Unlatching the Additional Zinc Storage Ability of Vanadium Nitride Nanocrystallites.

Vanadium-based materials, due to their diverse valence states and open-framework lattice, are promising cathodes for aqueous zinc ion batteries (AZIBs), but encounters the major challenges of in situ electrochemical activation process, potent polarity of the aqueous electrolyte and periodic expansion/contraction for efficient Zn2+ storage. Herein, architecting vanadium nitride (VN) nanosheets over titanium-based hollow nanoarrays skeletal host (denoted VNTONC) can simultaneously modulate address those challenges by creating multiple interfaces and maintaining the (1 1 1) phase of VN, which optimizes the Zn2+ storage and the stability of VN. Benefiting from the modulated crystalline thermodynamics during the electrochemical activation of VN, two outcomes are achieved; I) the cathode transforms into a nanocrystalline structure with increased active sites and higher conductivity and; II) a significant portion of the (1 1 1) crystal facets is retained in the process leading to the additional Zn2+ storage capacity. As a result, the as-prepared VNTONC electrode demonstrates remarkable discharge capacities of 802.5 and 331.8 mAh g-1 @ 0.5 and 6.0 A g-1 , respectively, due to the enhanced kinetics as validated by theoretical calculations. The assembled VNTONC||Zn flexible ZIB demonstrates excellent Zn storage properties up to 405.6 mAh g-1 , and remarkable robustness against extreme operating conditions.

Circulating Tumor Cell Phenotype Detection and Epithelial-Mesenchymal Transition Tracking Based on Dual Biomarker Co-Recognition in an Integrated PDMS Chip.

Circulating tumor cells (CTCs) are widely considered as a reliable and promising class of markers in the field of liquid biopsy. As CTCs undergo epithelial-mesenchymal transition (EMT), phenotype detection of heterogeneous CTCs based on EMT markers is of great significance. In this report, an integrated analytical strategy that can simultaneously capture and differentially detect epithelial- and mesenchymal-expressed CTCs in bloods of non-small cell lung cancer (NSCLS) patients is proposed. First, a commercial biomimetic polycarbonate (PCTE) microfiltration membrane is employed as the capture interface for heterogenous CTCs. Meanwhile, differential detection of the captured CTCs is realized by preparing two distinct CdTe quantum dots (QDs) with red and green emissions, attached with EpCAM and Vimentin aptamers, respectively. For combined analysis, a polydimethylsiloxane (PDMS) chip with simple structure is designed, which integrates the membrane capture and QDs-based phenotype detection of CTCs. This chip not only implements the analysis of the number of CTCs down to 2 cells mL-1, but enables EMT process tracking according to the specific signals of the two QDs. Finally, this method is successfully applied to inspect the correlations of numbers or proportions of heterogenous CTCs in 94 NSCLS patients with disease stage and whether there is distant metastasis.

Region-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans.

Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulation of the epigenome has been associated with increased susceptibility to age-related disorders. In this study, we aimed to characterize the age-dependent changes of the epigenome and, in turn, to understand epigenetic processes that drive aging phenotypes. We focused on the aging-associated changes in the repressive histone marks H3K9me3 and H3K27me3 in C. elegans. We observed region-specific gain and loss of both histone marks, but the changes are more evident for H3K9me3. We further found alteration of heterochromatic boundaries in aged somatic tissues. Interestingly, we discovered that the most statistically significant changes reflected H3K9me3-marked regions that are formed during aging, and are absent in developing worms, which we termed "aging-specific repressive regions" (ASRRs). These ASRRs preferentially occur in genic regions that are marked by high levels of H3K9me2 and H3K36me2 in larval stages. Maintenance of high H3K9me2 levels in these regions have been shown to correlate with a longer lifespan. Next, we examined whether the changes in repressive histone marks lead to de-silencing of repetitive DNA elements, as reported for several other organisms. We observed increased expression of active repetitive DNA elements but not global re-activation of silent repeats in old worms, likely due to the distributed nature of repetitive elements in the C. elegans genome. Intriguingly, CELE45, a putative short interspersed nuclear element (SINE), was greatly overexpressed at old age and upon heat stress. SINEs have been suggested to regulate transcription in response to various cellular stresses in mammals. It is likely that CELE45 RNAs also play roles in stress response and aging in C. elegans. Taken together, our study revealed significant and specific age-dependent changes in repressive histone modifications and repetitive elements, providing important insights into aging biology.

