A type I and type II chemical biology toolbox to overcome the hypoxic tumour microenvironment for photodynamic therapy.

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality employed for the treatment of various types of cancers, localized infections, and other diseases. Upon illumination, the photo-excited photosensitizer generates singlet oxygen and other reactive species, thereby inducing cytotoxicity in the target cells. The hypoxic tumour microenvironment (TME), however, poses a limitation on the supply of oxygen in tumour tissues. Moreover, under such conditions, tumour metastasis and drug resistance frequently occur, further compromising the efficacy of PDT in combating tumours. Traditionally, type I photosensitizers with lower oxygen consumption demonstrate significant potential in overcoming hypoxic environments and play a crucial role in determining the therapeutic efficacy of PDT because type I photosensitizers can generate highly cytotoxic free radicals. In comparison, type II photosensitizers exhibit high oxygen dependence. The rate of reactive oxygen species (ROS) generation in the type II process is significantly higher than that in the type I process. Thus, the efficiency and selectivity of PDT depend on the properties of the photosensitizer. Here, the recent development and application of type I and type II photosensitizers, mainly in the past year, are summarized. The design methods, electronic structures, photophysical properties, lipophilic properties, electric charge, and other molecular characteristics of these photosensitizers are discussed in detail. These modifications alter the microstructure of photosensitizers and directly impact the results of PDT. The main content of this paper will have a positive promoting and inspiring effect on the future development of PDT.

Karst fissures mitigate the negative effects of drought on plant growth and photosynthetic physiology.

Hard limestone substrates, which are extensively distributed, are believed to exacerbate drought and increase the difficulty of restoration in vulnerable karst regions. Fissures in such substrates may alleviate the negative effect of drought on plants, but the underlying mechanisms remain poorly understood. In a two-way factorial block design, the growth and photosynthesis of 2-year-old Phoebe zhennan seedlings were investigated in two water availabilities (high versus low) and three stimulated fissure habitat groups (soil, soil-filled fissure and non-soil-filled fissure). Moreover, the fissure treatments included both small and big fissures. Compared to the soil group, the non-soil-filled fissure group had decreased the total biomass, root biomass, total root length, and the root length of fine roots in the soil layer at both water availabilities, but increased net photosynthetic rate (Pn) and retained stable water use efficiency (WUE) at low water availability. However, there were no significant differences between the soil-filled fissure group and soil group in the biomass accumulation and allocation as well as Pn. Nevertheless, the SF group decreased the root distribution in total and in the soil layer, and also increased WUE at low water availability. Across all treatments, fissure size had no effect on plant growth or photosynthesis. Karst fissures filled with soil can alleviate drought impacts on plant root growth, which involves adjusting root distribution strategies and increasing water use efficiency. These results suggest that rock fissures can be involved in long-term plant responses to drought stress and vegetation restoration in rocky mountain environments under global climate change.

NADPH oxidase 2 mediates cardiac sympathetic denervation and myocyte autophagy, resulting in cardiac atrophy and dysfunction in doxorubicin-induced cardiomyopathy.

Doxorubicin has been used extensively as a potent anticancer agent, but its clinical use is limited by its cardiotoxicity. However, the underlying mechanisms remain to be fully elucidated. In this study, we tested whether NADPH oxidase 2 (Nox2) mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, resulting in cardiac atrophy and dysfunction in doxorubicin-induced heart failure. Nox2 knockout (KO) and wild-type (WT) mice were randomly assigned to receive a single injection of doxorubicin (15 mg/kg, i.p.) or saline. WT doxorubicin mice exhibited the decreases in survival rate, left ventricular (LV) wall thickness and LV fractional shortening and the increase in the lung wet-to-dry weight ratio 1 week after the injections. These alterations were attenuated in Nox2 KO doxorubicin mice. In WT doxorubicin mice, myocardial oxidative stress was increased, myocardial noradrenergic nerve fibers were reduced, myocardial expression of PGP9.5, GAP43, tyrosine hydroxylase and norepinephrine transporter was decreased, and these changes were prevented in Nox2 KO doxorubicin mice. Myocyte autophagy was increased and myocyte size was decreased in WT doxorubicin mice, but not in Nox2 KO doxorubicin mice. Nox2 mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy-both of which contribute to cardiac atrophy and failure after doxorubicin treatment.

