Sleep-related adverse events of smoking cessation drugs: A network meta-analysis of randomized controlled trials.

Smoking cessation medications have the potential to affect the functioning of the nervous system, leading to sleep disturbances. Our study aimed to compare the sleep-related side effects (such as insomnia, abnormal dreams, nightmares, and somnolence) induced by different smoking cessation medications in non-psychiatric smokers. We conducted a thorough search of five electronic databases (Cochrane, EMBASE, PubMed, PsycInfo, and Web of Science) for randomized controlled trials. This study was registered with the PROSPERO (registration number CRD42022347976). A total of 79 full-text articles, encompassing 36,731 participants, were included in our analysis. Individuals using bupropion, bupropion in combination with a nicotinic acetylcholine receptor agonist (NRA), and bupropion in conjunction with nicotine replacement therapy (NRT) exhibited a higher likelihood of experiencing insomnia compared to those using NRT alone. Bupropion plus NRA had the highest ranking on the surface under the cumulative ranking curve (SUCRA) for insomnia risk, while placebo had the lowest ranking. Additionally, NRA plus NRT ranked first for abnormal dream outcomes, NRA alone for nightmares, and nortriptyline for somnolence, based on the SUCRA results. Healthcare providers should exercise caution when prescribing smoking cessation drugs, particularly in consideration of their potential sleep-related side effects.

Association between the plasma concentration of melatonin and behavioral temperament in horses.

Aggression in horses may cause serious accidents during riding and non-riding activities. Hence, predicting the temperament of horses is essential for selecting suitable horses and ensuring safety during the activity. In certain animals, such as hamsters, plasma melatonin concentrations have been correlated with aggressive behavior. However, whether this relationship applies to horses remains unclear. To address this research gap, this study aimed to evaluate differences in the plasma melatonin concentrations among horses of different breeds, ages, and sexes and examine the correlation between plasma melatonin concentrations and the temperament of the horses, including docility, affinity, dominance, and trainability. Blood samples from 32 horses were collected from the Horse Industry Complex Center of Jeonju Kijeon College. The docility, affinity, dominance, and trainability of the horses were assessed by three professional trainers who were well-acquainted with the horses. Plasma melatonin concentrations were measured using an enzyme-linked immunosorbent assay. The consequent values were compared between the horses of different breeds, ages, and sexes using a three-way analysis of variance and least significant difference post hoc test. Linear regression analysis was employed to identify the relationship between plasma melatonin concentrations and docility, affinity, dominance, and trainability. The results showed that the plasma melatonin concentrations significantly differed with breeds in Thoroughbred and cold-blooded horses. However, there were no differences in the plasma melatonin concentrations between the horse ages and sexes. Furthermore, plasma melatonin concentrations did not exhibit a significant correlation with the ranking of docility, affinity, dominance, and trainability.

Equivalence of three thermal boundary conditions in compressible turbulent channel flows.

In this paper, direct numerical simulations have been performed to explore the equivalence of different thermal boundary conditions in compressible turbulent channel flows at fixed Re=6000,Ma=1.5. Three canonical types of thermal boundary conditions will be investigated at almost equivalent setups, including the first boundary condition with fixed wall temperature T_{w} (constant Dirichlet boundary condition), the second boundary condition with fixed wall heat-flux q_{w} (constant Neumann boundary condition), and the third boundary condition (Robin boundary condition). The turbulent statistics of the temperature and velocity fields, including mean profiles, root-mean-square values, second-order statistics, and normalized probability density functions, temperature stripes near the wall and the budget of internal energy have been analyzed in detail to clarify the differences caused by the different thermal boundary conditions. The results show that the three thermal boundary conditions have almost negligible effect on the velocity field, whereas some discernible deviations can be observed for the temperature field in the near-wall region with y^{+}≲30. Furthermore, the statistics from the second and third thermal boundary conditions are very close, enabling the usage of the second boundary condition to mimic the more complex third boundary conditions.

