Differential reinforcement of cGAS-STING pathway-involved immunotherapy by biomineralized bacterial outer membrane-sensitized EBRT and RNT.

Radiotherapy (RT), including external beam radiation therapy (EBRT) and radionuclide therapy (RNT), realizes physical killing of local tumors and activates systemic anti-tumor immunity. However, these effects need to be further strengthened and the difference between EBRT and RNT should be discovered. Herein, bacterial outer membrane (OM) was biomineralized with manganese oxide (MnO2) to obtain OM@MnO2-PEG nanoparticles for enhanced radio-immunotherapy via amplifying EBRT/RNT-induced immunogenic cell death (ICD) and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation. OM@MnO2-PEG can react with H2O2 and then gradually produce O2, Mn2+ and OM fragments in the tumor microenvironment. The relieved tumor hypoxia improves the radio-sensitivity of tumor cells, resulting in enhanced ICD and DNA damage. Mn2+ together with the DNA fragments in the cytoplasm activate the cGAS-STING pathway, further exhibiting a positive role in various aspects of innate immunity and adaptive immunity. Besides, OM fragments promote tumor antigen presentation and anti-tumor macrophages polarization. More importantly, our study reveals that OM@MnO2-PEG-mediated RNT triggers much stronger cGAS-STING pathway-involved immunotherapy than that of EBRT, owing to the duration difference of RT. Therefore, this study develops a powerful sensitizer of radio-immunotherapy and uncovers some differences between EBRT and RNT in the activation of cGAS-STING pathway-related anti-tumor immunity.

Quadruple valve replacement for patient with infective endocarditis 16 years after Fallot's Tetralogy Repair procedure: A case report.

A 33-year-old man, who had previously undergone repair for Tetralogy of Fallot, presented with extensive infective endocarditis. Following thorough preoperative preparation and evaluation, we performed a simultaneous quadruple valve replacement alongside the repatching of the remaining defect. We posit that this comprehensive one-stage surgical intervention not only enhanced the patient's quality of life but also reduced the necessity for future reoperations. Our approach offers valuable insights for managing adult patients with repaired congenital heart diseases and multiple valve pathologies.

Prediction of pathological complete response of breast cancer patients who received neoadjuvant chemotherapy with a nomogram based on clinicopathologic variables, ultrasound, and MRI.

OBJECTIVE: To establish a nomogram for predicting the pathologic complete response (pCR) in breast cancer (BC) patients after NAC by applying magnetic resonance imaging (MRI) and ultrasound (US). METHODS: A total of 607 LABC women who underwent NAC before surgery between January 2016 and June 2022 were retrospectively enrolled, and then were randomly divided into the training (n = 425) and test set (n = 182) with the ratio of 7:3. MRI and US variables were collected before and after NAC, as well as the clinicopathologic features. Univariate and multivariate logistic regression analyses were applied to confirm the potentially associated predictors of pCR. Finally, a nomogram was developed in the training set with its performance evaluated by the area under the receiver operating characteristics curve (ROC) and validated in the test set. RESULTS: Of the 607 patients, 108 (25.4%) achieved pCR. Hormone receptor negativity (odds ratio [OR], 0.3; P < .001), human epidermal growth factor receptor 2 positivity (OR, 2.7; P = .001), small tumour size at post-NAC US (OR, 1.0; P = .031), tumour size reduction ≥50% at MRI (OR, 9.8; P < .001), absence of enhancement in the tumour bed at post-NAC MRI (OR, 8.1; P = .003), and the increase of ADC value after NAC (OR, 0.3; P = .035) were all significantly associated with pCR. Incorporating the above variables, the nomogram showed a satisfactory performance with an AUC of 0.884. CONCLUSION: A nomogram including clinicopathologic variables and MRI and US characteristics shows preferable performance in predicting pCR. ADVANCES IN KNOWLEDGE: A nomogram incorporating MRI and US with clinicopathologic variables was developed to provide a brief and concise approach in predicting pCR to assist clinicians in making treatment decisions early.

