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The present work involved ultrasound-promoted KI-Oxone mediated oxidative C–N bond formation from a reaction of β-ketoester and 2-aminopyridines leading to novel functional imidazo[1,2-a]pridine-3-carboxylates (IPCs). The α-halogenation of β-ketoester has been easily carried out by in situ formed I+ OH− species from the KI-Oxone system. IR, NMR, and Mass spectra characterized all derivatives. The structure of the synthesized IPCs was confirmed by X-ray crystallographic analysis. A transition metal-free protocol, one-pot synthesis, non-toxic reagents, benign reaction conditions, high yield, short reaction time, and the synthesis of highly functional IPCs are the remarkable features of the present method. The synthesized IPCs show unusual anti-tubercular activity. [ABSTRACT FROM AUTHOR]

Skeletal muscle is a highly specialized tissue composed of myofibres that performs crucial functions in movement and metabolism. In response to external stimuli and injuries, a range of stem/progenitor cells, with muscle stem cells or satellite cells (MuSCs) being the predominant cell type, are rapidly activated to repair and regenerate skeletal muscle within weeks. Under normal conditions, MuSCs remain in a quiescent state, but become proliferative and differentiate into new myofibres in response to injury. In addition to MuSCs, some interstitial progenitor cells (IPCs) such as fibro-adipogenic progenitors (FAPs), pericytes, interstitial stem cells expressing PW1 and negative for Pax7 (PICs), muscle side population cells (SPCs), CD133-positive cells and Twist2-positive cells have been identified as playing direct or indirect roles in regenerating muscle tissue. Here, we highlight the heterogeneity, molecular markers, and functional properties of these interstitial progenitor cells, and explore the role of muscle stem/progenitor cells in skeletal muscle homeostasis, aging, and muscle-related diseases. This review provides critical insights for future stem cell therapies aimed at treating muscle-related diseases. [ABSTRACT FROM AUTHOR]

Aluminum/epoxy resin interpenetrating phase composites (IPCs) were directly strengthened by adding glass fiber of varying content (80 wt%, 100 wt%, 120 wt% and 140 wt%) inside the epoxy resin. The macro and micro structures of IPCs were intact, and the interface between aluminum and epoxy resin was well combined. As the content of glass fiber increased, the compressive strength of epoxy resin increased, but the failure was advanced, while IPCs displayed the opposite trend. IPCs exhibited three compression deformation modes, namely plastic deformation of aluminum, resin fracture and interface debonding. The digital image correlation and infrared thermal imager were used to characterize the apparent principal strain distribution and temperature distribution of IPCs to verify the deformation modes. The surface temperature damage evolution of IPCs included the rapid temperature rise stage, steady temperature stage and slight temperature drop stage, respectively, mainly corresponding to the linear elastic stage, plateau stage and densification stage in the stress-strain curves. [ABSTRACT FROM AUTHOR]

The corner detection plays an important role in the area of image processing and computer vision. The current corner detection methods often utilize few cues or single model to improve the detection correctness and repeatability. A composite model of both intensity, pattern, curvature, and scale is proposed as a possible solution to these problems. Firstly, a corner measure function that reflects both the intensity, pattern, and curvature difference is formulated based on the 8-neighbor pixel blocks. Secondly, some scale-based global scale importance factors are formulated based on the contour distribution and corner distribution. Thirdly, based on the corner measure and the importance factors, a high-performance corner detector (IPCS) is derived. The experiments based on both the ground truth and the standard image set are conducted to evaluate the correctness and repeatability of the proposed detector. The experiment results come up with that the proposed detector has remarkable performance advantages among the comprising state-of-the-art detectors. [ABSTRACT FROM AUTHOR]

Silicon carbide foams (SiCf) are used as potential materials for heat shielding elements in the aerospace, automotive, and chemical industries due to their exceptional thermal stability, low density, and high hardness. However, the very low strength of SiCf limits its use for developing load-bearing structural components. Impregnating a suitable metal into the SiCf makes them suitable for high-strength applications. The processing route designated for impregnating the metal into the SiCf determines the strength of the resulting material. This article outlines the mechanical behaviour of the novel LM25 aluminium alloy-SiCf-based interpenetrating phase composites (IPCs) developed using the gas pressure infiltration technique. The LM25 alloy was infiltrated into SiCf with three different pore sizes, namely 10, 20, and 30 pores per inch (PPI). The macroscopic morphology of the IPCs revealed that a strong bond has been established between LM25 and SiCf. The compressive strengths of IPCs developed using 10, 20, and 30 PPI-SiCf were 97.5, 53.65, and 32.18 times higher than those of the respective SiCf. Similarly, the fracture strength and fracture toughness of the IPCs manufactured using 10, 20, and 30 PPI-SiCf were 7.44, 5.85, and 6.05 times better than those of the respective SiCf. Amongst the three variants of IPCs, the IPC developed using 10 PPI-SiCf possessed the highest values of compressive strength, fracture strength, and fracture toughness. However, the IPC developed using 30 PPI-SiCf exhibited superior resistance to indentation. Macro- and micro-structural analyses were conducted to establish the failure modes of the IPCs under both compression and flexure loads. [ABSTRACT FROM AUTHOR]

This study aimed to identify the suitable induction protocol to produce highly qualified insulin producing cells (IPCs) from human adipose tissue derived stem cells (ADSCs) and evaluate the efficacy of the most functionally IPCs in management of diabetes mellitus (DM) in rats. The ADSCs were isolated and characterized according to the standard guidelines. ADSCs were further induced to be IPCs in vitro using three different protocols. The success of trans-differentiation was assessed in vitro through analysis of pancreatic endocrine genes expression, and insulin release in response to glucose stimulation. Then, the functionalization of the generated IPCs was evaluated in vivo. The in vitro findings revealed that the laminin-coated plates in combination with insulin-transferrin-selenium, B27, N2, and nicotinamide could efficiently up-regulate the expression of pancreatic endocrine genes. The in vivo study indicated effectual homing of the PKH-26-labelled IPCs in the pancreas of treated animals. Moreover, IPCs infusion in diabetic rats induced significant improvement in the metabolic parameters and prompted considerable up-regulation in the expression of the pancreatic related genes. The regenerative effect of infused IPCs was determined through histological examination of pancreatic tissue. Conclusively, the utilization of laminin–coated plates in concomitant with extrinsic factors promoting proliferation and differentiation of ADSCs could efficiently generate functional IPCs. [ABSTRACT FROM AUTHOR]

Insulin-producing cells (IPCs) generated by our established protocol have reached the non-clinical 'proof of concept' stage. Our strategy for their clinical application is the autotransplantation of IPCs into patients with type 1 diabetes mellitus (T1DM). In this context, the autoimmunity that characterized T1DM is important, rather than allorejection. We aimed to determine how these IPCs respond to T1DM autoimmunity. IPCs were generated from the subcutaneous fat tissue of non-obese diabetic (NOD) mice using our protocol. IPCs derived from NOD mice were transplanted under the kidney capsules of NOD mice at the onset of diabetes and the subsequent changes in blood glucose concentration were characterized. Blood glucose decreased within 30 days of transplantation, but increased again after 40–60 days in three of four recipient NOD mice. In tissue samples, the numbers of CD4+ and CD8+ T cells were significantly higher 60 days after transplantation than 30 days after transplantation. In conclusion, IPCs significantly ameliorate the diabetes of mice in the short term, but are damaged by autoimmunity in the longer term, as evidenced by local T cells accumulation. This study provides new insights into potential stem cell therapies for T1DM. [ABSTRACT FROM AUTHOR]

