Unraveling the Lignin Structural Variation in Different Bamboo Species.

The structure of cellulolytic enzyme lignin (CEL) prepared from three bamboo species (Neosinocalamus affinis, Bambusa lapidea, and Dendrocalamus brandisii) has been characterized by different analytical methods. The chemical composition analysis revealed a higher lignin content, up to 32.6% of B. lapidea as compared to that of N. affinis (20.7%) and D. brandisii (23.8%). The results indicated that bamboo lignin was a p-hydroxyphenyl-guaiacyl-syringyl (H-G-S) lignin associated with p-coumarates and ferulates. Advanced NMR analyses displayed that the isolated CELs were extensively acylated at the γ-carbon of the lignin side chain (with either acetate and/or p-coumarate groups). Moreover, a predominance of S over G lignin moieties was found in CELs of N. affinis and B. lapidea, with the lowest S/G ratio observed in D. brandisii lignin. Catalytic hydrogenolysis of lignin demonstrated that 4-propyl-substituted syringol/guaiacol and propanol guaiacol/syringol derived from ß-O-4' moieties, and methyl coumarate/ferulate derived from hydroxycinnamic units were identified as the six major monomeric products. We anticipate that the insights of this work could shed light on the sufficient understanding of lignin, which could open a new avenue to facilitate the efficient utilization of bamboo.

[Content analysis and quality evaluation of main active components and mineral elements of Cynomorium songaricum in different habitats].

To clarify the content characteristics of the main active components and mineral elements of Cynomorium songaricum under different habitat conditions, and further explore the relationship between the quality of C. songaricum and habitats, this study took C. songaricum from 25 different habitats in China as the research object, and measured the contents of 8 main active components and 12 mineral elements separately. Diversity analysis, correlation analysis, principal component analysis and cluster analysis were carried out. The results showed that the genetic diversity of total flavonoids, ursolic acid, ether extract, potassium(K), phosphorus(P) and zinc(Zn) in C. songaricum was high. The coefficient of variation of crude polysaccharide, ether extract, gallic acid, protocatechuic aldehyde, catechin, epicatechin, calcium(Ca), sodium(Na), magnesium(Mg), sulfur(S), iron(Fe), manganese(Mn), selenium(Se) and nickel(Ni) were all over 36%, indicating that the quality of C. songaricum was significantly affected by habitats. There were strong synergistic and weak antagonistic effects among the contents of the 8 active components, and complex antagonistic and synergistic effects among the contents of the 12 mineral elements. Principal component analysis revealed that crude polysaccharide, ursolic acid, catechin, epicatechin and total flavonoids could be used as the characteristic components to evaluate the quality of C. songaricum, and Na, copper(Cu), Mn and Ni were the characteristic elements to evaluate the quality of C. songaricum. In cluster ana-lysis, the second group with the main active components as cluster center had better quality in terms of the content of active substances, and the second group with the mineral elements as cluster center had higher utilization potential in the exploitation of mineral elements. This study could provide a basis for resource evaluation and breeding of excellent varieties of C. songaricum in different habitats, and provide a reference for cultivation and identification of C. songaricum.

Reduction of T Cells and Hsa-miR150-5p in Female Canoeing Athletes: Preliminary Evidence Between Exercise Training and Immune.

ABSTRACT: Xiao, F, Yang, Y, Xiao, L, Xia, Z, Wang, L, Yang, K, and Wang, S. Reduction of T cells and hsa-miR150-5p in female canoeing athletes: Preliminary evidence between exercise training and immune. J Strength Cond Res 36(11): e106-e113, 2022-This article aims to reveal the alteration of immune profile in teenage canoeing athletes, by which applies a clue for regulation of exercise on human immune. Thirty-one teenagers of female canoeing athletes and age-matched subjects participated in this research. Peripheral leukocytes' microRNAs (miRNAs) were analyzed using Agilent human microRNA 2.0 and gene software. The miRNA candidates were quantified by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). The percentages of various lymphocytes were tested using flow cytometry. There were 6 miRNAs (hsa-miR150-5p, 31-5p, 3659, 4419a, 650, and 8485) lower in canoeing athletes, and the reduction of miR-150 was identified by RT-qPCR ( p = 0.021). Canoeing athletes had lower percent of CD3 + T cells than the subjects with no exercise training had ( p < 0.001), but the ratio of CD4 + to CD8 + and the percent of CD4 + T cells and CD8 + T cells showed no significant difference between these 2 groups. T cells and hsa-miR150-5p are sensitive to the long-time heavy exercise training, and the exercise for winning competition regulates the immune system by inhibiting T cells and hsa-miR150-5p.

