Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission.

Anaplastic thyroid carcinoma (ATC) has a 100% disease-specific mortality rate. The JAK1/2-STAT3 pathway presents a promising target for treating hematologic and solid tumors. However, it is unknown whether the JAK1/2-STAT3 pathway is activated in ATC, and the anti-cancer effects and the mechanism of action of its inhibitor, ruxolitinib (Ruxo, a clinical JAK1/2 inhibitor), remain elusive. Our data indicated that the JAK1/2-STAT3 signaling pathway is significantly upregulated in ATC tumor tissues than in normal thyroid and papillary thyroid cancer tissues. Apoptosis and GSDME-pyroptosis were observed in ATC cells following the in vitro and in vivo administration of Ruxo. Mechanistically, Ruxo suppresses the phosphorylation of STAT3, resulting in the repression of DRP1 transactivation and causing mitochondrial fission deficiency. This deficiency is essential for activating caspase 9/3-dependent apoptosis and GSDME-mediated pyroptosis within ATC cells. In conclusion, our findings indicate DRP1 is directly regulated and transactivated by STAT3; this exhibits a novel and crucial aspect of JAK1/2-STAT3 on the regulation of mitochondrial dynamics. In ATC, the transcriptional inhibition of DRP1 by Ruxo hampered mitochondrial division and triggered apoptosis and GSDME-pyroptosis through caspase 9/3-dependent mechanisms. These results provide compelling evidence for the potential therapeutic effectiveness of Ruxo in treating ATC.

Metal nanoparticles as a promising technology in targeted cancer treatment.

Traditional anticancer treatments have several limitations, but cancer is still one of the deadliest diseases. As a result, new anticancer drugs are required for the treatment of cancer. The use of metal nanoparticles (NPs) as alternative chemotherapeutic drugs is on the rise in cancer research. Metal NPs have the potential for use in a wide range of applications. Natural or surface-induced anticancer effects can be found in metals. The focus of this review is on the therapeutic potential of metal-based NPs. The potential of various types of metal NPs for tumor targeting will be discussed for cancer treatment. The in vivo application of metal NPs for solid tumors will be reviewed. Risk factors involved in the clinical application of metal NPs will also be summarized.

Anterior segment OCT application in quantifying posterior capsule opacification severity with varied intraocular lens designs.

AIM: To evaluate the application of anterior segment-optical coherence tomography (AS-OCT) in posterior capsule opacification (PCO) severity assessment and analyse the relationship between PCO severity and intraocular lens (IOL) characters. METHODS: PCO patients were prospectively recruited. Cross-sectional images of the anterior segment at horizontal and vertical meridians were acquired with AS-OCT. The area of the IOL-PC (posterior capsular) space and PCO severity (area, thickness, and density at 3 mm and 5 mm IOL optic regions) were measured. The relationship between PCO severity and visual acuity, comparisons of PCO severity and IOL-PC space using varied IOL designs were analysed. RESULTS: One hundred PCO eyes were enrolled. IOL-PC space, PCO thickness and area were positively correlated with axial length. In addition, PCO area and thickness were positively correlated with visual acuity when it was ≤0.52 logMAR. The cut-off level of visual acuity should be 0.52 logMAR. With varied IOL designs, 3-piece C haptic IOL showed a smaller PCO area and thickness than the 1-piece 3 haptic IOL and 1-piece 4 haptic IOL. PCO area and thickness values for an IOL with a diameter ≤11.0 mm was greater than for an IOL with a diameter of 12.5 mm, and the differences were statistically significant. PCO area and thickness increased when IOL haptic angulation increased (from 0 to 12 degrees). CONCLUSION: In PCO eyes, cut-off level of visual acuity is 0.52 logMAR. With more severe PCO, visual acuity maybe not enough to describe the visual function impairment. PCO severity and IOL-PC space are significantly correlated with axial length and IOL design and material.

[Characteristics and Significance of Stable Isotopes and Hydrochemistry in Surface Water and Groundwater in Nanxiaohegou Basin].

