Trastuzumab-induced cardiomyopathy via ferroptosis-mediated mitochondrial dysfunction.

Trastuzumab (TRZ) is a first-line chemotherapeutic agent for HER-2 (ErbB2)-positive breast cancer. Unfortunately, its clinical use is limited due to its cardiotoxicity, referred to as TRZ-induced cardiotoxicity (TIC). However, the exact molecular mechanisms underlying the development of TIC remain unclear. Iron and lipid metabolism and redox reactions participate in the development of ferroptosis. Here, we show that ferroptosis-mediated mitochondrial dysfunction is involved in TIC in vivo and in vitro. We first established TIC models with BALB/c mice or neonatal rat cardiomyocytes and confirmed cardiomyopathy with echocardiography and inhibition of cell viability with a cell counting kit-8 examination, respectively. We showed that TRZ downregulated glutathione peroxidase 4 (GPx4) and elevated lipid peroxidation by-products, 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), by inactivating the ErbB2/PI3K/AKT/Nrf2 signalling pathway. Additionally, upregulated mitochondrial 4-HNE binds to voltage-dependent anion channel 1 (VDAC1), increases VDAC1 oligomerization, and subsequently induces mitochondrial dysfunction, as evidenced by mitochondrial permeability transition pore (mPTP) opening and decreased mitochondrial membrane potential (MMP) and ATP levels. Concomitantly, TRZ affected the mitochondrial levels of GSH/GSSG and iron ions and the stability of mitoGPx4. Ferroptosis inhibitors, such as ferrostatin-1 (Fer-1) or the iron chelator deferoxamine (DFO), ameliorate TRZ-induced cardiomyopathy. Overexpression of mitoGPx4 also suppressed mitochondrial lipid peroxidation and prevented TRZ-induced ferroptosis. Our study strongly suggests that targeting ferroptosis-mediated mitochondrial dysfunction is a potential cardioprotective strategy.

Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis.

An imbalance of human mesenchymal stem cells (MSCs) adipogenic and osteogenic differentiation plays an important role in the pathogenesis of osteoporosis. Our previous study verified that Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1)/myoferlin deficiency promotes adipogenic differentiation of MSCs by blocking autophagic flux in osteoporosis. However, the function of APPL1 in the osteogenic differentiation of MSCs remains unclear. This study aimed to investigate the role of APPL1 in the osteogenic differentiation of MSCs in osteoporosis and the underlying regulatory mechanism. In this study, we demonstrated the downregulation of APPL1 expression in patients with osteoporosis and osteoporosis mice. The severity of clinical osteoporosis was negatively correlated with the expression of APPL1 in bone marrow MSCs. We found that APPL1 positively regulates the osteogenic differentiation of MSCs in vitro and in vivo. Moreover, RNA sequencing showed that the expression of MGP, an osteocalcin/matrix Gla family member, was significantly upregulated after APPL1 knockdown. Mechanistically, our study showed that reduced APPL1 impaired the osteogenic differentiation of mesenchymal stem cells by facilitating Matrix Gla protein expression to disrupt the BMP2 pathway in osteoporosis. We also evaluated the significance of APPL1 in promoting osteogenesis in a mouse model of osteoporosis. These results suggest that APPL1 may be an important target for the diagnosis and treatment of osteoporosis.

m6 A-Dependent Modulation via IGF2BP3/MCM5/Notch Axis Promotes Partial EMT and LUAD Metastasis.

The importance of mRNA N6-methyladenosine (m6 A) modification during tumor metastasis is controversial as it plays distinct roles in different biological contexts. Moreover, how cancer cell plasticity is shaped by m6 A modification is interesting but remains uncharacterized. Here, this work shows that m6 A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) is remarkably upregulated in metastatic lung adenocarcinoma (LUAD) and indicates worse prognosis of patients. Interestingly, IGF2BP3 induces partial epithelial-mesenchymal-transition (EMT) and confers LUAD cells plasticity to metastasize through m6 A-dependent overactivation of Notch signaling. Mechanistically, IGF2BP3 recognized m6 A-modified minichromosome maintenance complex component (MCM5) mRNAs to prolong stability of them, subsequently upregulating MCM5 protein, which competitively inhibits SIRT1-mediated deacetylation of Notch1 intracellular domain (NICD1), stabilizes NICD1 protein and contributes to m6 A-dependent IGF2BP3-mediated cellular plasticity. Notably, a tight correlation of the IGF2BP3/MCM5/Notch axis is evidenced in clinical LUAD specimens. Therefore, this study elucidates a critical role of m6 A modification on LUAD cell plasticity in fostering tumor metastasis via the above axis, providing potential targets for metastatic LUAD.

