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Surface diffusion is intimately correlated with crystal orientation and surface structure. Fast surface diffusion accelerates phase transformation and structural evolution of materials. Here, through in situ transmission electron microscopy observation, we show that a copper nanowire with dense nanoscale coherent twin-boundary (CTB) defects evolves into a zigzag configuration under electric-current driven surface diffusion. The hindrance at the CTB-intercepted concave triple junctions decreases the effective surface diffusivity by almost 1 order of magnitude. The energy barriers for atomic migration at the concave junctions and different faceted surfaces are computed using density functional theory. We proposed that such a stable zigzag surface is shaped not only by the high-diffusivity facets but also by the stalled atomic diffusion at the concave junctions. This finding provides a defect-engineering route to develop robust interconnect materials against electromigration-induced failures for nanoelectronic devices.

Pulse measurements made using wearable devices can aid the monitoring of human physiological condition. Accurate estimation of waveforms is often difficult for nonexperts; motion artifacts may occur during tonometry measurements when the skin-sensor contact pressure is insufficient. An alternative approach is to extract only high-quality pulses for use in index calculations. The present study aimed to determine the effectiveness of using machine-learning analysis in discriminating between high-quality and low-quality pulse waveforms induced by applying different contact pressures. Radial blood pressure waveform (BPW) signals were measured noninvasively in healthy young subjects using a strain-gauge transducer. One-minute-long trains of pulse data were measured when applying the appropriate contact pressure (67.80 ± 1.55 mmHg) and a higher contact pressure (151.80 ± 3.19 mmHg). Eight machine-learning algorithms were employed to evaluate the following 40 harmonic pulse indices: amplitude proportions and their coefficients of variation and phase angles and their standard deviations. Significant differences were noted in BPW indices between applying appropriate and higher skin-surface contact pressures. The present appropriate contact pressure could not only provide a suitable holding force for the wearable device but also helped to maintain the physiological stability of the underlying tissues. Machine-learning analysis provides an effective method for distinguishing between the high-quality and low-quality pulses with excellent discrimination performance (leave-one-subject-out test: random-forest AUC = 0.96). This approach will aid the development of an automatic screening method for waveform quality and thereby improve the noninvasive acquisition reliability. Other possible interfering factors in practical applications can also be systematically studied using a similar procedure.

Early identification of cognitive impairment would allow affected patients to receive care at earlier stage. Changes in the arterial stiffness have been identified as a prominent pathological feature of dementia. This study aimed to verify if applying machine-learning analysis to spectral indices of the arterial pulse waveform can be used to discriminate different cognitive conditions of community subjects. 3-min Radial arterial blood pressure waveform (BPW) signals were measured noninvasively in 123 subjects. Eight machine-learning algorithms were used to evaluate the following 4 pulse indices for 10 harmonics (total 40 BPW spectral indices): amplitude proportion and its coefficient of variation; phase angle and its standard deviation. Significant differences were noted in the spectral pulse indices between Alzheimer's-disease patients and control subjects. Using them as training data (AUC = 70.32% by threefold cross-validation), a significant correlation ( R 2 = 0.36) was found between the prediction probability of the test data (comprising community subjects at two sites) and the Mini-Mental-State-Examination score. This finding illustrates possible physiological connection between arterial pulse transmission and cognitive function. The present findings from pulse-wave and machine-learning analyses may be useful for discriminating cognitive condition, and hence in the development of a user-friendly, noninvasive, and rapid method for the early screening of dementia.

Background: Multiple studies have revealed that idiopathic pulmonary fibrosis (IPF) patients are more at risk for cardiovascular diseases and that many IPF patients receive cardiovascular medications like statins, angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and anticoagulants. Existing studies have reported divergent findings on the link between cardiovascular medications and fibrotic disease processes. The aim of this study is to synthesize the evidence on the efficacy of cardiovascular medications in IPF. Methods: We searched studies reporting the effect of cardiovascular medications on IPF in the PubMed, Embase, Web of Science, Cochrane Library, and two Chinese databases (China National Knowledge Infrastructure database and China Wanfang database). We calculated survival data, forced vital capacity (FVC) decline, and IPF-related mortality to assess the efficacy of cardiovascular medications in IPF. We also estimated statistical heterogeneity by using I 2 and Cochran Q tests, and publication bias was evaluated by risk of bias tools ROBINS-I. Results: A total of 12 studies were included in the analysis. The included studies had moderate-to-serious risk of bias. Statin use was associated with a reduction in mortality (hazard ratio (HR), 0.89; 95% CI 0.83-0.97). Meta-analysis did not demonstrate any significant relationship between statin use and the FVC decline (HR, 0.86; 95% CI 0.73-1.02), ACEI/ARB use, and survival data (HR, 0.92; 95% CI 0.73-1.15) as well as anticoagulant use and survival data (HR, 1.16; 95% CI 0.62-2.19). Conclusion: Our study suggested that there is a consistent relationship between statin therapy and survival data in IPF population. However, there is currently insufficient evidence to conclude the effect of ACEI, ARB, and anticoagulant therapy on IPF population especially to the disease-related outcomes in IPF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Wang, Xue, Ji, Pan, Weng, Li, Hua and Zhu.)

