NUSAP1 Promotes Immunity and Apoptosis by the SHCBP1/JAK2/STAT3 Phosphorylation Pathway to Induce Dendritic Cell Generation in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is associated with high morbidity and mortality rates. The aims of this study were to investigate the immune-promoting action of nucleolar and spindle-associated protein 1 (NUSAP1) and identify an immunotherapy target for HCC. The Cancer Genome Atlas (TCGA) was used to analyze interaction molecules and immune correlation. The interaction between NUSAP1 and SHC binding and spindle associated 1 (SHCBP1) was examined. The role of the SHCBP1/Janus kinase 2/signal transducer and activator of transcription 3 (SHCBP1/JAK2/STAT3) pathway in this process was explored. After co-culture with HCC cell lines, the differentiation of peripheral blood mononuclear cells (PBMCs) into dendritic cells (DC) was evaluated by measuring the expression of surface factors CD1a and CD86. Pathological tissues from 50 patients with HCC were collected to validate the results of cell experiments. The expression levels of CD1a and CD86 in tissues were also determined. The results show that NUSAP1 interacted with SHCBP1 and was positively correlated with DC. In HCC cell lines, an interaction was observed between NUSAP1 and SHCBP1. It was verified that NUSAP1 inhibited the JAK2/STAT3 phosphorylation pathway by blocking SHCBP1. After co-culture, the levels of CD1a and CD86 in PBMC were elevated. In the clinical specimens, CD1a and CD86 expression levels were significantly higher in the high-NUSAP1 group versus the low-NUSAP1 group. In Summary, NUSAP1 enhanced immunity by inhibiting the SHCBP1/JAK2/STAT3 phosphorylation pathway and promoted DC generation and HCC apoptosis. NUSAP1 may be a target of immunotherapy for HCC.

Lipopeptides from Bacillus velezensis ZLP-101 and their mode of action against bean aphids Acyrthosiphon pisum Harris.

BACKGROUND: Natural products are important sources for the discovery of new biopesticides to control the worldwide destructive pests Acyrthosiphon pisum Harris. Here, insecticidal substances were discovered and characterized from the secondary metabolites of the bio-control microorganism Bacillus velezensis strain ZLP-101, as informed by whole-genome sequencing and analysis. RESULTS: The genome was annotated, revealing the presence of four potentially novel gene clusters and eight known secondary metabolite synthetic gene clusters. Crude extracts, prepared through ammonium sulfate precipitation, were used to evaluate the effects of strain ZLP-101 on Acyrthosiphon pisum Harris aphid pests via exposure experiments. The half lethal concentration (LC50) of the crude extract from strain ZLP-101 against aphids was 411.535 mg/L. Preliminary exploration of the insecticidal mechanism revealed that the crude extract affected aphids to a greater extent through gastric poisoning than through contact. Further, the extracts affected enzymatic activities, causing holes to form in internal organs along with deformation, such that normal physiological activities could not be maintained, eventually leading to death. Isolation and purification of extracellular secondary metabolites were conducted in combination with mass spectrometry analysis to further identify the insecticidal components of the crude extracts. A total of 15 insecticidal active compounds were identified including iturins, fengycins, surfactins, and spergualins. Further insecticidal experimentation revealed that surfactin, iturin, and fengycin all exhibited certain aphidicidal activities, and the three exerted synergistic lethal effects. CONCLUSIONS: This study improved the available genomic resources for B. velezensis and serves as a foundation for comprehensive studies of the insecticidal mechanism by Bacillus velezensis ZLP-101 in addition to the active components within biological control strains.

