A highly sensitive and specific Homo1-based real-time qPCR method for quantification of human umbilical cord mesenchymal stem cells in rats.

BACKGROUND: Owing to the characteristics of easier access in vitro, low immunogenicity, and high plasticity, human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are considered as a promising cell-based drugs for clinical application. No internationally recognized technology exists to evaluate the pharmacokinetics and distribution of cell-based drugs in vivo. METHODS: We determined the human-specific gene sequence, Homo1, from differential fragments Homo sapiens mitochondrion and Rattus norvegicus mitochondrion. The expression of Homo1 was utilized to determine the distribution of UC-MSCs in the normal and diabetic nephropathy (DN) rats. RESULTS: We observed a significant correlation between the number of UC-MSCs and the expression level of Homo1. Following intravenous transplantation, the blood levels of UC-MSCs peaked at 30 min. A large amount of intravenously injected MSCs were trapped in the lungs, but the number of them decreased rapidly after 24 h. Additionally, the distribution of UC-MSCs in the kidneys of DN rats was significantly higher than that of normal rats. CONCLUSIONS: In this study, we establish a highly sensitive and specific Homo1-based real-time quantitative PCR method to quantify the distribution of human UC-MSCs in rats. The method provides guidelines for the safety research of cells in preclinical stages.

Numerical implementation of three-dimensional vectorial complex ray model and application to rainbow scattering of spheroidal drops.

The rainbow patterns of oblate spheroidal drops have been observed in experiments nearly forty years ago [Nature312, 529 (1984)10.1038/312529a0]. However, the prediction for those complex patterns has been a challenge for conventional light scattering models. The vectorial complex ray model (VCRM) allows to account for the direction, the polarization, the phase, the amplitude and the wavefront curvature of waves and provides a powerful tool for the study of the light/electromagnetic wave interaction with a homogeneous object of any shape with smooth surface. In [Opt. Lett.46, 4585 (2021)10.1364/OL.434149], the authors have reported an important breakthrough of VCRM for the three-dimensional scattering (VCRM3D) and the simulated rainbow patterns of oblate drops. The present paper is devoted to the detailed description of the numerical implementation allowing the simulation of the 3D scattering field by a nonspherical particle. Its ability to predict both the fine and coarse intensity structures of the rainbows and the near-backward scattering patterns of spheroids is demonstrated. This work opens perspectives for exploring the 3D scattering characteristics of large objects with any smooth shape and developing relevant optical techniques for particle characterization.

A semantic union model for open domain Chinese knowledge base question answering.

In Open-domain Chinese Knowledge Base Question Answering (ODCKBQA), most common simple questions can be answered by a single relational fact in the knowledge base (KB). The abbreviations, aliases, and nesting of entities in Chinese question sentences, and the gap between them and the structured semantics in the knowledge base, make it difficult for the system to accurately return answers. This study proposes a semantic union model (SUM), which concatenates candidate entities and candidate relationships, using a contrastive learning algorithm to learn the semantic vector representation of question and candidate entity-relation pairs, and perform cosine similarity calculations to simultaneously complete entity disambiguation and relation matching tasks. It can provide information for entity disambiguation through the relationships between entities, avoid error propagation, and improve the system performance. The experimental results show that the system achieves a good average F1 of 85.94% on the dataset provided by the NLPCC-ICCPOL 2016 KBQA task.

Grating lobe-free silicon optical phased array with periodically bending modulation of dense antennas.

A grating lobe-free silicon optical phased array with large field of view is demonstrated. Antennas with periodically bending modulation are spaced at half wavelength or less. The experimental results show that the crosstalk between adjacent waveguides is negligible at 1550 nm wavelength. Additionally, to reduce the optical reflection caused by the sudden change of refractive index at the output antenna of the phased array, tapered antennas are added to the output end face so that more light will be coupled into the free space. The fabricated optical phased array shows a field of view of 120° without any grating lobes.

A new method for hosting and sharing MATLAB Web App.