VUV-UV-vis photoluminescence, X-ray radioluminescence and energy transfer dynamics of Ce3+ and Eu2+ in Sr2MgSi2O7.

Ce3+ and Eu2+ doped and Ce3+-Eu2+ co-doped Sr2MgSi2O7 phosphors are prepared via a high-temperature solid-state reaction technique. The synchrotron radiation vacuum ultraviolet-ultraviolet (VUV-UV) excitation and ultraviolet-visible (UV-vis) emission spectra of diluted Ce3+ and Eu2+ doped Sr2MgSi2O7 samples are measured at cryogenic temperatures. The electron-vibrational interaction (EVI) between Ce3+ and its surroundings is analyzed. The dependencies of the 4f-5d transitions of Ce3+ on the structure of the host compounds Sr2MgSi2O7, Ba2MgSi2O7 and BaMg2Si2O7 are discussed in detail. Then the thermal quenching channel is proposed based on the measurements of temperature dependent luminescence intensities and decay times of Ce3+ and Eu2+ in Sr2MgSi2O7, and the Ce3+ → Eu2+ energy transfer mechanism is understood by three luminescence dynamic models. In addition, Sr2MgSi2O7:Ce3+/Eu2+ samples are evaluated for the possibilities of X-ray detection applications using X-ray excited luminescence (XEL) spectroscopy, and it was found that they are not suitable.

Solving Robotic Trajectory Sequential Writing Problem via Learning Character's Structural and Sequential Information.

The writing sequence of numerals or letters often affects aesthetic aspects of the writing outcomes. As such, it remains a challenge for robotic calligraphy systems to perform, mimicking human writers' implicit intention. This article presents a new robot calligraphy system that is able to learn writing sequences with limited sequential information, producing writing results compatible to human writers with good diversity. In particular, the system innovatively applies a gated recurrent unit (GRU) network to generate robotic writing actions with the support of a prelabeled trajectory sequence vector. Also, a new evaluation method is proposed that considers the shape, trajectory sequence, and structural information of the writing outcome, thereby helping ensure the writing quality. A swarm optimization algorithm is exploited to create an optimal set of parameters of the proposed system. The proposed approach is evaluated using Arabic numerals, and the experimental results demonstrate the competitive writing performance of the system against state-of-the-art approaches regarding multiple criteria (including FID, MAE, PSNR, SSIM, and PerLoss), as well as diversity performance concerning variance and entropy. Importantly, the proposed GRU-based robotic motion planning system, supported with swarm optimization can learn from a small dataset, while producing calligraphy writing with diverse and aesthetically pleasing outcomes.

Numerical Simulation of the Shear Capacity of a GFRP-Strengthened Natural Bamboo-Bolt Composite Joint.

As an ecological green building material, natural bamboo has many advantages such as a light weight, high strength, and short growth cycle. Natural bamboo is widely used in landscape architecture and fabricated structures. However, in bamboo building structures, the most common bolted joints often appear cleaved along the grain. In this paper, glass fiber-reinforced polymer (GFRP) is designed to wrap and improve the shear capacity of natural bamboo-bolt composite joints. According to the corresponding material parameters, the finite element model of composite joints is established, and the key influencing variables of the bearing capacity, namely the bolt diameter, bamboo tube outer diameter, and screw end distance, are analyzed. In addition, according to the European analytical yield model of bolted connections, the analytical calculation method of the bearing capacity is proposed and compared with the experimental and simulated values. The results showed that the numerical model and the modified analytical model can suitably describe the bearing capacity of composite joints, and a higher bolt diameter, along with the bamboo outer diameter, will lead to a higher ultimate load of the composite joints. Moreover, the bearing capacity of composite joints has no obvious relationship with the end spacing.

