Relationships between quantitative retinal microvascular characteristics and cognitive function based on automated artificial intelligence measurements.

Introduction: The purpose of this study is to assess the relationship between retinal vascular characteristics and cognitive function using artificial intelligence techniques to obtain fully automated quantitative measurements of retinal vascular morphological parameters. Methods: A deep learning-based semantic segmentation network ResNet101-UNet was used to construct a vascular segmentation model for fully automated quantitative measurement of retinal vascular parameters on fundus photographs. Retinal photographs centered on the optic disc of 3107 participants (aged 50-93 years) from the Beijing Eye Study 2011, a population-based cross-sectional study, were analyzed. The main parameters included the retinal vascular branching angle, vascular fractal dimension, vascular diameter, vascular tortuosity, and vascular density. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Results: The results showed that the mean MMSE score was 26.34 ± 3.64 (median: 27; range: 2-30). Among the participants, 414 (13.3%) were classified as having cognitive impairment (MMSE score < 24), 296 (9.5%) were classified as mild cognitive impairment (MMSE: 19-23), 98 (3.2%) were classified as moderate cognitive impairment (MMSE: 10-18), and 20 (0.6%) were classified as severe cognitive impairment (MMSE < 10). Compared with the normal cognitive function group, the retinal venular average diameter was significantly larger (p = 0.013), and the retinal vascular fractal dimension and vascular density were significantly smaller (both p < 0.001) in the mild cognitive impairment group. The retinal arteriole-to-venular ratio (p = 0.003) and vascular fractal dimension (p = 0.033) were significantly decreased in the severe cognitive impairment group compared to the mild cognitive impairment group. In the multivariate analysis, better cognition (i.e., higher MMSE score) was significantly associated with higher retinal vascular fractal dimension (b = 0.134, p = 0.043) and higher retinal vascular density (b = 0.152, p = 0.023) after adjustment for age, best corrected visual acuity (BCVA) (logMAR) and education level. Discussion: In conclusion, our findings derived from an artificial intelligence-based fully automated retinal vascular parameter measurement method showed that several retinal vascular morphological parameters were correlated with cognitive impairment. The decrease in retinal vascular fractal dimension and decreased vascular density may serve as candidate biomarkers for early identification of cognitive impairment. The observed reduction in the retinal arteriole-to-venular ratio occurs in the late stages of cognitive impairment.

[Analysis of regularity of acupoint selection and compatibility of acupuncture in the treatment of postpartum depression].

OBJECTIVE: To analyze the regularity of acupoint selection, and compatibility of acupuncture in the treatment of postpartum depression. METHODS: Articles both in English and Chinese published in databases of CNKI, Wanfang, VIP, Chinese biomedical literature database (SinoMed), PubMed, Embase, Cochrane Library from the inception to February of 2021 were retrieved by using key words "acupuncture" or "moxibustion" or "electroacupuncture" or "acupoint application" or " acupoint burying" or "acupoint injection" or "fire needling" and "postpartum depression" or "puerperal depression". The frequencies of selected acupoints and meridians were counted by using data mining technology, and the points with high frequency were analyzed by cluster analysis. RESULTS: A total of 42 articles were included, containing 65 prescriptions and 80 points. The highest frequency of acupoints were Baihui (GV20), Sanyinjiao (SP6), Taichong (LR3), Neiguan (PC6), Zusanli (ST36) and Shenmen (HT7). The most frequently selected channels were Bladder Meridian, Governor Meridian and Liver Meridian. Among the specific points, intersection points, five-shu points, yuan-source points and back-shu points were widely used. Through cluster analysis, four effective cluster groups ï¼»GV20-SP6, LR3-PC6, Xinshu (BL15)-Ganshu (BL18)-Pishu (BL20)-Guanyuan (CV4), Hegu (LI4)-Qihai(CV6)-Qimen (LR14)ï¼½ were obtained, as well as a group of main points (GV20-SP6-LR3-PC6-ST36-HT7) and two groups of matching points ï¼»LI4-CV6-LR14 and BL15-BL18-BL20-CV4-Sishencong (EX-HN1)ï¼½. CONCLUSION: Through data mining technology, this paper summarized the acupoint selection and compatibility law of acupuncture in the treatment of postpartum depression, focusing on regulating Qi, blood and spirit, so as to provide reference for guiding the clinical acupuncture treatment and scientific research of postpartum depression.

