ACL injuries. Methods: A retrospective study was performed extracting data from the Osteoarthritis Initiative (OAI). A total of 1,589 knees (comprising 1,443 intact, 90 with partial tears, and 56 with full tears) were enrolled to construct the classification model. This one-stop detection pipeline was developed using a tailored YOLOv5m architecture and a ResNet-18 convolutional neural network (CNN) to facilitate tasks based on sagittal 2-dimensional (2D) intermediate-weighted fast spin-echo sequence at 3.0T. To ensure the reliability and robustness of the classification system, it was subjected to external validation across 3 distinct datasets. The accuracy, sensitivity, specificity, and the mean average precision (mAP) were utilized as the evaluation metric for the model performance by employing a 5-fold cross-validation approach. The radiologist's interpretations were employed as the reference for conducting the evaluation. Results: The localization model demonstrated an accuracy of 0.89 and a sensitivity of 0.93, achieving a mAP score of 0.96. The classification model demonstrated strong performance in detecting intact, partial tears, and full tears at the optimal threshold on the internal dataset, with sensitivities of 0.941, 0.833, and 0.929, specificities of 0.925, 0.947, and 0.991, and accuracies of 0.940, 0.941, and 0.989, respectively. In comparison, on a subset consisting of 171 randomly selected knees from the OAI, the radiologists demonstrated a sensitivity ranging between 0.660 and 1.000, specificity ranging between 0.691 and 1.000, and accuracy ranging between 0.689 and 1.000. On a subset consisting of 170 randomly selected knees from the Chinese dataset, the radiologists exhibited a sensitivity ranging between 0.711 and 0.948, specificity ranging between 0.768 and 0.977, and accuracy ranging between 0.683 and 0.917. After retraining, the model achieved sensitivities ranging between 0.630 and 0.961, specificities ranging between 0.860 and 0.961, and accuracies ranging between 0.832 and 0.951, respectively, on the external validation dataset. Conclusions: The proposed model utilizing knee MRI showcases robust performance in the domains of ACL localization and classification.

Mesencephalic astrocyte-derived neurotrophic factor inhibits cervical cancer progression via regulating macrophage phenotype.

BACKGROUND: Cervical cancer is a common gynecologic malignant tumor, but the critical factors affecting cervical cancer progression are still not well demonstrated. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been widely recognized as an anti-inflammatory factor to regulate macrophage polarization. In this study, the effect and mechanism of MANF on cervical cancer were preliminarily explored. METHODS AND RESULTS: Kaplan-Meier curve was used to show the overall survival time of the involved cervical cancer patients with high and low MANF expression in cervical cancer tissues. MANF was highly expressed in peritumoral tissues of cervical carcinoma by using immunohistochemistry and western blot. MANF mRNA level was detected by using qRT-PCR. Dual-labeled immunofluorescence showed MANF was mainly expressed in macrophages of cervical peritumoral tissues. Moreover, MANF-silenced macrophages promoted HeLa and SiHa cells survival, migration, invasion and EMT via NF-κB signaling activation. The results of tumor formation in nude mice indicated MANF-silenced macrophages promoted cervical tumor formation in vivo. CONCLUSION: Our study reveals an inhibitory role of MANF in cervical cancer progression, indicating MANF as a new and valuable therapeutic target for cervical cancer treatment.

Solvent-free synthesis of defective Zr-based metal-organic framework from waste plastic bottles for highly efficient lomefloxacin removal.

Large amount of polyethylene terephthalate (PET) plastics waster and emerging contaminants in water, including fluoroquinolone antibiotics, pose challenges to human survival. In this work, a green synthesis scheme is proposed in which the defective UiO-66 (d-UiO-66) is fabricated via a solvent-free routine by using PET plastics waster as raw materials for lomefloxacin (LOM) removal. In comparison with defect-free UiO-66, the created defect imparts d-UiO-66 with higher porosity and abundant defective Zr sites, which are beneficial to boost LOM adsorption. As expected, d-UiO-66 exhibited excellent LOM adsorption performances, showcasing a saturation adsorption capacity of 588 mg g-1 and a kinetic rate constant of 0.204 g mg-1 h-1, which are 3.5 and 2.0 times higher than those of the pristine UiO-66, respectively. Remarkably, the LOM saturation adsorption capacity of d-UiO-66 surpasses that of all reported adsorbents. Mechanism study reveals that this outstanding adsorption performance of d-UiO-66 is mainly ascribed to the abundant defective sites, high porosity, together with the strong hydrogen bonding interaction and π-π stacking interaction between d-UiO-66 and LOM. Therefore, the d-UiO-66 obtained by the solvent-free method can not only effectively upcycle PET plastic waster, but also efficiently remove LOM, demonstrating a potential routine to simultaneous address the solid PET waster and wastewater.