High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1-AMPK-ACC Pathway.

BACKGROUND: Nicotinamide mononucleotide (NMN) is the physiological circulating NAD precursor thought to elevate the cellular level of NAD+ and to ameliorate various age-related diseases. An inseparable link exists between aging and tumorigenesis, especially involving aberrant energetic metabolism and cell fate regulation in cancer cells. However, few studies have directly investigated the effects of NMN on another major ageing-related disease: tumors. METHODS: We conducted a series of cell and mouse models to evaluate the anti-tumor effect of high-dose NMN. Transmission electron microscopy and a Mito-FerroGreen-labeled immunofluorescence assay (Fe2+) were utilized to demonstrate ferroptosis. The metabolites of NAM were detected via ELISA. The expression of the proteins involved in the SIRT1-AMPK-ACC signaling were detected using a Western blot assay. RESULTS: The results showed that high-dose NMN inhibits lung adenocarcinoma growth in vitro and in vivo. Excess NAM is produced through the metabolism of high-dose NMN, whereas the overexpression of NAMPT significantly decreases intracellular NAM content, which, in turn, boosts cell proliferation. Mechanistically, high-dose NMN promotes ferroptosis through NAM-mediated SIRT1-AMPK-ACC signaling. CONCLUSIONS: This study highlights the tumor influence of NMN at high doses in the manipulation of cancer cell metabolism, providing a new perspective on clinical therapy in patients with lung adenocarcinoma.

Integrated analysis of competitive endogenous RNA networks in elder patients with non-small cell lung cancer.

BACKGROUND: Lung cancer is one of the most prevalent cancers and the leading cause of cancer-related deaths worldwide; non-small cell lung cancer (NSCLC) comprises approximately 80% of all lung cancer cases. This study aimed to construct a competing endogenous RNA (ceRNA) network and identify prognostic signatures in elderly patients with NSCLC. METHODS: We extracted data from elderly patients with NSCLC from The Cancer Genome Atlas and identified differentially expressed (DE) messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to investigate the functions of DEmRNAs. The interactions between RNAs were predicted using starBase, TargetScan, miRTarBase, and miRanda. Cytoscape version 3.0 was used to construct and visualize the lncRNA-miRNA-mRNA ceRNA network. The association between the expression levels of DERNAs in the constructed ceRNA network and overall survival was determined using the survival package in R software. Furthermore, another Gene Expression Omnibus cohort was studied to externally validate the ceRNA network. RESULTS: In total, 2865 DEmRNAs, 62 DEmiRNAs, and 131 DElncRNAs were identified. Dysregulated mRNAs are enriched in cancer-related processes and pathways. A ceRNA network was constructed using 38 miRNAs, 61 lncRNAs, and 164 mRNAs. Of these, 3 lncRNAs, 3 miRNAs, and 16 mRNAs were closely related to overall survival. The MIR99AHG-hsa-miR-31-5p-PRKCE axis has been identified as a potential ceRNA network involved in the development of NSCLC in elderly individuals. External validation of the MIR99AHG-hsa-miR-31-5p-PRKCE axis in the GSE19804 cohort showed that PRKCE was downregulated and that MIR99AHG was upregulated in the tumor tissues of elderly patients with NSCLC compared with normal lung tissues. CONCLUSIONS: This study provides novel insights into the lncRNA-miRNA-mRNA ceRNA network and reveals potential biomarkers for the diagnosis and prognosis of elderly patients with NSCLC.

Enhanced oxidative stress mediates pathological autophagy and necroptosis in cardiac myocytes in pressure overload induced heart failure in rats.

