Stimuli-responsive nanodelivery systems for amplifying immunogenic cell death in cancer immunotherapy.

Immunogenic cell death (ICD) is a special pattern of tumor cell death, enabling to elicit tumor-specific immune response via the release of damage-associated molecular patterns and tumor-associated antigens in the tumor microenvironment. ICD-induced immunotherapy holds the promise for completely eliminating tumors and long-term protective antitumor immune response. Increasing ICD inducers have been discovered for boosting antitumor immunity via evoking ICD. Nonetheless, the utilization of ICD inducers remains insufficient owing to serious toxic reactions, low localization efficiency within the tumor microenvironmental niche, etc. For overcoming such limitations, stimuli-responsive multifunctional nanoparticles or nanocomposites with ICD inducers have been developed for improving immunotherapeutic efficiency via lowering toxicity, which represent a prospective scheme for fostering the utilization of ICD inducers in immunotherapy. This review outlines the advances in near-infrared (NIR)-, pH-, redox-, pH- and redox-, or NIR- and tumor microenvironment-responsive nanodelivery systems for ICD induction. Furthermore, we discuss their clinical translational potential. The progress of stimuli-responsive nanoparticles in clinical settings depends upon the development of biologically safer drugs tailored to patient needs. Moreover, an in-depth comprehending of ICD biomarkers, immunosuppressive microenvironment, and ICD inducers may accelerate the advance in smarter multifunctional nanodelivery systems to further amplify ICD.

Intraplate volcanism originating from upwelling hydrous mantle transition zone.

Most magmatism occurring on Earth is conventionally attributed to passive mantle upwelling at mid-ocean ridges, to slab devolatilization at subduction zones, or to mantle plumes. However, the widespread Cenozoic intraplate volcanism in northeast China1-3 and the young petit-spot volcanoes4-7 offshore of the Japan Trench cannot readily be associated with any of these mechanisms. In addition, the mantle beneath these types of volcanism is characterized by zones of anomalously low seismic velocity above and below the transition zone8-12 (a mantle level located at depths between 410 and 660 kilometres). A comprehensive interpretation of these phenomena is lacking. Here we show that most (or possibly all) of the intraplate and petit-spot volcanism and low-velocity zones around the Japanese subduction zone can be explained by the Cenozoic interaction of the subducting Pacific slab with a hydrous mantle transition zone. Numerical modelling indicates that 0.2 to 0.3 weight per cent of water dissolved in mantle minerals that are driven out from the transition zone in response to subduction and retreat of a tectonic plate is sufficient to reproduce the observations. This suggests that a critical amount of water may have accumulated in the transition zone around this subduction zone, as well as in others of the Tethyan tectonic belt13 that are characterized by intraplate or petit-spot volcanism and low-velocity zones in the underlying mantle.

Endoscopic treatment for early duodenal papillary carcinoma: long-term outcomes.

BACKGROUND AND AIM: This study aims to determine whether endoscopic papillectomy (EP) is a safe and effective treatment for early duodenal papillary carcinoma with long-term follow-up. METHODS: From June 2012 to September 2022, 48 patients with early duodenal papilloma carcinoma who received endoscopic treatment were included. The histological types, percentage of complete resections, postoperative residuals, adverse events, and recurrences were evaluated. RESULTS: EP was successful in all patients; 46 were lumped, and two were fragmented, with a 95.8% intact removal rate (46/48). The preoperative biopsy pathological positive rate was 70.8% (34/48). The incidence of early postoperative adverse events (within 1 month after EP) were 16.7% (8/48), including four cases of acute pancreatitis, three cases of delayed bleeding, and one case of acute cholangitis. In addition, 4.2% (2/48) of the late adverse events were bile duct stenosis. After 6 months, the postoperative residual rate was 0%. The median time to recurrence was 17.5 months, and the postoperative recurrence rate was 16.7% (8/48) in patients treated with radiofrequency ablation. The median progression-free survival was 18.6 months (95% CI, 12.1-25.1), and the median overall survival was 121.5 months (95% CI, 105.6-120.9). CONCLUSIONS: EP is a safe and efficient alternative therapy for early duodenal papillary carcinoma. Endoscopic follow-up and treatment are essential because of the potential for recurrence.