Currently, using MATLAB Web App Server to deploy MATLAB Web applications for hosting and sharing interactive Web applications involves the following problems: slow loading of applications, incompatibility with some browser versions, and various shortcomings of deployment tools, such as poor scalability and difficulty in optimizing black boxes. These problems adversely affect the user experience. To address this situation, we propose the use of front-end technology to design application layouts and build an application hosting platform with front-end and back-end separation using Nginx and Python. This method is shown to be simple and efficient, and it can successfully overcome the aforementioned problems while providing new ideas for hosting and sharing.

The effect of afatinib in a pretreated patient with invasive mucinous adenocarcinoma of the lung harboring HER2 YVMA insertion: a case report.

Background: Invasive mucinous adenocarcinoma (IMA) is an uncommon variant of lung adenocarcinoma. The survival data and therapeutic methods for IMAs are limited. The frequency of human epidermal growth factor receptor 2 (HER2) mutations in IMAs is low, and the clinical benefit of HER2 inhibitors in patients with IMA is still being explored. Afatinib is a pan-HER inhibitor and the studies of afatinib treatment in IMA patients are very limited. Case Description: Herein, we present the case of a 49-year-old female, never-smoker stage IVa IMA patient with persistent cough and sputum expectoration diagnosed with stage IVa IMA. Polymerase chain reaction (PCR) and next-generation sequencing (NGS) were utilized to detect mutations for targeted therapies on lung biopsy, but no mutation was found. After treatment failures of chemotherapy and a multiple-kinase inhibitor, liquid biopsy identified HER2 exon 20 insertion p.A775_G776insYVMA with NGS. The patient was then treated with afatinib as the third-line treatment. Following administration for one month, the patient's symptoms of coughing, sputum expectoration, and dyspnea improved. Stable disease (SD) was observed, and the patient achieved durable clinical benefit with prolonged progression-free survival (PFS) of 20 months. Her overall survival was 5.8 years. Conclusions: This is the first report of afatinib treatment achieving long-lasting and stable disease control in an IMA patient with a HER2 exon 20 YVMA insertion. Our results will help to improve the treatment of IMA.

Prenatal ethanol exposure induces dynamic changes of expression and activity of hepatic cytochrome P450 isoforms in male rat offspring.

This study aimed at determining the effect of prenatal ethanol exposure (PEE) on the expression and activity of cytochrome P450 (CYP) isozymes at different life stages of male rat offspring. Pregnant Wistar rats were administered with ethanol (4 g/kg/d) intragastrically from gestational day (GD) 9-20. Male offspring's gene and activity of CYP isozymes were analyzed on GD 20 (only expression), postnatal day (PD) 84 and 196. Using aniline as probe, we compared the enzyme kinetics of hepatic CYP2E1 between two groups. Expression of CYP isozymes was examined in rat primary hepatocytes and human hepatic cell lines treated with ethanol or/and glucocorticoid. Gene level of Cyp1a2, 2b1, 2d1, 2e1, 3a1 and aryl hydrocarbon receptor were increased in PEE group on GD 20 and PD 84 and Cyp2e1 still exhibited an increasing trend on PD 196 compared with the control. PEE inhibited CYP2D1 and 2E1 activities in male offspring on PD 84. CYP activities in two groups became the same level on PD 196. PEE induced an opposite change in gene and protein level of hepatic CYP2E1 before and after birth. In consistent with lower protein level, aniline metabolism in PEE was weaker in liver microsome. Both single and combined use of ethanol or/and glucocorticoid increased CYPs expression in vitro. In conclusion, PEE programmed a higher gene and lower protein level of CYPs in male offspring, which dwindled with age. Impairment of protein levels and enzyme activities of CYPs may affect individual metabolism of endogenous and exogenous substances in early adulthood.

Human Umbilical Cord Mesenchymal Stem Cells Promote Macrophage PD-L1 Expression and Attenuate Acute Lung Injury in Mice.

BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) remains a serious clinical problem but has no approved pharmacotherapy. Mesenchymal stem cells (MSCs) represent an attractive therapeutic tool for tissue damage and inflammation owing to their unique immunomodulatory properties. The present study aims to explore the therapeutic effect and underlying mechanisms of human umbilical cord MSCs (UC-MSCs) in ALI mice. OBJECTIVE: In this study, we identify a novel mechanism for human umbilical cord-derived MSCs (UC-MSCs)-mediated immunomodulation through PGE2-dependent reprogramming of host macrophages to promote their PD-L1 expression. Our study suggests that UC-MSCs or primed- UC-MSCs offer new therapeutic approaches for lung inflammatory diseases. METHODS: Lipopolysaccharide (LPS)-induced ALI mice were injected with 5×105 UC-MSCs via the tail vein after 4 hours of LPS exposure. After 24 hours of UC-MSC administration, the total protein concentration and cell number in the bronchoalveolar lavage fluid (BALF) and cytokine levels in the lung tissue were measured. Lung pathological changes and macrophage infiltration after UCMSC treatment were analyzed. Moreover, in vitro co-culture experiments were performed to analyze cytokine levels of RAW264.7 cells and Jurkat T cells. RESULTS: UC-MSC treatment significantly improved LPS-induced ALI, as indicated by decreased total protein exudation concentration and cell number in BALF and reduced pathological damage in ALI mice. UC-MSCs could inhibit pro-inflammatory cytokine levels (IL-1ß, TNF-α, MCP-1, IL-2, and IFN-γ), while enhancing anti-inflammatory cytokine IL-10 expression, as well as reducing macrophage infiltration into the injured lung tissue. Importantly, UC-MSC administration increased programmed cell death protein ligand 1 (PD-L1) expression in the lung macrophages. Mechanistically, UC-MSCs upregulated cyclooxygenase-2 (COX2) expression and prostaglandin E2 (PGE2) secretion in response to LPS stimulation. UC-MSCs reduced the inflammatory cytokine levels in murine macrophage Raw264.7 through the COX2/PGE2 axis. Furthermore, UC-MSC- derived PGE2 enhanced PD-L1 expression in RAW264.7 cells, which in turn promoted programmed cell death protein 1 (PD-1) expression and reduced IL-2 and IFN-γ production in Jurkat T cells. CONCLUSION: Our results suggest that UC-MSCs attenuate ALI via PGE2-dependent reprogramming of macrophages to promote their PD-L1 expression.

High-precision two-dimensional beam steering with a 64-element optical fiber phased array.

Large-scale optical fiber phased arrays (OFPAs) are capable of realizing high-power lasers and high-speed beam steering, which are widely used in long-distance detection and communication. However, dephasing occurring from optical fiber jitter and power amplifier noise can reduce beam quality and steering precision in applications. We demonstrate a two-dimensional 64-element OFPA system that employs a stochastic parallel gradient descent algorithm to synchronize the phases and thus achieve high-quality multi-beam output. Using multi-beam steering, the total scan time for covering a certain field of view can be shorter compared to single-beam steering. Moreover, an avalanche photodiode array is used to enhance the precision of the voltage for beam steering. Experimental results show that the peak sidelobe ratio of the main beam achieves 23.7 dB, and the speed of the beam steering between two discretionary angles is 128 kHz.

Generalized rainbow patterns of oblate drops simulated by a ray model in three dimensions.

