M2 Macrophage Membrane-Camouflaged Fe3 O4 -Cy7 Nanoparticles with Reduced Immunogenicity for Targeted NIR/MR Imaging of Atherosclerosis.

Atherosclerosis （AS） is the primary reason behind cardiovascular diseases, leading to approximately one-third of global deaths. Developing a novel multi-model probe to detect AS is urgently required. Macrophages are the primary cells from which AS genesis occurs. Utilizing natural macrophage membranes coated on the surface of nanoparticles is an efficient delivery method to target plaque sites. Herein, Fe3 O4 -Cy7 nanoparticles (Fe3 O4 -Cy7 NPs), functionalized using an M2 macrophage membrane and a liposome extruder for Near-infrared fluorescence and Magnetic resonance imaging, are synthesized. These macrophage membrane-coated nanoparticles (Fe3 O4 @M2 NPs) enhance the recognition and uptake using active macrophages. Moreover, they inhibit uptake using inactive macrophages and human coronary artery endothelial cells. The macrophage membrane-coated nanoparticles (Fe3 O4 @M0 NPs, Fe3 O4 @M1 NPs, Fe3 O4 @M2 NPs) can target specific sites depending on the macrophage membrane type and are related to C-C chemofactor receptor type 2 protein content. Moreover, Fe3 O4 @M2 NPs demonstrate excellent biosafety in vivo after injection, showing a significantly higher Fe concentration in the blood than Fe3 O4 -Cy7 NPs. Therefore, Fe3 O4 @M2 NPs effectively retain the physicochemical properties of nanoparticles and depict reduced immunological response in blood circulation. These NPs mainly reveal enhanced targeting imaging capability for atherosclerotic plaque lesions.

Catalyst-free visible light-promoted defunctionalization of alkyl isocyanides with a hydrosilane through C-N bond cleavage.

A radical initiator-free defunctionalization reaction of alkyl isocyanides with a hydrosilane has been established through C-N bond cleavage under catalyst-free visible light irradiation. Various alkyl isocyanides participated in the defunctionalization with tris(trimethylsilyl)silane under blue light irradiation at room temperature, delivering the reduced products in good yields with high chemoselectivity.

Decrypting the skeletal toxicity of vertebrates caused by environmental pollutants from an evolutionary perspective: From fish to mammals.

The rapid development of modern society has led to an increasing severity in the generation of new pollutants and the significant emission of old pollutants, exerting considerable pressure on the ecological environment and posing a serious threat to both biological survival and human health. The skeletal system, as a vital supportive structure and functional unit in organisms, is pivotal in maintaining body shape, safeguarding internal organs, storing minerals, and facilitating blood cell production. Although previous studies have uncovered the toxic effects of pollutants on vertebrate skeletal systems, there is a lack of comprehensive literature reviews in this field. Hence, this paper systematically summarizes the toxic effects and mechanisms of environmental pollutants on the skeletons of vertebrates based on the evolutionary context from fish to mammals. Our findings reveal that current research mainly focuses on fish and mammals, and the identified impact mechanisms mainly involve the regulation of bone signaling pathways, oxidative stress response, endocrine system disorders, and immune system dysfunction. This study aims to provide a comprehensive and systematic understanding of research on skeletal toxicity, while also promoting further research and development in related fields.

[Modulation of gut microbiota during alleviation of antibiotic-associated diarrhea with Zingiberis Rhizoma].