The Association between ABCG2 421C>A (rs2231142) Polymorphism and Rosuvastatin Pharmacokinetics: A Systematic Review and Meta-Analysis

Although several studies have revealed the association between rosuvastatin pharmacokinetics and the ABCG2 421C>A (rs2231142) polymorphism, most studies were conducted with small sample sizes, making it challenging to apply the findings clinically. Therefore, the purpose of this study is to perform a meta-analysis of the relationship between the ABCG2 421C>A polymorphism and rosuvastatin pharmacokinetics. We searched three electronic databases, EMBASE, PubMed, and Web of Science, using search terms related to ABCG2 gene polymorphisms and rosuvastatin. In addition, we reviewed studies published before 12 August 2021, to examine the relationship between the ABCG2 421C>A polymorphism and rosuvastatin pharmacokinetics. To examine the magnitude of the association, the log geometric mean difference (lnGM) and 95% confidence intervals (CIs) were calculated and interpreted as the antilogarithm of a natural logarithm (elnGM). The meta-analysis was performed using Review Manager (version 5.4) and R Studio (version 4.0.2). Subgroup analysis was performed according to race and the types of mean values. Among the 318 identified studies, a total of 8 studies involving 423 patients is included in this meta-analysis. The A allele carriers of ABCG2 421C>A showed 1.5 times higher in both AUC0-∞ (lnGM = 0.43; 95% CI = 0.35−0.50; p < 0.00001) and Cmax (lnGM = 0.42; 95% CI = 0.33−0.51; p < 0.00001) than non-carriers, while there was no significant difference in Tmax and half-life. There was no significance in the pharmacokinetic parameters of the subgroups using either ethnicity or mean values. This meta-analysis demonstrates that subjects carrying the A allele of ABCG2 421C>A show significantly increased AUC0-∞ and Cmax values compared to subjects with the CC genotype. Therefore, information about ABCG2 genotypes might be useful for individualized rosuvastatin therapy.

Alternative negative weight for simpler hardware implementation of synapse device based neuromorphic system.

Lately, there has been a rapid increase in the use of software-based deep learning neural networks (S-DNN) for the analysis of unstructured data consumption. For implementation of the S-DNN, synapse-device-based hardware DNN (H-DNN) has been proposed as an alternative to typical Von-Neumann structural computing systems. In the H-DNN, various numerical values such as the synaptic weight, activation function, and etc., have to be realized through electrical device or circuit. Among them, the synaptic weight that should have both positive and negative numerical values needs to be implemented in a simpler way. Because the synaptic weight has been expressed by conductance value of the synapse device, it always has a positive value. Therefore, typically, a pair of synapse devices is required to realize the negative weight values, which leads to additional hardware resources such as more devices, higher power consumption, larger area, and increased circuit complexity. Herein, we propose an alternative simpler method to realize the negative weight (named weight shifter) and its hardware implementation. To demonstrate the weight shifter, we investigated its theoretical, numerical, and circuit-related aspects, following which the H-DNN circuit was successfully implemented on a printed circuit board.

Influence of CYP2C9 Genetic Polymorphisms on the Pharmacokinetics of Losartan and Its Active Metabolite E-3174: A Systematic Review and Meta-Analysis.

This study aimed to investigate the influence of CYP2C9 genetic polymorphisms on the pharmacokinetics of losartan and its active metabolite, E-3174, through a systematic review and meta-analysis. Eight studies published before March 2021 were included in this study. We used PubMed, the Cochrane Library, EMBASE, and Web of Science, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The data analysis was conducted through Review Manager (RevMan), version 5.3, and R software. We found that healthy volunteers with CYP2C9*2 or *3 carriers had higher area under the curve (AUC0-∞) of losartan (mean difference (MD) 0.17 µg·h/mL; 95% confidence intervals (CI): 0.04, 0.29) and lower AUC0-∞ of E-3174 (MD -0.35 µg·h/mL; 95% CI: -0.62, -0.08) than those with CYP2C9*1/*1. Subjects with CYP2C9*2 or *3 carriers showed lower maximum concentration (Cmax) of E-3174 than those with CYP2C9*1/*1 (MD -0.13 µg/mL; 95% CI: -0.17, -0.09). For half-life, subjects with CYP2C9*2 or *3 carriers had longer half-lives of losartan and E-3174 than those with CYP2C9*1/*1 (MD 0.47 h; 95% CI: 0.32, 0.61 and MD 0.68 h; 95% CI: 0.44, 0.92, respectively). This meta-analysis suggests that the pharmacokinetics of losartan and E-3174 are associated with the CYP2C9 polymorphisms.

