Clinical features and outcomes of advanced HER2+ esophageal/GEJ cancer with brain metastasis.

BACKGROUND: Brain metastasis (BRM) is uncommon in gastroesophageal cancer. As such, clinicopathologic and molecular determinants of BRM and impact on clinical outcome remain incompletely understood. METHODS: We retrospectively analyzed clinicopathologic data from advanced esophageal/gastroesophageal junction (E/GEJ) patients at Johns Hopkins from 2003 to 2021. We investigated the association between several clinical and molecular features and the occurrence of BRM, with particular focus on human epidermal growth factor receptor 2 (HER2) overexpression. Survival outcomes and time to BRM onset were also evaluated. RESULTS: We included 515 patients with advanced E/GEJ cancer. Tumors were 78.3% esophageal primary, 82.9% adenocarcinoma, 31.0% HER2 positive. Cumulative incidence of BRM in the overall cohort and within HER2+ subgroup was 13.8% and 24.3%, respectively. HER2 overexpression was associated with increased risk of BRM [odds ratio 2.45; 95% confidence interval (CI) 1.10-5.46]. On initial presentation with BRM, 50.7% had a solitary brain lesion and 11.3% were asymptomatic. HER2+ status was associated with longer median time to onset of BRM (14.0 versus 6.3 months, P < 0.01), improved median progression free survival on first-line systemic therapy (hazard ratio 0.35, 95% CI 0.16-0.80), and improved median overall survival (hazard ratio 0.20, 95% CI 0.08-0.54) in patients with BRM. CONCLUSION: HER2 overexpression identifies a gastroesophageal cancer molecular subtype that is significantly associated with increased risk of BRM, though with later onset of BRM and improved survival likely reflecting the impact of central nervous system-penetrant HER2-directed therapy. The prevalence of asymptomatic and solitary brain lesions suggests that brain surveillance for HER2+ patients warrants prospective investigation.

[Influential factors of non-motor symptoms prognosis in Parkinson's disease patients undergoing deep brain stimulation].

Objective: To investigate the effects of electrode activated contact location, volume of tissue activated (VTA) and age on non-motor symptoms, such as emotional symptoms and cognitive function, in Parkinson's disease (PD) patients with deep brain stimulation (DBS). Methods: PD patients who underwent DBS of subthalamic nucleus (STN) at the Department of Functional Neurosurgery of Beijing Tiantan Hospital from September 1, 2020 to August 31, 2022 were retrospectively enrolled. The International Parkinson and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination Scales (MMSE) were used at the preoperative, 1-month and 12-month postoperative time points. In this study, patients were divided into middle-aged (age<60 years,n=39) and elderly (age≥60 years,n=62) groups to investigate the effect of age factor on the clinical outcome of surgery. Lead-DBS software was used to convert the patients' electrode reconstruction results into Montreal standard space, and the patients were divided into sensorimotor(n=43) and combined groups(n=53) according to the distribution of activation contact locations in the subzones of the STN. In addition, the patients were divided into a cognitive improvement group(n=57)and a cognitive deterioration group(n=44) based on the results of MoCA at 12 months. The positional information of the electrode activation contacts was collected and the VTA was calculated to analyze the effects on electrode activation electroshock location and activated tissue volume on patients' non-motor symptoms. Results: A total of 101 patients with PD were enrolled, including 46 males and 55 females, aged (62.6±8.4) years. Middle-aged patients had significantly higher MoCA scores, delayed recall scores, attention scores, and naming scores than older patients at 12 months postoperatively (all P<0.05). At 12-month follow-up, the improvement rate of MoCA score, HAMA score and HAMD score were -1.77%±20.36%, 39.65%±42.91% and 36.23%±45.45% respectively in sensorimotor group. At 12-month follow-up, the improvement rate of MoCA score, HAMA score and HAMD score was 11.69%±22.24%, 16.62%±68.10% and 2.30%±95.04% respectively in the combined group, and the difference between the two groups was statistically significant (MoCA: P=0.002; HAMA: P=0.040; HAMD: P=0.033) The distribution of VTA in the sensory motor area and marginal area of the left hemisphere STN in patients with improved cognitive function was significantly smaller than that in the deterioration group [(60.53±52.04)mm³vs (84.55±61.00)mm³, P=0.035; (41.81±33.36)mm³vs (59.05±45.46)mm³, P=0.030]. Conclusion: The effect of STN-DBS on emotional symptoms and cognitive function in PD patients is influenced by various factors and is closely related to the patient's age, electrode activation contact location and VTA.