Metabolic reprogramming in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a malignancy with high incidence in China. Due to the lack of effective molecular targets, the prognosis of ESCC patients is poor. It is urgent to explore the pathogenesis of ESCC to identify promising therapeutic targets. Metabolic reprogramming is an emerging hallmark of ESCC, providing a novel perspective for revealing the biological features of ESCC. In the hypoxic and nutrient-limited tumor microenvironment, ESCC cells have to reprogram their metabolic phenotypes to fulfill the demands of bioenergetics, biosynthesis and redox homostasis of ESCC cells. In this review, we summarized the metabolic reprogramming of ESCC cells that involves glucose metabolism, lipid metabolism, and amino acid metabolism and explore how reprogrammed metabolism provokes novel opportunities for biomarkers and potential therapeutic targets of ESCC.

Identification of crucial inflammaging related risk factors in multiple sclerosis.

Background: Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammatory demyelinating lesions in the central nervous system. Studies have shown that the inflammation is vital to both the onset and progression of MS, where aging plays a key role in it. However, the potential mechanisms on how aging-related inflammation (inflammaging) promotes MS have not been fully understood. Therefore, there is an urgent need to integrate the underlying mechanisms between inflammaging and MS, where meaningful prediction models are needed. Methods: First, both aging and disease models were developed using machine learning methods, respectively. Then, an integrated inflammaging model was used to identify relative risk factors, by identifying essential "aging-inflammation-disease" triples. Finally, a series of bioinformatics analyses (including network analysis, enrichment analysis, sensitivity analysis, and pan-cancer analysis) were further used to explore the potential mechanisms between inflammaging and MS. Results: A series of risk factors were identified, such as the protein homeostasis, cellular homeostasis, neurodevelopment and energy metabolism. The inflammaging indices were further validated in different cancer types. Therefore, various risk factors were integrated, and even both the theories of inflammaging and immunosenescence were further confirmed. Conclusion: In conclusion, our study systematically investigated the potential relationships between inflammaging and MS through a series of computational approaches, and could present a novel thought for other aging-related diseases.

hP-MSCs attenuate severe acute pancreatitis in mice via inhibiting NLRP3 inflammasome-mediated acinar cell pyroptosis.

BACKGROUND: Severe acute pancreatitis (SAP) is a serious gastrointestinal disease that is facilitated by pancreatic acinar cell death. The protective role of human placental mesenchymal stem cells (hP-MSCs) in SAP has been demonstrated in our previous studies. However, the underlying mechanisms of this therapy remain unclear. Herein, we investigated the regularity of acinar cell pyroptosis during SAP and investigated whether the protective effect of hP-MSCs was associated with the inhibition of acinar cell pyroptosis. METHODS: A mouse model of SAP was established by the retrograde injection of sodium taurocholate (NaTC) solution in the pancreatic duct. For the hP-MSCs group, hP-MSCs were injected via the tail vein and were monitored in vivo. Transmission electron microscopy (TEM) was used to observe the pyroptosis-associated ultramorphology of acinar cells. Immunofluorescence and Western blotting were subsequently used to assess the localization and expression of pyroptosis-associated proteins in acinar cells. Systemic inflammation and local injury-associated parameters were evaluated. RESULTS: Acinar cell pyroptosis was observed during SAP, and the expression of pyroptosis-associated proteins initially increased, peaked at 24 h, and subsequently showed a decreasing trend. hP-MSCs effectively attenuated systemic inflammation and local injury in the SAP model mice. Importantly, hP-MSCs decreased the expression of pyroptosis-associated proteins and the activity of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in acinar cells. CONCLUSIONS: Our study demonstrates the regularity and important role of acinar cell pyroptosis during SAP. hP-MSCs attenuate inflammation and inhibit acinar cell pyroptosis via suppressing NLRP3 inflammasome activation, thereby exerting a protective effect against SAP.

