Overexpression of oilseed rape trehalose-6-phosphate synthesis gene BnaC02.TPS8 confers sensitivity to low nitrogen and high sucrose-induced anthocyanin accumulation in Arabidopsis.

MAIN CONCLUSION: Overexpression of BnaC02.TPS8 increased low N and high sucrose-induced anthocyanin accumulation. Anthocyanin plays a crucial role in safeguarding photosynthetic tissues against high light, UV radiation, and oxidative stress. Their accumulation is triggered by low nitrogen (N) stress and elevated sucrose levels in Arabidopsis. Trehalose-6-phosphate (T6P) serves as a pivotal signaling molecule, sensing sucrose availability, and carbon (C) metabolism. However, the mechanisms governing the regulation of T6P synthase (TPS) genes responsible for anthocyanin accumulation under conditions of low N and high sucrose remain elusive. In a previous study, we demonstrated the positive impact of a cytoplasm-localized class II TPS protein 'BnaC02.TPS8' on photosynthesis and seed yield improvement in Brassica napus. The present research delves into the biological role of BnaC02.TPS8 in response to low N and high sucrose. Ectopic overexpression of BnaC02.TPS8 in Arabidopsis seedlings resulted in elevated shoot T6P levels under N-sufficient conditions, as well as an increased carbon-to-nitrogen (C/N) ratio, sucrose accumulation, and starch storage under low N conditions. Overexpression of BnaC02.TPS8 in Arabidopsis heightened sensitivity to low N stress and high sucrose levels, accompanied by increased anthocyanin accumulation and upregulation of genes involved in flavonoid biosynthesis and regulation. Metabolic profiling revealed increased levels of intermediate products of carbon metabolism, as well as anthocyanin and flavonoid derivatives in BnaC02.TPS8-overexpressing Arabidopsis plants under low N conditions. Furthermore, yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) analyses demonstrated that BnaC02.TPS8 interacts with both BnaC08.TPS9 and BnaA01.TPS10. These findings contribute to our understanding of how TPS8-mediated anthocyanin accumulation is modulated under low N and high sucrose conditions.

An Artificial Enzyme for Asymmetric Nitrocyclopropanation of α,ß-Unsaturated Aldehydes - Design and Evolution.

The introduction of an abiological catalytic group into the binding pocket of a protein host allows for the expansion of enzyme chemistries. Here, we report the generation of an artificial enzyme by genetic encoding of a non-canonical amino acid that contains a secondary amine side chain. The non-canonical amino acid and the binding pocket function synergistically to catalyze the asymmetric nitrocyclopropanation of α,ß-unsaturated aldehydes by the iminium activation mechanism. The designer enzyme was evolved to an optimal variant that catalyzes the reaction in high yield with high diastereo- and enantioselectivity. This work demonstrates the application of genetic code expansion in enzyme design and expands the scope of enzyme-catalyzed abiological reactions.

Trehalose-6-phosphate synthase 8 increases photosynthesis and seed yield in Brassica napus.

Trehalose-6-phosphate (T6P) functions as a vital proxy for assessing carbohydrate status in plants. While class II T6P synthases (TPS) do not exhibit TPS activity, they are believed to play pivotal regulatory roles in trehalose metabolism. However, their precise functions in carbon metabolism and crop yield have remained largely unknown. Here, BnaC02.TPS8, a class II TPS gene, is shown to be specifically expressed in mature leaves and the developing pod walls of Brassica napus. Overexpression of BnaC02.TPS8 increased photosynthesis and the accumulation of sugars, starch, and biomass compared to wild type. Metabolomic analysis of BnaC02.TPS8 overexpressing lines and CRISPR/Cas9 mutants indicated that BnaC02.TPS8 enhanced the partitioning of photoassimilate into starch and sucrose, as opposed to glycolytic intermediates and organic acids, which might be associated with TPS activity. Furthermore, the overexpression of BnaC02.TPS8 not only increased seed yield but also enhanced seed oil accumulation and improved the oil fatty acid composition in B. napus under both high nitrogen (N) and low N conditions in the field. These results highlight the role of class II TPS in impacting photosynthesis and seed yield of B. napus, and BnaC02.TPS8 emerges as a promising target for improving B. napus seed yield.