Successful percutaneous coronary intervention with extracorporeal membrane oxygenation for patient with acute coronary syndrome and cardiac arrest: a case report.

BACKGROUND: The incidence rate of acute coronary syndrome (ACS) in China is on the rise and is considered a leading cause of death. Emergency percutaneous coronary intervention (PCI) is the preferred treatment method for ACS. However, severe complications may hinder emergency PCI and lead to increased mortality. Extracorporeal membrane oxygenation (ECMO) redirects blood flow and oxygenates it before returning. Therefore, ECMO support during PCI may improve functional recovery and outcomes. This case report presents a successful case of extracorporeal membrane oxygenation (ECMO)-assisted emergency PCI treatment of an outpatient with ACS. CASE REPORT: Male, 43 years old, experienced sudden, severe, and persistent squeezing-like chest pains accompanied by profuse sweating. After half an hour, the patient suddenly lost consciousness and was unable to exhale. After ECMO-assisted PCI, the patient's blood pressure and blood oxygen status improved, and the autonomous rhythm was restored. Imaging results showed 100% occlusion of the middle to distal anterior descending branch. After undergoing distal thrombus aspiration, a stent was implanted in the proximal end of the anterior descending branch. Repeated angiography showed good stent adhesion and restored blood flow in the anterior descending branch. The postoperative patient was transferred to the coronary care unit (CCU) ward with ECMO and ventilator for monitoring. CONCLUSIONS: ECMO-assisted emergency PCI effectively improved the blood pressure and oxygen status of the ACS patient with cardiac arrest, and restored the autonomous rhythm, with a good rehabilitation effect.

Reversible bonding of microfluidics: Review and applications.

With the development of microfluidic technology, new materials and fabrication methods have been constantly invented in the field of microfluidics. Bonding is one of the key steps for the fabrication of enclosed-channel microfluidic chips, which have been extensively explored by researchers globally. The main purpose of bonding is to seal/enclose fabricated microchannels for subsequent fluid manipulations. Conventional bonding methods are usually irreversible, and the forced detachment of the substrate and cover plate may lead to structural damage to the chip. Some of the current microfluidic applications require reversible bonding to reuse the chip or retrieve the contents inside the chip. Therefore, it is essential to develop reversible bonding methods to meet the requirements of various applications. This review introduces the most recent developments in reversible bonding methods in microfluidics and their corresponding applications. Finally, the perspective and outlook of reversible bonding technology were discussed in this review.

Relationship between apparent diffusion coefficient and survival as a function of distance from gross tumor volume on radiation planning MRI in newly diagnosed glioblastoma.

PURPOSE: To investigate the changes in apparent diffusion coefficient (ADC) within incrementally-increased margins beyond the gross tumor volume (GTV) on post-operative radiation planning MRI and their prognostic utility in glioblastoma. METHODS: Radiation planning MRIs of adult patients with newly diagnosed glioblastoma from 2017 to 2020 were assessed. The ADC values were normalized to contralateral normal white matter (nADC). Using 1 mm isotropic incremental margin increases from the GTV, the nADC values were calculated at each increment. Age, ECOG performance status, extent of resection and MGMT promoter methylation status were obtained from medical records. Using univariate and multivariable Cox regression analysis, association of nADC to progression-free and overall survival (PFS, OS) was assessed at each increment. RESULTS: Seventy consecutive patients with mean age of 53.6 ± 10.3 years, were evaluated. The MGMT promoter was methylated in 31 (44.3%), unmethylated in 36 (51.6%) and unknown in 3 (4.3%) patients. 11 (16%) underwent biopsy, 41 (44%) subtotal resection and 18 (26%) gross total resection. For each 1 mm increase in distance from GTV, the nADC decreased by 0.16% (p < 0.0001). At 1-5 mm increment, the nADC was associated with OS (p < 0.01). From 6 to 11 mm increment the nADC was associated with OS with the p-value gradually increasing from 0.018 to 0.046. nADC was not associated with PFS. CONCLUSION: The nADC values at 1-11 mm increments from the GTV margin were associated with OS. Future prospective multicenter studies are needed to validate the findings and to pave the way for the utilization of ADC for margin reduction in radiation planning.

[Exosomes secreted from human umbilical cord mesenchymal stem cells promote pancreatic ductal adenocarcinoma growth by transferring miRNAs].

Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.

Proposing a quantitative MRI-based linear measurement framework for response assessment following stereotactic body radiation therapy in patients with spinal metastasis.

PURPOSE: To provide evidence towards a quantitative response assessment framework incorporating MRI-based linear measurements for spinal metastasis that predicts outcome following stereotactic body radiation therapy (SBRT). METHODS: Adult patients with de novo spinal metastases treated with SBRT between 2008 and 2018 were retrospectively assessed. The metastatic lesions involving the pedicles, articular processes, lamina, transverse process, spinous process and vertebral body at leach level were measured separately using linear measurements on pre- and all post-SBRT MRIs. The outcome was segment-specific progression (SSP) using SPINO guidelines which was dated to the first clinical documentation of progression, or the date of the associated MRI if imaging was the reason for progression. Random forest analysis for variable selection and recursive partitioning analysis for SSP probability prediction were used. RESULTS: Five Hundred Ninety-three spinal levels (323 patients) from 4081 MRIs were evaluated. The appearance of new T1 hypointensity and increase in Bilsky grade had an odds ratio (OR) of 33.5 and 15.5 for SSP, respectively. Compared to baseline, an increase of > 3 mm in any lesion dimension, combined with a 1.67-fold increase in area, had an OR of 4.6 for SSP. The sensitivity, specificity, positive predictive value, negative predictive value, balanced accuracy and area under the curve of the training model were 96.7%, 89.6%, 28.6%, 99.8%, 93.2% and 0.905 and of the test model were 91.3%, 89.3%, 27.1% 99.6%, 90.3% and 0.933, respectively. CONCLUSION: With further refinement and validation in prospective multicentre studies, MRI-based linear measurements can help predict response assessment in SBRT-treated spinal metastases.

Mussel-Inspired Hydrogels for Fluoride Delivery and Caries Prevention.

Fluoride agents hold promise for the repair and prevention of caries lesions, but their interaction with enamel is often hampered and diminished because of the dynamic wet environment in the oral cavity, which affects the efficacy of fluoride delivery and limits treatment success. We herein developed a mussel-inspired wet adhesive fluoride system (denoted TS@NaF) fabricated by the self-assembly of tannic acid (TA), silk fibroin (SF), and sodium fluoride (NaF). TS@NaF demonstrated remarkable biological stability and biocompatibility, showed reliable wet adhesion, released fluoride ions (F-) topically, and induced significant deposition of calcium fluoride (CaF2) onto enamel in vitro. Furthermore, TS@NaF provided an anticaries effect in vitro and induced a detectable increase in enamel mineral density. Advanced fluoride-releasing bioadhesives are therefore promising candidates for caries prevention and highlight the great potential of mussel-inspired dental materials in clinical applications.

Effects of Selenium Supplementation on the Ion Homeostasis in the Reproductive Organs and Eggs of Laying Hens Fed With the Diet Contaminated With Cadmium, Lead, Mercury, and Chromium.

The objective of this study was to explore the toxic effects of different heavy metals in combination with their deposition and ion homeostasis in the reproductive organs and eggs of laying hens, as well as the alleviating action of selenized yeast. A total of 160 Lohmann pink-shell laying hens (63-week-old) were randomly allocated into four treatments with 10 replicates of four hens each. The four dietary treatments were the corn-soybean meal basal dietary (control; CON); the CON dietary supplemented with 0.4 mg/kg selenium from selenized yeast (Se); the CON dietary supplemented with 5 mg/kg Cd + 50 mg/kg Pb +3 mg/kg Hg + 5 mg/kg Cr (HEM), and the HEM dietary supplemented with 0.4 mg/kg selenium from selenized yeast (HEM+Se). The dietary HEM significantly increased Cd, Pb, and Hg deposition in the egg yolk and ovary, and Cd and Hg deposition in the oviduct and in the follicular wall (p < 0.05). The HEM elevated Fe concentration in the egg yolk, ovary, and oviduct (p < 0.05). The HEM decreased Mn concentration in the egg yolk, Fe, Mn, and Zn concentrations in the egg white, Cu concentration in the ovary, Mg concentration in the oviduct, as well as Ca, Cu, Zn, and Mg concentrations in the follicular walls (p < 0.05). Dietary Se addition elevated Se concentration in the egg yolk, oviduct, and follicular walls and Mg concentration (p < 0.05) in the oviduct, whereas it reduced Fe concentration in the oviduct compared with the HEM-treated hens. Some positive or negative correlations among these elements were observed. Canonical Correlation Analysis showed that the concentrations of Pb and Hg in the egg yolk were positively correlated with those in the ovary. The concentration of Cd in the egg white was positively correlated with that in the oviduct. In summary, dietary Cd, Pb, Hg, and Cr in combination caused ion loss and deposition of HEM in reproductive organs of laying hens. Dietary Se addition at 0.4 mg/kg from selenized yeast alleviated the negative effects of HEM on Fe and Mg ion disorder in the oviduct and follicle wall of hens.

