Endothelial Autophagy Promotes Atheroprotective Communication Between Endothelial and Smooth Muscle Cells via Exosome-Mediated Delivery of miR-204-5p.

BACKGROUND: Cellular communication among different types of vascular cells is indispensable for maintaining vascular homeostasis and preventing atherosclerosis. However, the biological mechanism involved in cellular communication among these cells and whether this biological mechanism can be used to treat atherosclerosis remain unknown. We hypothesized that endothelial autophagy mediates the cellular communication in vascular tissue through exosome-mediated delivery of atherosclerosis-related genes. METHODS: Rapamycin and adeno-associated virus carrying Atg7 short hairpin RNA under the Tie (TEK receptor tyrosine kinase) promoter were used to activate and inhibit vascular endothelial autophagy in high-fat diet-fed ApoE-/- mice, respectively. miRNA microarray, in vivo and in vitro experiments, and human vascular tissue were used to explore the effects of endothelial autophagy on endothelial function and atherosclerosis and its molecular mechanisms. Quantitative polymerase chain reaction and miRNA sequencing were performed to determine changes in miRNA expression in exosomes. Immunofluorescence and exosome coculture experiments were conducted to examine the role of endothelial autophagy in regulating the communication between endothelial cells and smooth muscle cells (SMCs) via exosomal miRNA. RESULTS: Endothelial autophagy was inhibited in thoracic aortas of high-fat diet-fed ApoE-/- mice. Furthermore, rapamycin alleviated high-fat diet-induced atherosclerotic burden and endothelial dysfunction, while endothelial-specific Atg7 depletion aggravated the atherosclerotic burden. miRNA microarray, in vivo and in vitro experiments, and human vascular tissue analysis revealed that miR-204-5p was significantly increased in endothelial cells after high-fat diet exposure, which directly targeted Bcl2 to regulate endothelial cell apoptosis. Importantly, endothelial autophagy activation decreased excess miR-204-5p by loading miR-204-5p into multivesicular bodies and secreting it through exosomes. Moreover, exosomal miR-204-5p can effectively transport to SMCs, alleviating SMC calcification by regulating target proteins such as RUNX2. CONCLUSIONS: Our study revealed the exosomal pathway by which endothelial autophagy protects atherosclerosis: endothelial autophagy activation transfers miR-204-5p from endothelial cells to SMCs via exosomes, both preventing endothelial apoptosis and alleviating SMC calcification. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2200064155.

Structural and molecular basis for urea recognition by Prochlorococcus.

Nitrogen (N) is an essential element for microbial growth and metabolism. The growth and reproduction of microorganisms in more than 75% of areas of the ocean are limited by N. Prochlorococcus is numerically the most abundant photosynthetic organism on the planet. Urea is an important and efficient N source for Prochlorococcus. However, how Prochlorococcus recognizes and absorbs urea still remains unclear. Prochlorococcus marinus MIT 9313, a typical Cyanobacteria, contains an ABC-type transporter, UrtABCDE, which may account for the transport of urea. Here, we heterologously expressed and purified UrtA, the substrate-binding protein of UrtABCDE, detected its binding affinity toward urea, and further determined the crystal structure of the UrtA/urea complex. Molecular dynamics simulations indicated that UrtA can alternate between "open" and "closed" states for urea binding. Based on structural and biochemical analyses, the molecular mechanism for urea recognition and binding was proposed. When a urea molecule is bound, UrtA undergoes a state change from open to closed surrounding the urea molecule, and the urea molecule is further stabilized by the hydrogen bonds supported by the conserved residues around it. Moreover, bioinformatics analysis showed that ABC-type urea transporters are widespread in bacteria and probably share similar urea recognition and binding mechanisms as UrtA from P. marinus MIT 9313. Our study provides a better understanding of urea absorption and utilization in marine bacteria.

Metagenomic insights into the dynamic degradation of brown algal polysaccharides by kelp-associated microbiota.

