The connectivity of the human frontal pole cortex, and a theory of its involvement in exploit versus explore.

The frontal pole is implicated in humans in whether to exploit resources versus explore alternatives. Effective connectivity, functional connectivity, and tractography were measured between six human frontal pole regions and for comparison 13 dorsolateral and dorsal prefrontal cortex regions, and the 360 cortical regions in the Human Connectome Project Multi-modal-parcellation atlas in 171 HCP participants. The frontal pole regions have effective connectivity with Dorsolateral Prefrontal Cortex regions, the Dorsal Prefrontal Cortex, both implicated in working memory; and with the orbitofrontal and anterior cingulate cortex reward/non-reward system. There is also connectivity with temporal lobe, inferior parietal, and posterior cingulate regions. Given this new connectivity evidence, and evidence from activations and damage, it is proposed that the frontal pole cortex contains autoassociation attractor networks that are normally stable in a short-term memory state, and maintain stability in the other prefrontal networks during stable exploitation of goals and strategies. However, if an input from the orbitofrontal or anterior cingulate cortex that expected reward, non-reward, or punishment is received, this destabilizes the frontal pole and thereby other prefrontal networks to enable exploration of competing alternative goals and strategies. The frontal pole connectivity with reward systems may be key in exploit versus explore.

Auditory cortical connectivity in humans.

To understand auditory cortical processing, the effective connectivity between 15 auditory cortical regions and 360 cortical regions was measured in 171 Human Connectome Project participants, and complemented with functional connectivity and diffusion tractography. 1. A hierarchy of auditory cortical processing was identified from Core regions (including A1) to Belt regions LBelt, MBelt, and 52; then to PBelt; and then to HCP A4. 2. A4 has connectivity to anterior temporal lobe TA2, and to HCP A5, which connects to dorsal-bank superior temporal sulcus (STS) regions STGa, STSda, and STSdp. These STS regions also receive visual inputs about moving faces and objects, which are combined with auditory information to help implement multimodal object identification, such as who is speaking, and what is being said. Consistent with this being a "what" ventral auditory stream, these STS regions then have effective connectivity to TPOJ1, STV, PSL, TGv, TGd, and PGi, which are language-related semantic regions connecting to Broca's area, especially BA45. 3. A4 and A5 also have effective connectivity to MT and MST, which connect to superior parietal regions forming a dorsal auditory "where" stream involved in actions in space. Connections of PBelt, A4, and A5 with BA44 may form a language-related dorsal stream.

Multiple cortical visual streams in humans.

The effective connectivity between 55 visual cortical regions and 360 cortical regions was measured in 171 HCP participants using the HCP-MMP atlas, and complemented with functional connectivity and diffusion tractography. A Ventrolateral Visual "What" Stream for object and face recognition projects hierarchically to the inferior temporal visual cortex, which projects to the orbitofrontal cortex for reward value and emotion, and to the hippocampal memory system. A Ventromedial Visual "Where" Stream for scene representations connects to the parahippocampal gyrus and hippocampus. An Inferior STS (superior temporal sulcus) cortex Semantic Stream receives from the Ventrolateral Visual Stream, from visual inferior parietal PGi, and from the ventromedial-prefrontal reward system and connects to language systems. A Dorsal Visual Stream connects via V2 and V3A to MT+ Complex regions (including MT and MST), which connect to intraparietal regions (including LIP, VIP and MIP) involved in visual motion and actions in space. It performs coordinate transforms for idiothetic update of Ventromedial Stream scene representations. A Superior STS cortex Semantic Stream receives visual inputs from the Inferior STS Visual Stream, PGi, and STV, and auditory inputs from A5, is activated by face expression, motion and vocalization, and is important in social behaviour, and connects to language systems.

The human posterior parietal cortex: effective connectome, and its relation to function.