Background: Administration of aspirin has the potential for significant side effects of gastrointestinal (GI) injury mainly caused by gastric acid stimulation, especially in long-term users or users with original gastrointestinal diseases. The debate on the optimal treatment of aspirin-induced gastrointestinal injury is ongoing. We aimed to compare and rank the different treatments for aspirin-induced gastrointestinal injury based on current evidence. Methods: We searched PubMed, EMBASE, Cochrane Library (Cochrane Central Register of Controlled Trials), and Chinese databases for published randomized controlled trials (RCTs) of different treatments for aspirin-induced gastrointestinal injury from inception to 1 May 2021. All of the direct and indirect evidence included was rated by network meta-analysis under a Bayesian framework. Results: A total of 10 RCTs, which comprised 503 participants, were included in the analysis. The overall quality of evidence was rated as moderate to high. Eleven different treatments, including omeprazole, lansoprazole, rabeprazole, famotidine, geranylgeranylacetone, misoprostol, ranitidine bismuth citrate, chili, phosphatidylcholine complex, omeprazole plus rebamipide, and placebo, were evaluated in terms of preventing gastrointestinal injury. It was suggested that omeprazole plus rebamipide outperformed other treatments, whereas geranylgeranylacetone and placebo were among the least treatments. Conclusion: This is the first systematic review and network meta-analysis of different treatments for aspirin-induced gastrointestinal injury. Our study suggested that omeprazole plus rebamipide might be considered the best option to treat aspirin-induced gastrointestinal injury. More multicenter, high quality, large sample size randomized controlled trials will confirm the advantages of these medicines in the treatment of aspirin-induced gastrointestinal injury in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Wang, Hua, Li, Wang, Lang, Weng, Xue and Zhu.)

Background: Aspirin is the first-line medication for prevention and treatment of coronary heart disease (CHD). However, long-term use of aspirin resulting in gastrointestinal mucosal injury and bleeding limits the regularity of medication. Xuesaitong is a marketed Chinese medicine contained main active component in Panax notoginseng saponins (PNS), which can significantly inhibit platelet aggregation in patients with CHD. Our previous studies have already showed that PNS could reduce the gastrointestinal mucosal injury caused by aspirin in preclinical study. However, there is a need for further clinical studies to evaluate synergy and attenuation effect of the combination., Methods: This trial is a prospectively planned, open-labeled, parallel-grouped, single-centered clinical trial. A total of eligible 480 participants will be randomly allocated into three groups: aspirin group, Xuesaitong group, and drug combination group at a ratio of 1 : 1 : 1. The primary outcome is the change of platelet aggregation rate and calprotectin activity. Secondary outcomes include PAC-1, P-selectin, P2Y12, I-FABP activity, and fecal occult blood. Discussion . The results of the study are expected to provide evidence of high methodological and reporting quality on the synergy function of Xuesaitong and aspirin upon the antiplatelet and anti-gastrointestinal injury effect for CHD. It also provides an experimental basis for clinical rational drug combination therapy. Trial Registration . This trial was registered in the Chinese Clinical Trail Registry, ChiCTR2000036311, on 22 August 2020, http://www.chictr.org.cn/edit.aspx?pid=58798&htm=4., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Bao-Chen Zhu et al.)

Cuprous oxide (Cu 2 O) that has a direct bandgap corresponding to visible-light absorption exhibits versatile functionalities, which are appealing to solar cell, photocatalyst, bio-sensing and water splitting applications. However, photolysis stability has long been a problem for Cu 2 O under light exposure and a humid environment. Here, we found that the Cu 2 O layer grown on Cu nanowires (CuNWs) with high-density nanoscale twin boundaries can maintain the integrity of Cu/Cu 2 O core-shell structure under ambient air conditions for more than one year. The Cu 2 O on nanotwinned CuNWs also demonstrates much higher stability in humid air and water with light exposure than its counterpart on nanocrystalline CuNWs. The superior photolysis stability of Cu 2 O is attributed to (1) photoelectrons drained to the Cu core, (2) limited vacancy sources in the Cu 2 O layer and (3) the suppressed out-diffusion of Cu cations through the oxide layer. It is suggested that the presence of nanoscale twin boundaries modifies the atomic surface structure of the CuNWs and alters the photolysis reaction of Cu 2 O.