This study is devoted to a comparison of morphofunctional peculiarities and the ratio of apoptosis and proliferation processes in the populations of insulin-producing cells (IPCs) of the pancreas of different localization (pancreatic islets (PIs), single IPCs, and agglomerates thereof) under physiological conditions. A quantitative estimation of the distribution of IPCs of different localization, intensity of immunofluorescent labeling of insulin, and ratio of proliferation and apoptosis processes was carried out on histological preparations of the pancreas. Single IPCs of acinar epithelium have the largest synthetic potential as compared with IPCs of another localization, which is indicated by the maximal values of the intensity of insulin fluorescence and cytoplasm area. Ki-67+ IPC are present only in PIs while they are not detected outside the insular part. A majority of TUNEL+ IPCs is typical for agglomerates, and TUNEL+ IPCs are absent among single IPCs. A direct interconnection between the intensity of fluorescence of islet β-cell insulin and the amount of Ki-67+ IPCs in them is detected. The islets with a high intensity of insulin fluorescence also a larger amount of TUNEL+ IPCs than do other PIs, which indicates a significant level of their self-renewal. At the same time, a PI with a low content of insulin is characterized by a significant predominance of the process of apoptosis over proliferation. Thus, our data indicate that the structure and functional activity of IPCs depend on the peculiarity of their localization, while their heterogeneity creates the basis for plasticity under the conditions of pathology. [ABSTRACT FROM AUTHOR]

To produce insulin-producing cells (IPCs) from bone marrow mesenchymal stem cells (BM-MSCs) using a simple and cost effective method. During the initial 7 days of three-dimensional (3D) culture, BM-MSCs were cultured on 1% agar or agarose to form multicellular spheroids. Spheroids and spheroid-derived single cells (SS and SSC, respectively) were cultured in the absence of any proteinaceous growth factor in a simple specific medium for a further 7 d. The insulin content of the differentiated cells was evaluated at the mRNA and protein levels. Furthermore, the expression of pancreatic beta cells-related genes other than INS as well as the in vitro responses of IPCs to different glucose concentrations were investigated. Cellular clusters generated on agar and SS conditions (agar+SS-IPCs) stained better with beta cell specific stains and were more reactive to serum-containing insulin reactive antibodies compared with agarose-SS-IPCs. Gene expression analysis revealed that in comparison to agarose + SS-IPCs, agar+SS-IPCs expressed significantly higher levels of INS-1, INS-2, PDX-1, NKX6.1, and XBP-1. Of interest, agar+SS-IPCs expressed 2215.3 ± 120.8-fold more INS-1 gene compared to BM-MSCs. The expression of β-cell associated genes was also higher in agar+SS-IPCs compared to the agar+SSC-IPCs. Moreover, the expression of INS-1 gene was significantly higher in agar+SS-IPCs compared with agar+SSC-IPCs after culture in media with high concentration of glucose. Compared to the most expensive and time-consuming protocols, 3D culture of MSCs on agar followed by 2D culture of cellular clusters in a minimally supplemented high glucose media produced highly potent IPCs which may pay the way to the treatment of diabetic patients. [ABSTRACT FROM AUTHOR]

The adoptive transfer of insulin-producing cells (IPCs) is one of the promising treatments for insulin-dependent diabetes mellitus. While the use of allogeneic cell resources is inevitable in the case of a series of patients, alloimmune responses are a major barrier ahead of the successful implementation of allogeneic therapeutic cells. This study is aimed at evaluating the potential of CTLA4-Ig, as an approved immunomodulatory biologic, in protecting the IPCs against allogeneic immune responses. The C57BL/6 and BALB/c mice were used to establish a murine model of allogeneic cell transplantation. The mouse bone-marrow-derived mesenchymal stem cells were in vitro differentiated into IPCs, and the in vitro as well as the in vivo immune responses against IPCs were evaluated in the presence and absence of CTLA4-Ig. The allogeneic IPCs induced the in vitro activation of CD4+ T-cells, IFN-γ release, and the proliferation of lymphocytes, which all were controlled by CTLA4-Ig. Upon in vivo transfer of IPC into an allogeneic host, the splenic CD4+ and CD8+ T-cells exhibited a significant activation, and there was a significant donor-specific antibody response. Either of the mentioned cellular and humoral responses were modulated by a CTLA4-Ig regimen. This regimen also reduced the infiltration of CD3+ T-cells into the IPC injection site along with the improved overall survival of diabetic mice. CTLA4-Ig could be a complementary therapy for improving the efficacy of allogeneic IPC therapy through modulating the cellular and humoral responses that can lead to prolonged durability of IPCs within an allogeneic host. [ABSTRACT FROM AUTHOR]

Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into insulin-producing cells (IPCs). Bio-scaffolds derived from decellularized organs can act as a carrier for seed cells and may have broad applications in regenerative medicine. This study investigated the effect of native pancreatic stroma obtained from decellularized pancreas on the proliferation, migration and differentiation of BMSCs into IPCs, and explored the potential underlying molecular mechanism. The decellularized pancreas bio-scaffold was obtained by perfusion with Triton X-100/ammonium hydroxide, followed by digestion with a mixture of pepsin and hydrochloric acid to prepare the stroma solution. Islet-like cells were differentiated from BMSCs by a three-step induction method. The differences on the cytological behavior with or without stroma were evaluated by morphological observation, insulin release assay, qRT-PCR assay and western blot analysis. Our results showed that, stroma derived from decellularized pancreas could promote the proliferation and migration of BMSCs. Furthermore, the formation of IPCs could also be promoted, which possessed similar morphology to endogenous islets. During the induced differentiation process, the presence of stroma significantly increased the expression of insulin 1, insulin 2 and Pdx-1, as well as insulin release. This was accompanied by an increase in the phosphorylation of Akt and ERK in third stage cell clusters, which was prevented by the addition of the inhibitors PD98059 and LY294002, respectively. In summary, decellularized pancreatic stroma could promote the proliferation, migration and differentiation of BMSCs into IPCs, and this involved the activation of Akt and ERK signal pathways. [ABSTRACT FROM AUTHOR]

Amid a patent boom and increase in patent infringement cases, China is a fast-growing catch-up country in the intellectual property (IP) regime, with arguments on effectiveness and standardization. In 2014, China installed three intellectual property courts (IPCs) in Beijing, Shanghai, and Guangzhou. This reform represents a crucial step in a series of reforms and actions that seek to establish a uniform and standardized judicial IP regime in China. Based on interviews, statistical reports, and an analysis of judicial documents, this study argues that the interpretation and execution of IP law vary across the three locations due to the embeddedness of those courts and their judges in the regions. Indications that the regional setting and presence of international firms affect the efficient proceedings of IP tribunals and courts were found as a result. Given that IP law is the same all over a country, it can be concluded that courts balance national regulation and regional realities. [ABSTRACT FROM AUTHOR]