Single-atom nanozymes shines diagnostics of gastrointestinal diseases.

Various clinical symptoms of digestive system, such as infectious, inflammatory, and malignant disorders, have a profound impact on the quality of life and overall health of patients. Therefore, the chase for more potent medicines is both highly significant and urgent. Nanozymes, a novel class of nanomaterials, amalgamate the biological properties of nanomaterials with the catalytic activity of enzymes, and have been engineered for various biomedical applications, including complex gastrointestinal diseases (GI). Particularly, because of their distinctive metal coordination structure and ability to maximize atom use efficiency, single-atom nanozymes (SAzymes) with atomically scattered metal centers are becoming a more viable substitute for natural enzymes. Traditional nanozyme design strategies are no longer able to meet the current requirements for efficient and diverse SAzymes design due to the diversification and complexity of preparation processes. As a result, this review emphasizes the design concept and the synthesis strategy of SAzymes, and corresponding bioenzyme-like activities, such as superoxide dismutase (SOD), peroxidase (POD), oxidase (OXD), catalase (CAT), and glutathione peroxidase (GPx). Then the various application of SAzymes in GI illnesses are summarized, which should encourage further research into nanozymes to achieve better application characteristics.

Imaging-based measurement of lunar dust velocity and particle size.

This paper introduces an optical-mechanical system designed for the dynamic detection and analysis of lunar dust, typically characterized as particles under 20 micrometers on the lunar surface. The system's design is both compact and lightweight, aligning with the payload constraints of lunar exploration missions. It is capable of real-time tracking and recording the motion of lunar dust at various altitudes, a crucial capability for understanding the environmental dynamics of the lunar surface. By capturing images and applying sophisticated algorithms, the system accurately measures the velocity and size of dust particles. This approach significantly advances the quantitative analysis of lunar dust, especially during agitation events, filling a critical gap in our current understanding of lunar surface phenomena. The insights gained from this study are not only pivotal for developing theoretical models of lunar surface air flow disturbances and dust movement but also instrumental in designing effective dust mitigation and hazard avoidance strategies for future lunar missions, thereby enhancing both scientific knowledge and the engineering applications in lunar exploration.

Visual outcome of various dose of glucocorticoids treatment in nonarteritic anterior ischemic optic neuropathy- a retrospective analysis.

BACKGROUND AND PURPOSE: The objective of this investigation was to assess the therapeutic efficacy of distinct glucocorticoid therapy dosages in the management of acute nonarteritic anterior ischemic optic neuropathy (NAION). MATERIALS AND METHODS: This retrospective, unmasked, and non-randomized study included a total of 85 patients. The patients were categorized into four groups: Group 1 (control) consisted of 15 patients who did not receive glucocorticoids, Group 2 included 16 patients administered with oral prednisone at a dosage of 1 mg/kg/d for 14 days, Group 3 comprised 30 patients who received 250 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days, and Group 4 encompassed 24 patients who received 500 units of methylprednisolone once daily for 3 days, followed by oral prednisone at a dosage of 1 mg/kg/d for 11 days. The best-corrected visual acuity (BCVA) was assessed at baseline and the final follow-up (> 7 days post-treatment). The changes in visual acuity between baseline and the 7-14 day follow-up, as well as between baseline and the concluding appraisal, were employed as metrics for assessing the extent of visual enhancement. RESULTS: No significant differences were noted in the final visual outcomes or in the changes between final visual acuity and baseline across the four groups. In Group 1 (control), the best-corrected visual acuity (BCVA) remained unchanged during final follow-ups compared to baseline. Conversely, the intervention groups exhibited statistically significant enhancements in BCVA during final follow-up (p = 0.012, p = 0.03, and p = 0.009 for Group 2, Group 3, and Group 4, respectively) when compared to baseline. During the 7-14 day follow-up, there was a significant difference in the changes between baseline BCVA and follow-up BCVA across the groups (p = 0.035). Go a step further by Bonferroni correction for multiple comparisons, group 4 showed a greater change in vision compared with group1 (p = 0.045). CONCLUSION: Our study on acute nonarteritic anterior ischemic optic neuropathy (NAION) showed no significant final visual outcome differences. Nevertheless, Groups 2, 3, and 4 demonstrated improved best-corrected visual acuity (BCVA) during the final follow-up. Notably, a 500-unit dose of methylprednisolone resulted in short-term BCVA enhancement. This suggests potential consideration of 500 units of methylprednisolone for short-term NAION vision improvement, despite its limited long-term impact.

