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Myocardial damage is the most serious pathological consequence of cardiovascular diseases and an important reason for their high mortality. In recent years, because of the high prevalence of systemic energy metabolism disorders (e.g., obesity, diabetes mellitus, and metabolic syndrome), complications of myocardial damage caused by these disorders have attracted widespread attention. Energy metabolism disorders are independent of traditional injury-related risk factors, such as ischemia, hypoxia, trauma, and infection. An imbalance of myocardial metabolic flexibility and myocardial energy depletion are usually the initial changes of myocardial injury caused by energy metabolism disorders, and abnormal morphology and functional destruction of the mitochondria are their important features. Specifically, mitochondria are the centers of energy metabolism, and recent evidence has shown that decreased mitochondrial function, caused by an imbalance in mitochondrial quality control, may play a key role in myocardial injury caused by energy metabolism disorders. Under chronic energy stress, mitochondria undergo pathological fission, while mitophagy, mitochondrial fusion, and biogenesis are inhibited, and mitochondrial protein balance and transfer are disturbed, resulting in the accumulation of nonfunctional and damaged mitochondria. Consequently, damaged mitochondria lead to myocardial energy depletion and the accumulation of large amounts of reactive oxygen species, further aggravating the imbalance in mitochondrial quality control and forming a vicious cycle. In addition, impaired mitochondria coordinate calcium homeostasis imbalance, and epigenetic alterations participate in the pathogenesis of myocardial damage. These pathological changes induce rapid progression of myocardial damage, eventually leading to heart failure or sudden cardiac death. To intervene more specifically in the myocardial damage caused by metabolic disorders, we need to understand the specific role of mitochondria in this context in detail. Accordingly, promising therapeutic strategies have been proposed. We also summarize the existing therapeutic strategies to provide a reference for clinical treatment and developing new therapies. [Display omitted] Myocardial damage caused by energy metabolism disorders has become a serious threat to human health. Abnormal mitochondrial behaviors play a key role in myocardial damage caused by energy metabolism disorders. Mitochondrial transfer can rescue myocardial injury and has strong therapeutic potential. Disruption of redox homeostasis affects mitochondrial behaviors and exacerbates myocardial injury. Sirtuins and coupling between mitochondrial behaviors are interesting research directions. [ABSTRACT FROM AUTHOR]

Introduction: Benzodiazepine anxiolytics are believed to cause urination disorders due to their anticholinergic effects. Objective: This study was carried out to investigate the potential inhibitory effects of 15 clinically available anxiolytics in Japan on acetylcholine (ACh)-induced contractions in rat detrusor smooth muscle (DSM) to predict whether these anxiolytics could induce urination disorders. Methods: -Effects of anxiolytics on contractions induced by ACh and 80 mmol/L KCl solution in rat DSM and effects of anxiolytics on specific binding of [N-methyl-3H]scopolamine ([3H]NMS) in mouse cerebral cortex were investigated. Results and Conclusions: ACh-induced contractions in rat DSM were inhibited by clotiazepam and diazepam (benzodiazepine anxiolytics) at concentrations that were clinically relevant. These contractions were also significantly inhibited by paroxetine, escitalopram (selective serotonin reuptake inhibitors -[SSRIs]), and hydroxyzine (a histamine H1 receptor antagonist), albeit at concentrations that substantially exceeded clinically achievable blood levels. At a concentration of 10–5 mol/L, paroxetine, escitalopram, and hydroxyzine inhibited 80 mmol/L high-KCl solution-induced rat DSM contractions but not clotiazepam and diazepam. Paroxetine, escitalopram, and hydroxyzine also inhibited specific binding of [3H]NMS in mouse cerebral cortex but clotiazepam and diazepam did not. In contrast to the effects of the abovementioned anxiolytics, ACh-induced contractions were not significantly affected by tofisopam, alprazolam, lorazepam, bromazepam, oxazolam, chlordiazepoxide, clonazepam, ethyl loflazepate (benzodiazepine anxiolytics), fluvoxamine (an SSRI), or tandospirone (a serotonin 5-HT1A receptor agonist). These findings suggest that most clinically used anxiolytics are not likely to result in anticholinergic-induced urination disorders within their clinically achievable blood concentration ranges. However, clotiazepam and diazepam may induce urination disorders within their clinical dose ranges via nonanticholinergic inhibition of DSM contractility. [ABSTRACT FROM AUTHOR]

Wilms tumor is one of the most common pediatric solid tumors. The pair-like homeobox 2b (PHOX2B) gene is an important transcription factor that regulates cellular proliferation and differentiation in early life. The association between PHOX2B single nucleotide polymorphisms (SNPs) and Wilms tumor risk has not been investigated. Therefore, we conducted a case-control study involving 145 Wilms tumor patients and 531 controls to explore the association between the PHOX2B rs28647582 T>C polymorphism and Wilms tumor susceptibility. The association between the PHOX2B rs28647582 T>C polymorphism and Wilms tumor susceptibility was assessed by odds ratios (ORs) and 95% confidence intervals (CIs). Our results indicated that PHOX2B rs28647582 T>C polymorphism did not significantly alter Wilms tumor susceptibility. However, in the stratified analysis, we found that TC/CC genotypes significantly increased Wilms tumor risk among children older than 18 months (adjusted OR = 1.77, 95% CI = 1.07-2.95, P=0.027) and those with clinical stages III+IV (adjusted OR = 1.75, 95% CI = 1.09-2.82, P=0.022), when compared with those with TT genotype. Our study suggested that PHOX2B rs28647582 T>C was weakly associated with Wilms tumor susceptibility. Our conclusions need further validation with a larger sample size. [ABSTRACT FROM AUTHOR]

The role of mixed states in the collision-induced thermalization, intersystem crossing, and reactive loss of CH2 (ã 1A1) has been monitored using Doppler-resolved transient frequency modulation absorption spectroscopy. Singlet CH2 is produced in a hot initial distribution of translation and rotational energy states in the 308 nm photodissociation of ketene in a large excess of argon. Collisions with Ar and ketene cool the translational and rotational degrees of freedom, while depleting the total singlet CH2 population through reaction and intersystem crossing. Direct monitoring of the time-dependent populations of rotational levels containing mixed singlet and triplet character reveals a rapid interconversion between the two components, but no discernable difference between the kinetics of the pure singlet and mixed states at longer times. [ABSTRACT FROM AUTHOR]

Reports on the measurements of state-to-state integral cross sections for rotational excitation of carbon monoxide by collisions with Ne. Measurements performed in crossed molecular beams with resonance enhanced multiphoton detection; Scattering calculations; Density to flux corrections; Comparison of experiment and predictions.

Studies the relative integral cross sections for rotational excitation of carbon dioxide in collisions with helium. Sensitivity of the cross sections to anisotropy in the repulsive wall of the helium-carbon dioxide interaction; Interference structure of the observed cross sections; fractional population of measurements of the precollision carbon dioxide rotational distribution.