Ethylene-propylene block copolymer (EbP) is a vital component in impact polypropylene copolymer (IPC), yet its distribution in the multiphase composite material and how it influences the phase structure and the mechanical properties are not well understood. In this work, four IPCs were investigated by atomic force microscopy-infrared (AFM-IR) to assess the phase compositions in situ, based on which in conjunction with the chain microstructure information obtained ex situ the distributions of the copolymer components were derived for each alloy. For the IPCs whose EbP comprises long P and long E segments, the EbP fraction was found to phase separate from the rubber and the PP matrix to form the cores of the disperse particles with the E-P segmented copolymer (EsP). In contrast, in the IPC with EbP composed of long P and short E segments, the EbP fraction formed an outer shell for the rubber particles with the cores comprising the EsP alone, and this IPC, containing a lower E comonomer content than its counterpart, exhibited both better impact resistance and higher flexural modulus. These results clarify how the chain structure of EbP governs the phase morphology in IPC, which in turn impacts the properties of the composite material. [ABSTRACT FROM AUTHOR]

Canine mesenchymal stem cells (cMSCs) have potential applications for regenerative therapy, including the generation of insulin-producing cells (IPCs) for studying and treating diabetes. In this study, we established a useful protocol for generating IPCs from canine adipose mesenchymal stem cells (cAD-MSCs). Subsequently, in vitro preservation of pluronic F127-coated alginate (ALGPA)-encapsulated cAD-MSC-derived IPCs was performed to verify ready-to-use IPCs. IPCs were induced from cAD-MSCs with the modulated three-stepwise protocol. The first step of definitive endoderm (DE) induction showed that the cooperation of Chir99021 and Activin A created the effective production of Sox17-expressed DE cells. The second step for pancreatic endocrine (PE) progenitor induction from DE indicated that the treatment with taurine, retinoic acid, FGF2, EGF, TGFβ inhibitor, dorsomorphin, nicotinamide, and DAPT showed the significant upregulation of the pancreatic endocrine precursor markers Pdx1 and Ngn3. The last step of IPC production, the combination of taurine, nicotinamide, Glp-1, forskolin, PI3K inhibitor, and TGFβ inhibitor, yielded efficiently functional IPCs from PE precursors. Afterward, the maintenance of ALGPA-encapsulated cAD-MSC-derived IPCs with VSCBIC-1, a specialized medium, enhanced IPC properties. Conclusion, the modulated three-stepwise protocol generates the functional IPCs. Together, the encapsulation of cAD-MSC-derived IPCs and the cultivation with VSCBIC-1 enrich the maturation of generated IPCs. [ABSTRACT FROM AUTHOR]

Bustling port activities give rise to serious air pollution in port cities of China's Yangtze River Delta (YRD). Understanding the characteristics and driving forces of air pollutants over port cities of the YRD is conducive to the prevention and control of air pollution. This study analyzed the spatiotemporal characteristics and influencing factors of three air pollutants—PM2.5, NO2, and SO2—over coastal port cities (CPCs) and inland port cities (IPCs) in YRD from 2015 to 2020. The concentrations of air pollutants vary across geographic locations (low in the south/east and high in the north/west) and seasons (low in summer and high in winter). IPCs show higher pollutant concentrations than CPCs. The PM2.5, NO2, and SO2 concentrations over port cities in the YRD declined by 41.48%, 18.68%, and 64.8% from 2015 to 2020; CPCs have reduced more PM2.5 and NO2 than IPCs, while IPCs have reduced more SO2 than CPCs. There is a high synergy among the three air pollutants, with a stronger synergy found in CPCs. The impacts of wind speed and boundary layer height on air pollution are greater in CPCs than in IPCs. Concentrations of different air pollutants are strongly associated with emissions from different sectors. NO2 is the only one among the three air pollutants that cargo throughput shows a significant impact on, with the impact greater in CPCs than in IPCs. Findings from this study deepen the understanding of air pollution in port cities of YRD and may support air quality control in this area. [ABSTRACT FROM AUTHOR]

Glucose-induced oxidative stress in the diabetic pancreas directly affects viability and the consequent therapeutic outcome of transplanted stem cells. Pretreatment of stem cells with growth factors induces tolerance in them against various stresses (hypoxia, thermal or hyperglycaemic). This study investigated the effect of pretreatment on insulin-producing cells (IPCs) differentiated from adipose-derived mesenchymal stem cells (ADMSCs), with a combination of stromal cell-derived factor 1 alpha (SDF1α) and basic fibroblast growth factor (bFGF) against hyperglycaemic stress (17 or 33 mM glucose). The results showed that IPCs pretreated with a combination of SDF1α and bFGF exhibited maximally alleviated apoptosis, senescence and cell damage with a concomitantly increased release of insulin, enhanced cell proliferation and greater up-regulation of Insulin 1, Insulin 2, Ngn3, Pdx1 and Nkx6.2 when stressed with 33 mM glucose. These findings may offer an improved therapeutic outcome for the treatment of diabetes. [ABSTRACT FROM AUTHOR]

The International Program on Chemical Safety (IPCS), a collaborative program of the United Nations Environment Program, the International Labour Organization (ILO), and the World Health Organization (WHO), includes the Environmental Health Criteria (EHC) Program inaugurated in 1973 by WHO. These EHC are integrated evaluations of the human health and environmental risks from exposure to specific chemicals carried out by a group of international scientists. Boron (B) was evaluated at an IPCS Task Group (TG) convened in November 1996. All TGs are convened under WHO rules and procedures. These procedures relate the overall process used to prepare an EHC including transparency of the process, conflict of interest, the roles of Members and Observers, and the conduct of the TG. The scope and purpose of an EHC, for an element such as B, and its possible role in national and international chemical safety programs will be discussed. In the early 1990s, countries asked that IPCS request TGs to prepare, where data permit, health-based guidance values (GVs) (both total daily intake and to recommend health-based guidelines for various environmental media). This final evaluation in an EHC reflects the collective consensus view of the TG Members. To foster the use of consistent methodology by TGs, IPCS prepared in 1994 an EHC on the methodology for the preparation of GVs for human exposure limits (EHC 170). In developing their final evaluation, TGs have been asked to consider using this methodology. This was done by the TG on B, and a total daily intake for humans of 0.4 mg/kg body wt was derived from animal studies of reproductive and developmental effects in rodents and pharmacokinetic data from both animals and humans. The application of the methodology described in EHC 170 regarding choice of critical effect and uncertainty factors will be discussed. [ABSTRACT FROM AUTHOR]

Pancreatic β cells secrete insulin in response to glucose elevation to maintain glucose homeostasis. A complex network of inter-organ communication operates to modulate insulin secretion and regulate glucose levels after a meal. Lipids obtained from diet or generated intracellularly are known to amplify glucose-stimulated insulin secretion, however, the underlying mechanisms are not completely understood. Here, we show that a Drosophila secretory lipase, Vaha (CG8093), is synthesized in the midgut and moves to the brain where it concentrates in the insulin-producing cells in a process requiring Lipid Transfer Particle, a lipoprotein originating in the fat body. In response to dietary fat, Vaha stimulates insulin-like peptide release (ILP), and Vaha deficiency results in reduced circulatory ILP and diabetic features including hyperglycemia and hyperlipidemia. Our findings suggest Vaha functions as a diacylglycerol lipase physiologically, by being a molecular link between dietary fat and lipid amplified insulin secretion in a gut-brain axis. Amplification of glucose stimulated insulin secretion by lipids is not fully understood due to complex inter organ communication in glycemic regulation. Here the authors show Vaha, a Drosophila lipase synthesized in the gut, concentrates in insulin producing cells in the brain to regulate insulin like peptide release. [ABSTRACT FROM AUTHOR]