Achieving ultrahigh electrochemical performance by surface design and nanoconfined water manipulation.

The effects of nanoconfined water and the charge storage mechanism are crucial to achieving the ultrahigh electrochemical performance of two-dimensional transition metal carbides (MXenes). We propose a facile method to manipulate nanoconfined water through surface chemistry modification. By introducing oxygen and nitrogen surface groups, more active sites were created for Ti3C2 MXene, and the interlayer spacing was significantly increased by accommodating three-layer nanoconfined water. Exceptionally high capacitance of 550 F g-1 (2000 F cm-3) was obtained with outstanding high-rate performance. The atomic scale elucidation of the layer-dependent properties of nanoconfined water and pseudocapacitive charge storage was deeply probed through a combination of 'computational and experimental microscopy'. We believe that an understanding of, and a manipulation strategy for, nanoconfined water will shed light on ways to improve the electrochemical performance of MXene and other two-dimensional materials.

FoxO3 restricts liver regeneration by suppressing the proliferation of hepatocytes.

Upon injury, the liver is capable of substantial regeneration from the original tissue until an appropriate functional size. The underlying mechanisms controlling the liver regeneration processes are not well elucidated. Previous studies have proposed that the transcription factor FoxO3 is involved in various liver diseases, but its exact role in the regulation of liver regeneration remains largely unclear. To directly test the detailed role of FoxO3 in liver regeneration, both a constitutive Albumin-Cre driver line and adeno-associated virus serotype 8 (AAV8)-Tbg-Cre (AAV-Cre)-injected adult FoxO3fl/fl mice were subjected to 70% partial hepatectomy (PH). Our data demonstrate that FoxO3 deletion accelerates liver regeneration primarily by limiting polyploidization and promoting the proliferation of hepatocytes during liver regeneration. RNA-seq analysis indicates that FoxO3 deficiency greatly alters the expression of gene sets associated with cell proliferation and apoptosis during liver regeneration. Chromatin immunoprecipitation-PCR (ChIP-PCR) and luciferase reporter assays reveal that FoxO3 promotes the expression of Nox4 but suppresses the expression of Nr4a1 in hepatocytes. AAV8 virus-mediated overexpression of Nox4 and knockdown of Nr4a1 significantly suppressed hepatocyte proliferation and liver regeneration in FoxO3-deficient mice. We demonstrate that FoxO3 negatively controls hepatocyte proliferation through Nox4 upregulation and Nr4a1 downregulation, thereby ensuring appropriate functional regeneration of the liver. Our findings provide novel mechanistic insight into the therapeutic mechanisms of FoxO3 in liver damage and repair.

Activating lattice oxygen in NiFe-based (oxy)hydroxide for water electrolysis.

Transition metal oxides or (oxy)hydroxides have been intensively investigated as promising electrocatalysts for energy and environmental applications. Oxygen in the lattice was reported recently to actively participate in surface reactions. Herein, we report a sacrificial template-directed approach to synthesize Mo-doped NiFe (oxy)hydroxide with modulated oxygen activity as an enhanced electrocatalyst towards oxygen evolution reaction (OER). The obtained MoNiFe (oxy)hydroxide displays a high mass activity of 1910 A/gmetal at the overpotential of 300 mV. The combination of density functional theory calculations and advanced spectroscopy techniques suggests that the Mo dopant upshifts the O 2p band and weakens the metal-oxygen bond of NiFe (oxy)hydroxide, facilitating oxygen vacancy formation and shifting the reaction pathway for OER. Our results provide critical insights into the role of lattice oxygen in determining the activity of (oxy)hydroxides and demonstrate tuning oxygen activity as a promising approach for constructing highly active electrocatalysts.

Enhancing the Intrinsic Activity and Stability of Perovskite Cobaltite at Elevated Temperature Through Surface Stress.

