Simultaneous Hydrogen Generation and Exciplex Stimulated Emission in Photobasic Carbon Dots.

Photocatalytic water splitting is a promising approach to generating sustainable hydrogen. However, the transport of photoelectrons to the catalyst sites, usually within ps-to-ns timescales, is much faster than proton delivery (∼µs), which limits the activity. Therefore, the acceleration of abstraction of protons from water molecules towards the catalytic sites to keep up with the electron transfer rate can significantly promote hydrogen production. The photobasic effect that is the increase in proton affinity upon excitation offers means to achieve this objective. Herein, we design photobasic carbon dots and identify that internal pyridinic N sites are intrinsically photobasic. This is supported by steady-state and ultrafast spectroscopic measurements that demonstrate proton abstraction within a few picoseconds of excitation. Furthermore, we show that in water, they form a unique four-level lasing scheme with optical gain and stimulated emission. The latter competes with photocatalysis, revealing a rather unique mechanism for efficiency loss, such that the stimulated emission can act as a toggle for photocatalytic activity. This provides additional means of controlling the photocatalytic process and helps the rational design of photocatalytic materials.

Atmospheric PM2.5 exposure and risk of ischemic heart disease: A systematic review and meta-analysis of observational studies.

Fine particulate matter <2.5 µm in diameter (PM2.5) has been validated to associate with cardiovascular diseases (CVD) incidence and mortality. So far, no study has quantitatively evaluated the relationship between the atmospheric PM2.5 exposure and ischemic heart disease (IHD). We conducted a meta-analysis to illustrate the relationship between PM2.5 and IHD. Published articles were systematically searched (until June 2022) from PubMed, EMBASE, Cochrane Library. A random-effect model was performed to summarize the total relative risks (RRs) and 95% confidence intervals (CIs). Meta-analysis was performed using Stata 12.0 software. A total of 28 studies among 23 cohorts (23.38 million individuals and 256256 IHD cases) were included. With PM2.5 increasing 10 µg/m3, the total RRs of IHD incidence and mortality were 1.07 (95% CI: 0.99-1.17), 1.21 (95% CI: 1.15-1.28), respectively. In sub-analyses, our study revealed that the combined RRs of exposure to PM2.5 on IHD mortality in Asian and European population [1.11 (95% CI: 0.93-1.33); 1.06 (95% CI: 1.02-1.11)] were much lower compared with American and Canadian people [1.27 (95% CI: 1.17-1.37); 1.30 (95% CI: 1.24-1.35)]. Furthermore, study duration, size and some adjustments were related with the total RR. Our findings indicated that exposure of an increase in the concentration of atmospheric PM2.5 may increase the risk of IHD incidence and mortality. Further evidence is needed to confirmed the association.

[Toxicology studies for compound preparations of traditional Chinese medicine in ancient classic prescriptions].

According to Provisions for Drug Registration and Categories and Requirements of Application Dossiers for Traditional Chinese Medicine(TCM), non-clinical safety research/toxicology research should be conducted for classical compound Chinese medicine prescriptions(Categories 3.1 and 3.2), and the data should be submitted at the application for the marketing authorization. Based on the requirements of toxicology research in Categories and Requirements of Application Dossiers for Traditional Chinese Medicine, this study further refined and clarified the requirements of toxicology research on classical compound Chinese medicine preparations(Categories 3.1 and 3.2).

Evaluation of the liver and blood micronucleus, and comet assay end points in a 14-day repeated-dose study with methyl carbamate and 1,3-propane sultone.