In vitro-generation of β-cells from Wharton’s jelly mesenchymal stem cells (WJ-MSCs) could provide a potential basis for diabetes mellitus cell therapy. However, the generation of functional insulin-producing cells (IPCs) from WJ-MSCs remains a challenge. Recently, obestatin, a gut hormone, was found to promote β-cell generation from pancreatic precursor cells. Accordingly, we hypothesize that obestatin can induce the differentiation of WJ-MSCs into IPCs. Therefore, the purpose of the current study is to examine the ability of obestatin to generate IPCs in comparison to well-known extrinsic factors that are commonly used in IPCs differentiation protocols from MSCs, namely exendin-4 and glucagon-like peptide-1 (GLP-1). To achieve our aims, WJ-MSCs were isolated, cultured and characterized by immunophenotyping and adipocytes differentiation. Afterwards, WJ-MSCs were induced to differentiate into IPCs using two differentiation protocols incorporating either exendin-4, GLP-1 or obestatin. The pancreatic progenitor marker, nestin and β-cell differentiation markers were assessed by qRT-PCR, while the functionality of the generated IPCs was assessed by glucose-stimulated insulin secretion (GSIS). Our results showed that WJ-MSCs exhibit all the characteristics of MSCs. Interestingly, using obestatin in both the short and long differentiation protocols managed to induce the expression of β-cell markers, similar to exendin-4. In GSIS, IPCs generated using either GLP-1 or obestatin showed higher secretion of insulin as compared to those generated using exendin-4 under low-glucose conditions but failed to show a significant response to increased glucose. These results indicate obestatin can be considered as a novel potential factor to consider for generation of IPCs from WJ-MSCs. [ABSTRACT FROM AUTHOR]

Today, significant success has been achieved in treating diabetes with cell therapy derived from various sources of stem and progenitors. The replacement of beta cells is one of the new diabetes treatment methods. To this end, the production of pancreatic beta precursors in cell culture has created an important research field for diabetes treatment. Endometrial stem cells were isolated using an enzymatic method, and after their identity was confirmed using a flow cytometry and differentiation potential assay, the isolated cells were cultured on an electrospun PCL/CS scaffold. Endometrial cells were differentiated into insulin-producing cells (IPCs), and gene expression was analyzed using the qRT-PCR and immunofluorescence to confirm the creation of IPCs. Then, IPCs on the scaffold along with berberine were applied to 5 groups of diabetic mice, and after 6 weeks, insulin, blood glucose, and weight of the animals were measured. The findings revealed that pancreatic markers were significantly expressed in IPCs compared to control cells. In addition, when compared to the control group and scaffolds, the receiving group of IPCs on scaffolds had a significant improvement (p ≤ 0.0015), and this improvement increased with the addition of berberine (decrease in blood sugar (133 mg/dL), and an increase in weight (5/39 g) and insulin (2.29 MIU/L). Thus, tissue engineering is a promising new strategy for treating diabetes and can be used in the future for cell therapy and suitable drugs for diabetic patients. [ABSTRACT FROM AUTHOR]

FDA has approved iron oxide nanoparticles (IONs) coated with organic compounds as a safe material with less toxic effects compared with the naked metal ions and nanoparticles. In this study, the biological and physicochemical characteristics of a nanostructured iron-polysaccharide complexes (Nano-IPC) biosynthesized by Enterobacter sp. were evaluated. Furthermore, the serum biochemical parameters, tissue iron level, red blood cell parameters, and organ ferritin of rats were measured for investigating the effect of the Nano-IPCs in comparison with FeSO4 as a supplement for iron deficiency. The biosafety data demonstrated 35% increment of viability in Hep-G2 hepatocarcinoma cell lines when treated with nanoparticles (500 μg/mL) for 24 h. Besides, iron concentration in serum and tissue as well as the expression of ferritin L subunit in animals treated with the Nano-IPCs supplement were meaningfully higher than the FeSO4-supplemented and negative control animals. Moreover, the expression level of ferritin H subunit and biochemical factors remained similar to the negative control animals in the Nano-IPC-supplemented group. These results indicated that Nano-IPCs can be considered as a nontoxic supplement for patients carrying iron-deficiency anemia (IDA). [ABSTRACT FROM AUTHOR]

Interpenetrating phase composites (IPCs) are interesting materials, in which each phase can contribute its most desirable attributes to the composite as a whole by its contiguous morphology. In the present study, molybdenum-copper (Mo-Cu) composites with interpenetrating microstructure were fabricated by open-celled porous Mo skeleton with infiltration of Cu. Effects of sintering temperature on the Mo-Mo contiguity and compressive properties of the Mo-Cu IPCs were examined. The contiguity of Mo-Mo and compressive strength increase with the sintering temperature increasing from 1473 to 1873 K, and decrease at 2073 K. Volume fraction of Cu infiltrated in Mo skeleton and failure strain of composites decrease with the sintering temperature increasing from 1473 to 1873 K and increase at 2073 K. Mutual dependency of compressive properties and contiguity of Mo-Cu IPCs are illustrated. [ABSTRACT FROM AUTHOR]

Introduction: Clinical outcomes of implantable port catheters (IPCs) placed via alternative veins such as the external jugular and cervical collaterals have not been well established. This investigation evaluates the short- and long-term outcomes of IPCs inserted via alternate cervical veins (ACV) compared to traditionally inserted IPCs via the internal jugular vein (IJV). Materials and Methods: A total of 24 patients who received an IPC between 2010 and 2020 via an ACV—defined as the external jugular vein, superficial cervical vein, or unnamed collateral veins—were identified. Based on power analysis, a matched control group of 72 patients who received IPCs via the IJV was identified. Non-inferiority analysis for port complications was performed between the two groups based on the selected non-inferiority margin of 20%. Secondary end points included complication-free survival and comparison of complications by the time at which they occurred. Results: ACV access was non-inferior to traditional access for overall complications. Alternate access resulted in fewer complications than traditional access with an estimated reduction of − 7.0% [95% CI − 23.6%, 39.7%]. There was no significant difference in peri-procedural and post-procedural complications between the two groups. Complication-free survival was also equivalent between the two groups. Conclusion: IPC placement via ACVs was non-inferior to IPCs placed via traditional access through the IJV. When abnormal pathology obviates the use of IJV access, other cervical veins may be considered prior to seeking alternate locations such as femoral, translumbar, inferior vena cava, and hepatic veins. [ABSTRACT FROM AUTHOR]

Generic drugs play an important role in public health. However, the first review cycle approval rate for Abbreviated New Drug Applications (ANDAs) is generally low. To identify if the drug product (DP) manufacturing related deficiencies are the potential root causes of low first review cycle approval of the modified release (MR) tablet ANDAs, we collected and analyzed the review recommendations from each review discipline and the DP manufacturing (process and facility) related deficiencies for original MR tablet ANDAs submitted between FY17 and FY19. We identified 193 original MR tablet ANDAs. The analysis showed that 12% of the applications were approved in first review cycle, while 88% received complete responses (CR). Of the 169 CR applications, 91% were found inadequate for multiple review disciplines. A total of 1345 DP manufacturing process-related deficiencies were issued to 184 ANDAs during the first review cycle. We have identified common deficiencies across ANDAs based on DP manufacturing process categories. The top deficiencies cited reasons include facilities are out of compliance/not ready to commercialize/not ready for inspection; critical process parameter (CPP) ranges are not proposed/proposed CPP ranges are too wide and/or not supported by studied range and no in-process controls (IPCs) are proposed/proposed IPCs acceptance criteria (limits) are too wide and/or not supported by observed data etc. Avoiding the common DP manufacturing deficiencies may reduce the need for issuing DP manufacturing related deficiencies in information requests (IRs), discipline review letters (DRLs), and CRs for MR tablet ANDAs. [ABSTRACT FROM AUTHOR]