Mutations in the Epithelial Cadherin-p120-Catenin Complex Cause Mendelian Non-Syndromic Cleft Lip with or without Cleft Palate.

Non-syndromic cleft lip with or without cleft palate (NS-CL/P) is one of the most common human birth defects and is generally considered a complex trait. Despite numerous loci identified by genome-wide association studies, the effect sizes of common variants are relatively small, with much of the presumed genetic contribution remaining elusive. We report exome-sequencing results in 209 people from 72 multi-affected families with pedigree structures consistent with autosomal-dominant inheritance and variable penetrance. Herein, pathogenic variants are described in four genes encoding components of the p120-catenin complex (CTNND1, PLEKHA7, PLEKHA5) and an epithelial splicing regulator (ESRP2), in addition to the known CL/P-associated gene, CDH1, which encodes E-cadherin. The findings were also validated in a second cohort of 497 people with NS-CL/P, comprising small families and singletons with pathogenic variants in these genes identified in 14% of multi-affected families and 2% of the replication cohort of smaller families. Enriched expression of each gene/protein in human and mouse embryonic oro-palatal epithelia, demonstration of functional impact of CTNND1 and ESRP2 variants, and recapitulation of the CL/P spectrum in Ctnnd1 knockout mice support a causative role in CL/P pathogenesis. These data show that primary defects in regulators of epithelial cell adhesion are the most significant contributors to NS-CL/P identified to date and that inherited and de novo single gene variants explain a substantial proportion of NS-CL/P.

Application of network pharmacology and molecular docking to elucidate the potential mechanism of Astragalus-Scorpion against prostate cancer.

The present study aimed to investigate the molecular mechanism of the Astragalus-Scorpion drug pair in the treatment of prostate cancer (PCa). We employed network pharmacology and molecular docking technology to retrieving the active ingredients and corresponding targets of Astragalus-Scorpion by using TCMSP, BATMAN-TCM, TCMID and Swiss Target Prediction Databases. The targets related to PCa were retrieved through GeneCards. Cytoscape software was used to construct the 'active ingredient-target disease' network, and GO and KEGG enrichment analyses were performed on the common targets. Autodock software was used for molecular docking verification. In total, 26 active ingredients, 340 potential targets related to active ingredients and 122 common targets were screened from Astragalus-Scorpion drug pair. The core targets of the protein-protein interaction (PPI) network were JUN, AKT1, IL6, MAPK1 and RELA, whereas the core active ingredients were quercetin, kaempferol, formononetin, 7-o-methylisomucronulatol and calycosin. Nearly 762 GO entries and 154 pathways were obtained by using the pathway enrichment analysis. Molecular docking results revealed that quercetin and kaempferol bind to AKT1 and formononetin binds to RELA, all of which were found to be stable bounds.

Phytochemical Profiles and Antioxidant Activity of Rehmannia glutinosa from Different Production Locations.