Depletion of ESCRT ameliorates APP-induced AD-like symptoms in Drosophila.

The amyloid-ß (Aß) peptide, produced from amyloid precursor protein (APP) by ß and γ-secretases, has been implicated in the etiology of Alzheimer's disease (AD). However, the precise intracellular trafficking pathway of APP and its subcellular locations to produce Aß have remained unclear. To address these issues, we established fly AD models that recapitulated multiple AD-like symptoms by expressing human APP in the Drosophila nerve system. The ESCRT (endosomal sorting complexes required for transport) machinery regulates the sorting and trafficking of endocytosed proteins, yet its role in AD pathogenesis has not been explored in vivo. We found that knockdown of distinct ESCRT components ameliorated APP-induced morphological and behavioral defects, including impaired wing expansion, eye degeneration, dopamine neuron loss, locomotor disability, lifespan shortening, and cognitive deficits. Mechanistically, we showed that impaired ESCRT impeded APP's intracellular transportation from early endosomes to late endosomes, resulting in reduced Aß production and amyloid deposit load. These data suggest that APP undergoes ESCRT-mediated endocytic trafficking, and Aß is generated mainly in late endosomes. Our data provide the first in vivo evidence to support a physiological role of ESCRT in AD pathogenesis, suggesting that interfering with ESCRT machinery might be an alternative therapeutic strategy for AD.

YY1 inactivated transcription co-regulator PGC-1α to promote mitochondrial dysfunction of early diabetic nephropathy-associated tubulointerstitial fibrosis.

The development of diabetic nephropathy (DN) could be promoted by the occurrence of tubulointerstitial fibrosis (TIF), which had a closely relationship with mitochondrial dysfunction of renal tubular epithelial cells (RTECs). As a key regulator of metabolic homeostasis, Yin Yang 1 (YY1) played an important role not only in regulating fibrosis process, but also in maintaining mitochondrial function of pancreatic ß cells. However, it was not clear whether YY1 participated in maintaining mitochondrial function of RTECs in early DN-associated TIF. In this study, we dynamically detected mitochondrial functions and protein expression of YY1 in db/db mice and high glucose (HG)-cultured HK-2 cells. Our results showed that comparing with the occurrence of TIF, the emergence of mitochondrial dysfunction of RTECs was an earlier even, besides the up-regulated and nuclear translocated YY1. Correlation analysis showed YY1 expressions were negatively associated with PGC-1α in vitro and in vivo. Further mechanism research demonstrated the formation of mTOR-YY1 heterodimer induced by HG upregulated YY1, the nuclear translocation of which inactivated PGC-1α by binding to the PGC-1α promoter. Overexpression of YY1 induced mitochondrial dysfunctions in normal glucose cultured HK-2 cells and 8-week-old db/m mice. While, dysfunctional mitochondria induced by HG could be improved by knockdown of YY1. Finally, downregulation of YY1 could retard the progression of TIF by preventing mitochondrial functions, resulting in the improvement of epithelial-mesenchymal transition (EMT) in early DN. These findings suggested that YY1 was a novel regulator of mitochondrial function of RTECs and contributed to the occurrence of early DN-associated TIF .

Identification of an Ultrathin Osteochondral Interface Tissue with Specific Nanostructure at the Human Knee Joint.

Cartilage adheres to subchondral bone via a specific osteochondral interface tissue where forces are transferred from soft cartilage to hard bone without conferring fatigue damage over a lifetime of load cycles. However, the fine structure and mechanical properties of the osteochondral interface tissue remain unclear. Here, we identified an ultrathin ∼20-30 µm graded calcified region with two-layered micronano structures of osteochondral interface tissue in the human knee joint, which exhibited characteristic biomolecular compositions and complex nanocrystals assembly. Results from finite element simulations revealed that within this region, an exponential increase of modulus (3 orders of magnitude) was conducive to force transmission. Nanoscale heterogeneity in the hydroxyapatite, coupled with enrichment of elastic-responsive protein-titin, which is usually present in muscle, endowed the osteochondral tissue with excellent mechanical properties. Collectively, these results provide novel insights into the potential design for high-performance interface materials for osteochondral interface regeneration.