High-Level Extracellular Production of a Trisaccharide-Producing Alginate Lyase AlyC7 in Escherichia coli and Its Agricultural Application.

Alginate oligosaccharides (AOS), products of alginate degradation by endotype alginate lyases, possess favorable biological activities and have broad applications. Although many have been reported, alginate lyases with homogeneous AOS products and secretory production by an engineered host are scarce. Herein, the alginate lyase AlyC7 from Vibrio sp. C42 was characterized as a trisaccharide-producing lyase exhibiting high activity and broad substrate specificity. With PelB as the signal peptide and 500 mM glycine as the additive, the extracellular production of AlyC7 in Escherichia coli reached 1122.8 U/mL after 27 h cultivation in Luria-Bertani medium. The yield of trisaccharides from sodium alginate degradation by the produced AlyC7 reached 758.6 mg/g, with a purity of 85.1%. The prepared AOS at 20 µg/mL increased the root length of lettuce, tomato, wheat, and maize by 27.5%, 25.7%, 9.7%, and 11.1%, respectively. This study establishes a robust foundation for the industrial and agricultural applications of AlyC7.

An empirical study of the flag rugby game programme to promote gross motor skills and physical fitness in 5-6 year old preschool children.

In order to investigate the effects of a flag rugby game programs on the development of gross motor skills and physical fitness in 5-6 year old preschool children. An overall random sampling method was adopted to select 56 preschoolers aged 5-6 years from class A and class B,class A was the ExG (28) implemented a flag rugby games intervention program,and class B was the ConG (28) implemented a regular physical education program,with a 12-week intervention period.The content and requirements of the experimental intervention program were determined through a systematic analysis method, and the subjects' gross motor skills level was tested using the TGMD-3, and their physical fitness level was measured using China's fifth national physical fitness monitoring of early childhood (3-6 years) component.Experimental data were statistically analyzed using independent samples t-test, paired samples t-test, and repeated measures ANOVA test.After 12 weeks of practice, 1）We found that the ExG outperformed the ConG in Skip,One hand stationary dribble, Overhand throw, Underhand throw, Forehand strike of self-bounced,Kick a stationary ball, Total object control subject score, Total gross motor score test results with significant differences (p < 0.05).The ExG differed significantly (p < 0.01) in Grip strength, Stand long jump,Sit forward bend, Continuous jump on both feet,15 m obstacle run,Walk the balance beam, while the ConG differed significantly (p < 0.05) only in Continuous jump on both feet,15 m obstacle run and Stand long jump.2）We also found gender differences in gross motor skills and Physical fitness test results, this difference is manifested in boys outperformed girls in Total object control subject Score, Grip strength and 15 m obstacle run with significant difference (p < 0.05), girls outperformed boys in Sit forward bend with significant difference (p < 0.05).The 12-week flag rugby game programs improved gross motor skills and physical fitness levels of 5-6 year old preschoolers more comprehensively than the regular program, and we recommend the purposeful and organized promotion of a flag rugby game programs in the physical activity curriculum for 5-6 year old preschoolers.

The application value of deep learning-based nomograms in benign-malignant discrimination of TI-RADS category 4 thyroid nodules.

Thyroid nodules are a common occurrence, and although most are non-cancerous, some can be malignant. The American College of Radiology has developed the Thyroid Imaging Reporting and Data System (TI-RADS) to standardize the interpretation and reporting of thyroid ultrasound results. Within TI-RADS, a category 4 designation signifies a thyroid nodule with an intermediate level of suspicion for malignancy. Accurate classification of these nodules is crucial for proper management, as it can potentially reduce unnecessary surgeries and improve patient outcomes. This study utilized deep learning techniques to effectively classify TI-RADS category 4 thyroid nodules as either benign or malignant. A total of 500 patients were included in the study and randomly divided into a training group (350 patients) and a test group (150 patients). The YOLOv3 model was constructed and evaluated using various metrics, achieving an 84% accuracy in the classification of TI-RADS category 4 thyroid nodules. Based on the predictions of the model, along with clinical and ultrasound data, a nomogram was developed. The performance of the nomogram was superior in both the training and testing groups. Furthermore, the calibration curve demonstrated good agreement between predicted probabilities and actual outcomes. Decision curve analysis further confirmed that the nomogram provided greater net benefits. Ultimately, the YOLOv3 model and nomogram successfully improved the accuracy of distinguishing between benign and malignant TI-RADS category 4 thyroid nodules, which is crucial for proper management and improved patient outcomes.