The glucose level is an important biological indicator for diabetes diagnosis. In contrast with costly and unstable enzymatic glucose sensing, oxide-based glucose sensors own the advantages of low fabrication cost, outstanding catalytic ability, and high chemical stability. Here, we fabricate a self-supporting spiky Cu x O/Cu nanowire array structure by electrochemical cycling treatment. The spiky Cu x O/Cu nanowire is identified to be a Cu core passivated by a conformal Cu 2 O layer with extruded CuO petals, which provides abundant active sites for electrocatalytic reaction in glucose detection. An interruptive potential sweeping experiment is presented to elucidate the growth mechanism of the spiky Cu x O/Cu nanostructure during the potential cycling treatment. The spiky Cu x O/Cu nanowire array electrode exhibits a sensitivity of 1210 ± 124 μA·mM -1 ·cm -2 , a wide linear detection range of 0.01-7 mM, and a short response time (<1 s) for amperometric glucose sensing. The study demonstrates a route to modulate oxide phase, crystal morphology, and electrocatalytic properties of metal/oxide core-shell nanostructures., Competing Interests: The authors declare no competing financial interest.

Objective: To evaluate the quality and consistency of recommendations in the clinical practice guidelines (CPGs) for hypertension in Chinese medicine (CM)., Methods: CM CPGs were identified from 5 electronic databases and hand searches through related handbooks published from January 1990 to December 2013. Three reviewers independently appraised the CPGs based on the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, and compared the CPGs' recommendations on CM syndrome pattern classification and treatment., Results: Five CM CPGs for hypertension were included. The quality score of the evidence-based (EB) guideline was higher than those of the consensus-based with no explicit consideration of evidence-based (CB-EB) and the consensus-based (CB) guidelines. Three out of five patterns in the CPGs were recommended by the EB guideline. Tianma Gouteng Formula () in the EB guideline was recommended mostly for hypertension patients with pattern of ascendant hyperactivity of Gan (Liver)-yang and pattern of yin deficiency with yang hyperactivity in the CPGs. Acupuncture and massage were recommended for Grade I and Grade II hypertension with severe symptoms weakening the quality of life in the EB guideline. For Grade I and Grade II hypertension, CM could be used alone, while for Grade III hypertension, they should be used in combination with Western medicines., Conclusion: The quality of EB guideline was higher than those of CB and CB-EB CPGs in CM for hypertension and CM should be prescribed alone or combined with Western medicines based on the grade of hypertension.

Lattice-mismatch is an important factor for the heteroepitaxial growth of core-shell nanostructures. A large lattice-mismatch usually leads to a non-coherent interface or a polycrystalline shell layer. In this study, a conformal Ag layer is coated on Cu nanowires with dense nanoscale twin boundaries through a galvanic replacement reaction. Despite a large lattice mismatch between Ag and Cu (∼12.6%), the Ag shell replicates the twinning structure in Cu nanowires and grows epitaxially on the nanotwinned Cu nanowire. A twin-mediated growth mechanism is proposed to explain the epitaxy of high lattice-mismatch bimetallic systems in which the misfit dislocations are accommodated by coherent twin boundaries.

Cavitation and hollow structures can be introduced in nanomaterials via the Kirkendall effect in an alloying or reaction system. By introducing dense nanoscale twins into copper nanowires (CuNWs), we change the surface structure and prohibit void formation in oxidation of the nanowires. The nanotwinned CuNW exhibits faceted surfaces of very few atomic steps as well as a very low vacancy generation rate at copper/oxide interfaces. Together they lower the oxidation rate and eliminate void formation at the copper/oxide interface. We propose that the slow reaction rate together with the highly effective vacancy absorption at interfaces leads to a lattice shift in the oxidation reaction. Our findings suggest that the nanoscale Kirkendall effect can be manipulated by controlling the internal and surface crystal defects of nanomaterials.