Marine bacteria play important roles in the degradation and cycling of algal polysaccharides. However, the dynamics of epiphytic bacterial communities and their roles in algal polysaccharide degradation during kelp decay are still unclear. Here, we performed metagenomic analyses to investigate the identities and predicted metabolic abilities of epiphytic bacterial communities during the early and late decay stages of the kelp Saccharina japonica. During kelp decay, the dominant epiphytic bacterial communities shifted from Gammaproteobacteria to Verrucomicrobia and Bacteroidetes. In the early decay stage of S. japonica, epiphytic bacteria primarily targeted kelp-derived labile alginate for degradation, among which the gammaproteobacterial Vibrionaceae (particularly Vibrio) and Psychromonadaceae (particularly Psychromonas), abundant in alginate lyases belonging to the polysaccharide lyase (PL) families PL6, PL7, and PL17, were key alginate degraders. More complex fucoidan was preferred to be degraded in the late decay stage of S. japonica by epiphytic bacteria, predominantly from Verrucomicrobia (particularly Lentimonas), Pirellulaceae of Planctomycetes (particularly Rhodopirellula), Pontiellaceae of Kiritimatiellota, and Flavobacteriaceae of Bacteroidetes, which depended on using glycoside hydrolases (GHs) from the GH29, GH95, and GH141 families and sulfatases from the S1_15, S1_16, S1_17, and S1_25 families to depolymerize fucoidan. The pathways for algal polysaccharide degradation in dominant epiphytic bacterial groups were reconstructed based on analyses of metagenome-assembled genomes. This study sheds light on the roles of different epiphytic bacteria in the degradation of brown algal polysaccharides.IMPORTANCEKelps are important primary producers in coastal marine ecosystems. Polysaccharides, as major components of brown algal biomass, constitute a large fraction of organic carbon in the ocean. However, knowledge of the identities and pathways of epiphytic bacteria involved in the degradation process of brown algal polysaccharides during kelp decay is still elusive. Here, based on metagenomic analyses, the succession of epiphytic bacterial communities and their metabolic potential were investigated during the early and late decay stages of Saccharina japonica. Our study revealed a transition in algal polysaccharide-degrading bacteria during kelp decay, shifting from alginate-degrading Gammaproteobacteria to fucoidan-degrading Verrucomicrobia, Planctomycetes, Kiritimatiellota, and Bacteroidetes. A model for the dynamic degradation of algal cell wall polysaccharides, a complex organic carbon, by epiphytic microbiota during kelp decay was proposed. This study deepens our understanding of the role of epiphytic bacteria in marine algal carbon cycling as well as pathogen control in algal culture.

Secure optical communication system based on polarization regulation of the data fragmentation multipath transmission technology.

We propose and demonstrate a data fragment multipath transmission scheme to achieve a secure optical communication based on polarization regulation. A dual-polarization Mach-Zehnder modulator (DPMZM) is driven by digital signals which are scattered by field-programmable gate array (FPGA) and transmitted in multiple paths. By utilizing two orthogonal polarization states, we have achieved a signal transmission under different optical parameters, and the transmission rate of the two paths can reach over 10 Gbps through a 20 km fiber with 2.5 Gbps hopping rate. In addition, we establish a theoretical model to analyze the security of the system and simulate brute force cracking; the probability of cracking the minimum information unit is 1.53 × 10-53. This proves that it is difficult to obtain a user data even using the fastest computers. Our scheme has provided, to our knowledge, a new approach for physical layer security.

Spartinivicinus marinus sp. nov., isolated from intertidal sediment.