Isoliquiritigenin inhibits gastric cancer growth through suppressing GLUT4 mediated glucose uptake and inducing PDHK1/PGC-1α mediated energy metabolic collapse.

BACKGROUND: Isoliquiritigenin (ISL), a natural flavonoid, has anti-tumor activity. But, the understanding of the impact and molecular mechanism of ISL on the growth of gastric cancer (GC) remains limited. PURPOSE: The study was to explore the tumor suppressive effect of ISL on GC growth both in vitro and in vivo, meanwhile, clarify its molecular mechanisms. METHODS: Cell viability was detected by cell counting kit-8 (CCK-8) assay. Apoptotic cells in vitro were monitored by Hoechst 33,342 solution. Protein expression was assessed by Western blot. Reactive oxygen species (ROS) level was evaluated by utilizing 2',7'- dichlorofluorescin diacetate (DCFH-DA). Lactic acid level was detected with L-lactate assay kit. Glucose uptake was monitored with fluorescently tagged glucose 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG). Glycolytic proton efflux rate (GlycoPER) was evaluated by glycolytic rate assay kit. Oxygen consumption rate (OCR) was conducted by mito stress test kit. A nude mouse model of gastric cancer cell xenograft was established by subcutaneous injection with MGC803 cells. Pathological changes were evaluated by using H&E staining. Cell apoptosis in vivo was evaluated by terminal deoxy-nucleotide transferase mediated dUTP nick end labeling (TUNEL) assay. RESULTS: ISL remarkably suppressed GC growth and increased cell apoptosis. It regulated apoptosis-related and metabolism-related protein expression both in vitro and in vivo. ISL blocked glucose uptake and suppressed production and secretion of lactic acid, which was accompanied with suppressed mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis but increased ROS accumulation. Overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), cellular-myelocytomatosis viral oncogene (c-Myc), hypoxia inducible factor-1α (HIF-1α), glucose transporter 4 (GLUT4) or pyruvate dehydrogenase kinase 1 (PDHK1), could abolish ISL-induced inhibition of cell viability in GC cells. CONCLUSION: These findings implicated that ISL inhibits GC growth by decreasing GLUT4 mediated glucose uptake and inducing PDHK1/PGC-1α-mediated energy metabolic collapse through depressing protein expression of c-Myc and HIF-1α in GC, suggesting its potential application for GC treatment.

Chemoenzymatic synthesis of (+)-isoagatholactone, (+)-spongian-16-one, and 3-deoxychavalone A via biocatalytic polyene cyclization.

The stereoselective cyclization of geranylgeraniol catalysed by squalene-hopene cyclase (SHC) was investigated. By use of this transformation, spongiane diterpenoids (+)-isoagatholactone and (+)-spongian-16-one, and meroterpenoid 3-deoxychavalone A were synthesized in a concise and redox-economic manner. This work showcases the application of SHC-catalysed cyclization as a key step in terpenoid synthesis.

Enantioselective conjugate addition of malonates to α,ß-unsaturated aldehydes catalysed by 4-oxalocrotonate tautomerase.

The enantioselective conjugate addition of malonates to α,ß-unsaturated aldehydes catalysed by 4-oxalocrotonate tautomerase is described. High conversions, high enantioselectivities, and good isolation yields were achieved for a range of substrates. We further completed a four-step synthesis of the antidepressant (+)-femoxetine by utilizing this reaction and an enzymatic reductive amination reaction.

Misdiagnosis of adult primary hemophagocytic lymphohistiocytosis as NK/T-cell lymphoma: A case report.