The scattering patterns near the primary rainbow of oblate drops are simulated by extending the vectorial complex ray model (VCRM) [Opt. Lett.36, 370 (2011)OPLEDP0146-959210.1364/OL.36.000370] to three-dimensional (3D) calculations. With the curvature of a wavefront as an intrinsic property of a ray, this advanced ray model permits, in principle, to predict the amplitudes and phases of all emergent rays with a rigorous algebraic formalism. This Letter reports a breakthrough of VCRM for 3D scattering with a line-by-line triangulation interpolation algorithm allowing to calculate the total complex amplitude of a scattered field. This makes possible to simulate not only the skeleton (geometrical rainbow angles, hyperbolic-umbilic caustics), but also the coarse (Airy bows, lattice) and fine (ripple fringes) structures of the generalized rainbow patterns (GRPs) of oblate drops. The simulated results are found qualitatively and quantitatively in good agreement with experimental scattering patterns for drops of different aspect ratios. The physical interpretation of the GRPs is also given. This work opens up prominent perspectives for simulating and understanding the 3D scattering of large particles of any shape with a smooth surface by VCRM.

Intra-articular injection of human umbilical cord mesenchymal stem cells ameliorates monosodium iodoacetate-induced osteoarthritis in rats by inhibiting cartilage degradation and inflammation.

AIMS: This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA). METHODS: Human UC-MSCs were characterized by their phenotype and multilineage differentiation potential. Two weeks after MIA induction in rats, human UC-MSCs were intra-articularly injected once a week for three weeks. The therapeutic effect of human UC-MSCs was evaluated by haematoxylin and eosin, toluidine blue, Safranin-O/Fast green staining, and Mankin scores. Markers of joint cartilage injury and pro- and anti-inflammatory markers were detected by immunohistochemistry. RESULTS: Histopathological analysis showed that intra-articular injection of human UC-MSCs significantly inhibited the progression of OA, as demonstrated by reduced cartilage degradation, increased Safranin-O staining, and lower Mankin scores. Immunohistochemistry showed that human UC-MSC treatment down-regulated the expression of matrix metalloproteinase-13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), and enhanced the expression of type II collagen and ki67 in the articular cartilage. Furthermore, human UC-MSCs significantly decreased the expression of interleukin (IL)-1ß and tumour necrosis factor-α (TNF-α), while increasing TNF-α-induced protein 6 and IL-1 receptor antagonist. CONCLUSION: Our results demonstrated that human UC-MSCs ameliorate MIA-induced OA by preventing cartilage degradation, restoring the proliferation of chondrocytes, and inhibiting the inflammatory response, which implies that human UC-MSCs may be a promising strategy for the treatment of OA. Cite this article: Bone Joint Res 2021;10(3):226-236.

Oxidized low-density lipoprotein activates extracellular signal-regulated kinase signaling to downregulate sortilin expression in liver sinusoidal endothelial cells.

BACKGROUND AND AIM: Both type 2 diabetes mellitus and non-alcoholic fatty liver disease are closely associated with elevated levels of low-density lipoprotein cholesterol and its oxidized form (ox-LDL). This study aimed to investigate the regulation of sortilin in liver tissue and its potential implications for lipid metabolism. METHODS: Sixty male Wistar rats were randomly divided into four groups: control group (n = 15), ox-LDL group (n = 15), PD98059 group (n = 15), and ox-LDL + PD98059 group (n = 15). Liver sinusoidal endothelial cells were extracted from liver tissue of the control group and were identified using an anti-CD31 antibody. Lipid droplet accumulation was observed by Oil red O and hematoxylin-eosin staining. The protein expression levels were detected by immunohistochemical staining, real-time reverse transcription-polymerase chain reaction, and western blot. Histopathologic examinations were performed by Gomori methenamine silver staining. RESULTS: The ox-LDL group exhibited increased lipid droplet accumulation. Further, ox-LDL activated the extracellular signal-regulated kinase (ERK)-mediated downregulation of sortilin expression, whereas blocking of ERK signaling by PD98059 increased sortilin protein expression. Consistently, hematoxylin-eosin staining showed that the structure of the hepatocytes was loose and disordered in arrangement, with lipid droplets present in the cytoplasm of the ox-LDL group. However, PD98059 significantly improved the integration of the scaffold structure. Gomori methenamine silver staining showed that the ox-LDL group had darker and more obvious fragmented silver nitrate deposits in the basement membrane and sinus space. CONCLUSIONS: Sortilin can protect liver sinusoidal endothelial cells from injury and maintain integration of the liver scaffold structure in ox-LDL-induced lipid-injured liver.

