Disulfiram-loaded CuO2 nanocarriers for enhanced synergistic chemodynamic chemotherapy.

Disulfiram (DSF) metabolites exhibit antitumor properties when bound to Cu2+. This combination also promotes the generation of reactive oxygen species (ROS), ultimately leading to tumor cell death. In this study, CuO2 served as a carrier for DSF, forming a dual-drug delivery system with Cu2+ and DSF encapsulated in polydopamine (PDA). In the final delivery system, CuO2 (DSF-CuO2@PDA) was hydrolyzed at the tumor site, releasing both Cu2+ and H2O2. Cu2+ reacts with DSF metabolites to form Bis(diethyldithiocarbamate)-Cu (CuET), which triggers a Fenton-like reaction that generates ROS. Chemotherapy and chemodynamic therapy exhibited significant tumor-suppressive capabilities, with an inhibition rate of 61 %. In addition, the DSF-CuO2@PDA complex demonstrated superlative tumor-targeting ability and biocompatibility.

Dextran-Based Antibacterial Hydrogel Dressings for Accelerating Infected Wound Healing by Reducing Inflammation Levels.

Infected wounds pose challenges such as exudate management, bacterial infections, and persistent inflammation, making them a significant challenge for modern dressings. To address these issues in infected wounds more effectively, aerogel-hydrogel biphase gels based on dextran are developed. The gel introduced in this study exhibits antibacterial and anti-inflammatory properties in the process of wound therapy, contributing to accelerated wound healing. The aerogel phase exhibits exceptional water-absorption capabilities, rapidly soaking up exudate from infected wound, thereby fostering a clean and hygienic wound healing microenvironment. Concurrently, the aerogel phase is enriched with hydrogen sulfide donors. Following water absorption and the formation of the hydrogel phase, it enables the sustained release of hydrogen sulfide around the wound sites. The experiments confirm that hydrogen sulfide, by promoting M2 macrophage differentiation and reducing the levels of inflammatory factors, effectively diminishes local inflammation levels at the wound site. Furthermore, the sodium copper chlorophyllin component within the hydrogel phase demonstrates effective antibacterial properties through photodynamic antimicrobial therapy, providing a viable solution to wound infection challenges.

In situ generation of copper(â ¡)/diethyldithiocarbamate complex through tannic acid/copper(â ¡) network coated hollow mesoporous silica for enhanced cancer chemodynamic therapy.

The Cu2+ complex formed by the coordination of disulfiram (DSF) metabolite diethyldithiocarbamate (DTC), Cu(DTC)2, can effectively inhibit tumor growth. However, insufficient Cu2+ levels in the tumor microenvironment can impact tumor-suppressive effects of DTC. In this study, we proposed a Cu2+ and DSF tumor microenvironment-targeted delivery system. This system utilizes hollow mesoporous silica (HMSN) as a carrier, after loading with DSF, encases it using a complex of tannic acid (TA) and Cu2+ on the outer layer. In the slightly acidic tumor microenvironment, TA/Cu undergoes hydrolysis, releasing Cu2+ and DSF, which further form Cu(DTC)2 to inhibit tumor growth. Additionally, Cu2+ can engage in a Fenton-like reaction with H2O2 in the tumor microenvironment to form OH, therefore, chemodynamic therapy (CDT) and Cu(DTC)2 are used in combination for tumor therapy. In vivo tumor treatment results demonstrated that AHD@TA/Cu could accumulate at the tumor site, achieving a tumor inhibition rate of up to 77.6 %. This study offers a novel approach, circumventing the use of traditional chemotherapy drugs, and provides valuable insights into the development of in situ tumor drug therapies.

pH/glutathione dual-responsive copper sulfide-coated organic mesoporous silica for synergistic chemo-photothermal therapy.

