Manipulation of Giant Multipole Resonances via Vortex γ Photons.

Traditional photonuclear reactions primarily excite giant dipole resonances, making the measurement of isovector giant resonances with higher multipolarities a great challenge. In this Letter, the manipulation of collective excitations of different multipole transitions in even-even nuclei via vortex γ photons is investigated. We develop the calculation method for photonuclear cross sections induced by the vortex γ photon beam using the fully self-consistent random-phase approximation plus particle-vibration coupling (RPA+PVC) model based on Skyrme density functional. We find that the electromagnetic transitions with multipolarity J<|m_{γ}| are forbidden for vortex γ photons due to the angular momentum conservation, with m_{γ} being the projection of total angular momentum of γ photon on its propagation direction. For instance, this allows for probing the isovector giant quadrupole resonance without interference from dipole transitions using vortex γ photons with m_{γ}=2. Furthermore, the electromagnetic transition with J=|m_{γ}|+1 vanishes at a specific polar angle. Therefore, the giant resonances with specific multipolarity can be extracted via vortex γ photons. Moreover, the vortex properties of γ photons can be meticulously diagnosed by measuring the nuclear photon-absorption cross section. Our method opens new avenues for photonuclear excitations, generation of coherent γ photon laser and precise detection of vortex particles, and consequently, has significant impact on nuclear physics, nuclear astrophysics and strong laser physics.

Anti-diabetic drug canagliflozin hinders skeletal muscle regeneration in mice.

Canagliflozin is an antidiabetic medicine that inhibits sodium-glucose cotransporter 2 (SGLT2) in proximal tubules. Recently, it was reported to have several noncanonical effects other than SGLT2 inhibiting. However, the effects of canagliflozin on skeletal muscle regeneration remain largely unexplored. Thus, in vivo muscle contractile properties recovery in mice ischemic lower limbs following gliflozins treatment was evaluated. The C2C12 myoblast differentiation after gliflozins treatment was also assessed in vitro. As a result, both in vivo and in vitro data indicate that canagliflozin impairs intrinsic myogenic regeneration, thus hindering ischemic limb muscle contractile properties, fatigue resistance recovery, and tissue regeneration. Mitochondrial structure and activity are both disrupted by canagliflozin in myoblasts. Single-cell RNA sequencing of ischemic tibialis anterior reveals a decrease in leucyl-tRNA synthetase 2 (LARS2) in muscle stem cells attributable to canagliflozin. Further investigation explicates the noncanonical function of LARS2, which plays pivotal roles in regulating myoblast differentiation and muscle regeneration by affecting mitochondrial structure and activity. Enhanced expression of LARS2 restores the differentiation of canagliflozin-treated myoblasts, and accelerates ischemic skeletal muscle regeneration in canagliflozin-treated mice. Our data suggest that canagliflozin directly impairs ischemic skeletal muscle recovery in mice by downregulating LARS2 expression in muscle stem cells, and that LARS2 may be a promising therapeutic target for injured skeletal muscle regeneration.

Alternations of cesarean section rates in a non-infected population after the outbreak of COVID-19: a cross-sectional study.

The pandemic of Coronavirus Disease 2019(COVID-19) could be sources of anxiety among pregnant women and health care workers, which might affect the decision making on the mode of delivery. The aim of this study was to explore whether the cesarean section rates had significantly increased after the outbreak of COVID-19. We analyzed the labor data with cesarean rates in a tertiary maternity center during COVID-19 epidemic months from January to March in 2020, compared with pre-epidemic parallel months in 2019 by using Z-score test for proportions. Even though none of the staff or patient suffered with COVID-19 in the hospital, we found the cesarean section rates slightly increased in a non-infected population after the outbreak of COVID-19. Obstetricians should beware of the possible effects of COVID-19 on the mode of delivery.

Is tubal endometriosis an asymmetric disease? A 17-year retrospective study.