Lignocellulosic biomass pretreatment with deep eutectic solvents (DESs) is a promising and challenging process for production of biofuels and valuable platform chemicals. In this work, rice straw was mainly fractionated into carbohydrate-rich materials (CRMs) and lignin-rich materials (LRMs) by 90% lactic acid/choline chloride (LC)-water solution with different molar ratio of hydrogen bond donor (HBD, lactic acid) and hydrogen bond acceptor (HBA, choline chloride). It was found that high HBD/HBA molar ratio of DESs was favorable for achieving CRMs and LRMs with high purity, and both HBD and HBA were responsible for effective biomass fractionation possibly due to their synergistic effect on highly efficient breakage of the linkage between hemicellulose and lignin and thus lignin extraction. About 30%–35% of lignin in native rice straw was fractionated as LRMs, and exceeding 70% of xylan were removed and fractionated into the liquid stream as forms of xylose, furfural and humins after pretreatment using aqueous LC (3:1, 5:1) solution. Consequently, polysaccharides enzymatic hydrolysis of the CRMs were significantly enhanced. Moreover, all the DESs could be recovered with high yields of around 90%, and 69% of the LC (3:1) was recovered after 5 cycles reuse at 90 °C. Besides, the recycled DES maintained a good pretreatment ability, and glucose yields of 60–70% were achieved in the enzymatic hydrolysis of CRMs obtained in each cycle. The facile process established in present work is promising for large scale production of fermentable sugars and other chemicals. [ABSTRACT FROM AUTHOR]

Rice straw pretreatment mediated by choline chloride (ChCl) or lactic acid (Lac) sequences deep eutectic solvents (DESs) was investigated in this work. Hydrogen bond acceptors (HBAs) and hydrogen bond donors (HBDs) proved to be both important for DESs pretreatment efficiency. DESs containing lots of hydroxyl or amino groups with a high intermolecular hydrogen-bond (H-bond) strength exhibited weak biomass deconstruction abilities. The presence of strong electron-withdrawing groups in DESs was benefit for xylan removal, thus furnishing higher cellulose digestibility. The relationships between the properties of DESs, xylan removal and cellulose digestibility of pretreated biomass were established. It was found that xylan removal was negatively correlated with the pKa values of HBDs, and the enzymatic cellulose digestibility of the residues was linearly and positively related to xylan removal instead of delignification. These results provide a preliminary reference for rational design of novel DESs for biomass pretreatment. [ABSTRACT FROM AUTHOR]

Nanos2 belongs to the Nanos gene-coding family and is an important RNA-binding protein that has been shown to have essential roles in male germline stem cells development and self-renewal in mouse. However, little is known about Nanos2 in inchoate buffalo spermatogonia. Here, rapid-amplification of cDNA ends (RACE) was used to obtain the full-length buffalo Nanos2 sequence and bioinformatic analysis revealed a highly conserved Nanos2 sequence between buffalo and other mammalian species. Although Nanos2 was expressed in various tissues, the highest mRNA expression levels were found in testes tissue. Moreover, Nanos2 mRNA was abundant in fetal and pre-puberal testes but markedly decreased in the testes of adults. At the protein level, immunohistochemistry in pre-puberal testes revealed a pattern of NANOS2 expression similar to that for the undifferentiated type A spermatogonia marker PGP9.5. Furthermore, NANOS2 expression was low in adult testes and restricted to elongating spermatids. Altogether, our data suggest that Nanos2 is a potential preliminary molecular marker of inchoate buffalo spermatogonia, and may play an important role in buffalo spermatogonial stem cells (SSCs) development and self-renewal, as has been observed in other model animals. [ABSTRACT FROM AUTHOR]

The proteasome is a key regulator of cellular protein homeostasis and is a clinically validated anticancer target. The immunoproteasome, a subtype of proteasome expressed mainly in hematopoietic cells, was initially recognized for its role in antigen presentation during the immune response. Recently, the immunoproteasome has been implicated in several disease conditions including cancer and autoimmune disorders, but many of the factors contributing to these pathological processes remain unknown. In particular, the codon 60 polymorphism of the PSMB9 gene encoding the β1i immunoproteasome catalytic subunit has been investigated in the context of a variety of diseases. Despite this, previous studies have so far reported inconsistent findings regarding the impact of this polymorphism on proteasome activity. Thus, we set out to investigate the impact of the PSMB9 codon 60 polymorphism on the expression and activity of the β1i immunoproteasome subunit in a panel of human cancer cell lines. The β1i-selective fluorogenic substrate Acetyl-Pro-Ala-Leu-7-amino-4-methylcoumarin was used to specifically measure β1i catalytic activity. Our results indicate that the codon 60 Arg/His polymorphism does not significantly alter the expression and activity of β1i among the cell lines tested. Additionally, we also examined the expression of β1i in clinical samples from colon and pancreatic cancer patients. Our immunohistochemical analyses showed that ∼70% of clinical colon cancer samples and ∼53% of pancreatic cancer samples have detectable β1i expression. Taken together, our results indicate that the β1i subunit of the immunoproteasome is frequently expressed in colon and pancreatic cancers but that the codon 60 genetic variants of β1i display similar catalytic activities and are unlikely to contribute to the significant inter-cell-line and inter-individual variabilities in the immunoproteasome activity. [ABSTRACT FROM AUTHOR]

1, 3-Butadiene (BD) is a high-efficiency carcinogen in rodents and was classified as a human carcinogen in 2008 by the International Agency for Research on Cancer. However, its ability to induce genetic damage and the influence of metabolic polymorphisms to such damage in humans are both controversial claims. This study was conducted to investigate the relationships between exposure to BD, the polymorphisms of metabolic genes and the chromosomal damage in 45 pairs of occupationally exposed workers in a BD product workshop and matched control workers in an administrative office and circulatory water workshop in China. Exposure to BD was evaluated by personal sampling and stationary sampling. Different chromosomal damage endpoints in peripheral blood lymphocytes were determined using the cytokinesis-blocked micronucleus (CBMN) cytome assay; polymorphisms of metabolic genes [cytochrome P450 2E1 (CYP2E1), glutathione S-transferases (GST) and microsomal epoxide hydrolase (mEH)] in BD-exposed group were detected by polymerase chain reaction (PCR) or PCR–restriction fragment length polymorphism analysis. The results show that the average BD measurements of the exposed group were significantly higher than those for the control group (a personal sampling and stationary sampling, respectively). The BD-exposed workers exhibited increased frequencies of micronuclei (MNi) (8.00 ± 3.78‰ versus 5.62 ± 2.41‰) and nucleoplasmic bridges (NPBs) (2.58 ± 2.79‰ versus 1.13 ± 1.34‰) and a decreased nuclear division index (2.20 ± 0.14 versus 2.35 ± 0.27) when compared subjects in the control group. Meanwhile, BD-exposed workers carrying CYP2E1 c1c2/c2c2 or mEH intermediate (I)/high (H) group had a significantly higher NPB frequency than those carrying CYP2E1 c1c1 [frequency ratio (FR) = 2.60, 95% confidence interval (CI) 1.72–3.93; P < 0.0001) or the mEH low(S) group (FR = 2.06, 95% CI% 1.17–3.62; P < 0.05), respectively. Our study suggests that MNi and NPB frequency in CBMN cytome assay could be potential genotoxic biomarkers for BD exposure in humans. The polymorphism of CYP2E1 and mEH could also affect the chromosomal instability of BD workers. [ABSTRACT FROM AUTHOR]

Abstract: A defective ratio between DNA damage and repair may result in the occurrence of a malignant phenotype. Previous studies have found that many genetic alterations in DNA repair genes occur frequently in lung cancer. However, the epigenetic mechanisms underlying this tumorigenesis are not clear. Herein, we have used a chemical-induced rat lung carcinogenesis model to study the evolution of methylation alterations of DNA repair genes BRCA1, ERCC1, XRCC1, and MLH1. Methylation-specific PCR and immunohistochemistry were used to analyze gene methylation status and protein expression during the progression of lung carcinogenesis. Promoter hypermethylation of BRCA1 was only detected in three samples of infiltrating carcinoma. CpG island hypermethylation of ERCC1, XRCC1, and MLH1 was found to increase gradually throughout lung carcinogenesis progression. Both the prevalence of at least one methylated gene and the average number of methylated genes were heightened in squamous metaplasia and dysplasia compared with normal tissue and hyperplasia, and was further increased in carcinoma in situ (CIS) and infiltrating carcinoma. Immunohistochemical analysis showed that BRCA1 and MLH1 protein expression decreased progressively during the stages of lung carcinogenesis, whereas ERCC1 and XRCC1 expression were only found in later stages. Although methylation levels were elevated for ERCC1 and XRCC1 during carcinogenesis, an inverse correlation with protein expression was found only for BRCA1 and MLH1. These results suggest that a continuous accumulation of DNA repair gene hypermethylation and the consequent protein alterations might be a vital molecular mechanism during the process of multistep chemical-induced rat lung carcinogenesis. [Copyright &y& Elsevier]