Prenatal Exposure to Retrorsine Induces Developmental Toxicity and Hepatotoxicity of Fetal Rats in a Sex-Dependent Manner: The Role of Pregnane X Receptor Activation.

Pyrrolizidine alkaloids (PAs) are a type of natural phytotoxin that contaminate food and feed and become an environmental health risk to humans and livestock. PAs exert toxicity that requires metabolic activation by cytochrome P450 (CYP) 3A, and case reports showed that fetuses are quite susceptible to PAs toxicity. The aim of this study was to explore the characteristics of developmental toxicity and fetal hepatotoxicity induced by retrorsine (RTS, a typcial toxic PA) and the underlying mechanism. Pregnant Wistar rats were intragastrically administered with 20 mg/(kg·day) RTS from gestation day (GD) 9 to 20. Results showed that prenatal RTS exposure lowered fetal bodyweights, reduced hepatocyte numbers, and potentiated hepatic apoptosis in fetuses, particularly females. Simutaneously, RTS increased CYP3A expression and pregnane X receptor (PXR) activation in female fetal liver. We further confirmed that RTS was a PXR agonist in LO2 and HepG2 cell lines. Furthermore, agonism or antagonism of androgen receptor (AR) either induced or blocked RTS-mediated PXR activation, respectively. As a PXR agonist, RTS toxicity was exacerbated in female fetus due to the increased CYP3A induction and self-metabolism, while the inhibitory effect of AR on PXR activation reduced the susceptibility of male fetus to RTS. Our findings indicated that PXR may be a potential therapeutic target for PA toxicity.

Chip scale GaAs optical phased arrays for high speed beam steering.

High speed photoelectronic optical phased arrays are demonstrated by vertically arranged GaAs-AlGaAs slab waveguides. The optical phased arrays are composed of 15-channel independently tuned waveguide with end-fire emission. We achieve a very fast beam steering step response of 0.34 µs, beam divergence of 4.7°, and beam steering ranges of around 30°with side lobe level better than 8 dB. The presented optical phased arrays provide a superior approach for high speed beam steering on a nano-photoelectronic integrated chip.

Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis.

BACKGROUND: Diabetic nephropathy (DN) is one of the most serious complications of diabetes and the leading cause of end-stage chronic kidney disease. Currently, there are no effective drugs for treating DN. Therefore, novel and effective strategies to ameliorate DN at the early stage should be identified. This study aimed to explore the effectiveness and underlying mechanisms of human umbilical cord mesenchymal stem cells (UC-MSCs) in DN. METHODS: We identified the basic biological properties and examined the multilineage differentiation potential of UC-MSCs. Streptozotocin (STZ)-induced DN rats were infused with 2 × 106 UC-MSCs via the tail vein at week 6. After 2 weeks, we measured blood glucose level, levels of renal function parameters in the blood and urine, and cytokine levels in the kidney and blood, and analyzed renal pathological changes after UC-MSC treatment. We also determined the colonization of UC-MSCs in the kidney with or without STZ injection. Moreover, in vitro experiments were performed to analyze cytokine levels of renal tubular epithelial cell lines (NRK-52E, HK2) and human renal glomerular endothelial cell line (hrGECs). RESULTS: UC-MSCs significantly ameliorated functional parameters, such as 24-h urinary protein, creatinine clearance rate, serum creatinine, urea nitrogen, and renal hypertrophy index. Pathological changes in the kidney were manifested by significant reductions in renal vacuole degeneration, inflammatory cell infiltration, and renal interstitial fibrosis after UC-MSC treatment. We observed that the number of UC-MSCs recruited to the injured kidneys was increased compared with the controls. UC-MSCs apparently reduced the levels of pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α) and pro-fibrotic factor (TGF-ß) in the kidney and blood of DN rats. In vitro experiments showed that UC-MSC conditioned medium and UC-MSC-derived exosomes decreased the production of these cytokines in high glucose-injured renal tubular epithelial cells, and renal glomerular endothelial cells. Moreover, UC-MSCs secreted large amounts of growth factors including epidermal growth factor, fibroblast growth factor, hepatocyte growth factor, and vascular endothelial growth factor. CONCLUSION: UC-MSCs can effectively improve the renal function, inhibit inflammation and fibrosis, and prevent its progression in a model of diabetes-induced chronic renal injury, indicating that UC-MSCs could be a promising treatment strategy for DN.