A Turn-On Lipid Droplet-Targeted Near-Infrared Fluorescent Probe with a Large Stokes Shift for Detection of Intracellular Carboxylesterases and Cell Viability Imaging.

Carboxylesterases (CEs) play important physiological roles in the human body and are involved in numerous cellular processes. Monitoring CEs activity has great potential for the rapid diagnosis of malignant tumors and multiple diseases. Herein, we developed a new phenazine-based "turn-on" fluorescent probe DBPpys by introducing 4-bromomethyl-phenyl acetate to DBPpy, which can selectively detect CEs with a low detection limit (9.38 × 10-5 U/mL) and a large Stokes shift (more than 250 nm) in vitro. In addition, DBPpys can also be converted into DBPpy by carboxylesterase in HeLa cells and localized in lipid droplets (LDs), emitting bright near-infrared fluorescence under the irradiation of white light. Moreover, we achieved the detection of cell health status by measuring the intensity of NIR fluorescence after co-incubation of DBPpys with H2O2-pretreated HeLa cells, indicating that DBPpys has great potential applications for assessing CEs activity and cellular health.

Capture of Heterogeneous Circulating Tumor Cells in Colorectal Cancer Patients on an Immunomagnetic and Anti-Nonspecific Adsorption Platform.

Circulating tumor cells (CTC) have been represented by different phenotypes due to the epithelial-mesenchymal transition (EMT), which are epithelial CTC (E-CTC), mesenchymal CTC (M-CTC), and mixed (epithelial, mesenchymal) CTC (EM-CTC). Limited work has systematically discussed the associations of CTC number, especially proportions of E-CTC, M-CTC, and EM-CTC in total CTC, with colorectal cancer (CRC) progressions via a simple method with high performances. To achieve this goal, this paper presents the fabrication of a novel anti-nonspecific adsorption immunomagnetic platform called Fe3O4@SiO2@PTMAO@Aptamer, which was obtained by modifying polymeric trimethylamine N-oxide (PTMAO) on magnetic Fe3O4@SiO2, which was then linked with dual aptamers of an epithelial cellular adhesion molecule (EpCAM) and cell surface vimentin (CSV), targeting different CTC phenotypes. Results demonstrated that the abundant coating of PTMAO on Fe3O4@SiO2 improved the anti-nonspecific adsorption and noncell adhesion abilities of the immunomagnetic particles and could capture heterogeneous CTC with higher efficiency within 10 min. These excellent performances of Fe3O4@SiO2@PTMAO@Aptamer allowed us to inspect the correlations of numbers of E-CTC, M-CTC, EM-CTC, or proportions of them in total CTC with clinical information on CRC patients in detail. Our data innovatively and clearly revealed that the captured CTC, especially M-CTC proportion, displayed more close associations with progression, diagnosis, surgery, and chemotherapeutic effects for CRC patients. Overall, we believe that our approach will bring a new understanding of CTC-based liquid biopsy for cancer diagnosis and treatment.

Heterostructures Stimulate Electric-Field to Facilitate Optimal Zn2+ Intercalation in MoS2 Cathode.