Construction of tissue-engineered vascular grafts with enhanced patency by integrating heparin, cell-adhesive peptide, and carbon monoxide nanogenerators into acellular blood vessels.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) have garnered significant attention as a potential treatment modality for vascular bypass grafting and replacement therapy. However, the intimal hyperplasia and thrombosis are two major complications that impair graft patency during transplantation. To address this issue, we fabricated the covalent-organic framework (COF)-based carbon monoxide (CO) nanogenerator-and co-immobilized with LXW-7 peptide and heparin to establish a multifunctional surface on TEVGs constructed from acellular blood vessels for preventing thrombosis and stenosis. The cell-adhesive peptide LXW-7 could capture endothelial-forming cells (EFCs) to promote endothelialization, while the antithrombotic molecule heparin prevented thrombus formation. The reactive oxygen species (ROS)-triggered CO release suppressed the adhesion and activation of macrophages, leading to the reduction of ROS and inflammatory factors. As a result, the endothelial-to-mesenchymal transition (EndMT) triggered by inflammation was restricted, facilitating the maintenance of the homeostasis of the neo-endothelium and preventing pathological remodeling in TEVGs. When transplanted in vivo, these vascular grafts exhibited negligible intimal hyperplasia and remained patent for 3 months. This achievement provided a novel approach for constructing antithrombotic and anti-hyperplastic TEVGs.

Identification of benzothiazoles as novel PCSK9 inhibitors.

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a clinically validated target on the treatment of cardiovascular disease (CVD). PCSK9 can regulate the hepatocyte surface low density lipoprotein receptor (LDLR) level by binding to LDLR and leading to their degradation in the lysosome. The clinical use of two monoclonal antibodies (alirocumab and evolocumab, approved in 2015) and one small interfering RNA (inclisiran, approved in 2020) which can inhibit PCSK9 function proved that they are very effective in lowering low density lipoprotein cholesterol (LDL-C). However, the high treatment costs and parenteral administration of these drugs prohibited widespread use and reduced their long-term advantage. Comparatively, small molecule drugs have many incomparable advantages of macromolecules, such as lower treatment cost, more drug administration options, superior pharmacokinetic properties, less adverse immunogenic responses and better affordable production. In this paper, we identified a series of benzothiazoles small molecule PCSK9 inhibitors through extensive screening. The structure and activity relationship (SAR) was summarized to facilitate further optimization. Moreover, the primary mechanism of action of the most potent compound was also investigated.

In vivo liver function reserve assessments in alcoholic liver disease by scalable photoacoustic imaging.

We present a rapid and high-resolution photoacoustic imaging method for evaluating the liver function reserve (LFR). To validate its accuracy, we establish alcoholic liver disease (ALD) models and employ dual-wavelength spectral unmixing to assess oxygen metabolism. An empirical mathematical model fits the photoacoustic signals, obtaining liver metabolism curve and LFR parameters. Liver oxygen metabolism significantly drops in ALD with the emergence of abnormal hepatic lobular structure. ICG half-life remarkably extends from 241 to 568 s in ALD. A significant decline in LFR occurs in terminal region compared to central region, indicated by a 106.9 s delay in ICG half-life, likely due to hepatic artery and vein damage causing hypoxia and inadequate nutrition. Reduced glutathione repairs LFR with a 43% improvement by reducing alcohol-induced oxidative damage. Scalable photoacoustic imaging shows immense potential for assessing LFR in alcoholic-related diseases, providing assistance to early detection and management of liver disease.

Energy transfer of imbalanced Alfvénic turbulence in the heliosphere.

Imbalanced Alfvénic turbulence is a universal process playing a crucial role in energy transfer in space,  astrophysical, and laboratory plasmas. A fundamental and long-lasting question about the imbalanced Alfvénic turbulence is how and through which mechanism the energy transfers between scales. Here, we show that the energy transfer of imbalanced Alfvénic turbulence is completed by coherent interactions between Alfvén waves and co-propagating anomalous fluctuations. These anomalous fluctuations are generated by nonlinear couplings instead of linear reflection. We also reveal that the energy transfer of the waves and the anomalous fluctuations is carried out mainly through local-scale and large-scale nonlinear interactions, respectively, responsible for their bifurcated power-law spectra. This work unveils the energy transfer physics of imbalanced Alfvénic turbulence, and advances the understanding of imbalanced Alfvénic turbulence observed by Parker Solar Probe in the inner heliosphere.