Abstract: The epigenetic mechanisms underlying the tumorigenesis caused by polycyclic aromatic hydrocarbons and nitrosamine compounds such as 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN) are currently unknown. We reported previously that dynamic changes in DNA methylation occurred during MCA/DEN-induced rat lung carcinogenesis. Here, we used the same animal model to further study the evolution of methylation alterations in tumor suppressor genes (TSGs) DAPK1, FHIT, RASSF1A, and SOCS-3. We found that none of these genes were methylated in either normal or hyperplasia tissue. However, as the severity of the cancer progressed through squamous metaplasia and dysplasia to carcinoma in situ (CIS) and infiltrating carcinoma, so methylation became more prevalent. Particularly dramatic increases in the level of methylation, the average number of methylated genes, and the incidence of concurrent methylation in three genes were observed in CIS and infiltrating carcinoma. Similar but less profound changes were seen in squamous metaplasia and dysplasia. Furthermore, methylation status was closely correlated to loss of protein expression for these genes, with protein levels markedly declining along the continuum of carcinogenesis. These results suggest that progressive CpG island hypermethylation leading to inactivation of TSGs might be a vital molecular mechanism in the pathogenesis of MCA/DEN-induced multistep rat lung carcinogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Identification of specific etiological carcinogens is one of the most important issues in environmental-toxicology studies. In this study, cDNA microarrays were used to analyze gene expression and discern chemical-associated profiles induced by a variety of tumor promoting agents in transformed cells. Two-stage transformation model of BALB/c 3T3 cells was established with MNNG as initiator, and 12-O-tetradecanoylphorbol-13-acetate (TPA), okadaic acid (OA), or cadmium chloride (CdCl2) as tumor promoters. Nine morphologically transformed foci were isolated and the anchorage-independent growth of transformed cells was verified. The gene expression alterations in foci were evaluated using cDNA microarray with 1796 mouse genes. Unsupervised hierarchical clustering analysis revealed that the nine foci were classified into three groups in concordance with the promoters used to induce them and characteristic clusters of genes were identified. In these clusters, genes associated with oxidative stress were specially upregulated following distinct promoter exposure. Moreover, common gene expression alterations were also observed in foci, including upregulated genes associated with cell proliferation and downregulated genes associated with extracellular matrix. Our results demonstrate the presence of unique gene expression profiles in transformed cells which reflect the etiological chemicals and indicate the importance of characteristic molecular alterations as potential biomarkers of exposure to tumor promoters. [Copyright &y& Elsevier]

Abstract: One challenge in aging research concerns identifying physiological parameters or biomarkers that can reflect the physical health of an animal and predict its lifespan. In C. elegans, a model organism widely used in aging research, motor deficits develop in old worms. Here we employed machine vision to quantify worm locomotion behavior throughout lifespan. We confirm that aging worms undergo a progressive decline in motor activity, beginning in early life. Importantly, the rate of motor activity decline rather than the absolute motor activity in the early-to-mid life of individual worms in an isogenic population inversely correlates with their lifespan, and thus may serve as a lifespan predictor. Long-lived mutant strains with deficits in insulin/IGF-1 signaling or food intake display a reduction in the rate of motor activity decline, suggesting that this parameter might also be used for across-strain comparison of healthspan. Our work identifies an endogenous physiological parameter for lifespan prediction and healthspan comparison. [Copyright &y& Elsevier]

In the present study, three different substituted-polynitrogen heterocyclic ligands, Hatzpa (Hatzpa = 3-(5-Amino-tetrazol-1-yl)-propionic acid), Hpytzipa (Hpytzipa = 2-(5-Pyridin-3-yl-tetrazol-2-yl)-propionic acid), Hphtz (Hphtz = 4-(4-hydroxyphenyl)-1,2,4-triazole) have been chosen to react with CuCl 2 ·2H 2 O, resulting in the formation of three new compounds [Cu(atzpa) 2 ] (1), [Cu(pytzipa) 2 ] (2) and [Cu 4 (Hphtz) 8 ](ClO 4) 4 ·4H 2 O (3). Complex 1 displays a complex 2D structure; complex 2 shows a 2D layer network; complex 3 shows a tetranuclear Cu(II) structure. These compounds show considerable cytotoxicity towards human cervical cancer cells (HeLa). The MTT assay suggests that compound 2 with lowest half maximum inhibitory concentration (IC 50) is the most cytotoxic, compared with compounds 1 and 3. In addition, the cytotoxicity was also confirmed by DAPI fluorescent staining method. The migration of HeLa cells is inhibited by NPs of the three compounds. The results show that complex 1 – 3 NPs can inhibit cell proliferation and migration in vitro. [Display omitted] • Three new Cu(II) coordination polymers have been prepared, namely [Cu(atzpa) 2 ] (1), [Cu(pytzipa) 2 ] (2) and [Cu 4 (Hphtz) 8 ](ClO 4) 4 ·4H 2 O (3). • Complex 1 displays a complex 2D structure; complex 2 shows a 2D layer network; complex 3 shows a tetranuclear Cu(II) structure. • These compounds show considerable cytotoxicity towards human cervical cancer cells (HeLa). • The complexes 1 – 3 NPs can inhibit cell proliferation and migration in vitro. Three different substituted multi-nitrogen heterocyclic ligands, Hatzpa (Hatzpa = 3-(5-Amino-tetrazol-1-yl)-propionic acid), Hpytzipa (Hpytzipa = 2-(5-Pyridin-3-yl-tetrazol-2-yl)-propionic acid), Hphtz (Hphtz = 4-(4-hydroxyphenyl)-1,2,4-triazole) have been chosen to react with CuCl 2 ·2H 2 O, resulting in the formation of three new complexes [Cu(atzpa) 2 ] (1), [Cu(pytzipa) 2 ] (2) and [Cu 4 (Hphtz) 8 ](ClO 4) 4 ·4H 2 O (3). The coordination sites of the three ligands are mainly affected by the different substituents of the polynitrogen heterocycle. These complexes have been characterized by elemental analysis, IR and single crystal X-ray diffraction. Complex 1 displays a 2D structure; complex 2 shows a 2D layer network; complex 3 shows a tetranuclear Cu(II) structure. These complexes show considerable cytotoxicity towards human cervical cancer cells (HeLa). The MTT assay suggested that, compared with complexes 1 and 2, complex 3 with lowest half maximum inhibitory concentration (IC 50) is the most cytotoxic. In addition, the cytotoxicity was also confirmed by DAPI fluorescent staining method. The migration of HeLa cells is inhibited by NPs of the three complexes. The results showed that the NPs of complexes 1 – 3 can inhibit cell proliferation and migration in vitro. [ABSTRACT FROM AUTHOR]

Abstract: Okadaic acid (OA) is a tumor promoter in two-stage carcinogenesis experiments. Nevertheless, the effects of OA on cell transformation, cell proliferation and apoptosis vary widely, and the molecular events underlying these effects of OA are not well understood. In the present study, we examined the promoting activity and the associated effects on cell growth and apoptosis mediated by OA in BALB/c 3T3 cells, and evaluated alterations of gene transcriptional expression by microarray analysis. The promoting activity of OA was estimated by a two-stage transformation assay, in which cells were treated first with a low dose of the initiator N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) and then with OA for 14 days. It showed that OA, at concentrations of 7.8–31.3ng/ml, enhanced the transformation of MNNG-treated cells. In the promotion phase, cells exposed to OA (7.8ng/ml) grew slowly for the first 2 days and subsequently died. As determined by Hoechst 33342 fluorescent dye and Annexin-V/PI dual-colored flow cytometry, OA induced morphologically apoptotic cells and increased the percentage of early apoptotic cells. The gene expression profile induced by OA at five time points in the promotion phase was determined by use of a specific mouse toxicological microarray containing 1796 clones, and a total of 177 differentially expressed genes were identified. By gene ontology analysis, 31 of these were determined to be functionally involved with cell growth and/or maintenance. In this group, numerous genes associated with the cell proliferation and cell cycle progression were down-regulated at early and/or middle time points. Among these was a subset of genes associated with apoptosis, in which Bnip3, Cycs, Casp3 and Bag1 genes are involved in the mitochondrial pathway of apoptosis. Ier3, Mdm2 and Bnip3 genes may be p53 targets. Furthermore, real-time PCR confirmed the expression changes of five genes selected at random from the differentially expressed genes. We conclude that OA induces cell growth inhibition and apoptosis in the two-stage, MNNG-initiated transformation of BALB/c 3T3 cells. The results of gene expression profile analysis imply that multiple molecular pathways are involved in OA-induced proliferation inhibition and apoptosis. Mitochondrial and p53-associated apoptotic pathways also may contribute to OA-induced apoptosis. [Copyright &y& Elsevier]