The electric-field effect is an important factor to enhance the charge diffusion and transfer kinetics of interfacial electrode materials. Herein, by designing a heterojunction, the influence of the electric-field effect on the kinetics of the MoS2 as cathode materials for aqueous Zn-ion batteries (AZIBs) is deeply investigated. The hybrid heterojunction is developed by hydrothermal growth of MoS2 nanosheets on robust titanium-based transition metal compound ([titanium nitride, TiN] and [titanium oxide, TiO2 ]) nanowires, denoted TNC@MoS2 and TOC@MoS2 NWS, respectively. Benefiting from the heterostructure architecture and electric-field effect, the TNC@MoS2 electrodes exhibit an impressive rate performance of 200 mAh g-1 at 50 mA g-1 and cycling stability over 3000 cycles. Theoretical studies reveal that the hybrid architecture exhibits a large-scale electric-field effect at the interface between TiN and MoS2 , enhances the adsorption energy of Zn-ions, and increases their charge transfer, which leads to accelerated diffusion kinetics. In addition, the electric-field effect can also be effectively applied to TiO2 and MoS2 , confirming that the concept of heterostructures stimulating electric-field can provide a relevant understanding for the architecture of other cathode materials for AZIBs and beyond.

Chrysin enhances antitumour immunity response through the IL-12-STAT4 signal pathway in the B16F10 melanoma mouse model.

Chrysin (CHR) is a flavonoid with extensive pharmacological activity. The molecular formula of CHR is C15 H10 O4 . CHR is reported to have antioxidative, antitumour and antiviral functions. To evaluate its potential function as a vaccine adjuvant, we prepared a melanoma vaccine using a soluble protein extract of B16F10 melanoma cells as antigen and CHR as an adjuvant. The melanoma model was developed after two immunizations, and it was discovered that combining B16F10 soluble protein antigen-mixed CHR vaccine could inhibit tumour growth in the mouse model, and the overall survival rate was higher than that of the B16F10 antigen vaccine alone. In vivo and in vitro experiments were conducted to determine whether CHR functioned as an adjuvant by activating antigen-presenting cells (APCs). We discovered that CHR activated APCs both in vivo and in vitro and may enhance Th1 cell function by activating the IL12-STAT4 signal pathway, thereby enhancing the antitumour response of cytotoxic T lymphocytes (CTLs) in vivo. Next, to verify the critical role of CD8+ T cells in suppressing melanoma development, we transplanted CD8+ T cells from immunized mice to B16F10 tumour-bearing mice and discovered that the survival rate of tumour-bearing mice was significantly prolonged. In summary, our experimental results indicate that CHR can be used as a potential adjuvant to enhance antigen immunogenicity, inhibit B16F10 tumour growth in mice and improve tumour immune response.

Mesenchymal stem cells regulate type 2 innate lymphoid cells via regulatory T cells through ICOS-ICOSL interaction.

Group 2 innate lymphoid cells (ILC2s) are recognized as key controllers and effectors of type 2 inflammation. Mesenchymal stem cells (MSCs) have been shown to alleviate type 2 inflammation by modulating T lymphocyte subsets and decreasing TH 2 cytokine levels. However, the effects of MSCs on ILC2s have not been investigated. In this study, we investigated the potential immunomodulatory effects of MSCs on ILC2s in peripheral blood mononuclear cells (PBMCs) from allergic rhinitis patients and healthy subjects. We further investigated the mechanisms involved in the MSC modulation using isolated lineage negative (Lin- ) cells. PBMCs and Lin- cells were cocultured with induced pluripotent stem cell-derived MSCs (iPSC-MSCs) under the stimulation of epithelial cytokines IL-25 and IL-33. And the ILC2 levels and functions were examined and the possible mechanisms were investigated based on regulatory T (Treg) cells and ICOS-ICOSL pathway. iPSC-MSCs successfully decreased the high levels of IL-13, IL-9, and IL-5 in PBMCs in response to IL-25, IL-33, and the high percentages of IL-13+ ILC2s and IL-9+ ILC2s in response to epithelial cytokines were significantly reversed after the treatment of iPSC-MSCs. However, iPSC-MSCs were found directly to enhance ILC2 levels and functions via ICOS-ICOSL interaction in Lin- cells and pure ILC2s. iPSC-MSCs exerted their inhibitory effects on ILC2s via activating Treg cells through ICOS-ICOSL interaction. The MSC-induced Treg cells then suppressed ILC2s by secreting IL-10 in the coculture system. This study revealed that human MSCs suppressed ILC2s via Treg cells through ICOS-ICOSL interaction, which provides further insight to regulate ILC2s in inflammatory disorders.