The Nanxiaohegou basin is a typical watershed in the gully region of the Loess Plateau, China. The stable isotopes of hydrogen and oxygen and the hydrochemistry of the surface water and groundwater in the region were characterized in this study. The interaction between the surface water and groundwater in the region was demonstrated based on stable isotopes and hydrochemical methods. Results show that the δD and δ18O values of precipitation change according to the seasons with high values in spring and summer and low values in autumn and winter. The δD and δ18O values of the reservoir water are higher in summer and autumn, while they are lower in the winter and spring. The seasonal variation of δD and δ18O in groundwater is not significant. The surface water and groundwater in the watershed mainly belong to Na·Mg-HCO3-type water. The hydraulic conductivity of surface water and groundwater is characterized by high values in winter and low values in summer. Results on stable isotopes and hydrochemistry indicate that local precipitation and deep groundwater may be the main recharge sources of surface water (reservoir water, channel water) and spring water in the Nanxiaohegou basin. The perennial spring in the basin may be mainly replenished by deep groundwater, while seasonal springs are replenished by deep groundwater and local precipitation, such as the springs of Dongzhuanggou and Yangjiagou sub-basins. This study provides a greater understanding of the hydrological processes in the gully region of the Loess Plateau.

CD8+ cytotoxic and FoxP3+ regulatory T lymphocytes serve as prognostic factors in breast cancer.

BACKGROUND: There is conflicting evidence regarding the prognostic value of cytotoxic T cell infiltration in breast cancer. The aims of this study were to detect the expression levels and localization of FoxP3 and CD8 in invasive ductal carcinoma of the breast and to investigate the correlations among FoxP3+ regulatory T cells (Tregs), CD8+ cytotoxic T lymphocytes (CTLs), clinicopathological features, and prognosis in patients with breast cancer. METHODS: Immunohistochemistry was used to detect the expression levels and localization of FoxP3 and CD8. One-sample t-test, one-way analysis of variance, and Kaplan-Meier log-rank tests were used to analyze correlations between the expression levels of CD8 and FoxP3; Kaplan-Meier Log-rank test was used to analyze clinicopathological features to explore the prognostic significance of CD8 and FoxP3 in patients with breast cancer. RESULTS: FoxP3 expression in the tumor bed was higher than that in the stroma, while CD8 was primarily expressed in the stroma. CD8 expression was associated with favorable prognostic factors. However, FoxP3 expression and an increased ratio of total FoxP3+ Tregs to CD8+ CTLs were significantly correlated with unfavorable prognostic factors. Additionally, an increased ratio was associated with molecular subtypes (ER+Her2+, ER+Her2-, ER-Her2+, and ER-Her2-) of breast cancer. Overexpression of FoxP3 and a high FoxP3+/CD8+ ratio were correlated with poor overall survival (OS) and disease-free survival (DFS). However, CD8 expression only affected OS in patients with breast cancer. CONCLUSIONS: Tumor-infiltrating lymphocytes are localized variously depending on the subtype. CD8+ CTLs were associated with a good prognosis, while FoxP3+ Tregs were associated with adverse outcomes in patients with breast cancer. CD8+ CTLs and FoxP3+ Tregs are potential predictive prognostic factors for patients with breast cancer.

Quantitative analysis of chloramphenicol, thiamphenicol, florfenicol and florfenicol amine in eggs via liquid chromatography-electrospray ionization tandem mass spectrometry.

A widely applicable method involving liquid chromatography-electrospray ionization tandem triple quadrupole mass spectrometry (LC-ESI/MS/MS) was developed for the simultaneous determination of chloramphenicol, thiamphenicol, florfenicol, and florfenicol amine in eggs. Samples were extracted with ethyl acetate-acetonitrile-ammonium hydroxide (49:49:2, v/v) and defatted with hexane saturated with acetonitrile. The analysis was carried out on a mass spectrometer via an electrospray interface operated in the positive and negative ionization modes using deuterated chloramphenicol-d5 as the internal standard. The limits of detection and limits of quantification were 0.04-0.5 µg/kg and 0.1-1.5 µg/kg in eggs, respectively. The average recoveries of the four analytes from egg samples were 90.84-108.23%, with relative standard deviations of less than 9.61%. The corresponding intra-day and inter-day variations were found to be less than 8.11% and 11.30%, respectively. Finally, the new approach was successfully applied to the quantitative determination of these analytes in 50 commercial eggs from local supermarkets.

[From random mutagenesis to precise genome editing: the development and evolution of genome editing techniques in Drosophila].