This study was aimed to explore the effect of Zingiberis Rhizoma extract on rats with antibiotic-associated diarrhea(AAD), and reveal the modulation of gut microbiota during alleviation of AAD. AAD rat model was successfully established by exposing rats to appropriate antibiotic mixed solution. Peficon(70 mg·kg~(-1)·d~(-1)) was used as positive control, then rats were treated with 200 mg·kg~(-1)·d~(-1) and 400 mg·kg~(-1)·d~(-1) of Zingiberis Rhizoma extract for low and high dosage groups of Zingiberis Rhizoma extract, respectively. The weight changes of the rats were observed, and the degree of diarrhea were evaluated by fecal score, 120 min fecal weight and fecal water content. Colon tissues for histopathological examination were stained with hematoxylin and eosin(HE), and 16 S rRNA sequencing analysis of gut microbiota was performed. The results showed that compared with the model group, the degree of diarrhea, indicated by fecal water content, fecal score, and 120 min fecal weight of positive control group, Zingiberis Rhizoma low-dose group and Zingiberis Rhizoma high-dose group were significantly ameliorated. And the treatment of Zingiberis Rhizoma could significantly improve the pathological condition of colon tissue in AAD rats, especially the high dose of Zingiberis Rhizoma. In addition, 16 S rRNA sequencing analysis of gut microbiota showed that the diversity and abundance of gut microbiota were significantly improved and the reco-very of gut microbiota was accelerated after given high-dose of Zingiberis Rhizoma, while no significant changes of alterations were observed after given Pefikon. Of note, compared with the pefikon group, the abundance and diversity of gut microbiota in Zingi-beris Rhizoma high-dose group were significantly elevated. At the phylum level, the abundance of Firmicutes in AAD rats increased and the abundance of Proteobacteria was decreased after the Zingiberis Rhizoma intervention. At the genus level, the abundance of Bacillus spp., Lachnoclostridium and Escherichia coli-Shigella were decreased, and the abundance of Lactobacillus spp., Trichophyton spp., and Trichophyton spp., etc., were increased. While compared with the AAD model group, there was no significant difference of gut microbiota after given Peficon. The results showed that Zingiberis Rhizoma exerted beneficial health effects against AAD, and positively affected the microbial environment in the gut of rats with AAD.

A Highly Selective Fluorescence "Turn on" and Absorbance-Ratiometric Detection of Al3+ in Totally H2O and its Application in Test Paper.

A novel naphthalene based fluorescence probe NBDH was designed and synthesized. Probe NBDH exhibited highly selective and sensitive responses towards Al3+ in HEPES-NaOH buffer solution (pH = 7.4). In addition, the detection of NBDH to Al3+ could be achieved through dual channels embodied in significant fluorescent turn-on signal and ratiometric absorbance response. The stoichiometry ratio of NBDH-Al3+ was 1:1 by fluorescence job' plot and binging mechanism was further varified by the FT-IR, NMR titration and HRMS. Furthermore, NBDH was achieved in real sample detection, and a series of color test paper were developed for visual detecting Al3+ ions.

The expression and prognostic value of SOX2, ß-catenin and survivin in esophageal squamous cell carcinoma.

Aim: We mainly explored the effect of SOX2, ß-catenin and survivin on prognosis in esophageal squamous cell carcinoma. Materials & methods: Immunohistochemistry was used to examine the expression of SOX2, ß-catenin and survivin. χ2 test was used to analyze the relationship between proteins and clinicopathological parameters. Survival analysis was used to investigate the effect of three proteins on prognosis. Results: SOX2 was related to lymph node metastasis (p = 0.004) and vascular invasion (p = 0.041). ß-catenin was associated with depth of invasion (p = 0.014), lymph node metastasis (p = 0.032) and postoperative chemoradiotherapy (p < 0.001). Survivin was related to gender (p = 0.022) and nerve invasion (p = 0.014). There was a positive correlation between SOX2 and ß-catenin. Patients with SOX2 and ß-catenin overexpression had poor prognosis. Survivin-positive patients who received postoperative chemoradiotherapy had a short time. Conclusion: SOX2, ß-catenin and survivin can be used as prognostic markers of esophageal squamous cell carcinoma.

A Highly Selective Naphthalimide-Based Chemosensor: "Naked-Eye" Colorimetric and Fluorescent Turn-On Recognition of Al3+ and Its Application in Practical Samples, Test Paper and Logic Gate.

A novel naphthalimide-based colorimetric and fluorescent turn-on chemosensor for Al3+ was synthesized and characterized with spectroscopic techniques. In MeOH solution, BPAM showed high selectivity and sensitivity to Al3+ by a 60-fold fluorescence enhancement and blue-shift absorption with visible color changes attributed to the contribution of chelation enhanced fluorescence (CHEF) and inhibition of intramolecular charge transfer (ICT). A 1:1 BPAM-Al3+ complex confirmed by job's plot and HRMS with a binding constant of 6.37 × 104 M- 1, and the detection limit for Al3+ was as low as 1.59 × 10- 7 M. BPAM was successfully applied in real sample detection and assessing the existence of Al3+ by a colorimetric method on filter paper. Furthermore, the fluorescent signals of BPAM were designed to construct an INHIBIT molecular logic gate.