Previous studies have shown that paeonol can antagonize acute myocardial ischemia and infarction in rat. This study further researched the effects of paeonol on blood pressure and blood flow in the artery of spontaneously hypertensive rats and its mechanisms related on vasomotion. Firstly, thirty spontaneously hypertensive rats were randomly divided into spontaneously hypertensive control group and paeonol-treating groups of high dose and low dose, and also, the other ten Wistar rats as healthy control group. Before and after the intraduodenal administration of the drug, arterial blood pressure was measured by carotid artery and blood flow through the renal artery and carotid artery in vivo were measured by animal flowmeter. The same volume of solvent was given to the spontaneously hypertensive control group and the healthy control group, and the other operations were same. In order to further study the effect of paeonol on vasomotor function, the superior mesenteric artery, renal artery and coronary artery of the spontaneously hypertensive rat were removed and separated, precontracted by a certain concentration of potassium chloride (KCl) and 5-serotonin (5-HT) respectively, and dilatory responses were assessed by cumulative addition of paeonol. Results showed that after duodenal one-time delivery of paeonol, the blood pressure significantly lowered, the renal arterial blood flow and the carotid arterial blood flow significantly increased in spontaneously hypertensive rat. And also, paeonol relaxed the mesenteric artery, renal artery and the coronary artery of spontaneously hypertensive rat in a concentration-dependent manner. These results indicated that the effect of paeonol on decreasing arterial blood pressure and increasing the arterial blood flow was related to its vasodilative effect.

Recent studies have demonstrated beneficial effects of specific probiotics on alleviating obesity-related disorders. Here we aimed to identify probiotics with potential antiobesity activity among 88 lactic acid bacterial strains via in vitro screening assays, and a Lactobacillus plantarum strain K21 was found to harbor abilities required for hydrolyzing bile salt, reducing cholesterol, and inhibiting the accumulation of lipid in 3T3-L1 preadipocytes. Furthermore, effects of K21 on diet-induced obese (DIO) mice were examined. Male C57Bl/6J mice received a normal diet, high-fat diet (HFD), or HFD with K21 administration (10(9) CFU in 0.2 mL PBS/day) for eight weeks. Supplementation of K21, but not placebo, appeared to alleviate body weight gain and epididymal fat mass accumulation, reduce plasma leptin levels, decrease cholesterol and triglyceride levels, and mitigate liver damage in DIO mice. Moreover, the hepatic expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) related to adipogenesis was significantly downregulated in DIO mice by K21 intervention. We also found that K21 supplementation strengthens intestinal permeability and modulates the amount of Lactobacillus spp., Bifidobacterium spp., and Clostridium perfringens in the cecal contents of DIO mice. In conclusion, our results suggest that dietary intake of K21 protects against the onset of HFD-induced obesity through multiple mechanisms of action.

Background: Multiple primary malignancies (MPM) have become increasingly prevalent worldwide. This investigation was aimed at establishing the clinicopathological characteristics of MPM patients and evaluating the impact of the living environment on MPM in the Taiwanese population., Materials and Methods: From January 2009 to December 2013, a total of 8,268 cancer patients were identified in our institutional center. Of these, 125 were diagnosed as MPM and thus enrolled. Data for clinicopathological features and treatment approaches for these MPM patients living in urban or suburb zone were obtained. Findings for the air pollution status in Taiwan were also collected., Results: The most common cancer match of MPM was esophageal cancer with hypopharyngeal cancer (12.8%), followed by colorectal cancer with gastric cancer (6.4%) and colorectal cancer with breast cancer (5.6%). The air quality was significantly worse in the urban than in the suburban zone and there was a remarkably higher portion of MPM patients in the urban zone suffering from grade III and IV post-chemotherapeutic neutropenia (30.8% vs 15.1%, P=0.036)., Conclusions: The tumor frequency and site distribution should be taken into the clinical evaluation because there is a relatively high risk of developing MPM. This study also highlighted the potential influence of environmental factors on post-chemotherapeutic neutropenia for patients with MPM.

Background: The prevalence of esophageal cancer (EC) with second primary cancers (SPC) is increasing worldwide. This study was aimed to understand the clinical features of EC patients with SPC in the Taiwanese population., Materials and Methods: Clinical and laboratory data for 180 EC patients with or without SPC were collected between January 2009 and December 2013. Information on treatment approaches, location of SPCs and ABO blood type were also collected and stratified., Results: The most common SPC in EC patients was hypopharyngeal cancer, followed by laryngeal cancer and hepatocellular carcinoma in our study. Malignancies of colon, prostate and lung were also found. There was a significant higher portion of blood type A in the EC patients with SPC compared with those without (42.4% vs 19.5%, P=0.006)., Conclusions: The frequency and SPC site distribution and blood type A should be considered in clinical evaluation of EC patients with a high risk of developing SPC in the Taiwanese population.

