Improving Ultrasound Diagnostic Precision for Breast Cancer and Adenosis with Modality-Specific Enhancement (MSE) - Breast Net.

Adenosis is a benign breast condition whose lesions can mimic breast carcinoma and is evaluated for malignancy with the Breast Imaging-Reporting and Data System (BI-RADS). We construct and validate the performance of modality-specific enhancement (MSE)-Breast Net based on multimodal ultrasound images and compare it to the BI-RADS in differentiating adenosis from breast cancer. A total of 179 patients with breast carcinoma and 229 patients with adenosis were included in this retrospective, two-institution study, then divided into a training cohort (institution I, n = 292) and a validation cohort (institution II, n=116). In the training cohort, the final model had a significantly greater AUC (0.82; P<0.05) than B-mode-based model (0.69, 95% CI [0.49-0.90]). In the validation cohort, the AUC of the final model was 0.81, greater than that of the BI-RADS (0.75, P<0.05). The multimodal model outperformed the individual and bimodal models, reaching a significantly greater AUC of 0.87 (95% CI = 0.69-1.0) (P<0.05). MSE-Breast Net, based on multimodal ultrasound images, exhibited better diagnostic performance than the BI-RADS in differentiating adenosis from breast cancer and may contribute to clinical diagnosis and treatment.

Classification of multiple primary lung cancer in patients with multifocal lung cancer: assessment of a machine learning approach using multidimensional genomic data.

Background: Multiple primary lung cancer (MPLC) is an increasingly well-known clinical phenomenon. However, its molecular characterizations are poorly understood, and still lacks of effective method to distinguish it from intrapulmonary metastasis (IM). Herein, we propose an identification model based on molecular multidimensional analysis in order to accurately optimize treatment. Methods: A total of 112 Chinese lung cancers harboring at least two tumors (n = 270) were enrolled. We retrospectively selected 74 patients with 121 tumor pairs and randomly divided the tumor pairs into a training cohort and a test cohort in a 7:3 ratio. A novel model was established in training cohort, optimized for MPLC identification using comprehensive genomic profiling analyzed by a broad panel with 808 cancer-related genes, and evaluated in the test cohort and a prospective validation cohort of 38 patients with 112 tumors. Results: We found differences in molecular characterizations between the two diseases and rigorously selected the characterizations to build an identification model. We evaluated the performance of the classifier using the test cohort data and observed an 89.5% percent agreement (PA) for MPLC and a 100.0% percent agreement for IM. The model showed an excellent area under the curve (AUC) of 0.947 and a 91.3% overall accuracy. Similarly, the assay achieved a considerable performance in the independent validation set with an AUC of 0.938 and an MPLC predictive value of 100%. More importantly, the MPLC predictive value of the classification achieved 100% in both the test set and validation cohort. Compared to our previous mutation-based method, the classifier showed better κ consistencies with clinical classification among all 112 patients (0.84 vs. 0.65, p <.01). Conclusion: These data provide novel evidence of MPLC-specific genomic characteristics and demonstrate that our one-step molecular classifier can accurately classify multifocal lung tumors as MPLC or IM, which suggested that broad panel NGS may be a useful tool for assisting with differential diagnoses.

Clinical effectiveness of a multitarget urine DNA test for urothelial carcinoma detection: a double-blinded, multicenter, prospective trial.