Nanodrug delivery systems (NDSs), such as mesoporous silica, have been widely studied because of their high specific surface area, high loading rate, and easy modification; however, they are not easily metabolized and excreted by the human body and may be potentially harmful. Hence, we aimed to examine the synergistic anti-tumor effects of ex vivo chemo-photothermal therapy to develop a rational and highly biocompatible treatment protocol for tumors. We constructed a biodegradable NDS using organic mesoporous silica with a tetrasulfide bond structure, copper sulfide core, and folic acid-modified surface (CuS@DMONs-FA-DOX-PEG) to target a tumor site, dissociate, and release the drug. The degradation ability, photothermal conversion ability, hemocompatibility, and in vitro and in vivo anti-tumor effects of the CuS@DMONs-FA-DOX-PEG nanoparticles were evaluated. Our findings revealed that the nanoparticles encapsulated in copper sulfide exhibited significant photothermal activity and optimal photothermal conversion rate. Further, the drug was accurately delivered and released into the target tumor cells, annihilating them. This study demonstrated the successful preparation, safety, and synergistic anti-tumor effects of chemo-photothermal therapeutic nanomaterials.

Impact of propofol versus sevoflurane anesthesia on molecular subtypes and immune checkpoints of glioma during surgery.

Background: Sevoflurane and propofol are two popular anesthetics used during glioblastoma (GBM) surgery. This investigation compared the molecular subtypes and immune checkpoints of cancer cells following GBM surgery under sevoflurane and propofol anesthesia. Method: The expression profile data and clinical information of glioma samples of different grades were downloaded from The Cancer Genome Atlas database. Weighted gene coexpression network analysis was used to identify hub modules and key genes related to glioma grades (G2 and G3). The GEO database (GSE179004) was used to retrieve glioma surgical specimens with different anesthetic gene expression profiles. The differential expression of immune checkpoint genes under various anesthetic settings was examined using the R-ggplot2. Results: Compared to sevoflurane, propofol significantly downregulated SERPINI1 and CAMK2A expression. These are also important factors in glioma grading. Simultaneously, SERPINI1 and CAMK2A were also significantly related to the prognosis of GBM and lower-grade glioma patients and acted as potential tumor suppressors. In addition, propofol increases the expression of the immune checkpoint molecule, PD-L1. Conclusions: Our study revealed that sevoflurane can more effectively prevent the development of glioma after surgery than propofol, and SERPINI1 can be used as a new independent prognostic factor for glioma.

Integrated transcriptomics and metabolomics analysis provide insight into the resistance response of rice against brown planthopper.

Introduction: The brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most economically significant pests of rice. The Bph30 gene has been successfully cloned and conferred rice with broad-spectrum resistance to BPH. However, the molecular mechanisms by which Bph30 enhances resistance to BPH remain poorly understood. Methods: Here, we conducted a transcriptomic and metabolomic analysis of Bph30-transgenic (BPH30T) and BPH-susceptible Nipponbare plants to elucidate the response of Bph30 to BPH infestation. Results: Transcriptomic analyses revealed that the pathway of plant hormone signal transduction enriched exclusively in Nipponbare, and the greatest number of differentially expressed genes (DEGs) were involved in indole 3-acetic acid (IAA) signal transduction. Analysis of differentially accumulated metabolites (DAMs) revealed that DAMs involved in the amino acids and derivatives category were down-regulated in BPH30T plants following BPH feeding, and the great majority of DAMs in flavonoids category displayed the trend of increasing in BPH30T plants; the opposite pattern was observed in Nipponbare plants. Combined transcriptomics and metabolomics analysis revealed that the pathways of amino acids biosynthesis, plant hormone signal transduction, phenylpropanoid biosynthesis and flavonoid biosynthesis were enriched. The content of IAA significantly decreased in BPH30T plants following BPH feeding, and the content of IAA remained unchanged in Nipponbare. The exogenous application of IAA weakened the BPH resistance conferred by Bph30. Discussion: Our results indicated that Bph30 might coordinate the movement of primary and secondary metabolites and hormones in plants via the shikimate pathway to enhance the resistance of rice to BPH. Our results have important reference significance for the resistance mechanisms analysis and the efficient utilization of major BPH-resistance genes.

Chinese expert consensus on the diagnosis and treatment of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high-risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow-up.

Single-Cell RNA sequencing of leaf sheath cells reveals the mechanism of rice resistance to brown planthopper (Nilaparvata lugens).