Perovskite-based oxides attract great attention as catalysts for energy and environmental devices. Nanostructure engineering is demonstrated as an effective approach for improving the catalytic activity of the materials. The mechanism for the enhancement, nevertheless, is still not fully understood. In this study, it is demonstrated that compressive strain can be introduced into freestanding perovskite cobaltite La0.8 Sr0.2 CoO3- δ (LSC) nanofibers with sufficient small size. Crystal structure analysis suggests that the LSC fiber is characterized by compressive strain along the ab plane and less distorted CoO6 octahedron compared to the bulk powder sample. Accompanied by such structural changes, the nanofiber shows significantly higher oxygen reduction reaction (ORR) activity and better stability at elevated temperature, which is attributed to the higher oxygen vacancy concentration and suppressed Sr segregation in the LSC nanofibers. First-principle calculations further suggest that the compressive strain in LSC nanofibers effectively shortens the distance between the Co 3d and O 2p band center and lowers the oxygen vacancy formation energy. The results clarify the critical role of surface stress in determining the intrinsic activity of perovskite oxide nanomaterials. The results of this work can help guide the design of highly active and durable perovskite catalysts via nanostructure engineering.

Geniposide protects pulmonary arterial smooth muscle cells from lipopolysaccharide-induced injury via α7nAchR-mediated TLR-4/MyD88 signaling.

Geniposide is a bioactive iridoid glucoside derived from Gardenia jasminoides that has proven anti-inflammatory effects against acute lung injury. The aim of this study was to determine whether geniposide could protect pulmonary arterial smooth muscle cells (PASMCs) from lipopolysaccharide (LPS)-induced injury and to explore the participation of α7 nicotinic acetylcholine receptor (α7nAChR), which was previously reported to suppress pro-inflammatory cytokine production in LPS-stimulated macrophages. In the present study, rat PASMCs were isolated and stimulated using LPS. The effect of geniposide on LPS-induced PASMC injury was then explored. Geniposide exerted anti-apoptotic and anti-inflammatory effects on LPS-treated PASMCs, as demonstrated by the downregulation of pro-apoptotic proteins and pro-inflammatory cytokines, respectively. Furthermore, the α7nAChR agonist PNU282987 accentuated the protective effect of geniposide against LPS-induced injury in PASMCs by inhibiting toll-like receptor-4/myeloid differentiation primary response 88 (TLR-4/MyD88) signaling and downregulating nuclear factor (NF)-κB expression. Conversely, methyllycaconitine, an inhibitor of α7nAChR, attenuated the effects of geniposide. These findings collectively suggested that in conjunction with geniposide, the activation of α7nAChR may contribute to further mitigating LPS-induced PASMC apoptosis and inflammation. In addition, the underlying mechanisms critically involve the NF-κB/MyD88 signaling axis. These results may provide novel insights into the treatment and management of lung diseases via geniposide administration.

Introducing Siloxane-Terminated Side Chains in Small Molecular Donors for All-Small-Molecule Organic Solar Cells: Modulated Molecular Orientation and Enhanced Efficiency.

In this work, three small molecular donors (SMDs) S35, S35-1Si, and S35-2Si, with 3,5-difluorophenyl-substituted benzodithiophene as the central 2-dimensional unit to combine different numbers of siloxane-terminated side chain, were synthesized for all-small-molecule organic solar cells (ASM-OSCs). The three SMDs showed comparable film absorption peaks at 570 nm and optical band gaps of 1.8 eV. Relative to S35 and S35-1Si with symmetric alkyl side chains and asymmetric side chains on the central unit, respectively, the S35-2Si carrying two symmetric siloxane-terminated side chains displayed largely elevated melting and crystalline temperatures, lowered surface energy, and modulated molecular orientation. The three SMDs possessed edge-on dominated molecular orientations of their neat films; however, a big difference was found for their blend films with nonfullerene acceptor Y6. The S35:Y6 and S35-1Si:Y6 blends exhibited edge-on and face-on bimodal orientations but the S35-2Si:Y6 blend showed pure face-on orientation, indicating quite different donor:acceptor intermolecular interactions. Some large domains existed in the S35:Y6 and S35-1Si:Y6 blends, but could be suppressed by the S35-2Si:Y6 blend, leading to a more balanced charge transport. In ASM-OSCs, the two S35:Y6 and S35-1Si:Y6 active layers showed comparable power conversion efficiencies (PCE) of ∼12% but a much higher efficiency of 13.50% could be achieved with the S35-2Si:Y6 active layer. Our results suggest that the siloxane-terminated side chain is promising to regulate crystalline ability of a SMD, paving a way for high performance ASM-OSCs.

