Improved Interfacial Interactions by Core-Shell CoFe2O4@SiO2 Composites to Enhance the Ability of Corrosion Resistance and Electromagnetic Wave Absorption.

With the rapid development of science and technology, stealth and anti-corrosion activities in oceans have attracted widespread attention. This study successfully prepares CoFe2O4@SiO2 with a core-shell structure. This core-shell structure endows the CoFe2O4@SiO2 with good impedance matching and interfacial polarization. Thus, the CoFe2O4@SiO2 exhibits an excellent electromagnetic wave absorption performance with a minimum reflection loss of -45.16 dB. Moreover, the CoFe2O4@SiO2 exhibits an excellent dispersion ability in epoxy. The corrosion resistance of the CoFe2O4@SiO2/epoxy is enhanced. After 60 days of immersion, the low-frequency impedance modulus of the CoFe2O4@SiO2/epoxy is still >109 Ω cm2. The CoFe2O4@SiO2 realize the dual functions of stealth and anti-corrosion, which provide ideas for developing marine stealth applications.

FABP4 facilitates epithelial-mesenchymal transition via elevating CD36 expression in glioma cells.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis. A better understanding of mechanisms concerned in glioma invasion might be critical for treatment optimization. Given that epithelial-mesenchymal transition in tumor cells is closely associated with glioma progression and recurrence, identifying pivotal mediators in GBM EMT process is urgently needed. As a member of Fatty acid binding protein (FABP) family, FABP4 serves as chaperones for free fatty acids and participates in cellular process including fatty acid uptake, transport, and metabolism. In this study, our data revealed that FABP4 expression was elevated in human GBM samples and correlated with a mesenchymal glioma subtype. Gain of function and loss of function experiments indicated that FABP4 potently rendered glioma cells increased filopodia formation and cell invasiveness. Differential expression genes analysis and GSEA in TCGA dataset revealed an EMT-related molecular signature in FABP4-mediated signaling pathways. Cell interaction analysis suggested CD36 as a potential target regulated by FABP4. Furthermore, in vitro mechanistic experiments demonstrated that FABP4-induced CD36 expression promoted EMT via non-canonical TGFß pathways. An intracranial glioma model was constructed to assess the effect of FABP4 on tumor progression in vivo. Together, our findings demonstrated a critical role for FABP4 in the regulation invasion and EMT in GBM, and suggest that pharmacological inhibition of FABP4 may represent a promising therapeutic strategy for treatment of GBM.

Therapeutic modulation of APP-CD74 axis can activate phagocytosis of TAMs in GBM.

Glioblastoma multiforme (GBM) remains the most lethal central nervous system cancer with poor survival and few targeted therapies. The GBM tumor microenvironment is complex and closely associated with outcomes. Here, we analyzed the cell-cell communication within the microenvironment and found the high level of cell communication between GBM tumor cells and tumor-associated macrophages (TAMs). We found that the amyloid protein precursor (APP)-CD74 axis displayed the highest levels of communication between GBM tumor cells and TAMs, and that APP and CD74 expression levels were significantly corelated with poorer patient outcomes. We showed that the expression of APP on the surface of GBM inhibited phagocytosis of TAMs through the binding of APP to the CD74/CXCR4 cell surface receptor complex. We further demonstrated that disrupting the APP-CD74 axis could upregulated the phagocytosis of TAMs in vitro and in vivo. Finally, we demonstrated that APP promotes the phosphorylation of SHP-1 by binding to CD74. Together, our findings revealed that the APP-CD74 axis was a highly expressed anti-phagocytic signaling pathway that may be a potential immunotherapeutic target for GBM.

Understanding food waste sorting behavior in institutional food services: An integrated psychological framework.