We reported a case of a 19-year-old male patient with central nervous system symptoms as the main clinical manifestations, and multiple intracranial and abdominal occupying lesions visualized by imaging examinations, who was initially misdiagnosed as NK/T-cell lymphoma but poorly responsive to the treatment. Finally, he was diagnosed as familial hemophagocytic lymphohistiocytosis type-2 by genome sequencing, perforin test and pedigree study. The patient survived well after allogeneic hematopoietic stem cell transplantation. Central nervous system symptoms could be the main clinical manifestations in patients with primary hemophagocytic lymphohistiocytosis , whose early-stage manifestations of blood system were usually atypical, easily leading to misdiagnosis. In clinical practice, primary hemophagocytic lymphohistiocytosis should be considered in patients with central nervous system symptoms and unknown causes. The combination of rapid immunological function test and genome sequencing contributes to the diagnosis of primary hemophagocytic lymphohistiocytosis.

[Berberine hydrochloride inhibits benign prostatic hyperplasia in rats by activating the Nrf2/ARE pathway].

Objective: To study the inhibitory effect of berberine hydrochloride (BBR) on BPH and its underlying mechanism in male rats. METHODS: Forty male rats were randomly divided into a normal control, a BPH model control, a BBR intervention, and a BBR+Bruceol intervention group, and the BPH model was established in the latter three groups. The animals in the normal and BPH model control groups were treated intragastrically with normal saline, and those in the BBR and BBR+Bruceol intervention groups with BBR at 200 mg/kg and BBR plus Bruceol at 1 mg/kg, respectively, once a day for 14 consecutive days. The prostates of the rats were harvested for measurement of their wet weight and prostatic index, detection of the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) and determination of the protein expressions of nuclear factor E2-related factor 2 (Nrf2), antioxidant response element (ARE) and reduced coenzyme I quinone oxidoreductase (NQO1) in the prostate tissue by Western blot. RESULTS: The wet weights of the prostate in the normal control, BPH model control, BBR intervention, and BBR+Bruceol intervention groups were (715.63 ± 28.57) mg, (1118.93 ± 36.41) mg, (896.21 ± 20.24) mg and (967.23 ± 24.98) mg, the prostate indexes were 2.10 ± 0.13, 3.45 ± 0.22, 2.75 ± 0.19 and 3.01 ± 0.14, the SOD contents in the prostate tissue were (38.54 ± 5.12) U/mg, (13.98 ± 2.01) U/mg, (26.75 ± 3.19) U/mg and (20.16 ± 4.10) U/mg, and the MDA contents were (3.59 ± 0.83) nmol/mg, (12.63 ± 3.26) nmol/mg, (7.20 ± 1.69) nmol/mg and (9.85 ± 1.71) nmol/mg, respectively. The relative expressions of the Nrf2 protein in the four groups were 0.53 ± 0.06, 0.12 ± 0.03, 0.36 ± 0.04 and 0.25 ± 0.03, those of the ARE protein were 0.69 ± 0.07, 0.21 ± 0.02, 0.50 ± 0.06 and 0.30 ± 0.04, and those of the NQO1 protein were 0.44 ± 0.05, 0.15 ± 0.03, 0.30 ± 0.04 and 0.22 ± 0.03, respectively. There were statistically significant differences in all the above indicators between the normal and BPH model control groups (P < 0.05), as well as between the BPH model control and BBR intervention groups (P < 0.05) and between the BPH model control and the BBR+Bruceol intervention groups (P < 0.05). CONCLUSIONS: BBR hydrochloride can inhibit prostatic hyperplasia in BPH rats and reduce oxidative stress and pathological changes by activating the Nrf2/ARE pathway.

Helichrysetin inhibits gastric cancer growth by targeting c-Myc/PDHK1 axis-mediated energy metabolism reprogramming.