In cardiac myocytes in vitro, hydrogen peroxide induces autophagic cell death and necroptosis. Oxidative stress, myocyte autophagy and necroptosis coexist in heart failure (HF). In this study, we tested the hypothesis that excessive oxidative stress mediates pathological autophagy and necroptosis in myocytes in pressure overload-induced HF. HF was produced by chronic pressure overload induced by abdominal aortic constriction (AAC) in rats. Rats with AAC or sham operation were randomised to orally receive an antioxidant N-acetylcysteine (NAC) or placebo for 4 weeks. Echocardiography was performed for the assessments of left ventricular (LV) structure and function. AAC rats exhibited decreased LV fractional shortening (FS) at 4 weeks after surgery. NAC treatment attenuated decreased LV FS in AAC rats. In AAC rats, myocardial level of 8-hydroxydeoxyguanosine assessed by immunohistochemical staining, indicative of oxidative stress, was increased, LC3 II protein, a marker of autophagy, Beclin1 protein and Atg4b, Atg5, Atg7 and Atg12 mRNA expression were markedly increased, RIP1, RIP3 and MLKL expression, indicative of necroptosis, was increased, and all of the alterations in AAC rats were prevented by the NAC treatment. NAC treatment also attenuated myocyte cross-sectional area and myocardial fibrosis in AAC rats. In conclusion, NAC treatment prevented the increases in oxidative stress, myocyte autophagy and necroptosis and the decrease in LV systolic function in pressure overload-induced HF. These findings suggest that enhanced oxidative stress mediates pathological autophagy and necroptosis in myocytes, leading to LV systolic dysfunction, and antioxidants may be of value to prevent HF through the inhibition of excessive autophagy and necroptosis.

Sphingosine-1-phosphate induces myocyte autophagy after myocardial infarction through mTOR inhibition.

Sphingosine-1-phosphate (S1P)/S1P receptor 1 signaling exerts cardioprotective effects including inhibition of myocyte apoptosis. However, little is known about the effect of S1P treatment on myocyte autophagy after myocardial infarction (MI). In the present study, we tested the hypothesis that S1P induces myocyte autophagy through inhibition of the mammalian target of rapamycin (mTOR), leading to improvement of left ventricular (LV) function after MI. Sprague-Dawley rats underwent MI or sham operation. The animals were randomized to receive S1P (50 µg/kg/day, i.p.) or placebo for one week. H9C2 cardiomyocytes cultured in serum- and glucose-deficient medium were treated with or without S1P for 3 h. MI rats exhibited an increase in LV end-diastolic dimension (EDD) and decreases in LV fractional shortening (FS) and the maximal rate of LV pressure rise (+dP/dt). S1P treatment attenuated the increase in LV EDD and decreases in LV FS and +dP/dt. In the MI placebo group, the LC3 II/I ratio, a marker of autophagy, was increased, and increased further by S1P treatment. S1P also enhanced the autophagy-related proteins Atg4b and Atg5 after MI. Similarly, in cultured cardiomyocytes, autophagy was increased under glucose and serum deprivation, and increased further by S1P treatment. The effect of S1P on myocyte autophagy was associated with mTOR inhibition after MI or in cultured cardiomyocytes under glucose and serum deprivation. S1P treatment prevents LV remodeling, enhances myocyte autophagy and inhibits mTOR activity after MI. These findings suggest that S1P treatment induces myocyte autophagy through mTOR inhibition, leading to the attenuation of LV dysfunction after MI.

Heralded entanglement distribution between two absorptive quantum memories.

Owing to the inevitable loss in communication channels, the distance of entanglement distribution is limited to approximately 100 kilometres on the ground1. Quantum repeaters can circumvent this problem by using quantum memory and entanglement swapping2. As the elementary link of a quantum repeater, the heralded distribution of two-party entanglement between two remote nodes has only been realized with built-in-type quantum memories3-9. These schemes suffer from the trade-off between multiplexing capacity and deterministic properties and hence hinder the development of efficient quantum repeaters. Quantum repeaters based on absorptive quantum memories can overcome such limitations because they separate the quantum memories and the quantum light sources. Here we present an experimental demonstration of heralded entanglement between absorptive quantum memories. We build two nodes separated by 3.5 metres, each containing a polarization-entangled photon-pair source and a solid-state quantum memory with bandwidth up to 1 gigahertz. A joint Bell-state measurement in the middle station heralds the successful distribution of maximally entangled states between the two quantum memories with a fidelity of 80.4 ± 2.2 per cent (±1 standard deviation). The quantum nodes and channels demonstrated here can serve as an elementary link of a quantum repeater. Moreover, the wideband absorptive quantum memories used in the nodes are compatible with deterministic entanglement sources and can simultaneously support multiplexing, which paves the way for the construction of practical solid-state quantum repeaters and high-speed quantum networks.

Apocynin prevents reduced myocardial nerve growth factor, contributing to amelioration of myocardial apoptosis and failure.

