Quantitative evaluation of breast density using a dual-energy technique on a digital breast tomosynthesis system.

PURPOSE: Although breast density is considered a strong risk factor of breast cancer, its quantitative assessment is difficult. To investigate a quantitative method of measuring breast density using dual-energy mammographic imaging with central digital breast tomosynthesis in physically uniform and nonuniform phantoms. MATERIAL AND METHODS: The dual-energy imaging unit used a tungsten anode and silver filter with 30 kVp for high-energy images and 20 kVp for low-energy images. Uniform glandular-equivalent phantoms were used to calibrate a dual-energy based decomposition algorithm. The first study used uniform breast phantoms which ranged in thicknesses from 20 to 70 mm, in 10-mm increments, and which provided 30%, 50%, and 70% of breast density. The second study used uniform phantoms ranging from 10% to 90% of breast density. The third study used non-uniform phantoms (at an average density of 50%) with a thickness which ranged from 20 to 90 mm, in 10-mm increments. RESULTS: The root mean square error of breast density measurements was 2.64-3.34% for the uniform, variable thickness phantoms, 4.17% for the uniform, variable density phantoms, and 4.49% for the nonuniform, variable thickness phantoms. CONCLUSION: The dual-energy technique could be used to measure breast density with a margin of error of < 10% using digital breast tomosynthesis.

The role of conformational heterogeneity in regulating the apoptotic activity of BAX protein.

While activation of BAX is required for initiating mitochondria-mediated apoptosis, the underlying mechanisms remain unsettled. We studied conformations of BAX protein using pressure- and temperature-resolved ESR techniques and obtained the thermodynamic properties of the conformations. We show that inactive BAX is structurally heterogeneous and exists in equilibrium between two major populations of the conformations, UM and UM', of which the former is thermodynamically favored at room temperature. An increase in the population of UM', induced by either pressure or point mutations of BAX, renders BAX susceptible to oligomerization, which leads to cell death. This study uncovers the biological significance of BAX conformations and shows that the pro-apoptotic activity of BAX can be triggered by altering the equilibrium between the two states. It suggests that therapeutic intervention may focus on shifting the balance in the conformational heterogeneity.

Overexpression of stathmin 1 confers an independent prognostic indicator in nasopharyngeal carcinoma.

Data mining on public domain identified that stathmin 1 (STMN1) transcript was significantly higher expressed in nasopharyngeal carcinoma (NPC). Also known as the oncoprotein 18, STMN1 performs an important function in regulating rapid microtubule remodeling of the cytoskeleton in response to the cellular conditions. Immunoexpression of STMN1 was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcome was correlated with clinicopathological features and patient survivals. Results indicated that high STMN1 expressions (50 %) were correlated with advanced age (p = 0.027), higher T stage (p = 0.003), and overall clinical stage (p = 0.006) by the 7th American Joint Committee of Cancer Staging. In multivariate analyses, high STMN1 expression emerged as an independent prognosticator for worse disease-specific survival (p = 0.001), distal metastasis-free survival (p = 0.003), and local recurrence-free survival (p = 0.006). Exogenous expression of E2F transcription factor 1 (E2F1) or/and its dimeric partner, transcription factor Dp-1 (TFDP1), notably induced the STMN1 protein level in a NPC-derived cell line, TW01. Accordingly, high STMN1 protein level is commonly associated with adverse prognosticators and confers tumor aggressiveness in patients with NPC, and its upregulation might be attributed to E2F1 and/or TFDP1 transactivation.

Mesopores provide an amorphous state suitable for studying biomolecular structures at cryogenic temperatures.