The repeated-dose liver micronucleus (RDLMN) assay is a novel method for detecting genotoxic chemicals. Two carcinogens methyl carbamate (MC) and 1,3-propane sultone (PS) were evaluated for the liver micronucleus in a 14-day repeated-dose study with Crl: CD (SD) IGS rats. Additionally, micronucleated reticulocytes (MN-RET) in peripheral blood and DNA damage (alkaline comet assay) in the liver were also assessed in the same animals. Ten groups of five male Crl: CD (SD) IGS rats were treated once daily with MC (300, 600 or 1200 mg/kg/day), PS (37.5, 75 or 150 mg/kg/day), negative control or three positive controls by oral gavage for 15 days. Blood samples were collected at 3 h after the last administration for determining MN-RET frequencies (%MN-RET), and the livers were sampled for determining the frequency of micronuclei and DNA damage. MC was negative in the comet assay, liver micronucleus assay and reticulocyte micronucleus assay, while PS was positive in all three assays. These results are consistent with the previous genotoxic findings of MC and PS. Therefore, the liver micronucleus assay can be effectively integrated into repeated-dose studies in animals. Moreover, integration of multiple genotoxicity end points into one study can reduce the number of animals, boost the experimental efficiency, and provides a comprehensive evaluation of the genotoxic potential of chemicals.

Perceptual influence of auditory pitch on motion speed.

There is a cross-modal mapping between auditory pitch and many visual properties, but the relationship between auditory pitch and motion speed is unexplored. In this article, the ball and baffle are used as the research objects, and an object collision experiment is used to explore the perceptual influence of auditory pitch on motion speed. Since cross-modal mapping can influence perceptual experience, this article also explores the influence of auditory pitch on action measures. In Experiment 1, 12 participants attempted to release a baffle to block a falling ball on the basis of speed judgment, and after each trial, they were asked to rate the speed of the ball. The speed score and baffle release time were recorded and used for analysis of variance. Since making explicit judgments about speed can alter the processing of visual paths, another group of participants in Experiment 2 completed the experiment without making explicit judgments about speed. Our results show that there is a cross-modal mapping between auditory pitch and motion speed, and high or low tones cause perception shift to faster or slower speeds.

DNA-Functionalized Metal-Organic Framework: Cell Imaging, Targeting Drug Delivery and Photodynamic Therapy.

Here, DNA-functionalized nanoscale PCN-224 is established with the aptamer of A549 lung cancer cells. The aptamer was modified with carboxyl and fluorescein at the two terminals. When touching the A549 cells, DOX@PCN-224-DNA can trace tumor cells and present good targeting therapy by the combination of chemotherapy and photodynamic therapy. This facile aptamer functionalization of PCN-224 offers an opportunity to develop metal-organic framework-based target-directed therapy and biosensors.

Puerarin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of inflammation.

Diabetic cardiomyopathy (DCM) is one of the chief diabetes mellitus complications. Inflammation factors may be one reason for the damage from DM. The purpose of this research is to study the potential protective effects of puerarin on DM and the possible mechanisms of action related to NF-κB signal pathway. Following administration of puerarin to the disease model rat, several changes were observed including the changes of serum biochemical index, improved diastolic dysfunction, and enhanced endogenous antioxidant enzymes activities, further NF-κB signaling activation. Puerarin showed cardio-protective effects on DCM by inhibiting inflammation, and it might be a potential candidate for the treatment of DCM.

A variant in the SCN10A enhancer may affect human mechanical pain sensitivity.

Expression of Nav1.8, encoded by SCN10A, can affect pain transmission and thus mediate the human pain phenotype. In the current study, we assessed whether the variant rs6801957, located in the SCN10A enhancer region, may have the potential to affect human pain. Through dual-luciferase reporter assays in 293T cells, we found that the SCN10A enhancer A (Enh-A) increased the activity of the SCN10A promoter ( P < 0.05). Additionally, in a cohort of 309 healthy women, mutant rs6801957 A/A was found to have a significant association with decreased human experimental mechanical pain sensitivity ( P < 0.05). We then found that mutant genotype A/A suppressed the increased effect of Enh-A compared with wild-type G/G ( P < 0.05). The association between rs6801957 and human experimental mechanical pain sensitivity was further validated in a larger cohort of 1005 women ( P < 0.05). In conclusion, these results demonstrated that the variant rs6801957 and Enh-A may affect SCN10A gene expression and play an important role in human mechanical pain sensitivity.