Food waste from institutional food services accounts for a significant part of global food waste. Food waste sorting (FWS) at the source reduces waste management costs and environmental impacts in organizations. Yet what drives individual FWS behavior remains underexplored. This study explores the psychological process of FWS in institutional catering environments, integrating the value-belief-norm model, the theory of planned behavior, and self-determination theory. Data were collected from 431 university students in China and analyzed using partial least squares structural equation modeling (PLS-SEM). Results indicated the interplay of values, beliefs, norms, and motivations in shaping FWS behaviors. Social value orientations (SVO) indirectly affected FWS through awareness of consequences and personal norms. Subjective norms, potentially attributed to external regulations in canteens, influenced FWS intention through personal norms and induced FWS primarily via controlled motivations. The findings imply that behavioral strategies to induce FWS may leverage social influence and external regulation while also translating values and knowledge into intrinsic motivations through educational programs and awareness campaigns.

Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001). CONCLUSIONS: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

Nanoparticles Coated with Brain Microvascular Endothelial Cell Membranes can Target and Cross the Blood-Brain Barrier to Deliver Drugs to Brain Tumors.

The blood-brain barrier (BBB) contains tightly connected brain microvascular endothelial cells (BMECs) that hinder drug delivery to the brain, which makes brain tumors difficult to treat. Previous studies have shown that nanoparticles coated with tumor cell membranes selectively target their homologous tumors. Therefore, this study investigated whether bEnd.3-line BMEC membrane-coated nanoparticles with poly(lactide-co-glycolide)-poly(ethylene glycol)-based doxorubicin-loaded cores (BM-PDs) can be used to target BMECs and cross the BBB. In vitro, the BM-PDs effectively target BMECs and cross a BBB model. The BM-PDs enter the BMECs via macropinocytosis, clathrin-mediated endocytosis, caveolin-mediated endocytosis, and membrane fusion, which result in excellent cellular uptake. The BM-PDs also show excellent cellular uptake in brain tumor cells. In vivo, the BM-PDs target BMECs, cross the BBB, accumulate in brain tumors, and efficiently kill tumor cells. Therefore, the proposed strategy has great therapeutic potential owing to its ability to cross the BBB to reach brain tumors.

IFITM3 promotes glioblastoma stem cell-mediated angiogenesis via regulating JAK/STAT3/bFGF signaling pathway.

Interferon-induced transmembrane protein 3 (IFITM3) has been previously verified to be an endosomal protein that prevents viral infection. Recent findings suggested IFITM3 as a key factor in tumor invasion and progression. To clarify the role and molecular mechanism of IFITM3 in Glioblastoma multiforme (GBM) progression, we investigated the expression of IFITM3 in glioma datasets culled from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). Primary GBM stem cells (GSCs) were cultured and identified in vitro. Loss-of-function and gain-of-function experiments were established by using shRNAs and lentiviral vectors targeting IFITM3. Co-culture system of GSCs and vascular endothelial cells was constructed in a Transwell chamber. Tube formation and spheroid-based angiogenesis assays were performed to determine the angiogenic capacity of endothelial cells. Results revealed that IFITM3 is elevated in GBM samples and predictive of adverse outcome. Mechanistically, GSCs-derived IFITM3 causes activation of Jak2/STAT3 signaling and leads to robust secretion of bFGF into tumor environment, which eventually results in enhanced angiogenesis. Taken together, these evidence indicated IFITM3 as an essential factor in GBM angiogenesis. Our findings provide a new insight into mechanism by which IFITM3 modulates GBM angiogenesis.

Structures, functions, and regulatory networks of universal stress proteins in clinically relevant pathogenic Bacteria.

Universal stress proteins are a class of proteins widely present in bacteria, archaea, plants, and invertebrates, playing essential roles in bacterial adaptation to various environmental stresses. The functions of bacterial universal stress proteins are versatile, including resistance to oxidative stress, maintenance of cell wall integrity, DNA damage repair, regulation of cell division and growth, among others. When facing stresses such as temperature changes, pH shifts, fluctuations in oxygen concentration, and exposure to toxins, these proteins can bind to specific DNA sequences and rapidly adjust bacterial metabolic pathways and gene expression patterns to adapt to the new environment. In summary, bacterial universal stress proteins play a crucial role in bacterial adaptability and survival. A comprehensive understanding of bacterial stress response mechanisms and the development of new antibacterial strategies are of great significance. This review summarizes the research progress on the structure, function, and regulatory factors of universal stress proteins in clinically relevant bacteria, aiming to facilitate deeper investigations by clinicians and researchers into universal stress proteins.