A Gram-stain-negative, aerobic, flagellated, and long rod-shaped bacterium, designated strain SM1973T, was isolated from an intertidal sediment sample collected from the coast of Qingdao, PR China. Strain SM1973T grew at 15-37 °C and with 0-5.5 % NaCl. It reduced nitrate to nitrite and hydrolysed aesculin but did not hydrolyse casein and gelatin. The strain showed the highest 16S rRNA gene sequence similarity (98.2 %) to the type strain of Spartinivicinus ruber. The phylogenetic trees based on the 16S rRNA genes and single-copy orthologous clusters showed that strain SM1973T clustered with S. ruber, forming a separate lineage within the family Zooshikellaceae. The major cellular fatty acids were summed feature 3 (C16 : 1 ω7с and/or C16 : 1 ω6с) and C16 : 0. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The main respiratory quinone was ubiquinone-9. The genomic DNA G+C content of strain SM1973T was 40.4 mol%. Based on the polyphasic evidence presented in this paper, strain SM1973T is considered to represent a novel species within the genus Spartinivicinus, for which the name Spartinivicinus marinus sp. nov. is proposed. The type strain is SM1973T (=MCCC 1K04833T=KCTC 72846T).

The Natural Alkaloid (-)-N-Hydroxyapiosporamide Suppresses Colorectal Tumor Progression as an NF-κB Pathway Inhibitor by Targeting the TAK1-TRAF6 Complex.

Colorectal cancer (CRC) is an exceptionally deadly disease, whereas effective therapeutic drugs for CRC have declined over the past few decades. Natural products have become a reliable source of anticancer drugs. Previously we isolated an alkaloid named (-)-N-hydroxyapiosporamide (NHAP), which exerts potent antitumor effects, but its effect and mechanism in CRC remain unclear. This study aimed to reveal the antitumor target of NHAP and identify NHAP as a promising lead compound for CRC. Various biochemical methods and animal models were used to investigate the antitumor effect and molecular mechanism for NHAP. These results showed that NHAP exhibited potent cytotoxicity, induced both apoptosis and autophagic cell death of CRC cells, and inhibited the NF-κB signaling pathway by blocking the interaction of the TAK1-TRAF6 complex. NHAP also markedly inhibited CRC tumor growth in vivo without obvious toxicities and possessed good pharmacokinetic characteristics. These findings identify, for the first time, that NHAP is an NF-κB inhibitor with potent antitumor activity in vitro and in vivo. This study clarifies the antitumor target of NHAP against CRC, which will contribute to the future development of NHAP as a novel therapeutic lead compound for CRC.

100 Gb/s NRZ OOK signal regeneration using four-wave mixing in a silicon waveguide with reverse-biased p-i-n junction.

A silicon waveguide with reverse-biased p-i-n junction is used to experimentally demonstrate all-optical regeneration of non-return-to-zero (NRZ) on-off keying (OOK) signal based on four-wave mixing. The silicon waveguide allows a high conversion efficiency of -12 dB. The 0.22 dB (1.1 dB) quality (Q) factor and 0.74 dB (6.3 dB) extinction ratio (ER) improvements on average are achieved for 100 Gb/s (50 Gb/s) NRZ OOK signal regeneration at different receiving powers via the optimal match between the input signal optical power and input-output transfer curve. To the best of our knowledge, this silicon-based all-optical regenerator exhibits superior regeneration performance, including large ER and Q factor improvements, and the highest regeneration speed of NRZ OOK signal, and it has wide applications in 5 G/6 G networks.

A novel 6-metabolite signature for prediction of clinical outcomes in type 2 diabetic patients undergoing percutaneous coronary intervention.