Urine-based testing is promising for noninvasive diagnosis of urothelial carcinoma (UC) but has suboptimal sensitivity for early-stage tumors. Herein, we developed a multitarget urine tumor DNA test, UI-Seek, for UC detection and evaluated its clinical feasibility. The prediction model was developed in a retrospective cohort (n = 382), integrating assays for FGFR3 and TERT mutations and aberrant ONECUT2 and VIM methylation to generate a UC-score. The test performance was validated in a double-blinded, multicenter, prospective trial (n = 947; ChiCTR2300076543) and demonstrated a sensitivity of 91.37% and a specificity of 95.09%. The sensitivity reached 75.81% for low-grade Ta tumors and exceeded 93% in high-grade Ta and higher stages (T1 to T4). Simultaneous identification of both bladder and upper urinary tract tumors was enabled with sensitivities exceeding 90%. No significant confounding effects were observed regarding benign urological diseases or non-UC malignancies. The test showed improved sensitivities over urine cytology, the NMP22 test, and UroVysion FISH alongside comparable specificities. The single-target accuracy was greater than 98% as confirmed by Sanger sequencing. Post-surgery UC-score decreased in 97.7% of subjects. Overall, UI-Seek demonstrated robust performance and considerable potential for the early detection of UC.

Chicken Interferon-Alpha and -Lambda Exhibit Antiviral Effects against Fowl Adenovirus Serotype 4 in Leghorn Male Hepatocellular Cells.

Hydropericardium hepatitis syndrome (HHS) is primarily caused by fowl adenovirus serotype 4 (FAdV-4), causing high mortality in chickens. Although vaccination strategies against FAdV-4 have been adopted, HHS still occurs sporadically. Furthermore, no effective drugs are available for controlling FAdV-4 infection. However, type I and III interferon (IFN) are crucial therapeutic agents against viral infection. The following experiments were conducted to investigate the inhibitory effect of chicken IFN against FadV-4. We expressed recombinant chicken type I IFN-α (ChIFN-α) and type III IFN-λ (ChIFN-λ) in Escherichia coli and systemically investigated their antiviral activity against FAdV-4 infection in Leghorn male hepatocellular (LMH) cells. ChIFN-α and ChIFN-λ dose dependently inhibited FAdV-4 replication in LMH cells. Compared with ChIFN-λ, ChIFN-α more significantly inhibited viral genome transcription but less significantly suppressed FAdV-4 release. ChIFN-α- and ChIFN-λ-induced IFN-stimulated gene (ISG) expression, such as PKR, ZAP, IRF7, MX1, Viperin, IFIT5, OASL, and IFI6, in LMH cells; however, ChIFN-α induced a stronger expression level than ChIFN-λ. Thus, our data revealed that ChIFN-α and ChIFN-λ might trigger different ISG expression levels, inhibiting FAdV-4 replication via different steps of the FAdV-4 lifecycle, which furthers the potential applications of IFN antiviral drugs in chickens.

Artificial intelligence-assisted system for the assessment of Forrest classification of peptic ulcer bleeding: a multicenter diagnostic study.

BACKGROUND: Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB). METHODS: A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists. RESULTS: The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists. CONCLUSION: The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy.

Newcastle disease virus activates the PI3K/AKT signaling pathway by targeting PHLPP2 degradation to delay cell apoptosis and promote viral replication.

Newcastle disease (ND) is a highly pathogenic, contagious, and fatal infectious disease in poultry caused by the Newcastle disease virus (NDV). The PI3K/AKT signaling pathway is a phosphorylation cascade that participates in regulating several cellular functions. Viruses reportedly regulate the course of infection through the PI3K/AKT axis. Here, we aimed to analyze the pathogenesis of NDV infection mediated by the PI3K/AKT signaling pathway activation. We found that NDV infection can phosphorylate AKT to activate the PI3K/AKT axis both in vitro and in vivo. Flow cytometry and Caspase-3 activity assay showed that NDV infection could inhibit cell apoptosis. The activation or inhibition of the PI3K/AKT signaling pathway activity significantly inhibited or promoted NDV-mediated apoptosis. Furthermore, inhibition of cell apoptosis significantly promoted NDV replication. Overall, our results showed that NDV infection activates the PI3K/AKT signaling pathway and inhibits cell apoptosis, thus promoting viral replication. In this context, the reduced expression of PHLPP2 protein mediated by NDV infection could be inhibited by MG132. PHLPP2 expression reversely and positively regulated NDV replication and cell apoptosis, respectively. These results indicated that NDV infection-mediated activation of the PI3K/AKT signaling pathway and the inhibition of apoptosis depend on the ubiquitin-proteasome degradation of the PHLPP2 protein. Co-IP and indirect immunofluorescence results showed that NDV V protein could interact with PHLPP2 protein, indicating that NDV targeted PHLPP2 protein degradation through V protein to activate the PI3K/AKT signaling pathway. This study deepens our understanding of the molecular mechanisms of NDV infection, providing a theoretical basis for ND prevention and control.