Ultrasound radiomics-based nomogram to predict lymphovascular invasion in invasive breast cancer: a multicenter, retrospective study.

OBJECTIVES: To develop and validate an ultrasound (US) radiomics-based nomogram for the preoperative prediction of the lymphovascular invasion (LVI) status in patients with invasive breast cancer (IBC). MATERIALS AND METHODS: In this multicentre, retrospective study, 456 consecutive women were enrolled from three institutions. Institutions 1 and 2 were used to train (n = 320) and test (n = 136), and 130 patients from institution 3 were used for external validation. Radiomics features that reflected tumour information were derived from grey-scale US images. The least absolute shrinkage and selection operator and the maximum relevance minimum redundancy (mRMR) algorithm were used for feature selection and radiomics signature (RS) building. US radiomics-based nomogram was constructed by using multivariable logistic regression analysis. Predictive performance was assessed with the receiving operating characteristic curve, discrimination, and calibration. RESULTS: The nomogram based on clinico-ultrasonic features (menopausal status, US-reported lymph node status, posterior echo features) and RS yielded an optimal AUC of 0.88 (95% confidence interval [CI], 0.84-0.91), 0.89 (95% CI, 0.84-0.94) and 0.95 (95% CI, 0.92-0.99) in the training, internal and external validation cohort. The nomogram outperformed the clinico-ultrasonic and RS model (p < 0.05). The nomogram performed favourable discrimination (C-index, 0.88; 95% CI: 0.84-0.91) and was confirmed in the validation (0.88 for internal, 0.95 for external) cohorts. The calibration and decision curve demonstrated the nomogram showed good calibration and was clinically useful. CONCLUSIONS: The radiomics nomogram incorporated in the RS and US and the clinical findings exhibited favourable preoperative individualised prediction of LVI. CLINICAL RELEVANCE STATEMENT: The US radiomics-based nomogram incorporating menopausal status, posterior echo features, US reported-ALN status, and radiomics signature has the potential to predict lymphovascular invasion in patients with invasive breast cancer. KEY POINTS: • The clinico-ultrsonic model of menopausal status, posterior echo features, and US-reported ALN status achieved a better predictive efficacy for LVI than either of them alone. • The radiomics nomogram showed optimal prediction in predicting LVI from patients with IBC (ROC, 0.88 and 0.89 in the training and validation sets). • A nomogram demonstrated favourable performance (area under the receiver operating characteristic curve, 0.95) and well calibration (C-index, 0.95) in an independent validation cohort (n = 130).

Case Report: Pericardial patch repair of mitral annulus and mitral valve for a left atrial dissection caused by parasitic infective endocarditis.

Introduction: Left atrial dissection is a rare event, typically associated with cardiac manipulation. We report the first case of a left atrial dissection caused by parasitic infectious endocarditis, which required the use of patch repair for the damaged mitral annulus and valve. Case Presentation: To treat heart failure in a 43-year-old man with left atrial dissection, we performed a patch repair of the mitral annulus and valve using autologous pericardium. Conclusion: We encourage novel surgery for complicated infectious endocarditis.

Case report: Open-heart removal for a cement embolism formed 10 years ago in the right ventricle and pulmonary artery.

Bone cement embolism is a known complication after a kyphoplasty operation. Cement embolisms without immediate fatal complication such as cardiac perforation or hypoxemia were often stable during observation. We report a case of a large volume bone cement embolism involving the right ventricle and the pulmonary artery system. The patient developed mild exertional shortness of breath and chest pain after a percutaneous kyphoplasty (PKP) operation 10 years ago. However, her mild symptoms were attributed to multiple myeloma, and no chest imaging was taken until the symptoms exacerbated after a COVID-19 infection 6 months ago. A large, tree-branch-shaped embolus was found, causing severe obstruction of the ascending and middle-lobe branch of the right pulmonary artery. The pulmonary perfusion scintigraphy demonstrated an impaired perfusion of the right upper and middle lobe. An open-heart removal was performed, and the symptoms were relieved afterward. We report this case to highlight the importance of routine chest imaging after a PKP operation and to claim that open-heart removal for chronic cement pulmonary embolism is technically feasible and safe.

