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AbstractTypical Pulmonary Carcinoid (TPC) is defined by its slow growth, frequently necessitating surgical intervention. Despite this, the long-term outcomes following tumor resection are not well understood. This study examined the factors impacting Overall Survival (OS) in patients with TPC, leveraging data from the Surveillance, Epidemiology, and End Results database spanning from 2000 to 2018. We employed Lasso-Cox analysis to identify prognostic features and developed various models using Random Forest, XGBoost, and Cox regression algorithms. Subsequently, we assessed model performance using metrics such as Area Under the Curve (AUC), calibration plot, Brier score, and Decision Curve Analysis (DCA). Among the 2687 patients, we identified five clinical features significantly affecting OS. Notably, the Random Forest model exhibited strong performance, achieving 5- and 7-year AUC values of 0.744/0.757 in the training set and 0.715/0.740 in the validation set, respectively, outperforming other models. Additionally, we developed a web-based platform aimed at facilitating easy access to the model. This study presents a machine learning model and a web-based support system for healthcare professionals, assisting in personalized treatment decisions for patients with TPC post-tumor resection. [ABSTRACT FROM AUTHOR]

Image semantic segmentation methods based on convolutional neural networks rely on supervised learning with labels, and their performance often drops significantly when applied to unlabelled datasets from different sources. The domain adaptation methods can reduce the inconsistency of feature distribution between the unlabelled target domain data used for testing and the labelled source domain data used for training, thus improve the segmentation performance and have more practical applications. However, in the field of remote sensing image processing, if the spatial resolutions of the source domain and the target domain are different and this problem is not to be solved, the performance of the transferred model will be affected. In this paper, we propose a bidirectional semantic segmentation method based on super-resolution and domain adaption (BSSM-SRDA), which is suitable for the transfer learning task of a semantic segmentation model from a low-resolution source domain data to a high-resolution target domain data. BSSM-SRDA mainly consists of three parts: a shared feature extraction network; a super-resolution image translation module, which incorporates a super-resolution approach to reduce spatial resolution differences and visual style differences of the two domains; a domain-adaptive semantic segmentation module, which combines an adversarial domain adaptation approach to reduce differences at the output level. At the same time, we design a new bidirectional self-supervised learning algorithm for BSSM-SRDA that facilitates mutually beneficial learning of the super-resolution image translation module and the domain-adaptive semantic segmentation module. The experiments demonstrate the superiority of the proposed method over other state-of-the-art methods on two remote-sensing image datasets, with mIoU improvements of 2.5% and 3.2%, respectively. Code: [ABSTRACT FROM AUTHOR]

Iron-based alloy coatings were deposited on grey cast iron through plasma transfer arc welding. Results showed that the iron-based alloy coatings are composed of pearlite, martensite, austenite, and secondary carbides. There formed a bonding transformation layer between coating and grey cast iron with the width of about 205 μm. The optimized plasma transfer arc current was 100 A with the coating's microhardness of 749 Hv. Meanwhile, the bonding strength between the deposit and the grey cast iron was 208 MPa which was comparable to the grey cast iron's strength. The thick coatings with similar properties to the grey cast iron formed the basis of remanufacturing grey cast iron parts. [ABSTRACT FROM AUTHOR]

Two oxidovanadium(V) complexes, [VOL1(OEt)] (1) and [V2O2(L2)2(OEt)2] (2), where L1 and L2 are the anions of 2-amino-N′-(2-hydroxybenzylidene)benzohydrazide (H2L1) and N′-(2-hydroxybenzylidene)-4-hydroxybenzohydrazide (H2L2), respectively, have been synthesized and characterized by elemental analysis, infrared and electronic spectra, and 1H NMR spectra. Structures of the complexes were further confirmed by single-crystal X-ray determination. The V atom in the mononuclear complex 1 is in square pyramidal coordination, and those in the dinuclear complex 2 are in octahedral coordination. Both aroylhydrazone ligands coordinate to the V atoms through the phenolate O, imino N, and enolate O atoms. The ethanol ligand in complex 1 is in terminal coordination mode, while that in complex 2 is in bridging coordination mode. The complexes function as effective olefin epoxidation catalysts with hydrogen peroxide as terminal oxidant and sodium hydrogen carbonate as a co-catalyst. [ABSTRACT FROM AUTHOR]

Traditional haemostatic materials generally have slow hemostasis rate and poor biocompatibility. This paper reports on the haemostatic properties and mechanism of silk fibroin (SF). SF-PEG sponge that could be solubilised and changed to gel form by blood was fabricated through mixing SF and polyethylene glycol (PEG, 1500 Da) followed by lyophilisation of the mixed solution. SF-PEG sponge, together with control samples of SF sponge (no PEG) and a commercially available haemostatic material, gelatine sponge, were subjected to the hemostasis tests using a liver trauma model of rabbit. The results showed that SF was superior to gelatine sponge in hemostasis time (136.17 ± 62.27 s and 249.83 ± 29.18 s) and blood loss (2.16 ± 1.27 g vs. 4.97 ± 1.44 g). Furthermore, in vitro experiments indicated SF-PEG sol-gel transition promoted platelet adhesion and aggregation, as well as platelet-fibrinogen interaction. Therefore, except for the physical blocking of bleeding port due to PEG-induced SF fast gelation, SF might also have an impact on blood coagulation process, a phenomenon that has not been reported before. In conclusion, SF is a new type of haemostatic material that might be able to meet the requirements of speed, efficiency and biosafety in a variety of clinical applications. [ABSTRACT FROM AUTHOR]

