Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.

Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8+ T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8+ T cells, driven by specific stromal cells such as CTHCR1+ fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8+ T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease.

Tet methylcytosine dioxygenase 2 (TET2) deficiency elicits EGFR-TKI (tyrosine kinase inhibitors) resistance in non-small cell lung cancer.

Despite epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC), acquired resistance inevitably develops, limiting clinical efficacy. We found that TET2 was poly-ubiquitinated by E3 ligase CUL7FBXW11 and degraded in EGFR-TKI resistant NSCLC cells. Genetic perturbation of TET2 rendered parental cells more tolerant to TKI treatment. TET2 was stabilized by MEK1 phosphorylation at Ser 1107, while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7FBXW11. Loss of TET2 resulted in the upregulation of TNF/NF-κB signaling that confers the EGFR-TKI resistance. Genetic or pharmacological inhibition of NF-κB attenuate the TKI resistance both in vitro and in vivo. Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2, and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency. Therefore, combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

Dual-energy computed tomography in the early evaluation of acute radiation pneumonia.

OBJECTIVE: To investigate the value of dual-energy dual-source computed tomography (DSCT) in evaluating pulmonary perfusion changes before and after radiotherapy for esophageal cancer, and its clinical use in the early diagnosis of acute radiation pneumonia (ARP). METHODS: We selected 45 patients with pathologically confirmed esophageal cancer who received radiotherapy (total irradiation dose of 60 Gy). Dual-energy DSCT scans were performed before and after radiotherapy and the normalized iodine concentrations (NIC) in the lung fields of the areas irradiated with doses of > 20 Gy, 10-20 Gy, 5-10 Gy, and < 5 Gy were measured. We also checked for the occurrence of ARP in the patients, and the differences in NIC values and NIC reduction rates before and after radiotherapy were calculated and statistically analyzed. RESULTS: A total of 16 of the 45 patients developed ARP. The NIC values in the lung fields of all patients decreased at different degrees after radiotherapy, and the NIC values in the area where ARP developed, decreased significantly. The rate of NIC reduction and incidence rate of ARP increased gradually with the increasing irradiation dose, and the inter-group difference in NIC reduction rate was statistically significant (P < 0.05). Based on the receiver operating characteristic (ROC) curve analysis, the areas under the curves of NIC reduction rate versus ARP occurrence in the V5-10 Gy, V10-20 Gy, and V> 20 Gy groups were 0.780, 0.808, and 0.772, respectively. Sensitivity of diagnosis was 81.3%, 75.0%, and 68.8% and the specificity was 65.5%, 82.8%, and 79.3%, when taking 12.50%, 16.50%, and 26.0% as the diagnostic thresholds, respectively. The difference in NIC values in the lung fields of V<5 Gy before and after radiotherapy was not statistically significant (P > 0.05). CONCLUSION: The dual-energy DSCT could effectively evaluate pulmonary perfusion changes after radiotherapy for esophageal cancer, and the NIC reduction rate was useful as a reference index to predict ARP and provide further reference for decisions in clinical practice.

SW-UNet: a U-Net fusing sliding window transformer block with CNN for segmentation of lung nodules.