Tumor Vascular Destruction and cGAS-STING Activation Induced by Single Drug-Loaded Nano-Micelles for Multiple Synergistic Therapies of Cancer.

Cancer and its metastasis/recurrence still threaten human health, despite various advanced treatments being employed. It is of great significance to develop simple drug formulations to enhance the efficacy and synergistic integration of various monotherapies. Herein, DMXAA, a vasodestructive agent with cGAS-STING stimulation capacity, is integrated with polyethylene glycol grafted poly (lactic-co-glycolic) acid co-polymer (PLGA-PEG), obtaining PLGA-PEG/DMXAA (PPD) nanoparticles to induce the tumor-specific vascular destruction for multiple synergistic therapies of cancer. PPD could induce the formation of blood clots in the tumor after intravenous injection, which subsequently mediate photothermal therapy and further promote the release of oxygen for enhanced radiotherapy. Meanwhile, the enhanced vascular injury can induce perfect starvation therapy of tumor. More importantly, PPD-mediated therapies could trigger potent systemic anti-tumor immunity via inducing the immunogenic death of tumor cells and activating the cGAS-STING pathway. Together with anti-PD-L1, PPD-mediated therapies could not only remove the primary tumors, but also effectively eliminate the distant tumors, metastasis, and recurrence. Therefore, the modulation of tumor composition induced by a single drug-loaded nano-micelle could be utilized to enhance the therapeutic effect of multiple treatments for synergistic and systemic antitumor response, providing a practical strategy for cancer therapy.

Surgery for angiosarcoma and other cardiac sarcomas: A single-institution experience.

Background: Cardiac sarcomas are rare malignancies with a poor prognosis. Although angiosarcoma is the most common histological subtype, its features are poorly characterized. This study aimed to compare the clinical characteristics of the various cardiac sarcomas and the surgical techniques used and to identify factors influencing the prognosis. Methods: Forty patients who underwent surgery for cardiac sarcomas were included; 60% of them had angiosarcoma. Clinical characteristics, tumor location, surgical techniques used, and the prognosis were compared between patients with angiosarcoma and patients with other subtypes. Kaplan-Meier curves and multivariable Cox regression were used to identify predictors of postoperative survival. Results: Angiosarcomas were more likely than the other subtypes to present as pericardial effusion (85% vs 50%, P = .014). Early surgery was performed (median 24.0 days) regardless of histological subtype. The surgical technique varied according to histological subtype. Mean postoperative survival was 10 months. A positive margin (P = .13), high Ki-67 index (P = .19), younger age (P = .86), and angiosarcoma (P = .87) were identified to be potentially poor prognostic factors in univariate analyses. Cox regression identified R0 resection to be the only significant independent predictor of the prognosis after surgery (hazard ratio, 0.423, P = .039). Conclusions: Angiosarcoma differs from other subtypes of cardiac sarcoma in terms of clinical symptoms, tumor location, surgical techniques used, and prognosis. Early surgery is needed regardless of subtype. R0 resection is the only independent predictor of postoperative survival, and complete resection is usually achievable. The prognosis may be poorer in patients with a positive margin, high Ki-67 index, younger age, and angiosarcoma.

Intra-atrial coronary artery reconstruction during surgery for cardiac angiosarcoma.

A cardiac angiosarcoma is usually located in the right atrium and tends to involve the right coronary artery. Our goal was to report a novel reconstruction technique after en bloc resection of a cardiac angiosarcoma with right coronary artery invasion. This technique includes orthotopic reconstruction of the invaded artery and atrial patch suturing onto the epicardium lateral to the reconstructed right coronary artery. Intra-atrial reconstruction with an end-to-end anastomosis can enhance the graft patency compared to a distal side-to-end anastomosis and can reduce the risk of anastomotic stenosis. Moreover, suturing the graft patch to the epicardium did not increase the risk of bleeding because the pressure in the right atrium was low.