Helichrysetin (HEL), a chalcone isolated from Alpinia katsumadai Hayata, has an antitumor activity in human lung and cervical cancers. However, the inhibitory effect and underlying mechanism of HEL in gastric cancer have not been elucidated. Here, HEL significantly inhibited the growth of gastric cancer MGC803 cells in vitro and in vivo. HEL decreased expression and transcriptional regulatory activity of c-Myc and mRNA expression of c-Myc target genes. HEL enhanced mitochondrial oxidative phosphorylation (OXPHOS) and reduced glycolysis as evidenced by increased mitochondrial adenosine triphosphate (ATP) production and excessive reactive oxygen species (ROS) accumulation, and decreased the pPDHA1/PDHA1 ratio and Glyco-ATP production. Pyruvate enhanced OXPHOS after HEL treatment. c-Myc overexpression abolished HEL-induced inhibition of cell viability, glycolysis, and protein expression of PDHK1 and LDHA. PDHK1 overexpression also counteracted inhibitory effect of HEL on cell viability. Conversely, c-Myc siRNA decreased cell viability, glycolysis, and PDHK1 expression. NAC rescued the decrease in viability of HEL-treated cells. Additionally, HEL inhibited the overactivated mTOR/p70S6K pathway in vitro and in vivo. HEL-induced cell viability inhibition was counteracted by an mTOR agonist. mTOR inhibitor also decreased cell viability. Similar results were obtained in SGC7901 cells. HEL repressed lactate production and efflux in MGC803 cells. These results revealed that HEL inhibits gastric cancer growth by targeting mTOR/p70S6K/c-Myc/PDHK1-mediated energy metabolism reprogramming in cancer cells. Therefore, HEL may be a potential agent for gastric cancer treatment by modulating cancer energy metabolism reprogramming.

[Galangin enhances autophagy by inhibiting NF-κB pathway in gastric cancer MGC-803 cells].

This study aimed to explore the effects of galangin on energy metabolism and autophagy in gastric cancer MGC803 cells and the underlying mechanism. Cell counting kit-8(CCK-8) was used to detect the effects of galangin at different concentrations on via-bility of MGC803 cells after 48 h intervention. Western blot was carried out to measure the effects of galangin on expression of proteins related to autophagy, nuclear factor-κB(NF-κB) pathway and energy metabolism, followed by the determination of its effects on mRNA expression of energy metabolism-related proteins by Real-time quantitative PCR(qPCR). The impact of galangin on autophagy was explored using AutophagyGreen dye reagent, with autophagosomes and lysosomes observed under the transmission electron microscope(TEM). Nude mice transplanted with gastric cancer MGC803 cells via subcutaneous injection were randomly divided into the following three groups: control(0.5% sodium carboxymethyl cellulose, once a day), 5-fluorouracil(5-FU, 50 mg·kg~(-1), twice a week), and galangin(120 mg·kg~(-1), once a day) groups. The body weight and tumor volume were measured once every three days with a vernier caliper at the same time point by the same person. After 21-d treatment, the tumor tissue was isolated and weighed for the calculation of the tumor-suppressing rate. The comparison with the control group revealed that galangin inhibited the viability of MGC803 cells, up-regulated the protein expression of microtuble-associated protein 1 light chain 3 B(LC3 B) Ⅱ, inhibited the phosphorylation of NF-κB pathway-related proteins, and promoted the formation of autophagosomes in MGC803 cells. However, it did not obviously affect the expression of energy metabolism-related proteins. Furthermore, galangin at 120 mg·kg~(-1) significantly reduced the tumor weight and volume in mice, enhanced LC3 BⅡ protein expression, and inhibited the phosphorylation of NF-κB pathway-related proteins. All these have suggested that galangin inhibited the growth of gastric cancer MGC803 cells both in vivo and in vitro, possibly by inhibiting the NF-κB pathway and enhancing autophagy.

Magnetic ferroferric oxide and polydopamine molecularly imprinted polymer nanocomposites based electrochemical impedance sensor for the selective separation and sensitive determination of dichlorodiphenyltrichloroethane (DDT).