Medical images are information carriers that visually reflect and record the anatomical structure of the human body, and play an important role in clinical diagnosis, teaching and research, etc. Modern medicine has become increasingly inseparable from the intelligent processing of medical images. In recent years, there have been more and more attempts to apply deep learning theory to medical image segmentation tasks, and it is imperative to explore a simple and efficient deep learning algorithm for medical image segmentation. In this paper, we investigate the segmentation of lung nodule images. We address the above-mentioned problems of medical image segmentation algorithms and conduct research on medical image fusion algorithms based on a hybrid channel-space attention mechanism and medical image segmentation algorithms with a hybrid architecture of Convolutional Neural Networks (CNN) and Visual Transformer. To the problem that medical image segmentation algorithms are difficult to capture long-range feature dependencies, this paper proposes a medical image segmentation model SW-UNet based on a hybrid CNN and Vision Transformer (ViT) framework. Self-attention mechanism and sliding window design of Visual Transformer are used to capture global feature associations and break the perceptual field limitation of convolutional operations due to inductive bias. At the same time, a widened self-attentive vector is used to streamline the number of modules and compress the model size so as to fit the characteristics of a small amount of medical data, which makes the model easy to be overfitted. Experiments on the LUNA16 lung nodule image dataset validate the algorithm and show that the proposed network can achieve efficient medical image segmentation on a lightweight scale. In addition, to validate the migratability of the model, we performed additional validation on other tumor datasets with desirable results. Our research addresses the crucial need for improved medical image segmentation algorithms. By introducing the SW-UNet model, which combines CNN and ViT, we successfully capture long-range feature dependencies and break the perceptual field limitations of traditional convolutional operations. This approach not only enhances the efficiency of medical image segmentation but also maintains model scalability and adaptability to small medical datasets. The positive outcomes on various tumor datasets emphasize the potential migratability and broad applicability of our proposed model in the field of medical image analysis.

Combining radiomics and deep learning features of intra-tumoral and peri-tumoral regions for the classification of breast cancer lung metastasis and primary lung cancer with low-dose CT.

PURPOSE: To investigate the performance of deep learning and radiomics features of intra-tumoral region (ITR) and peri-tumoral region (PTR) in the diagnosing of breast cancer lung metastasis (BCLM) and primary lung cancer (PLC) with low-dose CT (LDCT). METHODS: We retrospectively collected the LDCT images of 100 breast cancer patients with lung lesions, comprising 60 cases of BCLM and 40 cases of PLC. We proposed a fusion model that combined deep learning features extracted from ResNet18-based multi-input residual convolution network with traditional radiomics features. Specifically, the fusion model adopted a multi-region strategy, incorporating the aforementioned features from both the ITR and PTR. Then, we randomly divided the dataset into training and validation sets using fivefold cross-validation approach. Comprehensive comparative experiments were performed between the proposed fusion model and other eight models, including the intra-tumoral deep learning model, the intra-tumoral radiomics model, the intra-tumoral deep-learning radiomics model, the peri-tumoral deep learning model, the peri-tumoral radiomics model, the peri-tumoral deep-learning radiomics model, the multi-region radiomics model, and the multi-region deep-learning model. RESULTS: The fusion model developed using deep-learning radiomics feature sets extracted from the ITR and PTR had the best classification performance, with the area under the curve of 0.913 (95% CI 0.840-0.960). This was significantly higher than that of the single region's radiomics model or deep learning model. CONCLUSIONS: The combination of radiomics and deep learning features was effective in discriminating BCLM and PLC. Additionally, the analysis of the PTR can mine more comprehensive tumor information.

TROP2 translation mediated by dual m6A/m7G RNA modifications promotes bladder cancer development.

RNA modifications, including adenine methylation (m6A) of mRNA and guanine methylation (m7G) of tRNA, are crucial for the biological function of RNA. However, the mechanism underlying the translation of specific genes synergistically mediated by dual m6A/m7G RNA modifications in bladder cancer (BCa) remains unclear. We demonstrated that m6A methyltransferase METTL3-mediated programmable m6A modification of oncogene trophoblast cell surface protein 2 (TROP2) mRNA promoted its translation during malignant transformation of bladder epithelial cells. m7G methyltransferase METTL1 enhanced TROP2 translation by mediating m7G modification of certain tRNAs. TROP2 protein inhibition decreased the proliferation and invasion of BCa cells in vitro and in vivo. Moreover, synergistical knockout of METTL3/METTL1 inhibited BCa cell proliferation, migration, and invasion; however, TROP2 overexpression partially abrogated its effect. Furthermore, TROP2 expression was significantly positively correlated with the expression levels of METTL3 and METTL1 in BCa patients. Overall, our results revealed that METTL3/METTL1-mediated dual m6A/m7G RNA modifications enhanced TROP2 translation and promoted BCa development, indicating a novel RNA epigenetic mechanism in BCa.