Cold EMR vs. Hot EMR for the removal of sessile serrated polyps larger than 10 mm: a systematic review and meta-analysis.

BACKGROUND: Endoscopic mucosal resection (EMR) appears to be a promising technique for the removal of sessile serrated polyps (SSPs) ≥ 10 mm. To assess the effectiveness and safety of EMR for removing SSPs ≥ 10 mm, we conducted this systematic review and meta-analysis. METHODS: We conducted a thorough search of Embase, PubMed, Cochrane, and Web of Science databases for relevant studies reporting on EMR of SSPs ≥ 10 mm, up until December 2023. Our primary endpoints of interest were rates of technical success, residual SSPs, and adverse events (AE). RESULTS: Our search identified 426 articles, of which 14 studies with 2262 SSPs were included for analysis. The rates of technical success, AEs, and residual SSPs were 100%, 2.0%, and 3.1%, respectively. Subgroup analysis showed that the technical success rates were the same for polyps 10-19 and 20 mm, and en-bloc and piecemeal resection. Residual SSPs rates were similar in en-bloc and piecemeal resection, but much lower in cold EMR (1.0% vs. 4.2%, P = 0.034). AEs rates were reduced in cold EMR compared to hot EMR (0% vs. 2.9%, P = 0.168), in polyps 10-19 mm compared to 20 mm (0% vs. 4.1%, P = 0.255), and in piecemeal resection compared to en-bloc (0% vs. 0.7%, P = 0.169). CONCLUSIONS: EMR is an effective and safe technique for removing SSPs ≥ 10 mm. The therapeutic effect of cold EMR is superior to that of hot EMR, with a lower incidence of adverse effects. PROSPERO REGISTRATION NUMBER: CRD42023388959.

Minimizing Task Age upon Decision for Low-Latency MEC Networks Task Offloading with Action-Masked Deep Reinforcement Learning.

In this paper, we consider a low-latency Mobile Edge Computing (MEC) network where multiple User Equipment (UE) wirelessly reports to a decision-making edge server. At the same time, the transmissions are operated with Finite Blocklength (FBL) codes to achieve low-latency transmission. We introduce the task of Age upon Decision (AuD) aimed at the timeliness of tasks used for decision-making, which highlights the timeliness of the information at decision-making moments. For the case in which dynamic task generation and random fading channels are considered, we provide a task AuD minimization design by jointly selecting UE and allocating blocklength. In particular, to solve the task AuD minimization problem, we transform the optimization problem to a Markov Decision Process problem and propose an Error Probability-Controlled Action-Masked Proximal Policy Optimization (EMPPO) algorithm. Via simulation, we show that the proposed design achieves a lower AuD than baseline methods across various network conditions, especially in scenarios with significant channel Signal-to-Noise Ratio (SNR) differences and low average SNR, which shows the robustness of EMPPO and its potential for real-time applications.

A Joint Scheduling Scheme for WiFi Access TSN.

In the context of Industry 4.0, industrial production equipment needs to communicate through the industrial internet to improve the intelligence of industrial production. This requires the current communication network to have the ability of large-scale equipment access, multiple communication protocols/heterogeneous systems interoperability, and end-to-end deterministic low-latency transmission. Time-sensitive network (TSN), as a new generation of deterministic Ethernet communication technology, is the main development direction of time-critical communication technology applied in industrial environments, and Wi-Fi technology has become the main way of wireless access for users due to its advantages of high portability and mobility. Therefore, accessing WiFi in the TSN is a major development direction of the current industrial internet. In this paper, we model the scheduling problem of TSN and WiFi converged networks and propose a scheme based on a greedy strategy distributed estimation algorithm (GE) to solve the scheduling problem. Compared with the integer linear programming (ILP) algorithm and the Tabu algorithm, the algorithm implemented in this paper outperforms the other algorithms in being able to adapt to a variety of different scenarios and in scheduling optimization efficiency, especially when the amount of traffic to be deployed is large.