Dichlorodiphenyltrichloroethane (DDT) is a kind of broad-spectrum insecticides, which is potentially toxic and persistently threatens the safety of environment and food, due to their stability in nature and difficulty to degrade. For the first time, a novel impedance chemical sensor based on magnetic Fe3O4 and polydopamine molecularly imprinted polymer magnetic nanoparticles (PDA@Fe3O4 MIP MNPs) was designed. Bisphenol A (BPA) and dopamine were used as virtual template molecules and functional monomer for MIP synthesis, respectively. Recognition cavities formed in PDA layers could specifically recognize and effectively adsorb DDT molecules, with the help of virtual templates that had similar molecular structure to DDTs. The as-prepared PDA@Fe3O4-MIP MNPs could be used for specific adsorption and efficient extraction of target molecules 4,4'-DDT from food samples. The electrochemical impedance of the PDA@Fe3O4-MIP MNPs increased sensitively with the adsorption of 4,4'-DDT, the correlationship between of the electrochemical impedance response and the concentration of 4,4'-DDT were applied in the construction of electrochemical impedance sensors for the determination of 4,4'-DDT. The sensor showed a good linear relationship between the charge transfer resistance (Rct) and the 4,4'-DDT concentration over a range from 1 × 10-11 to 1 × 10-3 mol L-1 with a detection limit of 6 × 10-12 mol L-1. The sensor also exhibited excellent sensitivity and selectivity as well as high stability for the detection of pesticide residues and other environmentally harmful chemicals in various food samples.

Titanium dioxide and polypyrrole molecularly imprinted polymer nanocomposites based electrochemical sensor for highly selective detection of p-nonylphenol.

We developed a new electrochemical sensor based on TiO2 and polypyrrole (PPy) molecularly imprinted polymer (MIP) nanocomposites for the high selective detection of p-nonylphenol in food samples, which is considered as a kind of endocrine disrupting chemical and harmful to human health. With p-nonylphenol as template molecules, the molecularly imprinted polymer was synthesized by the chemical oxidative polymerization of pyrrole and deposited on the surface of TiO2 nanoparticles to form partially encapsulated PPy@TiO2 nanocomposites, denoted as NP-PPy@TiO2 MIP. p-Nonylphenol was bound in the PPy matrix through hydrogen bond and π-π interaction between p-nonylphenol and PPy skeleton. NP-PPy@TiO2 MIP nanocomposites were modified onto glassy carbon electrode (GCE) and p-nonylphenol molecules were excluded from PPy layers by potentiostatic sweeping at the potential of 1.3 V. The as-prepared electrochemical sensor obtained a large amount of micro cavities in PPy layer which could specially recognize and combine target molecules p-nonylphenol. After special adsorption of p-nonylphenol from samples, p-nonylphenol embedded in the PPy layer exhibited a strong differential pulse voltammetry (DPV) response at 0.56 V, which can be used for the detection of p-nonylphenol with a linearly proportional concentration range of 1.0 × 10-8 to 8 × 10-5 mol/L and a detection limit of 3.91 × 10-9 mol/L. The good stability, reproducibility and specificity of the resulting MIP electrochemical sensor are demonstrated. It might open a new window for investigation of selectively electrochemical sensing of small organic molecules from their analogues with the molecular imprinting technique.

[Comparative study of microendoscope-assisted and conventional minimally invasive transforaminal lumbar interbody fusion for degenerative lumbar diseases].