The effectiveness and safety of recombinant human growth hormone combined with alginate dressing in the treatment of diabetic foot ulcer: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic foot ulcer (DFU) is one of the serious complications of diabetes. It is the result of a joint effect of lower extremities vascular lesions, neuropathy, and infection, which require amputation and even threaten the life of the patient. At present, the conventional treatment for DFU includes infection control, wound care, wound reduction, reduction of foot pressure, use of dressings that are beneficial to wound surface healing, etc, but the effectiveness is not satisfactory. Recombinant human growth hormone and alginate dressing have been used in clinical, but there is lack of the relevant evidence of its effectiveness and safety, so this study evaluates the clinical effectiveness and safety of recombinant human growth hormone combined with alginate dressing in the treatment of DFU by systematic evaluation, the purpose is to provide a theoretical basis for the treatment of diabetic foot ulcer. METHODS: This study mainly retrieves the randomized controlled trial of recombinant human growth hormone combined alginate dressing in the treatment of DFU in 7 electronic databases, such as PubMed, EMbase, Cochrane Library, SinoMed, CNKI, WANGFANG database, and VIP database. All the retrieval dates of database are from the establishment of the database until May 31, 2020. At the same time, searching the related degree papers, conference papers, and other gray literature by manual. The original literature data are independently screened and extracted by 2 researchers on the basis of inclusion and exclusion criteria and literature information sheets, and cross-checked and resolved through group discussions and consultations when there are differences of the opinion. Assessing the methodological quality of inclusion in the study based on the "Bias Risk Assessment Form" of the Cochrane Collaboration Network. Using the software of RevMan 5.3.3 and STATA 13.0 for statistical analysis. RESULTS: This study compares the main and secondary outcome indicators by systematic evaluation and it will provide strong evidence of recombinant human growth hormone combined alginate dressing in the treatment of DFU. ETHICS AND DISSEMINATION: All data in this study are obtained through the web database and do not involve humans, so ethical approval is not suitable for this study. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/W6P24. CONCLUSION: This study will give positive conclusions about the effectiveness and safety of recombinant human growth hormone combined alginate dressing in the treatment of DFU.

Climate change, air pollution, and allergic respiratory diseases: a call to action for health professionals / 中华医学杂志(英文版)

Rising emissions of greenhouse gases in the atmosphere have warmed the planet substantially and are also accompanied by poor air quality. The increased prevalence of allergic airway disease worldwide can be partially attributed to those global environmental changes. Climate change and air pollution pose adverse impacts on respiratory allergies, and that the mechanisms are complex and interactive. Adverse weather conditions, such as extreme temperatures, can act directly on the respiratory tract to induce allergic respiratory illnesses. Thunderstorms and floods can alter the production and distribution of aeroallergens while wildfires and dust storms increase air pollution, and therefore indirectly enhance health risks. Concentrations of particulate matter and ozone in the air have been projected to increase with climate warming and air stagnation, and the rising temperatures and CO2 increase pollen, molds, and spores, which escalate the risk of allergic respiratory diseases. The synergistic effects of extreme heat and aeroallergens intensify the toxic effect of air pollutants, which in turn augment the allergenicity of aeroallergens. With the Earth's climate change, migration of humans and plants shift the living environments and allergens of susceptible people. Urban residents are exposed to multiple factors while children are sensitive to environmental exposure. Since climate change may pose many unexpected and persistent effects on allergic respiratory diseases, health professionals should advocate for effective mitigation and adaptation strategies to minimize its respiratory health effects.

Involvement of abscisic acid-responsive element-binding factors in cassava (Manihot esculenta) dehydration stress response.