Senile osteoporosis is closely related to the loss of function of stem cells. In this study, we tried to investigate the potential of secretome from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) in recovering stem cell ability from senescence and then delaying bone loss. We first harvested bone marrow-derived mesenchymal stem cells (BMSCs) from young and old rats and then compared their cellular characteristics such as cell growth, anti-senescence and differentiation. The results showed that these abilities were negatively affected by animal aging. Subsequently, aged BMSCs were exposed to secretome from hUCMSCs, and we found that this loss of cell potential can be modified by secretome treatment. Thereafter, the secretome was loaded into silk fibroin-based hydrogels and used for an in vivo animal study. The results showed that compared to the old untreated group, the bone formation capacity of aged rats was improved by local treatment of secretome-loaded silk fibroin hydrogels. In conclusion, these findings demonstrated that secretome from hUCMSCs has the capacity to recover stem cell potential and delay local bone loss in age-related osteoporosis, which could potentially be applied in osteoporosis therapy in the future. [ABSTRACT FROM AUTHOR]

The hypofunction of osteoblasts induced by glucocorticoids (GCs) has been identified as a major contributing factor for GC-induced osteoporosis (GIO). However, the biological mechanism underlying the effect of GC in osteoblasts are not fully elucidated. Recent studies implicated an important role of phosphoinositide 3-kinase (PI3K)/protein kinase B(Akt) signaling pathway in the regulation of bone growth. We propose that the PI3K/Akt signaling may be implicated in the process of GC-induced osteogenic inhibition in osteoblasts. In this study, primary osteoblasts were used in vitro and in rats in vivo to evaluate the biological significance of the PI3K/Akt pathway in GC-induced bone loss. In vivo, dexamethasone (Dex)-treated rats had low bone mineral density and decreased expression levels of alkaline phosphatase (ALP), osteocalcin (OCN), and phosphorylated Akt (p-Akt) in bone tissue. In vitro study shows that Dex over the dose of 10–8 M remarkably inhibited cellular osteogenesis, as represented by decreased cell viability, lessened ALP activity, and suppressed osteogenic protein expressions including ALP and OCN. Meanwhile, a dramatic downregulation in the PI3K/Akt pathway phosphorylation was also observed in Dex-treated osteoblasts. These changes were marked rescued by treatment with a PI3K agonist 740Y-P. Moreover, downregulation of ALP and OCN expressions by LY294002 can mimic the suppressive effects of Dex. These data together reveal that the suppressed PI3K/Akt pathway is involved in the regulatory action of Dex on osteogenesis. [ABSTRACT FROM AUTHOR]

Type A insulin resistance syndrome (TAIRS) is a rare subtype of congenital insulin resistance (IR), which is characterized by specific clinical manifestations without clear diagnostic criteria and is easily misdiagnosed or overlooked. Herein we present a case of TAIRS with acanthosis nigricans (AN), severe IR, polycystic ovaries, hyperandrogenism and its consequence such as menstrual disturbances, acne and hirsutism. A heterozygous mutation, p.Arg1201Gln, in the insulin receptor (INSR) was detected. This mutation in the tyrosine kinase domain has been described before and shown to impair tyrosine kinase activity and is responsible for IR. [ABSTRACT FROM AUTHOR]

In this work, poly(L-lactic acid) film was coated with SiOxby the plasma-enhanced chemical vapor deposition with different deposition times. Compared with the neat poly(L-lactic acid) film, the oxygen (O2), carbon dioxide (CO2), nitrogen (N2), and water vapor permeability of the poly(L-lactic acid)/SiOx60 film (depositing for 60 min) decreased by 40.7, 30.6, 58.7, and 53.4% at 25°C, respectively. After treated by the SiOxdeposition, the gas permselectivity of the poly(L-lactic acid)/SiOx60 film, such asα(CO2/O2),α(O2/N2), andα(CO2/N2), increased by 17.2, 43.9, and 67.5% at 25°C, respectively. In addition, Young’s modulus and tensile strength of poly(L-lactic acid)/SiOx60 film increased by 107.2 and 49.3%, respectively. Moreover, the poly(L-lactic acid)/SiOx60 films still kept good toughness with an elongation at break of 50.7%. [ABSTRACT FROM PUBLISHER]