The brown planthopper (BPH) (Nilaparvata lugens) sucks rice sap causing leaves to turn yellow and wither, often leading to reduced or zero yields. Rice co-evolved to resist damage by BPH. However, the molecular mechanisms, including the cells and tissues, involved in the resistance are still rarely reported. Single-cell sequencing technology allows us to analyze different cell types involved in BPH resistance. Here, using single-cell sequencing technology, we compared the response offered by the leaf sheaths of the susceptible (TN1) and resistant (YHY15) rice varieties to BPH (48 hours after infestation). We found that the 14,699 and 16,237 cells (identified via transcriptomics) in TN1 and YHY15 could be annotated using cell-specific marker genes into nine cell-type clusters. The two rice varieties showed significant differences in cell types (such as mestome sheath cells, guard cells, mesophyll cells, xylem cells, bulliform cells, and phloem cells) in the rice resistance mechanism to BPH. Further analysis revealed that although mesophyll, xylem, and phloem cells are involved in the BPH resistance response, the molecular mechanism used by each cell type is different. Mesophyll cell may regulate the expression of genes related to vanillin, capsaicin, and ROS production, phloem cell may regulate the cell wall extension related genes, and xylem cell may be involved in BPH resistance response by controlling the expression of chitin and pectin related genes. Thus, rice resistance to BPH is a complicated process involving multiple insect resistance factors. The results presented here will significantly promote the investigation of the molecular mechanisms underlying the resistance of rice to insects and accelerate the breeding of insect-resistant rice varieties.

Chinese expert consensus on the diagnosis and treatment of thymic epithelial tumors.

Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first- and second-line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow-up of TETs.

Transcriptome Analysis Revealed the Dynamic and Rapid Transcriptional Reprogramming Involved in Cold Stress and Related Core Genes in the Rice Seedling Stage.

Cold damage is one of the most important environmental factors influencing crop growth, development, and production. In this study, we generated a pair of near-isogenic lines (NILs), Towada and ZL31, and Towada showed more cold sensitivity than ZL31 in the rice seedling stage. To explore the transcriptional regulation mechanism and the reason for phenotypic divergence of the two lines in response to cold stress, an in-depth comparative transcriptome study under cold stress was carried out. Our analysis uncovered that rapid and high-amplitude transcriptional reprogramming occurred in the early stage of cold treatment. GO enrichment and KEGG pathway analysis indicated that genes of the response to stress, environmental adaptation, signal transduction, metabolism, photosynthesis, and the MAPK signaling pathway might form the main part of the engine for transcriptional reprogramming in response to cold stress. Furthermore, we identified four core genes, OsWRKY24, OsCAT2, OsJAZ9, and OsRR6, that were potential candidates affecting the cold sensitivity of Towada and ZL31. Genome re-sequencing analysis between the two lines revealed that only OsWRKY24 contained sequence variations which may change its transcript abundance. Our study not only provides novel insights into the cold-related transcriptional reprogramming process, but also highlights the potential candidates involved in cold stress.

A Novel Robotic Exoskeleton for Finger Rehabilitation: Kinematics Analysis.

A novel robotic exoskeleton for fingers rehabilitation is developed, which is driven by linear motors through Bowden cables. For each finger, in addition to three links acting as phalanxes, two more links acting as knuckles are also implemented. Links are connected through passive joints, by which translational and rotary movements can be realized simultaneously. Either flexion or extension motion is accomplished by one cable of adequate stiffness. This exoskeleton possesses good adaptability to finger length of different subjects and length variations during movement. The exoskeleton's kinematics model is built by the statistics method, and piecewise polynomial functions (PPF) are chosen to describe the relationship between motor displacement and joint variables. Finally, the relationship between motor displacement and the finger's total bending angle is obtained, which can be used for rehabilitation trajectory planning. Experimental results show that this exoskeleton achieves nearly the maximum finger bending angle of a healthy adult person, with the maximum driving force of 68.6 N.

Genome-wide identification of long non-coding (lncRNA) in Nilaparvata lugens's adaptability to resistant rice.