Interfacial regulation of BiOI@Bi2S3/MXene heterostructures for enhanced photothermal and photodynamic therapy in antibacterial applications.

Developing environmentally friendly, broad-spectrum, and long-lasting antibacterial materials remains challenging. Our ternary BiOI@Bi2S3/MXene composites, which exhibit both photothermal therapy (PTT) and photodynamic therapy (PDT) antibacterial properties, were synthesized through in-situ vulcanization of hollow flower-shaped BiOI on the surface of two-dimensional Ti3C2 MXene. The unique hollow flower-shaped BiOI structure with a high exposure of the (001) crystal plane amplifies light reflection and scattering, offering more active sites to improve light utilization. Under 808 nm irradiation, these composites achieved a photothermal conversion efficiency of 57.8 %, boosting the PTT antibacterial effect. The heterojunction between Bi2S3 and BiOI creates a built-in electric field at the interface, promoting hole and electron transfer. Significantly, the close-contact heterogeneous interface enhances charge transfer and suppresses electron-hole recombination, thereby boosting PDT bacteriostatic performance. EPR experiments confirmed that ∙O2- and •OH radicals play major roles in photocatalytic bacteriostatic reactions. The combined antibacterial action of PTT and PDT led to efficiencies of 99.7 % and 99.8 % against P. aeruginosa and S. aureus, respectively, under 808 nm laser irradiation. This innovative strategy and thoughtful design open new avenues for heterojunction materials in PTT and PDT sterilization. STATEMENT OF SIGNIFICANCE: Photodynamic and photothermal therapy is a promising antibacterial treatment, but its efficiency still limits its application. To overcome this limitation, we prepared three-dimensional heterogeneous BiOI@Bi2S3/MXene nanocomposites through in-situ vulcanization of hollow flower-shaped BiOI with a high exposure of the (001) crystal plane onto the surface of two-dimensional MXene material. The resulting ternary material forms a close-contact heterogeneous interface, which improves charge transfer channels, reduces electron-hole pair recombination, and amplifies photodynamic bacteriostatic performance. These nanocomposites exhibit photothermal conversion efficiency of 57.8 %, enhancing their photothermal bactericidal effects. They demonstrated antibacterial efficiencies of 99.7 % against P. aeruginosa and 99.8 % against S. aureus. Therefore, this study provides a promising method for the synthesis of environmentally friendly and efficient antibacterial materials.

Targeting TNFAIP2 induces immunogenic cell death and sensitizes glioblastoma multiforme to anti-PD-1 therapy.

BACKGROUND: The efficacy of current immunotherapeutic strategies for patients with glioblastoma multiforme (GBM) remains unsatisfactory. The purpose of this study was to investigate the correlation between tumor necrosis factor alpha-induced protein 2 (TNFAIP2) and immunogenic cell death (ICD) in GBM, and to examine the effect of TNFAIP2 knockdown and anti-PD-1 combination treatment in a mouse glioma model. METHODS: The CGGA and TCGA databases were used to explore the possible function of TNFAIP2 in GBM. Multiplex immunohistochemistry (mIHC) staining was performed to detect the immune infiltration of tissues. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, and enzyme linked immunosorbent assay (ELISA) were utilized to detect the release of damage-associated molecular patterns (DAMPs) and the activation of the immune response. A mouse glioma model was applied to examine the induction of immune response. RESULTS: In vitro and in vivo studies demonstrated that TNFAIP2 knockdown increased the surface exposure of calreticulin (CALR), heat shock protein 70 kDa (HSP70), and heat shock protein 90 kDa (HSP90) in GBM cell lines, thereby inducing immunogenic cell death (ICD). Importantly, the study found that TNFAIP2 knockdown in combination with anti-PD-1 therapy significantly improved the overall survival of glioma in a mouse model. CONCLUSIONS: TNFAIP2 knockdown induces ICD by downregulating TNFAIP2 in GBM. In addition, TNFAIP2 knockdown sensitized glioma to anti-PD-1 therapy. Hence, targeting TNFAIP2 alone or in combination with anti-PD-1 therapy may be a potential strategy for GBM treatment through ICD.