BACKGROUND: Outcome prediction tools for patients with type 2 diabetes mellitus (T2DM) undergoing percutaneous coronary intervention (PCI) are lacking. Here, we developed a machine learning-based metabolite classifier for predicting 1-year major adverse cardiovascular events (MACEs) after PCI among patients with T2DM. METHODS: Serum metabolomic profiling was performed in a nested case-control study of 108 matched pairs of patients with T2DM occurring and not occurring MACEs at 1 year after PCI, then the matched pairs were 1:1 assigned into the discovery and internal validation sets. External validation was conducted using targeted metabolite analyses in an independent prospective cohort of 301 patients with T2DM receiving PCI. The function of candidate metabolites was explored in high glucose-cultured human aortic smooth muscle cells (HASMCs). RESULTS: Overall, serum metabolome profiles differed between diabetic patients with and without 1-year MACEs after PCI. Through VSURF, a machine learning approach for feature selection, we identified the 6 most important metabolic predictors, which mainly targeted the nicotinamide adenine dinucleotide (NAD+) metabolism. The 6-metabolite model based on random forest and XGBoost algorithms yielded an area under the curve (AUC) of ≥ 0.90 for predicting MACEs in both discovery and internal validation sets. External validation of the 6-metabolite classifier also showed good accuracy in predicting MACEs (AUC 0.94, 95% CI 0.91-0.97) and target lesion failure (AUC 0.89, 95% CI 0.83-0.95). In vitro, there were significant impacts of altering NAD+ biosynthesis on bioenergetic profiles, inflammation and proliferation of HASMCs. CONCLUSION: The 6-metabolite model may help for noninvasive prediction of 1-year MACEs following PCI among patients with T2DM.

Celeribacter litoreus sp. nov., isolated from intertidal sediment.

A Gram-negative, aerobic, non-flagellated and rod-shaped bacterium, strain ASW11-22T, was isolated from an intertidal sediment collected from a coastal area of Qingdao, PR China. The strain grew at 15-40 °C (optimum, 37 °C), at pH 6.0-9.0 (optimum, pH 7.0) and with 0.5-10 % (w/v) NaCl (optimum, 1.0 %). It hydrolysed gelatin and aesculin but did not reduce nitrate to nitrite. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ASW11-22T belonged to the genus Celeribacter, showing the highest sequence similarity to the type strains of Celeribacter halophilus MCCC 1A06432T (98.20 %) and Celeribacter ethanolicus NH195T (97.84 %). The genomic DNA G+C content was 59.1 mol%. The major cellular fatty acid (>10 %) of the strain was summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and its main polar lipids were phosphatidylglycerol and one unidentified aminolipid. The sole respiratory quinone of strain ASW11-22T was ubiquinone-10. On the basis of the polyphasic evidence presented in this paper, strain ASW11-22T represents a novel Celeribacter species, for which the name Celeribacter litoreus sp. nov. is proposed. The type strain is ASW11-22T (=KCTC 82495T=MCCC 1K05584T).

Mechanistic insights into the amelioration effects of lipopolysaccharide-induced acute lung injury by baicalein: An integrated systems pharmacology study and experimental validation.

BACKGROUND: Acute lung injury is an acute progressive respiratory failure caused by several of non-cardiogenic factors which involves in excessive amplification or uncontrolled inflammatory response. OBJECTIVES: In this study, we investigated the protective effect of baicalein against acute lung injury induced by LPS and explored the underlying mechanisms. METHODS: Forty-eight SPF male C57BL/6 mice were randomly divided into normal group, model group, dexamethasone group and baicalein low-dose, medium-dose and high-dose groups. After 5 days of adaptive feeding, the mice were intraperitoneally injected with LPS and dissected after 12 h. Hematoxylin-eosin staining, ELISA assay, immunofluorescence assay and Western-Blot were applied to appraise microstructural changes and protein expressions of lung tissues. Systems pharmacology study was used to evaluate the protection of baicalein on acute lung injury. FINDINGS: The results showed that baicalein administration could significantly inhibit LPS-induced lung morphological changes, inhibit inflammatory response and pyroptosis. A total of forty-three potential targets of baicalein and acute lung injury were obtained. And PI3K-Akt, TNF and NF-κB were mainly signaling pathways. It is worth mentioning that this experiment also confirmed that NLRP3, caspase-1 and other inflammasome are involved in pyroptosis. CONCLUSION: Baicalein has protected against LPS-induced lung tissues injury via inhibiting inflammatory response and pyroptosis.

Trichopsistides A and B: Two Highly Oxygenated Pentacyclic Polyketides with Promising Inhibitory Effects on the NF-κB Signaling Pathway from the Fungus Trichoderma koningiopsis WZ-196.