Identification of bioactive compounds of Bacillus velezensis HNA3 that contribute to its dual effects as plant growth promoter and biocontrol against post-harvested fungi.

IMPORTANCE: The current study is an extension to our previous work on the plant growth-promoting rhizobacteria (PGPR) Bacillus velezensis HNA3 strain, which comes to confirm and reveals the huge stock of active secondary metabolites produced by HNA3. HNA3-emitted volatile organic compounds (VOCs) have demonstrated the capacity to impede the growth of phytopathogens affecting some fruits and vegetables, even in the absence of direct contact. Additionally, these volatiles enhanced soybean seed germination by breaking seed dormancy and inducing root system development. Furthermore, they promoted seedling growth, giving it prominence in soybean cultivation. The relevance of active volatiles derives from the fact that they can be developed as natural-safe biocontrol agents and plant promoters. This research validates the remarkable bioactivities exhibited by the Bacillus velezensis HNA3 and their potential applications in agriculture as an inoculant, encompassing biocontrol, plant growth promotion, and seed germination activities, thereby offering a safer alternative to hazardous chemicals.

A NaCrO2@C free-standing cathode via electrospinning for sodium-ion batteries.

A flexible free-standing cathode is innovatively constructed with NaCrO2 as the electrochemical active substance via an electrospinning technique. The as constructed NaCrO2@C flexible free-standing cathode exhibits exceptional rate performance (106 mA h g-1 at 10C) and cyclability (retention rate of 87.5% after 300 cycles at 0.2C). This work provides a brand-new perspective to the development of flexible free-standing cathodes.

Modelling porcine NAFLD by deletion of leptin and defining the role of AMPK in hepatic fibrosis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic hepatic disease and results in non-alcoholic steatohepatitis (NASH), which progresses to fibrosis and cirrhosis. Although the Leptin deficient rodent models are widely used in study of metabolic syndrome and obesity, they fail to develop liver injuries as in patients. METHODS: Due to the high similarity with humans, we generated Leptin-deficient (Leptin-/-) pigs to investigate the mechanisms and clinical trials of obesity and NAFLD caused by Leptin. RESULTS: The Leptin-/- pigs showed increased body fat and significant insulin resistance at the age of 12 months. Moreover, Leptin-/- pig developed fatty liver, non-alcoholic steatohepatitis and hepatic fibrosis with age. Absence of Leptin in pig reduced the phosphorylation of JAK2-STAT3 and AMPK. The inactivation of JAK2-STAT3 and AMPK enhanced fatty acid ß-oxidation and leaded to mitochondrial autophagy respectively, and both contributed to increased oxidative stress in liver cells. In contrast with Leptin-/- pig, although Leptin deletion in rat liver inhibited JAK2-STAT3 phosphorylation, the activation of AMPK pathway might prevent liver injury. Therefore, ß-oxidation, mitochondrial autophagy and hepatic fibrosis did not occurred in Leptin-/- rat livers. CONCLUSIONS: The Leptin-deficient pigs presents an ideal model to illustrate the full spectrum of human NAFLD. The activity of AMPK signaling pathway suggests a potential target to develop new strategy for the diagnosis and treatment of NAFLD.

The efficacy of pre-operative conization in patients undergoing surgical treatment for early-stage cervical cancer: A meta-analysis.