Liposomal vinorelbine formulation is desirable, as it might improve the therapeutic activity of vinorelbine. However, because of its lipophilic and membrane-permeable properties, vinorelbine is hard to be formulated into liposomes using conventional drug-loading technologies. To improve vinorelbine retention, ammonium salts of several anionic agents were employed to prepare liposomal vinorelbine formulations. It was found that 5-sulfosalicylate (5ssa) could form stable complexes with vinorelbine and stabilize entrapped vinorelbine. The resultant vesicles had an in vitro release t1/2 of ~12.49 hours in NH3-containing media, which is longer than those of sulfate and phytate vesicles (~0.57 hours). The circulation half-life of vinorelbine after the injection of 5ssa vesicles into normal mice was ~13.01 hours, accounting for ~2-fold increase relative to that of sulfate vesicles. Improved drug retention correlated with enhanced antitumor efficacy. In the RM-1/c57 model, 5ssa vesicles were more efficacious than sulfate vesicles ( P < 0.05). In RM-1/BDF1 and Lewis lung cancer/c57 models, antitumor efficacy was also considerably improved after vinorelbine encapsulation into 5ssa vesicles. For instance, in the RM/BDF1 model, liposomal vinorelbine was at least 4-fold more therapeutically active than free vinorelbine. Our results demonstrated that 5ssa could stabilize vinorelbine relative to other anions, resulting in the formulation with improved drug retention and efficacy. Improved vinorelbine retention might be associated with the formation of insoluble precipitate, which could be proved by precipitation study and decreased drug-release rate at a high D/L ratio. [ABSTRACT FROM AUTHOR]

Smad4/DPC4, a common signal transducer in transforming growth factor beta (TGF-β) signaling, is frequently inactivated in human cancer. Although the ubiquitin-proteasome pathway has been established as one mechanism of inactivating Smad4 in cancer, the specific ubiquitin E3 ligase for ubiquitination-mediated proteolysis of Smad4 cancer mutants remains unclear. In this report, we identified the SCFSkp2 complex as candidate Smad4-interacting proteins in an antibody array-based screen and further elucidated the functions of SCFSkp2 in mediating the metabolic instability of cancer-derived Smad4 mutants. We found that Skp2, the F-box component of SCFSkp2, physically interacted with Smad4 at the physiological levels. Several cancer-derived unstable mutants exhibited significantly increased binding to Skp2, which led to their increased ubiquitination and accelerated proteolysis. These results suggest an important role for the SCFSkp2 complex in switching cancer mutants of Smad4 to undergo polyubiquitination-dependent degradation. [ABSTRACT FROM AUTHOR]

Smad4/DPC4, a common signal transducer in transforming growth factor beta (TGF-β) signaling, is frequently inactivated in human cancer. Although the ubiquitin-proteasome pathway has been established as one mechanism of inactivating Smad4 in cancer, the specific ubiquitin E3 ligase for ubiquitination-mediated proteolysis of Smad4 cancer mutants remains unclear. In this report, we identified the SCFSkp2 complex as candidate Smad4-interacting proteins in an antibody array-based screen and further elucidated the functions of SCFSkp2 in mediating the metabolic instability of cancer-derived Smad4 mutants. We found that Skp2, the F-box component of SCFSkp2, physically interacted with Smad4 at the physiological levels. Several cancer-derived unstable mutants exhibited significantly increased binding to Skp2, which led to their increased ubiquitination and accelerated proteolysis. These results suggest an important role for the SCFSkp2 complex in switching cancer mutants of Smad4 to undergo polyubiquitination-dependent degradation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To study the effects of progesterone (P) and 18-methyl levonorgestrel (LNG) on the expression of P receptors (PRA and PRB), c-fos, c-jun, and osteocalcin in the human osteosarcoma cell line MG-63 and human normal osteoblasts in order to understand the mechanism of progestin action on the proliferation and differentiation of osteoblasts. METHODS: Cell proliferation was tested by MTT assay. The expression of PR, c-fos, c-jun, and osteocalcin was measured by semi-quantitative RT-PCR, Western immunoblot or immunocytochemistry. RESULTS: Progesterone and LNG (10−10–10−6 M) stimulated cell proliferation in a dose-dependent manner. Progesterone and LNG did not affect the expression of PRA and PRB mRNA and protein, but c-fos and c-jun mRNA and protein were upregulated in a dose-dependent manner. The expression of osteocalcin mRNA was also increased in human osteoblasts in a dose and time-dependent manner with greater effects of LNG than P, while the expression of osteocalcin mRNA in MG-63 cells was not changed by P or LNG. CONCLUSION: Progesterone and LNG promote osteocalcin gene transcription by stimulating the expression of c-fos and c-jun, and result in osteoblast proliferation and differentiation. [ABSTRACT FROM AUTHOR]

Zebrias zebrinus belongs in the family Soleidae of Pleuronectiformes. There are overlaps in the ranges of identification characters between Z. zebrinus and another striped sole Z. fasciatus. In this study, the complete mitochondrial genome of Z. zebrinus was first determined. The total length was 16,758 bp, including 13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes ( 12S and 16S), as well as a putative control region and a putative L-strand replication origin (OL). Gene contents, locations, and arrangements were identical to those of typical bony fishes. The overall base composition of the mitogenome was 28.7%, 30.0%, 15.2%, and 26.1% for A, C, G, and T, respectively, with an A+T content of 54.8%. This result would expect the contribution to the molecular identification of this species and further phylogenetic study of Soleidae and Pleuronectiformes. [ABSTRACT FROM AUTHOR]