Female-specific activation of pregnane X receptor mediates sex difference in fetal hepatotoxicity by prenatal monocrotaline exposure.

Pyrrolizidine alkaloids (PAs) are a group of hepatic toxicant widely present in plants. Cytochrome P450 (CYP) 3A plays a key role in metabolic activation of PAs to generate electrophilic metabolites, which is the main cause of hepatotoxicity. We have previously demonstrated the sex difference in developmental toxicity and hepatotoxicity in fetal rats exposed to monocrotaline (MCT), a representative toxic PA. The aim of this study was to explore the underlying mechanism. 20 mg·kg-1·d-1 MCT was intragastrically given to pregnant Wistar rats from gestation day 9 to 20. CYP3As expression and pregnane X receptor (PXR) activation were specifically enhanced in female fetal liver. After MCT treatment, we also observed a significant increase of CYP3As expression in LO2 cells (high PXR level) or hPXR-transfected HepG2 cells (low PXR level). Employing hPXR and CYP3A4 dual-luciferase reporter gene assay, we confirmed the agonism effect of MCT on PXR-dependent transcriptional activity of CYP3A4. Agonism and antagonism of the androgen receptor (AR) either induced or blocked MCT-induced PXR activation, respectively. This study was the first report identifying that MCT served as PXR agonist to induce CYP3A expression. CYP3A induction may increase self-metabolic activation of MCT and subsequently lead to more severe hepatotoxicity in female fetus. While in male, during the intrauterine period, activated AR by testosterone secretion from developing testes represses MCT-induced PXR activation and CYP3A induction, which may partially protect male fetus from MCT-induced hepatotoxicity.

CTRP13 attenuates the expression of LN and CAV-1 Induced by high glucose via CaMKKß/AMPK pathway in rLSECs.

OBJECTIVE: To investigate the effect and mechanism of CTRP13 on hepatic sinusoidal capillarization induced by high glucose in rat liver sinusoidal endothelial cells (rLSECs). RESULTS: CTRP13 was reduced in high glucose-treated rLSECs. High glucose increased LN and CAV-1 expression and inhibited CaMKKß and AMPK phosphorylation. CTRP13 overexpression protected rLSECs against high glucose-induced increase of LN and CAV-1 expression. Moreover, CTRP13 overexpression increased high glucose-induced inhibition of CaMKKß and AMPK activation in CTRP13-overexpressing rLSECs. Inhibition of CaMKKß and AMPK disturbed the protective effects of CTRP13 in high glucose-induced increase of LN and CAV-1. Hepatic steatosis was enhanced and basement membrane was thickened in liver of diabetic fatty liver rats. CONCLUSIONS: Our data identified the protective role of CTRP13 in hepatic sinusoidal capillarization induced by high glucose via activating CAMKKß/AMPK pathway. CTRP13 may be a potential target for screening and treating diabetic fatty liver. METHODS: Construct lentiviral CTRP13 overexpression vector and transfect rLSECs. Use STO-609 (a CaMKKß inhibitor) or Compound C (an AMPK inhibitor) to treat rLSECs. CTRP13, CaMKKß, AMPK, laminin (LN) and caveolin-1 (CAV-1) were detected by qRT-PCR and Western blotting. Establish rat model of diabetic fatty liver. Use immunohistochemistry, hematoxylin-eosin and silver staining to observe the histopathological features of liver.

Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorate Nephrocyte Injury and Proteinuria in a Diabetic Nephropathy Rat Model.

Mesenchymal stem cells (MSCs) are shown to alleviate renal injury of diabetic nephropathy (DN) in rats. However, the underlying mechanism of this beneficial effect is not fully understood. The aims of this study are to evaluate effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on renal cell apoptosis in streptozotocin- (STZ-) induced diabetic rats and explore the underlying mechanisms. Characteristics of UC-MSCs were identified by flow cytometry and differentiation capability. Six weeks after DN induction by STZ injection in Sprague-Dawley rats, the DN rats received UC-MSCs once a week for consecutive two weeks. DN-related physical and biochemical parameters were measured at 2 weeks after UC-MSC infusion. Renal histological changes were also assessed. Moreover, the apoptosis of renal cells and expression of apoptosis-related proteins were evaluated. Compared with DN rats, rats treated with UC-MSCs showed suppressed increase in 24-hour urinary total protein, urinary albumin to creatinine ratio, serum creatinine, and blood urea nitrogen. UC-MSC treatment ameliorated pathological abnormalities in the kidney of DN rats as evidenced by H&E, PAS, and Masson Trichrome staining. Furthermore, UC-MSC treatment reduced apoptosis of renal cells in DN rats. UC-MSCs promoted expression of antiapoptosis protein Bcl-xl and suppressed expression of high mobility group protein B1 (HMGB1) in the kidney of DN rats. Most importantly, UC-MSCs suppressed upregulation of thioredoxin-interacting protein (TXNIP), downregulation of thioredoxin 1 (TRX1), and activation of apoptosis signal-regulating kinase 1 (ASK1) and P38 MAPK in the kidney of DN rats. Our results suggest that UC-MSCs could alleviate nephrocyte injury and albuminuria of DN rats through their antiapoptotic property. The protective effects of UC-MSCs may be mediated by inhibiting TXNIP upregulation in part.

l-amino acid ligase: A promising alternative for the biosynthesis of l-dipeptides.

Given their special action mechanisms and structural simplicity, L-amino acid ligases (Lals) are considered to be desirable tools for the catalytic biosynthesis of dipeptides. Ywf E (BacD) was the first Lal identified and was shown to be involved in the biosynthesis of a potent antibacterial, bacilysin, since then, various novel Lals have been discovered. Each Lal has different substrate spectra and is capable of synthesizing different dipeptides. Owning to their great potentials for producing bioactive dipeptides of industrial importance, in this review, recent developments of Lals are discussed, including their structures, action mechanisms, applications and the advantages and disadvantages of different Lals. In addition, protein engineering of Lals to improve their substrate specificity and catalytic performance is also discussed.

High glucose/ox-LDL induced hepatic sinusoidal capillarization via αvß5/FAK/ERK signaling pathway.

OBJECTIVE: The main purpose of this study is to explore the role of integrin αvß5 in hepatic sinusoidal capillarization under high glucose/ox-LDL conditions. METHODS: Establish rat model of diabetic fatty liver disease. LSECs were extracted from tissue obtained from rats of control group, cultured and treated with media containing glucose (25 mM, 24 h)/ox-LDL (100 µg/ml, 24 h) in different inhibitors. The expression of integrin αvß5, FAK, ERK, VN in LSECs were detected by RT-PCR and Western blot. Hematoxylin-eosin staining and gomori methenaminutese silver stain was used to observe the basement membrane histopathological features of the liver tissue. Immunohistochemical to detected the protein expression of integrin αvß5 and VN in liver tissue. Using scanning electron microscopy to visualise the fenestration frequency and fenestration diameter. Protein expression of VN was also testified by immunofluorescence assay. RESULTS: CONCLUSIONS: Integrin αvß5 which induces LSECs dysfunction, promoting hepatic sinusoidal capillarization regulates VN expression via ERK/FAK pathway under high glucose/ox-LDL, may be a potential target for prevention and treatment of T2DM with fatty liver disease.