[Mechanical circulatory support combined with immunomodulation treatment for patients with fulminant myocarditis: a single-center real-world study].

Objective: To investigate the relationship between the mechanical circulatory support (MCS) combined with immunomodulation and the prognosis of patients with fulminant myocarditis. Methods: This is a retrospective study. A total of 88 patients with fulminant myocarditis admitted to Dongguan Kanghua hospital from Aug. 2008 to Dec. 2020 were included. Medical histories, results of laboratory tests, treatment regimens and clinical outcomes of these patients during their hospitalization were collected from the medical record system. According to the treatment methods, the patients were divided into MCS+immunomodulation group (38 cases), MCS group (20 cases) and traditional treatment group (30 cases). Patients in the MCS+immunomodulation group received intra-aortic balloon pump (IABP) or IABP combined with extracorporeal membrane oxygenation (ECMO) and immunoglobulin or glucocorticoid. Patients in the MCS group only received mechanical circulatory support. Patients in the traditional treatment group received neither mechanical circulatory support nor immunomodulatory therapy, and only used vasoactive drugs and cardiotonic drugs. The in-hospital mortality and length of stay were compared among the three groups. Results: A total of 88 patients with fulminant myocarditis aged (35.0±10.8) years were included, and there were 46 males (52.3%). The mortality of MCS+immunomodulation group (7.9% (3/38) vs. 56.7% (17/30), P=0.001 2) and MCS group (30.0% (6/20) vs. 56.7% (17/30), P=0.002 8) were lower than that of traditional treatment group. Compared with the MCS group, the in-hospital mortality in the MCS+immunomodulation group was lower (P=0.005 4). The most common cause of death was multiple organ dysfunction syndrome (MODS). The constituent ratios of death in MCS+immunomodulation group, MCS group and traditional treatment group were 3/3, 4/6 and 12/17, respectively. The incidence of MODS in the MCS group (20% (4/20)) and the traditional treatment group (40% (12/30)) was significantly higher than that in the MCS+immunomodulation group (7.9% (3/38)) (both P<0.01). In discharged patients, the hospitalization time of MCS+immunomodulation group was shorter than that of traditional treatment group ((13.4±5.5)d vs. (18.5±7.4)d, P<0.05) and MCS group ((13.4±5.5)d vs. (16.9±8.5)d, P<0.05). Conclusion: MCS combined with immunomodulatory therapy is associated with lower in-hospital mortality and shorter hospital stay in patients with fulminant myocarditis.

microRNA-377-3p inhibits osteosarcoma progression by targeting CUL1 and regulating Wnt/B-catenin signaling pathway

Objective Emerging studies highlight the crucial effects of microRNAs on cancer initiation and malignant progression of various tumors. This study focused on the biological effect of miR-377-3p on CUL1 and epithelial–mesenchymal transition (EMT) and Wnt/β-catenin pathways in osteosarcoma (OS). Methods We performed quantitative real-time polymerase chain reaction (qRT-PCR) to analyze miR-377-3p and CUL1 expression levels in OS tissues and MG-63 cells. Then, cell counting kit (CCK)-8 and Transwell assay were used to examine the functions of miR-377-3p in OS cell growth and metastasis abilities. Meanwhile, luciferase reporter assay was used to validate CUL1 as direct target of miR-377-3p. qRT-PCR and Western blot were then carried out to detect the impact of miR-377-3p on EMT and Wnt/β-catenin pathways. Tumor xenograft models were established to further examine the effects of miR-377-3p on OS tumorigenesis in vivo. Results miR-377-3p downregulation was frequently identified in OS tissues and cells, which was associated with worse prognosis of OS patients. Functional experiments showed miR-377-3p restoration could dramatically repress OS cell growth and migration by regulation of EMT and Wnt/β-catenin pathways. Moreover, luciferase reporter assay revealed that CUL1 acted as a functional target of miR-377-3p. Additionally, the elevated CUL1 expressions in OS tissues also indicated poor prognosis of OS patients. Furthermore, the OS tumor growth was also obviously inhibited by miR-377-3p overexpression in vivo. Conclusions Collectively, all the above findings revealed that miR-377-3p exerted anti-OS functions via CUL1 and EMT and Wnt/β-catenin pathways. These results may contribute to the development of clinical OS treatment (AU)

High accuracy measurement of the ground-state hyperfine splitting in a 113Cd+ microwave clock: erratum.