Dynamic Variation of Ecosystem Services Value under Land Use/Cover Change in the Black Soil Region of Northeastern China.

A better understanding of the dynamic variation in the ecosystem service value (ESV) under land use/cover change (LUCC) is conductive to improving ecosystem services and environmental protection. The present study took Landsat TM/ETM remote sensing images and socio-economic statistic data as data sources and extracted land-use data using RS and GIS technology at 5-year intervals from 1990 to 2020. Then, we interpreted the spatio-temporal characteristics of LUCC and analyzed ESV changes using the value equivalence method in the black soil region of northeastern China (BSRNC). The main results showed that land use changed significantly during the study period. Cultivated land continued to expand, especially paddy areas, which increased by 1.72 × 106 ha, with a relative change of 60.9% over 30 years. However, grassland decreased by 2.47 × 106 ha, with a relative change of -60.6% over 30 years. The ESV showed a declining trend, which decreased by CNY 607.96 million during 1990-2020. The decline in forest and grassland caused a significant decline in the ESV. Furthermore, the ESV sensitivity coefficients were less than one for all of the different categories of ecosystem services. LUCC has a considerable impact on ESV in the BSRNC, resulting in ecosystem function degradation. As a result, future policies must emphasize the relationship between food security and environmental protection in situations of significant land-use change.

Metastatic Tumor Cell-Specific FABP7 Promotes NSCLC Metastasis via Inhibiting ß-Catenin Degradation.

Metastasis accounts for 90% of cancer-related deaths and represents a prominent malignant feature in non-small cell lung cancer (NSCLC), while tumor cell-specific mechanisms and molecules pivotal for the metastatic capacity remain unclear. By analyzing single-cell RNA sequencing data, we found that fatty acid binding protein 7 (FABP7) was specifically up-regulated in tumor cells of metastatic NSCLC patients and might be a prognostic indicator for poor survival. Experimental studies based on NSCLC cell lines showed that FABP7 promoted the metastatic competencies of NSCLC cells in vitro and in vivo. Mechanistically, we demonstrated that FABP7 was important to canonical Wnt signaling activation and competitively inhibited the interaction between ß-catenin and components of its cytoplasmic degradation complex, thereby repressing the phosphorylation-dependent ubiquitination and degradation of ß-catenin. Our present study identifies FABP7 as a metastatic tumor cell-specific pro-metastatic gene and uncovers a previously unknown regulatory mechanism underlying Wnt hyperactivation via FABP7-impaired cytoplasmic ß-catenin degradation, implicating a novel molecule in regulating NSCLC metastasis.

An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness.

Notch signaling represents a key mechanism mediating cancer metastasis and stemness. To understand how Notch signaling is overactivated to couple tumor metastasis and self-renewal in NSCLC cells, we performed the current study and showed that RFC4, a DNA replication factor amplified in more than 40% of NSCLC tissues, directly binds to the Notch1 intracellular domain (NICD1) to competitively abrogate CDK8/FBXW7-mediated degradation of NICD1. Moreover, RFC4 is a functional transcriptional target gene of Notch1 signaling, forming a positive feedback loop between high RFC4 and NICD1 levels and sustained overactivation of Notch signaling, which not only leads to NSCLC tumorigenicity and metastasis but also confers NSCLC cell resistance to treatment with the clinically tested drug DAPT against NICD1 synthesis. Furthermore, together with our study, analysis of two public datasets involving more than 1500 NSCLC patients showed that RFC4 gene amplification, and high RFC4 and NICD1 levels were tightly correlated with NSCLC metastasis, progression and poor patient prognosis. Therefore, our study characterizes the pivotal roles of the positive feedback loop between RFC4 and NICD1 in coupling NSCLC metastasis and stemness properties and suggests its therapeutic and diagnostic/prognostic potential for NSCLC therapy.