Improving Graph Convolutional Network with Learnable Edge Weights and Edge-Node Co-Embedding for Graph Anomaly Detection.

The era of Industry 4.0 is gradually transforming our society into a data-driven one, which can help us uncover valuable information from accumulated data, thereby improving the level of social governance. The detection of anomalies, is crucial for maintaining societal trust and fairness, yet it poses significant challenges due to the ubiquity of anomalies and the difficulty in identifying them accurately. This paper aims to enhance the performance of the current Graph Convolutional Network (GCN)-based Graph Anomaly Detection (GAD) algorithm on datasets with extremely low proportions of anomalous labels. This goal is achieved through modifying the GCN network structure and conducting feature extraction, thus fully utilizing three types of information in the graph: node label information, node feature information, and edge information. Firstly, we theoretically demonstrate the relationship between label propagation and feature convolution, indicating that the Label Propagation Algorithm (LPA) can serve as a regularization penalty term for GCN, aiding in training and enabling learnable edge weights, providing a basis for incorporating node label information into GCN networks. Secondly, we introduce a method to aggregate node and edge features, thereby incorporating edge information into GCN networks. Finally, we design different GCN trainable weights for node features and co-embedding features. This design allows different features to be projected into different spaces, greatly enhancing model expressiveness. Experimental results on the DGraph dataset demonstrate superior AUC performance compared to baseline models, highlighting the feasibility and efficacy of the proposed approach in addressing GAD tasks in the scene with extremely low proportions of anomalous data.

Rheological Tunable Magnetic Fluids with Long-Term Stability.

Magnetic fluids have advantages such as flow ability and solid-like property in strong magnetic fields, but have to suffer from the tradeoff between suspension stability and flow resistance. In this work, a thermal/photo/magnetorheological water-based magnetic fluid is fabricated by using oleic acid-coated Fe3 O4 (Fe3 O4 @OA) nanoparticles as the magnetic particles and the amphiphilic penta block copolymer (PTMC-F127-PTMC)-based aqueous solution as the carrier fluid. Due to the hydrophobic self-assembly between Fe3 O4 @OA and PTMC-F127-PTMC, the Newtonian-like magnetic fluid has outstanding long-term stability and reversible rheological changes between the low-viscosity flow state and the 3D gel structure. In the linear viscoelastic region, the viscosity exhibits an abrupt increase from below 0.10 Pa s at 20 °C to ≈1.3 × 104  Pa s at 40 °C. Benefitting from the photothermal and magnetocaloric effects of the Fe3 O4 @OA nanoparticles, the rheological change process also can be controlled by near infrared light and alternating magnetic field, which endows the magnetic fluid with the applications in the fields of mobile valves, moveable switches, buffer or damping materials in sealed devices, etc.

Diversified chemical profiles of cuticular wax on alpine meadow plants of the Qinghai-Tibet Plateau.

MAIN CONCLUSION: The alpine meadow plants showed great intra- and inter-genera variations of chemical profiles of cuticular waxes. Developing an understanding of wax structure-function relationships that will help us tackle global climate change requires a detailed understanding of plant wax chemistry. The goal in this study was to provide a catalog of wax structures, abundances, and compositions on alpine meadow plants. Here, leaf waxes from 33 plant species belonging to 11 families were sampled from alpine meadows of the east side of the Qinghai-Tibet Plateau. Across these species, total wax coverage varied from 2.30 µg cm-2 to 40.70 µg cm-2, showing variation both within as well as between genera and suggesting that wax variation is subject to both environmental and genetic effects. Across all wax samples, more than 140 wax compounds belonging to 13 wax compound classes were identified, including both ubiquitous wax compounds and lineage-specific compounds. Among the ubiquitous compounds (primary alcohols, alkyl esters, aldehydes, alkanes, and fatty acids), chain length profiles across a wide range of species point to key differences in the chain length specificity of alcohol and alkane formation machinery. The lineage-specific wax compound classes (diols, secondary alcohols, lactones, iso-alkanes, alkyl resorcinols, phenylethyl esters, cinnamate esters, alkyl benzoates, and triterpenoids) nearly all consisted of isomers with varying chain lengths or functional group positions, making the diversity of specialized wax compounds immense. The comparison of species relationships between chemical data and genetic data highlighted the importance of inferring phylogenetic relationships from data sets that contain a large number of variables that do not respond to environmental stimuli.