Insulin signaling regulates lifespan, reproduction, metabolic homeostasis, and resistance to stress in the adult organism. In Drosophila, there are seven insulin-like peptides (DILP1-7). Three of these (DILP2, 3 and 5) are produced in median neurosecretory cells of the brain, designated IPCs. Previous work has suggested that production or release of DILPs in IPCs can be regulated by a factor secreted from the fat body as well as by neuronal GABA or short neuropeptide F. There is also evidence that serotonergic neurons may regulate IPCs. Here, we investigated mechanisms by which serotonin may regulate the IPCs. We show that the IPCs in adult flies express the 5-HT, but not the 5-HT or 5-HT receptors, and that processes of serotonergic neurons impinge on the IPC branches. Knockdown of 5-HT in IPCs by targeted RNA interference (RNAi) leads to increased sensitivity to heat, prolonged recovery after cold knockdown and decreased resistance to starvation. Lipid metabolism is also affected, but no effect on growth was seen. Furthermore, we show that DILP2-immunolevels in IPCs increase after 5-HT knockdown; this is accentuated by starvation. Heterozygous 5-HT mutant flies display the same phenotype in all assays, as seen after targeted 5-HT RNAi, and flies fed the 5-HT antagonist WAY100635 display reduced lifespan at starvation. Our findings suggest that serotonin acts on brain IPCs via the 5-HT receptor, thereby affecting their activity and probably insulin signaling. Thus, we have identified a second inhibitory pathway regulating IPC activity in the Drosophila brain. [ABSTRACT FROM AUTHOR]

This study aims at examining the psychometric properties of the Chinese version of the Intimacy, Passion, and Commitment Scale (IPCS), which measures the three components of love (intimacy, passion, and commitment) in the triangular theory of love. Participants were 263 Hong Kong Chinese (108 males and 155 females) aged from 17 to 57 years (M = 24.34, SD = 6.01), who were involved in heterosexual romantic relationships. As predicted, the results of parallel analysis suggested a three-factor solution. The results of confirmatory factor analysis showed an acceptable model fit for the hypothesized three-factor structure. Multiple-group confirmatory factor analyses demonstrated the factorial invariance of the three-factor model across gender. The intimacy, passion, and commitment subscales demonstrated high internal consistency reliability. The three factors had substantial associations with relationship satisfaction, indicating adequate concurrent validity. Overall, the findings of this study provide initial support for the psychometric properties of the Chinese version of the IPCS. [ABSTRACT FROM AUTHOR]

Neurogenesis persists in two locations of the adult mammalian brain, the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. In the adult subgranular zone, radial gliallike cells (RGLs) are multipotent stem cells that can give rise to both astrocytes and neurons. In the process of generating neurons, RGLs divide asymmetrically to give rise to one RGL and one intermediate progenitor cell (IPC). IPCs are considered to be a population of transit amplifying cells that proliferate and eventually give rise to mature granule neurons. The properties of individual IPCs at the clonal level are not well understood. Furthermore, it is not clear whether IPCs can generate astrocytes or revert back to RGLs, besides generating neurons. Here we developed a genetic marking strategy for clonal analysis and lineage-tracing of individual Tbr2-expressing IPCs in the adult hippocampus in vivo using Tbr2-CreER mice. Using this technique we identified Tbr2-CreER labeled IPCs as unipotent neuronal precursors that do not generate astrocytes or RGLs under homeostasis. Additionally, we showed that these labeled IPCs rapidly generate immature neurons in a synchronous manner and do not undergo a significant amount of amplification under homeostasis, in animals subjected to an enriched environment/running, or in animals with different age. In summary, our study suggests that Tbr2-expressing IPCs in the adult mouse hippocampus are unipotent precursors and rapidly give rise to immature neurons without major amplification. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare the difference between insulin-producing cells (IPCs) and normal human pancreatic beta cells both in physiological function and morphological features in cellular level. Methods: The levels of insulin secretion were measured by enzyme-linked immunosorbent assay. The insulin gene expression was determined by real-time quantitative polymerase chain reaction. The morphological features were detected by atomic force microscopy (AFM) and laser confocal scanning microscopy. Results: IPCs and normal human pancreatic beta cells were similar to each other under the observation in AFM with the porous structure features in the cytoplasm. Both number of membrane particle size and average roughness of normal human beta cells were higher than those of IPCs. Conclusions: Our results firstly revealed that the cellular ultrastructure of IPCs was closer to that of normal human pancreatic beta cells, but they still could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells. [ABSTRACT FROM AUTHOR]

The trend of regenerative therapy for diabetes in human and veterinary practices has conceptually been proven according to the Edmonton protocol and animal models. Establishing an alternative insulin-producing cell (IPC) resource for further clinical application is a challenging task. This study investigated IPC generation from two practical canine mesenchymal stem cells (cMSCs), canine bone marrow-derived MSCs (cBM-MSCs) and canine adipose-derived MSCs (cAD-MSCs). The results illustrated that cBM-MSCs and cAD-MSCs contain distinct pancreatic differentiation potential and require the tailor-made induction protocols. The effective generation of cBM-MSC-derived IPCs needs the integration of genetic and microenvironment manipulation using a hanging-drop culture of PDX1-transfected cBM-MSCs under a three-step pancreatic induction protocol. However, this protocol is resource- and time-consuming. Another study on cAD-MSC-derived IPC generation found that IPC colonies could be obtained by a low attachment culture under the three-step induction protocol. Further, Notch signaling inhibition during pancreatic endoderm/progenitor induction yielded IPC colonies through the trend of glucose-responsive C-peptide secretion. Thus, this study showed that IPCs could be obtained from cBM-MSCs and cAD-MSCs through different induction techniques. Also, further signaling manipulation studies should be conducted to maximize the protocol's efficiency. [ABSTRACT FROM AUTHOR]

Additive manufacturing has been recognized as an industrial technological revolution for manufacturing, which allows fabrication of materials with complex three-dimensional (3D) structures directly from computer-aided design models. Using two or more constituent materials with different physical and mechanical properties, it becomes possible to construct interpenetrating phase composites (IPCs) with 3D interconnected structures to provide superior mechanical properties as compared to the conventional reinforced composites with discrete particles or fibers. The mechanical properties of IPCs, especially response to dynamic loading, highly depend on their 3D structures. In general, for each specified structural design, it could take hours or days to perform either finite element analysis (FEA) or experiments to test the mechanical response of IPCs to a given dynamic load. To accelerate the physics-based prediction of mechanical properties of IPCs for various structural designs, we employ a deep neural operator (DNO) to learn the transient response of IPCs under dynamic loading as surrogate of physics-based FEA models. We consider a 3D IPC beam formed by two metals with a ratio of Young's modulus of 2.7, wherein random blocks of constituent materials are used to demonstrate the generality and robustness of the DNO model. To obtain FEA results of IPC properties, 5000 random time-dependent strain loads generated by a Gaussian process kennel are applied to the 3D IPC beam, and the reaction forces and stress fields inside the IPC beam under various loading are collected. Subsequently, the DNO model is trained using an incremental learning method with sequence-to-sequence training implemented in JAX, leading to a 100X speedup compared to widely used vanilla deep operator network models. After an offline training, the DNO model can act as surrogate of physics-based FEA to predict the transient mechanical response in terms of reaction force and stress distribution of the IPCs to various strain loads in one second at an accuracy of 98%. Also, the learned operator is able to provide extended prediction of the IPC beam subject to longer random strain loads at a reasonably well accuracy. Such superfast and accurate prediction of mechanical properties of IPCs could significantly accelerate the IPC structural design and related composite designs for desired mechanical properties. [ABSTRACT FROM AUTHOR]

Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex. [ABSTRACT FROM AUTHOR]

The nervous and endocrine systems coordinate with each other to closely influence physiological and behavioural responses in animals. Here we show that WAKE (encoded by wide awake, also known as wake) modulates membrane levels of GABAA receptor Resistance to Dieldrin (Rdl), in insulin-producing cells of adult male Drosophila melanogaster. This results in changes to secretion of insulin-like peptides which is associated with changes in juvenile hormone biosynthesis in the corpus allatum, which in turn leads to a decrease in 20-hydroxyecdysone levels. A reduction in ecdysone signalling changes neural architecture and lowers the perception of the male-specific sex pheromone 11-cis-vaccenyl acetate by odorant receptor 67d olfactory neurons. These finding explain why WAKE-deficient in Drosophila elicits significant male-male courtship behaviour. The authors show that the Drosophila master regulator WAKE modulates the secretion of insulin-like peptides, triggering a decrease in 20-hydroxyecdysone levels. This lowers the perception of a male-specific sex pheromone and explains why WAKE-deficient Drosophila flies show male-male courtship behaviour. [ABSTRACT FROM AUTHOR]

The human brain's distinctive folding pattern has attracted the attention of researchers from different fields. Neuroscientists have provided insights into the role of four fundamental cell types crucial during embryonic development: radial glial cells, intermediate progenitor cells, outer radial glial cells, and neurons. Understanding the mechanisms by which these cell types influence the number of cortical neurons and the emerging cortical folding pattern necessitates accounting for the mechanical forces that drive the cortical folding process. Our research aims to explore the correlation between biological processes and mechanical forces through computational modeling. We introduce cell-density fields, characterized by a system of advection-diffusion equations, designed to replicate the characteristic behaviors of various cell types in the developing brain. Concurrently, we adopt the theory of finite growth to describe cortex expansion driven by increasing cell density. Our model serves as an adjustable tool for understanding how the behavior of individual cell types reflects normal and abnormal folding patterns. Through comparison with magnetic resonance images of the fetal brain, we explore the correlation between morphological changes and underlying cellular mechanisms. Moreover, our model sheds light on the spatiotemporal relationships among different cell types in the human brain and enables cellular deconvolution of histological sections. [ABSTRACT FROM AUTHOR]

Numerous studies utilizing magnetic resonance imaging (MRI) have observed sex and interhemispheric disparities in sulcal morphology, which could potentially underpin certain functional disparities in the human brain. Most of the existing research examines the precentral sulcus comprehensively, with a rare focus on its subsections. To explore the morphology, asymmetry, and sex disparities within the inferior precentral sulcus (IPCS), we acquired 3.0T magnetic resonance images from 92 right-handed Chinese adolescents. Brainvisa was used to reconstruct the IPCS structure and calculate its mean depth (MD). Based on the morphological patterns of IPCS, it was categorized into five distinct types. Additionally, we analyzed four different types of spatial relationships between IPCS and inferior frontal sulcus (IFS). There was a statistically significant sex disparity in the MD of IPCS, primarily observed in the right hemisphere. Females exhibited significantly greater asymmetry in the MD of IPCS compared to males. No statistically significant sex or hemispheric variations were identified in sulcal patterns. Our findings expand the comprehension of inconsistencies in sulcal structure, while also delivering an anatomical foundation for the study of related regions' function. [ABSTRACT FROM AUTHOR]

Recent studies comparing the insulin-producing cell (IPC) differentiation capacity of mesenchymal stem cells (MSCs) derived from four different sources (bone marrow, Wharton's jelly, adipose tissue, and the periosteum) demonstrated that IPC differentiation of periosteum-derived progenitor cells (PDPCs) progressed faster than any other MSCs within 7 days, indicating that PDPCsare most suited to IPC differentiation. Here, two different cell culture methods, adhesion and cluster culture, were assessed for their ability to support in vitro IPC differentiation. The induction of IPC differentiation was confirmed by RTqPCR analysis of insulin gene expression levels and immunofluorescence analysis of insulin protein. An enzyme-linked immunosorbent assay was used to quantify secreted insulin. PDPC-derived IPCs from cluster cultures demonstrated a significantly increased expression of insulin and an enhanced secretion of insulin of insulin protein in response to glucose compared to IPCs derived from adhesion cultures. Thus, pancreatic islet-like cluster cultures appear to provide the optimal conditions such as cluster culture for IPC differentiation of PDPCs. [ABSTRACT FROM AUTHOR]

Insulin/IGF-like signaling regulates the development, growth, fecundity, metabolic homeostasis, stress resistance and lifespan in worms, flies and mammals. Eight insulin-like peptides (DILP1-8) are found in Drosophila. Three of these (DILP2, 3 and 5) are produced by a set of median neurosecretory cells (insulin-producing cells, IPCs) in the brain. Activity in the IPCs of adult flies is regulated by glucose and several neurotransmitters and neuropeptides. One of these, short neuropeptide F (sNPF), regulates food intake, growth and Dilp transcript levels in IPCs via the sNPF receptor (sNPFR1) expressed on IPCs. Here we identify a set of brain neurons that utilizes sNPF to activate the IPCs. These sNPF-expressing neurons (dorsal lateral peptidergic neurons, DLPs) also produce the neuropeptide corazonin (CRZ) and have axon terminations impinging on IPCs. Knockdown of either sNPF or CRZ in DLPs extends survival in flies exposed to starvation and alters carbohydrate and lipid metabolism. Expression of sNPF in DLPs in the sNPF mutant background is sufficient to rescue wild-type metabolism and response to starvation. Since CRZ receptor RNAi in IPCs affects starvation resistance and metabolism, similar to peptide knockdown in DLPs, it is likely that also CRZ targets the IPCs. Knockdown of sNPF, but not CRZ in DLPs decreases transcription of Dilp2 and 5 in the brain, suggesting different mechanisms of action on IPCs of the two co-released peptides. Our findings indicate that sNPF and CRZ co-released from a small set of neurons regulate IPCs, stress resistance and metabolism in adult Drosophila. [ABSTRACT FROM AUTHOR]

The interaction of a molecular brush consisting of a polyimide backbone and luminescence-labeled poly(methacrylic acid) side chains with poly-N-vinylamides (poly-N-vinylpyrrolidone and poly-N-vinylcaprolactam) with different molecular weights is studied via polarized luminescence under stationary excitation in organic solvents with different thermodynamic qualities in relation to the chain blocks of the polymers, namely, selective (methanol) and common (dimethylformamide). The decrease in the mobility of the grafted poly(methacrylic acid) chains with the growth in the molecular weight of poly-N-vinylamide observed in both selective and common solvents gives evidence of the transition from a "loose" structure to a more compact structure of the interpolymer complex. It is shown on the basis of the analysis of the nanosecond relaxation times characterizing the mobility of the sections of the grafted poly(methacrylic acid) chains and reflecting the change in the intra- and intermolecular interactions that the formation of interpolymer complexes in dimethylformamide leads to a looser structure. [ABSTRACT FROM AUTHOR]