The chemical components and antioxidant activity of 16 Rehmannia glutinosa samples were investigated to reveal the high-quality raw resource for pharmaceutical products. 22 main chemical components were detected with significant content differences (P<0.05). The contents of 14 substances reached the maximum in S1 sample such as catalpol (6.74 mg g-1 ), rehmaionoside A (1.93 mg g-1 ) and rehmannioside D (5.13 mg g-1 ). However, the content distribution of the other eight substances had no obvious change regulation. Three antioxidant evaluation methods commonly showed that S1 sample had strong antioxidant activity with a low IC50 value of 0.022 mg mL-1 , a high ABTS value of 524.196 µmol equiv. Trolox g-1 , and a high FRAP value of 200.517 µmol equiv. Trolox g-1 . Considered the medicinal value, S1 had high quality based on the present phytochemical profiles and antioxidant activity. These results also indicated that the root extracts of R. glutinosa could become useful supplement for pharmaceutical products as new antioxidant agents.

Discovery of Novel Inhibitors Targeting Multi-UDP-hexose Pyrophosphorylases as Anticancer Agents.

To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention. In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance. We hypothesize that the enzymes required for the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis, could serve as therapeutic targets for cancers. Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM. The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively. One of GAL-012 derivatives GAL-012-2 also demonstrated the inhibitory activity against GALT and UGP2. Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM. Western blot analysis revealed reduced expression of pAKT (Ser473), pAKT (Thr308) by 77% and 72%, respectively in the treated cells. siRNA experiments against the respective genes encoding the pyrophosphorylases were also performed and the results further validated the proposed roles in cancer growth inhibition. Finally, synergistic relationships between GAL-012 and tunicamycin, as well as bortezomib (BTZ) in killing cultured cancer cells were observed, respectively. With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.

Impact of diet on the persistence of early vascular remodeling and stiffening induced by intrauterine growth restriction and a maternal high-fat diet.

Intrauterine growth restriction (IUGR) and maternal high-fat diet (HFD) independently predispose offspring to hypertension. In a rat model, IUGR more so than maternal HFD increases arterial stiffness with vascular remodeling as early as postnatal day (PND) 21. The trajectory of such early vascular changes remains unknown. We hypothesized that IUGR would increase blood pressure (BP), arterial stiffness, and markers of ongoing detrimental vascular remodeling in adult rats exposed to a maternal HFD regardless of weaning diet. Adult female rats were fed either a regular diet (RD) or an HFD before mating through lactation. IUGR was induced by uterine artery ligation. Offspring were weaned to either a RD or HFD through PND 60. For both control and IUGR rats, this design resulted in the following three diet groups: offspring from RD dams weaned to a RD and offspring from HFD dams weaned to a RD or to an HFD (IHH). In both males and females, only IHH increased systolic BP, but IUGR and HFD both alone and in combination increased arterial stiffness. Aortas contained fewer but thicker elastin bands in IHH rats and IUGR offspring from dams fed an HFD and weaned to a regular diet. IHH increased aortic lysl oxidase protein. In summary, the PND 21 rat mediators of vascular remodeling from IUGR and maternal HFD normalize by PND 60 while changes in elastin and arterial stiffness persist. We speculate that the longer-term risk of hypertension from dietary mediators is augmented by underlying IUGR-induced structural changes to the extracellular matrix.NEW & NOTEWORTHY We report that a combined insult of intrauterine growth restriction and maternal high-fat diet increases the risk of early cardiovascular pathology both independently and in conjunction with a continued high-fat diet in offspring.

A novel phosphoglucomutase-deficient mouse model reveals aberrant glycosylation and early embryonic lethality.

Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes. Midline cleft defects are present at birth. Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation. To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology. After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes. Ultrasound studies of the course of pregnancy confirmed Pgm2-deficient pups succumb before E9.5. Oral galactose supplementation (9 mg/mL drinking water) did not rescue the lethality. Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content. However, glycomics analyses in serum revealed an abnormal glycosylation pattern in the Pgm2+/- animals, similar to that seen in PGM1-CDG.

Selective predation on acorn weevils by seed-caching Siberian chipmunk Tamias sibiricus in a tripartite interaction.