FSS-inspired transmitarray for dynamic beamforming and gain control.

In this paper, we propose a concept of combining the methodology of phase coding modulation with frequency selective surface (FSS) inspired transmitarray (TA) to achieve the ability of dynamical beamforming and gain control in microwave regime. The TA element composed of five-layer stacked bandpass FSS units separated by small air gaps. Each FSS unit comprises a metallic octagon slot with a pair of varactor diodes loaded along the polarization direction. The elaborately designed feeding network makes it possible to modulate the transmission phase of each element. Different phase coding sequences are performed through changing the bias voltage configurations, then the radiation far field of the proposed TA can be tailored in real time. Dynamic beamforming and gain control under different encoding arrangements are exhibited to demonstrate the physical mechanism of electromagnetic (EM) manipulation with this method. The proposed strategy is verified by numerical simulations and experiment. This work adds new function for TA and can reshape its application prospect, such as reconfigurable beam emitter for multilink data transmission, long range point-to-point (PTP) wireless links and radio frequency energy harvesting.

Efficacy and Safety of Radiofrequency Ablation Plus Stent Versus Stent-alone Treatments for Malignant Biliary Strictures: A Systematic Review and Meta-analysis.

BACKGROUND/AIMS: Malignant biliary strictures (MBS) are very aggressive and cannot be diagnosed in the early stages due to their asymptomatic nature. Stenting the stricture area of the biliary tree is palliative treatment but has poor survival time. Radiofrequency ablation plus stent (RFA+S) have been recently used to improve the survival and stent patency time in patients with MBS. In this systematic review and meta-analysis, we tried to evaluate the efficacy and safety of radiofrequency ablation. MATERIALS AND METHODS: Study search up to December 2021 was performed in different medical databases such as PubMed, Web of Science, and Cochrane library, etc. We selected eligible studies reporting survival time, stent patency time, and adverse events in patients with MBS. We compare the outcomes of RFA+S and stent-alone treatment groups. RESULTS: A total of 15 studies (6 randomized controlled trials and 9 observational studies) with 1815 patients were included for meta-analysis of which 701 patients were in RFA+S group and 1114 patients in the stent-alone group. Pooled mean difference of survival time was 2.88 months (95% CI: 1.78-3.97) and pooled mean difference of stent patency time was 2.11 months (95% CI: 0.91-3.30) and clinical success risk ratio was 1.05 (95% CI: 1.01-1.09). Risk ratios for adverse events are given; Bleeding 0.84 (95% CI: 0.34-2.11), abdominal pain 1.06 (95% CI: 0.79-1.40), pancreatitis 0.93 (95% CI: 0.43-2.01), cholangitis 1.07 (95% CI: 0.72-1.59), and stent dysfunction 0.87 (95% CI: 0.70-1.07). CONCLUSIONS: Radiofrequency ablation is involved in increased survival and stent patency time for MBS patients. With the help of better techniques, adverse events can be limited.

Imitation Learning-Based Performance-Power Trade-Off Uncore Frequency Scaling Policy for Multicore System.

As the importance of uncore components, such as shared cache slices and memory controllers, increases in processor architecture, the percentage of uncore power consumption in the overall power consumption of multicore processors rises significantly. To maximize the power efficiency of a multicore processor system, we investigate the uncore frequency scaling (UFS) policy and propose a novel imitation learning-based uncore frequency control policy. This policy performs online learning based on the DAgger algorithm and converts the annotation cost of online aggregation data into fine-tuning of the expert model. This design optimizes the online learning efficiency and improves the generality of the UFS policy on unseen loads. On the other hand, we shift our policy optimization target to Performance Per Watt (PPW), i.e., the power efficiency of the processor, to avoid saving a percentage of power while losing a larger percentage of performance. The experimental results show that our proposed policy outperforms the current advanced UFS policy in the benchmark test sequence of SPEC CPU2017. Our policy has a maximum improvement of about 10% relative to the performance-first policies. In the unseen processor load, the tuning decision made by our policy after collecting 50 aggregation data can maintain the processor stably near the optimal power efficiency state.