Case report: Autosomal recessive type 3 Stickler syndrome caused by compound heterozygous mutations in COL11A2.

Background: Stickler syndrome (SS) is a group of hereditary collagenopathies caused by a variety of collagen and non-collagen genes. Affected patients have characteristic manifestations involving ophthalmic, articular, craniofacial and auditory disorders. SS is classified into several subtypes according to clinical and molecular features. Type 3 SS is an ultra-rare disease, known as non-ocular SS or otospondylomegaepiphyseal dysplasia (OSMED) with only a few pathogenic COL11A2 variants reported to date. Case presentation: A 29-year-old Chinese male was referred to our hospital for hearing loss and multiple joint pain. He presented a phenotype highly suggestive of OSMED, including progressive sensorineural deafness, spondyloepiphyseal dysplasia with large epiphyses, platyspondyly, degenerative osteoarthritis, and sunken nasal bridge. We detected compound heterozygous mutations in COL11A2, both of which were predicted to be splicing mutations. One is synonymous mutation c.3774C>T (p.Gly1258Gly) supposed to be a splice site mutation, the other is a novel intron mutation c.4750 + 5 G>A, which is a highly conservative site across several species. We also present a review of the current known pathogenic mutation spectrum of COL11A2 in patients with type 3 SS. Conclusion: Both synonymous extonic and intronic variants are easily overlooked by whole-exome sequencing. For patients with clinical manifestations suspected of SS syndrome, next-generation whole-genome sequencing is necessary for precision diagnosis and genetic counseling.

High-efficient capture and degradation of formaldehyde based on the electric-field-enhanced catalytic effect.

Enhancing the generation of active groups is of great significance for alleviating the catalyst deactivation of formaldehyde (HCHO) by accelerating the decomposition of intermediate products. Herein, an electric-field-enhanced catalytic effect was proposed for the efficient capture and degradation of HCHO base on carbon cloth loaded manganese oxide catalyst (MnOx-CC). Under the action of electric field, MnOx can generate more hydroxyl radicals (•OH) and superoxide radicals (•O2-), thus accelerating the degradation of HCHO and intermediates at room temperature. After the introduction electric field (∼1 ×104 V/m), •O2- and •OH radical on the surface of MnOx-CC catalyst can be increased by 8 times and 23 times, respectively. At weight hourly space velocity of 300,000 mL/(gcat h) for ∼15 ppm HCHO, MnOx-CC-Electric Field catalyst reached the removal efficiency of 99.4%, and the CO2 conversion efficiency of 81.2%, without decrease significantly within 80 h. Theoretical calculation shows that the electric field can increase the electron state density of Mn atom at the Fermi level and reduce the adsorption energy of HCHO, O2 and H2O, thus promoting the generation of active groups and degradation of intermediate products. The electric-field-enhancement catalytic effect provides a new approach for the degradation of Volatile Organic Compounds.

Sphenoid sinus is a rare site for tumor-induced osteomalacia: A case report and literature review.