ABCA1 69C>T Polymorphism and the Risk of Type 2 Diabetes Mellitus: A Systematic Review and Updated Meta-Analysis.

Background: The ATP-binding cassette transporter A1 (ABCA1) is likely associated with the risk of type 2 diabetes mellitus (T2DM) via ß cell function modification, but the evidence on the association remains unclear. This study aimed to investigate the relationship between the ABCA1 69C>T polymorphism and the risk of T2DM through a systematic review and meta-analysis. Materials and Methods: The PubMed, Web of Science, and Embase databases were searched for qualified studies published until August 2020. Studies that included the association between the ABCA1 69C>T polymorphism and the risk of T2DM were reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated. Results: We analyzed data from a total of 10 studies involving 17,742 patients. We found that the CC or CT genotype was associated with increased risk of T2DM than the TT genotype (OR, 1.41; 95% CI, 1.02-1.93). In the Asian population, the C allele carriers had a higher risk of T2DM than those with the TT genotype; the ORs of the CC and CT genotypes were 1.80 (95% CI, 1.21-2.68) and 1.61 (95% CI, and 1.29-2.01), respectively. Conclusions: This meta-analysis confirmed that the ABCA1 69C>T genotype showed a decrease risk of T2DM compared to the CC or CT genotypes.

Synthesis of ginsenoside Re-based carbon dots applied for bioimaging and effective inhibition of cancer cells.

BACKGROUND: Fluorescent carbon-based nanomaterials have promising properties such as biosensing, cell imaging, tracing and drug delivery. However, carbon dots (CDs) with specific inherent biological functions have not been investigated. Ginsenosides are the components with multiple bioactivities found in plants of the genus Panax, which have attracted a lot of attention for their anticancer effect. MATERIALS AND METHODS: In this study, we prepared a kind of novel photoluminescent CDs from ginsenoside Re by one-step hydrothermal synthesis method. The conventional methods including transmission electron microscopy, Fourier transform infrared spectroscopy, HPLC and fluorescence spectrum were used for characterization of CDs. In vitro anticancer effect was investigated by cytotoxicity assay, flow cytometry and Western blot analysis. RESULTS: The as-prepared Re-CDs had an average diameter of 4.6±0.6 nm and excellent luminescent properties. Cellular uptake of Re-CDs was facilitated by their tiny nanosize, with evidence of their bright excitation-dependent fluorescent images. Compared with ginsenoside Re, the Re-CDs showed greater inhibition efficiency of cancer cell proliferation, with lower toxicity to the normal cells. The anticancer activity of Re-CDs was suggested to be associated with the generation of large amount of ROS and the caspase-3 related cell apoptosis. CONCLUSION: Hopefully, the dual functional Re-CDs, which could both exhibit bioimaging and anticancer effect, are expected to have great potential in future clinical applications.

Hydrothermal Addition Polymerization for Ultrahigh-Yield Carbonized Polymer Dots with Room Temperature Phosphorescence via Nanocomposite.