Objective: To investigate the vasodilative effect of paeonol in rat mesenteric artery and the mechanisms responsible for it., Methods: Rats were anaesthetized and sacrificed. The superior mesenteric artery was removed, dissected free of adherent tissue and cut into 2.0 mm long cylindrical segments. Isometric tension of artery rings was recorded by a myograph system in vitro. Concentration-relaxation curves of paeonol (17.8 μ mol/L to 3.16 mmol/L) were recorded on artery rings precontracted by potassium chloride (KCl) and concentration-contraction curves of KCl, 5-hydroxytryptamine (5-HT), noradrenaline (NA) or calcium chloride (CaCl2) were recorded in the presence of paeonol (10(-4.5), 10(-3.8), 10(-3.5) mol/L) respectively. And also, concentration-relaxation curves of paeonol were recorded in the presence of different potassium channel inhibitors and propranolol on rings precontracted with KCl respectively. To investigate the role of intracellular Ca(2+) release from Ca(2+) store, the contraction induced by NA (100 μ mol/L) and CaCl2 (2 mmol/L) in Ca(2+) free medium was observed in the presence of paeonol respectively., Results: Paeonol relaxed artery rings precontracted by KCl in a concentration-dependent manner and the vasodilatation effect was not affected by endothelium denudation. Paeonol significant decreased the maximum contractions (Emax) induced by KCl, CaCl2, NA and 5-HT, as well as Emax induced by NA and CaCl2 in Ca(2+) -free medium, suggesting that paeonol dilated the artery via inhibiting the extracellular Ca(2+) influx mediated by voltage-dependent calcium channel, and receptor-mediated Ca(2+)-influx and release. Moreover, none of glibenclamide, tetraethylammonium, barium chlorded and propranolol affected the paeonol-induced vasodilatation, indicating that the vasodilatation was not contributed to ATP sensitive potassium channel, calcium-activated potassium channel, inwardly rectifying potassium channel, and β-adrenoceptor., Conclusion: Paeonol induces non-endothelium dependent-vasodilatation in rat mesenteric artery via inhibiting voltage-dependent calcium channel-mediated extracellular Ca(2+) influx and receptor-mediated Ca(2+) influx and release.

Nonalcoholic fatty liver (NAFL) is also called hepatic steatosis and has become an emergent liver disease in developed and developing nations. This study was to exam the preventive effects of taurine (Tau) on the development of hepatic steatosis via a hamster model. Although hepatic steatosis of hamsters was induced by feeding a high-fat/cholesterol diet, drinking water containing 0.35 and 0.7% Tau improved (p < 0.05) the serum lipid profile. Meanwhile, the smaller (p < 0.05) liver sizes and lower (p < 0.05) hepatic lipids in high-fat/cholesterol dietary hamsters drinking Tau may be partially due to higher (p < 0.05) fecal cholesterol, triacylglycerol, and bile acid outputs. In the regulation of lipid homeostasis, drinking a Tau solution upregulated (p < 0.05) low-density lipoprotein receptor and CYP7A1 gene expressions in high-fat/cholesterol dietary hamsters, which result in increased fecal cholesterol and bile acid outputs. Drinking a Tau solution also upregulated (p < 0.05) peroxisome proliferator-activated receptor-α (PPAR-α) and uncoupling protein 2 (UPC2) gene expressions in high-fat/cholesterol dietary hamsters, thus increasing energy expenditure. Besides, Tau also enhanced (p < 0.05) liver antioxidant capacities (GSH, TEAC, SOD, and CAT) and decreased (p < 0.05) lipid peroxidation (MDA), which alleviated liver damage in the high-fat/cholesterol dietary hamsters. Therefore, Tau shows preventive effects on the development of hepatic steatosis induced by a high-fat/cholesterol dietary habit.

Beginning with 4-level quality control measures of clinical research in traditional Chinese medicine (TCM), we elaborated the implementation process and demands of quality control measures of each level, including quality control, monitoring, auditing, and inspection. On the basis of joint inspection experience of 41 projects of the "Prevention and Treatment of Difficult and Complicated Diseases of TCM" plan of the "11th Five-year National Key Technology R&D Program", we analyzed the ensuring effect of 4-level quality control system and joint inspection model, and then pointed out the existing problems in the executing process of quality control system at different levels and joint inspection model. Finally we investigated what should be revised in the quality control system and joint inspection model, thus providing the theoretical support for quality inspection improvement of TCM clinical research.