We present an erratum to our Letter [Opt. Lett.40, 4249 (2015)OPLEDP0146-959210.1364/OL.40.004249]. This erratum corrects the nuclear Lande factor gI in Eq. (2). After correcting the error, the final ground-state hyperfine splitting frequency of the 113Cd+ ion is determined to be 15199862855.0287(10) Hz.

The spatial form periosteal-bone complex promotes bone regeneration by coordinating macrophage polarization and osteogenic-angiogenic events.

Bone defects associated with soft tissue injuries are an important cause of deformity that threatens people's health and quality of life. Although bone substitutes have been extensively explored, effective biomaterials that can coordinate early inflammation regulation and subsequent repair events are still lacking. We prepared a spatial form periosteal bone extracellular matrix (ECM) scaffold, which has advantages in terms of low immunogenicity, good retention of bioactive ingredients, and a natural spatial structure. The periosteal bone ECM scaffold with the relatively low-stiffness periosteum (41.6 ± 3.7 kPa) could inhibit iNOS and IL-1ß expression, which might be related to actin-mediated YAP translocation. It also helped to promote CD206 expression with the potential influence of proteins related to immune regulation. Moreover, the scaffold combined the excellent properties of decalcified bone and periosteum, promoted the formation of blood vessels, and good osteogenic differentiation (RUNX2, Col 1α1, ALP, OPN, and OCN), and achieved good repair of a cranial defect in rats. This scaffold, with its natural structural and biological advantages, provides a new idea for bone healing treatment that is aligned with bone physiology.

[Analysis of the short-and medium-term curative effect of TIPS approach combined with AngioJet thrombus aspiration technology treatment in acute portal vein thrombosis].

Objective: To evaluate the short- and medium-term clinical efficacy of TIPS approach combined with AngioJet thrombus aspiration technology treatment in acute portal vein thrombosis. Methods: 63 cases with acute portal vein thrombosis treated in our center from May 2017 to July 2019 were studied retrospectively, including 49 males and 14 females, aged 35-61 (46 ± 5) years. TIPS approach (with/without) combined with Angiojet thrombus aspiration and gastroesophageal varices embolization was performed simultaneously according to the patient's condition. Regular follow-up for 3-33 (22 ± 3) months after surgery was used to observe the curative effect. Results: The technical success rate was 100%. Portal vein and superior mesenteric vein blood flow were returned to normal after the operation. Two cases of biliary tract injury were untreated. Simultaneously, two cases of intrahepatic arteriovenous fistula were treated with superselective arterial embolization. During the follow-up period, 47 cases (74.61%) had complete portal vein recanalization, 13 cases (20.63%) had partial recanalization, 3 cases (4.76%) had complete portal cavernoma, 7 cases (11.11%) had symptomatic hepatic encephalopathy, 1 case had received artificial liver treatment (1.59%), 1 case had peptic ulcer (11.11%), 6 cases (9.52%) had lost to follow-up, and there was no portal hypertension-related bleeding or death. Conclusion: TIPS approach combined with AngioJet thrombus aspiration technology is safe, effective and feasible in the treatment of acute portal vein thrombosis, and the short- and medium-term clinical effects are satisfactory.

Multifunctional Thio-Stabilized Gold Nanoparticles for Near-Infrared Fluorescence Detection and Imaging of Activated Caspase-3.