Decreased Sirt3 contributes to cyclic production of reactive oxygen species and islet ß-cell apoptosis in high glucose conditions.

BACKGROUND: Reactive oxygen species (ROS) plays a vital role in the apoptosis of islet ß-cells in type 2 diabetes mellitus (T2DM). Sirt3 (Sirtuin 3, a deacetylase) and FoxO1 (a transcription factor) might be involved in ROS production. This study was to investigate mechanism of ROS production and ß-cell apoptosis in T2DM. METHODS: Oxidative stress and apoptosis in islets of db/db mice and high glucose cultured ß-cells were observed by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay and western blotting. Then, H2O2 was used to ascertain the effect of ROS on the expression of Sirt3. Meanwhile, FoxO1, antioxidant enzymes - catalase (CAT) and manganese superoxide dismutase (MnSOD) and ß-cell apoptosis were also determined by western blotting. Finally, Sirt3 was knocked down to evaluate the effect on oxidative stress and apoptosis of ß-cells. RESULTS: Under high glucose environment, enhanced ROS made a decrease of Sirt3 expression, which increased acetylation of FoxO1, thus reduced the expression of its target proteins -MnSOD and CAT, and further significantly increased ROS levels. Increased ROS finally led to the apoptosis of ß-cells. CONCLUSION: Down-regulation of Sirt3 plays an important role in the cyclic production of ROS and ß-cell apoptosis. Targeting Sirt3 may be favorable for the treatment of T2DM.

Sleep quality, caregiver burden, and individual resilience among parents of children with epilepsy.

PURPOSE: Parents caring for children with epilepsy have poor sleep quality and experience a certain level of caregiving burden. Individual resilience is a crucial psychological variable that contributes to health during extraordinary challenges. This study aimed to determine the relationships among individual resilience, caregiver burden, and sleep quality. METHODS: This was a descriptive cross-sectional study with a convenience sample, following the STROBE guidelines. One hundred and ninety-one parents of children with epilepsy were invited to participate in the study. Of these, 173 participants completed measures of sleep quality, caregiver burden, and individual resilience. Path analysis was performed to probe the indirect relationship between individual resilience and sleep quality via caregiver burden. RESULTS: Correlation analysis revealed that individual resilience total scores were significantly and marginally negatively correlated with caregiver burden and sleep quality total scores (r = -0.215, P <.01; r = -0.250, P <.01). Moreover, there was a significant moderate positive correlation between the total caregiver burden scores and total sleep quality scores (r = 0.389, P <.001). The path model showed that individual resilience is indirectly associated with sleep quality via caregiver burden. CONCLUSION: The higher the level of individual resilience, the less the caregiver burden and the better the sleep quality for parents of children with epilepsy.

Conversion from rice fields to vegetable fields alters product stoichiometry of denitrification and increases N2O emission.

Information about effects of conversion from rice fields to vegetable fields on denitrification process is still limited. In this study, denitrification rate and product ratio (i.e., N2O/(N2O + N2) ratio) were investigated by soil-core incubation based N2/Ar technique in one rice paddy field (RP) and two vegetable fields (VF4 and VF7, 4 and 7 years vegetable cultivating after conversion from rice fields, respectively). Genes related to denitrification and bacterial community composition were quantified to investigate the microbial mechanisms behind the effects of land-use conversion. The results showed that conversion of rice fields to vegetable fields did not significantly change denitrification rate although the abundance of denitrification related genes was significantly reduced by 79.22%-99.84% in the vegetable soils. Whereas, compared with the RP soil, N2O emission rate was significantly (P < 0.05) increased by 53.5 and 1.6 times in the VF4 and VF7 soils, respectively. Correspondingly, the N2O/(N2O + N2) ratio increased from 0.18% (RP soil) to 5.65% and 0.65% in the VF4 and VF7 soils, respectively. These changes were mainly attributed to the lower pH, higher nitrate content, and the altered bacterial community composition in the vegetable soils. Overall, our results showed that conversion of rice fields to vegetable fields increased the N2O emission rate and altered the product ratio of denitrification. This may increase the contribution of land-use conversion to global warming and stratospheric ozone depletion.