Construction and validation of a personalized nomogram of ultrasound for pretreatment prediction of breast cancer patients sensitive to neoadjuvant chemotherapy.

OBJECTIVE: To construct a combined radiomics model based on pre-treatment ultrasound for predicting of advanced breast cancers sensitive to neoadjuvant chemotherapy (NAC). METHODS: A total of 288 eligible breast cancer patients who underwent NAC before surgery were enrolled in the retrospective study cohort. Radiomics features reflecting the phenotype of the pre-NAC tumors were extracted. With features selected using the least absolute shrinkage and selection operator (LASSO) regression, radiomics signature (Rad-score) was established based on the pre-NAC ultrasound. Then, radiomics nomogram of ultrasound (RU) was established on the basis of the best radiomic signature incorporating independent clinical features. The performance of RU was evaluated in terms of calibration curve, area under the curve (AUC), and decision curve analysis (DCA). RESULTS: Nine features were selected to construct the radiomics signature in the training cohort. Combined with independent clinical characteristics, the performance of RU for identifying Grade 4-5 patients was significantly superior than the clinical model and Rad-score alone (p < 0.05, as per the Delong test), which achieved an AUC of 0.863 (95% CI, 0.814-0.963) in the training group and 0.854 (95% CI, 0.776-0.931) in the validation group. DCA showed that this model satisfactory clinical utility, suggesting its robustness as a response predictor. CONCLUSION: This study demonstrated that RU has a potential role in predicting drug-sensitive breast cancers. ADVANCES IN KNOWLEDGE: Aiming at early detection of Grade 4-5 breast cancer patients, the radiomics nomogram based on ultrasound has been approved as a promising indicator with high clinical utility. It is the first application of ultrasound-based radiomics nomogram to distinguish drug-sensitive breast cancers.

Repair versus replacement for active endocarditis of the mitral valve: 9 years of experience.

BACKGROUND AND AIM: To determine the factors contributing to successful mitral valve repair (MVP) and to discuss the effect of complex techniques on the durability of MVP for active infective endocarditis (IE) affecting the mitral valve. METHODS: One hundred and eighty-seven patients were enrolled; 39.6% underwent mitral valve replacement (MVR) and 60.4% underwent MVP. We used logistic regression to identify influencing factors of the choice of surgical technique. The results were compared between groups and subgroups after propensity score matching (PSM). RESULTS: Risk factors for MVR included poor valve quality (odds ratio [OR] 23.3, p = .001), a large defect after debridement (OR 16.4, p < .001), and heavy valve infection (OR 3.7, p = .027). After PSM, we did not find a significant difference in the frequency of major postoperative complications or the in-hospital or postdischarge death rate. The reintervention rate for MVP was significantly higher than that for MVR (p = .047). Subgroup analysis found a significant relationship between the use of a complex repair technique and the need for reoperation (p = .020). CONCLUSIONS: The choice of valve repair or replacement for patients with active IE affecting the mitral valve was influenced by the intraoperative characteristics of the infected valve rather than the severity of systemic infection or overall health status. The choice of surgical treatment strategy had no effect on major postoperative complications, in-hospital mortality, or medium-term survival. However, the medium-term durability of MVP was poorer than that of MVR. The use of the patch technique for free margins or extensive leaflet defects was associated with a need for reintervention.

Anode modification of sediment microbial fuel cells (SMFC) towards bioremediating mariculture wastewater.