OBJECTIVE: To analyze the medium and long-term effectiveness of microendoscope-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for lumbar degenerative diseases in comparison with conventional tubular retractor-assisted MIS-TLIF. METHODS: Between November 2008 and March 2013, 53 patients with single segment lumbar degenerative diseases were enrolled. According to the different working channel performed, 28 patients were treated by microendoscope-assisted MIS-TLIF (observation group), while the remaining cases received conventional tubular retractor-assisted MIS-TLIF via Wiltse approach (control group). Preoperative baseline data, including age, gender, body mass index, disease etiology, operated level, the ration for requiring bilateral canal decompression, and preoperative visual analogue scale (VAS) socre of low back pain and leg pain, Japanese Orthopedic Association (JOA) score, Oswestry disability index (ODI) score, showed no significant difference between the two groups ( P>0.05). The operation time, intraoperative blood loss, intraoperative fluoroscopy time, postoperative analgesic drug dose, postoperation in-bed time, and perioperative complication incidence were recorded respectively and compared between the two groups. Radiographic evaluation of interbody fusion was performed based on Bridwell grading system at 2 years after operation. VAS scores of low back pain and leg pain, JOA score, and ODI score were assessed before operation, at 2 years after operation, and at last follow-up respectively. Surgical outcome satisfaction was assessed by modified MacNab criteria at last follow-up. RESULTS: When compared with those in control group, both intraoperative blood loss and postoperative analgesic drug dose were significantly decreased in observation group ( P<0.05); similarly, the operation time and intraoperative fluoroscopy time were also significantly increased in observation group ( P<0.05). There was no significant difference of postoperative in-bed time between the two groups ( t=-0.812, P=0.420). Both groups were followed up 6-10.3 years, with an average of 7.9 years. Regarding perioperative complication, its incidence was 14.3% and 20.0% in observation group and control group, respectively, showing no significant difference between both groups ( χ 2=0.306, P=0.580). Specifically, there were intraspinal hematoma formation in 1 case, incision infection in 1 case, urinary infection in 1 case, transient delirium in 1 case in observation group. By contrast, there were dural tear and cerebrospinal fluid leakage in 1 case, urinary infection in 1 case, pneumonia in 1 case, transient delirium in 2 cases in control group. Bridwell criterion was used to judge the intervertebral fusion at 2 years after operation, the fusion rates of observation group and control group were 92.9% and 92.0%, respectively, showing no significant difference ( χ 2=0.162, P=0.687). At both 2-year postoperatively and last follow-up, the VAS scores of low back pain and leg pain, JOA score, and ODI score were significantly improved when compared with those before operation ( P<0.01), whereas no significant difference between the two groups at either time point was found ( P>0.05). At last follow-up, the results of patients' satisfaction with surgery evaluated by modified MacNab criteria, and the excellent and good rates of the observation group and the control group were 96.4% and 92.0%, respectively, showing no significant difference ( χ 2=0.485, P=0.486). CONCLUSION: The medium and long-term effectiveness of microendoscope-assisted MIS-TLIF are similar to those of conventional tubular retractor-assisted MIS-TLIF for lumbar degenerative diseases. The former operation has the additional advantages in terms of more clear surgical site visually, less intraoperative blood loss, and reduced postoperative analgesic dose, all of which seem more feasible to clinical teaching.

The public health emergency management system in China: trends from 2002 to 2012.

BACKGROUND: Public health emergencies have challenged the public health emergency management systems (PHEMSs) of many countries critically and frequently since this century. As the world's most populated country and the second biggest economy in the world, China used to have a fragile PHEMS; however, the government took forceful actions to build PHEMS after the 2003 SARS outbreak. After more than one decade's efforts, we tried to assess the improvements and problems of China's PHEMS between 2002 and 2012. METHODS: We conducted two rounds of national surveys and collected the data of the year 2002 and 2012, including all 32 provincial, 139 municipal, and 489 county CDCs. The municipal and county CDCs were selected by systematic random sampling. Twenty-one indicators of four stages (preparation, readiness, response and recovery) from the National Assessment Criteria for CDC Performance were chosen to assess the ten-year trends. RESULTS: At the preparation stage, organization, mechanisms, workforce, and stockpile across all levels and regions were significantly improved after one decade's efforts. At the readiness stage, the capability for formulating an emergency plan was also significantly improved during the same period. At the response stage, internet-based direct reporting was 98.8%, and coping scores were nearly full points of ten in 2012. At the recovery stage, the capabilities were generally lower than expected. CONCLUSIONS: Due to forceful leadership, sounder regulations, and intensive resources, China's PHEMS has been improved at the preparation, readiness, and response stages; however, the recovery stage was still weak and could not meet the requirements of crisis management and preventive governance. In addition, CDCs in the Western region and counties lagged behind in performance on most indicators. Future priorities should include developing the recovery stage, establishing a closed feedback loop, and strengthening the capabilities of CDCs in Western region and counties.

The Centers for Disease Control and Prevention System in China: Trends From 2002-2012.