BACKGROUND: Minimal invasive surgery (MIS) has been reported to increase the risk of cancer relapse and death compared with traditional open surgery in patients with early-stage cervical cancer (CC). Pre-operative conization is a protective procedure that as developed to reduce the risk caused by MIS. METHODS: Relevant publications were identified by searching medical databases prior to the December 31, 2022. The primary aim of this meta-analysis was to evaluate the efficacy of pre-operative conization on disease-free survival (DFS) in early-stage CC. The secondary objective was to assess the efficacy of pre-operative conization on overall survival (OS) in early-stage CC. RESULTS: Twelve studies were eligible for analysis. The pooled result of pre-operative conization showed a significantly improved DFS when compared with non-conization patients (HR, 0.28; 95% CI, 0.19-0.41), furthermore, pre-operative conization improved DFS by 75% (HR, 0.25; 95% CI, 0.13-0.46) in stage IB1 patients. In patients who underwent MIS, pre-operative conization also led to a significant improvement in DFS when compared with non-conization patients (HR, 0.21; 95% CI, 0.09-0.54). However, in patients who underwent pre-operative conization, MIS increased the risk of recurrence by 34% when compared with open abdominal radical hysterectomy (HR, 1.34; 95% CI, 0.41-4.38), although this difference was not statistically significant. Finally, the OS of early-stage CC was not significantly affected by surgical approach or conization. CONCLUSION: Pre-operation conization represents a protective effect and can improve DFS when compared with non-conization in early-stage CC, especially in stage IB CC. There was no statistical evidence to indicate that pre-operation conization could improve OS. High-quality randomized controlled trials are required to verify these results.

Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis.

Nasopharyngeal carcinoma (NPC) is one of the most ordinary malignant tumors. Current research has suggested that circular RNAs play an important role in tumor genesis and progression. The purpose of this study is to explore the function and underlying mechanisms of circ_0028007 in NPC. The levels of circ_0028007, miR-1179, and Squalene epoxidase (SQLE) were detected by quantitative real-time polymerase chain reaction. Cell proliferation was detected by colony formation assay and thymidine analog 5-ethynyl-2'-deoxyuridine assay. Cell apoptosis was detected by flow cytometry. Relevant kits detected caspase-3, glucose, and lactate levels. Western blot assay was used to detect the related protein content. Dual-luciferase reporter assay and RNA pull-down assay were used to examine the target relationship between miR-1179 and circ_0028007 or SQLE. circ_0028007 and SQLE were highly expressed in NPC, while miR-1179 was lowly expressed. circ_0028007 silencing inhibited NPC cell proliferation and promoted apoptosis. However, the effect of circ_0028007 down-regulation on NPC cells was partially restored by co-transfection with miR-1179 inhibitor. Overexpression of SQLE partially restored the cell proliferation inhibited by circ_0028007 knockdown. circ_0028007 could regulate NPC progression via the miR-1179/SQLE axis. Therefore, circ_0028007 might be a new therapeutic target for NPC.

Construction of multi-program responsive vitamin E succinate-chitosan-histidine nanocarrier and its response strategy in tumor therapy.

Multifunctional drug delivery carriers have emerged as a promising cancer drug delivery strategy. Here, we developed a vitamin E succinate-chitosan-histidine (VCH) multi-program responsive drug carrier. The structure was characterized by FT-IR and 1H NMR spectrum, and the DLS and SEM results showed typical nanostructures. The drug loading content was 21.0 % and the corresponding encapsulation efficiency was 66.6 %. The UV-vis and fluorescence spectra demonstrated the existence of the π-π stacking interaction between DOX and VCH. Drug release experiments implied good pH sensitivity and sustained-release effect. The DOX/VCH nanoparticles could be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate was up to 56.27 %. The DOX/VCH reduced the tumor volume and weight efficiently with a TIR of 45.81 %. The histological analysis results showed that DOX/VCH could effectively inhibit tumor growth and proliferation, and there was no damage to normal organs. VCH nanocarriers could combine the advantages of VES, histidine and chitosan to achieve pH sensitivity and P-gp inhibition, and effectively improve the drug solubility, targeting and lysosomal escape. Through the program response of different micro-environment, the newly developed polymeric micelles could successfully be utilized as a multi-program responsive nanocarrier system for the treatment of cancers.