Background: In this paper, we present a rare case of tumor-induced osteomalacia (TIO) and a literature review of this rare disease. Methods: A case of TIO of the isolated sphenoid sinus was reported. Furthermore, the clinical features of TIO in the sphenoid sinus and other sinonasal sinuses were also reviewed and summarized. Results: A 35-year-old man with muscle weakness and lower back pain came to the Department of Neurology. No obvious neurological disease was found; however, magnetic resonance imaging of the extremities accidentally showed a tumor in the axilla. Bone scintigraphy showed suspicious bone metastasis. Hypophosphatemia was neglected. Interestingly, 2-deoxy-2-[fluorine-18]fluoro-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) detected a tumor in the axilla and another in the sphenoid sinus, but only the tumor in the sphenoid sinus had somatostatin receptor (SSTR) expression in 68-gallium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid octreotate (Ga-68 DOTATATE) PET/CT. The sphenoid sinus tumor was proven to be a phosphaturic mesenchymal tumor (PMT), and the phosphate levels returned to normal after surgery. The literature review showed only 17 cases of TIOs that occurred in the sphenoid sinus, with an average age of 43.3 ± 13.7 years. Only three cases of TIOs in the sphenoid sinus did not invade the nasal cavity or other paranasal sinuses, which could be identified as isolated sphenoid sinus diseases. We compared the clinical features of sphenoid TIOs with those of non-sphenoid sinonasal TIOs, and it was found that the concentration of 1,25-dihydroxy vitamin D in the group with sphenoid TIOs was much higher than that in the group with non-sphenoid sinonasal TIOs. A total of 153 cases of TIOs in the sinonasal sinus were reviewed. The ethmoid sinus was found to be the major site (64.7%), followed by the nasal cavity (50.3%), maxillary sinus (19.0%), frontal sinus (16.4%), and sphenoid sinus (11.8%). There were 66 patients (43.1%) who showed tumors invading more than one sinus. Most of the tumors (69.3%) were diagnosed as PMTs by pathology, followed by hemangiopericytoma (14.3%). Immunostaining was beneficial in the differential diagnosis of these tumors; however, larger sample sizes are needed for better accuracy. Conclusion: TIO in the sinonasal sinus, especially in the sphenoid sinus, is rare. Moreover, isolated sphenoid sinus disease can be easily misdiagnosed. When the clinical manifestation of osteomalacia is atypical, associating it with sphenoid sinus disease is even more difficult. Thus, TIO in the sphenoid sinus needs further exploration.

8Spheres conformal microspheres as embolic agents for symptomatic uterine leiomyoma therapy in uterine artery embolization (UAE): A prospective clinical trial.

To evaluate the treatment efficacy of uterine artery embolization (UAE) using 8Spheres conformal microspheres for symptomatic uterine leiomyoma. In this prospective observational study, 15 patients were enrolled and underwent UAE by 2 experienced interventionalists from September 1, 2018, to September 1, 2019. All patients underwent menstrual bleeding scores, the symptom severity domain of the Uterine Fibroid Symptom and Quality of Life questionnaire scores (with lower scores indicating mild symptoms), pelvic contrast-enhanced magnetic resonance imaging, ovarian reserve tests (estradiol, prolactin, testosterone, follicle-stimulating, luteinizing, and progesterone), and other appropriate preoperative examinations within 1 week before UAE. During follow-up, menstrual bleeding scores and the symptom severity domain of the Uterine Fibroid Symptom and Quality of Life questionnaire scores were recorded at 1, 3, 6, and 12 months after UAE to assess the efficacy of symptomatic uterine leiomyoma. Pelvic contrast-enhanced magnetic resonance imaging was performed 6 months after the interventional therapy. Biomarkers of ovarian reserve function were reviewed at 6 and 12 months after treatment. All 15 patients successfully underwent UAE, without severe adverse effects. Six patients experienced abdominal pain, nausea, or vomiting, all of which improved significantly after symptomatic treatment. The menstrual bleeding scores declined from baseline (350.2 ± 61.9 mL) to (131.8 ± 42.7 mL), (140.3 ± 42.4 mL), (68.0 ± 22.8 mL), and (64.43 ± 17.0 mL) at 1, 3, 6, and 12 months, respectively. The symptom severity domain scores at 1, 3, 6, and 12 months postoperatively were significantly lower and statistically significant compared to the preoperative scores. The uterus and dominant leiomyoma volumes decreased from baseline (340.0 ± 35.8 cm3), (100.6 ± 24.3 cm3) to (266.6 ± 30.9 cm3), (56.1 ± 17.3 cm3) at 6 months after UAE, respectively. Moreover, the ratio of leiomyoma volumes and uterus decreased from (27.4 ± 4.5%) to (18.7 ± 3.9%). At the same time, there was no significant effect on changes in the biomarkers of ovarian reserve levels. Only the changes in testosterone levels before and after UAE were statistically significant (P < .05). 8Spheres conformal microspheres are ideal embolic agents for UAE therapy. This study showed that 8Spheres conformal microsphere embolization for symptomatic uterine leiomyoma could effectively relieve heavy menstrual bleeding, improve the symptom severity of patients, reduce the volume of leiomyoma, and have no significant effect on ovarian reserve function.