Background: The brown planthopper (BPH), Nilaparvata lugens (Stål), is a very destructive pest that poses a major threat to rice plants worldwide. BPH and rice have developed complex feeding and defense strategies in the long-term co-evolution. Methods: To explore the molecular mechanism of BPH's adaptation to resistant rice varieties, the lncRNA expression profiles of two virulent BPH populations were analyzed. The RNA-seq method was used to obtain the lncRNA expression data in TN1 and YHY15. Results: In total, 3,112 highly reliable lncRNAs in TN1 and YHY15 were identified. Compared to the expression profiles between TN1 and YHY15, 157 differentially expressed lncRNAs, and 675 differentially expressed mRNAs were identified. Further analysis of the possible regulation relationships between differentially expressed lncRNAs and differentially expressed mRNAs, identified three pair antisense targets, nine pair cis-regulation targets, and 3,972 pair co-expressed targets. Function enriched found arginine and proline metabolism, glutathione metabolism, and carbon metabolism categories may significantly affect the adaptability in BPH when it is exposed to susceptible and resistant rice varieties. Altogether, it provided scientific data for the study of lncRNA regulation of brown planthopper resistance to rice. These results are helpful in the development of new control strategies for host defense against BPH and breeding rice for high yield.

Osteoblastoma of the Rib Mimicking Lymphomatous Involvement on 18F-FDG PET/CT Imaging.

ABSTRACT: We present a case of rib osteoblastoma in a patient with NK/T cell lymphoma. Osteoblastoma was incidentally found in a 63-year-old man in the axillary segment of the fifth rib and was misdiagnosed as lymphomatous involvement on staging 18F-FDG PET/CT. The radiological features in the CT component of PET/CT were atypical. After surgery, the diagnosis of osteoblastoma was confirmed by histopathologic findings.

Identification and verification of grain shape QTLs by SNP array in rice.

Grain shape strongly influences the economic value and grain yield of rice. Thus, identifying quantitative trait loci (QTLs) for grain shape has been a longstanding goal in rice genetic research and breeding programs. Single nucleotide polymorphism (SNP) markers are ubiquitous in the rice genome and are more abundant and evenly distributed on the 12 rice chromosomes than traditional markers. An F2 population was genotyped using the RICE6K SNP array to elucidate the mechanisms governing grain shape. Thirty-five QTLs for grain shape were detected on 11 of 12 chromosomes over 2 years. The major QTL cluster qGS7 was detected in both years and displayed strong genetic effects on grain length and width, showing consistency with GL7/GW7. Some minor QTLs were also detected, and the effects of four QTLs on seed size were then validated using BC1F6 populations with residual heterozygous lines in each QTL region. Our findings provide insights into the molecular basis of grain shape as well as additional resources and approaches for producing hybrid high-yield rice varieties.

Perioperative crizotinib in a patient with stage IIIB ALK-positive non-small cell lung cancer: a case report.

We present a case of a 43-year-old female patient with clinical stage IIIB (T3N2M0) anaplastic lymphoma kinase (ALK)-positive adenocarcinoma of the lung. Surgery was not performed initially because of multiple mediastinal lymph nodes invasion, although the mass was technically resected. With the assessment of upfront multidisciplinary consultation, administration of neoadjuvant crizotinib was selected to induce the downstaging and facilitate the subsequent surgical treatment. After 10 weeks of neoadjuvant crizotinib treatment, a partial response was achieved and the tumor could be radically resected. There were no sever toxic effects and treatment-related surgical delay during the whole neoadjuvant crizotinib therapy. The patient then successfully underwent video-assisted single port thoracoscopic right upper lobectomy and lymphadenectomy. Concurrent chemotherapy and radiotherapy were applied postoperatively. Perioperative targeted therapy demonstrated good curative effect in this case, and no recurrence was observed at the clinic 8 months after surgery. In this case, the safety and effectiveness of neoadjuvant crizotinib and subsequent surgery are preliminarily proved. We here intend to investigate the optimal setting of neoadjuvant targeted therapy combined with minimally invasive surgery and postoperative adjuvant therapy, inspire more potential targeted treatment based schedules and to apply these strategies in treating patients with locally advanced mutant-positive non-small cell lung cancer (NSCLC).

Relationship between histogram metrics of pharmacokinetic parameters of DCE-MRI and histological phenotype in breast cancer.