The effective connectivity between 21 regions in the human posterior parietal cortex, and 360 cortical regions was measured in 171 Human Connectome Project (HCP) participants using the HCP atlas, and complemented with functional connectivity and diffusion tractography. Intraparietal areas LIP, VIP, MIP, and AIP have connectivity from early cortical visual regions, and to visuomotor regions such as the frontal eye fields, consistent with functions in eye saccades and tracking. Five superior parietal area 7 regions receive from similar areas and from the intraparietal areas, but also receive somatosensory inputs and connect with premotor areas including area 6, consistent with functions in performing actions to reach for, grasp, and manipulate objects. In the anterior inferior parietal cortex, PFop, PFt, and PFcm are mainly somatosensory, and PF in addition receives visuo-motor and visual object information, and is implicated in multimodal shape and body image representations. In the posterior inferior parietal cortex, PFm and PGs combine visuo-motor, visual object, and reward input and connect with the hippocampal system. PGi in addition provides a route to motion-related superior temporal sulcus regions involved in social interactions. PGp has connectivity with intraparietal regions involved in coordinate transforms and may be involved in idiothetic update of hippocampal visual scene representations.

Prefrontal and somatosensory-motor cortex effective connectivity in humans.

Effective connectivity, functional connectivity, and tractography were measured between 57 cortical frontal and somatosensory regions and the 360 cortical regions in the Human Connectome Project (HCP) multimodal parcellation atlas for 171 HCP participants. A ventral somatosensory stream connects from 3b and 3a via 1 and 2 and then via opercular and frontal opercular regions to the insula, which then connects to inferior parietal PF regions. This stream is implicated in "what"-related somatosensory processing of objects and of the body and in combining with visual inputs in PF. A dorsal "action" somatosensory stream connects from 3b and 3a via 1 and 2 to parietal area 5 and then 7. Inferior prefrontal regions have connectivity with the inferior temporal visual cortex and orbitofrontal cortex, are implicated in working memory for "what" processing streams, and provide connectivity to language systems, including 44, 45, 47l, TPOJ1, and superior temporal visual area. The dorsolateral prefrontal cortex regions that include area 46 have connectivity with parietal area 7 and somatosensory inferior parietal regions and are implicated in working memory for actions and planning. The dorsal prefrontal regions, including 8Ad and 8Av, have connectivity with visual regions of the inferior parietal cortex, including PGs and PGi, and are implicated in visual and auditory top-down attention.

Dissecting the temporal genetic networks programming soybean embryo development from embryonic morphogenesis to post-germination.

KEY MESSAGE: Desiccation-stage transcription factors perform similar functions, with early ones focused on desiccation tolerance and later ones on development. Gene networks governing late embryo development diverge between soybean and Arabidopsis. To understand gene activities programming seed embryo development, we profiled the soybean embryo transcriptome across embryonic morphogenesis through post-germination. Transcriptomic landscapes across embryo development feature highly prevalent transcripts, categorized into early and late groups, with shared and distinct functions. During the mid-storage reserve accumulation stage, the upregulated genes are enriched with regulatory tasks at both the transcriptional and chromatin levels, including DNA methylation and chromatin remodeling. The epigenetic-related functions also dominate in the upregulated genes during germination, involving core histone variants and histone chaperones. Gene network analysis reveals both stage-specific modules and modules active across multiple stages. The desiccation-associated gene module integrates diverse transcription factors (TFs) that are sequentially active during different desiccation stages, transitioning from abiotic stress functions early on to developmental functions later. Two TFs, active during the early and mid-desiccation stages were functionally assessed in Arabidopsis overexpression lines to uncover their potential roles in desiccation processes. Interestingly, nearly half of the Arabidopsis orthologs of soybean TFs active in the desiccation-associated module are inactive during Arabidopsis desiccation. Our results reveal that chromatin and transcriptional regulation coordinate during mid-storage reserve accumulation, while distinct epigenetic mechanisms drive germination. Additionally, gene modules either perform stage-specific functions or are required across multiple stages, and gene networks during late embryogenesis diverge between soybean and Arabidopsis. Our studies provide new information on the biological processes and gene networks underlying development from embryonic morphogenesis to post-germination.

Genetics in neovascular age-related macular degeneration susceptibility and treatment response to anti-VEGF intravitreal injection: A case series study.

BACKGROUND: To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response. METHODS: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. RESULTS: In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). CONCLUSIONS: Among the 16 SNPs found in the GWAS, four loci-CFH, ARMS2/HTRA1, and two novel loci-were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.