Hydrothermal/solvothermal treatments have been widely used to prepare carbonized polymer dots (CPDs) through the condensation and carbonization of small molecules and/or polymers. However, the basic scientific issues, such as the nucleation and growth process, morphology and size control, yield increase, and photoluminescence (PL) mechanism have not been well investigated. In this work, enlightened by the principle of soap-free emulsion polymerization, CPDs with ultrahigh yields (ca. 85 %) were obtained by hydrothermal addition polymerization and carbonization (HAPC) of monomers. The unprecedented initiator-induced addition polymerization was exploited to synthesize CPDs for the first time. As expected in typical emulsion polymerization processes, the developed HAPC method can produce CPDs with designed sizes by systematically regulating the HAPC parameter, uncovering an unprecedented strategy for regulating the size of CPDs. In addition, the obtained CPDs were provided with high photoluminescence quantum yields (PLQY) up to 45.58 %, while the relationship between the photoluminescence (PL) mechanism and chemical structure was investigated. The viscosity parameter was first adopted to measure the polymer property of CPDs. Moreover, the ultrahigh yield and low-cost CPDs elicited the high-performance CPDs/PVA nanocomposite (PVA=poly(vinyl alcohol)) with fluorescence and room-temperature phosphorescence dual-mode emission, demonstrating potential for advanced anti-counterfeit applications.

Design of Metal-Free Polymer Carbon Dots: A New Class of Room-Temperature Phosphorescent Materials.

Polymer carbon dots (PCDs) are proposed as a new class of room-temperature phosphorescence (RTP) materials. The abundant energy levels in PCDs increase the probability of intersystem crossing (ISC) and their covalently crosslinked framework structures greatly suppress the nonradiative transitions. The efficient methods allow the manufacture of PCDs with unique RTP properties in air without additional metal complexation or complicated matrix composition. They thus provide a route towards the rational design of metal-free RTP materials that may be synthesized easily. Furthermore, we find that RTP is associated with a crosslink-enhanced emission (CEE) effect, which provides further routes to design improved PCDs with diverse RTP performance. Our results show the potential of PCDs as a universal route to achieve effective metal-free RTP.

Berberine-based carbon dots for selective and safe cancer theranostics.

Fluorescent berberine-based carbon dots (Ber-CDs) were prepared through a facile synthesis strategy. Ber-CDs exhibited excellent optical properties for bioimaging and retained the biofunctions of berberine, and enabled selective and safe anti-tumor performance, demonstrating their promising application potential in cancer theranostics.

Full-Color Emission Polymer Carbon Dots with Quench-Resistant Solid-State Fluorescence.

Polymer carbon dots (PCDs) represent a new class of carbon dots (CDs) possessing sub-fluorophores and unique polymer-like structures. However, like small molecule dyes and traditional CDs, PCDs often suffer from self-quenching effect in solid state, limiting their potential applications. Moreover, it is hard to prepare PCDs that have the same chemical structure, exhibiting full-color emission under one fixed excitation wavelength by only modulating the concentration of the PCDs. Herein, self-quenching-resistant solid-state fluorescent polymer carbon dots (SSFPCDs) are prepared, which exhibit strong red SSF without any other additional solid matrices, while having a large production yield (≈89%) and a considerable quantum yield of 8.50%. When dispersed in water or solid matrices in gradient concentrations, they can exhibit yellow, green, and blue fluorescence, realizing the first SSFPCDs with the same chemical structure emitting in full-color range by changing the ratio of SSFPCDs to the solid matrices.

Carbon dots for tracking and promoting the osteogenic differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) hold great potential for tissue engineering and regeneration medicine. However, for clinical use, MSCs may be detrimental due to their uncertain fate during the transplantation. It is therefore highly desirable to develop biocompatible nanomaterials to integrate cell fate regulation with monitoring for MSC-based therapy. Herein, we employ recently developed citric acid-based carbon dots (CDs) and their derivatives (Et-IPCA) for labeling and tracking of rat bone marrow mesenchymal stem cells (rBMSCs). We further investigate their biocompatibility and effects on the osteogenic differentiation of rBMSCs. These highly fluorescent probes provide labeling of rBMSCs by internalization without affecting cell viability or inducing apoptosis when the concentration is lower than 50 µg mL-1. Importantly, the presence of the CDs and Et-IPCA facilitates high-efficiency osteogenic differentiation of rBMSCs by promoting osteogenic transcription and enhancing matrix mineralization. Compared to Et-IPCA, CDs considerably provide long-term tracking and promote the differentiation of rBMSCs toward osteoblasts through the ROS-mediated MAPK pathway. Taken together, our results consistently demonstrate that carbon dots are capable of both tracking and enhancing the osteogenic differentiation of MSCs. This study sheds new light on the potential of carbon dots as a bifunctional tool in the thriving field of MSC-based therapy.