Cassava (Manihot esculenta) is a major staple food, animal feed and energy crop in the tropics and subtropics. It is one of the most drought-tolerant crops, however, the mechanisms of cassava drought tolerance remain unclear. Abscisic acid (ABA)-responsive element (ABRE)-binding factors (ABFs) are transcription factors that regulate expression of target genes involved in plant tolerance to drought, high salinity, and osmotic stress by binding ABRE cis-elements in the promoter regions of these genes. However, there is little information about ABF genes in cassava. A comprehensive analysis of Manihot esculenta ABFs (MeABFs) described the phylogeny, genome location, cis-acting elements, expression profiles, and regulatory relationship between these factors and Manihot esculenta betaine aldehyde dehydrogenase genes (MeBADHs). Here we conducted genome-wide searches and subsequent molecular cloning to identify seven MeABFs that are distributed unevenly across six chromosomes in cassava. These MeABFs can be clustered into three groups according to their phylogenetic relationships to their Arabidopsis (Arabidopsis thaliana) counterparts. Analysis of the 5'-upstream region of MeABFs revealed putative cis-acting elements related to hormone signaling, stress, light, and circadian clock. MeABF expression profiles displayed clear differences among leaf, stem, root, and tuberous root tissues under non-stress and drought, osmotic, or salt stress conditions. Drought stress in cassava leaves and roots, osmotic stress in tuberous roots, and salt stress in stems induced expression of the highest number of MeABFs showing significantly elevated expression. The glycine betaine (GB) content of cassava leaves also was elevated after drought, osmotic, or salt stress treatments. BADH1 is involved in GB synthesis. We show that MeBADH1 promoter sequences contained ABREs and that MeBADH1 expression correlated with MeABF expression profiles in cassava leaves after the three stress treatments. Taken together, these results suggest that in response to various dehydration stresses, MeABFs in cassava may activate transcriptional expression of MeBADH1 by binding the MeBADH1 promoter that in turn promotes GB biosynthesis and accumulation via an increase in MeBADH1 gene expression levels and MeBADH1 enzymatic activity. These responses protect cells against dehydration stresses by preserving an osmotic balance that enhances cassava tolerance to dehydration stresses.

Atmospheric deposition and air-soil exchange of polybrominated diphenyl ethers (PBDEs) in a background site in Central China.

Jinsha (JSH) is one of the regional background sites in Central China. In this study, eight polybrominated diphenyl ethers (PBDEs) were measured in atmospheric deposition samples (dry particle, wet particle, and wet dissolved), air (gaseous and particle) samples, and soil samples that were collected from March 2012 to March 2013. Of all eight PBDEs, BDE-209 was the most abundant congener in both deposition samples and air/soil samples. Average dry particle, wet particle, and wet dissolved deposition fluxes of Σ8PBDEs were 270 ± 310 pg m-2 day-1, 130 ± 210 pg m-2 day-1, and 250 ± 330 pg m-2 day-1, respectively, while those of BDE-209 were 210 ± 290 pg m-2 day-1, 80 ± 120 pg m-2 day-1, and 160 ± 290 pg m-2 day-1, respectively. Dry deposition velocities of individual PBDE ranged from 0.11 ± 0.15 cm s-1 (BDE-183) to 0.24 ± 0.38 cm s-1 (BDE-209), and total washout ratios ranged from 5.0 × 103 (BDE-28) to 4.2 × 104 (BDE-209). The calculated net air-soil gas exchange flux of Σ8PBDEs was - 16 ± 13 pg m-2 day-1, suggesting the deposition status of PBDEs. The gas exchange flux at the air-soil interface was significantly lower than the deposition flux, which only accounted for 2.5% of the total deposition flux, implying that atmospheric deposition was an important input pathway for PBDEs to soils. Overall, the pollution level of the soil was relatively low, and the soil serves as a sink for PBDEs from adjacent regions.

Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.

Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds is highly desirable. Now a very simple and mild strategy has been developed to synthesize them by Suzuki polymerization on a water-toluene interface in a refrigerator. The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF. Both 2D-COF films have large lateral size and their crystalline domains were visualized by high resolution TEM. Based on the wide compatibility of Suzuki reaction, our breakthrough work opened a door for the synthesis of various 2D conjugated COF films. For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.

Optimization of fermentation conditions through response surface methodology for enhanced antibacterial metabolite production by Streptomyces sp. 1-14 from cassava rhizosphere.