Artificial intelligence for video game visualization, advancements, benefits and challenges.

In recent years, the field of artificial intelligence (AI) has witnessed remarkable progress and its applications have extended to the realm of video games. The incorporation of AI in video games enhances visual experiences, optimizes gameplay and fosters more realistic and immersive environments. In this review paper, we systematically explore the diverse applications of AI in video game visualization, encompassing machine learning algorithms for character animation, terrain generation and lighting effects following the PRISMA guidelines as our review methodology. Furthermore, we discuss the benefits, challenges and ethical implications associated with AI in video game visualization as well as the potential future trends. We anticipate that the future of AI in video gaming will feature increasingly sophisticated and realistic AI models, heightened utilization of machine learning and greater integration with other emerging technologies leading to more engaging and personalized gaming experiences.

Acupuncture improves the emotion domain and lipid profiles in women with polycystic ovarian syndrome: a secondary analysis of a randomized clinical trial.

Objective: This study aims to evaluate the effect of acupuncture on the emotion domain and metabolic parameters of Chinese women with polycystic ovarian syndrome (PCOS) by secondary analysis of a randomized clinical trial, conducted from 6 July 2012 to 7 October 2015. Method: In this study, we investigated the effects of acupuncture (458 patients) and sham acupuncture (468 patients) on metabolic parameters, serum ions, and all quality-of-life scale scores related to PCOS. The quality of life of patients was evaluated using five relevant scales, operated by the research assistant, namely, PCOSQ, SF-36, and ChiQOL, as well as Zung-SAS and Zung-SDS. Metabolic parameters and serum ions were measured. Results: A reduction in acne score, AN, Hcy, and LDL-C, and an increase in the level of lipoprotein α, Apo A1, and Apo A1/Apo B were observed in the acupuncture group after 4 months' intervention after adjusting clomiphene and reproductive outcome (p< 0.05). An increase in SF-36 total scores, RP and RE scores, ChiQOL total scores, and emotion domain scores was observed in the acupuncture group after 4 months' intervention, while PF and HT scores were decreased (adjusted p< 0.05). Those same changes were observed in sham acupuncture. Meanwhile, the serum levels of Ca, K, and Cl were elevated in the acupuncture group after the interventions (adjusted p< 0.005). There were no significant differences in HOMA-IR, MetS, FPG, FINS, HDL-C, TG, Apo B, and level of serum P, Mg, and Na. Also, no changes in BP, GH, VT, SF, physical form domain, and spirit domain were observed after treatment. Conclusion: Acupuncture can improve not only the emotional changes in SF-36 scores and ChiQOL scores, but also lipid metabolism, implying that it may have a correlation between emotional change and lipid metabolism. Furthermore, acupuncture can also regulate the changes of serum Ca, K, and Cl. Clinical trial registration: ClinicalTrials.gov, identifier NCT01573858.

Cross-platform comparisons for targeted bisulfite sequencing of MGISEQ-2000 and NovaSeq6000.