In nano-confinements, aqueous solutions can be found to remain in a liquid state at subfreezing temperatures. The finding provides a means of entering into previously inaccessible temperature regions for studying the dynamics and structure of bulk liquid. Here we show that studying biomolecular structures in nano-confinements improves the accuracy of cryostructures and provides better insight into the relationship between hydration water and biomolecules. Synthetic prion protein peptides are studied in two experimental conditions: (i) in confined nanochannels within mesoporous materials, and (ii) in vitrified bulk solvents, with a temperature range of 50-275 K, using cw/pulse ESR techniques. A large inhomogeneous lineshape broadening is only observed for the spectra from the vitrified bulk solvent below 70 K, suggesting a possible peptide clustering in the solution. The spin-counting and distance measurements by DEER-ESR provide further evidence that peptides are dispersed homogeneously in mesopores but heterogeneously in vitrified solvents wherein the biomolecular structure is disturbed due to heterogeneity in the bulk solvent structure. Our study demonstrates that the nanospace within mesoporous materials provides an amorphous environment that is better than vitrified bulk solvent for studying biostructures at cryogenic temperatures.

Longitudinal artificial intelligence-based deep learning models for diagnosis and prediction of the future occurrence of polyneuropathy in diabetes and prediabetes.

OBJECTIVE: The objective of this study was to develop artificial intelligence-based deep learning models and assess their potential utility and accuracy in diagnosing and predicting the future occurrence of diabetic distal sensorimotor polyneuropathy (DSPN) among individuals with type 2 diabetes mellitus (T2DM) and prediabetes. METHODS: In 394 patients (T2DM=300, Prediabetes=94), we developed a DSPN diagnostic and predictive model using Random Forest (RF)-based variable selection techniques, specifically incorporating the combined capabilities of the Clinical Toronto Neuropathy Score (TCNS) and nerve conduction study (NCS) to identify relevant variables. These important variables were then integrated into a deep learning framework comprising Convolutional Neural Networks (CNNs) and Long Short-Term Memory (LSTM) networks. To evaluate temporal predictive efficacy, patients were assessed at enrollment and one-year follow-up. RESULTS: RF-based variable selection identified key factors for diagnosing DSPN. Numbness scores, sensory test results (vibration), reflexes (knee, ankle), sural nerve attributes (sensory nerve action potential [SNAP] amplitude, nerve conduction velocity [NCV], latency), and peroneal/tibial motor NCV were candidate variables at baseline and over one year. Tibial compound motor action potential amplitudes were used for initial diagnosis, and ulnar SNAP amplitude for subsequent diagnoses. CNNs and LSTMs achieved impressive AUC values of 0.98 for DSPN diagnosis prediction, and 0.93 and 0.89 respectively for predicting the future occurrence of DSPN. RF techniques combined with two deep learning algorithms exhibited outstanding performance in diagnosing and predicting the future occurrence of DSPN. These algorithms have the potential to serve as surrogate measures, aiding clinicians in accurate diagnosis and future prediction of DSPN.

Overexpression of thymidylate synthetase confers an independent prognostic indicator in nasopharyngeal carcinoma.

Data mining on public domain identified that thymidylate synthetase (TYMS) and dihydrofolate reductase (DHFR) transcripts were significantly higher expressed in nasopharyngeal carcinoma (NPC). In the folate pathway, TYMS catalyzes the methylation of deoxyuridylate to deoxythymidylate using 5,10-methylenetetrahydrofolate [5,10-CH2=THF, derived from tetrahydrofolate (THF)], as a cofactor. This function maintains the thymidine-5-prime monophosphate pool critical for DNA replication and repair and, THF is generated from dihydrofolate (DHF) through the activity of DHFR. Immunoexpression of TYMS and DHFR were retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcome was correlated with clinicopathological features and patient survivals. Results indicated that high TYMS (50%) expressions were correlated with primary tumor (p=0.008) and AJCC stage (p=0.006), and high DHFR (50%) expression were correlated with nodal status (p=0.039) and AJCC stage (p=0.029) (7th American Joint Committee on Cancer), respectively. In multivariate analyses, high TYMS expression emerged as an independent prognosticator for worse disease-specific survival (p<0.001), distal metastasis-free survival (p=0.002) and local recurrence-free survival (p<0.001), along with AJCC stage. Therefore, TYMS expression is common and associated with adverse prognosticators and might confer tumor aggressiveness through dysregulation of the nucleotide biosynthetic process.