Multifunctional nanoplatforms application in the transcatheter chemoembolization against hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has the sixth-highest new incidence and fourth-highest mortality worldwide. Transarterial chemoembolization (TACE) is one of the primary treatment strategies for unresectable HCC. However, the therapeutic effect is still unsatisfactory due to the insufficient distribution of antineoplastic drugs in tumor tissues and the worsened post-embolization tumor microenvironment (TME, e.g., hypoxia and reduced pH). Recently, using nanomaterials as a drug delivery platform for TACE therapy of HCC has been a research hotspot. With the development of nanotechnology, multifunctional nanoplatforms have been developed to embolize the tumor vasculature, creating conditions for improving the distribution and bioavailability of drugs in tumor tissues. Currently, the researchers are focusing on functionalizing nanomaterials to achieve high drug loading efficacy, thorough vascular embolization, tumor targeting, controlled sustained release of drugs, and real-time imaging in the TACE process to facilitate precise embolization and enable therapeutic procedures follow-up imaging of tumor lesions. Herein, we summarized the recent advances and applications of functionalized nanomaterials based on TACE against HCC, believing that developing these functionalized nanoplatforms may be a promising approach for improving the TACE therapeutic effect of HCC.

Autophagy-Targeted Calcium Phosphate Nanoparticles Enable Transarterial Chemoembolization for Enhanced Cancer Therapy.

Transarterial chemoembolization (TACE) is commonly used for treating advanced hepatocellular carcinoma (HCC). However, the instability of lipiodol-drug emulsion and the altered tumor microenvironment (TME, such as hypoxia-induced autophagy) postembolization are responsible for the unsatisfactory therapeutic outcomes. Herein, pH-responsive poly(acrylic acid)/calcium phosphate nanoparticles (PAA/CaP NPs) were synthesized and used as the carrier of epirubicin (EPI) to enhance the efficacy of TACE therapy through autophagy inhibition. PAA/CaP NPs have a high loading capacity of EPI and a sensitive drug release behavior under acidic conditions. Moreover, PAA/CaP NPs block autophagy through the dramatic increase of intracellular Ca2+ content, which synergistically enhances the toxicity of EPI. TACE with EPI-loaded PAA/CaP NPs dispersed in lipiodol shows an obvious enhanced therapeutic outcome compared to the treatment with EPI-lipiodol emulsion in an orthotopic rabbit liver cancer model. This study not only develops a new delivery system for TACE but also provides a promising strategy targeting autophagy inhibition to improve the therapeutic effect of TACE for the HCC treatment.

ICL-Net: Global and Local Inter-Pixel Correlations Learning Network for Skin Lesion Segmentation.