BACKGROUND: An accurate and reproducible next-generation sequencing platform is essential to identify malignancy-related abnormal DNA methylation changes and translate them into clinical applications including cancer detection, prognosis, and surveillance. However, high-quality DNA methylation sequencing has been challenging because poor sequence diversity of the bisulfite-converted libraries severely impairs sequencing quality and yield. In this study, we tested MGISEQ-2000 Sequencer's capability of DNA methylation sequencing with a published non-invasive pancreatic cancer detection assay, using NovaSeq6000 as the benchmark. RESULTS: We sequenced a series of synthetic cell-free DNA (cfDNA) samples with different tumor fractions and found MGISEQ-2000 yielded data with similar quality as NovaSeq6000. The methylation levels measured by MGISEQ-2000 demonstrated high consistency with NovaSeq6000. Moreover, MGISEQ-2000 showed a comparable analytic sensitivity with NovaSeq6000, suggesting its potential for clinical detection. As to evaluate the clinical performance of MGISEQ-2000, we sequenced 24 clinical samples and predicted the pathology of the samples with a clinical diagnosis model, PDACatch classifier. The clinical model performance of MGISEQ-2000's data was highly consistent with that of NovaSeq6000's data, with the area under the curve of 1. We also tested the model's robustness with MGISEQ-2000's data when reducing the sequencing depth. The results showed that MGISEQ-2000's data showed matching robustness of the PDACatch classifier with NovaSeq6000's data. CONCLUSIONS: Taken together, MGISEQ-2000 demonstrated similar data quality, consistency of the methylation levels, comparable analytic sensitivity, and matching clinical performance, supporting its application in future non-invasive early cancer detection investigations by detecting distinct methylation patterns of cfDNAs.

Early detection and stratification of lung cancer aided by a cost-effective assay targeting circulating tumor DNA (ctDNA) methylation.

BACKGROUND: Detection of lung cancer at earlier stage can greatly improve patient survival. We aim to develop, validate, and implement a cost-effective ctDNA-methylation-based plasma test to aid lung cancer early detection. METHODS: Case-control studies were designed to select the most relevant markers to lung cancer. Patients with lung cancer or benign lung disease and healthy individuals were recruited from different clinical centers. A multi-locus qPCR assay, LunaCAM, was developed for lung cancer alertness by ctDNA methylation. Two LunaCAM models were built for screening (-S) or diagnostic aid (-D) to favor sensitivity or specificity, respectively. The performance of the models was validated for different intended uses in clinics. RESULTS: Profiling DNA methylation on 429 plasma samples including 209 lung cancer, 123 benign diseases and 97 healthy participants identified the top markers that detected lung cancer from benign diseases and healthy with an AUC of 0.85 and 0.95, respectively. The most effective methylation markers were verified individually in 40 tissues and 169 plasma samples to develop LunaCAM assay. Two models corresponding to different intended uses were trained with 513 plasma samples, and validated with an independent collection of 172 plasma samples. In validation, LunaCAM-S model achieved an AUC of 0.90 (95% CI: 0.88-0.94) between lung cancer and healthy individuals, whereas LunaCAM-D model stratified lung cancer from benign pulmonary diseases with an AUC of 0.81 (95% CI: 0.78-0.86). When implemented sequentially in the validation set, LunaCAM-S enables to identify 58 patients of lung cancer (90.6% sensitivity), followed by LunaCAM-D to remove 20 patients with no evidence of cancer (83.3% specificity). LunaCAM-D significantly outperformed the blood test of carcinoembryonic antigen (CEA), and the combined model can further improve the predictive power for lung cancer to an overall AUC of 0.86. CONCLUSIONS: We developed two different models by ctDNA methylation assay to sensitively detect early-stage lung cancer or specifically classify lung benign diseases. Implemented at different clinical settings, LunaCAM models has a potential to provide a facile and inexpensive avenue for early screening and diagnostic aids for lung cancer.

Engineered Salmonella inhibits GPX4 expression and induces ferroptosis to suppress glioma growth in vitro and in vivo.