Remediation of mariculture wastewater is of great practical importance. In this study, sediment microbial fuel cells (SMFCs) were adopted and carbon felt anodes were modified to enhance COD and ammonia removal in mariculture system. The results showed that the SMFC anode with 5 % (w/w) graphene oxide (GO) coating performed best in pollutants removal and electricity generation. The maximum power density approached 132 mW/m2, nearly 4.5 times higher than the unmodified anode. The removal efficiency of COD and ammonia reached 82.1 % and 95.8 % respectively, both improved compared with the control and chemical modification. The modified anode effectively enriched the electrogenic Sulfurovum and Lactobacillus and thus led to a significant improvement in the electrochemical performance of SMFC. This study demonstrates the successful application of SMFCs with GO modified anodes in the in-situ removing pollutants and SMFCs present obvious remediation potential on the contaminated mariculture inhabitant.

Characteristics and Diagnostic Challenge of Antineutrophil Cytoplasmic Antibody Positive Infective Endocarditis.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA) has been reported in patients with infective endocarditis. Whether ANCA is associated with certain characteristics of infective endocarditis is unclear. The principal aim of this study is to investigate the clinical implications of ANCA in infective endocarditis and highlight the diagnostic challenge in ANCA-positive patients with infective endocarditis. METHODS: A retrospective study was conducted in a tertiary hospital in China from August 2012 to December 2021. Patients with a diagnosis of infective endocarditis and available ANCA results were included in the study. The clinical and pathological characteristics were compared between ANCA-positive and ANCA-negative patients. RESULTS: A total of 237 patients were included. Forty three (18.1%) were ANCA-positive, predominantly c-ANCA/anti-PR3. Compared to ANCA-negative patients, ANCA-positive patients had longer disease duration (P = .004), more frequent purpura (P = .015), macrohematuria (P = .002), proteinuria (P = .043), acute kidney injury (P = .004), and rapidly progressive glomerulonephritis (P = .010). Histologic findings of 8 patients with infective endocarditis-associated glomerulonephritis were reviewed. Two ANCA-positive patients with infective endocarditis presented with pauci-immune necrotizing and crescentic glomerulonephritis. A total of 18.6% of ANCA-positive patients with infective endocarditis were misdiagnosed as ANCA-associated vasculitis. CONCLUSIONS: ANCA is detected in a substantial proportion of patients with infective endocarditis. The presence of ANCA in infective endocarditis is associated with longer disease duration, more frequent purpura, and kidney involvement. ANCA-positive infective endocarditis may mimic ANCA-associated vasculitis, and the differential diagnosis is challenging. Whether ANCA is pathogenic in infective endocarditis-associated small vessel vasculitis requires further study.

Ultrasound-based radiomics nomogram for differentiation of triple-negative breast cancer from fibroadenoma.

OBJECTIVE: This study aimed to develop a radiomics nomogram that incorporates radiomics, conventional ultrasound (US) and clinical features in order to differentiate triple-negative breast cancer (TNBC) from fibroadenoma. METHODS: A total of 182 pathology-proven fibroadenomas and 178 pathology-proven TNBCs, which underwent preoperative US examination, were involved and randomly divided into training (n = 253) and validation cohorts (n = 107). The radiomics features were extracted from the regions of interest of all lesions, which were delineated on the basis of preoperative US examination. The least absolute shrinkage and selection operator model and the maximum relevance minimum redundancy algorithm were established for the selection of tumor status-related features and construction of radiomics signature (Rad-score). Then, multivariate logistic regression analyses were utilized to develop a radiomics model by incorporating the radiomics signature and clinical findings. Finally, the usefulness of the combined nomogram was assessed by using the receiver operator characteristic curve, calibration curve, and decision curve analysis (DCA). RESULTS: The radiomics signature, composed of 12 selected features, achieved good diagnostic performance. The nomogram incorporated with radiomics signature and clinical data showed favorable diagnostic efficacy in the training cohort (AUC 0.986, 95% CI, 0.975-0.997) and validation cohort (AUC 0.977, 95% CI, 0.953-1.000). The radiomics nomogram outperformed the Rad-score and clinical models (p < 0.05). The calibration curve and DCA demonstrated the good clinical utility of the combined radiomics nomogram. CONCLUSION: The radiomics signature is a potential predictive indicator for differentiating TNBC and fibroadenoma. The radiomics nomogram associated with Rad-score, US conventional features, and clinical data outperformed the Rad-score and clinical models. ADVANCES IN KNOWLEDGE: Recent advances in radiomics-based US are increasingly showing potential for improved diagnosis, assessment of therapeutic response and disease prediction in oncology. Rad-score is an independent predictive indicator for differentiating TNBC and fibroadenoma. The radiomics nomogram associated with Rad-score, US conventional features, and clinical data outperformed the Rad-score and clinical models.