Cold atmospheric plasma attenuates skin cancer via ROS induced apoptosis.

BACKGROUND: Cold atmospheric plasma (CAP) has been widely used in biomedical research, especially in vitro cancer therapy. Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor originating from epidermal keratinocytes. However, the mechanism of CAP therapy on CSCC remains unclear. METHODS AND RESULTS: The animal models of CSCC induced by 7,12-dimethylbenz(a) anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) were constructed. For the CAP treatment group, after each TPA application, CAP was administered for 3 min twice weekly after drying. HE staining were used to detect the pathological status of tumor tissue in each group. The levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 were evaluated by western blot and qPCR. TUNEL staining were used to detect apoptosis in tumor tissues. In vivo, serum samples were used for ELISA of total ROS. MTT assay was used to detect the viability of A431 cells. Western blot and qPCR were used to detect the levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 in A431 cells. A431 cell proliferation was examined by colony formation assay. The proportions of apoptosis of A431 cells were detected by flow cytometry. Transwell assessed the ability of A431 cells migration and proliferation. We found that CAP could induce skin cancer cells apoptosis and inhibit the progress of skin cancer. Through experiments in vitro, reactive oxygen species (ROS) generated by N-acetylcysteine (NAC) and CAP inhibited the proliferation and migration of A431 skin cancer cells while promoting apoptosis. CONCLUSIONS: These evidences suggest the protective effect of CAP in CSCC, and CAP has the potential clinical application of CSCC.

Nervonic acid alleviates MPTP-induced Parkinson's disease via MEK/ERK pathway.

Nervonic acid (NA) is a primary long-chain fatty acid and has been confirmed to have neuroprotective effects in neurologic diseases. Oxidative stress and neuronal damage are the main causes of Parkinson's disease (PD). This study mainly explored whether NA is involved in regulating oxidative stress and apoptosis in MPTP-induced mouse model and MPP-induced cell model. Through behavior tests, we proved that MPTP-induced motor dysfunction in mice was recovered by NA treatment. NA can reduce MPTP-induced neuronal damage, manifested by elevated levels of TH and dopamine, as well as decreased levels of α-syn. In the in vitro model, we observed from CCK8 assay and flow cytometry that the induction of MPP markedly suppressed cell activity and enhanced cell apoptosis, but these functions were all reversed by NA. Furthermore, NA administration reversed the increase in ROS production and MDA levels induced by MPTP or MPP, as well as the decrease in SOD levels, suggesting the antioxidant properties of NA in PD. Meanwhile, we confirmed that NA can regulate oxidative stress and neuronal damage by activating the MEK/ERK pathway. Overall, we concluded that NA could alleviate MPTP-induced PD via MEK/ERK pathway.

Mesencephalic astrocyte-derived neurotrophic factor ameliorates inflammatory response in polycystic ovary syndrome via inhibiting TLR4-NF-κB-NLRP3 pathway.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in women of reproductive age, which often leads to female infertility. Chronic inflammation is a significant factor in the development of PCOS. Our study aimed to explore the impact of mesencephalic astrocyte-derived neurotrophic factor (MANF), a scientifically validated anti-inflammatory factor, on 99 diagnosed PCOS patients. We also investigated its effects on PCOS mice induced with dehydroepiandrosterone (DHEA) and KGN cells induced with dihydrotestosterone (DHT). Our findings revealed a decrease in serum MANF levels in PCOS patients, which were negatively associated with serum tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels. The administration of recombinant human MANF (rhMANF) in PCOS mice demonstrated a decrease in pro-inflammatory cytokines and monocytes/macrophages in both peripheral blood and ovarian tissues. Furthermore, the inclusion of rhMANF notably ameliorated DHEA-induced ovarian dysfunction and fibrosis by negatively regulating the toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB)-NLR family, pyrin domain containing protein 3 (NLRP3) pathway. Additionally, in vitro experiments showed that the up-regulation of MANF offset DHT-induced inhibition of viability and apoptosis in KGN cells. Collectively, this study highlights the anti-inflammatory properties of MANF in PCOS and suggests its potential as a therapeutic approach for the management of PCOS.