Most of our knowledge about the regulation of aging comes from mutants originally isolated for other phenotypes. To ask whether our current view of aging has been affected by selection bias, and to deepen our understanding of known longevity pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones that extend lifespan. We identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Our most important findings are (i) that dietary restriction extends C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii) that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii) that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias. [ABSTRACT FROM AUTHOR]

The Caenorhabditis elegans transcription factor HSF-1, which regulates the heat-shock response, also influences aging. Reducing hsf-1 activity accelerates tissue aging and shortens life-span, and we show that hsf-1 overexpression extends life-span. We find that HSF-1, like the transcription factor DAF-16, is required for daf-2-insulin/IGF-1 receptor mutations to extend life-span. Our findings suggest this is because HSF-1 and DAF-16 together activate expression of specific genes, including genes encoding small heat-shock proteins, which in turn promote longevity. The small heat-shock proteins also delay the onset of polyglutamine-expansion protein aggregation, suggesting that these proteins couple the normal aging process to this type of age-related disease. [ABSTRACT FROM AUTHOR]

To explore the role of mitochondrial activity in the aging process, we have lowered the activity of the electron transport chain and adenosine 5'-triphosphate (ATP) synthase with RNA interference (RNAi) in Caenorhabditis elegans. These perturbations reduced body size and behavioral rates and extended adult life-span. Restoring messenger RNA to near-normal levels during adulthood did not elevate ATP levels and did not correct any of these phenotypes. Conversely, inhibiting respiratory-chain components during adulthood only did not reset behavioral rates and did not affect life-span. Thus, the developing animal appears to contain a regulatory system that monitors mitochondrial activity early in life and, in response, establishes rates of respiration, behavior, and aging that persist during adulthood. [ABSTRACT FROM AUTHOR]

Investigates the findings of a genetic analysis of tissue aging in Caenorhabditis elegans. Implications for heat-shock factor and bacterial proliferation; Use of the Nomarski optics to examine tissues of aging worms; Effect on the germline.

S‐adenosylmethionine (SAM), generated from methionine and ATP by S‐adenosyl methionine synthetase (SAMS), is the universal methyl group donor required for numerous cellular methylation reactions. In Caenorhabditis elegans, silencing sams‐1, the major isoform of SAMS, genetically or via dietary restriction induces a robust mitochondrial unfolded protein response (UPRmt) and lifespan extension. In this study, we found that depleting SAMS‐1 markedly decreases mitochondrial SAM levels. Moreover, RNAi knockdown of SLC‐25A26, a carrier protein responsible for transporting SAM from the cytoplasm into the mitochondria, significantly lowers the mitochondrial SAM levels and activates UPRmt, suggesting that the UPRmt induced by sams‐1 mutations might result from disrupted mitochondrial SAM homeostasis. Through a genetic screen, we then identified a putative mitochondrial tRNA methyltransferase TRMT‐10C.2 as a major downstream effector of SAMS‐1 to regulate UPRmt and longevity. As disruption of mitochondrial tRNA methylation likely leads to impaired mitochondrial tRNA maturation and consequently reduced mitochondrial translation, our findings suggest that depleting mitochondrial SAM level might trigger UPRmt via attenuating protein translation in the mitochondria. Together, this study has revealed a potential mechanism by which SAMS‐1 regulates UPRmt and longevity. [ABSTRACT FROM AUTHOR]

Provides information on a study which investigated the regulatory impact of the exogenous D-3 phosphoinositides on the platelets of the washed rabbit. Stimulation of the phosphatidylinositol; Platelet activation of the phosphoinositide 3-kinase; Methodology used to conduct the study; Results of the study.

Presents a study in which permuted isomers of L-...-phosphatidyl-d-myo-inositol trisphosphate (PtdInsP3) was used to understand the underlying principles governing ligand selection for PtdIns(3,4,5)P3-specific binding proteins. Examination of the PtdInsP3; Comparison of the isomers to the SH2 domain; What the interaction with the PtdIns(3,4,5)P3-binding motif requires.

Presents a study in which biochemical and immunochemical data from present investigations reveal the existence of a phosphoinositide 3-kinase (PI 3-kinase) in rat liver nuclei. What the nuclear soluble fraction contains; Examination of the effect of CapG, a nuclear actin-regulatory protein, on PI 3-kinase activity; Methodology of the study; Results of the study.

Multi-mode quantum memory is a basic element required for long-distance quantum communication, as well as scalable quantum computation. For on-demand readout and long storage times, control pulses are crucial in order to transfer atomic excitations back and forth into spin excitations. Here, we introduce noise-robust composite pulse sequences for high-fidelity excitation transfer in multi-mode quantum memory. These pulses are robust to the deviations in amplitude and the detuning parameters of realistic conditions. We show the efficiency of these composite pulses with a typical rare-earth ion-doped system. This approach could be applied to a variety of quantum memory schemes. [ABSTRACT FROM AUTHOR]

In recent years, poly(lactic acid) (PLA) has attracted more and more attention as one of the most promising biobased and biodegradable polymers. However, the inherent brittleness significantly limits its wide application. Here, ternary blends of PLA, poly(ε-caprolactone) (PCL) with various amounts of ethylene-methyl acrylate-glycidyl methacrylate (EMA-GMA) terpolymer were fabricated through reactive melt blending in order to improve the toughness of PLA. The effect of different addition amounts of EMA-GMA on the mechanical properties, interfacial compatibility and phase morphology of PLA/PCL blends were studied. The reactions between the epoxy groups of EMA-GMA and carboxyl and hydroxyl end groups of PLA and PCL were investigated thorough a Fourier transform infrared (FT-IR). The miscibility and thermal behavior of the blends were studied through a dynamic mechanical analysis (DMA), differential scanning calorimetric (DSC) and X-ray diffraction (XRD). The phase morphology and impact fracture surface of the blends were also investigated through a scanning electron microscope (SEM). With the addition of 8 phr EMA-GMA, a PLA/PCL (90 wt %:10 wt %)/EMA-GMA ternary blend presenting a suitable multiple stacked phase structure with an optimum interfacial adhesion exhibited an elongation at break of 500.94% and a notched impact strength of 64.31 kJ/m2 with a partial break impact behavior. Finally, the toughening mechanism of the supertough PLA based polymers have been established based on the above analysis. [ABSTRACT FROM AUTHOR]

A new structure named reinforced concrete grid moment‐resisting frame (RC‐GMRF) have been adopted in high‐rise buildings in China. However, complex construction due to numerous beam‐column joints restricts the application of this structure. A novel precast reinforced concrete GMRF (PC‐GMRF) is proposed in this paper to solve this problem. Three specimens, including one traditional reinforced concrete moment‐resisting frame (RC‐MRF) as reference, were tested under reverse cyclic loading to evaluate the seismic performance. All three specimens were designed using the same amount of construction material. The experimental results showed that PC‐GMRF exhibited comparable seismic performance with that of RC‐GMRF. The load‐carrying capacity, initial stiffness and energy dissipation capacity were improved by an average of 43%, 29%, and 21%, respectively, compared with those of RC‐MRF. This study indicated that the performance of PC‐GMRF was acceptable and could be used in the moment‐resisting frame as a novel structure. [ABSTRACT FROM AUTHOR]