Research on Similarity Simulation Experiment of Mine Pressure Appearance in Surface Gully Working Face Based on BOTDA.

In order to study the mountain deflection characteristics and the pressure law of the working face after the mining of a shallow coal seam under the valley terrain, a geometric size of 5.0 × 0.2 × 1.33 m is used in the physical similarity model. Brillouin optical time domain analysis (BOTDA) technology is applied to a similar physical model experiment to monitor the internal strain of the overlying rock. In this paper, the strain law of the horizontal optical fiber at different stages of the instability of the mountain structure is analyzed. Combined with the measurement of the strain field on the surface of the model via digital image correlation (DIC) technology, the optical fiber strain characteristics of the precursor of mountain instability are given. The optical fiber characterization method of working face pressure is proposed, and the working face pressures at different mining stages in gully terrain are characterized. Finally, the relationship between the deflection instability of the mountain and the strong ground pressure on the working face is discussed. The sudden increase in the strain peak point of the horizontally distributed optical fiber strain curve can be used to distinguish the strong ground pressure. At the same time, this conclusion is verified by comparing the measured underground ground pressure values. The research results can promote the application of optical fiber sensing technology in the field of mine engineering.

The Effects of Epicuticular Wax on Anthracnose Resistance of Sorghum bicolor.

Cuticular waxes are mixtures of hydrophobic compounds covering land plant surfaces and play key roles in plant resistance to abiotic and biotic stresses. However, it is still not clear whether the epicuticular wax could protect the plants from infection by anthracnose, one of the most important plant diseases worldwide, which seriously infects sorghum and causes great yield loss. In this study, Sorghum bicolor L., an important C4 crop with high wax coverage, was selected to analyze the relationship between epicuticular wax (EW) and anthracnose resistance. In vitro analysis indicated that the sorghum leaf wax significantly inhibited the anthracnose mycelium growth of anthracnose on potato dextrose agar (PDA) medium, with the plaque diameter smaller than that grown on medium without wax. Then, the EWs were removed from the intact leaf with gum acacia, followed by the inoculation of Colletotrichum sublineola. The results indicated that the disease lesion was remarkably aggravated on leaves without EW, which showed decreased net photosynthetic rate and increased intercellular CO2 concentrations and malonaldehyde content three days after inoculation. Transcriptome analysis further indicated that 1546 and 2843 differentially expressed genes (DEGs) were regulated by C. sublineola infection in plants with and without EW, respectively. Among the DEG encoded proteins and enriched pathways regulated by anthracnose infection, the cascade of the mitogen-activated protein kinases (MAPK) signaling pathway, ABC transporters, sulfur metabolism, benzoxazinoid biosynthesis, and photosynthesis were mainly regulated in plants without EW. Overall, the EW increases plant resistance to C. sublineola by affecting physiological and transcriptome responses through sorghum epicuticular wax, improving our understanding of its roles in defending plants from fungi and ultimately benefiting sorghum resistance breeding.

Dynamic radiation steering with transmission-type coding metasurface.

In this paper, we integrate continuous transmission amplitude modulation and phase coding into a metasurface, and dynamic transmitted electromagnetic field manipulation is realized in microwave regime. The active metasurface is obtained by placing a PIN diodes loaded amplitude modulation metasurface on a binary phase coding metasurface whose coding matrix is optimized by genetic algorithm. Changing the bias voltage applied on the diodes, the transmission amplitude of the phase coding units covered by amplitude modulation units can be tuned continuously while other coding units are not affected, leading to the fact that the transmitted field pattern of the metasurface varies from strongly directional transmission to diffusion-like radiation. By this means, two degrees of freedom of dynamic amplitude modulation and predesigned phase coding are achieved to control the electromagnetic waves. Additionally, a bias network is designed to ensure the polarization-stability of the metasurface. The proposed concept is predicted by analytical model, and verified by numerical simulations and experiment. This design with low profile and diverse functionalities can yield potential applications ranging from radio frequency energy harvesting to wireless communication systems.