Skin lesion segmentation is a fundamental procedure in computer-aided melanoma diagnosis. However, due to the diverse shape, variable size, blurry boundary, and noise interference of lesion regions, existing methods may struggle with the challenge of inconsistency within classes and indiscrimination between classes. In view of this, we propose a novel method to learn and model inter-pixel correlations from both global and local aspects, which can increase inter-class variances and intra-class similarities. Specifically, under the encoder-decoder architecture, we first design a pyramid transformer inter-pixel correlations (PTIC) module, aiming at capturing the non-local context information of different levels and further exploring the global pixel-level relationship to deal with the large variance of shape and size. Further, we devise a local neighborhood metric learning (LNML) module to strengthen the local semantic correlations learning capability and increase the separability between classes in the feature space. These two modules can complementarily strengthen the feature representation capability via exploiting the inter-pixel semantic correlations, thus further improving intra-class consistency and inter-class variance. Comprehensive experiments are performed on public skin lesion segmentation datasets: ISIC 2018, ISIC2016, and PH2, and experimental results demonstrate that the proposed method achieves better segmentation performance than other state-of-the-art methods.

Novel Janus MoSiGeN4 nanosheet: adsorption behaviour and sensing performance for NO and NO2 gas molecules.

A novel Janus MoSiGeN4 nanosheet is proposed for detecting poisonous gas molecules. Herein, the adsorption behaviour and sensing performance of both sides of the MoSiGeN4 monolayer to NO and NO2 gas molecules were investigated by first-principles calculations. Firstly, it is found that the MoSiGeN4 monolayer exhibits structural stability and indirect gap semiconductor characteristics. The largest adsorption energy of NO2 molecules on the MoSiGeN4 monolayer is -0.24 eV, which is higher than the -0.13 eV for NO molecules. Of course, the physisorption between gas molecules and the MoSiGeN4 monolayer appears with slight charge transfer. It is confirmed that NO molecules and NO2 molecules act as electron donors and electron acceptors, respectively. Meanwhile, the generation of small band gaps and impurity levels in the electronic structures after gas adsorption is in favour of the enhancement of electronic conductivity. Furthermore, the longest recovery times of NO and NO2 molecules are predicted to be 0.15 and 10.67 ns at room temperature, and the lateral diffusion at the surface requires crossing a large energy barrier. These findings provide indisputable evidence for further design and fabrication of highly sensitive gas sensors based on the MoSiGeN4 monolayer.

Multi-System Langerhans Cell Histiocytosis as a Mimic of IgG4-Related Disease: A Case Report and Literature Review.

Langerhans cell histiocytosis (LCH) is a rare disease characterized by the clonal accumulation and/or proliferation of specific dendritic cells resembling normal epidermal Langerhans cells (LCs). Clinical manifestations are variable, depending on the affected tissues or organs, however, LCH with elevated serum IgG4 has not been reported. Herein, we reported a 26-year-old Chinese female multi-system LCH (MS-LCH) who first presented with central diabetes insipidus (CDI), accompanied by panhypopituitarism and hepatic dysfunction. Diagnostic investigations were strongly suspicious of IgG4-RD because of elevated serum IgG4 levels during the process. Furtherly, thyroid and lymph node involvement and biopsy led to the diagnosis of MS-LCH; the strongly positive staining of CD1a, S100, CD207 (langerin), and Ki67 was found. Moreover, after systemic treatment with five cycles of chemotherapy, many lesions were greatly improved. Since both LCH and IgG4-RD are orphan diseases that can affect any organ, the differential diagnosis is challenging, especially when LCH is associated with unexplained serum IgG4 elevation. In this article, the case of a young woman suffering from MS-LCH that affected organs including the pituitary, thyroid, lymph node, and liver was summarized, and relevant literature was reviewed to better equip the diagnosis and treatment in its early stages.

Application value of double-layer spectral detector CT in differentiating central lung cancer from atelectasis.