Outcomes of surgical treatment for active infective endocarditis under COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has been and will continue to be a challenge to the healthcare system worldwide. In this context, we aimed to discuss the impact of the COVID-19 pandemic on the diagnosis, timing, and prognosis of surgical treatment for active infective endocarditis (IE) during the pandemic and share our coping strategy. METHODS: A total of 39 patients were admitted for active IE in the year 2020. The number of the same period last year was 50. Medical information of these two groups was extracted from our surgical database. Data were compared between the two groups and differences with or without statistical significance were discussed. RESULTS: In the pandemic year, we admitted fewer transferred patients (64.1% vs. 80%, p = .094). Timespan for diagnosis were prolonged (60 vs. 34.5 days, p = .081). More patients were admitted in emergency (41% vs. 20%, p = .030) More patients had heart failure (74.4% vs. 40%, p = .001), sepsis (69.2% vs. 42.0%, p = .018), or cardiogenic shock (25.6% vs. 8.0%, p = .038). Overall surgical risk (EuroSCORE II) was higher (4.15% vs. 3.24%, p = .019) and more commando surgery was performed (7.7% vs. 2.0%, p = .441). However, we did not see more postoperative complications, and early mortality was not worse either (0 vs. 4%, p = .502). CONCLUSIONS: The negative impact of the COVID-19 pandemic on the clinical practice of surgical treatment for active IE was multifaceted. However, with the preservation of the effectiveness of multidisciplinary IE surgical team, the early outcomes were comparable with those in the normal years.

Photo-Driven Delivery of 125I-Labeled Nanomicelles for Nucleus-Targeted Internal Conversion Electron-Based Cancer Therapy.

As a kind of high linear energy transfer (LET) radiation, internal conversion electrons are emitted from some radionuclides, such as 125I, triggering severe DNA damage to tumor cells when transported into the nucleus. Herein, we develop a curcumin-loaded nanomicelle composed of a photosensitizer chlorin e6 (Ce6) and amphiphilic poly(ethylene glycol) (poly(maleic anhydride-alt-1-octadecene)-poly(ethylene glycol) (C18-PMH-PEG)) to deliver 125I into the nucleus under 660 nm laser irradiation, leading to the optimized imaging-guided internal conversion electron therapy of cancer. Ce6-containing nanomicelles (Ce6-C18-PEG) self-assemble with nucleus-targeted curcumin (Cur), obtaining Ce6-C18-PEG/Cur nanoparticles. After labeling Cur with 125I, Ce6-C18-PEG/Cur enables single-photon emission computed tomography and fluorescence imaging of the tumor, serving as a guide for follow-up laser irradiation. Notably, the 660 nm laser-triggered photodynamic reaction of Ce6 optimizes the delivery of Ce6-C18-PEG/125I-Cur at various stages, including tumor accumulation, cellular uptake, and lysosome escape, causing plenty of 125I-Cur to enter the nucleus. By this strategy, Ce6-C18-PEG/125I-Cur showed optimal antitumor efficacy and high biosafety in mice treated with local 660 nm laser irradiation using efficient energy deposition of internally converted electrons over short distances. Therefore, our work provides a novel strategy to optimize 125I delivery for tumor treatment.

Emerging strategies based on nanomaterials for ionizing radiation-optimized drug treatment of cancer.