Two highly oxygenated pentacyclic polyketides with two new carbon skeletons, trichopsistide A (1) and trichopsistide B (2), were isolated from the plant endophyte Trichoderma koningiopsis WZ-196 derived from the leaf of Rubia podantha Diels. The structures of these polyketides with full configurations were determined by comprehensive spectroscopic analysis, computer-assisted structure elucidation software, computational calculation, and X-ray crystal diffraction. Among them, 1 represented the first example of an unprecedented 5/6/6/6/5 pentacyclic ketal-containing polyketide pyridine alkaloid, and 2 possessed a novel 6/6/6/6/5 pentacyclic ketal-containing polyketide scaffold fused with an α-pyrone. The plausible biosynthetic route for 1 and 2 was also proposed. Moreover, biological activity assays showed that 1 and 2 possessed inhibitory effects on the NF-κB signaling pathway with IC50 values of 14.77 and 8.58 µM, respectively. Furthermore, 1 and 2 could also inhibit the expression of IκBα and p65 phosphorylation, decrease the expression of MCP-1, E-selectin, and IL-8 at the mRNA level, and inhibit the TNF-α-induced nuclear translocation of p65.

Dihydroartemisinin suppresses renal fibrosis in mice by inhibiting DNA-methyltransferase 1 and increasing Klotho.

Renal fibrosis is an unavoidable end result of all forms of progressive chronic kidney diseases (CKD). Discovery of efficacious drugs against renal fibrosis is in crucial need. In a preliminary study we found that a derivative of artemisinin, dihydroartemisinin (DHA), exerted strong renoprotection, and reversed renal fibrosis in adenine-induced CKD mouse model. In this study we investigated the anti-fibrotic mechanisms of DHA, particularly its specific target in renal cells. Renal fibrosis was induced in mice by unilateral ureteral obstruction (UUO) or oral administration of adenine (80 mg · kg-1), the mice received DHA (30 mg · kg-1 · d-1, i.g.) for 14 or 21 days, respectively. We showed that DHA administration markedly attenuated the inflammation and fibrotic responses in the kidneys and significantly improved the renal function in both the renal fibrosis mouse models. In adenine-treated mice, DHA was more effective than 5-azacytidine against renal fibrosis. The anti-fibrotic effects of DHA were also observed in TGF-ß1-treated HK-2 cells. In order to determine the target protein of DHA, we conducted pull-down technology coupled with shotgun proteomics using a small-molecule probe based on the structure of DHA (biotin-DHA). As a results, DNA methyltransferase 1 (DNMT1) was identified as the anti-fibrotic target of DHA in 3 different types of renal cell lines (HK-2, HEK293 and 3T3). We demonstrated that DHA directly bound to Asn 1529 and Thr 1528 of DNMT1 with a Kd value of 8.18 µM. In primary mouse renal tubular cells, we showed that DHA (10 µM) promoted DNMT1 degradation via the ubiquitin-proteasome pathway. DHA-reduced DNMT1 expression effectively reversed Klotho promoter hypermethylation, which led to the reversal of Klotho protein loss in the kidney of UUO mice. This subsequently resulted in inhibition of the Wnt/ß-catenin and TGF-ß/Smad signaling pathways and consequently conferred renoprotection in the animals. Knockdown of Klotho abolished the renoprotective effect of DHA in UUO mice. Our study reveals a novel pharmacological activity for DHA, i.e., renoprotection. DHA exhibits this effect by targeting DNMT1 to reverse Klotho repression. This study provides an evidence for the possible clinical application of DHA in the treatment of renal fibrosis.

Description of Aureibaculum luteum sp. nov. and Aureibaculum flavum sp. nov. isolated from Antarctic intertidal sediments.