PURPOSE: To investigate whether there are left-right asymmetries in tubal endometriosis and the factors affecting this predisposition. METHODS: Women who underwent salpingectomy for gynecological diseases and were diagnosed with tubal endometriosis between January 2002 and July 2019 were included in the study. The frequencies of left and right tubal endometriosis were compared with the expected 50% using a binominal test. The demographic characteristics and presence of ovarian endometrioid cysts, adenomyosis, and hydrosalpinx were also analyzed. RESULTS: During the study period of more than 17 years, 305 women were diagnosed with tubal endometriosis. The distribution of tubal endometriosis in the left or right fallopian tubes was analyzed. Tubal endometriosis was found in the left fallopian tube in 168 (55.08%) women, in the right fallopian tube in 93 (30.49%), and bilaterally in 44 (14.43%). Left unilateral tubal endometriosis was found most frequently (64.37%, 168/261), and its incidence was significantly higher than 50% (P < 0.001, binominal test). Furthermore, the frequency of left ovarian endometrioid cysts (58.82%) was higher than that of right ovarian endometrioid cysts (41.18%) (P < 0.001, binominal test). CONCLUSION: Our study confirms that tubal endometriosis is a left-side asymmetric disease, and this predisposition is highly consistent with ovarian endometrioid cysts, which supports the transplantation theory of the origin of endometriosis.

LncRNA SNHG16 Functions as an Oncogene by Sponging MiR-4518 and Up-Regulating PRMT5 Expression in Glioma.

BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) have recently emerged as novel and potentially promising therapeutic targets in various cancers. However, the expression pattern and biological function of lncRNAs in glioma remain largely elusive. In the present study, we investigated the functional role of an lncRNA, small nucleolar RNA host gene 16 (SNHG16), in glioma. METHODS: The expression levels of SNHG16 and miR-4518 were measured using qRT-PCR. The relationship between the levels of SNHG16 and clinicopathologic features were statically analyzed. The levels of proteins were detected using western blot. Bioinformatics analysis and luciferase reporter assays were applied to the analysis of the relationship between SNHG16, miR-4518 and PRMT5. Cell viability and apoptosis were measured using MTT and apoptosis ELISA assay, respectively. RESULTS: SNHG16 was highly expressed in glioma tissues and cell lines, which was related to poorer clinicopathologic features and shorter survival time. Knockdown of SNHG16 inhibits the viability and induces apoptosis of glioma cells. Further investigation revealed that SNHG16 could up-regulate the expression of miR-4518 targeted gene PRMT5 via acting as an endogenous sponge of miR-4518. Moreover, SNHG16 also affects the expression of Bcl-2 family proteins and the activation of PI3K/Akt signaling pathway. CONCLUSION: Our study revealed a novel SNHG16-miR-4518-PRMT5 pathway regulatory axis in glioma pathogenesis. SNHG16 could be used as a potential therapeutic target in the treatment of glioma.

Adipocyte-derived IL-6 and leptin promote breast Cancer metastasis via upregulation of Lysyl Hydroxylase-2 expression.