BACKGROUND: Central lung cancer with obstructive atelectasis is very common in clinical practice. Determination of the tumor borderline is important. Conventional computed tomography (CT) alone may not be sufficiently accurate to distinguish central lung cancer from obstructive atelectasis. Spectral CT can improve the soft-tissue resolution greatly. In this study, we evaluated the application value of double-layer spectral detector CT in differentiating central lung cancer from atelectasis. METHODS: A total of 51 patients (37 males) with pathologically confirmed central lung cancer accompanied by atelectasis were enrolled. The rates of differentiation between tumors and atelectasis were retrospectively analyzed using conventional CT and three types of spectral images (40 keV virtual monoenergetic imaging, iodine density map, and their fusion image) of unenhanced scans as well as arterial and venous phases. Cochran's Q test and Friedman test were used to compare the differentiation rates and the maximal diameters of the tumors in each image. RESULTS: Among the 51 cases, conventional CT, 40 keV monoenergetic, iodine density, and their fusion images of the venous phase were successful in differentiating tumors from atelectasis in 17 (33.33%), 35 (68.63%), 39 (76.47%), and 38 (74.51%) cases, respectively. The differentiation rates of the 40 keV monoenergetic, iodine density, and fusion images were significantly higher than those of conventional images (χ2=-0.35, -0.43, and -0.41, respectively, all P<0.001). There were no significant differences in the differentiation rates among the 40 keV monoenergetic, iodine density, and fusion images (χ2=-0.06, -0.08, 0.02, respectively, all P=1.00). The maximal tumor diameters in the four images did not significantly differ (χ2=3.61, P=0.31). Conventional and spectral images of unenhanced and arterial phases could not/barely identify the tumor borderlines. CONCLUSIONS: Venous-phase spectral images of double-layer spectral detector CT can differentiate most central lung cancers from atelectasis, and the maximal diameter measurement of the tumor is reliable. Double-layer spectral detector CT can accurately identify the borderlines of most central lung cancers through spectral images during routine CT examinations without requiring other imaging modalities. Therefore, this method has considerable clinical value for applications in tumor staging, efficacy evaluation, and radiotherapy.

Antibiotics-free nanoparticles eradicate Helicobacter pylori biofilms and intracellular bacteria.

Biofilms and intracellular survival tremendously help Helicobacter pylori (H. pylori) escape from antibacterial agents attacking, therefore issuing extreme challenges to clinical therapies. Herein, we constructed fucoidan (FU)-coated nanoparticles (FU/ML-LA/EB NPs) via simple self-assembly of biguanide derivative (metformin-linoleic acid, ML) and linoleic acid (LA), encapsulating urease inhibitor ebselen (EB) instead of antibiotics to take antibacterial effect. Negatively charged FU/ML-LA/EB NPs easily penetrated through the gastric mucus layer to arrive at infection sites, then eradicated extracellular polymeric substances (EPS) to destroy H. pylori biofilms structure. After strengthening bacterial membrane permeability, the nanoparticles could enter H. pylori and kill bacteria by inhibiting the activity of urease. FU/ML-LA/EB NPs also entered H. pylori-infected host cells through receptor-mediated internalization, in which they activated AMPK to recover lysosomal acidification for killing intracellular H. pylori. Additionally, FU/ML-LA/EB NPs alleviated oxidative stress, hence reducing gastric mucosal damage and cutting off the pathways of carcinogenesis. Notably, H. pylori burden after FU/ML-LA/EB NPs treatment was reduced to a great extent in vivo, which was significantly lower than that after treatment with clinical therapy. Antibiotics-free FU/ML-LA/EB NPs improving bacterial eradication and alleviating oxidation stress made it a powerful approach against H. pylori.

Chemo-Phototherapy with Carfilzomib-Encapsulated TiN Nanoshells Suppressing Tumor Growth and Lymphatic Metastasis.