PURPOSE: Glioma is a life-threatening malignancy where conventional therapies are ineffective. Bacterial cancer therapy has shown potential for glioma treatment, in particular, the facultative anaerobe Salmonella has been extensively studied. Meanwhile, ferroptosis is a newly characterized form of cell death. Nevertheless, the role of ferroptosis in Salmonella-induced tumour cell death remains unclear. Therefore, we aim to elucidate whether Salmonella YB1 exerts therapeutic effects via inducing ferroptosis in glioma. METHODS: Following Salmonella YB1 infection, mRNA sequencing was applied to detect ferroptosis-related gene expression and the levels of reactive oxygen species, malondialdehyde, and glutathione were quantified. Transmission electron microscopy (TEM) was then used to observe the changes in the mitochondrial morphology of glioma cells. The role of ferroptosis in the anti-tumor effect of YB1 was assessed in vivo in mouse tumor xenograft models. RESULTS: Whole-transcriptome analysis revealed that Salmonella YB1 infection alters ferroptosis-related gene expression in the U87 glioma cell line. Moreover, we found that Salmonella-induced ferroptosis is correlated with reduced levels of glutathione and glutathione peroxidase-4 (GPX4) and increased levels of reactive oxygen species and malondialdehyde in vitro. Meanwhile, TEM revealed that mitochondria are shrunken and mitochondrial membrane density increases in infected glioma cells. Experiments in vivo further showed that tumor growth in the Salmonella-treated group was significantly slower compared to the control and Fer-1 groups. However, Salmonella-induced tumor suppression can be reversed in vivo by Fer-1 treatment. CONCLUSION: Salmonella YB1 inhibits GPX4 expression and induces ferroptosis to suppress glioma growth. Hence, ferroptosis regulation might represent a promising strategy to improve the efficacy of bacterial cancer therapy.

Fabrication of direct Z-scheme Cu2O@V-CN (octa) heterojunction with exposed (111) lattice planes and nitrogen-rich vacancies for rapid sterilization.

The Z-scheme heterojunction has demonstrated significant potential for promoting photogenerated carrier separation. However, the rational design of all-solid Z-scheme heterojunctions catalysts and the controversies about carrier transfer path of direct Z-scheme heterojunctions catalysts face various challenges. Herein, a novel heterojunction, Cu2O@V-CN (octa), was fabricated using V-CN (carbon nitride with nitrogen-rich vacancies) in-situ electrostatic self-wrapping Cu2O octahedra. Density functional theory (DFT) calculations revealed that the separation of carriers across the Cu2O@V-CN (octa) heterointerface was directly mapped to the Z-scheme mechanism compared to Cu2O/V-CN (sphere). This is because the Cu2O octahedra expose more highly active (111) lattice planes with more terminal Cu atoms and V-CN with abundant nitrogen vacancies to form delocalized electronic structures like electronic reservoirs. This facilitates the wrapping of Cu2O octahedra by V-CN and protects their stability via tighter interfacial contact, thus enhancing the tunneling of carriers for rapid photocatalytic sterilization. These findings provide novel approaches for designing high-efficiency Cu2O-based photocatalytic antifoulants for practical applications.

Cell-free DNA methylation biomarker for the diagnosis of papillary thyroid carcinoma.

BACKGROUND: Cell-free DNA (cfDNA) is being explored as biomarker for non-invasive diagnosis of cancer. We aimed to establish a cfDNA-based DNA methylation marker panel to differentially diagnose papillary thyroid carcinoma (PTC) from benign thyroid nodule (BTN). METHODS: 220 PTC- and 188 BTN patients were enrolled. Methylation markers of PTC were identified from patients' tissue and plasma by reduced representation bisulfite sequencing and methylation haplotype analyses. They were combined with PTC markers from literatures and were tested on additional PTC and BTN samples to verify PTC-detecting ability using targeted methylation sequencing. Top markers were developed into ThyMet and were tested in 113 PTC and 88 BTN cases to train and validate a PTC-plasma classifier. Integration of ThyMet and thyroid ultrasonography was explored to improve accuracy. FINDINGS: From 859 potential PTC plasma-discriminating markers that include 81 markers identified by us, the top 98 most PTC plasma-discriminating markers were selected for ThyMet. A 6-marker ThyMet classifier for PTC plasma was trained. In validation it achieved an Area Under the Curve (AUC) of 0.828, similar to thyroid ultrasonography (0.833) but at higher specificity (0.722 and 0.625 for ThyMet and ultrasonography, respectively). A combinatorial classifier by them, ThyMet-US, improved AUC to 0.923 (sensitivity = 0.957, specificity = 0.708). INTERPRETATION: The ThyMet classifier improved the specificity of differentiating PTC from BTN over ultrasonography. The combinatorial ThyMet-US classifier may be effective in preoperative diagnosis of PTC. FUNDING: This work was supported by the grants from National Natural Science Foundation of China (82072956 and 81772850).