Calixarene-based cryoprotectants for ice recrystallization inhibition and cell cryopreservation.

The development of new cryoprotectants for cryopreservation of cells has attracted considerable interest. Herein, five calixarene-based CPAs (SC4A, S-S-C4A, S-SO2-C4A, SBAC4A, and CAC4A) were developed, and their IRI activity, DIS property and cryoprotective effect were studied. SBAC4A with a sulphobetaine zwitterion and SC4A with sulfo group modification possessed better cryoprotective effects than the other calixarene-based CPAs, especially for SBAC4A with the enhanced cell viabilities of 16.16 ± 1.78%, 12.60 ± 1.15% and 14.90 ± 1.66% against MCF-7, hucMSCs and A549 cells, respectively. This result provides a supramolecular principle for developing novel CPAs with consideration of the factors of hydrogen bonding, the macromolecular crowding principle and the three-dimensional (3D) structure.

Applying sheet iron to enhance the treatment efficiency of digested effluent with continuous flow and the corresponding mechanism.

Because of the unstable wastewater quantity and quality, the biological treatment efficiency of digested effluent was not as expected. A convenient and effective way was eagerly required to improve the efficiency of biological treatment. By sheet iron addition (R1), the COD and TN removal efficiencies under continuous flow condition increased by 59% and 37% respectively. The bulk pH maintained at around 7.5 which benefited most bacteria, while in the control (R0, without sheet iron addition) the pH decreased to 5.0. Both chemical and bio-removal of COD existed in R1, but the chemical removal dominated (63.71%). The enhanced COD removal efficiency came from the chemical oxidation by Fe3+ (47.43%) and Fe0 (10.86%). For the TN removal, the enhancement mainly came from the improvement of anammox activity by Fe3+ (14.87%), the bio-oxidation of ammonium with Fe3+ as electron acceptor (8.78%), and the bio-reduction of nitrate/nitrite with Fe2+ and H2 as electron donor (35.76%). By the first-order kinetic fitting analysis, the COD and TN removal rate in R1 was higher than that in R0. Thus, for a quick and high COD and TN removal from digested effluent, the addition of Fe0/Fe2+/Fe3+ was suggested, and the best form should be Fe0 (e.g., sheet iron). The addition of sheet iron reduces the cost of nitrogen removal and improves the efficiency of COD and TN removal. Comparing with the combined processes, this novel approach has potential advantages with simple operation and high efficiency. It endows the biological process much broader application in digested effluent treatment.

YAP at the progression of inflammation.

Yes-associated protein (YAP) is a transcriptional regulator that affects cell proliferation, organ size and tissue development and regeneration, and has therefore, been an important object of study. In recent years, there has been an increasing research focus on YAP in inflammation and immunology, and the role of YAP in the development of inflammation and in immune escape by tumors has been progressively elucidated. Because YAP signaling involves a variety of different signal transduction cascades, the full range of functions in diverse cells and microenvironments remains incompletely understood. In this article, we discuss the complex involvement of YAP in inflammation, the molecular mechanisms through which it exercises pro- and anti-inflammatory effects under different conditions, and the progress achieved in elucidating the functions of YAP in inflammatory diseases. A thorough understanding of YAP signaling in inflammation will provide a foundation for its use as a therapeutic target in inflammatory diseases.

Newcastle disease virus activates methylation-related enzymes to reprogram m6A methylation in infected cells.