Drosophila melanogaster, an important model organism for studying life science, has contributed more to the research of genetics, developmental biology and biomedicine with the development of genome editing techniques. Drosophila genome-editing techniques have evolved from random mutagenesis to precise genome editing and from simple mutant construction to diverse genome editing methods since the 20th century. Chemical mutagenesis, using Ethyl methanesulfonate (EMS), is an important technique to study gene function in forward genetics, however, the precise knockout of Drosophila genes could not be achieved. The gene targeting technology, based on homologous recombination, has accomplished the precise editing of Drosophila genome for the first time, but with low efficiency. The CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein)-mediated precise genome editing is simple, fast and highly efficient compared with the gene targeting technology in Drosophila. In this review, we focus on Drosophila gene knockout, and summarize the evolution of genome editing techniques in Drosophila, emphasizing the development and applications of gene targeting, zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN) and CRISPR/Cas9 techniques.

Effects of Notch-1 down-regulation on malignant behaviors of breast cancer stem cells.

This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer.

Comparison of the Retinal Straylight in Pseudophakic Eyes with PMMA, Hydrophobic Acrylic, and Hydrophilic Acrylic Spherical Intraocular Lens.

Purpose. To investigate the intraocular straylight value after cataract surgery. Methods. In this study, 76 eyes from 62 patients were subdivided into three groups. A hydrophobic acrylic, a hydrophilic acrylic, and a PMMA IOL were respectively, implanted in 24 eyes, 28 eyes, and 24 eyes. Straylight was measured using C-Quant at 1 week and 1 month postoperatively in natural and dilated pupils. Results. The hydrophilic acrylic IOLs showed significantly lower straylight values than those of the hydrophobic acrylic IOLs in dilated pupils at 1 week and 1 month after surgery (P < 0.05). However, the straylight values of the hydrophilic acrylic IOLs were the lowest among the three IOL groups. No significant difference was observed in straylight between 1 week and 1 month postoperatively in each group with natural and dilated pupils (P > 0.05). Moreover, no significant difference was found in straylight between natural and dilated pupils in each group at 1 week and 1 month postoperatively (P > 0.05). Conclusions. Although the hydrophobic acrylic IOL induced more intraocular straylight, straylight differences among the 3 IOLs were minimal. Pupil size showed no effect on intraocular straylight; the intraocular straylight was stable 1 week after surgery.

[The value of Pentacam in diagnosis of intralenticular foreign body].

OBJECTIVE: To study the value of Pentacam in the diagnosis and localization of intralenticular foreign body. METHODS: It was a comparative study. In this retrospective study, 9 cases with intralenticular foreign bodies were examined by using slit-lamp, B-mode ultrasound, ultrasound biomicroscopy (UBM), CT and Pentacam. The results were confirmed by operation. RESULTS: Foreign bodies in 4 cases were detected by slit-lamp, with 1 case suspected; 5 cases by B-mode ultrasound; and 6 cases by UBM, CT and Pentacam. Projectile foreign bodies penetrated cornea and were remained in the lens in all 9 cases. In all cases, Pentacam detected all related signs of intralenticular foreign body, including corneal wound of entry, wound or organized wound in the anterior lens capsule, bulge of cortex lentis and traumatic cataract. Pentacam also could localize the meridian of foreign body precisely and could recognize the relationship between foreign body and neighbour tissues. But it was difficult to recognize the nature of foreign body. The measured size of foreign bodies in Pentacam image was a little smaller than the actual size. CONCLUSIONS: Pentacam has a valuable role in the diagnosis of intralenticular foreign body and the related damages. Pentacam could indicate precise location of intralenticular foreign body. Combined with multiple image-related methods. Pentacam can provide accurate and comprehensive information in the diagnosis and localization of intralenticular foreign body.

[Distribution character of synthetic musks in urban sewage sludges].

The characteristics of occurrence and distribution of 8 synthetic musks in 15 sewage sludges in Shanghai were studied. The results indicated that HHCB and AHTN were the two main components in all sludges, with the mean concentration of 2.92 mg x kg(-1) (0.81-6.39 mg x kg(-1)) and 1.96 mg x kg(-1) (0.35-3.11 mg x kg(-1)), respectively; and the concentrations of ADBI, AHMI, MK were less. The distributions detected in sludges are in accordance with the usage patterns in China. Total concentrations of 8 synthetic musks were ranged from 1.16-9.57 mg x kg(-1), which were lower than the results in previous studies. Concentrations in sludges are influenced by ratio of domestic wastewater in influent, sewage load and sewage treatment methods. The good linear relationships among HHCB, AHTN and ADBI indicate that these components have the same source: domestic wastewater. The consumption rates of HHCB and AHTN connected to per inhabitant in Shanghai region were estimated, which are low compared with those found in European. The potential impacts on agricultural soil were also assessed.