BACKGROUND: Adipocytes make up the major component of breast tissue, accounting for 90% of stromal tissue. Thus, the crosstalk between adipocytes and breast cancer cells may play a critical role in cancer progression. Adipocyte-breast cancer interactions have been considered important for the promotion of breast cancer metastasis. However, the specific mechanisms underlying these interactions are unclear. In this study, we investigated the mechanisms of adipocyte-mediated breast cancer metastasis. METHODS: Breast cancer cells were cocultured with mature adipocytes for migration and 3D matrix invasion assays. Next, lentivirus-mediated loss-of-function experiments were used to explore the function of lysyl hydroxylase (PLOD2) in breast cancer migration and adipocyte-dependent migration of breast cancer cells. The role of PLOD2 in breast cancer metastasis was further confirmed using orthotopic mammary fat pad xenografts in vivo. Clinical samples were used to confirm that PLOD2 expression is increased in tumor tissue and is associated with poor prognosis of breast cancer patients. Cells were treated with cytokines and pharmacological inhibitors in order to verify which adipokines were responsible for activation of PLOD2 expression and which signaling pathways were activated in vitro. RESULTS: Gene expression profiling and Western blotting analyses revealed that PLOD2 was upregulated in breast cancer cells following coculture with adipocytes; this process was accompanied by enhanced breast cancer cell migration and invasion. Loss-of-function studies indicated that PLOD2 knockdown suppressed cell migration and disrupted the formation of actin stress fibers in breast cancer cells and abrogated the migration induced by following coculture with adipocytes. Moreover, experiments performed in orthotopic mammary fat pad xenografts showed that PLOD2 knockdown could reduce metastasis to the lung and liver. Further, high PLOD2 expression correlated with poor prognosis of breast cancer patients. Mechanistically, adipocyte-derived interleukin-6 (IL-6) and leptin may facilitate PLOD2 upregulation in breast cancer cells and promote breast cancer metastasis in tail vein metastasis assays. Further investigation revealed that adipocyte-derived IL-6 and leptin promoted PLOD2 expression through activation of the JAK/STAT3 and PI3K/AKT signaling pathways. CONCLUSIONS: Our study reveals that adipocyte-derived IL-6 and leptin promote PLOD2 expression by activating the JAK/STAT3 and PI3K/AKT signaling pathways, thus promoting breast cancer metastasis.

Knockdown of DNMT1 and DNMT3a Promotes the Angiogenesis of Human Mesenchymal Stem Cells Leading to Arterial Specific Differentiation.

Human mesenchymal stem cells (hMSCs) possess the potential to differentiate into endothelial cells (EC). DNA methylation plays an important role in cell differentiation during development. However, the role of the DNA methyltransferases Dnmt1 and Dnmt3a in specific arterial differentiation of hMSCs is not clear. Here, we show that the CpG islands in the promoter regions of the EC specification and arterial marker genes were highly methylated in hMSCs based on bisulfite genomic sequencing. Treatment with the DNMT inhibitor 5-aza-dc induced the reactivation of EC specification and arterial marker genes by promoting demethylation of these genes as well as stimulating tube-like structure formation. The hMSCs with stable knockdown of Dnmt1/Dnmt3a were highly angiogenic and expressed several arterial specific transcription factors and marker genes. A Matrigel plug assay confirmed that Dnmt1/Dnmt3a stable knockdown hMSCs enhanced blood vessel formation compared with WT MSCs. We also identified that the transcription factor E2F1 could upregulate the transcription of arterial marker genes by binding to the promoters of arterial genes, suggesting its critical role for arterial specification. Moreover, miRNA gain/loss-of-function analyses revealed that miR152 and miR30a were involved in endothelial differentiation of hMSCs by targeting Dnmt1 and Dnmt3a, respectively. Taken together, these data suggest that Dnmt1 and Dnmt3a are critical regulators for epigenetic silencing of EC marker genes and that E2F1 plays an important role in promoting arterial cell determination. Stem Cells 2016;34:1273-1283.

Enantioselective syntheses of sulfoxides in octahedral ruthenium(II) complexes via a chiral-at-metal strategy.