Berberine-induced TFEB deacetylation by SIRT1 promotes autophagy in peritoneal macrophages.

Atherosclerosis is a chronic inflammatory disease that commonly affects the elderly and is characterized by vascular damage, macrophage infiltration, and plaque formation. Moreover, it increases the risk of cardiovascular disease. The pathogenesis of atherosclerosis involves an interplay between macrophage autophagy and apoptosis. A recently discovered transcription factor, transcription factor EB (TFEB) is known to activate autophagy in macrophages. Sirtuin deacetylase 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, activates several transcription factors, including TFEB. We studied the effects of berberine on the NAD+ synthesis pathway and interactions between SIRT1 and TFEB. We also studied the effects of berberine-induced TFEB activation via SIRT1 on autophagy and apoptosis of peritoneal macrophages. We found that berberine promoted autophagy of peritoneal macrophages by activating SIRT1 via the NAD+ synthesis pathway and, in turn, promoting TFEB nuclear translocation and deacetylation. The functional regulation of SIRT1 and TFEB by berberine could be exploited as a potential therapeutic strategy for atherosclerosis.

Electrical stimulation inhibits Val-boroPro-induced pyroptosis in THP-1 macrophages via sirtuin3 activation to promote autophagy and inhibit ROS generation.

The incidence of atherosclerosis (AS), a major contributor to cardiovascular disease, is steadily rising along with an increasingly older population worldwide. Pyroptosis, a form of inflammatory programmed cell death, determines the release of pro-inflammatory mediators by endothelial cells, smooth muscle cells, and atheroma-associated macrophages and foam cells, thereby playing a critical role in AS progression. Canonical pyroptosis is mediated by inflammasome formation, activation of caspase-1, and maturation and release of proinflammatory cytokines. Electrical stimulation (ES) is a noninvasive, safe therapy that has been shown to alleviate symptoms in several health conditions. Here, we investigated the anti-inflammatory and anti-pyroptotic effects of ES in human THP-1 macrophages treated with the dipeptidyl peptidase inhibitor Val-boroPro (VbP). We found that ES downregulated NOD-like receptor family protein 3 (NLRP3) inflammasome, ASC, and caspase-1 expression and abrogated the release of Interleukin-1ß (IL-1ß) and Interleukin-18 (IL-18), indicating effective pyroptosis inhibition. These changes were paralleled by a reduction in reactive oxygen species (ROS) production, reversal of VbP-induced sirtuin3 (Sirt3) downregulation, deacetylation of ATG5, and induction of autophagy. These findings suggest that ES may be a viable strategy to counteract pyroptosis-mediated inflammation in AS by raising Sirt3 to promote autophagy and inhibit ROS generation.

OsmiR528 regulates rice-pollen intine formation by targeting an uclacyanin to influence flavonoid metabolism.

The intine, the inner layer of the pollen wall, is essential for the normal development and germination of pollen. However, the composition and developmental regulation of the intine in rice (Oryza sativa) remain largely unknown. Here, we identify a microRNA, OsmiR528, which regulates the formation of the pollen intine and thus male fertility in rice. The mir528 knockout mutant aborted pollen development at the late binucleate pollen stage, significantly decreasing the seed-setting rate. We further demonstrated that OsmiR528 affects pollen development by directly targeting the uclacyanin gene OsUCL23 (encoding a member of the plant-specific blue copper protein family of phytocyanins) and regulating intine deposition. OsUCL23 overexpression phenocopied the mir528 mutant. The OsUCL23 protein localized in the prevacuolar compartments (PVCs) and multivesicular bodies (MVBs). We further revealed that OsUCL23 interacts with a member of the proton-dependent oligopeptide transport (POT) family of transporters to regulate various metabolic components, especially flavonoids. We propose a model in which OsmiR528 regulates pollen intine formation by directly targeting OsUCL23 and in which OsUCL23 interacts with the POT protein on the PVCs and MVBs to regulate the production of metabolites during pollen development. The study thus reveals the functions of OsmiR528 and an uclacyanin during pollen development.