(cRGD)2 peptides modified nanoparticles increase tumor-targeting therapeutic effects by co-delivery of albendazole and iodine-131.

Albendazole (ABZ), a clinical antiparasitic drug, has shown potential antitumor effects in various tumors. Herein, we prepared dimeric cRGD [(cRGD)2] modified human serum albumin (HSA) nanosystem to co-delivery of albendazole (ABZ) and iodine-131 (131I) for chemoradiotherapy of triple-negative breast cancer (TNBC). HSA@ABZ NPs were synthesized by the self-assembly method. 131I-(cRGD)2/HSA@ABZ NPs were fabricated through covalently binding HSA@ABZ NPs with (cRGD)2 peptides, followed by chloramine T direct labeling with 131I. In vitro therapeutic effects on TNBC (MDA-MB-231 and 4T1 cells) were determined using MTT assay, crystal violet assay, wound-healing assay and western blotting analysis. In vivo treatment was performed using 4T1-bearing mice, and the tumor-targeting efficacy was assessed by gamma imaging. The distribution of NPs was quantitatively analyzed by detecting the gamma counts in tumor and main organs. The nanoparticles possessed negative charge, moderate size and good polydispersity index. Dual responding to pH and redox, the in vitro release rate of ABZ was more than 80% in 72 h. In vitro, NPs inhibited the proliferation of TNBC cells in a concentration-dependent manner and decreased cell migration. Western blotting analysis showed that the NPs, as well as free ABZ, cell-dependently induced autophagy and apoptosis by restraining or promoting the expression of p-p38 and p-JNK MAPK. In vivo, gamma imaging exhibited an earlier and denser radioactivity accumulation in tumor of 131I-(cRGD)2/HSA@ABZ NPs compared to NPs free of (cRGD)2 conjugating. Furthermore, 131I-(cRGD)2/HSA@ABZ NPs significantly suppressed tumor growth by restraining proliferation and promoting apoptosis in vivo. Our study suggested that the nanoparticles we developed enhanced tumor-targeting of ABZ and increased antitumor effects by combination of chemotherapy and radiotherapy.

Comparing the diagnostic performance of radiotracers in prostate cancer biochemical recurrence: a systematic review and meta-analysis.

OBJECTIVES: To systematically assess the early detection rate of biochemical prostate cancer recurrence using choline, fluciclovine, and PSMA. METHODS: Under the guidance of the Preferred Reporting Items for Systematic reviews and Meta-Analysis Diagnostic Test Accuracy guidelines, literature that assessed the detection rates (DRs) of choline, fluciclovine, and PSMA in prostate cancer biochemical recurrence was searched in PubMed and EMBASE databases for our systematic review from 2012 to July 15, 2021. In addition, the PSA-stratified performance of detection positivity was obtained to assess the DRs for various methods, including fluciclovine, PSMA, or choline PET/CT, with respect to biochemical recurrence based on different PSA levels. RESULTS: In total, 64 studies involving 11,173 patients met the inclusion criteria. Of the studies, 12, 7, and 48 focused on choline, fluciclovine, and PSMA, respectively. The pooled DRs were 24%, 37%, and 44%, respectively, for a PSA level less than 0.5 ng/mL (p < 0.001); 36%, 44%, and 60% for a PSA level of 0.5-0.99 ng/mL (p < 0.001); and 50%, 61%, and 80% for a PSA level of 1.0-1.99 ng/mL (p < 0.001). The DR with 18F-labeled PSMA was higher than that with 68Ga-labeled PSMA, and the DR was 58%, 72%, and 88% for PSA levels < 0.5 ng/mL, 0.5-0.9 ng/mL, and 1.0-1.99 ng/mL, respectively. CONCLUSION: The DRs of PSMA-radiotracers were greater than those of choline-radiotracers and fluciclovine-radiotracers at the patient level. 18F-labeled PSMA achieved a higher DR than 68Ga-labeled PSMA. KEY POINTS: • The DRs of PSMA-radiotracers were greater than those of choline-radiotracers and fluciclovine-radiotracers at the patient level. • 18F-labeled PSMA achieved a higher DR than 68Ga-labeled PSMA.