Streptomyces species 1-14 isolated from cassava rhizosphere soil were evaluated for their antibacterial efficacy against Fusarium oxysporum f.sp. cubense race 4 (FOC4). Of the 63 strains tested, thirteen exhibited potent antibacterial properties and were further screened against eight fungal pathogens. The strain that showed maximum inhibition against all of the test pathogens was identified by 16S rDNA sequencing as Streptomyces sp. 1-14, was selected for further studies. Through the propagation of Streptomyces sp. 1-14 in soil under simulated conditions, we found that FOC4 did not significantly influence the multiplication and survival of Streptomyces sp. 1-14, while indigenous microorganisms in the soil did significantly influence Streptomyces sp. 1-14 populations. To achieve maximum metabolite production, the growth of Streptomyces 1-14 was optimized through response surface methodology employing Plackett-Burman design, path of steepest ascent determinations and Box-Behnken design. The final optimized fermentation conditions (g/L) included: glucose, 38.877; CaCl2•2H2O, 0.161; temperature, 29.97°C; and inoculation amount, 8.93%. This optimization resulted in an antibacterial activity of 56.13% against FOC4, which was 12.33% higher than that before optimization (43.80%). The results obtained using response surface methodology to optimize the fermentation medium had a significant effect on the production of bioactive metabolites by Streptomyces sp. 1-14. Moreover, during fermentation and storage, pH, light, storage temperature, etc., must be closely monitored to reduce the formation of fermentation products with reduced antibacterial activity. This method is useful for further investigations of the production of anti-FOC4 substances, and could be used to develop bio-control agents to suppress or control banana fusarium wilt.

[Changes in C-reactive protein and procalcitonin levels in neonates with necrotizing enterocolitis and their clinical significance].

OBJECTIVE: To study the changes in C-reactive protein (CRP) and procalcitonin (PCT) levels in neonates with necrotizing enterocolitis (NEC) and their clinical significance. METHODS: According to the modified Bell's staging criteria, 142 neonates with NEC were divided into stage I group (n=40), stage II group (n=72), and stage III group (n=30). All the 18 neonates who underwent surgical treatment had stage III NEC, and among the 124 neonates who underwent conservative treatment, 12 had stage III NEC and the others had stage I or II NEC. CRP and PCT were measured before treatment, on the next day after treatment, and during the recovery stage. RESULTS: Before treatment, on the next day after treatment, and during the recovery stage, the stage III group had a higher level of CRP than the stage I and stage II groups (P<0.05). On the next day after treatment, the stage II and stage III groups had an increase in CRP (P<0.05), and the stage III group had an increase in PCT (P<0.05). The stage II and stage III groups had lower CRP and PCT in the recovery stage than before treatment and on the next day after treatment (P<0.05). The stage III group had higher incidence rate of respiratory failure and rate of mechanical ventilation than the stage I and stage II groups (P<0.05), and the stage III group had a higher incidence rate of sepsis than the stage II group (P=0.010). Gastrointestinal perforation and intestinal stenosis were observed in 10 and 8 neonates respectively in the stage III group. CRP on the next day after treatment had a value in predicting stage III NEC (P<0.05), and CRP before treatment and on the next day after treatment had a value in predicting the need for surgery (P<0.05). CONCLUSIONS: Levels of CRP and PCT and their changes can help with the early diagnosis of Bell stage II/III NEC, and CRP can be used to predict the development of stage III NEC and the need for surgery.

CpG oligodeoxynucleotide preconditioning improves cardiac function after myocardial infarction via modulation of energy metabolism and angiogenesis.

Unmethylated CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) ligand, has been shown to protect against myocardial ischemia/reperfusion injury. However, the potential effects of CpG-ODN on myocardial infarction (MI) induced by persistent ischemia remains unclear. Here, we investigated whether and how CpG-ODN preconditioning protects against MI in mice. C57BL/6 mice were treated with CpG-ODN by i.p. injection 2 hr prior to MI induction, and cardiac function, and histology were analyzed 2 weeks after MI. Both 1826-CpG and KSK-CpG preconditioning significantly improved the left ventricular (LV) ejection fraction (LVEF) and LV fractional shortening (LVFS) when compared with non-CpG controls. Histological analysis further confirmed the cardioprotection of CpG-ODN preconditioning. In vitro studies further demonstrated that CpG-ODN preconditioning increases cardiomyocyte survival under hypoxic/ischemic conditions by enhancing stress tolerance through TLR9-mediated inhibition of the SERCA2/ATP and activation of AMPK pathways. Moreover, CpG-ODN preconditioning significantly increased angiogenesis in the infarcted myocardium compared with non-CpG. However, persistent TLR9 activation mediated by lentiviral infection failed to improve cardiac function after MI. Although CpG-ODN preconditioning increased angiogenesis in vitro, both the persistent stimulation of CpG-ODN and stable overexpression of TLR9 suppressed the tube formation of cardiac microvascular endothelial cells. CpG-ODN preconditioning significantly protects cardiac function against MI by suppressing the energy metabolism of cardiomyocytes and promoting angiogenesis. Our data also indicate that CpG-ODN preconditioning may be useful in MI therapy.