Reduced nerve growth factor (NGF) is associated with cardiac sympathetic nerve denervation in heart failure (HF) which is characterized by increased oxidative stress. Apocynin is considered an antioxidant agent which inhibits NADPH oxidase activity and improves reactive oxygen species scavenging. However, it is unclear whether apocynin prevents reduced myocardial NGF, leading to improvement of cardiac function in HF. In this study, we tested the hypothesis that apocynin prevents reduced myocardial NGF, contributing to amelioration of myocardial apoptosis and failure. Rabbits with myocardial infarction (MI) or sham operation were randomly assigned to receive apocynin or placebo for 4 weeks. MI rabbits exhibited left ventricular (LV) dysfunction, and elevation in oxidative stress, as evidenced by a decreased reduced-to-oxidized glutathione ratio and an increased 4-hydroxynonenal expression, and reduction in NGF and NGF receptor tyrosine kinase A (TrKA) expression in the remote non-infarcted myocardium. Apocynin treatment ameliorated LV dysfunction, reduced oxidative stress, prevented decreases in NGF and TrKA expression and reduced cardiomyocyte apoptosis after MI. In cultured H9C2 cardiomyocytes, hypoxia or hydrogen peroxide decreased NGF expression, and apocynin normalized hypoxia-induced reduction of NGF. Recombinant NGF attenuated hypoxia-induced apoptosis. Apocynin prevented hypoxia-induced apoptosis, and the suppressive effect of apocynin on apoptosis was abolished by NGF receptor TrKA inhibitor K252a. We concluded that apocynin prevented reduced myocardial NGF, leading to attenuation of cardiomyocyte apoptosis and LV remodelling and dysfunction in HF after MI. These findings suggest that strategies to prevent NGF reduction by inhibition of oxidative stress may be of value in amelioration of LV dysfunction in HF.

QKI-5 regulates the alternative splicing of cytoskeletal gene ADD3 in lung cancer.

Accumulating evidence indicates that the alternative splicing program undergoes extensive changes during cancer development and progression. The RNA-binding protein QKI-5 is frequently downregulated and exhibits anti-tumor activity in lung cancer. Howeve-r, little is known about the functional targets and regulatory mechanism of QKI-5. Here, we report that upregulation of exon 14 inclusion of cytoskeletal gene Adducin 3 (ADD3) significantly correlates with a poor prognosis in lung cancer. QKI-5 inhibits cell proliferation and migration in part through suppressing the splicing of ADD3 exon 14. Through genome-wide mapping of QKI-5 binding sites in vivo at nucleotide resolution by iCLIP-seq analysis, we found that QKI-5 regulates alternative splicing of its target mRNAs in a binding position-dependent manner. By binding to multiple sites in an upstream intron region, QKI-5 represses the splicing of ADD3 exon 14. We also identified several QKI mutations in tumors, which cause dysregulation of the splicing of QKI targets ADD3 and NUMB. Taken together, our results reveal that QKI-mediated alternative splicing of ADD3 is a key lung cancer-associated splicing event, which underlies in part the tumor suppressor function of QKI.

Transplantation of neural stem cells preconditioned with high­mobility group box 1 facilitates functional recovery after spinal cord injury in rats.

Spinal cord injury (SCI) is a devastating disorder that often results in temporary and/or permanent functional impairment below the injured level. To date, few satisfactory therapeutic strategies are available to treat SCI. Hence, exploring novel strategies for SCI is an essential public health concern. Cell transplantation therapy, which is associated with neuroprotection, immunomodulation, axon regeneration, neuronal relay formation and myelin regeneration, provides a promising therapeutic strategy for SCI. The neuronal stem cell (NSC) preconditioning method is an emerging approach, which facilitates NSC survival and neuronal differentiation after implantation. The aim of the present study was to develop a feasible candidate for cell­based therapy following SCI in rats and to investigate the role of high mobility group box­1 (HMGB1) in NSC activation. The results of the present study showed that transplantation of NSCs, preconditioned with 1 ng/ml HMGB1, facilitated functional improvement of injured spinal cords, as indicated by Basso, Beattie and Bresnahan mean scores, mechanical hypersensitivity and cold stimulation. Meanwhile, the histological examination of hematoxylin and eosin staining indicated that engraftment of HMGB1­preconditioned NSCs resulted in decreased atrophy of the injured spinal cord. Meanwhile, the transplantation of HMGB1­preconditioned NSCs resulted in an increased number of functional Nissl bodies in neurons, as detected by Nissl staining, and an increase in the number of ßIII­tubulin+ cells in the epicenter of injured spinal cords in rats with SCI. In addition, the results also demonstrated that 1 ng/ml HMGB1 promoted the differentiation of NSCs into neurons, and that the ERK signaling pathway played an important role in this process. In conclusion, the present data indicated that the preconditioning strategy with 1 ng/ml HMGB1 may present a feasible candidate for cell­based therapy following SCI in rats, which may enlarge the scope of HMGB1 in NSC activation.