Although food-hoarding animals benefit plant seeds by generating predation pressure on granivorous insects, we lack experimental evidence of whether the tripartite interactions maintain a mutualistic relationship between the third trophic level and primary producers. Relying on the behavior of shelling, Siberian chipmunks (Tamias sibiricus) selectively consumed weevil larvae infested in acorns of Mongolian oak (Quercus mongolica) but chose the non-infested acorns to scatter-hoard. Shelling not only reduced volatile emission from acorns but also decreased cache loss to pilferers, weevil larvae and fungi, allowing T. sibiricus to gain more rewards from their caches. Moreover, shelling by T. sibiricus enhanced acorn germination and seedling establishment of Q. mongolica, possibly due to the diminishment of the negative effects of weevil infestation on acorn viability. Here, we show that both food-hoarding animal T. sibiricus and oak Q. mongolica can be conditionally benefited from selective predation on weevil larvae inside acorns. Our results highlight the need to integrate the mutualisms between the third and first trophic level into the tripartite interaction model. We suggest that more efforts should be made in the tripartite interactions of food-hoarding animals, seeds and granivorous insects.

Effects of Growing Location on the Contents of Main Active Components and Antioxidant Activity of Dasiphora fruticosa (L.) Rydb. by Chemometric Methods.

Traditional Chinese Medicine (TCM) is a very important raw material source for natural medicines in China. The content and activity of active component are main indexes that evaluate the quality of TCM, however, they may vary with environmental factors. In this study, the effects of environmental factors on the active component contents and antioxidant activity of Dasiphora fruticosa collected from the five main growing areas of China were investigated. The contents of tannin, total flavonoids and rutin were determined to be 7.65 - 10.69%, 2.30 - 5.39% and 0.18 - 0.81%, respectively. Antioxidant activity was determined by DPPH assay, with the DPPH IC50 values ranged from 8.791 to 32.534 µg mL-1 . In order to further explore the cause of these significant geographical variations, the chemometric methods including correlation analysis, principal component analysis, gray correlation analysis and path analysis were applied. The results showed that environmental factors had significant effect on the contents of active components and antioxidant activity. Rapidly available phosphorus (RAP) and rapidly available nitrogen (RAN) were common dominant factors, and a significant positive action existed between RAP and active components and antioxidant activity (P < 0.05). Contributed by their high active components and strong antioxidant activity, Bange in Tibet and Geermu in Qinghai Province were selected as a favorable growing location, respectively.

Intrauterine growth restriction influences vascular remodeling and stiffening in the weanling rat more than sex or diet.

Intrauterine growth restriction (IUGR) increases the incidence of adult cardiovascular disease (CVD). The sex-specific developmental mechanisms for IUGR-induced and Western high-fat diet (HFD) modification of CVD remain poorly understood. We hypothesized a maternal HFD in the Sprague-Dawley rat would augment IUGR-induced CVD in the offspring through decreased cardiac function and increased extracellular matrix (ECM) remodeling and stiffness in a sex-specific manner. HFD or regular diet (Reg) was given from 5 wk before mating through postnatal day (PND) 21. IUGR was induced by uterine artery ligation at embryonic day 19.5 (term = 21.5 days). At PND 21, echocardiographic assessments were made and carotid arteries tested for vascular compliance using pressure myography. Arterial samples were quantified for ECM constituents or fixed for histologic evaluation. The insult of IUGR (IUGR + Reg and IUGR + HFD) led to increased mechanical stiffness in both sexes (P < 0.05). The combination of IUGR + HFD increased diastolic blood pressure 47% in males (M) and 35% in females (F) compared with the Con + Reg (P < 0.05). ECM remodeling in IUGR + HFD caused fewer (M = -29%, F = -24%) but thicker elastin bands (M = 18%, F = 18%) and increased total collagen (M = 49%, F = 34%) compared with Con + Reg arteries. Remodeling in IUGR + HFD males increased medial collagen and soluble collagen (P < 0.05). Remodeling in IUGR + HFD females increased adventitial collagen and wall thickness (P < 0.05) and decreased matrix metalloproteinase 2 (MMP-2), advanced glycosylation end products (AGE), and receptor AGE (RAGE; P < 0.05). In summary, both IUGR + Reg and IUGR + HFD remodel ECM in PND 21 rats. While IUGR + HFD increases blood pressure, IUGR but not HFD increases vascular stiffness suggesting a specific mechanism of vascular remodeling that can be targeted to limit future disease. NEW & NOTEWORTHY: We report intrauterine growth restriction (IUGR) increases vascular stiffening in both male and female rats through increased collagen content and altered elastin structure more than a high-fat diet (HFD) alone. Our study shows the importance of stiffness supporting the hypothesis that there are physiologic differences and potential windows for early intervention targeting vascular remodeling mechanisms.