Standardized patients' experiences of portraying characters in difficult communication scenarios: Narrative inquiry.

BACKGROUND: There are limited studies that explored the preparation and challenges faced by standardized patients (SPs) in portraying characters in difficult communication scenarios, and the strategies used to overcome these challenges. The purpose of this study was to understand the experience of SPs in interpreting difficult communication situations and the learning needs of performing similar scenarios. And it allows the researchers to explore the meaning, beliefs, values, and aspiration associated with their role as SPs. The findings could shade light on the significance of their experiences and provide valuable insights for the development of future SP training programs. METHODS: The design of this study is framed by a narrative inquiry, using semi-structured guidelines to conduct in-depth interviews with 11 SPs who have participated in the performances of difficult communication situations. Research data were analyzed by Polkinghorne narrative analysis, and Riessman's four criteria were used to establish rigor. RESULTS: Analysis revealed the following five themes: scenarios to real life connections, process of preparing for a performance, methods to detach from character, obtaining unexpected rewards, and needs for performance training. There are two to three subthemes that are subsumed under each theme. CONCLUSIONS: To strengthen training in difficult communication for healthcare professionals, the use of SPs to interpret challenging difficult communication scenarios will continue to increase. Educators need to ensure that SPs are fully prepared physically and emotionally before, during and after their performance. Offering of continuing education and training in feedback techniques are crucial to extend the tenure of SPs, reduce their frustration, prevent attrition, and ultimately, reduce training costs. In the future, SP training should also include detachment and feedback techniques to alleviate SPs' stress.

Enhancing antioxidant levels and mitochondrial function in porcine oocyte maturation and embryonic development through notoginsenoside R1 supplementation.

This study examines the impact of Notoginsenoside R1 (NGR1), a compound from Panax notoginseng, on the maturation of porcine oocytes and their embryonic development, focusing on its effects on antioxidant levels and mitochondrial function. This study demonstrates that supplementing in vitro maturation (IVM) medium with NGR1 significantly enhances several biochemical parameters. These include elevated levels of glutathione (GSH), nuclear factor erythrocyte 2-related factor 2 (NRF2) and mRNA expression of catalase (CAT) and GPX. Concurrently, we observed a decrease in reactive oxygen species (ROS) levels and an increase in JC-1 immunofluorescence, mitochondrial distribution, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and nuclear NRF2 mRNA levels. Additionally, there was an increase in ATP production and lipid droplets (LDs) immunofluorescence. These biochemical improvements correlate with enhanced embryonic outcomes, including a higher blastocyst rate, increased total cell count, enhanced proliferative capacity and elevated octamer-binding transcription factor 4 (Oct4) and superoxide dismutase 2 (Sod2) gene expression. Furthermore, NGR1 supplementation resulted in decreased apoptosis, reduced caspase 3 (Cas3) and BCL2-Associated X (Bax) mRNA levels and decreased glucose-regulated protein 78 kD (GRP78) immunofluorescence in porcine oocytes undergoing in vitro maturation. These findings suggest that NGR1 plays a crucial role in promoting porcine oocyte maturation and subsequent embryonic development by providing antioxidant levels and mitochondrial protection.

Carrier-Free Nano-PROTACs to Amplify Photodynamic Therapy Induced DNA Damage through BRD4 Degradation.

Therapy-induced DNA damage is the most common strategy to inhibit tumor cell proliferation, but the therapeutic efficacy is limited by DNA repair machinery. Carrier-free nanoproteolysis targeting chimeras (PROTACs), designed as SDNpros, have been developed to enhance photodynamic therapy (PDT) by blocking the DNA damage repair pathway through BRD4 degradation. Specifically, SDNpros are constructed through noncovalent interactions between the photosensitizer of chlorine e6 (Ce6) and PROTACs of BRD4 degrader (dBET57) via self-assembly. SDNpro has favorable dispersibility and a uniform nanosize distribution without drug excipients. Upon light irradiation, SDNpro produces abundant reactive oxygen species (ROS) to induce DNA oxidative damage. Meanwhile, the DNA repair pathway would be interrupted by the concurrent degradation of BRD4, which could intensify the oxidative DNA damage and elevate PDT efficiency. Beneficially, SDNpro suppresses tumor growth and avoids systemic side effects, providing a promising strategy to promote the clinical translation of PROTACs for tumor treatment.