Improved microcalcification visualization using dual-energy digital mammography.

BACKGROUND: Dual-energy digital mammography (DEDM), involving a combination of high-energy (HE) and low-energy (LE) images, has been investigated as offering a potential improvement in microcalcification detection obscured by overlapping tissue structures. PURPOSE: To explore the possibility to improve detection of microcalcifications using the DEDM technique. MATERIAL AND METHODS: Three DEDM protocols were performed by adjusting the effective tube current time product (mAs) of LE image at the same (100%), one half (50%), and one-quarter (25%) of that used in HE image acquisition, named DEDM100%, DEDM50%, and DEDM25%, respectively. A single-energy digital mammography (SEDM) method was also used as a control. A total of 525 regions of interest (ROIs) were used to compare the performance of the DEDM to that of SEDM using free-response receiver-operating characteristic (FROC) and areas under the FROC curve (Az). RESULTS: All DEDM protocols ranked significantly higher than the SEDM method (P < 0.001). The true-positive fraction was 0.90 for an average of 0.017-0.042 false-positive per image using the DEDM100%, 0.017-0.114 using the DEDM50%, 0.021-0.148 using the DEDM25%, and 0.134-0.422 using the SEDM. The estimated Az values were 0.915-0.940, 0.867-0.935, 0.824-0.930, and 0.567-0.673, respectively. CONCLUSION: The DEDM50% protocol provided a trade-off benefit between accurate microcalcification detectability and radiation dose for any tissue density. Therefore, the DEDM50% has the potential to minimize excess radiation dose without a negative impact on image quality which could improve earlier diagnosis of breast cancer.

Spontaneous Retro-Orbital Subperiosteal Hemorrhage with Complete Resolution Following Percutaneous Coronary Intervention for Acute Myocardial Infarction.

UNLABELLED: Among the several treatment strategies available for acute myocardial infarction, primary percutaneous coronary intervention concomitant with antithrombotic agents is the primary treatment used to facilitate coronary reperfusion. However, bleeding can create major complications. Here we have presented a case of acute myocardial infarction treated with reperfusion therapy, after which developed a sudden onset of proptosis, with high intraocular pressure, blurred vision, and ecchymosis of the left eye. Spontaneous retro-orbital subperiosteal hemorrhage, a rare complication, was diagnosed based on those symptoms as noted above, as well as other orbital signs and imaging evaluation. Multiple antithrombotic agents, including antiplatelets, low molecular weight heparin, and glycoprotein IIb/IIIa receptor inhibitor were thought to be the main precipitating factors of this complication. Thereafter, conservative medical treatment was applied. In the following 2 weeks, all the patient's orbital signs resolved gradually without visual impairment. In conclusion, our experience with a rare case of complications arising from reperfusion therapy used to treat myocardial infarction suggests that clinicians should remain vigilant for any hemorrhagic events during acute myocardial infarction treatment. KEY WORDS: Acute myocardial infarction; Percutaneous coronary intervention; Retro-orbital subperiosteal hemorrhage.

The Effects of Biologics on Hematologic Malignancy Development in Patients with Ankylosing Spondylitis, Psoriasis, or Psoriatic Arthritis: A National Cohort Study.

Biologics are used for ankylosing spondylitis (AS), psoriasis, and psoriatic arthritis (PsA) treatment. The association between biologics and the development of hematologic malignancies is controversial, and data on patients with AS, psoriasis, and PsA are scarce. This retrospective cohort study used data from 2010 to 2020 from Taiwan's National Health Insurance Research Database (NHIRD). Patients with AS, psoriasis, and PsA were divided into a biologics and non biologics group after 1:10 propensity score matching. The hematologic malignancy incidences and the time-/dose-dependent effects on biologics were analyzed by Poisson regression to evaluate the incidence rate ratio (IRR). Of the 4157 biologics users and 38,399 non biologics users included in the study, 10 and 72 persons developed hematologic malignancies, respectively. Biologics only significantly increased the risk of hematologic malignancies in non-Hodgkin's lymphoma (IRR: 2.48, 95% confidence interval (CI): 1.28-4.80). Different treatment patterns, types of biologics prescribed, cumulative defined daily doses, comorbidities, and comedications did not significantly affect hematologic malignancy development. A significantly increased risk was observed when biologics had been prescribed for 1-2 years (IRR: 2.95, 95% CI: 1.14-7.67). Clinical professionals should be aware of a patients' risk of hematologic malignancies during the second year of biologic treatment.