Depression and Opioid Misuse in Elderly Individuals With Chronic Pain: A Latent Class Analysis.

BACKGROUND: Chronic pain patients tend to have comorbid depressive symptoms, and empirical data investigating differences related to depressive symptoms classes and opioid misuse are scant. AIMS: The aim of this study was to identify heterogeneous depressive symptoms trajectories in elderly individuals with chronic pain who take opioids, and investigate the association between depressive symptoms subgroups and opioid misuse. DESIGN: Secondary data analysis of a cross-sectional study. SETTINGS: Twelve communities were selected from a city in Shandong Province, China, using multi-stage cluster sampling. PARTICIPANTS/SUBJECTS: Individuals aged ≥60 years with self-reported chronic pain lasting more than one year and who took opioids under prescription were screened. METHODS: Latent class analysis was used to identify homogeneous depressive symptoms groups within the elderly population with chronic pain. Multinomial logistic regression, and one-way analysis of variance were also performed. RESULTS: The best-fitted model suggested three depressive symptoms subgroups: "Impaired Memory," "Perceived Stress in Life and Work," and "Low Mood." Age, education level, and marital status were depression risk factors. The odds of opioid misuse varied among the depressive symptoms subgroups. CONCLUSIONS: These findings may help improve depressive symptoms and chronic pain management by identifying high-risk elderly individuals for early intervention and personalizing treatment according to the depressive symptoms subgroup and severity of opioid misuse.

Ultrasonic-Assisted Method for the Preparation of Carbon Nanotube-Graphene/Polydimethylsiloxane Composites with Integrated Thermal Conductivity, Electromagnetic Interference Shielding, and Mechanical Performances.

Due to the rapid development of the miniaturization and portability of electronic devices, the demand for polymer composites with high thermal conductivity and mechanical flexibility has significantly increased. A carbon nanotube (CNT)-graphene (Gr)/polydimethylsiloxane (PDMS) composite with excellent thermal conductivity and mechanical flexibility is prepared by ultrasonic-assisted forced infiltration (UAFI). When the mass ratio of CNT and Gr reaches 3:1, the thermal conductivity of the CNT-Gr(3:1)/PDMS composite is 4.641 W/(m·K), which is 1619% higher than that of a pure PDMS matrix. In addition, the CNT-Gr(3:1)/PDMS composite also has excellent mechanical properties. The tensile strength and elongation at break of CNT-Gr(3:1)/PDMS composites are 3.29 MPa and 29.40%, respectively. The CNT-Gr/PDMS composite also shows good performance in terms of electromagnetic shielding and thermal stability. The PDMS composites have great potential in the thermal management of electronic devices.

Multifunctional Metal-Organic Framework as a Versatile Nanoplatform for Aß Oligomer Imaging and Chemo-Photothermal Treatment in Living Cells.

In view of the close association of ß-amyloid oligomers (AßO) with the clinical development of Alzheimer's disease (AD) symptoms, it is urgent to design a promising sensing and therapeutic strategy that can target AßO for preventing or delaying the onset of AD. Herein, a core-shell nanocomposite CeONP-Res-PCM@ZIF-8/polydopamine (PDA) was synthesized through an in situ encapsulated strategy, in which resveratrol (Res), ceria nanoparticles (CeONPs), and PCM (tetradecanol) were embedded into the ZIF-8/PDA matrix via a water-based mild approach. Using the AßO aptamer, the ability of CeONP-Res-PCM@ZIF-8/PDA/Apt as the fluorescent sensing platform for AßO detection and intracellular imaging was demonstrated. The nanocomposite was high in Res loading (27.5%) and could be activated to release the encapsulated Res upon illumination with NIR through PCM regulation. Moreover, due to the synergetic interactions of PDA, CeONPs, and Res in one system, CeONP-Res-PCM@ZIF-8/PDA/Apt nanocomposites exhibited multifunctional effects on inhibiting Aß aggregation, degrading Aß fibrils, and alleviating Aß-induced oxidative stress and neural apoptosis. These therapeutic effects could be enhanced under NIR irradiation by virtue of the excellent photothermal property of PDA. As far as we know, there is no report of using ZIF-8-based materials for simultaneous sensing and therapeutic applications. This work boosted the development of multifunctional nanoagents for biomedical research studies.