The preparation of chiral 2-(alkylsulfinyl)phenol compounds by enantioselective coordination-oxidation of the thioether ruthenium complexes with a chiral-at-metal strategy has been developed. The enantiomerically pure sulfoxide complexes Δ-[Ru(bpy)2{(R)-LO-R}](PF6) (bpy is 2,2'-bipyridine, HLO-R is 2-(alkylsulfinyl)phenol, R = Me (Δ-1a), Et (Δ-2a), iPr (Δ-3a), Bn (Δ-4a), and Nap (Δ-5a)) and Λ-[Ru(bpy)2{(S)-LO-R}](PF6) (R = Me (Λ-1a), Et (Λ-2a), iPr (Λ-3a), Bn (Λ-4a), and Nap (Λ-5a)) have been synthesized by the reaction of Δ-[Ru(bpy)2(py)2](2+) or Λ-[Ru(bpy)2(py)2](2+) with the prochiral thioether ligands 2-(alkylthio)phenol (HL-R), followed by enantioselective oxidation with m-CPBA as oxidant. The X-ray crystallography was used to verify the stereochemistry of ruthenium complexes and sulfur atoms. The configurations of the ruthenium complexes are stable during the coordination and oxidation reactions. Moreover, the chiral sulfoxide ligands are enantioselectively generated by controlling of the configuration of ruthenium centers in the course of oxidation reaction. That is, the Λ configuration at the ruthenium center generates the S sulfoxide ligand; on the contrary, the Δ configuration of the ruthenium complex originates the R sulfoxide ligand. Acidolysis of Λ-[Ru(bpy)2{(R)-LO-R}](PF6) and Δ-[Ru(bpy)2{(S)-LO-R}](PF6) complexes in the presence of TFA-MeCN afforded the chiral ligands (R)-HLO-R and (S)-HLO-R in 96-99% ee values, respectively. Importantly, the chiral ruthenium complexes can be recycled as Δ/Λ-[Ru(bpy)2(MeCN)2](PF6)2 and reused in a next reaction cycle with complete retention of the configurations at ruthenium centers.

Visible-light-induced photooxidation of ruthenium(II) complex with 2,2'-biimidazole-like ligand by singlet oxygen.

Four new ruthenium(II) complexes [Ru(bpy)2(TMBiimH2)](ClO4)2 (Ru-5; bpy is 2,2'-bipyridine and TMBiimH2 is 4,5,4',5'-tetramethyl-2,2'-biimidazole), [Ru(bpy)2(L1H2)](ClO4)2·H2O (Ru-6; L1H2 is 4,5-dimethyl-2-(N,N-diacetyl)carboximidamide-1H-imidazole), [Ru(bpy)2(L2H2)](ClO4)2 (Ru-7; L2H2 is N(1),N(1),N(2),N(2)-tetrakis(acetyl)ethanediimidamide), and [Ru(phen)2(TMBiimH2)](ClO4)2 (Ru-8; phen is 1,10'-phenanthroline) have been synthesized and characterized. Their photophysical and electrochemical properties have been studied and compared to the previously reported [Ru(bpy)2(BiimH2)](PF6)2 (Ru-1), [Ru(bpy)2(BbimH2)](PF6)2 (Ru-2), [Ru(bpy)2(DMBbimH2)](PF6)2 (Ru-3), and [Ru(bpy)2(TMBbimH2)](PF6)2 (Ru-4). Under irradiation with either sunlight or household light in atmosphere, Ru-5 reacts with molecular oxygen to produce Ru-6 in an acetonitrile solution with a relatively high concentration and Ru-7 in a methanol or dilute acetonitrile solution, respectively. The mechanism studies show that singlet oxygen is the reactive oxygen species in the ring-opening reaction and the photooxidation reaction is solvent- and concentration-dependent. The photoreaction product Ru-6 is an intermediate, which has been isolated and structurally characterized by single-crystal X-ray diffraction. Ru-6 is stable in the solid state and an acetonitrile solution with a high concentration, but can be further oxidized to Ru-7 in a methanol or dilute acetonitrile solution.

A Novel ASCT2 Inhibitor, C118P, Blocks Glutamine Transport and Exhibits Antitumour Efficacy in Breast Cancer.