Phosphorylated p38 and JNK MAPK proteins in hepatocellular carcinoma.

BACKGROUND: The p38 and JNK MAPK proteins function as key mediators in cellular responses to extracellular stimuli. Deregulated p38 and JNK expressions have been associated with cancer development. This study aimed to investigate the association of p-p38 and p-JNK levels of the cancerous tissues with hepatocellular carcinoma (HCC) development. MATERIALS AND METHODS: One hundred and four liver cancer tissues of patients with HCC who underwent curative resection were prospectively collected. The levels of activated/p-p38 and p-JNK were determined by the enzyme-linked immunosorbent assay. The associations of results with clinicopathological characteristics and overall survival were further statically analysed using chi-squared test, two-tailed Student's t-test and Kaplan-Meier survival curve. RESULTS: The p-p38 levels were significantly higher in the HCC patients with a larger tumour (≥ 3 cm) and satellite tumour, and significantly correlated with the p-JNK levels. High p-p38 and low p-JNK expressions were associated with a poor survival in the patients with HCC (odds ratio, 4·24 and 0·20; P = 0·03 and 0·03, respectively). The Kaplan-Meier survival analysis showed that the HCC patients with high p-p38 expressions had a poor overall survival than those with low p-p38 expressions (P = 0·04), and a coexistent and high p-JNK expression remarkably improved this trend. CONCLUSIONS: Increasing p-p38 levels in HCC tissues were associated with tumour size and the formation of satellite tumours. High p-p38 expression could serve as a predictor for a poor survival for the patients with HCC. Simultaneous expression of p-JNK in HCC tissues might antagonize the promoting effect of p-p38 in human liver cancer.

The promoting effect of adiponectin in hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Adipokines may explain the newly established association of obesity with hepatocellular carcinoma (HCC). This study investigated if adiponectin levels in HCC patients differed from healthy controls and their potential effect in the development of HCC. METHODS: Radioimmunoassay was used to determine serum adiponectin levels of 65 HCC patients and 165 healthy controls. The expressions of adiponectin protein in the tumor and adjacent non-tumor parts were examined by the immunoblotting method. Cell proliferation assays were used to assess the bioeffects of adiponectin in two human liver cancer cell lines. RESULTS: Serum adiponectin levels were significantly higher in the HCC patients than the controls. Significant correlations of serum adiponectin levels with serum triglyceride levels and insulin resistance were found in the controls, but not in the HCC patients. In contrast, serum adiponectin levels significantly correlated with serum albumin and alkaline phosphatase levels in the HCC patients, but this trend was not observed in the controls. The expression pattern of adiponectin protein between the paired tumor and adjacent non-tumor tissues significantly correlated with tumor size. In vitro, adiponectin increased cell proliferation in a dose-dependent manner. CONCLUSIONS: Increased adiponectin expressions were found in HCC and this increase might contribute to tumor growth.

Prolactin promotes hepatocellular carcinoma through Janus kinase 2.