Red muscadine (Vitis rotundifolia Michx.) juices with natural organic, phenolic acids and polyphenol compounds were tested against Cronobacter sakazakii. The concentration of total phenolic compounds of commercial baby juices ranged from 176.7 to 347.7 mg/mL. Commercial baby juices showed poor antimicrobial activity, reducing less than 1-log of C. sakazakii in juice samples for 2 h at 37 degrees C. Red muscadine juices, regardless of processing methods (filtration, pasteurization, and sterilization), achieved a 6-log reduction of C. sakazakii in the same time period (2 h). The mixture of synthetic organic acids (malic and tartaric acids) and polyphenolic acid (tannic acid) showed strong antimicrobial activity against C. sakazakii. Among synthetic organic acids, tannic acid was undetected in commercial baby juices. Tannic acid showed the highest antimicrobial activity (1.4- to 3.8-log reduction) against C. sakazakii, while malic and tartaric acids showed less than 0.5-log reduction. These results suggest that red muscadine juice could be utilized as a natural antimicrobial in baby food formulations to inhibit C. sakazakii.

Hot and cold water-soluble muscadine (Vitis rotundifolia) seed extracts and their polar and polyphenol fractions from two Muscadine cultivars ('Ison', purple and 'Carlos', bronze) were investigated for their inhibition of Enterobacter sakazakii. The heat treatment on each seed extract not only increased total phenolics and tannic acid but also enhanced antimicrobial activity against two strains of E. sakazakii. Within 1 h, all seed extracts reduced an initial population (approximately 6 log CFU/mL) of E. sakazakii to a non-detectable level (minimum detection limit, 10 CFU/mL). Regardless of extraction method and cultivar, only the polar fractions which contained malic, tartaric and tannic acids showed antimicrobial activity against two strains of E. sakazakii. The polyphenol fractions which contained gallic acid, catechin, epicatechin, ellagic acid and pigments showed slight inhibition against E. sakazakii. Results showed that water-soluble muscadine seed extracts (pH 3.3-3.78) contained strong antimicrobial inhibitors against E. sakazakii while acidified peptone water (pH 3.3) did not show any antimicrobial activity.

Water-soluble extracts were prepared from purple (cultivar Ison) and bronze (cultivar Carlos) muscadine seeds with or without heating. The Ison extracts had strong antimicrobial activity against a cocktail of three strains of Escherichia coli O157: H7. This extract had higher acidity (pH 3.39 to 3.43), total phenolics (2.21 to 3.49 mg/ml), tartaric acid (5.6 to 10.7 mg/ml), tannic acid (5.7 to 8.1 mg/ml), and gallic acid (0.33 to 0.59 mg/ml) than did the Carlos extracts. Heat treatment on both extracts increased antimicrobial activity, possibly because of increased acidity, tartaric acid, total phenolics, and individual phenolics. Heating of Ison extracts increased ellagic acid up to 83%. Up to 10.7 mg/ml tartaric acid alone was not as effective against E. coli O157:H7 as were water-soluble seed extracts. This finding suggests the involvement of other factors, such as tannic and gallic acids, in inactivation of this pathogen. Water-soluble muscadine seed extracts may be useful for incorporation into juice and other beverage products as natural preservatives.

Purpose: To examine whether promiscuous Cre/LoxP recombination happens during gametogenesis in double transgenic mice carrying LoxP modified alleles and Cre transgene driven by tissue-specific promoter outside the gonads of adult mice., Methods: Cre driver mice were crossbred with reporter mouse lines (e.g., ZEG and Rosa26R) to obtain Cre/ZEG and Cre/Rosa26R double transgenic mice. The frequency of promiscuous LoxP/Cre recombination was determined by the expression of second reporter genes in the offspring of double transgenic mice., Results: The frequency of promiscuous LoxP/Cre recombination varied in different lines of Cre driver mice and in the sex of the same driver mice with higher penetrance in male than in female double transgenic mice. Polymerase chain reaction (PCR) and recombination analysis demonstrate that the recombination of floxed allele occurs during the transition from spermatogonia (diploid) to primary spermatocyte (tetraploid) in the testis. Thereby, target-floxed allele(s) may be ubiquitously ablated in experimental animals intended for tissue-specific gene deletion., Conclusions: Gametogenesis-associated recombination should always be examined in tissue-specific gene ablation studies.