OBJECTIVES: To assess the improvements of the Chinese Centers for Disease Control and Prevention (CDCs) system between 2002 and 2012, and problems the system has encountered. METHODS: We obtained data from 2 national cross-sectional surveys in 2006 and 2013, including 32 provincial, 139 municipal, and 489 county-level CDCs throughout China. We performed a pre-post comparative analysis to determine trends in resource allocation and service delivery. RESULTS: The overall completeness of public health services significantly increased from 47.4% to 76.6%. Furthermore, the proportion of CDC staff with bachelor's or higher degrees increased from 14.6% to 32.6%, and governmental funding per CDC increased 5.3-fold (1.283-8.098 million yuan). The working area per CDC staff increased from 37.9 square meters to 63.3 square meters, and configuration rate of type A devices increased from 28.1% to 65.0%. Remaining problems included an 11.9% reduction in staff and the fact that financial investments covered only 71.1% of actual expenditures. CONCLUSIONS: China's CDC system has progressed remarkably, enabling quicker responses to emergent epidemics. Future challenges include establishing a sustainable financing mechanism and retaining a well-educated, adequately sized public health workforce.

Effectiveness and safety of warfarin and anti-platelet drugs for the primary prevention of stroke in patients with non-valvular atrial fibrillation: a meta-analysis.

OBJECTIVE: To evaluate the effectiveness and safety of warfarin and anti-platelet drugs as the primary approach to the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). METHODS: Three English databases (the Cochrane library, Embase, and Medline), and three Chinese databases (the Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Chinese Periodical Full-text Database of Science and Technology) were searched to select potentially eligible studies published before May, 2014. The studies were randomized controlled trials (RCTs) that investigated the effectiveness and safety of using warfarin and anti-platelet drugs in preventing stroke in NVAF patients; The statistical analysis was performed using the Review Manager 5.2 software provided by the Cochrane Collaboration. RESULTS: nine articles were finally included. Compared with antiplatelet drugs, warfarin treatment significantly reduced the risk of stroke (OR = 0.62, 95% CI 0.50-05.77), systemic embolism events (OR = 0.49, 95% CI 0.31-0.77), ischemic stroke events (OR = 0.46, 95% CI 0.36-0.59), stroke-related disability or death events (OR = 0.66, 95% CI 0.52-0.84). Warfarin did not increase the incidence of All-cause death events (OR = 0.92, 95% CI 0.78-1.08), intracranial hemorrhage events (OR = 1.28, 95% CI 0.85-1.93), major hemorrhage events (OR = 1.01, 95% CI 0.79-1.29). CONCLUSIONS: This meta-analysis found that compared with antiplatelet drugs, warfarin treatment significantly reduced the risk of stroke, systemic embolism events, ischemic stroke events, stroke-related disability or death events. And warfarin did not increase the incidence of All-cause death events, intracranial hemorrhage events, major hemorrhage events.

Lysosomal pH Decrease in Inflammatory Cells Used To Enable Activatable Imaging of Inflammation with a Sialic Acid Conjugated Profluorophore.

Inflammation causes significant morbidity and mortality, necessitating effective in vivo imaging of inflammation. Prior approaches often rely on combination of optical agents with entities specific for proteinaceous biomarkers overexpressed in inflammatory tissues. We herein report a fundamentally new approach to image inflammation by targeting lysosomes undergoing acidification in inflammatory cells with a sialic acid (Sia) conjugated near-infrared profluorophore (pNIR). Sia-pNIR contains a sialic acid domain for in vivo targeting of inflamed tissues and a pNIR domain which isomerizes into fluorescent and optoacoustic species in acidic lysosomes. Sia-pNIR displays high inflammation-to-healthy tissue signal contrasts in mice treated with Escherichia coli, Staphylococcus aureus, or lipopolysaccharide. In addition, inflammation-associated fluorescence is switched off upon antibiotics treatment in mice. This report shows the potentials of Sia-pNIR for activatable dual-modality inflammation imaging, and particularly the use of lysosomes of inflamed cells as a previously unappreciated biomarker for inflammation imaging.

[Cephalometric analysis of the soft tissue profile in Hunan Han adults with normal occlusion].