The effect of Glut1 and c-myc on prognosis in esophageal squamous cell carcinoma of Kazakh and Han patients.

AIM: Glucose transporter type 1 (Glut1) plays a crucial role in cancer-specific metabolism. We explored the expression of Glut1 and c-myc, the relationship between them and the effect of Glut1, c-myc on prognosis in esophageal squamous cell carcinoma. MATERIALS & METHODS: Immunohistochemistry was used to examine the expression of Glut1 and c-myc. χ2 test analyzes the relationship between c-myc, Glut1 and pathological parameters. Spearman correlation analyzes the relationship between c-myc and Glut1. Survival analysis was used to investigate the effect of Glut1 and c-myc on prognosis. RESULTS: Glut1 positivity was associated with tumor size (p < 0.01), depth of invasion (p = 0.021), Tumor, Node, Metastasis stage (IA+IB,II+IIB,IIIA+IIIB,IVA+IVB; p = 0.004), lymph node metastasis (p = 0.002) and nerve invasion (p = 0.050). C-myc positivity was associated with tumor location (p = 0.015), depth of invasion (p = 0.022) and lymph node metastasis (p = 0.035). There was a positive correlation between c-myc and Glut1 (r = 0.321). Patients with Glut1 c-myc co-expression had poorer prognosis. CONCLUSION: Inhibiting Glut1 c-myc co-expression may improve the prognosis of esophageal squamous cell carcinoma.

Silyl Radical as an Isocyanide Transfer Agent for Giese-Type Reactions Involving Aliphatic Amines.

Herein we report silyl radicals serve as isocyanide transfer agents for Giese-type reaction from aliphatic amines and electron-deficient olefins. α-Primary, α-secondary, and sterically encumbered α-tertiary primary amines could be easily converted into isocyanides for coupling with electron-deficient olefins by employing latent silyl radicals under visible light irradiation. Notably, the abstraction of silane-mediated isocyanide not only enables voltage-independent activation of strong C-N bonds but also represents a mechanistic alternative Giese-type reaction in which single electron reduction and protonation processes are replaced by direct hydrogen atom transfer. This transformation occurs under photoinduced catalyst-free conditions and exhibits excellent functional group compatibility and mild reaction conditions.

Long-term tralopyril exposure results in endocrinological and transgenerational toxicity: A two-generation study of marine medaka (Oryzias melastigma).

This study aims to investigate the impact of tralopyril, a newly developed marine antifouling agent, on the reproductive endocrine system and developmental toxicity of offspring in marine medaka. The results revealed that exposure to tralopyril (0, 1, 20 µg/L) for 42 days resulted in decreased reproductive capacity in marine medaka. Moreover, it disrupted the levels of sex hormones E2 and T, as well as the transcription levels of genes related to the HPG axis, such as cyp19b and star. Sex-dependent differences were observed, with females experiencing more pronounced effects. Furthermore, intergenerational toxicity was observed in F1 offspring, including increased heart rate, changes in retinal morphology and cartilage structure, decreased swimming activity, and downregulation of transcription levels of relevant genes (HPT axis, GH/IGF axis, cox, bmp4, bmp2, runx2, etc.). Notably, the disruption of the F1 endocrine system by tralopyril persisted into adulthood, indicating a transgenerational effect. Molecular docking analysis suggested that tralopyril's RA receptor activity might be one of the key factors contributing to the developmental toxicity observed in offspring. Overall, our study highlights the potential threat posed by tralopyril to the sustainability of fish populations, as it can disrupt the endocrine system and negatively impact aquatic organisms for multiple generations.

Chlorin e6 (Ce6)-loaded plaque-specific liposome with enhanced photodynamic therapy effect for atherosclerosis treatment.