Huangqi powder injection's positive rate of skin-test was 12.3%. Qingkailing powder injection was 3.0%. Qingkailing injection was 7.6%. Shuanghuanglian injection was 6.3%. Penicillin's rate of allergic reactions was 0.7%-10%. Different form of a drug (power or injection) and different drug consistency could influence the positive rate of skin-test. We don't use drug in positive group, and we use drug in negative group. Some trial subjects still happened allergic reactions in negative group of skin-test. In negative group of skin-test, Huangqi power injection's rate of allergic reactions was 2.1%. Qingkailing injection was 0.4%. Shuanghuanglian injection was 0.9%-2.6%. Shuanghuanglian injection's rate of allergic reactions was 8.6% in all subjects (31/360 include the subjects with positive skin-test and allergic reactions). Qingkailing powder injection's rate of allergic reactions was 4.5% (6/132). Qingkailing injection' s rate of allergic reactions was 9.1% (12/132). Huangqi power injection's rate of allergic reactions was 15.4% (62/402). The total rate of allergic reactions was 10.8%. The main appearance of Penicillin's skin-test was welling under skin, and with some blush. But the main appearance of traditional Chinese medicine skin-test was blush, and with a little welling under skin. Skin-test can reduce the allergic reactions of Qingkailing powder injection, Shuanghuangiian injection, Huangqi power injection. It can be the one measure of reducing adverse reactions.

The standard method of detecting neurogenesis uses bromodeoxyuridine (BrdU) to label DNA synthesis followed by double labeling with neuronal markers. However, DNA synthesis may occur in events unrelated to neurogenesis including aneuploidy and abortive cell cycle reentry. Hence, it is important to confirm neurogenesis with methods other than BrdU incorporation. To this end, we have generated transgenic nestin-CreER mice that express tamoxifen-inducible Cre recombinase under the control of a nestin enhancer. When crossed with a ubiquitous Enhanced Green Fluorescent Protein (EGFP)-Cre-reporter line, the bitransgenic animals can reveal the nestin-positive progenitors and their progeny with EGFP after tamoxifen induction. This system has many applications including visualization of embryonic neural progenitors, detection of postnatally transformed radial glial cells, and labeling adult neural progenitors in the subventricular zone (SVZ). To examine the contribution of SVZ progenitors to cell replacement after stroke, tamoxifen-induced mice were challenged with focal ischemia or combined ischemia-hypoxia followed by BrdU injection. This analysis revealed only very few EGFP-positive cells outside the SVZ after focal ischemia but robust DNA synthesis by hippocampal neurons without immediate cell death following ischemia-hypoxia. These results suggest that the nestin-CreER system is a useful tool for detecting embryonic and adult neurogensis. They also confirm the existence of nonproliferative DNA synthesis by old neurons after experimental brain injury.

Recent studies suggest that postmitotic neurons can reenter the cell cycle as a prelude to apoptosis after brain injury. However, most dying neurons do not pass the G1/S-phase checkpoint to resume DNA synthesis. The specific factors that trigger abortive DNA synthesis are not characterized. Here we show that the combination of hypoxia and ischemia induces adult rodent neurons to resume DNA synthesis as indicated by incorporation of bromodeoxyuridine (BrdU) and expression of G1/S-phase cell cycle transition markers. After hypoxia-ischemia, the majority of BrdU- and neuronal nuclei (NeuN)-immunoreactive cells are also terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL)-stained, suggesting that they undergo apoptosis. BrdU+ neurons, labeled shortly after hypoxia-ischemia, persist for >5 d but eventually disappear by 28 d. Before disappearing, these BrdU+/NeuN+/TUNEL+ neurons express the proliferating cell marker Ki67, lose the G1-phase cyclin-dependent kinase (CDK) inhibitors p16INK4 and p27Kip1 and show induction of the late G1/S-phase CDK2 activity and phosphorylation of the retinoblastoma protein. This contrasts to kainic acid excitotoxicity and traumatic brain injury, which produce TUNEL-positive neurons without evidence of DNA synthesis or G1/S-phase cell cycle transition. These findings suggest that hypoxia-ischemia triggers neurons to reenter the cell cycle and resume apoptosis-associated DNA synthesis in brain. Our data also suggest that the demonstration of neurogenesis after brain injury requires not only BrdU uptake and mature neuronal markers but also evidence showing absence of apoptotic markers. Manipulating the aberrant apoptosis-associated DNA synthesis that occurs with hypoxia-ischemia and perhaps neurodegenerative diseases could promote neuronal survival and neurogenesis.