Preoperative administration of a biomimetic platelet nanodrug enhances postoperative drug delivery by bypassing thrombus.

The postoperative thrombus attached to the damaged blood vessels severely obstructs drugs from crossing the damaged blood-brain barrier (BBB) and targeting residual glioma cells around surgical margins, leading to glioblastoma (GBM) recurrence. A thrombus-bypassing, BBB-crossing, and surgical margin-targeted nanodrug is needed to address this phenomenon. Encouraged by the intrinsic damaged vascular endothelium chemotaxis of platelets, a platelet membrane-coated nanodrug (PM-HDOX) delivering doxorubicin (DOX) for postoperative GBM treatment is proposed and systematically investigated. Because surgery damages the vascular endothelium on the BBB around the surgical margin, the platelet membrane coating endows PM-HDOX with its inherent capacity to cross the broken BBB and target the surgical margin. Moreover, preoperative administration combined with fast-targeted PM-HDOX can realize the potential of bypassing thrombus. In GBM resection models, PM-HDOX with preoperative administration demonstrated significantly enhanced BBB-crossing and surgical margin-targeted efficacy. In particular, the PM-HDOX intensities around the surgical margins of the preoperative administration group were more than twice that of the postoperative administration group due to bypassing the thrombus formed in the broken BBB. In the antitumor experiment, the preoperative administration of PM-HDOX significantly inhibited the growth of postoperative residual tumors and prolonged the median survival time of mice. In conclusion, preoperative administration of a biomimetic platelet nanodrug can be an efficient and promising drug delivery strategy for residual GBM after surgery.

Full solar spectrum-driven Cu2O/PDINH heterostructure with enhanced photocatalytic antibacterial activity and mechanism insight.

Marine biofouling hazards the sustainable development of the environment and has become a potential threat to environmental and ecological security. Photocatalytic antibacterial agents driven by the full solar spectrum are promising antifouling agents for environmental protection. The cuprous oxide/perylene-3,4,9,10-tetracarboximide (Cu2O/PDINH) heterostructure was successfully constructed by integrating p-type Cu2O and n-type PDINH to improve photocatalytic antibacterial efficiency. PDINH extended the absorption spectrum from ultraviolet to near-infrared, improving light utilization by 75 %. The Cu2O/PDINH heterostructure reduced the toxicity risk of Cu2O for environmental pollution, achieved full solar spectrum drive and overcame the inherent defect that Cu2O cannot produce singlet oxygen. The Cu2O/PDINH heterostructure exhibited excellent long-term and photocatalytic antibacterial activity with an antibacterial rate of > 90 % due to the sterilization of copper ions and the continuous generation of ROS driven by the full solar spectrum. This inorganic-organic Cu2O/PDINH heterostructure shows great application prospects in energy and the environment. The Cu2O/PDINH heterostructure with effective ROS increase and superior photocatalytic sterilization efficiency has great potential for environmentally friendly marine antifouling agents.

Blunt dopamine transmission due to decreased GDNF in the PFC evokes cognitive impairment in Parkinson's disease.

Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson's disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson's disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson's disease. We then established a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson's disease.