Ferrostatin-1 improves prognosis and regulates gut microbiota of steatotic liver transplantation recipients in rats.

Aims: To investigate the effects of Ferrostatin-1 (Fer-1) on improving the prognosis of liver transplant recipients with steatotic liver grafts and regulating gut microbiota in rats. Methods: We obtained steatotic liver grafts and established a liver transplantation model. Recipients were divided into sham, liver transplantation and Fer-1 treatment groups, which were assessed 1 and 7 days after surgery (n = 6). Results & conclusion: Fer-1 promotes recovery of the histological structure and function of steatotic liver grafts and the intestinal tract, and improves inflammatory responses of recipients following liver transplantation. Fer-1 reduces gut microbiota pathogenicity, and lowers iron absorption and improves fat metabolism of recipients, thereby protecting steatotic liver grafts.

Integration of a Cu2O/ZnO heterojunction and Ag@SiO2 into a photoanode for enhanced solar water oxidation.

Photoelectrochemical water splitting (PEC-WS) has attracted considerable attention owing to its low energy consumption and sustainable nature. Constructing semiconductor heterojunctions with controllable band structure can effectively facilitate photogenerated carrier separation. In this study, a FTO/ZnO/Cu2O/Ag@SiO2 photoanode with a Cu2O/ZnO p-n heterojunction and Ag@SiO2 nanoparticles is constructed to investigate its PEC-WS performance. Compared with a bare ZnO photoanode, the photocurrent density of the FTO/ZnO/Cu2O/Ag@SiO2 photoanode (0.77 mA cm-2) at 1.23 VRHE exhibits an increment of 88%, and a cathodic shift of 0.1 V for the on-set potential (0.4 VRHE). Detailed photoelectrochemical analyses reveal that the Cu2O/ZnO p-n heterojunction formed between Cu2O and ZnO can effectively promote photogenerated carrier separation. The surface plasmonic effect of the Ag@SiO2 nanoparticles can further promote the photogenerated carrier transfer efficiency, which synergistically improves the PEC-WS performance.

Entropy-Based Node Importance Identification Method for Public Transportation Infrastructure Coupled Networks: A Case Study of Chengdu.

Public transportation infrastructure is a typical, complex, coupled network that is usually composed of connected bus lines and subway networks. This study proposes an entropy-based node importance identification method for this type of coupled network that is helpful for the integrated planning of urban public transport and traffic flows, as well as enhancing network information dissemination and maintaining network resilience. The proposed method develops a systematic entropy-based metric based on five centrality metrics, namely the degree centrality (DC), betweenness centrality (BC), closeness centrality (CC), eigenvector centrality (EC), and clustering coefficient (CCO). It then identifies the most important nodes in the coupled networks by considering the information entropy of the nodes and their neighboring ones. To evaluate the performance of the proposed method, a bus-subway coupled network in Chengdu, containing 10,652 nodes and 15,476 edges, is employed as a case study. Four network resilience assessment metrics, namely the maximum connectivity coefficient (MCC), network efficiency (NE), susceptibility (S), and natural connectivity (NC), were used to conduct group experiments. The experimental results demonstrate the following: (1) the multi-functional fitting analysis improves the analytical accuracy by 30% as compared to fitting with power law functions only; (2) for both CC and CCO, the improved metric's performance in important node identification is greatly improved, and it demonstrates good network resilience.

On the genetic basis of tail-loss evolution in humans and apes.

The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the 'anthropomorphous apes'1-3, with a proposed role in contributing to human bipedalism4-6. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element-inserted into an intron of the TBXT gene7-9-pairs with a neighbouring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of Tbxt, mimicking the expression pattern of its hominoid orthologue TBXT. Mice expressing both Tbxt isoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of Tbxt isoforms expressed at the embryonic tail bud. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped Tbxt isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans10. Thus, tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today.

Photosynthetic mechanisms of carbon fixation reduction in rice by cadmium and polycyclic aromatic hydrocarbons.