Gene delivery of hypoxia-inducible VEGF targeting collagen effectively improves cardiac function after myocardial infarction.

Vascular endothelial growth factor (VEGF) plays important roles in improvement of cardiac function following myocardial infarction (MI). However, the lack of a steerable delivery system of VEGF targeting the infarcted myocardium reduces the therapeutic efficacy and safety. Here, we constructed a series of lentiviral vector systems which could express a fusion protein consisted of a collagen-binding domain (CBD) and hVEGF (CBDhVEGF), under the control of 5HRE-hCMVmp (5HRE), the hypoxia-inducible promoter consists of five copies of the hypoxia-responsive element (HRE) and a human cytomegalovirus minimal promoter (hCMVmp). We demonstrated that 5HRE has the comparable ability to strongly drive CBDhVEGF under hypoxic condition as the ubiquitous CMV promoter, but it can hardly drive target gene under normoxic condition. 5HRE-drived CBDhVEGF specifically bound to type I collagen and significantly promoted the viability of HUVEC cells. Moreover, after injection of lentivirus into heart of mouse with MI, CBDhVEGF was mainly retained in infarcted myocardium where containing rich collagen and significantly improved angiogenesis and cardiac function when compared with hVEGF. Moreover, CBDhVEGF mediated by lentivirus has little leakage from infarcted zone into blood than hVEGF. Taken together, our results indicate that 5HRE-CBDhVEGF lentiviral vector system could improve cardiac function in the collagen-targeting and hypoxia-inducible manners.

Expression profile of rrbp1 genes during embryonic development and in adult tissues of Xenopus laevis.

Recent studies suggest that ribosome-binding protein 1 (RRBP1) is involved in multiple diseases such as tumorigenesis and cardiomyopathies. However, its function during embryonic development remains largely unknown. We searched Xenopus laevis database with human RRBP1 protein sequence and identified two cDNA sequences encoding Xenopus orthologs of RRBP1 including rrbp1a (NM_001089623) and rrbp1b (NM_001092468). Both genes were firstly detected at blastula stage 8 with weak signals in animal hemisphere by whole mount in situ hybridization. Evident expression of rrbp1 was mainly detected in cement gland and notochord at neurula and tailbud stages. Heart expression of rrbp1 was detected at stage 36. RT-PCR results indicated that very weak expression of rrbp1a was firstly detected in oocytes, followed by increasing expression until stage 39. Differently, very weak expression of rrbp1b was firstly observed at stage 2, and then maintained at a lower level to stage 17 followed by an intense expression from stages 19-39. Moreover, both expression profiles were also different in adult tissues. This study reports Xenopus rrbp1 expression during early embryonic development and in adult tissues. Our study will facilitate the functional analysis of Rrbp1 family during embryonic development.

Prognostic value of hematological parameters in patients with paraquat poisoning.

Paraquat (PQ) is a non-selective contact herbicide, and acute PQ poisoning has a high mortality. The aim of the present study is to evaluate the prognostic value of hematological parameters in patients with acute PQ poisoning. We retrospectively reviewed the records of patients with acute PQ poisoning from January 2010 to December 2015 at the First Affiliated Hospital, Anhui Medical University (Hefei, China). A total of 202 patients were included in the study, and the 30-day mortality was 51.98%. Leukocyte, neutrophil counts and neutrophil-lymphocyte ratio (NLR) were significantly higher in non-survivors than in survivors. In the receiver operating characteristic (ROC) curve analysis, the NLR had an area of 0.916(95%CI, 0.877-0.954) and the optimal cut-off value was 10.57 (sensitivity, 86.70%; specificity, 83.51%; Youden's index, 0.702). The leukocyte counts had an area of 0.849(95%CI, 0.796-0.902) and the optimal cut-off value was 13.15 × 103/mm3 (sensitivity, 77.10%; specificity, 83.50%; Youden's index, 0.606). The neutrophil counts had an area of 0.878(95%CI, 0.830-0.925) and the optimal cut-off value was 10.10 × 103/mm3 (sensitivity, 83.80%; specificity, 79.38%; Youden's index, 0.632). NLR, leukocyte and neutrophil counts are associated with the 30-day mortality, which may be useful and simple parameters in predicting the prognosis of PQ poisoning.