OBJECTIVE: To analyze the characteristics soft tissue profile in Hunan Han adults with normal occlusion and to explore the differences of the soft tissue profile in gender, region and race. METHODS: Lateral cephalometric radiographs were performed for 323 volunteers (164 females and 159 males) from Hunan Province. The digital cephalometric radiographs were imported into the WinCeph8.0 measurement and analysis system in a same computer. According to the Holdaway analysis method, the mean and standard deviation were calculated. Then the results were compared to the data from Liaoning, Nepalese, Japanese, North American Caucasians. RESULTS: The normal value of cephalometric facial soft tissue profile in Han population adults with normal occlusion in Hunan Province were obtained. There were significant differences in subnasale to H line (Sn-H), upper lip tension, lower lip sulcus depth (Si-PgsLs), and soft tissue chin thickness (Pg-Pgs) between males and females (all P<0.05). Compared with Liaoning Province, significant regional differences in soft tissue facial angle (FH-NsPgs), upper lip sulcus depth (Ss-Ls), Sn-H, lower lip thickness, upper lip thickness, H angle, lower lip to H line (Li-PgsLs), Si-PgsLs, and Pg-Pgs were found in Hunan Province (all P<0.05). Compared with the Japan, significant regional differences in FH-NsPgs, nose prominence (Sn-Pn), lower lip thickness, upper lip tensity, H angle, Li-PgsLs, Si-PgsLs, and Pg-Pgs were found in Hunan Province (all P<0.05). Compared with the Nepalese, significant regional differences in Sn-Pn, Ss-Ls, Sn-H, skeletal profile convexity (A-NPs), basic upper lip thickness, upper lip tensity, H angle, Li-PgsLs and Pg-Pgs were found in Hunan Province (all P<0.05). Compared with the North America, significant regional differences in Sn-Pn, Ss-Ls, Sn-H, A-NPs, basic upper lip thickness, upper lip tensity, H angle, Li-PgsLs, Si-PgsLs and Pg-Pgs were found in Hunan Province (all P<0.05). CONCLUSION: There are both similarities and differences in facial soft tissue profile between males and females with normal occlusion in Hunan Province. The characteristics of facial soft tissue profile in Hunan Province are different from that in Liaoning area, Nepal, Japan and North America.

A sialic acid-targeted near-infrared theranostic for signal activation based intraoperative tumor ablation.

Agents enabling tumor staging are valuable for cancer surgery. Herein, a targetable sialic acid-armed near-infrared profluorophore (SA-pNIR) is reported for fluorescence guided tumor detection. SA-pNIR consists of a sialic acid entity effective for in vivo tumor targeting and a profluorophore which undergoes lysosomal acidity-triggered fluorogenic isomerization. SA-pNIR displays a number of advantageous biomedical properties in mice, e.g. high tumor-to-normal tissue signal contrast, long-term retention in tumors and low systemic toxicity. In addition, SA-pNIR effectively converts NIR light into cytotoxic heat in cells, suggesting tumor-activatable photothermal therapy. With high performance tumor illumination and lysosome-activatable photothermal properties, SA-pNIR is a promising agent for detection and photothermal ablation of surgically exposed tumors.

A carbohydrate-grafted nanovesicle with activatable optical and acoustic contrasts for dual modality high performance tumor imaging.

Activatable molecular systems enabling precise tumor localization are valuable for complete tumor resection. Herein, we report sialic acid-capped polymeric nanovesicles encapsulating the near infrared profluorophore (pNIR@P@SA) for lysosome activation based dual modality tumor imaging. The probe features surface-anchored sialic acid for tumor targeting and a core of near infrared profluorophore (pNIR) which undergoes lysosomal acidity triggered isomerization to give optical and optoacoustic signals upon cell internalization. Imaging studies reveal high-efficiency uptake and signal activation of pNIR@P@SA in subcutaneous tumors and millimeter-sized liver tumor foci in mice. The high tumor-to-healthy organ signal contrasts and discernment of tiny liver tumors from normal liver tissues validate the potential of pNIR@P@SA for high performance optical and optoacoustic imaging guided tumor resection.