Two Gram-stain-negative, aerobic, non-motile, and rod-shaped bacterial strains, designated SM1352T and A20T, were isolated from intertidal sediments collected from King George Island, Antarctic. They shared 99.8% 16S rRNA gene sequence similarity with each other and had the highest sequence similarity of 98.1% to type strain of Aureibaculum marinum but < 93.4% sequence similarity to those of other known bacterial species. The genomes of strains SM1352T and A20T consisted of 5,108,092 bp and 4,772,071 bp, respectively, with the G + C contents both being 32.0%. They respectively encoded 4360 (including 37 tRNAs and 6 rRNAs) and 4032 (including 36 tRNAs and 5 rRNAs) genes. In the phylogenetic trees based on 16S rRNA gene and single-copy orthologous clusters (OCs), both strains clustered with Aureibaculum marinum and together formed a separate branch within the family Flavobacteriaceae. The ANI and DDH values between the two strains and Aureibaculum marinum BH-SD17T were all below the thresholds for species delineation. The major cellular fatty acids (> 10%) of the two strains included iso-C15:0, iso-C15:1 G, iso-C17:0 3-OH. Their polar lipids predominantly included phosphatidylethanolamine, one unidentified aminophospholipid, one unidentified aminolipid, and two unidentified lipids. Genomic comparison revealed that both strains possessed much more glycoside hydrolases and sulfatase-rich polysaccharide utilization loci (PULs) than Aureibaculum marinum BH-SD17T. Based on the above polyphasic evidences, strains SM1352T and A20T represent two novel species within the genus Aureibaculum, for which the names Aureibaculum luteum sp. nov. and Aureibaculum flavum sp. nov. are proposed. The type strains are SM1352T (= CCTCC AB 2014243 T = JCM 30335 T) and A20T (= CCTCC AB 2020370 T = KCTC 82503 T), respectively.

Rubichaetoglobin A, a new cytochalasan alkaloid isolated from the plant endophytic fungus Chaetomium tectifimeti S104.

Rubichaetoglobin A (1), a new cytochalasan alkaloid, together with nine closely related known ones (2-10), were isolated from the ethyl acetate extracts of the endophytic fungus Chaetomium tectifimeti S104 harbored in the root of Rubia podantha Diels. Their structures were elucidated based on comprehensive spectroscopic analysis. All isolated compounds were tested for cytotoxic, antibacterial, and nitric oxide inhibitory activities. The results showed that 2, 4, and 5 possessed moderate cytotoxicity against MDA-MB-231 cells with the IC50 values of 19.14, 11.43, and 10.27 µM, respectively.

[Huayu Jiedu Shengjing Decoction improves semen quality and reduces TCM syndrome scores in patients with varicocele-induced asthenospermic infertility].

OBJECTIVE: To observe the clinical efficacy of "Huayu Jiedu Shengjing Decoction" (HJSD) in the treatment of varicocele (VC)-induced asthenospermic infertility and its action mechanism. METHODS: Using computer-generated random numbers, we equally divided 88 patients meeting the study criteria into an experimental and a control group, the former treated orally with HJSD plus or minus, while the latter with Maizhiling Tablets and levocarnitine, both for a course of 12 weeks. After medication, we obtained TCM syndrome scores, sperm motility, sperm DNA fragmentation index (DFI), the seminal cord venous ultrasonographic index, and levels of nitric oxide (NO), reactive oxygen species (ROS) and superoxide dismutase (SOD) in the seminal plasma from the patients, compared the therapeutic effects between the two groups, and analyzed the correlation among the obtained parameters. RESULTS: The total effectiveness rate was dramatically higher in the experimental than in the control group (86.04% vs 73.74%, P < 0.01). The TCM syndromes scores, sperm motility, sperm DFI, and seminal plasma NO, ROS and SOD were all more significantly improved in the former than in the latter group (P < 0.05). CONCLUSION: Huayu Jiedu Shengjing Decoction can improve semen quality and reduce TCM syndrome scores without adverse reactions in patients with VC-induced asthenospermic infertility, which may be attributed to its effect of improving antioxidation and local blood flow.