Reliable information transmission between spatially separated nodes is fundamental to a network architecture for scalable quantum technology. Spin qubit in semiconductor quantum dots is a promising candidate for quantum information processing. However, there remains a challenge to design a practical path from the existing experiments to scalable quantum processor. Here we propose a module consisting of spin singlet-triplet qubits and single microwave photons. We show a high degree of control over interactions between the spin qubit and the quantum light field can be achieved. Furthermore, we propose preparation of a shaped single photons with an efficiency of 98%, and deterministic quantum state transfer and entanglement generation between remote nodes with a high fidelity of 90%. This spin-photon module has met the threshold of particular designed error-correction protocols, thus provides a feasible approach towards scalable quantum network architecture. [ABSTRACT FROM AUTHOR]

Effective obtaining fermentable sugar s and other platform chemicals from rice straw mediated by choline chloride- oxalic acid dihydrate (CO) and the corresponding micro-mechanism investigation were conducted in this work. Choosing a suitable constituents molar ratio of CO appeared to be a feasible method to achieve an appropriate pretreatment severity for a good biomass fractionation. Pretreatment by using CO with high oxalic acid dihydrate to choline chloride molar ratio could afford easily digestible cellulose-rich materials (CMRs, >80% of enzymatic digestion) and lignin-rich materials (LRMs) of high purity (>82%) due to extensive hemicellulose removal (>93%) and delignification (around 70%). Cell wall microstructure characterizations based on confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM) verified the stronger xylan and lignin removal ability of CO with higher oxalic acid dihydrate content. Moreover, the considerable removal of xylan confirmed by CLSM was beneficial to delignification and the subsequent cellulose enzymatic hydrolysis. Furthermore, ultra-structural changes of lignin distribution in cell walls based on TEM indicated the occurrence of partial delignification, preferentially in cell corner (CC) and compound middle lumen (CML) rather than in the secondary cell walls. These findings provides a new insight into the detailed mechanism of acidic DESs mediated biomass deconstruction. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is sperm telomere length (STL) associated with sperm nuclear DNA damage and mitochondrial DNA abnormalities? SUMMARY ANSWER Sperm telomere length is related to sperm nuclear DNA integrity and mitochondrial DNA abnormalities in healthy young college students. WHAT IS KNOWN ALREADY Many studies have revealed the correlations between sperm genetic alterations in both the nucleus and mitochondria and sperm functionality, however, the possible associations between the telomere, an important component of chromosome, and conventional indicators of mitochondrial DNA and nuclear DNA changes have not been investigated. STUDY DESIGN, SIZE, DURATION A prospective cohort study, Male Reproductive Health in Chongqing College Students (MARHCS), was conducted from June 2013 to June 2015. We pooled data collected from the follow-up study in 2014 and a total of 444 participants were included. PARTICIPANTS/MATERIALS, SETTING, METHODS STL was measured by quantitative (Q)-PCR. Sperm nuclear DNA integrity was determined using sperm chromatin structure assay (SCSA) and comet assay. Mitochondrial DNA damage was assessed by mitochondrial DNA copy number (mtDNAcn) evaluated with Q-PCR, and mtDNA integrity was determined with long PCR. MAIN RESULTS AND THE ROLE OF CHANCE The univariable-linear regression analysis revealed that STL was significantly positively correlated with markers of sperm nuclear DNA damage including the DNA fragmentation index (DFI) and comet parameters (the percentage of DNA in the tail, tail length, comet length, and tail moment). Additionally, STL was also significantly positively correlated with mtDNAcn and significantly negatively correlated with mtDNA integrity. After adjustment for potential confounders, these relationships remained appreciable. Moreover, we investigated potential effects of biometric factors, including age, parental age at conception, and BMI on STL and found that STL was increased with paternal age at conception. LIMITATIONS, REASONS FOR CAUTION A mechanistic explanation of the correlation between STL, sperm nuclear DNA integrity, and mtDNA abnormalities cannot be provided with a cross-sectional study design, so well-designed longitudinal studies are still necessary. In addition, a single semen samples were provided and were not all obtained at the same time point, which may increase the intraindividual bias in this study. WIDER IMPLICATIONS OF THE FINDINGS The findings extend the literature including assessment of mitochondrial dysfunction, sperm nuclear DNA damage, and telomere length and provide new insights into the relevance of STL in male reproduction. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China (No. 82073590), the National Natural Science Foundation of China (No. 81903363), the National Natural Science Foundation of China (No. 82130097), and the National Key R&D Program of China (2022YFC2702900). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Moderate invasion of trophoblasts into the endometrium is crucial for successful pregnancy. Benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a carcinogenic metabolite of benzo[a]pyrene which causes various diseases. We investigated the effects of BPDE on migration and invasion of trophoblast HTR-8/SVneo cells. Migration and invasion of cells exposed to 0.25-1.0 μM BPDE for 24 h were significantly inhibited. Moreover, tube formation of human umbilical vein endothelial cell (HUVEC) was also significantly reduced after incubation with HTR-8/SVneo cells treated with 0.5-1.0 μM BPDE. The protein and mRNA levels of FAK, SRC, PI3K, p -PI3K, AKT, p -AKT, endothelial nitric oxide synthase (eNOS) and its activity, and matrix metalloproteinase 2 (MMP2) significantly decreased with increasing BPDE concentration. The presence of SC79, activator of AKT, partially attenuates the inhibition effect of BPDE on migration and invasion, confirming the involvement of AKT pathway. Thus, BPDE suppresses migration and invasion of human trophoblast HTR-8/SVneo cells by inhibiting the expression of FAK, SRC and PI3K, consequently down-regulating PI3K/AKT signaling pathway. This study reveals the mechanism of Polycyclic aromatic hydrocarbons-inhibited migration and invasion of trophoblast, and enhanced our experimental understanding of the adverse effects of PAHs on embryo implantation in early pregnancy. [ABSTRACT FROM AUTHOR]

Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) leads to dysfunctions of human trophoblast cells and further induces miscarriage. In our previous study, we have found that lnc-HZ03 and miR-hz03 are upregulated in BPDE-exposed human trophoblast cells and in recurrent miscarriage tissues; and the upregulated miR-hz03 caused by lnc-HZ03 further promotes the apoptosis of human trophoblast cells and induces miscarriage. However, how lnc-HZ03 upregulates miR-hz03 is completely unknown. In this study, we find that lnc-HZ03 upregulates the expression level of a transcription factor TFIID (a TATA-binding protein) and promotes TFIID-mediated transactivation response element RNA-binding protein (TRBP) transcription. Subsequently, the upregulated TRBP promotes the maturation of miR-hz03 by splicing its precursor pre-miR-hz03 in human trophoblast cells. In BPDE-exposed trophoblast cells or in recurrent miscarriage tissues, lnc-HZ03 was upregulated, which accelerates the TFIID-mediated TRBP transcription and thus promotes TRBP-mediated miR-HZ03 maturation. Subsequently, the upregulated miR-hz03 further promotes the apoptosis of human trophoblast cells and induces miscarriage. This work provides new insights into the regulation of miRNA expression levels by lncRNAs in BPDE-exposed human trophoblast cells. [ABSTRACT FROM AUTHOR]