Drug-radiotherapy is a common and effective combinational treatment for cancer. This study aimed to explore the ionizing radiation-optimized drug treatment based on nanomaterials so as to improve the synergistic efficacy of drug-radiotherapy against cancer and limit the adverse effect on healthy organs. In this review, these emerging strategies were divided into four parts. First, the delivery of the drug-loaded nanoparticles was optimized owing to the strengthened passive targeting process, active targeting process, and cell targeting process of nanoparticles after ionizing radiation exposure. Second, nanomaterials were designed to respond to the ionizing radiation, thus leading to the release of the loading drugs controllably. Third, radiation-activated pro-drugs were loaded onto nanoparticles for radiation-triggered drug therapy. In particular, nontoxic nanoparticles with radiosensitization capability and innocuous radio-dynamic contrast agents can be considered as radiation-activated drugs, which were discussed in this review. Fourth, according to the various synergetic mechanisms, radiotherapy could improve the drug response of cancer, obtaining optimized drug-radiotherapy. Finally, relative suggestions were provided to further optimize these aforementioned strategies. Therefore, a novel topic was selected and the emerging strategies in this region were discussed, aiming to stimulate the inspiration for the development of ionizing radiation-optimized drug treatment based on nanomaterials.

Diagnostic Radionuclides Labeled on Biomimetic Nanoparticles for Enhanced Follow-Up Photothermal Therapy of Cancer.

Imaging-guided local therapy is the most effective strategy to treat primary cancers in patients. However, the local therapeutic effect should be further improved under the premise of absence of induction of additional side effects. It would be meaningful to analyze the potential assistance of nuclear imaging to the follow-up treatments. In this study,cancer-targeted copper sulfide nanoparticles with 99m Tc labeling (99m Tc-M-CuS-PEG) are prepared using-cancer cell membranes as a synthesis reactor and applied for the potential single-photon emission computed tomography/photoacoustic imaging-guided and 99m Tc-amplified photothermal therapy of cancer. Owing to the homologous targeting capability of the cancer cell membrane, M-CuS-PEG selectively accumulates in homologous tumor sites. After labeling with 99m Tc, M-CuS-PEG with a high near-infrared light absorbance can realize bimodal imaging-guided photothermal therapy of cancer. Furthermore, the labeled 99m Tc significantly enhances the cell uptake of M-CuS-PEG by inducing G2/M arrest of the cell cycle, further improving the photothermal antitumor effect, which is positively correlated with endocytosis of the photothermal conversion reagent. Therefore, a novel cancer-targeted theranostic nanoplatform is developed and it is revealed that the labeled 99m Tc can not only guide but also amplify the subsequent therapy of cancer, providing a conceptual strategy for cancer theranostics with a high biosafety.

Interleukin-33-Dependent Accumulation of Regulatory T Cells Mediates Pulmonary Epithelial Regeneration During Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) triggered mostly by infection, is a syndrome that involves respiratory failure. ARDS induces strong local infiltration of regulatory T cells (Treg cells) in the lungs, and Treg cells were recently highlighted as being related to the repair of various tissue. However, at present, there is still a lack of adequate evidence showing the impact of Treg cells on pulmonary regeneration during ARDS. Here, we verified that Treg cells are strongly induced in ARDS mice and Treg depletion results in impaired lung repair. Moreover, Treg cells show high expression of ST2, a cellular receptor for the tissue alarmin IL-33, which is strongly upregulated in the lung during ARDS. In addition, we demonstrated that IL-33 signaling is crucial for Treg cell accumulation, and ST2-blocked mice show a decrease in the Treg cell population. Critically, transfer of exogenous IL-33 into Treg depleted mice restored Treg cells and facilitated lung regeneration by promoting alveolar type II cell (AEC2) recovery in ARDS, with elevated neutrophils infiltration and upregulated TGF-ß1 release. These results emphasized the importance of IL-33 in accelerating the expansion of pulmonary Treg cells and promoting their activity to mediate pulmonary epithelial regeneration during ARDS in a TGF-ß1-dependent manner.