Recently, photodynamic therapy (PDT) has been considered as a new strategy for atherosclerosis treatment. Targeted delivery of photosensitizer could significantly reduce its toxicity and enhance its phototherapeutic efficiency. CD68 is an antibody that can be conjugated to nano-drug delivery systems to actively target plaque sites, owing to its specific binding to CD68 receptors that are highly expressed on the surfaces of macrophage-derived foam cells. Liposomes are very popular nanocarriers due to their ability to encapsulate a wide range of therapeutic compounds including drugs, microRNAs and photosensitizers, and their ability to be surface-modified with targeting moieties leading to the development of nanocarriers with an improved targeted ability. Hence, we designed a Ce6-loaded liposomes using the film dispersion method, followed by the conjugation of CD68 antibody on the liposomal surface through a covalent crosslinking reaction, forming CD68-modified Ce6-loaded liposomes (CD68-Ce6-mediated liposomes). Flow cytometry results indicated that Ce6-containing liposomes were more effective in promoting intracellular uptake after laser irradiation. Furthermore, CD68-modified liposomes significantly strengthened the cellular recognization and thus internalization. Different cell lines have been incubated with the liposomes, and the results showed that CD68-Ce6-mediated liposomes had no significant cytotoxicity to coronary artery endothelial cells (HCAEC) under selected conditions. Interestingly, they promoted autophagy in foam cells through the increase in LC3-Ⅰ, LC3-Ⅱ expression and the decrease in p62 expression, and restrained the migration of mouse aortic vascular smooth muscle cells (MOVAS) in vitro. Moreover, the enhancement of atherosclerotic plaque stability and the reduction in the cholesterol content by CD68-Ce6-mediated liposomes were dependent on transient reactive oxygen species (ROS) generated under laser irradiation. In summary, we demonstrated that CD68-Ce6-mediated liposomes, as a photosensitizer nano-drug delivery system, have an inhibitory effect on MOVAS migration and a promotion of cholesterol efflux in foam cells, and thereby, represent promising nanocarriers for atherosclerosis photodynamic therapy.

[Clinical and pathologic analysis of astrocytic tumors with loss of heterozygosity on chromosome 10q].

OBJECTIVE: To study the correlation between loss of heterozygosity (LOH) on chromosome 10q and pathologic features, pathogenesis, prognosis of astrocytic tumors. METHODS: LOH on 10q was studied by interphase fluorescence in-situ hybridization (FISH) in 85 cases of astrocytic tumor, including 35 cases of WHO grade II tumors and 50 cases of WHO grade IV tumors. RESULTS: LOH on 10q was detected in 6 cases (17.1%) of diffuse astrocytoma (WHO grade II) and 34 cases (68.0%) of glioblastoma (WHO grade IV). 10q polysomy was detected in 7 cases (20.0%) of diffuse astrocytoma and 11 cases (22.0%) of glioblastoma. The rates of LOH on 10q in young age group and elderly group were 36.4% (12/33) and 82.4% (28/34), respectively. The difference was of statistical significance (P < 0.05). The rates of LOH on 10q in the diffuse astrocytoma and glioblastoma were 21.4% (6/28) and 87.2% (34/39), respectively. The difference was also statistically significant (P < 0.05). Univariate survival analysis showed that patient age, pathologic grade and 10q on LOH correlated with duration of survival (P < 0.05). CONCLUSIONS: There are correlation between 10q LOH, patient age and pathologic grade of astrocytic tumors. LOH on 10q is also related to the pathogenesis of astrocytic tumors and is helpful in predicting prognosis.

Prognostic significance of sex determining region Y-box 2, E-cadherin, and vimentin in esophageal squamous cell carcinoma.