The NADPH oxidase inhibitor apocynin improves cardiac sympathetic nerve terminal innervation and function in heart failure.

NEW FINDINGS: What is the central question of this study? Does NADPH oxidase activation mediate cardiac sympathetic nerve denervation and dysfunction in heart failure. What is the main findings and its importance? Cardiac sympathetic nerve terminal density and function were reduced in heart failure after myocardial infarction in rabbits. The NADPH oxidase inhibitor apocynin prevented the reduction in cardiac sympathetic nerve terminal density and function in heart failure. This suggest that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in heart failure. NADPH oxidase may be a potential therapeutic target for cardiac sympathetic denervation and dysfunction in heart failure. ABSTRACT: Congestive heart failure (CHF) is characterized by cardiac sympathetic nerve terminal abnormalities, as evidenced by decreased noradrenaline transporter (NAT) density and cardiac catecholaminergic and tyrosine hydroxylase (TH) profiles. These alterations are associated with increased reactive oxygen species (ROS). NADPH oxidase is a major source of ROS in CHF. In this study, we tested the hypothesis that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in CHF. CHF was produced by myocardial infarction (MI) in rabbits. Rabbits with MI or a sham operation were randomized to orally receive an NADPH oxidase inhibitor, apocynin (6 mg kg-1  day-1 ), or placebo for 30 days. MI rabbits exhibited left ventricular dilatation, systolic dysfunction, and increases in NADPH oxidase activity and 4-hydroxynonenal expression in the remote non-infarcted myocardium, all of which were prevented by treatment with apocynin. Cardiac catecholaminergic histofluorescence profiles and immunostained TH and PGP9.5 expression were decreased, and the decreases were ameliorated by apocynin treatment. NAT, TH and PGP9.5 protein and mRNA expression were reduced and the reduction was mitigated by apocynin treatment. The effects of apocynin were confirmed by utilizing the NADPH oxidase inhibitor diphenyleneiodonium in a separate experiment. In conclusion, the NADPH oxidase inhibitor apocynin attenuated increased myocardial oxidative stress and decreased cardiac sympathetic nerve terminals in CHF after MI in rabbits. These findings suggest that the activation of NADPH oxidase mediates cardiac sympathetic nerve terminal abnormalities in CHF, and the inhibition of NADPH oxidase may be beneficial for the treatment of heart failure.

Cord blood leptin DNA methylation levels are associated with macrosomia during normal pregnancy.

BACKGROUND: We previously demonstrated an association between placental leptin (LEP) methylation levels and macrosomia without gestational diabetes mellitus (non-GDM). This study further explored the association between LEP methylation in cord blood and non-GDM macrosomia. METHOD: We carried out a case-control study of 61 newborns with macrosomia (birth weight ≥4000 g) and 69 newborns with normal birth weight (2500-3999 g). Methylation in the LEP promoter region was mapped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: Average cord blood LEP methylation levels were lower in macrosomia newborns than in control newborns (P < 0.001). Eleven CpG sites were associated with macrosomia. Multivariate logistic regression revealed that low LEP methylation levels [adjusted odds ratio (AOR) = 2.84, 95% confidence interval (CI): 1.72-4.17], high pre-pregnancy body mass index (AOR = 7.44, 95% CI: 1.99-27.75), long gestational age (AOR = 3.18, 95% CI: 1.74-5.79), high cord blood LEP concentration (AOR = 2.25, 95% CI: 1.34-3.77), and male newborn gender (AOR = 3.91, 95% CI: 1.31-11.69) significantly increased the risk of macrosomia. CONCLUSIONS: Lower cord blood LEP methylation levels and certain maternal and fetal factors are associated with non-GDM macrosomia.

Genetic variations in miR-125 family and the survival of non-small cell lung cancer in Chinese population.