BACKGROUND: Hepatocellular carcinoma (HCC) is one human cancer with obvious gender disparity. This study investigated the association of aberrant prolactin levels with HCC risk and the potential impacts on HCC of the prolactin receptor (PRLR)/Janus kinase 2 (JAK2) signaling. METHODS: Serum prolactin of 63 HCC patients and 162 subjects without HCC was measured by radioimmunoassay. The expressions of PRLR and phosphorylated JAK2 (p-JAK2) in 82 retrospectively collected HCC specimens were evaluated by immunohistochemistry and further incorporated into the survival analysis. The immunoblotting and proliferation assays were used to analyze the effects of PRLR/JAK2 signaling on liver cancer cells with prolactin treatment. RESULTS: Serum prolactin level was significantly higher in HCC patients than in controls. Hepatocellular carcinoma patients with high p-JAK2 expression had a significantly higher postoperative risk than those with low p-JAK2 expression. Moreover, results from the multivariate analysis indicated the prognostic role of p-JAK2 expression with respect to overall survival in HCC patients. In addition, the Kaplan-Meier survival curve showed that high p-JAK2 expression was associated with poor survival in HCC patients with high PRLR expression. The immunoblotting assay showed that prolactin induced the expression of both p-JAK2 and cyclin D1 in Hep-G2 cells. Importantly, the proliferative effects induced by prolactin could be effectively attenuated by adding AG490, a JAK2 inhibitor. CONCLUSIONS: Increased circulating prolactin was found in HCC patients and high p-JAK2 expression could predict poor overall survival in those patients expressing high PRLR. In addition, prolactin contributed to the proliferation of liver cancer cells through PRLR/JAK2 signaling.

Feasibility study for the improvement of microcalcification visualization in different breast thicknesses and tissue components using a dual-energy approach in digital mammography.

OBJECTIVE: The purpose of this study was to improve detectability of microcalcifications using a dual-energy digital mammographic (DEDM) technique. METHODS: Slabs of uniform breast-equivalent plastic and an additional plate were used to mimic various breast thicknesses, from 3 to 7 cm, and to simulate microcalcification with diameters from 0.16 to 0.39 mm. Free-response receiver operating characteristics and area under the curves (Az) were used to evaluate the sensitivity of detecting microcalcifications using the DEDM compared with using the conventional single-energy digital mammography (SEDM). RESULTS: The mean number of false-positives per image was 0.0198 (Az = 0.956 ± 0.027) using DEDM compared with 0.292 (Az = 0.681 ± 0.235) using SEDM. A lower radiation dose could be possibly obtained for the DEDM technique with a thickness of less than 5 cm compared with the SEDM with a thickness larger than 5 cm. CONCLUSIONS: Microcalcifications could be more accurately and efficiently detected using the DEDM, which might bring reliable and promising applications on early computer-aided diagnosis of breast cancer.

Dual-Energy Computed Tomography for Evaluation of Breast Cancer Follow-Ups: Comparison of Virtual Monoenergetic Images and Iodine-Map.

Differentiating tumor tissue from dense breast tissue can be difficult. Dual-energy CT (DECT) could be suitable for making diagnoses at breast cancer follow-ups. This study investigated the contrast in DECT images and iodine maps for patients with breast cancer being followed-up. Chest CT images captured in 2019 were collected. Five cases of metastatic breast cancer in the lungs were analyzed; the contrast-to-noise ratio (for breast tissue and muscle: CNRb and CNRm, respectively), tumor-to-breast mammary gland ratio (T/B), and tumor-to-muscle ratio (T/M) were calculated. For 84 cases of no metastasis, monochromatic spectral and iodine maps were obtained to compare differences under various breast densities using the K-means algorithm. The optimal T/B, T/M, and CNRb (related to mammary glands) were achieved for the 40-keV image. Conversely, CNRm (related to lungs) was better for higher energy. The optimal balance was achieved at 80 keV. T/B, T/M, and CNR were excellent for iodine maps, particularly for density > 25%. In conclusion, energy of 80 keV is the parameter most suitable for observing the breast and lungs simultaneously by using monochromatic spectral images. Adding iodine mapping can be appropriate when a patient's breast density is greater than 25%.

Optimization of Emulsification Conditions on Ethanol Extract of Taiwanese Green Propolis Using Polysorbate and Its Immunomodulatory Effects in Broilers.