BACKGROUND: Sex determining region Y-box 2 (SOX2) can promote squamous cell carcinoma (SSC) because it regulates the migration and invasion of several different types of squamous carcinoma cells. However, few studies have examined the prognostic value of SOX2 and its effect on the epithelial-mesenchymal transition (EMT) in esophageal SSC (ESCC), a cancer characterized by high invasion and rapid metastasis. AIM: To verify the relationship of SOX2 and the EMT in ESCC and determine the prognostic value and significance of SOX2 and protein markers of the EMT in ESCC. METHODS: One hundred and eighty-five postsurgical ESCC patients were retrospectively examined. Immunohistochemistry was used to detect SOX2, E-cadherin, and vimentin in ESCC tissues. The chi-square test was used to determine the relationships of the expression of these proteins with clinical data. Kaplan-Meier survival curves were used to evaluate factors associated with overall survival (OS). RESULTS: SOX2 and vimentin had high expression in ESCC tissues and correlated with the depth of local carcinoma invasion. SOX2 expression had positive correlations with tumor size, vimentin expression, and the EMT, and a negative correlation with E-cadherin expression. Expression of SOX2 and vimentin had negative correlations with OS. SOX2 expression was an independent prognostic risk factor for poor OS in patients with ESCC. CONCLUSION: SOX2 expression was an independent risk factor for OS in patients with ESCC and its expression had a positive correlation with the expression of vimentin, a classic marker of the EMT. SOX2 promoted the migration and invasion of ESCC, and this may related to its effect on vimentin in promoting the EMT.

The Relationship between MACC1/c-Met/Cyclin D1 Axis Expression and Prognosis in ESCC.

BACKGROUND: Esophageal cancer is one of the most common malignant tumors of the digestive system, with high incidence and mortality. METHODS: Immunohistochemical method was used to detect the expression of MACC1, c-Met, and cyclin D1 in ESCC and its adjacent tissues. Statistical analysis was done by SPSS 23.0. RESULTS: The high expression of MACC1 and cyclin D1 was significantly correlated with tumor size. High c-Met expression was associated with patient ethnicity. MACC1 expression was positively correlated with both c-Met and cyclin D1. c-Met expression was also positively correlated with cyclin D1. Patients with high expression of MACC1 and c-Met had worse OS; patients with high c-Met expression also had worse PFS. CONCLUSION: MACC1, c-Met, and cyclin D1 proteins are closely related to the occurrence and development of esophageal squamous cell carcinoma. MACC1 may affect the prognosis of ESCC by regulating the expression of the c-Met/cyclin D1 axis.

[Application of serum proteomic patterns for the detection of esophageal carcinoma in Kazakh in Xinjiang].

OBJECTIVE: To detect the serum protein profiles of Kazakh's esophageal carcinoma (EC) patients in Xinjiang by SELDI-TOF-MS (surface enhanced laser desorption & ionization time-of-flight mass spectrometry) and build up a diagnostic model of Kazakh's EC in Xinjiang. METHODS: The serum samples from 41 Kazakh's EC patients and 20 Kazakh's healthy controls were collected and analyzed on weak cation exchange and hydrophobic surface protein chip by SELDI-TOF-MS technology. The differentially expressed markers of esophageal carcinoma were detected. RESULTS: The values of M/Zs were significantly different between Kazakh's EC patients and controls (P < 0.05). Among these, 6 proteins peaks were up-regulated (5495.2265, 15 964.6951, 16 152.0872, 4488.4818, 8164.7652, 4979.4223) and 4 down-regulated (6900.3285, 13 790.9241, 8790.8130, 8714.7915) in the Kazakh's EC group. According to cross validation, the model of Kazakh's EC made up of 7 proteins (M/Z 6900.3285, 13 790.9241, 8790.8130, 15 964.6951, 16 152.0872, 4488.4818, 4979.4223) was established. The sensitivity and specificity of this model were 100% (41/41) and 100% (20/20) respectively. CONCLUSION: The model with 7 proteins markers has a higher sensitivity and specificity for Kazakh's EC patients in Xinjiang. It may provide a new serum diagnostic tool for Kazakh's EC patients in Xinjiang.

[Correlation of amplification of chromosome 1 with histologic typing of thymic epithelial tumors].