Precisely Controllable Core-Shell Ag@Carbon Dots Nanoparticles: Application to in Situ Super-Sensitive Monitoring of Catalytic Reactions.

Carbon dots (CDs) have attracted extensive interest owing to their unparalleled physical and chemical characteristics. CDs based nanocomposites have also drawn increasing attention because the combination of different characteristics could offer additional brilliant properties (such as photocatalysis and Raman scattering). In this work, we developed a fast, facile, and controllable method for fabricating core-shell Ag@CDs nanoparticles (NPs) based on the ability of CDs to directly reduce Ag+ to Ag NPs without an external photoirradiation process or additional reductants. The as-prepared Ag@CDs NPs caused efficient CDs fluorescence quenching, and the typical bands of carbon species were obtained in the Raman spectrum of CDs. In addition, we found that the Ag@CDs NPs could be utilized as an efficient surface-enhanced Raman scattering (SERS) substrate, showing a discernible detection concentration as low as 10-8 M by using p-aminothiophenol (PATP) as the probe molecules. The as-prepared Ag@CDs NPs used as the SERS substrate also exhibited excellent peroxidase-like catalytic activity for in situ super-sensitive monitoring of the oxidation of 3,3',5,5'-tetramethylbenzidine by H2O2, a plasmon-enhanced driven photocatalytic reaction of p-nitrothiophenol (PNTP) dimerizing into 4,4'-dimercaptoazobenzene, and catalytic driven reduction of PNTP to PATP in the presence of NaBH4 in real time. Moreover, the determination of H2O2 with a significantly lower discernible detection concentration was obtained. This work demonstrated that the hybrid nanostructures not only exhibited unique SERS properties but also showed excellent catalytic activities, especially as an ultrasensitive SERS substrate for monitoring heterogeneous catalytic reactions in real time. This would make it possible to not only obtain the information about catalytic molecular changes but also conduct quantitative and qualitative analysis, and widen the application of CDs in SERS and catalytic reactions.

The effects of a series of carbon dots on fibrillation and cytotoxicity of human islet amyloid polypeptide.

Carbon dots (CDs) have been widely used as candidates for drug carriers and bio-imaging probes because of their high drug loading capacity and intrinsic fluorescence property, as well as their good biocompatibility. In this study, the potential role of CDs in regulating the aggregation behavior of human islet amyloid polypeptide (hIAPP) was explored for the first time. Five kinds of CDs belonging to three categories, namely polymer dots (PDs-1 and PDs-2), carbon nanodots (CNDs and CQDs), and graphene quantum dots (GQDs), were prepared and characterized. The fibrillation behaviors of hIAPP in the presence of these CDs were monitored by the ThT assay and TEM/AFM imaging, and the cytotoxicity of the systems was tested by the MTT and LDH release assays. Our results showed that the polymer dots and carbon nanodots inhibit hIAPP fibrillation, while the GQDs promoted the formation of hIAPP fibrils. The PDs and GQDs that were nontoxic in INS-1 cells exerted effects leading to decreasing cell death induced by hIAPP through different mechanisms. The inhibitory activity and mechanism of the CDs were closely associated with their structures and surface properties. Our results shed light on a new potential application of CDs in therapeutics.

Non-Conjugated Polymer Dots with Crosslink-Enhanced Emission in the Absence of Fluorophore Units.