Beeswax and resin are the main components of propolis, both of which are hydrophobic. The use of emulsifiers helps to improve the extraction of active propolis compounds and makes them more widely used. In this study, we investigated the optimal parameters for the emulsification of Taiwanese green propolis (TGP) using different polysorbates (polysorbate-20, polysorbate-60, and polysorbate-80) and evaluated the effects on the immunomodulatory response in broilers. The results showed that 4 mg/mL of TGP in combination with 2% polysorbate-60 at 60 °C for 60 min significantly decreased the undissolved particle size of ethanol extract of TGP during the emulsification. The bioactive compounds of TGP, the propolins (C, D, F, G, and H), were also detected after emulsification. Supplementation of emulsified TGP (eTGP) in the drinking water of broilers before and after vaccination significantly enhanced the antibody titer response to infectious bronchitis virus at 28 days of age. In the lipopolysaccharide-challenged model, supplementation of eTGP in the drinking water of broilers decreased pro-inflammatory gene expression and increased anti-inflammatory gene expression. These results together suggested that the polysorbate-60 could effectively emulsify the ethanol extract of TGP. Moreover, eTGP could be used as a vaccine adjuvant and an immunomodulator to improve the immune response of broilers.

Variation in global distribution, population structures, and demographic history for four Trichiurus cutlassfishes.

BACKGROUND: Species-specific information on distribution and demographic patterns provides important implications for conservation and fisheries management. However, such information is often lacking for morphologically-similar species, which may lead to biases in the assessments of these species and even decrease effort towards sustainable management. Here, we aimed to uncover the distribution range, population structure and demographic history for four exploited Trichiurus cutlassfishes using genetics. These cutlassfishes contribute substantial global fisheries catch, with a high proportion of catch harvested from the NW Pacific. METHODS: We chose the widely available mitochondrial 16S ribosomal RNA (16S) as the genetic marker for cutlassfishes. We compiled the 16S sequence data from both the GenBank and a survey of trawler catch samples along the NW Pacific coasts 22-39°N. Genealogical relationships within each species was visualized with haplotype networks and potential population differentiations were further evaluated with AMOVA. Demographic histories were estimated using neutrality test, mismatch analysis, and the Bayesian skyline plot. The reconstructed phylogenetic trees were used to delimit and estimate the divergence time of species and included populations. RESULTS: In each of two cosmopolitan species, T. lepturus and T. nanhaiensis, we observed distinct populations along the coasts of warm oceans; such population differentiation might result from historical geographic barriers in the Pleistocene. In the NW Pacific, four Trichiurus species vary in their distribution habitats, which reflect differential ecological niches among these species. The small-sized T. brevis are primarily found in nearshore habitats; the warm-affiliated T. nanhaiensis are present along the path of the Kuroshio Current; the cold-affiliated T. japonicus spatially diverged from the widely-distributed T. lepturus, with the latter mainly occupy in warmer regions. Despite these differences, a single well-mixing fish stock, thus one management unit, was identified in each of the four species, presumably due to expansion of their population sizes predated the Last Glacial Maximum and a lack of distribution barrier. The most dominant T. japonicus, which have at least one magnitude higher effective population size than the others, show a unique abrupt size expansion event at 75 to 50-kilo years ago when the low sea level occurred during the ice age. MAIN CONCLUSIONS: The demographic history revealed by our genetic analyses advances understanding of the current distribution and population structure for these congeneric species. Moreover, the uncovered population structure provides insight into the assessment and management of these species. Such information complements contemporary knowledge about these species and enables us to forecast their ability to resist future environmental and anthropogenic disturbances.

Copine-7 is required for REM sleep regulation following cage change or water immersion and restraint stress in mice.