BACKGROUND: The microtubule protein inhibitor C118P shows excellent anti-breast cancer effects. However, the potential targets and mechanisms of C118P in breast cancer remain unknown. METHODS: Real-time cellular analysis (RTCA) was used to detect cell viability. Apoptosis and the cell cycle were detected by flow cytometry. Computer docking simulations, surface plasmon resonance (SPR) technology, and microscale thermophoresis (MST) were conducted to study the interaction between C118P and alanine-serine-cysteine transporter 2 (ASCT2). Seahorse XF technology was used to measure the basal oxygen consumption rate (OCR). The effect of C118P in the adipose microenvironment was explored using a co-culture model of adipocytes and breast cancer cells and mouse cytokine chip. RESULTS: C118P inhibited proliferation, potentiated apoptosis, and induced G2/M cell cycle arrest in breast cancer cells. Notably, ASCT2 was validated as a C118P target through reverse docking, SPR, and MST. C118P suppressed glutamine metabolism and mediated autophagy via ASCT2. Similar results were obtained in the adipocyte-breast cancer microenvironment. Adipose-derived interleukin-6 (IL-6) promoted the proliferation of breast cancer cells by enhancing glutamine metabolism via ASCT2. C118P inhibited the upregulation of ASCT2 by inhibiting the effect of IL-6 in co-cultures. CONCLUSION: C118P exerts an antitumour effect against breast cancer via the glutamine transporter ASCT2.

Genetic inactivation of the adenosine A(2A) receptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis.

Studies with multiple sclerosis patients and animal models of experimental autoimmune encephalomyelitis (EAE) implicate adenosine and adenosine receptors in modulation of neuroinflammation and brain injury. Although the involvement of the A(1) receptor has been recently demonstrated, the role of the adenosine A(2A) receptor (A(2A)R) in development of EAE pathology is largely unknown. Using mice with genetic inactivation of the A(2A) receptor, we provide direct evidence that loss of the A(2A)R exacerbates EAE pathology in mice. Compared with wild-type mice, A(2A)R knockout mice injected with myelin oligodendroglia glycoprotein peptide had a higher incidence of EAE and exhibited higher neurological deficit scores and greater decrease in body weight. A(2A)R knockout mice displayed increased inflammatory cell infiltration and enhanced microglial cell activation in cortex, brainstem, and spinal cord. In addition, demyelination and axonal damage in brainstem were exacerbated, levels of Th1 cytokines increased, and Th2 cytokines decreased. Collectively, these findings suggest that extracellular adenosine acting at A(2A)Rs triggers an important neuroprotective mechanism. Thus, the A(2A) receptor is a potential target for therapeutic approaches to multiple sclerosis.

Highly flexible and superhydrophobic MOF nanosheet membrane for ultrafast alcohol-water separation.

High-performance pervaporation membranes have potential in industrial separation applications, but overcoming the permeability-selectivity trade-off is a challenge. We report a strategy to create highly flexible metal-organic framework nanosheet (MOF-NS) membranes with a faveolate structure on polymer substrates for alcohol-water separation. The controlled growth followed by a surface-coating method effectively produced flexible and defect-free superhydrophobic MOF-NS membranes. The reversible deformation of the flexible MOF-NS and the vertical interlamellar pathways were captured with electron microscopy. Molecular simulations confirmed the structure and revealed transport mechanism. The ultrafast transport channels in MOF-NS exhibited an ultrahigh flux and a separation factor of 8.9 in the pervaporation of 5 weight % ethanol-water at 40°C, which can be used for biofuel recovery. MOF-NS and polydimethylsiloxane synergistically contribute to the separation performance.

Do Health Expenditures Converge Among ASEAN Countries?

This paper aims to determine the existence of convergence in health expenditures among Association for South East Asian Nations (ASEAN) countries. Based on the SPSM procedure and panel KSS unit root test results, the public health expenditures (PUHE) in Indonesia, Lao PDR, Cambodia, the Philippines, and Myanmar are converging, while that of Brunei Darussalam, Malaysia, Vietnam, Singapore, and Thailand are diverging. In addition, the sequences of private health expenditures (PRHE) in ASEAN member states are stationary, which implies convergence. This finding is in accordance with Wagner's law, that is, as nations develop, they are forced to expand public expenditure. Specifically, countries with low levels of PUHE tend to catch up with the high health spending countries. This research has policy implications with regard to the convergence of health expenditure across countries. The government in low- and lower-middle income countries should raise PUHE to provide access to health services for those who are unaffordable individuals.

Association of high maternal triglyceride levels early and late in pregnancy with adverse outcomes: A retrospective cohort study.