A SCN10A SNP biases human pain sensitivity.

BACKGROUND: Nav1.8 sodium channels, encoded by SCN10A, are preferentially expressed in nociceptive neurons and play an important role in human pain. Although rare gain-of-function variants in SCN10A have been identified in individuals with painful peripheral neuropathies, whether more common variants in SCN10A can have an effect at the channel level and at the dorsal root ganglion, neuronal level leading to a pain disorder or an altered normal pain threshold has not been determined. RESULTS: Candidate single nucleotide polymorphism association approach together with experimental pain testing in human subjects was used to explore possible common SCN10A missense variants that might affect human pain sensitivity. We demonstrated an association between rs6795970 (G > A; p.Ala1073Val) and higher thresholds for mechanical pain in a discovery cohort (496 subjects) and confirmed it in a larger replication cohort (1005 female subjects). Functional assessments showed that although the minor allele shifts channel activation by -4.3 mV, a proexcitatory attribute, it accelerates inactivation, an antiexcitatory attribute, with the net effect being reduced repetitive firing of dorsal root ganglion neurons, consistent with lower mechanical pain sensitivity. CONCLUSIONS: At the association and mechanistic levels, the SCN10A single nucleotide polymorphism rs6795970 biases human pain sensitivity.

Identification of metabolites of the novel anti-tumor drug candidate MDH-7 in rat urine by liquid chromatography coupled with triple quadrupole linear ion trap mass spectrometry.

RATIONALE: Our previous preliminary pharmacokinetic study demonstrated that the novel double pyrimidine tricyclic nucleoside MDH-7 in rats had a very short half-life (<30 min) after oral administration. As a result, the in vivo metabolic profile of MDH-7 should be investigated during early stages of drug development to better select drug candidates. METHODS: In this study, a rapid method was developed to identify the metabolites of MDH-7 in rat urine by means of ultra-performance liquid chromatography (UPLC) coupled with electrospray ionization mass spectrometry (ESI-MS) using a triple quadrupole linear ion trap instrument. MDH-7 and its metabolites were detected and characterized by the combined use of the multiple reaction monitoring-information-dependent acquisition-enhanced product ion (MRM-IDA-EPI) mode and the precursor scan information-dependent acquisition-enhanced product ion (PREC-IDA-EPI) mode. RESULTS: Ten novel metabolites of MDH-7 were identified and characterized in rat urine by LC/ESI-MS and collision-induced dissociation tandem mass spectrometry (CID-MS/MS) analyses. M1 was identified as 5-fluoro-N(4) -[(pentyloxy)carbonyl]cytosine; M2 and M3 were formed by hydroxylation products of M1. Metabolites M4-M10 were formed by a series of degradation reactions such as: deacetylation, hydroxylation, loss of the defluorocytosine base, oxidative-deamination, loss of the defluorouracil base, N-dealkylation and amide hydrolysis. CONCLUSIONS: Based on the profiles of the metabolites, possible metabolic pathways of MDH-7 in rats were proposed for the first time. This study provides new and available information on the metabolism of MDH-7 which is very useful to further understand its in vivo metabolic fate. Copyright © 2016 John Wiley & Sons, Ltd.

Endotracheal Administration of Sufentanil and Tetracaine During Awake Fiberoptic Intubation.