Newcastle disease virus (NDV) is a paramyxovirus with high incidence and transmissibility in birds and is currently being developed for cancer therapy. N6-methyladenosine (m6A) is a common epigenetic modification of RNA. In this study, we aimed to determine whether this modification plays an important role in NDV infection. We found that methylation-related enzymes were activated in NDV-infected cells, and the abundance of m6A notably increased in vivo and in vitro. Further functional experiments showed that m6A methylation negatively regulates NDV infection. Methylated RNA immunoprecipitation sequencing revealed that the m6A-methylated peaks on different functional components of host genes shifted, underwent reprogramming, and were primarily enriched in the coding sequence after NDV infection. The differentially modified genes were mainly enriched in cellular components, as well as autophagy and ubiquitination-mediated proteolysis signaling pathways. Association analysis of RNA sequencing results showed changes in m6A regulated mRNA transcription and revealed that YTHDC1 is a methylation-related enzyme with important catalytic and recognition roles during NDV infection. Additionally, m6A-methylated peaks were detected in the NDV genome, which may be regulated by methylation-related enzymes in the host, subsequently affecting viral replication. Comprehensive analysis of the m6A expression profile after NDV infection indicated that NDV may cause reprogramming of m6A methylation and that m6A plays important roles during infection. Overall, these findings provide insights into the epigenetic etiology and pathogenesis of NDV.

Construction of a molecular inflammatory predictive model with histone modification-related genes and identification of CAMK2D as a potential response signature to infliximab in ulcerative colitis.

Background: Ulcerative colitis (UC) is a lifelong inflammatory disease affecting the rectum and colon with numerous treatment options that require an individualized treatment plan. Histone modifications regulate chromosome structure and gene expression, resulting in effects on inflammatory and immune responses. However, the relationship between histone modification-related genes and UC remains unclear. Methods: Transcriptomic data from GSE59071 and GSE66407 were obtained from the Gene Expression Omnibus (GEO), encompassing colonic biopsy expression profiles of UC patients in inflamed and non-inflamed status. Differentially expressed gene (DEG) analyses, functional enrichment analyses, weighted gene co-expression network analysis (WGCNA), and random forest were performed to identify histone modification-related core genes associated with UC inflammation. Features were screened through the least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE), establishing a molecular inflammatory predictive model using logistic regression. The model was validated in the GSE107499 dataset, and the performance of the features was assessed using receiver operating characteristic (ROC) and calibration curves. Immunohistochemistry (IHC) staining of colonic biopsy tissues from UC patients treated with infliximab was used to further confirm the clinical application value. Univariate logistic regression on GSE14580 highlighted features linked to infliximab response. Results: A total of 253 histone modification-related DEGs were identified between inflammatory and non-inflammatory patients with UC. Seven key genes (IL-1ß, MSL3, HDAC7, IRF4, CAMK2D, AUTS2, and PADI2) were selected using WGCNA and random forest. Through univariate logistic regression, three core genes (CAMK2D, AUTS2, and IL-1ß) were further incorporated to construct the molecular inflammatory predictive model. The area under the curve (AUC) of the model was 0.943 in the independent validation dataset. A significant association between CAMK2D protein expression and infliximab response was observed, which was validated in another independent verification set of GSE14580 from the GEO database. Conclusion: The molecular inflammatory predictive model based on CAMK2D, AUTS2, and IL-1ß could reliably distinguish the mucosal inflammatory status of UC patients. We further revealed that CAMK2D was a predictive marker of infliximab response. These findings are expected to provide a new evidence base for personalized treatment and management strategies for UC patients.

Antibiotics use and risk of colorectal neoplasia: An updated meta-analysis.