Temperature potently modulates various physiologic processes including organismal motility, growth rate, reproduction, and ageing. In ectotherms, longevity varies inversely with temperature, with animals living shorter at higher temperatures. Thermal effects on lifespan and other processes are ascribed to passive changes in metabolic rate, but recent evidence also suggests a regulated process. Here, we demonstrate that in response to temperature, daf-41/ZC395.10, the C. elegans homolog of p23 co-chaperone/prostaglandin E synthase-3, governs entry into the long-lived dauer diapause and regulates adult lifespan. daf-41 deletion triggers constitutive entry into the dauer diapause at elevated temperature dependent on neurosensory machinery (daf-10/IFT122), insulin/IGF-1 signaling (daf-16/FOXO), and steroidal signaling (daf-12/FXR). Surprisingly, daf-41 mutation alters the longevity response to temperature, living longer than wild-type at 25°C but shorter than wild-type at 15°C. Longevity phenotypes at 25°C work through daf-16/FOXO and heat shock factor hsf-1, while short lived phenotypes converge on daf-16/FOXO and depend on the daf-12/FXR steroid receptor. Correlatively daf-41 affected expression of DAF-16 and HSF-1 target genes at high temperature, and nuclear extracts from daf-41 animals showed increased occupancy of the heat shock response element. Our studies suggest that daf-41/p23 modulates key transcriptional changes in longevity pathways in response to temperature. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Tripterygium hypoglaucum (levl.) Hutch (Celastraceae) (THH) root is a traditional Chinese medicinal herb commonly used for treating autoimmune diseases and cancer. Alkaloid is one of the most bioactive components of THH extract. To evaluate the in vitro and in vivo antitumor properties of the total alkaloids of THH (THHta). Materials and methods: THHta was extracted in pilot-scale. HCT116 cells were chose to establish human colon cancer xenograft model. The in vitro anti-tumor activity of THHta was tested by Cell malignant transformation test, Soft agar colony formation assay and MTT assay. The in vivo anti-tumor effect of THHta was confirmed by xenograft mouse model. THHta-induced apoptosis was examined by flow cytometry. The levels of apoptosis-related proteins were investigated by Western blot. Results: TPA-induced cell transformation was significantly inhibited by THHta in JB6 Cl41 cells. THHta inhibits the growth of colon cancer cells in vitro in a significant dose-dependent manner. Compared to the control set, i.p. administration of THHta to xenograft mice significantly reduced both tumor weight and volume. Apoptosis induction of THHta was mediated by activation of caspase-3, PARP and inhibiting of Bcl-2, Bcl-xL and XIAP. Conclusion: THHta was effective in inhibiting tumor growth both in vitro and in vivo at less toxic concentrations by inducing apoptosis which suggested it could be developed as a potential anticancer agent. [ABSTRACT FROM AUTHOR]

Objectives: To explore the role of folate metabolism in 1,3-Butadiene (BD)'s genotoxicity, we conducted a match-up study in BD-exposed workers in China to analyze the associations between the polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and the chromosomal damage induced by BD exposure, and culture-based experiments in TK-6 cells to examine the global DNA methylation levels and chromosomal damage when exposed both to BD's genotoxic metabolite, 1,2:3,4-diepoxybutane (DEB), and MTHFR's direct catalytic product, 5-methyltetrahydrofolate (5-MTHF). Methods: Cytokinesis block micronucleus assay (CBMN) was used to examine the chromosomal damage induced by BD or DEB. Poisson regression models were produced to quantify the relationship of chromosomal damage and genetic polymorphisms in the BD-exposed workers. Global DNA methylation levels in TK6 cells were examined using DNA Methylation Quantification Kit. Results: We found that BD-exposed workers carrying MTHFR C677T CC (2.00 ± 2.00‰) (FR = 0.36, 95%CI: 0.20–0.67, P < 0.01) or MTHFR C677T CT (2.87 ± 1.98‰) (FR = 0.49, 95%CI: 0.32–0.77, P < 0.01) genotypes had significantly lower nuclear bud (NBUD) frequencies than those carrying genotype MTHFR 677 TT (5.33 ± 2.60‰), respectively. The results in TK6 cells showed that there was a significant increment in frequencies of micronucleus (MN), nucleoplasmic bridge (NPB) and nuclear bud (NBUD) with exposure to DEB at each 5-MTHF dose (ANOVA, P < 0.01). Additionally, there was a significant decrease in frequencies of MN, NPB and NBUD in DEB-exposed cultures with increasing concentration of 5-MTHF (ANOVA, P < 0.05). The levels of global DNA methylation were significantly decreased by DEB treatment in a dose-dependent manner within each 5-MTHF concentration in TK-6 cells (ANOVA, P < 0.01), and were significantly increased by 5-MTHF supplementation within each DEB concentration (ANOVA, P < 0.01). Conclusion: We reported that folate metabolism could modify the association between BD exposure and chromosomal damage, and such effect may be partially mediated by DNA hypomethylation, and 5-MTHF supplementation could rescue it. [ABSTRACT FROM AUTHOR]

Abstract: Our previous studies revealed more than 100 pollutants, most of which were endocrine disruptors (EDs) in two Chinese rivers, the Jialing and the Yangtze near Chongqing. Most EDs, such as dibutyl phthalate (DBP) and benzo(a)pyrene (BaP), are known to act individually as reproductive toxicants. However, little is known about the combined toxicity of DBP and BaP. In the current study, male Sprague Dawley rats were subchronically exposed to single doses of DBP (250mg/kg), single doses of BaP (5mg/kg) and combined doses of DBP and BaP. Significant adverse effects were observed on the reproductive system, including decreased sperm count, increased production of abnormal sperm, changes in serum testosterone levels and irregular arrangements of the seminiferous epithelium. Biochemical analyses showed that the activities of superoxide dismutase and glutathione peroxidase decreased after exposure to these EDs. Therefore, our data suggest that exposure to DBP and BaP, in either separate or combined doses, can affect the reproductive system of male rats adversely via oxidative stress-related mechanisms. No significant additive effect was observed after combined exposure. These results indicate that exposure to mixtures of EDs have unexpected and elusive effects. Our findings provide preliminary but important data for assessing water safety in China. [Copyright &y& Elsevier]

Abstract: To evaluate the significance of alterations in cell adhesion-related genes methylation during lung multistep carcinogenesis induced by the genotoxic carcinogens 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN), tissue samples microdissected from MCA/DEN-induced rat lung carcinogenesis model were subjected to methylation-specific PCR to evaluate the DNA methylation status of CADM1, TIMP3, E-cadherin and N-cadherin. Immunohistochemistry was used to determine protein expression of CADM1, TIMP3, N-cadherin and the DNA methyltransferases (DNMTs) 1, 3a and 3b. E-cadherin hypermethylation was not detected in any tissue. CADM1, TIMP3 and N-cadherin hypermethylation was correlated with the loss of their protein expression during the progression of pathologic lesions. The prevalence of DNA methylation of at least one gene and the average number of methylated genes increased with the histological progression. DNMT1 and DNMT3a protein expression increased progressively during the stages of lung carcinogenesis, whereas DNMT3b overexpression was only found in several samples. Furthermore, DNMT1 protein expression levels were correlated with CADM1 methylation, and DNMT3a protein expression levels were correlated with CADM1, TIMP3 and N-cadherin methylation. The average number of methylated genes during carcinogenesis was significantly correlated with DNMT1 and DNMT3a protein expression levels. Moreover, mRNA expression of CADM1 significantly increased after treatment with DNMT inhibitor 5-aza-2′-deoxycytidine in CADM1-methylated primary tumor cell lines. Our findings suggest that an accumulation of hypermethylation accounts for cell adhesion-related gene silencing is associated with dynamic changes in the progression of MCA/DEN-induced rat lung carcinogenesis. We suggest that DNMT1 and DNMT3a protein overexpression may be responsible for this aberrant DNA methylation. [ABSTRACT FROM AUTHOR]