[Yishen Tongluo Prescription for repairing benzo(a)pyrene-induced sperm DNA damage in male rats: Effect and mechanism].

OBJECTIVE: To investigate the repairing effect of Yishen Tongluo Prescription (YTP) on sperm DNA fragmentation index (DFI) in male rats exposed to benzo(a)pyrene (BaP) and its possible mechanism. METHODS: Thirty Wistar male rats were equally randomized into a blank control, a BaP-exposure and a YTP intervention group, those in the latter two groups exposed to BaP at 20 mg/kg/d for 60 consecutive days, and those in the YTP intervention group treated intragastrically with YTP from the 31st day of BaP exposure for a total of 30 days. After the last administration, the sperm DFI of the rats was detected by sperm chromatin structure analysis, the levels of FSH, LH and T in the serum and superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and adenosine triphosphate (ATP) in the testis were measured by ELISA. RESULTS: Compared with the blank controls, the rats in the BaP-exposure group showed significantly increased DFI ( ï¼»4.23 ± 1.40ï¼½% vs ï¼»12.46 ± 3.07ï¼½%, P < 0.05), serum FSH (ï¼»1.76 ± 0.31ï¼½ vs ï¼»2.53 ± 0.28ï¼½ U/L, P < 0.05) and LH (ï¼»30.59 ± 2.14ï¼½ vs ï¼»39.72 ± 2.80ï¼½ U/L, P < 0.05), decreased levels of serum T (ï¼»5.33 ± 0.43ï¼½ vs ï¼»4.42 ± 0.38ï¼½ nmol/L, P < 0.05) and testicular SOD (ï¼»166.18 ± 3.74ï¼½ vs ï¼»113.23 ± 10.76ï¼½ U/ml, P < 0.05) and ATP (ï¼»41.23 ± 2.21ï¼½ vs ï¼»33.48 ± 2.74ï¼½ mol/L, P < 0.05), and elevated contents of MDA (ï¼»7.55 ± 0.93ï¼½ vs ï¼»10.59 ± 1.17ï¼½ nmol/ml, P < 0.05) and NO (ï¼»44.23±4.47ï¼½ vs ï¼»54.49 ± 3.13ï¼½ mol/L, P < 0.05). All the above parameters returned to normal after YTP intervention (DFI: ï¼»5.73 ± 2.46ï¼½%, FSH: ï¼»2.07 ± 0.45ï¼½ U/L, LH: ï¼»33.94 ± 4.44ï¼½ U/L, T: ï¼»4.96 ± 0.24ï¼½ nmol/L, SOD: ï¼»135.22 ± 7.26ï¼½ U/ml, ATP: ï¼»38.26 ± 2.14ï¼½ mol/L, MDA: ï¼»8.37 ± 1.29ï¼½ nmol/ml, NO: ï¼»48.36 ± 3.98ï¼½ mol/L), with statistically significant difference from those in the BaP-exposure group (all P < 0.05). CONCLUSION: Yishen Tongluo Prescription can repair BaP-induced sperm DNA damage in male rats, which may be attributed to its effects of suppressing oxidative damage.

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli.

The clerodane and ent-kaurane diterpenoids are two typical categories of diterpenoid natural products with complicated polycyclic carbon skeletons and significant pharmacological activities. Despite exciting advances in organic chemistry, access to these skeletons is still highly challenging. Using synthetic biology to engineer microbes provides an innovative alternative to bypass synthetic challenges. In this study, we constructed two truncated artificial pathways to efficiently produce terpentetriene and ent-kaurene, two representative clerodane and ent-kaurane diterpenes, in Escherichia coli. Both pathways depend on the exogenous addition of isoprenoid alcohol to reinforce the supply of IPP and DMAPP via two sequential phosphorylation reactions. Optimization of these constructs provided terpentetriene and ent-kaurene titers of 66 ± 4 mg/L and 113 ± 7 mg/L, respectively, in shake-flask fermentation. The truncated pathways to overproduce clerodane and ent-kaurane skeletons outlined here may provide an attractive route to prepare other privileged diterpene scaffolds.