PURPOSE: Accumulating evidence indicate that antibiotic use could induce microbiome dysbiosis, which was a critical driver to the onset and progression of colorectal cancer (CRC). But the relationship between antibiotics use and CRC was still disputed. Hence, we conducted this systematic review and meta-analysis to appraise and synthesize the present available evidence to clarify the association. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for relevant observational studies from inception to June 5, 2020. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to explore the association between antibiotics use and CRC using random-effects model. Subgroup analyses, sensitive analyses, and publication bias were conducted to assess the robust reliability of pooled results. RESULTS: A total of 15 observational studies containing 5,164,138 patients were included in this meta-analysis. The pooled analysis indicated that the total antibiotic use was correlated with increased risk of CRC (OR, 1.11; 95% CI, 1.05-1.18). The subgroup analyses suggested that antibiotic use significantly elevated risk of colon cancer, but not rectal cancer. Furthermore, we found that penicillin, cephalosporin, anti-anaerobic, and anti-aerobic antibiotics increased the risk of CRC, in particular metronidazole but no significant associations were identified in macrolide, tetracycline, sulfonamides, nitrofurans, and quinolone use. The results of sensitive analyses and publication bias indicated the conclusions were robust. CONCLUSION: The findings showed that antibiotics use may be associated with the onset of CRC. Policy-makers and clinicians should adequately assess possible benefits and harms of antibiotics use, especially in some high-risk populations. Also, for high-risk patients with previous antibiotics use, it was suggested to perform early colonoscopy screening to find or even eliminate early-stage CRC.

TiSe2-mediated sonodynamic and checkpoint blockade combined immunotherapy in hypoxic pancreatic cancer.

BACKGROUND: Pancreatic cancer remains among the most prevalent and aggressive forms of cancer. While immunotherapeutic treatment strategies have shown some promise in affected patients, the benefits of these interventions have been limited by insufficient tumor infiltration by activated T cells. RESULTS: Here, Titanium diselenide (TiSe2) nanosheets were synthesized with good stability. When exposed to ultrasound (US), the TiSe2 nanosheets served as a reliable nano-sensitizer capable of inducing large amounts of reactive oxygen species (ROS) mediating sonodynamic therapy (SDT) under hypoxic and normoxic conditions. The tumor-released TAAs induced by TiSe2 nanosheet-mediated SDT promoted immunogenic cell death (ICD) conducive to the maturation of dendritic cells (DCs), and cytokine secretion and the subsequent activation and infiltration of T cells into the tumor. Combining TiSe2-mediated SDT with anti-PD-1 immune checkpoint blockade treatment led to the efficient suppression of the growth of both primary tumor and distant tumor, while simultaneously preventing lung metastasis. These improved immunotherapeutic and anti-metastatic outcomes were associated with activated systematic antitumor immune responses, including the higher levels of DC maturation and cytokine secretion, the increased levels of CD8+ T cells and the decreased levels of Treg cells infiltrated in tumors. CONCLUSION: TiSe2 can be used as a sonosensitizer with good efficacy and high safety to mediate efficient SDT. The combination treatment strategy comprised of TiSe2-mediated SDT and PD-1 blockade activate anti-tumor immune responses effectively thorough inducing ICD, resulting in the inhibition the growth and metastasis of tumor. The combination therapy holds promise as a novel immunotherapy-based intervention strategy for pancreatic cancer patients.

Ultrasound improved immune adjuvant delivery to induce DC maturation and T cell activation.

Tumor immunotherapy has emerged as a promising approach to tumor treatment. Currently, immune adjuvant-based therapeutic modalities are rarely curative in solid tumors owing to challenges including the low permeability and extremely poor water solubility of these adjuvants, limiting their ability to effectively promote dendritic cell (DC) maturation. Herein, we employed ultrasound-mediated cavitation (UMC) to promote the delivery of Toll-like receptor agonist (R837)-loaded pH-responsive liposomes (PEOz-Lip@R837) to tumors. The tumor-associated antigens (TAAs) produced by UMC treatment exhibited vaccinal activity, particularly in the presence of immune adjuvants, together promoting the maturation of DC and inducing cytokine production. Importantly, UMC can down-regulate immune checkpoint molecules, like Cd274, Foxp3 and Ctla4, synergistically stimulating the activation and proliferation of T cells in the body to facilitate tumor treatment. This UMC-enhanced PEOz-Lip@R837 approach was able to induce a robust antitumor immune response capable of arresting primary and distant tumor growth, while also developing immunological memory, protecting against tumor rechallenge following initial tumor clearance. Overall, these results highlight a promising UMC- and pH-sensitive immune adjuvant delivery-based treatment for tumors with the potential for clinical application.