To investigate the associations between the functional single nucleotide polymorphisms (SNPs) in the miR-125 family and the survival of non-small cell lung cancer (NSCLC) patients, we systematically selected six functional SNPs located in three pre-miRNAs (miR-125a, miR-125b-1, miR-125b-2). Cox proportional hazard regression analyses were conducted to estimate the crude and adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs). Reporter gene luciferase assay was performed to examine the relationship between the SNPs and transcriptive activity of the miRNAs. The expression of miRNAs in different cells was detected using quantitative real-time PCR assay. We found that rs2241490 (upstream of miR-125b-1, G > A, adjusted HR = 1.24, 95%CI = 1.05-1.48, P = 0.014, in dominant model; adjusted HR = 1.18, 95%CI = 1.03-1.35, P = 0.014, in additive model), rs512932 (upstream of miR-125b-1, A > G, dominant model: adjusted HR = 1.25, 95%CI = 1.05-1.48, P = 0.013) and rs8111742 (upstream of miR-125a, G > A, dominant model: adjusted HR = 0.84, 95%CI = 0.71-1.00, P = 0.047) were associated with the prognosis of 1001 Chinese NSCLC patients. The combined analysis of the three SNPs related the number of risk alleles (rs2241490-A, rs512932-G and rs8111742-G) to death risk of NSCLC in a locus-dosage mode (P for trend <0.001). Furthermore, luciferase reporter gene assay showed significantly higher levels of luciferase activity with rs512932 variant G than that with A allele in 293T, SPC-A1 and A549 cell lines. Besides, miR-125b was highly expressed in lung cancer cells than the normal lung cell. Our study indicated that genetic variations in miR-125 family were implicated in the survival of NSCLC patients. Larger population-based and functional studies are needed to verify these findings.

Acacetin protects against cerebral ischemia-reperfusion injury via the NLRP3 signaling pathway.

Acacetin (5,7-dihydroxy-4'-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3 (NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin (acacetin group) or an equal volume of saline (0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1 (Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1ß and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1ß, and interleukin-1ß were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protective effect on cerebral ischemia-reperfusion injury, and its mechanism of action is associated with inhibition of microglia-mediated inflammation and the NLRP3 signaling pathway.

Storage of telecom-C-band heralded single photons with orbital-angular-momentum encoding in a crystal.

A memory-based quantum repeater architecture provides a solution to distribute quantum information to an arbitrary long distance. Practical quantum repeaters are likely to be built in optical-fiber networks which take advantage of the low-loss transmission between quantum memory nodes. Most quantum memory platforms have characteristic atomic transitions away from the telecommunication band. A nondegenerate photon pair source is therefore useful for connection of a quantum memory to optical fibers. Here, we report a high-brightness narrowband photon-pair source which is compatible with a rare-earth-ion-doped crystal Pr3+:Y2SiO5. The photon-pair source is generated through a cavity-enhanced spontaneous parametric down-conversion process with the signal photon at 606 nm and the idler photon at 1540 nm. Moreover, using the telecom C-band idler photons for heralding, we demonstrate the reversible transfer of orbital-angular-momentum qubit between the signal photon and the quantum memory based on Pr3+:Y2SiO5.

Enzymatic Synthesis of Unnatural Ginsenosides Using a Promiscuous UDP-Glucosyltransferase from Bacillus subtilis.