A warm white emission of Bi3+-Eu3+ and Bi3+-Sm3+ codoping Lu2Ge2O7 phosphors by energy transfer of Bi3+-sensitized Eu3+/Sm3.

In the last few years, multicolor-tunable phosphors, especially single-composition white-light-emitting phosphors, have attracted increasing attention and interest for UV-converted white LEDs. In this paper, Lu2Ge2O7:Bi3+ phosphor presents a doublet emission ranging from UV to visible spectrum with a high QE of 76%. To obtain a warm white emission, we tried to codope Eu3+ or Sm3+ into Lu2Ge2O7 with Bi3+ ions. Multicolor-tunable emission colors of Bi3+-Eu3+ and Bi3+-Sm3+ codoped Lu2Ge2O7 samples are adjusted from cold white light, warm white light, light pink, pink, to red by changing the Eu3+ or Sm3+ doping concentration. Energy transfer process occurring from Bi3+ to Eu3+ or Sm3+ is discussed in detail and the corresponding ηETE of Bi3+-Eu3+ and Bi3+-Sm3+ can reach as high as 42% and 35%, respectively. This paper not only provides a novel UV-converted multicolor-tunable phosphor, but also discovery novel single-composition white-light-emitting phosphors for UV-converted white LEDs.

Available energy and amino acid digestibility of yellow dent corn fed to growing pigs1.

Two experiments were conducted to determine the DE and ME as well as the apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of CP and AA in corn fed to growing pigs. All corn was yellow dent corn collected from different areas in China. In Exp. 1, 60 crossbred barrows (Duroc × Landrace × Yorkshire; 40.7 ± 3.5 kg BW) were randomly allotted to 1 of 10 diets to determine the DE and ME of corns. Diets were formulated to contain 96.8% of 1 of the 10 corn samples and 3.2% of other microingredients. In Exp. 2, 11 crossbred barrows (Duroc × Landrace × Yorkshire; 30.5 ± 2.3 kg) fitted with a T-cannula at the distal ileum were assigned to a 6 × 11 Youden square design with 6 periods and 11 diets. Diets included a N-free diet based on cornstarch and sucrose and 10 test diets formulated with 96.6% 1 of the 10 corns as the sole source of AA. Chromic oxide (0.3%) was added to each diet as an indigestible marker for calculating the AA digestibility. On a DM basis, the starch, ether extract (EE), CP, NDF, and ADF contents of corns averaged 74.05% (69.98 to 78.59%), 3.83% (2.04 to 4.73%), 9.63% (7.74 to 10.43%), 10.80% (10.27 to 11.46%), and 2.27% (2.03 to 2.57%), respectively. The CV of EE, CP, and ADF was 22.59, 8.22, and 8.21%, respectively. The DE and ME of corns averaged 4,087 and 3,981 kcal/kg, respectively, and ranged from 3,999 to 4,161 kcal/kg and from 3,898 to 4,067 kcal/kg, respectively. The DE and ME values were positively correlated (P < 0.05) with the EE content. Optimal prediction equations of ME were ME = 940.35 + (0.72 × DE) + (21.88 × EE) (R2 = 0.94) or ME = 1,051.50 + (0.82 × DE) - (282.05 × ash) (R2 = 0.99). In Exp. 2, significant differences (P < 0.05) were observed in the SID of Arg, His, Phe, Ala, Pro, Cys, and Tyr. The SID of Lys (average 73.79%), Met (average 87.32%), and Thr (average 80.06%) ranged from 61.45 to 78.47%, from 74.09 to 90.91%, and from 79.19 to 85.79%, respectively. The standardized ileal digestible Met was positively correlated (P < 0.01) with the Met and CP contents. The obtained prediction equations were standardized ileal digestible Met = 31.34 + (3.43 × CP) + (116.04 × Met) and standardized ileal digestible Met = 104.92 + (294.71 × Met) - (7.03 × NDF). In conclusion, sources had an effect on the energy values and ileal digestibility of most AA in corn. The ME can be predicted by the DE combined with either the EE or ash content. The AA concentrations and SID of AA in corn varied largely.