Plasmacytoid dendritic cell (pDC) precursors, also called type I IFN (a/ß/?)-producing cells (IPCs), are the key effectors in the innate immune system because of their extraordinary capacity to produce type I IFNs against microbial infection, particularly viral infection. In contrast to myeloid DCs, human pDC/IPCs selectively express Toll-like receptor (TLR) 7 and TLR9 within the endosomal compartment. These receptors are specifically designed to recognize the nucleoside-based products derived from RNA viruses and DNA viruses. Therefore, this expression profile potentially enables pDC/IPCs to sense a variety of viruses. Stimulation of TLR7 or TLR9 leads to type I IFN responses through the MyD88 pathway. Thus, pDC/IPCs may play a central role in host defense against viral infection through the TLR7 and TLR9 system. [ABSTRACT FROM AUTHOR]

Transcriptional co-activator with PDZ-binding motif (TAZ) is a key mediator of the Hippo signaling pathway and regulates structural and functional homeostasis in various tissues. TAZ activation is associated with the development of pancreatic cancer in humans, but it is unclear whether TAZ directly affects the structure and function of the pancreas. So we sought to identify the TAZ function in the normal pancreas. TAZ defect caused structural changes in the pancreas, particularly islet cell shrinkage and decreased insulin production and β-cell markers expression, leading to hyperglycemia. Interestingly, TAZ physically interacted with the pancreatic and duodenal homeobox 1 (PDX1), a key insulin transcription factor, through the N-terminal domain of TAZ and the homeodomain of PDX1. TAZ deficiency decreased the DNA-binding and transcriptional activity of PDX1, whereas TAZ overexpression promoted PDX1 activity and increased insulin production even in a low glucose environment. Indeed, high glucose increased insulin production by turning off the Hippo pathway and inducing TAZ activation in pancreatic β-cells. Ectopic TAZ overexpression along with PDX1 activation was sufficient to produce insulin in non-β-cells. TAZ deficiency impaired the mesenchymal stem cell differentiation into insulin-producing cells (IPCs), whereas TAZ recovery restored normal IPCs differentiation. Compared to WT control, body weight increased in TAZ-deficient mice with age and even more with a high-fat diet (HFD). TAZ deficiency significantly exacerbated HFD-induced glucose intolerance and insulin resistance. Therefore, TAZ deficiency impaired pancreatic insulin production, causing hyperglycemia and exacerbating HFD-induced insulin resistance, indicating that TAZ may have a beneficial effect in treating insulin deficiency in diabetes. [ABSTRACT FROM AUTHOR]

The study of inherited cardiac disorders is hampered by the lack of suitable in vitro human cardiac disease models and relevant functional assays. A potential solution to this cell-sourcing challenge may be the recently described human induced pluripotent stem cell (hiPSC) technology. Pioneering studies were successful in establishing patient-specific, hiPSC-derived cardiomyocyte models of the most common inherited cardiac arrhythmogenic disorders, such as the different long QT syndrome subtypes (types 1, 2, 3, 8), overlap syndrome LQTS3/Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT) types 1 and 2, and arrhythmogenic right ventricular cardiomyopathy (ARVC). These studies initially demonstrated the ability of the generated hiPSC models to recapitulate the disease processes in the culture dish. More recently, such studies were also able to provide new mechanistic insights into the disease processes, as well as to derive a unique drug-screening platform to test existing and novel therapeutic treatment options in an environment resembling the human physiological milieu. Moreover, initial evidence suggests that such models can help to optimize drug treatment in a personalized manner in the future. Nevertheless, several hurdles still exist for using hiPSC-based models for the aforementioned tasks, such as the hiPSC-derived cardiomyocytes' relatively immature phenotype, and also the resulting cell heterogeneity. Extensive research work is ongoing to address these challenges, as well as to add new opportunities for the field by utilizing recent advances in gene editing technologies. Here, we discuss the significant findings that hiPSC-based models have provided for each of the inherited cardiac arrhythmia syndromes so far, and the current challenges that this technique is facing. [ABSTRACT FROM AUTHOR]

Purpose: To investigate incidental pancreatic cysts (IPCs) size discrepancy in a cohort of patients receiving both computed tomography (CT) and magnetic resonance imaging (MRI) and its impact on clinical management based on the 2010 American College of Radiology (ACR) guidelines. Methods: This was a HIPAA-compliant, retrospective, IRB-approved study. Informed consent was waived. Patients with known IPCs and at least one case-pair, consisting of an abdominal CT and MRI examination within 180 days between 05/1999 and 12/2011, were included. Maximum diameter of cysts was measured in both the CT and MR examinations. A subset of 30 patients was measured by three radiologists independently to assess inter-observer variability. Absolute difference in diameter measurements between CT and MRI was calculated. Influence of cyst size, cyst location, and patient characteristics such as weight, height, and body mass index (BMI) on variability of size measurements were evaluated. Clinical impact in terms of current ACR guidelines was assessed. Results: Overall, 267 case-pairs of cysts in 113 patients were included in this study. 59/267 cysts were visualized on MRI but not on CT (22.1%, 95% CI 17.1%-27.1%; 32 patients, 64.6 ± 11.7 years, BMI 28.5 ± 4.8 kg/m), with a median MRI cyst size of 7.8 mm, IQR 6.0-9.0 mm, range 2-17.8 mm. 208 case-pairs in 113 patients with a mean BMI of 26.9 ± 5.1 kg/m (range 16.9-39.5 kg/m) and mean cysts size of 13.4 ± 8.1 mm (range 3-49 mm) were seen in both CT and MRI. The mean absolute size difference for IPCs measured on MRI and CT was 2.1 ± 1.8 mm (median 1.5 mm, IQR 0.9-2.9 mm, range 0-9 mm). Absolute size difference between CT and MRI measurements increased with size of the cyst ( r = 0.31, p < 0.001), whereas location of the cyst did not influence the absolute difference between CT and MRI measurements ( p = 0.44). Patient weight and BMI had a negative correlation with the difference in cyst size between CT and MRI (weight r = −0.17, p = 0.023; BMI r = −0.17, p = 0.027), with cyst measurements being larger on MRI in thin patients and on CT in obese patients. Inter-reader variability was excellent (ICC = 0.99). In 12/208 (5.7%, 95% CI 2.7%-9.1%), variability between CT and MRI would have changed ACR-based follow-up recommendation. Conclusion: There was a median difference of 1.5 mm between measurements of IPCs on CT vs. MRI. If imaging modality was switched during follow-up, variability of measurements may lead to inappropriate change of follow-up regimen in 6% of all cases. A single follow-up CT for incidental IPCs does not seem sufficient due to a high number (22%) of missed IPCs on CT. [ABSTRACT FROM AUTHOR]