Environmental pollutants interfere with plant photosynthesis, thus reduce the crop yield and carbon storage capacity of farmland. This study comparatively explored the effects and mechanisms of polycyclic aromatic hydrocarbons (PAHs, e.g., phenanthrene, pyrene, and benzo[a]pyrene) and cadmium (Cd) on the carbon fixation capacity of rice throughout the growth period. Cd posed severer inhibition on the net carbon fixation of rice than PAHs, with the inhibition rates of 1.40-14.8-fold over PAHs at the concentrations of 0.5 or 5 mg/kg soil. Ribulose diphosphate carboxylase/oxygenase (Rubisco) involved in the Calvin cycle was identified as the common target of these pollutants to inhibit the photosynthetic carbon fixation. Further investigation demonstrated that the different inhibitory effects of Cd and PAHs was resulted from their different interference on the dual catalysis function (carboxylation and oxygenation) of Rubisco. Cd disturbed the balance of the intercellular CO2/O2, thus promoting the oxygenation and inhibiting the carboxylation of the substrate of Rubisco. Under the stress of Cd, the downstream metabolites (e.g. glycolate, glyoxylate, and serine) of Rubisco oxygenation were upregulated by over 2.01-3.24-fold, whereas the carboxylation efficiency (Vcmax) was decreased by 5.58-29.3%. Comparatively, PAHs inhibited both the carboxylation and oxygenation by down-regulating the expression of Rubisco coding gene (OsRBCS2, Log2FC < -2). This study broadens the understanding of the mechanisms of different environmental pollutants on the carbon fixation, providing valuable information for the quantitative estimation of their impacts on the farmland carbon sink. The results would be constructive to develop strategies for eliminating the adverse effects of contaminants and assist the carbon-neutral programs.

Use microalgae to treat coke wastewater for producing biofuel: Influence of phenol on photosynthetic properties and intracellular components of microalgae.

Using microalgae to treat coking wastewater has important application prospects and environmental significance. Previous studies have suggested that phycoremediation of pollutants from coking wastewater is feasible and can potentially enhance biodiesel production. This work investigates the effects of phenol in coking wastewater on C. pyrenoidosa and S. obliquus growth, photosynthesis activity, and intracellular components. The results indicated that when the phenol concentration was lower than 300 mg L-1, both microalgae maintained good photosynthetic and physiological activity, with a maximum quantum yield potential ranging from 0.6 to 0.7. At the phenol concentration of 300 mg L-1, the biomass of C. pyrenoidosa was 2.4 times that of the control group. For S. obliquus, at the phenol concentration of 150 mg L-1, the biomass was approximately 0.85 g L-1, which increased by 68% than that of the control group (0.58 g L-1). The lipid content in both microalgae increased with the phenol concentrations, with the maximum content exceeding 40%. The optimal phenol concentrations for C. pyrenoidosa and S. obliquus growth were determined to be 246.18 and 152.73 mg L-1, respectively, based on a developed kinetic model. This work contributes to further elucidating the effects of phenol on microalgae growth, photosynthesis, and intracellular components, and suggests that using microalgae to treat phenol-containing coking wastewater for producing biofuel is not only environmentally friendly but also holds significant energy promise.

Improving biomass yields of microalgae biofilm by coculturing two microalgae species via forming biofilms with uniform microstructures and small cell-clusters.

Microalgae coculture has the potential to promote microalgae biofilm growth. Herein, three two-species cocultured biofilms were studied by determining biomass yields and detailed microstructure parameters, including porosity, average pore length, average cluster length, etc. It was found that biomass yields could reduce by 21-53 % when biofilm porosities decreased from about 35 % to 20 %; while at similar porosities (∼20 %), biomass yields of cocultured biofilms increased by 37 % when they possessed uniform microstructure and small cell-clusters (pores and clusters of 1 âˆ¼ 10 µm accounted for 96 % and 68 %, respectively). By analyzing morphologies and surface properties of cells, it was found that cells with small size, spherical shape, and reduced surface polymers could hinder the cell-clusters formation, thereby promoting biomass yields. The study provides new insights into choosing cocultured microalgae species for improving the biomass yield of biofilm via manipulating biofilm microstructures.

Hepatocytes-derived Prdx1 regulates macrophage phenotypes via TLR4 activation in acute liver injury.