Highly bright multicolor-tunable KSrLu(PO4)2:Ce3+, Tb3+, Mn2+ phosphors via efficient energy transfer.

Research hotspots about Ce3+-Tb3+ and Ce3+-Mn2+ codoped multicolor-tunable materials, has grown rapidly and is still growing. However, few feasible strategies can be employed to achieve the multicolor-tunable luminescence under the premise of maintaining high QE. In this paper, KSrLu(PO4)2:0.25Ce presents a high luminescence efficiency with approximately 78% quantum efficiency. Furthermore, Ce3+-Tb3+ and Ce3+-Mn2+ codoped optimal samples give a green and red luminescence, which corresponds to a high 61% and 55% quantum efficiency due to a high energy transfer efficiency of Ce3+→Tb3+ and Ce3+→Mn2+. Besides, we achieved the precise adjustment of blue, green, orange and pink emissions of KSrLu(PO4)2:Ce3+, Tb3+, Mn2+ samples. Meanwhile, KSrLu(PO4)2:Ce3+, Tb3+ and KSrLu(PO4)2:Ce3+, Mn2+ phosphors present a weak thermal quenching: their integrated emission intensity at 500K still keep more than 80% of their initial intensity at room temperature. Therefore, the results might provide a novel multicolor-tunable phosphor for backlight display application.

Thioredoxin 2 Offers Protection against Mitochondrial Oxidative Stress in H9c2 Cells and against Myocardial Hypertrophy Induced by Hyperglycemia.

Mitochondrial oxidative stress is thought to be a key contributor towards the development of diabetic cardiomyopathy. Thioredoxin 2 (Trx2) is a mitochondrial antioxidant that, along with Trx reductase 2 (TrxR2) and peroxiredoxin 3 (Prx3), scavenges H2O2 and offers protection against oxidative stress. Our previous study showed that TrxR inhibitors resulted in Trx2 oxidation and increased ROS emission from mitochondria. In the present study, we observed that TrxR inhibition also impaired the contractile function of isolated heart. Our studies showed a decrease in the expression of Trx2 in the high glucose-treated H9c2 cardiac cells and myocardium of streptozotocin (STZ)-induced diabetic rats. Overexpression of Trx2 could significantly diminish high glucose-induced mitochondrial oxidative damage and improved ATP production in cultured H9c2 cells. Notably, Trx2 overexpression could suppress high glucose-induced atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression. Our studies suggest that high glucose-induced mitochondrial oxidative damage can be prevented by elevating Trx2 levels, thereby providing extensive protection to the diabetic heart.

Laccase-13 Regulates Seed Setting Rate by Affecting Hydrogen Peroxide Dynamics and Mitochondrial Integrity in Rice.

Seed setting rate is one of the most important components of rice grain yield. To date, only several genes regulating setting rate have been identified in plant. In this study, we showed that laccase-13 (OsLAC13), a member of laccase family genes which are known for their roles in modulating phenylpropanoid pathway and secondary lignification in cell wall, exerts a regulatory function in rice seed setting rate. OsLAC13 expressed in anthers and promotes hydrogen peroxide production both in vitro and in the filaments and anther connectives. Knock-out of OsLAC13 showed significantly increased seed setting rate, while overexpression of this gene exhibited induced mitochondrial damage and suppressed sugar transportation in anthers, which in turn affected seed setting rate. OsLAC13 also induced H2O2 production and mitochondrial damage in the root tip cells which caused the lethal phenotype. We also showed that high abundant of OsmiR397, the suppressor of OsLAC13 mRNA, increased the seed setting rate of rice plants, and restrains H2O2 accumulation in roots during oxidative stress. Our results suggested a novel regulatory role of OsLAC13 gene in regulating seed setting rate by affecting H2O2 dynamics and mitochondrial integrity in rice.

Circular RNAs roll into the regulatory network of plants.