Combined use of local anesthetics and low-dose opioids enhances the effects of local anesthetics. This study aimed to evaluate the efficacy of combined administration of sufentanil and tetracaine through the cricothyroid membrane during awake nasal intubation using fiberoptic bronchoscopy in patients with difficult airways. Forty patients were divided into 2 groups: group A received endotracheal administration of 25 µg of sufentanil and 2 mL of 1% tetracaine mixture; group B received endotracheal administration of 2 mL 1% tetracaine and routine local anesthetic sprays followed by slow intravenous injection of 25 µg of sufentanil. The results showed that endotracheal intubation was safely completed in all patients and vital signs including blood pressure, heart rate, and pulse oxygen saturation were not significantly different between groups A and B. However, time required for local anesthesia to take effect, time required to complete intubation, cough reflex, patient tolerance during intubation, and hemodynamic indices were significantly better in group A than in group B. In conclusion, our results suggest that endotracheal administration of sufentanil combined with tetracaine is safe, effective, and feasible in the context of awake nasal intubation using fiberoptic bronchoscopy.

[Progress of clinical trials in Alzheimer's disease drugs].

Alzheimer's disease(AD) is a chronic progressive neurodegenerative disease. The pathogenesis of AD is unclear, and it is presently incurable. Medicines currently available for AD treatment are only for improving the cognitive symptoms, but not able to stop or delay disease progression. Here, we summarized the interventions in early phases of AD in clinical trial. As a complex disease, AD is difficult to be restored through a treatment on a single target. Multi-target and cocktail drugs might be a strategy for development of AD therapies. In addition, AD is characterized by progressive neuronal loss in the cortex and hippocampus. The induction of neurogenesis by small molecule compounds has drawn attention in the AD field. The study of natural products in China is leading the way in the AD world. Numerous natural products have been identified for pharmacological effects on multi-targets in the regulation of neurogenic activity, which may open up a new avenue for AD treatments.

Rhodium-catalyzed enantioselective hydrogenation of tetrasubstituted α-acetoxy ß-enamido esters: a new approach to chiral α-hydroxyl-ß-amino acid derivatives.

Asymmetric hydrogenation of tetrasubtitued α-acetoxy ß-enamido esters with rhodium catalysts based on chiral diphosphine ligands provides an efficient and concise route to the synthesis of chiral α-hydroxyl-ß-amino acid derivatives in excellent enantioselectivities. The products are valuable chiral building blocks in many biologically active compounds and have important applications in organic synthesis.

Study on the Bending-Shear Properties of Concrete-Filled Circular Carbon Fibre Reinforced Plastic Steel Tubes.

In order to study the bending-shear performance of CFRP concrete-filled steel tubes, static tests were conducted on 15 circular concrete-filled CFRP steel tube bending-shear specimens. For all specimens, Ds was 120 mm, ts was 2 mm, and ml was 1. The shear displacement (V-Δ) curve of the specimen and the collaborative work between the steel tube and CFRP are discussed. ABAQUS was applied to simulate the V-Δ curve and failure mode of the specimen. We explored the effects of CFRP layers, material strength, the steel ratio, and the shear span ratio on the bending-shear performance of components. The experimental results show that a steel tube and CFRP can work together. As the shear span ratio increased, the bearing capacity and stiffness of the specimen decreased. An increase in the number of transverse CFRP layers could improve the bearing capacity of the specimen, but it had no significant effect on the stiffness. Calculating the elastic stage stiffness and bearing capacity of 15 short columns of test and FE curves revealed an average error of 6.71% and a mean square error of 0.83 for the elastic stage stiffness. The simulation results of the established finite element model are in good agreement with the experimental results. The average error of the bearing capacity was 3.88%, with a mean square error of 0.94. Based on experimental and finite element results, the moment shear correlation equation for concrete-filled CFRP steel tube bending-shear members is presented.

Comparison of three-colour flow cytometry and slide-based microscopy for the scoring of micronucleated reticulocytes in rat bone-marrow and peripheral blood.