BACKGROUND: Excess maternal triglyceride (mTG) exposure during early or late pregnancy increases risks of adverse pregnancy outcomes. However, it is inconclusive whether persistently high maternal triglyceride during whole pregnancy has more negative associations. OBJECTIVE: To explore whether persistently high maternal triglyceride (mTG) levels from early to late pregnancy further increases the risk of adverse pregnancy outcomes. METHODS: We included 12,715 women who had a singleton birth and who underwent routine serum lipid screenings in both early (9-13 weeks) and late (28-42 weeks) pregnancy during May 2018 to July 2019 in a university-based maternity center. Risks for gestational diabetes mellitus (GDM), preeclampsia, preterm delivery, small/large for gestational age (LGA) were estimated. RESULTS: Elevated mTG levels during early pregnancy were associated with increased risks of preterm delivery (AOR, 1.52; 95% CI, 1.21 to 1.90), preeclampsia (1.75; 1.29 to 2.36), gestational diabetes mellitus (1.95; 1.69 to 2.25), and LGA (1.28; 1.12 to 1.46). Compared with those with low mTG levels both in the 1st and 3rd trimesters, persistently high mTG levels increased the risks of preeclampsia (2.53; 1.66 to 3.84), GDM (1.97; 1.57 to 2.47), and LGA (1.68; 1.37 to 2.07). However, persistently high mTG levels only slightly increased risk of LGA when compared with high mTG levels during the 1st trimester alone (1.34, 1.01 to 1.77). CONCLUSIONS: Elevated mTG levels during early pregnancy not in late pregnancy could be the crucial risk factor associated with adverse pregnancy outcomes. These results suggest the importance of lipid screenings and preventions during early pregnancy, which may help to improve pregnancy outcomes.

2-(3,5-Dibromo-4-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthrolinoruthenium(II) complexes: synthesis, characterization, cytotoxicity, apoptosis, DNA-binding and antioxidant activity.

A new ligand DBHIP and its two ruthenium(II) complexes [Ru(dmb)(2)(DBHIP)](ClO(4))(2) (1) and [Ru(dmp)(2)(DBHIP)](ClO(4))(2) (2) have been synthesized and characterized. The cytotoxicity of DBHIP and complexes 1 and 2 has been assessed by MTT assay. The apoptosis studies were carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were studied by absorption titration, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants of complexes 1 and 2 were determined to be 8.64 +/- 0.16 x 10(4) (s = 1.34) and 2.79 +/- 0.21 x 10(4) (s = 2.17) M(-1). The results suggest that these complexes interact with DNA through intercalative mode. The studies on the mechanism of photocleavage demonstrate that superoxide anion radical (O(2)(*-)) and singlet oxygen ((1)O(2)) may play an important role in the DNA cleavage. The experiments on antioxidant activity show that these compounds also exhibit good antioxidant activity against hydroxyl radical (OH*).

Bis(2,9-dimethyl-1,10-phenanthroline-κN,N')(10,11,12,13-tetra-hydro-dipyrido[3,2-a:2',3'-c]phenazine-κN,N)ruthenium(II) bis-(perchlorate) dihydrate.

The title compound, [Ru(C(14)H(12)N(2))(2)(C(18)H(14)N(4))](ClO(4))(2)·2H(2)O, consists of an Ru(II) complex cation, two perchlorate anions and two uncoordinated water mol-ecules. The Ru(II) ion is chelated by a 10,11,12,13-tetra-hydro-dipyrido[3,2-a:2',3'-c]phenazine ligand and two 2,9-dimethyl-1,10-phenanthroline ligands in a distorted octa-hedral geometry. The two uncoord-inated water mol-ecules are disordered over five positions, with an occupancy factor of about 0.4 for each site. A supra-molecular structure is formed by weak π-π inter-actions between neighbouring mol-ecules, with centroid-centroid distances of 3.618 (2) and 3.749 (2) Å.

The novel testicular enrichment protein Cfap58 is required for Notch-associated ciliogenesis.