As a novel class of endogenous non-coding RNAs, circular RNAs (circRNAs) have become a new research hotspot in recent years. The wide distribution of circRNAs in different plant species has been proven. Furthermore, circRNAs show significant tissue-specific expression patterns in plant development and are responsive to a variety of biotic and abiotic stresses, indicating that circRNAs might have important biological functions in plant development. Here, we summarize the current knowledge of plant circRNAs in recent years and discuss views and perspectives on the possible regulatory roles of plant circRNAs, including the function of miRNA sponges, regulating the expression of their parental genes or linear mRNAs, translating into peptides or proteins and responses to different stresses. These advances have sculpted a framework of plant circRNAs and provide new insights for functional RNA regulation research in the future.

Sulfiredoxin involved in the protection of peroxiredoxins against hyperoxidation in the early hyperglycaemia.

As a direct consequence of hyperglycaemia, the excessive generation of ROS is central to the pathogenesis of diabetic cardiomyopathy. We hypothesize that stimulation of high glucose (HG) results in an increased sulfiredoxin (Srx) expression, which regulates ROS signaling through reducing the hyperoxidized peroxiredoxins (Prxs). We show that hyperoxidized Prxs were initially reduced in the preliminary stage but then dramatically increased in advanced stage and these changes corresponded to a significant increase of Srx expression in the heart of diabetic rats. These time-dependent changes were also confirmed in neonatal cardiomyocytes and H9c2 cells treated with HG. Moreover, the reduction rate of hyperoxidized Prxs was greatly improved in the HG 24h group, which had an elevated expression of Srx. Our data also show that HG-induced AP1 activation and Srx expression were almost abolished by JNK inhibitor and N-acetylcysteine (NAC). In addition, siRNA-Srx suppressed HG-induced ANP and ß-MHC gene expression. These observations suggest that activation of AP1 induced by HG is important for the expression of Srx and the reduction of hyperoxidized Prxs in cardiomyocytes. This Srx induction maybe is the pivotal compensatory protection mechanism against oxidative stress in diabetes or hyperglycaemia. Most interestingly, hyperoxidized Prxs/Srx pathway may be involved in the cardiac hypertrophy signaling of diabetes.

Effects of variety and storage duration on the nutrient digestibility and the digestible and metabolisable energy content of maize fed to growing pigs.

The objective of this research was to determine the effects of variety and storage duration on the nutrient digestibility and the digestible (DE) and metabolisable (ME) energy content in maize when fed to growing pigs. Four maize varieties (LS1, LS2, LS3 and LS4) were hand-harvested from the same growing area in China in early October of 2012. The samples were sun dried to about 14% moisture content and then stored in the warehouse of the Fengning Pig Experiment Base at China Agricultural University for 0, 3 or 10 months. Twenty-four barrows of about 33 kg body weight were used and allotted to a completely randomised block design with four diets and six replicate pigs per diet. Pigs were individually housed in metabolic crates. The four experimental diets were formulated by mixing 96.8% of each variety of maize with 3.2% vitamins and minerals. A 5-day collection period followed a 7-day diet acclimation period. The results indicated that the DE and ME contents of maize and the apparent total tract digestibility (ATTD) of organic matter (OM), dry matter, gross energy (GE), neutral detergent fibre, acid detergent fibre (ADF), crude protein (CP) and ether extract (EE) were significantly (p < 0.05) influenced by maize variety and storage duration. With an extension of storage duration from 0 to 10 months, the DE and ME of maize and the ATTD of OM, GE, ADF, CP and EE changed in a quadratic manner (p < 0.05), and 3 months of storage exceeded 0 months of storage by 1.84%, 1.43%, 0.31%, 0.32%, 15.37%, 2.11% and 5.02%, respectively. The DE, ME of maize and the ATTD of OM, GE, ADF, CP and EE decreased by 3.67%, 6.00%, 0.97%, 1.40%, 30.54%, 3.92% and 20.93%, respectively, at 10 months of storage compared to 3 months of storage. No interaction was observed between maize variety and storage duration in DE and ME contents in maize. In conclusion, under the conditions of this study, most of the nutrient digestibility and the DE and ME contents of maize increased from 0 to 3 months and decreased from 3 to 10 months.