The aim of this study was to perform the first transferability assessment in China of the micronucleus (MN) scoring method based on three-colour flow cytometry (FCM). This was accomplished for both rat bone-marrow and peripheral blood specimens following exposure to a variety of genotoxic and non-genotoxic chemicals, whereby micronucleus induction was measured both with FCM and with traditional microscopy. In an initial study, rats were treated with vehicle or cyclophosphamide (CP) for 2 consecutive days by oral gavage, and blood and bone marrow were sampled at 24 h after the second treatment. Staining with acridine orange (AO) of methanol-fixed slides was used for microscopical analysis and 2000 reticulocytes (RET) or polychromatic erythrocytes (PCE) were scored for MN frequency. The erythrocytes in the remaining bone-marrow cell suspensions were eluted on cellulose columns. The eluted bone marrow as well as the peripheral blood cells was fixed, incubated and analyzed by FCM. In another experiment, the performance of the FCM-MN method was further evaluated with five clastogens (urethane, 5-fluorouracil, mitomycin C, methylmethane sulfonate and 6-thioguanine), two aneugens (vincristine sulfate and colchicine) and two non-genotoxic new drugs (compounds A and B), whose results were negative in the routine mouse-micronucleus test (MNT). The MN frequencies in rat peripheral blood induced by the positive chemicals were found to be lower than the frequencies in rat bone-marrow by both scoring methods. However, a high level of agreement for the MN frequencies in both compartments was obtained. Good correspondence between the two analysis methods was also achieved. These data provide support that the three-colour FCM method is more rapid and objective than manual microscopy, while yielding comparable data. It further supports the premise that rat peripheral blood may be an alternative to rat bone marrow in the MNT.

Electricity-driven asymmetric bromocyclization enabled by chiral phosphate anion phase-transfer catalysis.

Electricity-driven asymmetric catalysis is an emerging powerful tool in organic synthesis. However, asymmetric induction so far has mainly relied on forming strong bonds with a chiral catalyst. Asymmetry induced by weak interactions with a chiral catalyst in an electrochemical medium remains challenging due to compatibility issues related to solvent polarity, electrolyte interference, etc. Enabled by a properly designed phase-transfer strategy, here we have achieved two efficient electricity-driven catalytic asymmetric bromocyclization processes induced by weak ion-pairing interaction. The combined use of a phase-transfer catalyst and a chiral phosphate catalyst, together with NaBr as the bromine source, constitutes the key advantages over the conventional chemical oxidation approach. Synergy over multiple events, including anodic oxidation, ion exchange, phase transfer, asymmetric bromination, and inhibition of Br2 decomposition by NaHCO3, proved critical to the success.

Characteristics and risk assessment of chilling injury on Morchella esculenta in Western Sichuan Plateau, China.

The development of precise climate risk zoning for chilling injury of Morchella esculenta can provide scientific basis for agricultural cultivation planning, dynamic assessment of chilling injury, and disaster prevention strategies. Based on meteorological data from 17 counties (cities) that located below the altitude of 3000 m in the Western Sichuan Plateau from 2011 to 2020, we analyzed the critical meteorological conditions for M. esculenta disasters in typical years. With the average yearly cold accumulation and cold injury frequency during the first day when the temperature remained stable between 5 ℃ and 10 ℃ during mushroom emergence as zoning indicators, we established a geographical spatial distribution model of the cold injury index, and then divided the risk level of M. esculenta cold injury in the Western Sichuan Plateau, evaluated the risk of cold injury. The results showed that the temperature index for chilling injury risk of M. esculenta in the study area was the daily minimum temperature ≤2.0 ℃. The daily average temperature <6.0 ℃ would cause slow growth or the cessation of growth, which was set as a warning indicator for chilling injury risk. Along the Dadu River and Minjiang River basins, the frequency of chilling injury on M. esculenta increased from south to north. Wenchuan, Maoxian, and Lixian had the fewest overall chilling injuries during the study period, whereas Jiulong, Yajiang, and Batang had the most. The duration for cold injury was mainly 1-3 d, followed by 4-5 d, and rarely for >5 d. The frequency of chilling injury lasting for more than 5 d in Xiangcheng, Batang, Jiulong, Yajiang, and Xiaojin was more than that lasting for 4-5 d. The annual average days of chilling injury of was 3.0-27.4 d, the daily average minimum temperature was -0.84-1.36 ℃, the extreme lowest temperature was -5.8-0.1 ℃, and the average accumulated cold was 0.16-9.64 ℃·d during the period of chilling injury. With the increases of elevation and latitude, the average days of chilling injury and the average accumulated cold increased. The largest duration of chilling injury was 3-20 d, the maximum accumulated cold was 0.44-13.34 ℃·d. The risk of chilling injury to M. esculenta increased from south to north and from low elevation to high elevation. The suitable planting areas were distributed in strips and branches along the direction of mountains and rivers, mainly in the flat areas of low mountains and valleys below the altitude of 2200 m, including Kangding, Luding, Danba, Wenchuan, Lixian, Maoxian, Jiuzhaigou, and Songpan.