The design of nanomedicine for cancer therapy, especially the treatment of tumor metastasis has received great attention. Proteasome inhibition is accepted as a new strategy for cancer therapy. Despite being a big breakthrough in multiple myeloma therapy, carfilzomib (CFZ), a second-in-class proteasome inhibitor is still unsatisfactory for solid tumor and metastasis therapy. In this study, hollow titanium nitride (TiN) nanoshells are synthesized as a drug carrier of CFZ. The TiN nanoshells have a high loading capacity of CFZ, and their intrinsic inhibitory effect on autophagy synergistically enhances the activity of CFZ. Due to an excellent photothermal conversion efficiency in the second near-infrared (NIR-II) region, TiN nanoshell-based photothermal therapy further induces a synergistic anticancer effect. In vivo study demonstrates that TiN nanoshells readily drain into the lymph nodes, which are responsible for tumor lymphatic metastasis. The CFZ-loaded TiN nanoshell-based chemo-photothermal therapy combined with surgery offers a remarkable therapeutic outcome in greatly inhibiting further metastatic spread of cancer cells. These findings suggest that TiN nanoshells act as an efficient carrier of CFZ for realizing enhanced outcomes for proteasome inhibitor-based cancer therapy, and this work also presents a "combined chemo-phototherapy assisted surgery" strategy, promising for future cancer treatment.

The Role and Mechanisms of Action of Natural Compounds in the Prevention and Treatment of Cancer and Cancer Metastasis.

Cancer has emerged as one of the world's most concerning health problems. The progression and metastasis mechanisms of cancer are complex, including metabolic disorders, oxidative stress, inflammation, apoptosis, and intestinal microflora disorders. These pose significant challenges to our efforts to prevent and treat cancer and its metastasis. Natural drugs have a long history of use in the prevention and treatment of cancer. Many effective anti-tumor drugs, such as Paclitaxel, Vincristine, and Camptothecin, have been widely prescribed for the prevention and treatment of cancer. In recent years, a trend in the field of antitumor drug development has been to screen the active antitumor ingredients from natural drugs and conduct in-depth studies on the mechanisms of their antitumor activity. In this review, high-frequency keywords included in the literature of several common Chinese and English databases were analyzed. The results showed that five Chinese herbal medicines (Radix Salviae, Panax Ginseng C. A. Mey, Hedysarum Multijugum Maxim, Ganoderma, and Curcumaelongae Rhizoma) and three natural compounds (quercetin, luteolin, and kaempferol) were most commonly used for the prevention and treatment of cancer and cancer metastasis. The main mechanisms of action of these active compounds in tumor-related research were summarized. Finally, we found that four natural compounds (dihydrotanshinone, sclareol, isoimperatorin, and girinimbin) have recently attracted the most attention in the field of anti-cancer research. Our findings provide some inspiration for future research on natural compounds against tumors and new insights into the role and mechanisms of natural compounds in the prevention and treatment of cancer and cancer metastasis.

Treg Cell Evaluation in Patients with Acquired Immune Deficiency Syndrome with Poor Immune Reconstitution and Human Immunodeficiency Virus-Infected Treg Cell Prevention by Polymeric Nanoparticle Drug Delivery System.

To better deliver antiretroviral drugs for treating patients with acquired immune deficiency syndrome (AIDS) with poor immune reconstitution, a novel nanopole capsule was designed in this study. Forty-eight patients with AIDS with poor immune reconstitution were chosen as subjects to test their immune state. CD4+ T and Regulatory T cells (Treg) infected with HIV were cultured to test polyethyleneimine (PEI) and polychitosan (PC) drug delivery system efficiency. The infiltration efficiency test was performed to study the drug delivery efficiency of the delivery systems, and the cell numbers of CD4+ T and Treg cells infected with HIV were calculated to evaluate the therapeutic effect. The results showed that patients with AIDS with poor immune reconstitution had lower CD4+ T cell count and higher Treg cell count. Furthermore, the infiltration efficiency of the PC drug delivery system was higher than that of the PEI drug delivery system, and the therapy efficiency of antiretroviral drugs was greatly improved in the PC group. Additionally, the improvement of CD4+ T and Treg cells damaged by HIV was greater in the PC group. Sequentially, the PC system can better deliver and release loaded antiretroviral drugs and may be a better choice for treating patients with AIDS with poor immune reconstitution in the future.