Application of the Ohio Nurse Competency Model in a BSN Leadership/Management Course.

ABSTRACT: Strategically preparing students to meet practice expectations is a priority for nursing educators. The Ohio Nurse Competency Model (ONCM) was applied as the organizing framework for a senior baccalaureate leadership/management course. The purpose of this pretest/posttest descriptive study was to evaluate changes in students' confidence in understanding, applying, and valuing the ONCM. Paired t -tests found statistically significant increases in confidence levels for all ONCM competencies among 56 students with greatest increases in systems-based practice and informatics and technology. Nurse educators are encouraged to intentionally structure and organize course content and curricula according to state and national competency models/guidelines.

Nurse-led World Café approach in promoting interprofessional collaborative behaviors and learning engagement among healthcare professionals.

Effective interprofessional collaboration practice (IPCP) promotes healthcare outcomes but is often hindered by poor communication. Traditional teaching methods with limited interdisciplinary interactions may not effectively foster IPCP behaviors. This study evaluated the effectiveness of nurse-led World Cafe (NWC) approach in promoting IPCP behaviors and learning engagement. Seventy-six healthcare professionals (38 in each group) participated in this quasi-experimental study. Data were collected before, one-week, and four-week post-intervention, using Lee's (2016) Interprofessional Collaborative Practice Behavior Inventory (IPCPBI) and Ciou's (2020) Learning Engagement Scale. Five medical technologists in the control group were excluded from data analysis to ensure group equivalence. Before the intervention, there were no significant differences in IPCPBI between groups. One week post-intervention, the experimental group scored higher in IPCPBI, yet lacked statistical significance (p > .05). Four weeks post-intervention, the experimental group significantly improved in IPCPBI (p < .05). While no statistically significance was found in learning engagement between groups, the experimental group scored significantly higher in the active engagement sub-domain (p < .05). The NWC approach boosted IPCP behaviors and learning engagement, fostering a collaborative learning environment that improves outcomes through interdisciplinary interactions. Healthcare settings could benefit from adopting the NWC approach to enhance clinicians' IPCP competency.

Effects of New Psychoactive Substance Esketamine on Behaviors and Transcription of Genes in Dopamine and GABA Pathways in Zebrafish Larvae.

Esketamine (ESK) is the S-enantiomer of ketamine racemate (a new psychoactive substance) that can result in illusions, and alter hearing, vision, and proprioception in human and mouse. Up to now, the neurotoxicity caused by ESK at environmental level in fish is still unclear. This work studied the effects of ESK on behaviors and transcriptions of genes in dopamine and GABA pathways in zebrafish larvae at ranging from 12.4 ng L- 1 to 11141.1 ng L- 1 for 7 days post fertilization (dpf). The results showed that ESK at 12.4 ng L- 1 significantly reduced the touch response of the larvae at 48 hpf. ESK at 12.4 ng L- 1 also reduced the time and distance of larvae swimming at the outer zone during light period, which implied that ESK might potentially decrease the anxiety level of larvae. In addition, ESK increased the transcription of th, ddc, drd1a, drd3 and drd4a in dopamine pathway. Similarly, ESK raised the transcription of slc6a1b, slc6a13 and slc12a2 in GABA pathway. This study suggested that ESK could affect the heart rate and behaviors accompanying with transcriptional alterations of genes in DA and GABA pathways at early-staged zebrafish, which resulted in neurotoxicity in zebrafish larvae.

[Excelling in the AI Era: Cultivating AI Literacy].

In light of the rapid advancements in artificial intelligence (AI), the future of the nursing profession is expected to be closely intertwined with AI applications. In response to this challenge, nursing educators must cultivate AI literacy in students to ensure their ability to communicate and collaborate effectively with their interdisciplinary peers. Nursing educators should comprehend the essence of AI literacy, integrate AI literacy into their curriculum designs, and regularly assess the effectiveness of AI literacy cultivation efforts among their students to ensure nursing graduates are able to effectively fulfill their roles in nursing and healthcare. The purpose of this paper is to explain the essence of AI literacy, approaches for cultivating AI literacy in students, and methods for assessing AI literacy with the aim of educating nursing students to become competent nurses for tomorrow.