[Killing effect of garlic extract on Schistosoma japonicum cercariae and Oncomelania snails].

The killing effect of different concentrations of garlic extract solution on Schistosoma japonicum cercariae and Oncomelania snails was observed under dissecting microscope. Mice were infected by cercariae through the abdominal skin daubed by garlic solution or by deionized water as control. The results showed that the cercariae were killed in (77.33 +/- 25.01) s in average, it needed (73.00 +/- 1.73)- (299.67 +/- 18.96) s under the garlic solution concentrations of 50.00%-0.79% respectively, while the cercariae kept alive in 600 s in the control. The snails were killed in 1 d by 100% garlic solution but no death in the control in 2 d. No mouse daubed with different concentrations of garlic solution was found infected by schistosomes while 100% of the control mice got infected. It is concluded that the garlic shows satisfactory effect in killing cercariae and Oncomelania snails, and may prevent schistosome infection by daubing the skin.

Study of the Behavior of Square Concrete-Filled CFRP Steel Tubular under a Bending-Torsion Load.

To study the behavior of square concrete-filled CFRP (carbon fiber polymer) steel tubular under bending-torsional load, nine square section concrete-filled CFRP steel tubular specimens are designed. The T-θ curve and failure mode of square concrete-filled CFRP steel tubular are studied under a bending-torsional load. Based on the test results, a finite element modeling method is proposed by using the finite element software ABAQUS, and the simulation results are compared with the experimental results. The results show that the simulation is in good agreement with the experimental results. On the basis of verifying the reliability of the model, the whole stress process and parameter analysis of the component are studied, and the calculation expression of bearing capacity of square concrete-filled CFRP steel tubular under bending-torsion load is proposed. The predicted specimen-bearing capacity of the proposed calculation expression of the bearing capacity of square concrete-filled CFRP steel tubular under bending-torsion load is basically consistent with the test results.

Test on Compressive Performance of Concrete Filled Circular Steel Tube Connected by Thread through Inner Lining Tube.

The connection method of lengthening the steel tube of concrete filled circular steel tubes by inner lining tube and threaded connection is proposed. Taking the length, depth, and position of the thread as the basic parameters, 12 concrete filled circular steel tubes connected by thread through inner lining tube were designed and manufactured, and an axial compressive test was carried out. The axial compressive loading-longitudinal compressive displacement curves, axial compressive loading-strain of steel tube curves, and failure mode of the specimens were analyzed, and the effects of different parameters on the axial compressive bearing capacity and stiffness of the specimens were studied. The results show that the axial compressive loading-longitudinal compressive displacement curves of the specimen can be divided into the elastic stage, elasto-plastic stage, and plastic reinforcement stage in the range of parameters studied in this paper. The bearing capacity and stiffness of the specimens connected by thread through inner lining tube are no worse than those of the unconnected specimen or the specimen connected by weld. Bearing capacity and stiffness of the specimen increase with the increase of thread length. The calculation method of the axial compressive bearing capacity of concrete filled circular steel tubes connected by thread through inner lining tube are suggested.