Advanced Pt-based electrocatalysts for the hydrogen evolution reaction in alkaline medium.

Water electro-splitting driven by renewable energy is significant in energy conversion for the development of hydrogen energy sources. The hydrogen evolution reaction (HER) directly generating hydrogen products occurs in cathode catalysis. Over the years, significant progress has been made to boost the HER efficiency by exploratively designing highly active and economical Pt-based electrocatalysts. However, there are still some urgent problems to be solved for Pt-based HER catalysts in more economical alkaline electrolytes, such as the slow kinetics caused by additional hydrolysis dissociation steps, which greatly hinders the practical application. This review systematically summarizes several strategies for optimizing alkaline HER kinetics and provides direct guidelines for the design of highly active Pt-based electrocatalysts. Specifically, the intrinsic HER activity in alkaline water electrolysis can be boosted by accelerating the water dissociation, optimizing the hydrogen binding energy or modulating the spatial dimensions of the electrocatalyst based on the HER mechanism. Finally, we prospect the challenges for the alkaline HER on novel Pt-based electrocatalysts, including the active site study, the HER mechanism exploration and the extensible catalyst preparation technologies.

Prophylactic cranial irradiation for extensive stage small cell lung cancer: a meta-analysis of randomized controlled trials.

Background: Previous studies have demonstrated that prophylactic cranial irradiation (PCI) could reduce the risk of brain metastases and prolong the overall survival (OS) of patients with small cell lung cancer (SCLC). However, it remains controversial whether the efficacy and safety of PCI would be subjected to the different characteristics of patients with extensive stage of SCLC. This meta-analysis aims to evaluate the efficacy and safety of PCI in patients with extensive stage SCLC. Methods: PubMed, Embase, and the Cochrane Library were searched for relevant studies from inception to May, 2021. Hazard ratios (HRs) were used to measure the OS and progression-free survival (PFS), and relative risks (RRs) were employed to calculate the incidence of brain metastases, survival rate, and adverse events. Summary results were pooled using random-effect models. Results: There were 1215 articles identified, and 15 trials were included, with a total of 1,623 participants. Patients who received PCI did not result in significantly improved OS [HR=0.87, 95%CI (0.70, 1.08) p=0.417] and PFS [HR=0.81, 95%CI (0.69, 0.95) p=0.001], compared with those who did not receive PCI, while patients who received PCI had a significantly decreased incidence of brain metastases [RR=0.57, 95%CI (0.45, 0.74), p<0.001]. PCI group showed no improvements in 2-year (RR=1.03, p=0.154), 3-year (RR=0.97, p=0.072), 4-year (RR=0.71, p=0.101) and 5-year survival rates (RR=0.32, p=0.307), compared with non-PCI group, whereas the overall RR indicated that PCI was associated with a higher 1-year survival rate [RR=1.46, 95%CI (1.08, 1.97), p=0.013]. In addition, PCI treatment was shown to be associated with increased incidence of adverse events, including fatigue, dermatitis, anorexia, nausea, vomiting, malaise, and cognitive impairment. Conclusion: This meta-analysis suggests that PCI can reduce the incidence of brain metastases in extensive stage SCLC. Although PCI has no significant effect on the OS, it improves 1-year survival in patients with extensive stage SCLC. However, PCI does not significantly affect 2,3,4,5-year survival and may result in a significantly increased risk of adverse events.

Effectiveness and safety of novel motorized spiral enteroscopy: a systematic review and meta-analysis.