P84 and integrin associated protein (IAP) are heterophilic binding partners that are expressed in the central nervous system in addition to a variety of other tissues. Both molecules are known to be involved in cell signaling in nonneural tissues. In the retina, both molecules are expressed prominently in plexiform layers, suggesting a possible association with synapses. Here, we examined the cellular expression and ultrastructural localization of the two molecules in the developing mouse retina. Both appeared to be expressed at one or both sides of synaptic sites, although the expression of IAP in the retina precedes that of P84. Examination of transgenic IAP-null retinae revealed a failure of P84 to become associated with synaptic sites, suggesting the interaction of P84 with IAP was necessary for P84's synaptic localization. These findings suggest that the signaling activities of P84 and IAP are localized to sites of synaptic contact in the retina. Thus this pair of synapse-associated molecules represents a bidirectional signaling system that could function to modify synaptic activity or possibly trophic interactions between central neurons., (Copyright 2000 Wiley-Liss, Inc.)

Unlabelled: 55 cases of Qi-deficiency and Blood-Stasis syndrome of coronary heart disease (CHD) and angina pectoris (AP) were divided randomly into two groups. Qi Xue granule (QXG) was administered to 30 cases of treated group, while compound Salvia tablet (CST) was administered to 25 cases of control group. Besides, both group were also given one placebo tablet or granule so as to eliminate the patient's psychological effects., Results: (1) Effects on clinical symptoms: Total effective rate for AP: 90% in QXG group, marked effective rate and effective rate for ischemic ECG changes were 30% and 46.6% respectively. All of these were better than that of CST group significantly (P < 0.05). Besides, QXG group could alleviate symptoms including asthenia. (2) Effects on submaximal paddle work load test: QXG group could prolong the capacity of exercise (from 336.2 +/- 34.7 to 437.5 +/- 43.8 seconds, P < 0.05), magnify the work load (from 73 +/- 7.18 to 94 +/- 8.5 W, P < 0.05) and elevate the ST segment (from 0.218 +/- 0.03 to 0.176 +/- 0.03 mV) significantly in comparison with CST group, which had little change only. (3) Effects on plasma TXB2, 6-keto-PGF1 alpha (6 Kp) level and ration of TXB2/6Kp in 10 normal subjects were 165 +/- 12.1 pg/ml, 142.6 +/- 17.4 pg/ml and 1.16 +/- 0.19 pg/ml respectively, while in 36 cases AP were 390.6 +/- 14.3, 106.0 +/- 7.9 and 3.67 +/- 0.85 pg/ml respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

SK&F 104524 (bis-[1,2-bis(diphenylphosphino)-ethane]-gold(I)-lactate) ([Au(dppe)2]+) is a lipophilic phosphine-coordinated gold complex that has significant antineoplastic activity. However, this agent has significant hepato- and cardiotoxicity and preclinical preliminary experiments indicate potential pneumotoxic effects. Accordingly, we sought to evaluate the acute effects of [Au(dppe)2]+ on pulmonary removal of two radioiodinated benzylguanidines [metaiodobenzylguanidine (MIBG) and 3-iodo-4-amino-benzylguanidine (AIBG)]. Pulmonary removal of MIBG or AIBG was measured by application of indicator dilution techniques in rabbit lungs, perfused with Kreb's bicarbonate (3% albumin; 50 ml/min). A bolus containing either [125I]MIBG or--AIBG and [99mTc]sulfur colloid was injected into the pulmonary artery and effluent was diverted to an in-line nuclear detection system. In initial experiments we characterized some pharmacokinetic aspects of the disposition of these amines. Removal of MIBG [R(MIBG)] and R(AIBG) were 59 +/- 3% (n = 14) and 24 +/- 2% (n = 7), respectively. Addition of unlabeled norepinephrine, MIBG or AIBG (3-100 nmol) to the injection caused similar dose-dependent reductions in removal of either amine. Lowering the temperature (13 degrees C) or reducing the sodium concentration caused significant reductions in removal. After 15 min of perfusion with [Au(dppe)2]+ (50 micrograms/ml), perfusion pressure doubled and R(MIBG) and R(AIBG) were each decreased significantly. At 30 min, perfusion pressure returned to control values whereas there was still a 36 and 61% reduction in R(MIBG) and R(AIBG), respectively. These data confirm that removal of benzylguanidines involves a saturable, sodium- and temperature-dependent process similar to that responsible for the removal of norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)