Targeting the ILK/YAP axis by LFG-500 blocks epithelial-mesenchymal transition and metastasis.

Metastasis is the main cause of mortality in patients with cancer. Epithelial-mesenchymal transition (EMT), a crucial process in cancer metastasis, is an established target for antimetastatic drug development. LFG-500, a novel synthetic flavonoid, has been revealed as a potential antitumor agent owing to its various activities, including modulation of EMT in the inflammatory microenvironment. Here, using a transforming growth factor beta (TGF-ß)-induced EMT models, we found that LFG-500 inhibited EMT-associated migration and invasion in human breast cancer, MCF-7, and lung adenocarcinoma, A549, cell lines, consistent with the observed downregulation of YAP activity. Further studies demonstrated that LGF-500-induced suppression of YAP activation was mediated by integrin-linked kinase (ILK), suggesting that the ILK/YAP axis might be feasible target for anti-EMT and antimetastatic treatments, which was verified by a correlation analysis with clinical data and tumor specimens. Hence, our data support the use of LGF-500 as an antimetastatic drug in cancer therapy and provide evidence that the ILK/YAP axis is a feasible biomarker of cancer progression and a promising target for repression of EMT and metastasis in cancer therapy.

Cytidine deaminase 435C>T polymorphism relates to gemcitabine-platinum efficacy and hematological toxicity in Chinese non-small-cell lung cancer patients.

CDA 435C>T is reported as a functional SNP but there is no relevant research on the efficacy/hematological toxicity of gemcitabine-platinum treatment in Chinese non-small-cell lung cancer (NSCLC) patients. In this study, 63 patients who received radical resection (stage IB or IIIA) and 100 advanced NSCLC (stage IIIB or IV) patients have been collected, and all were treated with gemcitabine-platinum regimens from February of 2017 to February 2019. CDA 435C>T polymorphisms have been detected by PCR and direct sequencing. CT scan results and blood routine examinations have been collected to evaluate the efficacy and hematological toxicity. Then the relationships have been analyzed about CDA 435C>T. We found that T allele carriers have better therapy response (p<0.05). Patients carrying CDA 435C/T or T/T genotypes are statistically associated with a better efficacy (p<0.05) but are more prone to leukopenia (p<0.05). Although there is no difference in grade III-IV hematologic toxicity of 163 patients (p>0.05), in the case of 100 stage IIIB-IV patients, the CDA 435C/T and T/T have an increased risk (p<0.05). Regarding the CDA 435C>T polymorphism in the Chinese population, in patients with the mutant T allele, gemcitabine is more effective, but they are more prone to suffering from hematological toxicity, especially the late-stage patients.

Quantitative Assessment of the Pupil: An Underrecognized Yet Important Factor Related to Orbital Blowout Fracture Repair.

PURPOSE: To investigate dynamic pupil changes after orbital blowout fracture repair. To compare postoperative changes in under photopic and mesopic pupil size and center position after orbital blowout fracture repair surgery. METHODS: The study evaluated 19 eyes. Pupils were imaged for pupil size and center position before and 3 months after orbital blowout fracture repair surgery. Pupil size changes were measured, and the correlation between preoperative and postoperative pupil centroid shift was evaluated. RESULTS: After repair, operative eyes exhibited a growth of 9.3% ±â€Š8.6% in pupil size, and contralateral eyes showed a growth of 8.6% ±â€Š8.2% (P = 0.011, P = 0.007). Similar findings were noted in mesopic conditions. Under mesopic conditions, the pupil of operative eyes in medial orbital wall fracture deviated 0.030 ±â€Š0.019 mm towards the nasal side along the X-axis (P = 0.031). The postoperative orbital floor fracture group demonstrated statistical significance at a spatial frequency of 5 (P = 0.041). CONCLUSIONS: Orbital blowout fracture repair surgery affects pupil size and center position.