Regulation mechanism of PDK1 on macrophage metabolism and function.

PDK1 is a member of the atypical glandular cell kinases family that regulates the activities of most atypical glandular cell kinases during different development stages and treatment of cancers. PDK1 is also a critical glucose metabolism enzyme regulating glucolysis or glucose oxidase in cells, and more research is needed to further understand the underlying mechanism. The research of PDK1 presented by recent studies focuses much on cancer treatment and has helped researchers gain much insight in this regard. Given the close relationship between inflammation and cancer, it is of great significance to discover the function of PDK1 and its regulating mechanism on special immune cells-macrophages. This review summarizes the recent findings regarding PDK1 in terms of regulating the function and metabolism of macrophage. The mechanism of PDK1 in regulating inflammatory secretion, migration, phagocytosis, and the energy metabolism of macrophage and a possible path to develop PDK1 related pharmaceutical products are discussed as well.

IUGR prevents IGF-1 upregulation in juvenile male mice by perturbing postnatal IGF-1 chromatin remodeling.

BACKGROUND: Intrauterine growth restriction (IUGR) offspring with rapid catch-up growth are at increased risk for early obesity especially in males. Persistent insulin-like growth factor-1 (IGF-1) reduction is an important risk factor. Using a mouse model of maternal hypertension-induced IUGR, we examined IGF-1 levels, promoter DNA methylation, and histone H3 covalent modifications at birth (D1). We additionally investigated whether prenatal perturbations could reset at preadolescence (D21). METHODS: IUGR was induced via maternal thromboxane A2-analog infusion in mice. RESULTS: IUGR uniformly decreased D1 IGF-1 mRNA and protein levels with reduced promoter 1 (P1) transcription and increased P1 DNA methylation. IUGR males also had increased H3K4ac at exon 5 and 3' distal UTR. At D21, IUGR males continued to have decreased IGF-1 levels, originating from both P1 and P2 with reduced 1A variant. IUGR males also had decreased activation mark of H3K4me3 at P1 compared with sham males. In contrast, D21 IUGR females normalized their IGF-1 levels, in association with an increased activation mark of H3K4me3 at P1 compared with sham females. CONCLUSION: IUGR uniformly affected D1 hepatic IGF-1 epigenetic modifications in both sexes. However, at preadolescence, IUGR males are unable to correct for the prenatal reduction possibly due to a more perturbed IGF-1 chromatin structure.

The influencing mechanism of scenic spot online attention and tourists' purchase behavior: an AISAS model based investigation.

Introduction: In the era of the Internet, online digital traces have become a new way to study the online attention of scenic spots and tourists' purchase behavior. The public's information search on major search platforms is a series of manifestations of potential tourists' attention and interest in scenic spots, but there are few studies on how attention, interest and information search affect potential tourists to generate real purchase behavior. Method: This paper selects four dimensions of short video platform, travel website, search engine and social media to comprehensively measure the online attention of high-quality scenic spots in Yunnan Province, and then establishes a gray association analytic hierarchy process based on the relevant variables of the AISAS model to empirically analyze the primary and secondary factors affecting tourists' purchase behavior. Results: (1) From the perspective of the online attention of scenic spots on different platforms, the intensity of the public's scenic spots online attention on the four types of media platforms is in the order of travel websites, search engines, short videos and social media (2) From the perspective of spatial distribution characteristics, the online attention of high-quality scenic spots in Yunnan Province is unevenly distributed, that is, there is a big difference between the attention of higher star scenic spots and their star rating and popularity, while the attention of low-star scenic spots is not much different from their star rating and popularity (3) From the perspective of spatial agglomeration characteristics, the comprehensive online attention of high-quality scenic spots in Yunnan Province presents the spatial agglomeration characteristics of "the multi-core linkage of high-density in the east and north, and sub-high-density in the south" (4) The factors influencing the purchase behavior of potential tourists are sharing experience, attracting attention, generating interest and searching information. Discussion: By exploring the formation mechanism of high-quality scenic spots online attention in Yunnan Province and the mechanism of its spatial differentiation, this study not only enriches the logical chain of "tourism information source → potential tourists → demand driven → tourism information search → travel preference → destination selection → purchase decision → travel experience → real tourists → feelings after traveling → focus on feedback → tourism information source," but also broadens the application scenarios and application boundaries of travel preference theory and AISAS behavior model to a certain extent.