Diabetes mellitus, which is the result of autoimmune destruction of the insulin-producing β cells, occurs by loss of insulin-secreting capacity. The insufficient source of insulin-producing cells (IPCs) is the major obstacle for using transplantation as diabetes treatment method. The present study suggests a method to form islet-like clusters of IPCs derived from mouse embryonic stem cells (mESCs). This protocol consists of several steps. Before starting this protocol, embryoid bodies (EBs) should be cultured in suspension in conditioned medium of isolated mouse pancreatic islet in combination with activing A to be induced. Then differentiated mESCs were replaced with dishes supplemented with basic fibroblast growth factor (bFGF). Next, bFGF was withdrawn, and cyclopamine and noggin were added. Then the cells were treated with B27, nicotinamide, and islet-conditioned medium for maturation. mESCs, as the control group, were cultured without any treatment. An enhanced expression of pancreatic-specific genes was detected by qRT-PCR and immunofluorescence in the differentiated mESCs. The differentiated mESCsco express other markers of pancreatic islet cells as well as insulin. This method exhibited higher insulin generation and further improvement in IPCs protocol that may result in an unlimited source of ES cells suitable for transplantation. The results indicated that conditioned medium, just as critical components of the stem cell niche associated with other factors, had high potential to differentiate mESCs into IPCs. [ABSTRACT FROM AUTHOR]

Type 1 diabetes occurs when pancreatic islet β-cells are damaged and are thus unable to secrete insulin. Pancreas- or islet-grafting therapy offers highly efficient treatment but is limited by inadequate donor islets or pancreases for transplantation. Stem-cell therapy holds tremendous potential and promises to enhance treatment efficiency by overcoming the limitations of traditional therapies. In this study, we evaluated the efficiency of preclinical diabetic treatment. Diabetes was induced in mice by injections of streptozotocin. Mesenchymal stem cells (MSCs) were derived from mouse bone marrow or human umbilical cord blood and subsequently differentiated into insulin-producing cells. These insulin-producing cells were encapsulated in an alginate membrane to form capsules. Finally, these capsules were grafted into diabetic mice by intraperitoneal injection. Treatment efficiency was evaluated by monitoring body weight and blood glucose levels. Immune reactions after transplantation were monitored by counting total white blood cells. Allografting or xenografting of encapsulated insulin-producing cells (IPCs) reduced blood glucose levels and increased body weight following transplantation. Encapsulation with alginate conferred immune isolation and prevented graft rejection. These results provide further evidence supporting the use of allogeneic or xenogeneic MSCs obtained from bone marrow or umbilical cord blood for treating type 1 diabetes. [ABSTRACT FROM AUTHOR]

The International Society for Exposure Analysis (ISEA) and its Nomenclature Committee have been involved since the mid-1990s in an intermittent but ongoing effort to develop an official ISEA glossary. Several related activities have stimulated greater interest and discussion nationally and internationally on a common exposure language. Among these activites are a 1997 Journal of Exposure Analysis and Environmental Epidemiology feature article on exposure and dose definitions and a 1999-initiated project of the International Programme on Chemical Safety (IPCS) (WHO/ILO/UNEP) to confront terminology issues hindering harmonization in the area of exposure assessment. Recently, the ISEA members voted in support of adopting the IPCS glossary as the official ISEA glossary, and the ISEA Executive Board agreed to accept this recommendation. In this feature article, we (1) describe the process through which the ISEA adopted the IPCS glossary as the official ISEA glossary, (2) present the joint IPCS/ISEA glossary of terms and their definitions, and (3) discuss plans for how the glossary can be used by ISEA and updated over time by ISEA and IPCS. The glossary is intended to be a living document that reflects the latest usage and maintains international harmonization of exposure terminology that can be practically applied to improve communication in exposure and related fields.Journal of Exposure Analysis and Environmental Epidemiology (2005) 15, 1-5. doi:10.1038/sj.jea.7500411 Published online 24 November 2004 [ABSTRACT FROM AUTHOR]

In the recent century, geopolymer materials have grown significantly due to their unique properties applicable in many different fields. In the present work, the heat evolution, thermal and mechanical behavior of inorganic geopolymer composites (IPCs), based on solid solution of feldspathic minerals (pegmatite and granite) or sand quartz that were altered by a low fraction (15–20 mass%) of calcined clay (metakaolin or calcined halloysite). The isothermal calorimeter tests revealed that the heat flow evolution (dQ/dt) of mix design of different compositions was low compared to standard geopolymer materials due to low reactivity in alkaline medium of solid solution used. It was also found that the integrated heat flow during the geopolymerization decreases with the crystallinity of solid solution. The thermogravimetric analysis of all the samples revealed two main changes, before 120 °C and between 700 and 890 °C. The changes are attributed to the loss of water molecules and crystallization of albite and nepheline, respectively with an overall loss of mass which varies from 14.0 to 21.6%. The heating microscope up to 1200 °C shows a shrinkage of 50% for D3C4 and R2C1 samples. The study of mechanical and physical behaviors of geopolymer composites with different compositions showed that samples based on pegmatite and MK developed higher strengths (42.11 MPa and 106.75 MPa for flexural and compression) associated with lower water absorption (7.01%). The high strengths obtained were due to the combination of denser and homogeneous microstructure of IPCs. These materials are potential candidates for eco-friendly construction materials. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the impact of cancer on intraoperative and postprocedural complications (IPCs) in Germany. Methods: Patients with first diagnosis of IPCs between 2010 and 2015 were identified in 982 general practitioners in the IMS Disease Analyzer database. Controls were included after individual matching (1:1) to IPC cases by age, gender, type of health insurance (private or statutory) and the physician. Demographic data included: age, sex and health insurance type (private or statutory). Clinical data included: cancer, diabetes, coronary heart disease including myocardial infarction, stroke including TIA, heart failure, chronic respiratory diseases, fractures and depression. A multivariate logistic model was used to calculate the risk of IPC on the basis of patient characteristics. Results: A total of 5817 IPC patients and 5817 controls were included in this study. The mean age was 63.9 years, the proportion of people with private health insurance coverage was equal to 3.0 %, and the proportion of men was equal to 36.0 % in both groups; 21.5 % of IPC patients and 5.8 % of controls had cancer ( p value <0.0001). Moreover, diabetes, coronary heart disease, stroke, heart failure, chronic respiratory disease, fractures and depression were also significantly more common in IPC patients than in controls. Cancer had a negative impact on the risk of IPC (OR 4.27, 95 % CI 3.76-4.85 and p value <0.0001). Coronary heart diseases, depression, fractures and chronic respiratory diseases were also significantly associated with an increased risk of IPC. Conclusion: The present study indicates that cancer increases the risk of IPCs and may reduce the clinical benefits of surgery. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the characteristics of insulin producing cells (IPCs) differentiated from adipose-tissue derived stem cells (ADSCs) isolated from human subcutaneous and visceral adipose tissues and identify ADSCs suitable for differentiation into efficient and functional IPCs. Subcutaneous and visceral adipose tissues collected from four (4) patients who underwent digestive surgeries at The Tokushima University (000035546) were included in this study. The insulin secretion of the generated IPCs was investigated using surface markers by: fluorescence activated cell sorting (FACS) analysis; cytokine release; proliferation ability of ADSCs; in vitro (glucose-stimulated insulin secretion: (GSIS) test/in vivo (transplantation into streptozotocin-induced diabetic nude mice). The less fat-related inflammatory cytokines secretions were observed (P < 0.05), and the proliferation ability was higher in the subcutaneous ADSCs (P < 0.05). Insulin expression and GISI were higher in the subcutaneous IPCs (P < 0.01 and P < 0.05, respectively). The hyperglycaemic state of all mice that received IPCs from subcutaneous fat tissue converted into normo-glycaemia in thirty (30) days post-transplantation (4/4,100%). Transplanted IPCs were stained using anti-insulin and anti-human leukocyte antigen antibodies. The IPCs generated from the ADSCs freshly isolated from the human fat tissue had sufficient insulin secreting ability in vitro and in vivo. [ABSTRACT FROM AUTHOR]