Anticancer effects of tanshinone IIA in bladder urothelial carcinoma by down-regulating aurora A, HIF-1α and Bcl-2 both in vitro and in vivo.

The mechanisms of the anticancer effect of Tanshinone IIA (Tan IIA) on Bladder urothelial carcinoma (BUC) remain mostly unknown. In this study, BUC T24 cells were treated with Tan IIA at different concentrations and durations. The apoptosis, proliferation and invasion of T24 cells were evaluated using MTT assays, Annexin V-FITC Staining, Hoechst staining and Trans well assay. One group of T-24 cell xenograft mice was treated with Tan IIA, while the other group received normal saline for 25 days. Subsequently, the size of tumors as well as mRNA and protein expression of Aurora A, HIF-1α and Bcl-2 were measured both in vitro and in vivo. Tan IIA induced apoptosis, inhibited proliferation, suppressed invasion of T24 cells in a time- and dose-dependent manner in vitro and attenuated growth in vivo. The decreasing of mRNA and protein expression of Aurora A, HIF-1α and Bcl-2 in T-24 cells treated with Tan IIA were detected in a time- and dose-dependent manner both in vitro and in vivo. The pro-apoptotic, anti-proliferative and anti-invasive effects of Tan IIA on T-24 cells may be derived from inhibition of mRNA and protein expression of Aurora A, HIF-1α and Bcl-2. Tan IIA could potentially serve as a novel potential anti-cancer agent for BUC.

The human posterior cingulate, retrosplenial, and medial parietal cortex effective connectome, and implications for memory and navigation.

The human posterior cingulate, retrosplenial, and medial parietal cortex are involved in memory and navigation. The functional anatomy underlying these cognitive functions was investigated by measuring the effective connectivity of these Posterior Cingulate Division (PCD) regions in the Human Connectome Project-MMP1 atlas in 171 HCP participants, and complemented with functional connectivity and diffusion tractography. First, the postero-ventral parts of the PCD (31pd, 31pv, 7m, d23ab, and v23ab) have effective connectivity with the temporal pole, inferior temporal visual cortex, cortex in the superior temporal sulcus implicated in auditory and semantic processing, with the reward-related vmPFC and pregenual anterior cingulate cortex, with the inferior parietal cortex, and with the hippocampal system. This connectivity implicates it in hippocampal episodic memory, providing routes for "what," reward and semantic schema-related information to access the hippocampus. Second, the antero-dorsal parts of the PCD (especially 31a and 23d, PCV, and also RSC) have connectivity with early visual cortical areas including those that represent spatial scenes, with the superior parietal cortex, with the pregenual anterior cingulate cortex, and with the hippocampal system. This connectivity implicates it in the "where" component for hippocampal episodic memory and for spatial navigation. The dorsal-transitional-visual (DVT) and ProStriate regions where the retrosplenial scene area is located have connectivity from early visual cortical areas to the parahippocampal scene area, providing a ventromedial route for spatial scene information to reach the hippocampus. These connectivities provide important routes for "what," reward, and "where" scene-related information for human hippocampal episodic memory and navigation. The midcingulate cortex provides a route from the anterior dorsal parts of the PCD and the supracallosal part of the anterior cingulate cortex to premotor regions.

Integrated diffusion image operator (iDIO): A pipeline for automated configuration and processing of diffusion MRI data.