Glycosylation, which is catalyzed by UDP-glycosyltransferases (UGTs), is an important biological modification for the structural and functional diversity of ginsenosides. In this study, the promiscuous UGT109A1 from Bacillus subtilis was used to synthesize unnatural ginsenosides from natural ginsenosides. UGT109A1 was heterologously expressed in Escherichia coli and then purified by Ni-NTA affinity chromatography. Ginsenosides Re, Rf, Rh1, and R1 were selected as the substrates to produce the corresponding derivatives by the recombinant UGT109A1. The results showed that UGT109A1 could transfer a glucosyl moiety to C3-OH of ginsenosides Re and R1, and C3-OH and C12-OH of ginsenosides Rf and Rh1, respectively, to produce unnatural ginsenosides 3,20-di-O-ß-d-glucopyranosyl-6-O-[α-l-rhamnopyrano-(1→2)-ß-d-glucopyranosyl]-dammar-24-ene-3ß,6α,12ß,20S-tetraol (1), 3,20-di-O-ß-d-glucopyranosyl-6-O-[ß-d-xylopyranosyl-(1→2)-ß-d-glucopyranosyl]-dammar-24-ene-3ß,6α,12ß,20S-tetraol (6), 3-O-ß-d-glucopyranosyl-6-O-[ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranosyl]-dammar-24-ene-3ß,6α,12ß,20S-tetraol (3), 3,12-di-O-ß-d-glucopyranosyl-6-O-[ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranosyl]-dammar-24-ene-3ß,6α,12ß,20S-tetraol (2), 3,6-di-O-ß-d-glucopyranosyl-dammar-24-ene-3ß,6α,12ß,20S-tetraol (5), and 3,6,12-tri-O-ß-d-glucopyranosyl-dammar-24-ene-3ß,6α,12ß,20S-tetraol (4). Among the above products, 1, 2, 3, and 6 are new compounds. The maximal activity of UGT109A1 was achieved at the temperature of 40 °C, in the pH range of 8.0⁻10.0. The activity of UGT109A1 was considerably enhanced by Mg2+, Mn2+, and Ca2+, but was obviously reduced by Cu2+, Co2+, and Zn2+. The study demonstrated that UGT109A1 was effective in producing a series of unnatural ginsenosides through enzymatic reactions, which could pave a way to generate promising leads for new drug discovery.

Multiplexed storage and real-time manipulation based on a multiple degree-of-freedom quantum memory.

The faithful storage and coherent manipulation of quantum states with matter-systems would enable the realization of large-scale quantum networks based on quantum repeaters. To achieve useful communication rates, highly multimode quantum memories are required to construct a multiplexed quantum repeater. Here, we present a demonstration of on-demand storage of orbital-angular-momentum states with weak coherent pulses at the single-photon-level in a rare-earth-ion-doped crystal. Through the combination of this spatial degree-of-freedom (DOF) with temporal and spectral degrees of freedom, we create a multiple-DOF memory with high multimode capacity. This device can serve as a quantum mode converter with high fidelity, which is a fundamental requirement for the construction of a multiplexed quantum repeater. This device further enables essentially arbitrary spectral and temporal manipulations of spatial-qutrit-encoded photonic pulses in real time. Therefore, the developed quantum memory can serve as a building block for scalable photonic quantum information processing architectures.

Progress on the Studies of the Key Enzymes of Ginsenoside Biosynthesis.

As the main bioactive constituents of Panax species, ginsenosides possess a wide range of notable medicinal effects such as anti-cancer, anti-oxidative, antiaging, anti-inflammatory, anti-apoptotic and neuroprotective activities. However, the increasing medical demand for ginsenosides cannot be met due to the limited resource of Panax species and the low contents of ginsenosides. In recent years, biotechnological approaches have been utilized to increase the production of ginsenosides by regulating the key enzymes of ginsenoside biosynthesis, while synthetic biology strategies have been adopted to produce ginsenosides by introducing these genes into yeast. This review summarizes the latest research progress on cloning and functional characterization of key genes dedicated to the production of ginsenosides, which not only lays the foundation for their application in plant engineering, but also provides the building blocks for the production of ginsenosides by synthetic biology.

Expression of Clara cell 10-kDa protein and trefoil factor family 1 in patients with chronic rhinosinusitis and nasal polyps.

The current study measured the expression of Clara cell 10-kDa protein (CC10) and trefoil factor family 1 (TFF1) in the sinus mucosa of patients exhibiting chronic rhinosinusitis (CRS) and nasal polyps (NP). CC10 and TFF1 expression in the sinus mucosa of the control group and patients with CRS and NP was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry. The correlation between CC10 and TFF1 expression was further analyzed using Spearman's correlation analysis. The expression of TFF1 was significantly increased in the sinus mucosa of patients with CRS and NP, whereas CC10 expression was significantly decreased compared with controls. Spearman's correlation analysis identified a negative correlation between CC10 and TFF1 expression in the sinus mucosa of patients with CRS and NP. The results of immunohistochemistry and RT-qPCR were consistent with each other. Hematoxylin and eosin staining revealed notable lesions in the mucous membranes, goblet cells and cilia of sinus mucosa samples from patients with CRS and NP. The negative correlation between CC10 and TFF1 expression during the progression of CRS and NP suggest that CC10 and TFF1 may serve important roles in its pathogenesis.