Sleep is affected by the environment. In rodents, changes in the amount of rapid eye movement sleep (REMS) can precede those of other sleep/wake stages. The molecular mechanism underlying the dynamic regulation of REMS remains poorly understood. Here, we focused on the sublaterodorsal nucleus (SLD), located in the pontine tegmental area, which plays a crucial role in the regulation of REMS. We searched for genes selectively expressed in the SLD and identified copine-7 (Cpne7), whose involvement in sleep was totally unknown. We generated Cpne7-Cre knock-in mice, which enabled both the knockout (KO) of Cpne7 and the genetic labeling of Cpne7-expressing cells. While Cpne7-KO mice exhibited normal sleep under basal conditions, the amount of REMS in Cpne7-KO mice was larger compared to wildtype mice following cage change or water immersion and restraint stress, both of which are conditions that acutely reduce REMS. Thus, it was suggested that copine-7 is involved in negatively regulating REMS under certain conditions. In addition, chemogenetically activating Cpne7-expressing neurons in the SLD reduced the amount of REMS, suggesting that these neurons negatively regulate REMS. These results identify copine-7 and Cpne7-expressing neurons in the SLD as candidate molecular or neuronal components of the regulatory system that controls REMS.

Synthetic dysmobility screen unveils an integrated STK40-YAP-MAPK system driving cell migration.

Integrating signals is essential for cell survival, leading to the concept of synthetic lethality. However, how signaling is integrated to control cell migration remains unclear. By conducting a "two-hit" screen, we revealed the synergistic reduction of cell migration when serine-threonine kinase 40 (STK40) and mitogen-activated protein kinase (MAPK) were simultaneously suppressed. Single-cell analyses showed that STK40 knockdown reduced cell motility and coordination by strengthening focal adhesion (FA) complexes. Furthermore, STK40 knockdown reduced the stability of yes-associated protein (YAP) and subsequently decreased YAP transported into the nucleus, while MAPK inhibition further weakened YAP activities in the nucleus to disturb FA remodeling. Together, we unveiled an integrated STK40-YAP-MAPK system regulating cell migration and introduced "synthetic dysmobility" as a novel strategy to collaboratively control cell migration.

Lenvatinib Induces AKT/NF-κB Inactivation, Apoptosis Signal Transduction and Growth Inhibition of Non-small Cell Lung Cancer In Vivo.

BACKGROUND/AIM: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with poor prognosis. Lenvatinib is a multi-kinase inhibitor that has the potential to suppress tumor progression. Our previous study suggested that lenvatinib induces cytotoxicity and apoptosis in CL-1-5-F4 cells in vitro. However, whether lenvatinib suppresses NSCLC progression in vivo remains unclear. MATERIALS AND METHODS: Tumor growth inhibition and normal tissue toxicity evaluation following lenvatinib treatment were performed on CL-1-5-F4-bearing mice. RESULTS: Tumor growth calculated by caliper and living cell intensity decreased by lenvatinib treatment as analysed by bioluminescence imaging. Phosphorylation of AKT, NF-κB, and NF-κB downstream proteins involved in tumor progression were reduced by lenvatinib in the tumor tissue. No pathological changes were found in the liver, kidney, and spleen after lenvatinib treatment. CONCLUSION: Induction of apoptosis and suppression of AKT/NF-κB were associated with lenvatinib-induced inhibition of the progression of NSCLC in vivo.

Cerebral capillary blood flow upsurge during REM sleep is mediated by A2a receptors.

Sleep is generally viewed as a period of recovery, but how the supply of cerebral blood flow (CBF) changes across sleep/wake states has remained unclear. Here, we directly observe red blood cells (RBCs) within capillaries, where the actual substance exchange between the blood and neurons/glia occurs, by two-photon microscopy. Across multiple cortical areas, average capillary CBF is largely increased during rapid eye movement (REM) sleep, whereas it does not differ between periods of active wakefulness and non-REM sleep. Capillary RBC flow during REM sleep is further elevated following REM sleep deprivation, suggesting that capillary CBF reflects REM sleep pressure. At the molecular level, signaling via adenosine A2a receptors is crucial; in A2a-KO mice, capillary CBF upsurge during REM sleep is dampened, and effects of REM sleep pressure are abolished. These results provide evidence regarding the dynamics of capillary CBF across sleep/wake states and insights to the underlying mechanisms.