BACKGROUND: Gold nanoparticles (AuNPs) are commonly used in nanomedicine because of their unique spectral properties, chemical and biological stability, and ability to quench the fluorescence of organic dyes attached to their surfaces. However, the utility of spherical AuNPs for activatable fluorescence sensing of molecular processes have been confined to resonance-matched fluorophores in the 500 nm to 600 nm spectral range to maximize dye fluorescence quenching efficiency. Expanding the repertoire of fluorophore systems into the NIR fluorescence regimen with emission >800 nm will facilitate the analysis of multiple biological events with high detection sensitivity. OBJECTIVE: The primary goal of this study is to determine if spherical AuNP-induced radiative rate suppression of non-resonant near-infrared (NIR) fluorescent probes can serve as a versatile nanoconstruct for highly sensitive detection and imaging of activated caspase-3 in aqueous media and cancer cells. This required the development of activatable NIR fluorescence sensors of caspase-3 designed to overcome the nonspecific degradation and release of the surface coatings in aqueous media. METHOD: We harnessed the fluorescence-quenching properties and multivalency of spherical AuNPs to develop AuNP-templated activatable NIR fluorescent probes to detect activated caspase-3, an intracellular reporter of early cell death. Freshly AuNPs were coated with a multifunctional NIR fluorescent dye-labeled peptide (LS422) consisting of an RGD peptide sequence that targets αvß3-integrin protein (αvß3) on the surface of cancer cells to mediate the uptake and internalization of the sensors in tumor cells; a DEVD peptide sequence for reporting the induction of cell death through caspase-3 mediated NIR fluorescence enhancement; and a multidentate hexacysteine sequence for enhancing self-assembly and stabilizing the multifunctional construct on AuNPs. The integrin binding affinity of LS422 and caspase-3 kinetics were determined by a radioligand competitive binding and fluorogenic peptide assays, respectively. Detection of intracellular caspase-3, cell viability, and the internalization of LS422 in cancer cells were determined by confocal NIR fluorescence spectroscopy and microscopy. RESULTS: Narrow size AuNPs (13 nm) were prepared and characterized by transmission electron microscopy and dynamic light scattering. When assembled on the AuNPs, the binding constant of LS422 for αvß3 improved 11-fold from 13.2 nM to 1.2 nM. Whereas the catalytic turnover of caspase-3 by LS422-AuNPs was similar to the reference fluorogenic peptide, the binding affinity for the enzyme increased by a factor of 2. Unlike the αvß3 positive, but caspase-3 negative breast cancer MCF-7 cells, treatment of the αvß3 and caspase-3 positive lung cancer A549 cells with Paclitaxel showed significant fluorescence enhancement within 30 minutes, which correlated with caspase-3 specific activation of LS422-AuNPs fluorescence. Incorporation of a 3.5 mW NIR laser source into our spectrofluorometer increased the detection sensitivity by an order of magnitude (limit of detection ~0.1 nM of cypate) and significantly decreased the signal noise relative to a xenon lamp. This gain in sensitivity enabled the detection of substrate hydrolysis at a broad range of inhibitor concentrations without photobleaching the cypate dye. CONCLUSION: The multifunctional AuNPs demonstrate the use of a non-resonant quenching strategy to design activatable NIR fluorescence molecular probes. The nanoconstruct offers a selective reporting method for detecting activated caspase-3, imaging of cell viability, identifying dying cells, and visualizing the functional status of intracellular enzymes. Performing these tasks with NIR fluorescent probes creates an opportunity to translate the in vitro and cellular analysis of enzymes into in vivo interrogation of their functional status using deep tissue penetrating NIR fluorescence analytical methods.

Propagation of Gaussian Schell-model beams in modulated graded-index media.

The evolution of partially coherent beams in longitudinally modulated graded-index media is studied. The special cases of Gaussian Schell-model beams and parametric modulation, when the modulation period is half the fiber self-imaging period, are examined in detail. We show that the widths of the intensity and coherence of Gaussian Schell-model beams undergo amplification in parametrically modulated parabolic graded-index media. The process is an analog of quantum mechanical parametric amplification and generation of squeezed states. Our work may find application in spatial and temporal imaging of partially coherent beams in fiber-based imaging systems.

microRNA-377-3p inhibits osteosarcoma progression by targeting CUL1 and regulating Wnt/ß-catenin signaling pathway.