Abstract: 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN) are typical genotoxic carcinogens that can induce tumors in a variety of human and rodent tissues. However, the epigenetic mechanisms underlying their tumorigenesis are unclear. In this study we used a MCA/DEN-induced multistep lung carcinogenesis rat model to study the evolution of alterations in DNA methylation. Rats were treated with a single dose of MCA and DEN in iodized oil by left intra-bronchial instillation. The animals were killed on days 15, 35, 55, 65 and 75 and samples of various pathological phases during carcinogenesis were obtained on these days. The status of global methylation was analyzed for each sample using a monoclonal antibody specific for 5-methycytosine (5-mC) and quantified by image analysis software. We found that the degree of global methylation was, in general, higher in basal cells compared to luminal cells of normal, precancerous and tumor tissues. The combined 5-mC scores of different types of tissues decreased gradually during the progression of carcinogenesis. We also used methylation-sensitive arbitrarily primed PCR (MS-AP-PCR) to screen a total of eight differentially methylated DNA fragments in both precancerous and tumor tissues isolated using laser capture microdissection (LCM), and observed that both unique hypomethylation and hypermethylation fragments coexist after exposure to genotoxic carcinogens. Remarkably, epigenetic alterations in p16 (CDKN2A), but not in p15 (CDKN2B), were observed, and these correlated with the presence of pathologic lung lesions and loss of p16 protein expression. Moreover, defective expression of p16 in methylated primary tumor cell lines recovered markedly after treated with 5-aza-2′-deoxycytidine (5-aza-dC). These results suggest that DNA methylation alterations are an early event in tumorigenesis and play an important role during MCA/DEN-induced multistep rat lung carcinogenesis. [Copyright &y& Elsevier]

Recent studies have shown that the reduction of sperm count is associated with sleep behaviors, including restricted/excessive sleep duration, late sleep time midpoint, and shift of sleep midpoint time (social jetlag). Chronotype is suggested to regulate sleep behaviors; however, the relationship between chronotype and human sperm count is unknown. The relationship between sleep behaviors and human sperm count, when sleep behaviors as well as chronotype are controlled is also unclear. We performed a path analysis of the data obtained from 667 Chinese men recruited into the MARHCS (Male Reproductive Health in Chongqing College Students) study. Chronotype, sleep duration, sleep time midpoint, and social jetlag were estimated by the Munich Chronotype Questionnaire. Sperm count was measured by computer-aided sperm analysis. The comprehensive relationship between chronotype, all sleep behaviors, and sperm count was tested by path analysis, in which the standardized residual of sperm count was used for adjustment of age, abstinence period, body mass index, tobacco smoking, alcohol drinking, and intake of tea, cola, and coffee. Our major findings are: (1) Chronotype negatively correlated with sleep duration (correlation coefficient (R) = −0.32, P <.001) and positively correlated with sleep midpoint (R = 0.65, P <.001) and social jetlag (R = 0.37, P <.001). (2) Sleep duration (U-shape transformed; R = −0.11, P =.005), sleep midpoint (R = −0.09, P =.021), and social jetlag (R = −0.12, P =.001), respectively, correlated with sperm count in univariate analysis. The relationship between sleep midpoint and sperm count disappeared when social jetlag was controlled. (3) Path analysis showed that chronotype is connected with sperm count through two pathways: via sleep duration (standardized path coefficient = −0.09, 95% CI: −0.17 to −0.01, P =.030) and via social jetlag (standardized path coefficient = −0.09, 95% CI: −0.17 to −0.01, P =.031). For men of earlier, intermediate, and later tertile of chronotype, the sleep-duration-related decrease of sperm count was separately estimated to be 16.3%, 12.8%, and 11.6%, while the social-jetlag-related decrease of sperm count was estimated to be 9.3%, 12.8%, and 19.2%. The total effect of sleep behaviors on sperm count was estimated to be 25.7%, 25.6%, and 30.7%, with an average of 27.4% for men of different chronotypes. The present study showed that men of earlier chronotype were prone to restricted/excessive sleep duration, while men of later chronotype were prone to social jetlag, both of which correlated with reduced sperm count, suggesting that chronotype may modulate the sleep behaviors and exert dual effects on sperm count via different sleep behaviors, leading to a ubiquitous sperm decline. Men of different chronotypes should take care to avoid different types of improper sleep behaviors, so as to prevent such deleterious effect on sperm count. [ABSTRACT FROM AUTHOR]

The microenvironment in the seminiferous tubules of buffalo changes with age, which affects the self‐renewal and growth of spermatogonial stem cells (SSCs) and the process of spermatogenesis, but the mechanism remains to be elucidated. RNA‐seq was performed to compare the transcript profiles of pre‐pubertal buffalo (PUB) and adult buffalo (ADU) seminiferous tubules. In total, 17,299 genes from PUB and ADU seminiferous tubules identified through RNA‐seq, among which 12,271 were expressed in PUB and ADU seminiferous tubules, 4,027 were expressed in only ADU seminiferous tubules, and 956 were expressed in only PUB seminiferous tubules. Of the 17,299 genes, we identified 13,714 genes that had significant differences in expression levels between PUB and ADU through GO enrichment analysis. Among these genes, 5,342 were significantly upregulated and possibly related to the formation or identity of the surface antigen on SSCs during self‐renewal; 7,832 genes were significantly downregulated, indicating that genes in PUB seminiferous tubules do not participate in the biological processes of sperm differentiation or formation in this phase compared with those in ADU seminiferous tubules. Subsequently, through the combination with KEGG analysis, we detected enrichment in a number of genes related to the development of spermatogonial stem cells, providing a reference for study of the development mechanism of buffalo spermatogonial stem cells in the future. In conclusion, our data provide detailed information on the mRNA transcriptomes in PUB and ADU seminiferous tubules, revealing the crucial factors involved in maintaining the microenvironment and providing a reference for further in vitro cultivation of SSCs. [ABSTRACT FROM AUTHOR]

S-adenosyl methionine synthetase (SAMS) catalyzes the biosynthesis of S-adenosyl methionine (SAM), which serves as a universal methyl group donor for numerous biochemical reactions. Previous studies have clearly demonstrated that SAMS-1, a C. elegans homolog of mammalian SAMS, is critical for dietary restriction (DR)-induced longevity in Caenorhabditis elegans. In addition to SAMS-1, three other SAMS paralogs have been identified in C. elegans. However, their roles in longevity regulation have never been explored. Here, we show that depletion of sams-5, but not sams-3 or sams-4, can extend lifespan in worms. However, the phenotypes and expression pattern of sams-5 are distinct from sams-1, suggesting that these two SAMSs might regulate DR-induced longevity via different mechanisms. Through the genetic epistasis analysis, we have identified that sams-5 is required for DR-induced longevity in a pha-4/FOXA dependent manner. [ABSTRACT FROM AUTHOR]

The article discusses Heat shock factor–1 (HSF-1) has a master regulator of stress responses across taxa. Topics include overexpression of HSF-1 or genetic ablation of conserved negative regulator, heat shock factor binding protein 1, results in robust life-span extension in Caenorhabditis elegans; and the rate of aging in multicellular organisms has determined by evolutionarily conserved cellular and metabolic processes.

The article offers information on High-throughput small molecule screening which reveals Nrf2-dependent and -independent pathways of cellular stress resistance. It mentions Cellular stress resistance is an evolutionarily conserved feature of longevity. Here, we identify compounds that induced resistance to the superoxide generator paraquat (PQ), the heavy metal cadmium (Cd), and the DNA alkylator methyl methanesulfonate (MMS).