BACKGROUND: To investigate the correlation between quantitative pharmacokinetic parameters and clinicopathological prognostic biomarkers including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and MiB1 (Ki-67) in patients with breast cancer, the image histogram analysis was performed on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: The reference region model (RRM) was used to calculate the quantitative permeability parameters, including reference region volume transfer constant (Ktrans,RR ), the rate constant of tissue of interest (Kep,TOI ), and the rate constant of reference region (Kep,RR ). Histogram analysis was performed to compare these parameters between ER/PR/HER2/Ki-67 positive and negative groups. The performance of the histogram parameters Ktrans,RR , Kep,TOI and Kep,RR in differential diagnosis of immunohistochemistry results was conducted by receiver operating characteristic (ROC) curve analysis. RESULTS: All the histogram metrics of Kep,TOI significantly differed between ER/PR positive and negative groups (P<0.05). However, Ktrans,RR and Kep,RR did not significantly differ between ER/PR positive and negative groups (P>0.05). The 10th percentile, energy, entropy and variance of Ktrans,RR , and almost all the histogram parameters of Kep,TOI except for variance significantly differed between HER2 positive and negative groups (all P<0.05). The energy of Ktrans,RR significantly differed between Ki-67 positive and negative groups (P<0.05). The skewness and energy of Kep,TOI showed the highest AUC of 0.977 and 0.879 in differentiating ER/PR status. The energy of Ktrans,RR presented the highest AUC in the differentiation of HER2 and Ki-67. CONCLUSIONS: Histogram analysis on quantitative pharmacokinetic breast parameters using DCE-MRI improves the performance in differentiation of histological phenotypes of breast cancer.

Quantitative Proteomics of Potato Leaves Infected with Phytophthora infestans Provides Insights into Coordinated and Altered Protein Expression during Early and Late Disease Stages.

In order to get a better understanding of protein association during Solanum tuberosum (cv. Sarpo Mira)⁻Phytophthora infestans incompatible interaction, we investigated the proteome dynamics of cv. Sarpo Mira, after foliar application of zoospore suspension from P. infestans isolate, at three key time-points: zero hours post inoculation (hpi) (Control), 48 hpi (EI), and 120 hpi (LI); divided into early and late disease stages by the tandem mass tagging (TMT) method. A total of 1229 differentially-expressed proteins (DEPs) were identified in cv. Sarpo Mira in a pairwise comparison of the two disease stages, including commonly shared DEPs, specific DEPs in early and late disease stages, respectively. Over 80% of the changes in protein abundance were up-regulated in the early stages of infection, whereas more DEPs (61%) were down-regulated in the later disease stage. Expression patterns, functional category, and enrichment tests highlighted significant coordination and enrichment of cell wall-associated defense response proteins during the early stage of infection. The late stage was characterized by a cellular protein modification process, membrane protein complex formation, and cell death induction. These results, together with phenotypic observations, provide further insight into the molecular mechanism of P. infestans resistance in potatos.

The Expression and Related Clinical Significance of SIRT3 in Non-Small-Cell Lung Cancer.

OBJECTIVE: To examine the relationship between the Sirtuin-3 (SIRT3) expression and the clinical indicators/prognosis of patients with non-small-cell lung cancer (NSCLC). METHODS: The mRNA level of SIRT3 was detected by real-time PCR, while the protein level was detected by Western blot and immunohistochemical staining. SPSS 16.0 software was used for statistical analysis. RESULTS: The expression of SIRT3 was significantly higher in NSCLC tissue than in adjacent tissue. The SIRT3 level was correlated significantly with lymph node metastasis and clinical stage of NSCLC patients. Moreover, univariate analysis showed that the expression of SIRT3, tumor size, lymph node metastasis, degree of differentiation, and clinical stage were correlated with the prognosis of NSCLC patients. Multivariate analysis demonstrated that lymph node metastasis, the tumor size, and SIRT3 expression were independent prognostic factors for NSCLC patients. CONCLUSIONS: SIRT3 is associated with the development and progression of NSCLC. The SIRT3 expression can be used as an independent prognostic factor for NSCLC patients and help identify prognosis of NSCLC. Therefore, SIRT3 has the potential to become a new factor for prognosis prediction and personalized treatment of NSCLC.