Acute liver injury (ALI) is a significant causative factor for multiple hepatic diseases. The excessive inflammatory response triggers proinflammatory immune cells recruitment, infiltration and differentiation, further contributing to inflammatory injuries in liver. As a proinflammatory factor, circulating Peroxiredoxin 1 (Prdx1) is elevated in ALI patients and mice. In this study, through carbon tetrachloride (CCl4) and cecal puncture and ligation (CLP)-induced liver injury mice model, we found hepatocytes-derived Prdx1 expression was increased in ALI. After AAV8-Prdx1-mediated Prdx1 knockdown, CCl4 and CLP-induced ALI was alleviated, along with the reduced proinflammatory cytokines, suppressed myeloid cells recruitment, decreased proportions of hepatic macrophages and neutrophils, restrained proinflammatory macrophage differentiation and infiltration. Mechanistically, hepatocyte-derived Prdx1 regulated macrophages through paracrine activation of the TLR4 signal. Our data support the immune and inflammatory regulatory role of Prdx1 in ALI pathological process to suggest its potential therapeutic application and clinical value.

Pulmonary Surfactant Homeostasis Dysfunction Mediates Multiwalled Carbon Nanotubes Induced Lung Fibrosis via Elevating Surface Tension.

Multiwalled carbon nanotubes (MWCNTs) have been widely used in many disciplines and raised great concerns about their negative health impacts, especially environmental and occupational exposure. MWCNTs have been reported to induce fibrotic responses; however, the underlying mechanisms remain largely veiled. Here, we reported that MWCNTs inhalation induced lung fibrosis together with decreased lung compliance, increased elastance in the mice model, and elevated surface tension in vitro. Specifically, MWCNTs increased surface tension by impairing the function of the pulmonary surfactant. Mechanistically, MWCNTs induced lamellar body (LB) dysfunction through autophagy dysfunction, which then leads to surface tension elevated by pulmonary surfactant dysfunction in the context of lung fibrosis. This is a study to investigate the molecular mechanism of MWCNTs-induced lung fibrosis and focus on surface tension. A direct mechanistic link among impaired LBs, surface tension, and fibrosis has been established. This finding elucidates the detailed molecular mechanisms of lung fibrosis induced by MWCNTs. It also highlights that pulmonary surfactants are expected to be potential therapeutic targets for the prevention and treatment of lung fibrosis induced by MWCNTs.

Nanotechnologies meeting natural sources: Engineered lipoproteins for precise brain disease theranostics.

Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity, from preventive and diagnostic to therapeutic fields. Lipoproteins, because of their inherent blood-brain barrier permeability and lesion-homing capability, have been identified as promising strategies for high-performance theranostics of brain diseases. However, the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes, which can be critical for individual therapeutics and clinical translation. To address these issues, lipoprotein-inspired nano drug-delivery systems (nano-DDSs), which have been learned from nature, have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions. In this review, the barriers in brain disease treatment, advantages of state-of-the-art lipoprotein-inspired nano-DDSs, and bio-interactions of such nano-DDSs are highlighted. Furthermore, the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized. Specifically, the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed. Finally, the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles, such as exosomes, cell membranes, and bacteria, are discussed.

Configurationally regulated half-sandwich iridium(III)-ferrocene heteronuclear metal complexes: Potential anticancer agents.

Half-sandwich iridium(III) (IrIII) complexes and ferrocenyl (Fc) derivatives are becoming the research hotspot in the field of anticancer because of their good bioactivity and unique anticancer mechanism different from platinum-based drugs. Then, a series of half-sandwich IrIII-Fc pyridine complexes have been prepared through the structural regulation in this study. The incorporation of half-sandwich IrIII complex with Fc unit successfully improves their anticancer activity, and the optimal performance (IrFc5) is almost 3-fold higher than that of cisplatin against A549 cells, meanwhile, which also shows better anti-proliferative activity against A549/DDP cells. Complexes can aggregate in the intracellular lysosome of A549 cells and induce lysosomal damage, disrupt the cell cycle, increase the level of intracellular reactive oxygen species, and eventually lead to cell apoptosis. Half-sandwich IrIII-Fc heteronuclear metal complexes possess a different anticancer mechanism from cisplatin, which can serve as a potential alternative to platinum-based drugs and show a good application prospect.