Study Question: Is circadian desynchrony a risk factor of male reproductive damage in semen parameters and/or reproductive hormones?Summary Answer: Circadian desynchrony correlates with decrease of sperm count, which was improved when circadian desynchrony was attenuated.What Is Known Already: Circadian desynchrony caused by work (shift work) and non-work-related reasons is prevalent worldwide and has been found to be associated with decreased female fertility, but whether it harms male reproductive health is unclear.Study Design, Size, Duration: A hybrid research was conducted. (i) A cross-sectional study of 1346 Chinese men in 2007 was used to analyze the association between semen/hormone biomarkers and work-related circadian desynchrony, which was divided into rotating shift work and permanent shift work against non-shift work. (ii) A cohort of 796 Chinese undergraduates from 2013 to 2014 was used to analyzed the association between semen/hormone biomarkers and non-work-related circadian desynchrony (between school days and days off). (iii) The biomarker identified simultaneously in both populations was further validated in male C57BL/6J mice housed under conditions simulating circadian desynchrony.Participants/materials, Setting, Methods: A total of 17 semen/hormone biomarkers were compared among rotating shift workers and permanent shift workers against non-shift workers in the 1346 reproductive-age Chinese men. A total of 14 semen/hormone biomarker was analyzed in the undergraduate cohort for correlation with non-work-related circadian desynchrony (measured by Munich Chronotype Questionnaire) in 2013 and 2014 and compared between the 2 years. Photoperiod-shifting method was used to establish the mouse model, in which the biomarker was examined and molecular mechanism was explored by apoptosis analysis, DNA content analysis, transcriptome sequencing, real-time PCR and western blotting.Main Results and the Role Of Chance: Among the semen/hormone biomarkers, sperm count was found to be lower in rotating shift workers, who had a higher risk of low sperm count defined by Chinese Ministry of Health (total sperm/ejaculate < 120 × 106) than non-shift workers (odds ratio = 1.26, 95% CI 1.05-1.52). This biomarker was replicated in the undergraduate cohort, where each hour of circadian desynchrony was associated with 1.16 (95% CI 1.02-1.31) fold odds of low sperm count, and sperm count increased during 2014 in men who reduced circadian desynchrony after 2013. A decrease of sperm count with circadian desynchrony and its recovery after removal of circadian desynchrony was also observed in the mouse model. During asynchrony, increased apoptosis was found in seminiferous tubules and the marker genes of post-spermatocyte stage cells were down-regulated. The most enriched functional pathway was homologous recombination, which happened during meiosis.Limitations, Reasons For Caution: The study of human beings was observational while the animal study has potential difference in circadian desynchrony exposure and species susceptibility. Further researches are needed to clarify the causal relationship in men.Wider Implications Of the Findings: These findings provide novel insight to the effect of circadian desynchrony on male reproductive health and a potential strategy for prevention of reproductive damage.Study Funding/competing Interest(s): This study was supported by the National Key R&D Program of China [2017YFC1002001] and National Natural Science Foundation of China [81871208]. There are no conflicts of interest to declare.Trial Registration Number: NA. [ABSTRACT FROM AUTHOR]

Stress granules (SGs) are nonmembranous organelles that are dynamically assembled and disassembled in response to various stressors. Under stressed conditions, polyadenylated mRNAs and translation factors are sequestrated in SGs to promote global repression of protein synthesis. It has been previously demonstrated that SG formation enhances cell survival and stress resistance. However, the physiological role of SGs in organismal aging and longevity regulation remains unclear. In this study, we used TIAR‐1::GFP and GTBP‐1::GFP as markers to monitor the formation of SGs in Caenorhabditis elegans. We found that, in addition to acute heat stress, SG formation could also be triggered by dietary changes, such as starvation and dietary restriction (DR). We found that HSF‐1 is required for the SG formation in response to acute heat shock and starvation but not DR, whereas the AMPK‐eEF2K signaling is required for starvation and DR‐induced SG formation but not heat shock. Moreover, our data suggest that this AMPK‐eEF2K pathway‐mediated SG formation is required for lifespan extension by DR, but dispensable for the longevity by reduced insulin/IGF‐1 signaling. Collectively, our findings unveil a novel role of SG formation in DR‐induced longevity. [ABSTRACT FROM AUTHOR]

Strand displacement DNA synthesis is essential for DNA replication. Gp90, the sole DNA polymerase of Pseudomonas aeruginosa phage 1, can bypass multiply DNA lesions. However, whether it can perform strand displacement synthesis is still unknown. In this work, we found that gp90 exo― could perform strand displacement synthesis, albeit its activity and processivity were lower than those of primer extension. Gp90 exo― itself could not unwind Y-shaped or fork DNA. Tail and gap at DNA fork were necessary for efficient synthesis. High GC content obviously inhibited strand displacement synthesis. Consecutive GC sequence at the entrance of fork showed more inhibition effect on DNA synthesis than that in the downstream DNA fork. The fraction of productive polymerase and DNA complex (A values) was higher for fork than gap; while their average extension rates (k p values) were similar. However, both A and k p values were lower than those for the primer/template (P/T) substrate. The binding of gp90 exo― to fork was tighter than P/T or gap in the absence of dATP. In the presence of dATP to form ternary complex, the binding affinity of gp90 exo― to P/T or gap was increased compared with that in the binary complex. Abasic site, 8-oxoG, and O 6-MeG inhibited and even blocked strand displacement synthesis. This work shows that gp90 exo― could perform strand displacement DNA synthesis at DNA fork, discovering the presence of new functions of PaP1 DNA polymerase in DNA replication and propagation of PaP1. • Gp90 exo― could perform strand displacement DNA synthesis. • Tail and gap at DNA fork were necessary for efficient synthesis. • High GC content and DNA lesions obviously inhibited strand displacement synthesis. • E. coli Pol I KF exo― and Pol T7 ― could perform this synthesis, but Dpo4 and hPol ι could nearly not. • This work discovers new functions of polymerase in DNA replication and propagation of PaP1. [ABSTRACT FROM AUTHOR]

There is increasing evidence that indicates benzo[ a ]pyrene (B[ a ]P) and its active metabolite benzo[ a ]pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE) are endocrine disruptors that can cause reproductive toxicity. Nevertheless, the underlying mechanisms are still obscure. The present study investigates the impacts of B[ a ]P and BPDE on mitochondria, a sensitive target affected by multiple chemicals, in spermatogenic cells. It showed that BPDE treatment induced mitochondrial dysfunction and the inhibition of mitochondrial biogenesis in mouse spermatocyte-derived cells (GC-2). These effects were efficiently mitigated by pretreatment with ZLN005, an activator of PGC-1α, in GC-2 cells. TERT knockdown and re-expression cell models were established to demonstrate that TERT regulated the BPDE-induced mitochondrial damage via PGC-1α signaling in GC-2 cells. Moreover, upregulating or knockdown SIRT1 expression attenuated or aggravated BPDE-induced mitochondrial compromise by activating or inhibiting, respectively, the TERT and PGC-1α molecules in GC-2 cells. Finally, we observed that BPDE markedly elevated oxidative stress in GC-2 cells. Resveratrol and N -acetylcysteine, as reactive oxygen species (ROS) scavengers, attenuated BPDE-mediated mitochondrial damage by increasing SIRT1 activity and expression in GC-2 cells. The in vitro results were corroborated by in vivo experiments in rats treated with B[ a ]P for 4 weeks. B[ a ]P administration caused mitochondrial damage and mitochondria-dependent apoptosis in spermatogenic cells, as well as the decreased expression of SIRT1, TERT, and PGC-1α. In summary, the results of the present study demonstrate that B[ a ]P and BPDE induce mitochondrial damage through ROS production that suppresses SIRT1/TERT/PGC-1a signaling and mediate B[ a ]P- and BPDE-mediated reproductive toxicity. Unlabelled Image • Mitochondria are the target of male reproductive toxicity induced by BPDE/B[ a ]P. • BPDE and B[ a ]P induce mitochondrial compromise in spermatogenic cells. • SIRT1/TERT/PGC-1α pathway accounts for BPDE/B[ a ]P-induced mitochondrial damage. • BPDE/B[ a ]P-induced ROS causes the suppression of SIRT1/TERT/PGC-1α pathway. [ABSTRACT FROM AUTHOR]

The spin qubit in quantum dots is one of the leading platforms for quantum computation. A crucial requirement for scalable quantum information processing is the high efficient measurement. Here we analyze the measurement process of a quantum-dot spin qubit coupled to a superconducting transmission line resonator. Especially, the phase shift of the resonator is sensitive to the spin states and the gate operations. The response of the resonator can be used to measure the spin qubit efficiently, which can be extend to read out the multiple spin qubits in a scalable solid-state quantum processor. [ABSTRACT FROM AUTHOR]