Cilia and flagella are critical organelles with conserved internal structures and diverse developmental and physiological processes according to cell type. Although the core components of structures are shared with thousands of associated proteins involved in cilia or flagella formation, we hypothesized that some unknown proteins, such as outer dense fiber 2 (Odf2/Cenexin) perform distinct functions in these organelles. In the present study, we identified several uncharacterized proteins through mass spectrometry interactome analysis of Odf2/Cenexin proteins. We further examined the expression patterns and functions of a protein named cilia and flagella associated protein 58 (Cfap58) in cultured astrocytes and sperm flagella. The results of a combination of biochemical analyses and drug administration studies reveal that Cfap58 is a testis-enrichment protein that exhibits similar localization to Odf2/Cenexin proteins and is required for the elongation of the primary cilium and sperm midpiece via modulation of the Notch signaling pathway. However, the cell cycle-related functions and localization of Odf2/Cenexin in the mother centriole were not altered in Cfap58 knockdown cells. These findings indicate that Cfap58 may be partially recruited by Odf2/Cenexin proteins and is indispensable for the cilia and flagellar assembly. These data provide us with a better understanding of ciliogenesis and flagellar elongation and may aid in identifying new targets for diseases caused by Notch-mediated ciliopathies and flagellar abnormalities.

Autism-like behaviors and abnormality of glucose metabolism in offspring derived from aging males with epigenetically modified sperm.

Accumulating evidence from epidemiological studies of humans and genetic models in rodents has shown that offspring from males of advanced paternal age (APA) are susceptible to metabolic and neurological disorders. However, knowledge of molecular mechanism(s) underlying these metabolic and behavioral changes at the intergeneration and trans-generation levels from APA is limited. Here, we characterized changes on glucose and cholesterol metabolism, and also autism spectrum disorders (ASD)-like behaviors in 1st and 2nd generations from 12- and 18-month-old male mice, respectively. Whole Genome Bisulfite Sequencing (WGBS) of sperm from APA mice identified differentially methylated regions (DMRs) within the whole genome, and DMRs within promoter regions, suggesting that specific genes and relevant pathways might be associated with autism and aberrant glucose metabolism in the offspring from APA males. These results strongly suggest that epigenetic reprogramming induced by aging in male sperm may lead to high risks of aberrant glucose metabolism and the development of ASD behaviors in intergenerational and transgenerational offspring.

Integrin α2ß1 is involved in T-2 toxin-induced decrease of type II collagen in C28/I2 chondrocytes.

The T-2 toxin exerts a variety of toxic effects on both experimental animals and humans. The integrin family plays a major role in mediating cell-ECM interactions. Therefore, the present study aimed to investigate the involvement of integrin α2ß1 in T-2 toxin-induced C28/I2 chondrocyte damage. The pathological damage of articular cartilage injury induced by T-2 toxin was observed by H&E staining. The expression levels of collagen 2 and MMP-13 (Matrix metalloproteinases 13) were detected using immunohistochemistry in articular cartilage tissues and western blotting in the cells. The blocking effect of integrin α2ß1 inhibitor on T-2 toxin-induced chondrocyte matrix degradation was examined by western blotting. Further, the effect of integrin α2ß1 inhibitor on T-2 toxin-induced chondrocyte apoptosis was analyzed. About 100 ng/g body weight (BW)/day T-2 toxin was fed to Sprague-Dawley (SD) rats, T-2 toxin treatment (0, 6, 12, and 24 ng/mL) induced C28/I2 chondrocytes. Both in vivo and in vitro, chondrocyte survival was inhibited, and the production of type II collagen was significantly reduced (p < 0.05). However, the level of MMP-13 was up-regulated (p < 0.05). Matrix degradation was effectively blocked after the pre-treatment by integrin α2ß1 inhibitor (p < 0.05). Conclusively, Integrin α2ß1 is a critical signaling pathway for communication between cells and the extracellular matrix, the present study provides a new clue to elucidate the mechanism of T-2 toxin-induced chondrocyte damage.