OBJECTIVE: Emerging studies highlight the crucial effects of microRNAs on cancer initiation and malignant progression of various tumors. This study focused on the biological effect of miR-377-3p on CUL1 and epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin pathways in osteosarcoma (OS). METHODS: We performed quantitative real-time polymerase chain reaction (qRT-PCR) to analyze miR-377-3p and CUL1 expression levels in OS tissues and MG-63 cells. Then, cell counting kit (CCK)-8 and Transwell assay were used to examine the functions of miR-377-3p in OS cell growth and metastasis abilities. Meanwhile, luciferase reporter assay was used to validate CUL1 as direct target of miR-377-3p. qRT-PCR and Western blot were then carried out to detect the impact of miR-377-3p on EMT and Wnt/ß-catenin pathways. Tumor xenograft models were established to further examine the effects of miR-377-3p on OS tumorigenesis in vivo. RESULTS: miR-377-3p downregulation was frequently identified in OS tissues and cells, which was associated with worse prognosis of OS patients. Functional experiments showed miR-377-3p restoration could dramatically repress OS cell growth and migration by regulation of EMT and Wnt/ß-catenin pathways. Moreover, luciferase reporter assay revealed that CUL1 acted as a functional target of miR-377-3p. Additionally, the elevated CUL1 expressions in OS tissues also indicated poor prognosis of OS patients. Furthermore, the OS tumor growth was also obviously inhibited by miR-377-3p overexpression in vivo. CONCLUSIONS: Collectively, all the above findings revealed that miR-377-3p exerted anti-OS functions via CUL1 and EMT and Wnt/ß-catenin pathways. These results may contribute to the development of clinical OS treatment.

Epinephrine modulates memory of latent learning in an inhibitory avoidance task.

The present study examined the memory modulatory effect of epinephrine on latent learning of an inhibitory avoidance task. Male Sprague-Dawley rats on the first day were subjected to one of three conditions (no, short or long) in pre-exposure to the task apparatus. One day or several days later, they received the typical inhibitory avoidance training with a 0.5 mA/0.5 s foot shock. Memory of the inhibitory avoidance response was tested one day after the foot-shock training. The long pre-exposure group showed better memory than the no or short pre-exposure group, and this latent memory could last for 6 days: Retention scores of the long pre-exposure group were significantly better than those of the no pre-exposure group if the shock training was given 3 or 6 days, but not 12 or 21 days, after the pre-exposure. Epinephrine injected after the pre-exposure training modulated the latent memory in a dose- and time-dependent manner: 0.01 mg/kg given shortly after the short pre-exposure enhanced the memory, but 0.5 mg/kg given shortly after the long pre-exposure impaired it. Epinephrine injected 4 h after the pre-exposure had no effect, neither did that given to rats pre-exposed to a different context. Epinephrine (0.01 mg/kg) also made the latent memory lasting longer as the rats treated with it showed significant avoidance behavior when they had the shock training at 12 or 21 days after the pre-exposure. These findings suggest that epinephrine could modulate memory formed in the latent learning.

MicroRNA-29 targets FGF2 and inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma cells via PI3K/AKT signaling pathway.

The article "MicroRNA-29 targets FGF2 and inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma cells via PI3K/AKT signaling pathway, by M. Xu, G.-L. Tian, C.-C. Hao, M. Shi, D.-J. Zha, K. Liang, published in Eur Rev Med Pharmacol Sci 2019; 23 (12): 5215-5222. DOI: 10.26355/eurrev_201906_18186. PMID: 31298371" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18186.

[The association between carotid atherosclerosis and ischemic stroke in patients with nonvalvular atrial fibrillation].

Objective: To investigate the relationship between indicators of carotid atherosclerosis and onset of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Methods: This is a case-control study, a total of 397 NVAF patients with newly diagnosed ischemic stroke (case group) and 3 038 NVAF patients without ischemic stroke (control group) from January 2015 to December 2017 were included in the study. Differences in general clinical features and carotid atherosclerosis indexes between the two groups were compared. Univariate and multivariate logistic regressions were used to analyze the correlation between carotid atherosclerosis indexes and ischemic stroke. Results: Proportions of patients with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, and moderate to severe stenosis were higher in the ischemic stroke group than those in the control group (82.1% vs. 64.4%, 69.3% vs. 50.3%, 43.6% vs. 30.6%, 25.7% vs. 19.7%, and 7.3% vs. 4.0%, respectively, all P <0.05). After adjustment of age, gender, heart failure, hypertension, low density lipoprotein -cholesterol and drug use, multivariate analyses showed that subjects with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, moderate to severe stenosis had 1.766, 2.111, 1.892, 2.256 and 1.824 times the risk for the development of ischemic stroke compared with the subjects without any carotid atherosclerosis indicators. Conclusion: Carotid atherosclerosis, especially with unstable carotid plaque, is associated with ischemic stroke in patients with NVAF.