Ultrasound-Mediated Cavitation Enhances EGFR-Targeting PLGA-PEG Nano-Micelle Delivery for Triple-Negative Breast Cancer Treatment.

Triple-negative breast cancer (TNBC) is highly recurring and metastatic breast cancer with overexpressing epidermal growth factor receptor (EGFR). Herein, a series of in vitro and in vivo analyses were used to explore the therapeutic effect of EGFR-targeting nano-micelles (PLGA-PEG/DOX@anti-EGFR) combined with ultrasound-mediated cavitation (UMC). The prepared nano-micelle drug carriers have good biocompatibility and can greatly increase the drug accumulation in tumor regions, thereby reducing off-target toxicity while enhancing anti-tumor efficacy. Moreover, an in vivo analysis of the practical utility of this treatment modality was conducted by using SonoVueTM microbubbles to achieve cavitation under different power intensity levels, with an ultrasonic power intensity of 0.5 W/cm2 maximizing the intra-tumoral blood perfusion. Relative to PLGA-PEG@DOX/anti-EGFR nano-micelles treatment alone, the combination with UMC was better able to suppress tumor growth even at low concentrations. As such, combining actively targeted drug-carrier molecules with UMC represents an effective approach to enhancing therapeutic efficacy while reducing the adverse, systemic effects associated with DOX and other chemotherapeutic drugs, and it can be considered as a promising clinical prospect in the treatment of TNBC.

Contrast-enhanced ultrasound of breast fibromatosis: a case report.

We herein present a rare case of breast fibromatosis, the contrast-enhanced ultrasonography (CEUS) findings of which we believe have never been described. The high similarity between the clinical and imaging manifestations of breast cancer makes its differential diagnosis difficult. In this report, we describe the CEUS findings of a less common type of fibromatosis, discuss the potential value of CEUS to differentiate it from malignant breast lesions, and briefly review the literature.

MSIFinder: a python package for detecting MSI status using random forest classifier.

BACKGROUND: Microsatellite instability (MSI) is a common genomic alteration in colorectal cancer, endometrial carcinoma, and other solid tumors. MSI is characterized by a high degree of polymorphism in microsatellite lengths owing to the deficiency in the mismatch repair system. Based on the degree, MSI can be classified as microsatellite instability-high (MSI-H) and microsatellite stable (MSS). MSI is a predictive biomarker for immunotherapy efficacy in advanced/metastatic solid tumors, especially in colorectal cancer patients. Several computational approaches based on target panel sequencing data have been used to detect MSI; however, they are considerably affected by the sequencing depth and panel size. RESULTS: We developed MSIFinder, a python package for automatic MSI classification, using random forest classifier (RFC)-based genome sequencing, which is a machine learning technology. We included 19 MSI-H and 25 MSS samples as training sets. First, we selected 54 feature markers from the training sets, built an RFC model, and validated the classifier using a test set comprising 21 MSI-H and 379 MSS samples. With this test set, MSIFinder achieved a sensitivity (recall) of 1.0, a specificity of 0.997, an accuracy of 0.998, a positive predictive value of 0.954, an F1 score of 0.977, and an area under the curve of 0.999. To further verify the robustness and effectiveness of the model, we used a prospective cohort consisting of 18 MSI-H samples and 122 MSS samples. MSIFinder achieved a sensitivity (recall) of 1.0 and a specificity of 1.0. We discovered that MSIFinder is less affected by a low sequencing depth and can achieve a concordance of 0.993 while exhibiting a sequencing depth of 100×. Furthermore, we realized that MSIFinder is less affected by the panel size and can achieve a concordance of 0.99 when the panel size is 0.5 M (million bases). CONCLUSION: These results indicate that MSIFinder is a robust and effective MSI classification tool that can provide reliable MSI detection for scientific and clinical purposes.