BACKGROUND: Motorized spiral enteroscopy (MSE) is a novel advance in small bowel examination that is characterized as fast with a deep insertion. The aim of this study was to elucidate the effectiveness and safety of MSE. METHODS: Relevant articles that were published before November 1, 2022 were identified by searching PubMed, EMBASE, Cochrane, and the Web of Science. The technical success rate (TSR), total (pan)-enteroscopy rate (TER), depth of maximum insertion (DMI), diagnostic yield, and adverse events were extracted and analyzed. Forest plots were graphed based on random effects models. RESULTS: A total of 876 patients from 8 studies were eligible for analysis. The pooled results of the TSR were 95.0% [95% confidence interval (CI) 91.0-98.0%, I2 = 78%, p < 0.01] and the pooled outcome of the TER was 43.1% (95% CI 24.7-62.5%, I2 = 95%, p < 0.01). The pooled results of the diagnostic and therapeutic yields were 77.2% (95% CI 69.0-84.5%, I2 = 84%, p < 0.01) and 49.0% (95% CI 38.0-60.1%, I2 = 89%, p < 0.01), respectively. The pooled estimates of adverse and severe adverse events were 17.2% (95% CI 11.9-23.2%, I2 = 75%, p < 0.01) and 0.7% (95% CI 0.0-2.1%, I2 = 37%, p = 0.13), respectively. CONCLUSION: MSE is a novel alternative approach for small bowel examination that can achieve high TER and diagnostic and therapeutic yields, and relatively low rates of severe adverse events. Head-to-head studies comparing MSE and other device-assisted enteroscopies are warranted.

Long-Lived Photoacid-Doped Conducting Composites Induce Photocurrent for Efficient Wound Healing.

Electrical stimulation is an effective strategy for facilitating wound healing. However, it is hindered by unwieldy electrical systems. In this study, a light-powered dressing based on long-lived photoacid generator (PAG)-doped polyaniline composites is used, which can generate a photocurrent under visible light irradiation to interact with the endogenous electric field and facilitate skin growth. Light-controlled proton binding and dissociation result in oxidation and reduction of the polyaniline backbone, inducing charge transfer to generate a photocurrent. Due to the rapid intramolecular photoreaction of PAG, a long-lived proton-induced localized acidic environment is formed, which protects the wound from microbial infection. In summary, a simple and effective therapeutic strategy is introduced for light-powered and biocompatible wound dressings that show great potential for wound treatment.

Mild photothermal/radiation therapy potentiates ferroptosis effect for ablation of breast cancer via MRI/PA imaging guided all-in-one strategy.

BACKGROUND: Nanotheranostics advances anticancer management by providing therapeutic and diagnostic functions, that combine programmed cell death (PCD) initiation and imaging-guided treatment, thus increasing the efficacy of tumor ablation and efficiently fighting against cancer. However, mild photothermal/radiation therapy with imaging-guided precise mediating PCD in solid tumors, involving processes related to apoptosis and ferroptosis, enhanced the effect of breast cancer inhibition is not fully understood. RESULTS: Herein, targeted peptide conjugated gold nano cages, iRGD-PEG/AuNCs@FePt NPs ternary metallic nanoparticles (Au@FePt NPs) were designed to achieve photoacoustic imaging (PAI)/Magnetic resonance imaging (MRI) guided synergistic therapy. Tumor-targeting Au@FePt forms reactive oxygen species (ROS), initiated by X-ray-induced dynamic therapy (XDT) in collaboration with photothermal therapy (PTT), inducing ferroptosis-augmented apoptosis to realize effective antitumor therapeutics. The relatively high photothermal conversion ability of Au@FePt increases the temperature in the tumor region and hastens Fenton-like processes to achieve enhanced synergistic therapy. Especially, RNA sequencing found Au@FePt inducting the apoptosis pathway in the transcriptome profile. CONCLUSION: Au@FePt combined XDT/PTT therapy activate apoptosis and ferroptosis related proteins in tumors to achieve breast cancer ablation in vitro and in vivo. PAI/MRI images demonstrated Au@FePt has real-time guidance for monitoring synergistic anti-cancer therapy effect. Therefore, we have provided a multifunctional nanotheranostics modality for tumor inhibition and cancer management with high efficacy and limited side effects.