OBJECTIVE: To study the correlation between amplification of chromosome 1 and histological typing and clinical staging of thymic epithelial tumors according to the WHO classification. METHODS: Amplification of chromosome 1 was detected by interphase fluorescence in-situ hybridization (FISH) in 60 cases of thymic epithelial tumors, including type A thymoma (2 cases), type AB (19 cases), B1 (4 cases), B2 (14 cases), B3 (11 cases), metaplastic thymoma (2 cases), and thymic carcinoma (8 cases) and 11 samples of normal thymus. RESULTS: Gain on chromosome 1 was found in 19 cases (31.7%) of thymic epithelial tumors, and none was detected in normal thymic tissues (P < 0.05). The positive rates of gain on chromosome 1 were statistically different among various histological subtypes of thymic epithelial tumors (P < 0.05), in which the highest rate of detection was in thymic carcinoma (6/8), the second, type B3 (6/11), followed by type A (1/2), type AB (4/19), type B2 (2/14) and type B1 (0). The positive rate of gain on chromosome 1 in type B3 had no statistical difference from thymic carcinoma (P > 0.05), but significantly higher than that in other types of thymoma (P < 0.05). In addition, the polysomy rate of chromosome 1 was significantly different among the thymic epithelial tumors at different clinical stages (P = 0.023), and that at stages III and IV was statistically higher than that in stages I and II (P = 0.003) but there was no significant difference between stage I and stage II tumors (P = 0.750). CONCLUSIONS: Gain on chromosome 1 is more common in thymic carcinoma and type B3 thymoma than that in other subtypes of thymic epithelial tumors. Thymoma of type B3 may have different genetic features from other subtypes. Detection of gain on chromosome 1 by FISH is helpful in the differential diagnosis and prediction of prognosis in patients with thymic epithelium tumors.

Effect of ticagrelor on acute kidney injury in septic rats and its underlying mechanism.

The aim of the present study was to determine whether the effects and underlying mechanisms of ticagrelor in a rat model of sepsis-induced acute kidney injury (AKI) were mediated via the CD62P pathway. A total of 15 rats were randomly assigned to the following groups: Normal, sham, cecal ligation and puncture (CLP), CLP + clinical dose of ticagrelor (CCD) and CLP + loading dose of ticagrelor (CLD). Ticagrelor was administered 12 h before modeling, immediately after modeling, and 12 h after modeling at a dose of 8.6 and 46.42 mg/kg in the CCD and CLD groups, respectively. Rats in the normal, sham and CLP groups were treated with the same volume of distilled water. Serum creatinine (SCr), CD62P and interleukin-1ß (IL-1ß) levels, myeloperoxidase (MPO) activity in the renal tissue and the apoptosis rate of renal cells were increased in the CLP group, compared with in the normal and sham groups (P<0.05). In addition, ticagrelor treatment reduced SCr, CD62P and IL-1ß expression levels, renal tissue MPO activity and renal cell apoptosis in rats with sepsis-induced AKI (P<0.05). CD62P expression was closely associated with the occurrence of sepsis-induced AKI. The mechanism of ticagrelor-mediated reductions in inflammation, renal neutrophil infiltration and renal cell apoptosis is possibly associated with reductions in CD62P expression.

Rice Glycosyltransferase Gene UGT85E1 Is Involved in Drought Stress Tolerance Through Enhancing Abscisic Acid Response.

Drought is one of the most important environmental constraints affecting plant growth and development and ultimately leads to yield loss. Uridine diphosphate (UDP)-dependent glycosyltransferases (UGTs) are believed to play key roles in coping with environmental stresses. In rice, it is estimated that there are more than 200 UGT genes. However, most of them have not been identified as their physiological significance. In this study, we reported the characterization of a putative glycosyltransferase gene UGT85E1 in rice. UGT85E1 gene is significantly upregulated by drought stress and abscisic acid (ABA) treatment. The overexpression of UGT85E1 led to an enhanced tolerance in transgenic rice plants to drought stress, while the ugt85e1 mutants of rice showed a more sensitive phenotype to drought stress. Further studies indicated that UGT85E1 overexpression induced ABA accumulation, stomatal closure, enhanced reactive oxygen species (ROS) scavenging capacity, increased proline and sugar contents, and upregulated expression of stress-related genes under drought stress conditions. Moreover, when UGT85E1 was ectopically overexpressed in Arabidopsis, the transgenic plants showed increased tolerance to drought as well as in rice. Our findings suggest that UGT85E1 plays an important role in mediating plant response to drought and oxidative stresses. This work may provide a promising candidate gene for cultivating drought-tolerant crops both in dicots and monocots.