Site-specific, covalent immobilization of PNGase F on magnetic particles mediated by microbial transglutaminase.

In the workflow of global N-glycosylation analysis, endoglycosidase-mediated removal of glycans from glycoproteins is an essential and rate-limiting step. Peptide-N-glycosidase F (PNGase F) is the most appropriate and efficient endoglycosidase for the removal of N-glycans from glycoproteins prior to analysis. Due to the high demand for PNGase F in both basic and industrial research, convenient and efficient methods are urgently needed to generate PNGase F, preferably in the immobilized form to solid phases. However, there is no integrated approach to implement both efficient expression, and site-specific immobilization of PNGase F. Herein, efficient production of PNGase F with a glutamine tag in Escherichia coli and site-specific covalent immobilization of PNGase F with this special tag via microbial transglutaminase (MTG) is described. PNGase F was fused with a glutamine tag to facilitate the co-expression of proteins in the supernatant. The glutamine tag was covalently and site-specifically transformed to primary amine-containing magnetic particles, mediated by MTG, to immobilize PNGase F. Immobilized PNGase F could deglycosylate substrates with identical enzymatic performance to that of the soluble counterpart, and exhibit good reusability and thermal stability. Moreover, the immobilized PNGase F could also be applied to clinical samples, including serum and saliva.

Spontaneous and site-specific immobilization of PNGase F via spy chemistry.

Protein N-glycosylation plays a critical role in a wide range of biological processes, and aberrant N-glycosylation is frequently associated with various pathological states. For global N-glycosylation analysis, N-glycans are typically released from glycoproteins mediated by endoglycosidases, primarily peptide N-glycosidase F (PNGase F). However, conventional N-glycan release by in-solution PNGase F is time-consuming and nonreusable. Although some immobilization methods can save time and reduce the enzyme dosage, including affinity interaction and covalent binding, the immobilized PNGase F by these traditional methods may compromises the immobilized enzyme's stability and biofunction. Therefore, a new approach is urgently needed to firmly and steadily immobilize PNGase F. To meet this demand, we have developed a spontaneous and site-specific way to immobilize PNGase F onto magnetic nanoparticles via Spy chemistry. The magnetic nanoparticles were synthesized and modified with SpyTag as a solid surface. The PNGase F fused with SpyCatcher can then be site-specifically and covalently immobilized onto this solid phase, forming a firm isopeptide bond via self-catalysis between the SpyTag peptide and SpyCatcher. Importantly, the immobilization process mediated by mild spy chemistry does not result in PNGase F inactivation; and allows immobilized PNGase F to rapidly release various types of glycans (high-mannose, sialylated, and hybrid) from glycoproteins. Moreover, the immobilized PNGase F exhibited good deglycosylation activity and facilitated good reusability in consecutive reactions. Deglycosylation of clinical samples was completed by the immobilized PNGase F as fast as several minutes.

Large artery stiffening and mortality in a rat model of early vascular remodeling induced by intrauterine growth restriction and a high-fat diet.