The preprocessing of diffusion magnetic resonance imaging (dMRI) data involve numerous steps, including the corrections for head motion, susceptibility distortion, low signal-to-noise ratio, and signal drifting. Researchers or clinical practitioners often need to configure different preprocessing steps depending on disparate image acquisition schemes, which increases the technical threshold for dMRI analysis for nonexpert users. This could cause disparities in data processing approaches and thus hinder the comparability between studies. To make the dMRI data processing steps transparent and adapt to various dMRI acquisition schemes for researchers, we propose a semi-automated pipeline tool for dMRI named integrated diffusion image operator or iDIO. This pipeline integrates features from a wide range of advanced dMRI software tools and targets at providing a one-click solution for dMRI data analysis, via adaptive configuration for a set of suggested processing steps based on the image header of the input data. Additionally, the pipeline provides options for post-processing, such as estimation of diffusion tensor metrics and whole-brain tractography-based connectomes reconstruction using common brain atlases. The iDIO pipeline also outputs an easy-to-interpret quality control report to facilitate users to assess the data quality. To keep the transparency of data processing, the execution log and all the intermediate images produced in the iDIO's workflow are accessible. The goal of iDIO is to reduce the barriers for clinical or nonspecialist users to adopt the state-of-art dMRI processing steps.

Sex disparity of cerebral white matter hyperintensity in the hypertensive elderly: The Shanghai Changfeng study.

White matter hyperintensity (WMH) is associated with vascular hemodynamic alterations and reflects white matter injury. To date, the sex difference of tract-specific WMH and the relationship between high blood pressure (BP) and tract-specific WMH remain unclear. We recruited 515 subjects from the Shanghai Changfeng study (range 53-89 years, mean age 67.33 years). Systolic and diastolic blood pressure (SBP and DBP) were collected and used to calculate pulse pressure (PP). Magnetic resonance T1 and T2 FLAIR images were acquired to measure WMH and calculate WMH index. The ANCOVA test was performed to test the difference between sexes, and the linear regression model was used to examine the associations between BP and WMH index. Men showed higher WMH index than women in all white matter tracts (p < .001, respectively) except for the bilateral superior longitudinal fasciculus (SLF) and its left temporal part (tSLF). High SBP and PP was associated with a lower WMH index on the left corticospinal tract (CST), SLF, tSLF and right cingulum in hippocampus (p ≤ .001, respectively) in women, while high DBP was associated with a higher WMH index on the bilateral CST (left p < .001; right p = .001), left inferior longitudinal fasciculus (p < .001) and inferior fronto-occipital fasciculus (p = .002) in men. Men tend to have more WMH compared to women. A high SBP/PP relates to a lower WMH burden in women. This suggests that women could benefit from higher blood pressure in older age.

Chimeric Peptide-Engineered Self-Delivery Nanomedicine for Photodynamic-Triggered Breast Cancer Immunotherapy by Macrophage Polarization.

A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide-engineered self-delivery nanomedicine (designated as ChiP-CeR) for photodynamic-triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP-CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc-K(Fmoc)-PEG8 -CREKA. ChiP-CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high-mobility group box-1(HMGB1) and expose calreticulin (CRT). Moreover, ChiP-CeR can also polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP-CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.

Cascade Immune Activation of Self-Delivery Biomedicine for Photodynamic Immunotherapy Against Metastatic Tumor.

Photodynamic therapy (PDT) can generate reactive oxygen species (ROS) to cause cell apoptosis and induce immunogenic cell death (ICD) to activate immune response, becoming a promising antitumor modality. However, the overexpressions of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand 1 (PD-L1) on tumor cells would reduce cytotoxic T cells infiltration and inhibit the immune activation. In this paper, a simple but effective nanosystem is developed to solve these issues for enhanced photodynamic immunotherapy. Specifically, it has been constructed a self-delivery biomedicine (CeNB) based on photosensitizer chlorine e6 (Ce6), IDO inhibitor (NLG919), and PD1/PDL1 blocker (BMS-1) without the need for extra excipients. Of note, CeNB possesses fairly high drug content (nearly 100%), favorable stability, and uniform morphology. More importantly, CeNB-mediated IDO inhibition and PD1/PDL1 blockade greatly improve the immunosuppressive tumor microenvironments to promote immune activation. The PDT of CeNB not only inhibits tumor proliferation but also induces ICD response to activate immunological cascade. Ultimately, self-delivery CeNB tremendously suppresses the tumor growth and metastasis while leads to a minimized side effect. Such simple and effective antitumor strategy overcomes the therapeutic resistance against PDT-initiated immunotherapy, suggesting a potential for metastatic tumor treatment in clinic.