Maximize Contact Availability of SmallSat Clusters through MSPA Technique on GSaaS

The Mission Launch date: 07 November 2021 Mission name: KSM1 (Kleos Scouting Mission) Satellites names: KSM1-A, KSM1-B, KSM1-C, KSM1-D NORAD-ID: 46912, 46914, 46906, 46907 Application: RF Reconnaissance and Geospatial Intelligence Mission characteristics: Kleos Space SA (KSS) Scouting Mission (KSM) first cluster of spacecraft, was launched on the 7th of November 2021, comprising four 6U cubesat flying in a close formation. The formation maintains the along and across track distance between the four spacecraft, enabling KSS proprietary algorithms to geolocate Radio Frequency transmitters. GSaaS: Leaf Space provides communication through their Leaf Line GSaaS (Ground Segment as-a-Service) with stations in Italy and Spain supporting the mission with UH

GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growth in vitro and in vivo

We have previously demonstrated that estrogen receptor (ER) alpha (ESR1) increases proliferation of adrenocortical carcinoma (ACC) through both an estrogen-dependent and -independent (induced by IGF-II/IGF1R pathways) manner. Then, the use of tamoxifen, a selective estrogen receptor modulator (SERM), appears effective in reducing ACC growth in vitro and in vivo. However, tamoxifen not only exerts antiestrogenic activity, but also acts as full agonist on the G protein-coupled estrogen receptor (GPER). Aim of this study was to investigate the effect of a non-steroidal GPER agonist G-1 in modulating ACC cell growth. We found that G-1 is able to exert a growth inhibitory effect on H295R cells both in vitro and, as xenograft model, in vivo. Treatment of H295R cells with G-1 induced cell cycle arrest, DNA damage and cell death by the activation of the intrinsic apoptotic mechanism. These events required sustained extracellular regulated kinase (ERK) 1/2 activation. Silencing of GPER by a specific shRNA partially reversed G-1-mediated cell growth inhibition without affecting ERK activation. These data suggest the existence of G-1 activated but GPER-independent effects that remain to be clarified. In conclusion, this study provides a rational to further study G-1 mechanism of action in order to include this drug as a treatment option to the limited therapy of ACC

Increased FGF23 serum level is associated with unstable carotid plaque in type 2 diabetic subjects with internal carotid stenosis.

BACKGROUND: The object of this study was to investigate the potential role of FGF23 on plaque stability in type 2 diabetic patients with internal carotid artery stenosis. METHODS: In this retrospective observational study, we analyzed FGF23 serum level in 361 type 2 diabetic patients with internal carotid artery stenosis undergoing carotid endarterectomy and in 598 diabetic controls without carotid atherosclerosis. RESULTS: We found that FGF23 median serum levels was significantly higher in patients than in diabetic controls [67.7 (59.5-77.8) pg/mL and 43.89 (37.5-50.4), P < 0.001] and was significantly and independently associated with unstable plaque in patients with internal carotid artery stenosis [OR, 5,71 (95% CI, 2.09-15.29]. CONCLUSIONS: We have found, for the first time, that FGF23 could be associated with unstable plaque in type 2 diabetic patients with internal carotid artery stenosis

Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents

Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEADbox polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus. Herein, we showed for the first time, to our knowledge, that the inhibition of DDX3 by a small molecule could be successfully exploited for the development of a broad spectrum antiviral agent. In addition to the multiple antiviral activities, hit compound 16d retained full activity against drug-resistant HIV-1 strains in the absence of cellular toxicity. Pharmacokinetics and toxicity studies in rats confirmed a good safety profile and bioavailability of 16d. Thus, DDX3 is here validated as a valuable therapeutic target

COVID-19 and RA share SPP1 myeloid pathway that drives PD-L1pos neutrophils and CD14pos monocytes

We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that BALF macrophage clusters FCN1pos and FCN1posSPP1pos predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48highS100A12pos and CD48posSPP1pos that drive Rheumatoid Arthritis (RA) synovitis. BALF macrophage cluster FABP4pos predominant in healthy lung was transcriptionally related to STM cluster TREM2pos that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and remained high in post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared to other causes of severe pneumonia, and immunohistochemistry localized SPP1pos macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives pro-inflammatory activation of CD14pos monocytes and development of PD-L1pos neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post-COVID-19 monitoring

A new micro-forceps for endoscopic ultrasound-guided through-the-needle biopsy in the diagnosis of pancreatic cystic lesions: single center experience

Background and aim: Endoscopic ultrasound (EUS)-guided through-the-needle biopsy (TTNB) has improved the diagnostic algorithm of pancreatic cystic neoplasms (PCNs). Recently, a new through-the-needle micro-forceps device (Micro Bite, MTW Endoskopie Manufakture) has been introduced. The primary aim was to assess the safety and technical success of this new type of micro-forceps. The secondary aim was to evaluate the diagnostic role of EUS-TTNB. Methods: Retrospective study of consecutive patients receiving EUS-TTNB for the diagnosis of PCNs. Two micro-forceps were used: Moray Micro-forceps and Micro-Bite. Cystic fluid was collected for cytological analysis. Categorical variables were analyzed by Fisher's exact test, and continuous variables were analyzed by Student's t-test. P &lt; 0.05 was considered significant. Results: Forty-nine patients enrolled in the study (24% male; mean age 63 ± 14 years). TTNB was successfully performed in all patients. A diagnostic sample was obtained in 67.3% PCNs with TTNB compared with 36.7% with cyst fluid cytology (P 0.01). Adverse events rate was 10.2% and occurred in older patients (76.6 ± 5.4 vs 61.3 ± 13.7 P = 0.02). The 51% underwent EUS-TTNB with Micro Bite. A diagnostic sample was obtained in 52% PCNs with Micro Bite compared with 24% obtained with cyst fluid cytology (P = 0.07). Comparing the two devices, the rate of diagnostic sample obtained with the micro-forceps Moray was higher than that obtained with the Micro Bite (20/24 [83.3%] vs 13/25 [52%] P 0.03). Conclusions: EUS-TTNB increases the diagnostic yield of PCNs. The new Micro-Bite could represent a valid alternative to the currently used Moray Micro-forceps, but its diagnostic rate is still suboptimal and further studies are needed. Keywords: endoscopic ultrasound; increased diagnosis; micro‐forceps; new device; pancreatic cystic neoplasm