Intrauterine growth restriction (IUGR) and exposure to a high-fat diet (HFD) independently increase the risk of cardiovascular disease (CVD) and hyperlipidemia. In our previous studies, IUGR increased blood pressure and promoted vascular remodeling and stiffness in early life, a finding that persisted and was augmented by a maternal HFD through postnatal day (PND) 60. The impact of these findings with aging and the development of hyperlipidemia and atherosclerosis remain unknown. We hypothesized that the previously noted impact of IUGR on hypertension, vascular remodeling, and hyperlipidemia would persist. Adult female rats were fed either a regular diet (RD) or high fat diet (HFD) prior to conception through lactation. IUGR was induced by uterine artery ligation. Offspring were weaned to either RD or HFD through PND 365. For both control (C) and IUGR (I) and rats, this resulted in the following six groups per sex: offspring from RD dams weaned to an RD (CRR and IRR), or offspring from HFD dams weaned to either an RD (CHR and IHR) or to an HFD (CHH and IHH). IHH male and female rats had increased large artery stiffness, a suggestion of fatty streaks in the aorta, and persistent decreased elastin and increased collagen in the aorta and carotid arteries. Post-weaning HFD intake increased blood lipids regardless of IUGR status. IUGR increased HFD-induced mortality. We speculate that HFD-induced risk of CVD and mortality is potentiated by developmental programming of the ECM.

[Effects of oxidative stress on MuRF1 expression in skeletal muscle of diabetic rats].

OBJECTIVE: To determine whether muscle-specific RING finger protein 1 (MuRF1) expression induced by oxidative stress lead to muscle wasting in diabetes rats. METHODS: The diabetes rat model was established by high-carbohydrate, high-fat diet and injection of streptozotocin. The expression of MuRF1 in gastrocnemius was detected by immunohistochemistry and real time PCR. The level of lipid peroxidation, SOD and fiber size of gastrocnemius was also detected. Further more, C2C12 myotubes were cultured with different concentration of H2O2 (0, 0.01, 0.05, 0.10 and 0.20 mmol/L), the level of MuRF1 protein was detected by western blot. RESULTS: Compared with the control group, the diabetes rats showed higher level of thiobarbituric acid reactive substances (TBARS) and MuRF1 mRNA and lower fiber size in gastrocnemius (P < 0.01). The oxidative stress induced by H2O2 (0.05, 0.10 and 0.20 mmol/L) upregulated the expression of MuRF1 (P < 0.01) in C2C12 myotube cells. CONCLUSION: Our results indicated that diabetes modulated the expression of MuRF1 leading to muscle wasting, and the mechanism might be involved with oxidative stress.

Exercise May Promote Skeletal Muscle Hypertrophy via Enhancing Leucine-Sensing: Preliminary Evidence.

Several studies have indicated a positive effect of exercise (especially resistance exercise) on the mTOR signaling that control muscle protein synthesis and muscle remodeling. However, the relationship between exercise, mTOR activation and leucine-sensing requires further clarification. Two month old Sprague-Dawley rats were subjected to aerobic exercise (treadmill running at 20 m/min, 6° incline for 60 min) and resistance exercise (incremental ladder climbing) for 4 weeks. The gastrocnemius muscles were removed for determination of muscle fibers diameter, cross-sectional area (CSA), protein concentration and proteins involved in muscle leucine-sensing and protein synthesis. The results show that 4 weeks of resistance exercise increased the diameter and CSA of gastrocnemius muscle fibers, protein concentration, the phosphorylation of mTOR (Ser2448), 4E-BP1(Thr37/46), p70S6K (Thr389), and the expression of LeuRS, while aerobic exercise just led to a significant increase in protein concentration and the phosphorylation of 4E-BP1(Thr37/46). Moreover, no difference was found for Sestrin2 expression between groups. The current study shows resistance exercise, but not aerobic exercise, may increase muscle protein synthesis and protein deposition, and induces muscle hypertrophy through LeuRS/mTOR signaling pathway. However, further studies are still warranted to clarify the exact effects of vary intensities and durations of aerobic exercise training.