A new type of fluorescent material is presented, which is called non-conjugated polymer dots (NCPDs). The NCPDs only possess sub-fluorophores (which are groups such as C=O, C=N, N=O) instead of typical conjugated fluorophore groups, and thus these materials should not have strong photoluminescence (PL) in the usual sense. Nevertheless, the PL of these sub-fluorophores can be enhanced by chemical crosslinking or physical immobilization of polymer chains, which is named the crosslink-enhanced emission (CEE) effect. The significant advances achieved by us and other groups on both experimental and theoretical aspects are discussed, and the covalent-bond CEE, rigidity-aggregated CEE, or supramolecular CEE in NCPDs is elaborated. Moreover, synthetic strategies, unique optical properties, and the promise of NCPDs in bio-related fields, such as bioimaging and drug delivery, are systematically discussed.

A novel fluorescent retrograde neural tracer: cholera toxin B conjugated carbon dots.

The retrograde neuroanatomical tracing method is a key technique to study the complex interconnections of the nervous system. Traditional tracers have several drawbacks, including time-consuming immunohistochemical or immunofluorescent staining procedures, rapid fluorescence quenching and low fluorescence intensity. Carbon dots (CDs) have been widely used as a fluorescent bio-probe due to their ultrasmall size, excellent optical properties, chemical stability, biocompatibility and low toxicity. Herein, we develop a novel fluorescent neural tracer: cholera toxin B-carbon dot conjugates (CTB-CDs). It can be taken up and retrogradely transported by neurons in the peripheral nervous system of rats. Our results show that CTB-CDs possess high photoluminescence intensity, good optical stability, a long shelf-life and non-toxicity. Tracing with CTB-CDs is a direct and more economical way of performing retrograde labelling experiments. Therefore, CTB-CDs are reliable fluorescent retrograde tracers.

Investigating the surface state of graphene quantum dots.

A universal route to GQDs is developed based on "solution phase-based scissor" methods. The PL centers of the GQDs are systematically studied and are proved to be the surface state. This is related to the hybridization structure of the edge groups and the connected partial graphene core. Through experiment and analysis, we have preliminarily proved that the efficient edge groups for green emission are mainly carboxyl, carbonyl and amide. This is indicated by the following three factors: firstly, the PL of GQDs is enhanced by UV exposure, during which partial -OH groups are converted into carboxyl groups; secondly, the PL properties of GQDs can be further improved by one-step solvothermal treatment, in which partial carboxyl groups are converted to amide groups and the surface state of the GQDs is enhanced; thirdly, reduced m-GQDs possess more -OH groups compared with reduced GQDs, resulting in more blue PL centers (the carboxyl, carbonyl and amide-based green centers are converted to -OH-based blue centers). The present work highlights a very important direction for the understanding of the PL mechanism of GQDs and other related carbon-based materials.

Novel cookie-with-chocolate carbon dots displaying extremely acidophilic high luminescence.

A fluorescent carbon dot with a cookie-with-chocolate film structure (about 5 × 5 µm(2)) showed a high fluorescence quantum yield (61.12%) at low pH. It was hydrothermally synthesized from l-serine and l-tryptophan. The formation mechanism of the film with carbon dots (CDs) was investigated. The film structure was formed by hydrogen bonding and π-π stacking interactions between aromatic rings. The strong blue fluorescence of the CDs increased under strong acidic conditions owing to the changes in the N-groups. These cookie-like CDs are attractive for their potential use as effective fluorescent probes for the sensitive detection of aqueous H(+) and Fe(3+).

The crosslink enhanced emission (CEE) in non-conjugated polymer dots: from the photoluminescence mechanism to the cellular uptake mechanism and internalization.

The crosslink enhanced emission (CEE) in a new type of non-conjugated polymer dots (PDs) is proved. The enhanced PL originates from the decreased vibration and rotation of amino-based chromophores. Furthermore, the cellular uptake mechanism and internalization of PDs were investigated in detail.