Ultrahigh spectral resolution single passband microwave photonic filter.

Microwave photonic filters (MPFs) with only one ultra-narrow passband are able to provide high frequency selectivity and wide spectral range, and they are of great importance in radio-frequency (RF) signal processing. However, currently all MPFs are limited by trade-offs between key parameters such as spectral resolution and range, tunability, and stability. Here, we report the first demonstration of a single passband MPF with unprecedented performance including ultrahigh spectral resolution of 650 kHz, 0-40 GHz spectral range, and high stability of center frequency drifting within ±50 kHz. This record performance is accomplished by breaking the amplitude equality of a phase-modulated signal via a Brillouin dynamic grating (BDG) which has an ultra-narrow reflection spectrum of sub-MHz. The results point to new ways of creating high performance microwave photonic systems, such as satellite and mobile communications, radars, and remote-sensing systems.

Photonic generation of quadruple bandwidth dual-band dual-chirp microwave waveforms with immunity to power fading.

A photonic method to generate and transmit quadruple bandwidth dual-band dual-chirp microwave waveforms with immunity to fiber chromatic dispersion induced power fading is proposed and experimentally demonstrated, which is suitable for Doppler blind-speed elimination, small target detection, and multiband detection in multiband radar systems. A dual-polarization dual-parallel Mach-Zehnder modulator is utilized to realize carrier-suppressed harmonic single-sideband modulation of a radio frequency carrier and carrier-suppressed DSB modulation of a baseband single-chirped waveform at two orthogonal polarization states. After photoelectronic conversion, dual-band bandwidth-quadrupling dual-chirp waveforms are generated. Moreover, different from traditional DSB-based dual-chirp signal generation, the generated dual-chirp microwave waveforms can be transmitted over fiber without power fading, which is significant in dual-band radars for one to multiple base station transmissions.

Poly(ADP-Ribose) Polymerase Activity and Coronary Artery Disease in Type 2 Diabetes Mellitus: An Observational and Bidirectional Mendelian Randomization Study.

OBJECTIVE: Experimental evidence suggests a close link between PARP (poly[ADP-ribose] polymerase) activation and diabetic endothelial dysfunction. Here, we tested whether PARP activity in circulating leukocytes was associated with coronary artery disease (CAD) among patients with type 2 diabetes mellitus (T2DM). Approach and Results: We performed observational and bidirectional Mendelian randomization studies of 3149 Chinese individuals with T2DM who underwent coronary angiography, with leukocyte PARP activity, 16 tag single-nucleotide polymorphisms in PARP1 and PARP2, and 17 CAD risk single-nucleotide polymorphisms analyzed. Of 3149 participants, 1180 who further received percutaneous coronary intervention were prospectively followed for 1 year to track major adverse cardiovascular and cerebrovascular events. Overall, greater PARP activity was cross-sectionally associated with an odds ratio of 1.23 for obstructive CAD, and prospectively with a hazard ratio of 1.34 for 1-year major adverse cardiovascular and cerebrovascular events after percutaneous coronary intervention (both P<0.001). Using a genetic score of 5 screened single-nucleotide polymorphisms in PARP1 and PARP2 as the instrumental variable, genetically predicted elevation in PARP activity showed a causal association with obstructive CAD (odds ratio=1.35, P<0.001). In contrast, the genetic risk of CAD had no significant effect on PARP activity. Ex vivo and in vitro cultures of human monocytes showed that rs747657, as the lead single-nucleotide polymorphism strongly associated with PARP activity, caused the differential binding of transcription factor GATA2 (GATA-binding protein 2) to an intronic regulatory region in PARP1, thus modulating PARP1 expression and PARP activity. CONCLUSIONS: Greater PARP activity may have causal roles in the development of obstructive CAD among patients with diabetes mellitus.