Hsp90 inhibitor-loaded IR780 micelles for mitochondria-targeted mild-temperature photothermal therapy in xenograft models of human breast cancer.

Mitochondria-targeted mild-temperature photothermal therapy (MT-PTT) is a promising strategy that can maximize anticancer effects and reduce adverse reactions. Here, a novel photosensitizer with mitochondrial targeting based on IR780 iodide and heat shock protein 90 inhibitor (BIIB021), which can passively accumulate in MCF-7 cells and achieve effective MT-PTT effect is synthesized. The prepared PEG-IR780-BIIB021 nano-micelles possess considerable biocompatibility and biological stability, with an encapsulation efficiency of about 84% for BIIB021. They can selectively enrich in mitochondria, and release BIIB021 after NIR irradiation to reduce cell tolerance to heat, thereby reducing the mitochondrial membrane potential and rapidly affecting key intrinsic apoptotic factors (Cyt-C, Caspase-9, Bcl-2 and Bax) to achieve the effect of MT-PTT. It is believed that mitochondria-targeted MT-PTT generated by the PEG-IR780-BIIB021 nano-micelles is a promising therapeutic strategy in clinical practice.

A lipid transfer protein variant with a mutant eight-cysteine motif causes photoperiod- and thermo-sensitive dwarfism in rice.

Plant height is an important trait for architecture patterning and crop yield improvement. Although the pathways involving gibberellins and brassinosteroids have been well studied, there are still many gaps in our knowledge of the networks that control plant height. In this study, we determined that a dominant photoperiod- and thermo-sensitive dwarf mutant is caused by the active role of a mutated gene Photoperiod-thermo-sensitive dwarfism 1 (Ptd1), the wild-type of which encodes a non-specific lipid transfer protein (nsLTP). Ptd1 plants showed severe dwarfism under long-day and low-temperature conditions, but grew almost normal under short-day and high-temperature conditions. These phenotypic variations were associated with Ptd1 mRNA levels and accumulation of the corresponding protein. Furthermore, we found that the growth inhibition in Ptd1 may result from the particular protein conformation of Ptd1 due to loss of two disulfide bonds in the eight-cysteine motif (8-CM) that is conserved among nsLTPs. These results contribute to our understanding of the novel function of disulfide bonds in the 8-CM, and provide a potential new strategy for regulation of cell development and plant height by modifying the amino acid residues involved in protein conformation patterning.

Diagnostic value and safety of color doppler ultrasound-guided transthoracic core needle biopsy of thoracic disease.

Objective: The aim of the present study was to explore the diagnostic value and safety of color Doppler ultrasound (US)-guided transthoracic core needle biopsy (CNB) of peripheral lung, chest wall and mediastinal lesions using automated biopsy guns.Materials and methods: We analyzed clinical and image data, histopathologic and microbiologic details and complications from 121 patients with peripheral lung, chest wall and mediastinal lesions who underwent color Doppler US-guided transthoracic CNB in Ningbo First Hospital between January 2015 and June 2018.Results: Color Doppler US-guided transthoracic CNB performed with a freehand technique using automated biopsy guns had a sensitivity of 93.94%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 78.57%, and a diagnostic accuracy of 95.04%. Lesion size did not affect the diagnostic rate (P=0.40). No serious complications of the procedure were noted.Conclusion: Color Doppler US-guided transthoracic CNB of peripheral lung, chest wall and mediastinal lesions is a safe and inexpensive procedure. The diagnostic accuracy of color Doppler US-guided transthoracic CNB was higher than that of color Doppler US-guided transthoracic fine needle aspiration biopsy (FNAB).