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With the emergence of the new generation vision architecture Vmamba and the further demand for agricultural yield and efficiency, we propose an efficient and high-accuracy target detection network for automated pear picking tasks based on Vmamba, aiming to address the issue of low efficiency in current Transformer architectures. The proposed network, named SRSMamba, employs a Reward and Punishment Mechanism (RPM) to focus on important information while minimizing redundancy interference. It utilizes 3D Selective Scan (SS3D) to extend scanning dimensions and integrates global information across channel dimensions, thereby enhancing the model's robustness in complex agricultural environments and effectively adapting to the extraction of complex features in pear orchards and farmlands. Additionally, a Stacked Feature Pyramid Network (SFPN) is introduced to enhance semantic information during the feature fusion stage, particularly improving the detection capability for small targets. Experimental results show that SRSMamba has a low parameter count of 21.1 M, GFLOPs of 50.4, mAP of 72.0%, mAP50 reaching 94.8%, mAP75 at 68.1%, and FPS at 26.9. Compared with other state-of-the-art (SOTA) object detection methods, it achieves a good trade-off between model efficiency and detection accuracy. [ABSTRACT FROM AUTHOR]

Graphene field‐effect transistors (GFETs) are widely used in biosensing due to their excellent properties in biomolecular signal amplification, exhibiting great potential for high‐sensitivity and point‐of‐care testing in clinical diagnosis. However, difficulties in complicated fabrication steps are the main limitations for the further studies and applications of GFETs. In this study, a modular fabrication technique is introduced to construct microfluidic GFET biosensors within 3 independent steps. The low‐melting metal electrodes and intricate flow channels are incorporated to maintain the structural integrity of graphene and facilitate subsequent sensing operations. The as‐fabricated GFET biosensor demonstrates excellent long‐term stability, and performs effectively in various ion environments. It also exhibits high sensitivity and selectivity for detecting single‐stranded nucleic acids at a 10 fm concentration. Furthermore, when combined with the CRISPR/Cas12a system, it facilitates amplification‐free and rapid detection of nucleic acids at a concentration of 1 fm. Thus, it is believed that this modular‐fabricated microfluidic GFET may shed light on further development of FET‐based biosensors in various applications. [ABSTRACT FROM AUTHOR]

Exosome-like nanovesicles (ELNs) derived from plants are nanoscale vesicles isolated from edible plant sources. Lycium ruthenicum Murray (LRM) has garnered growing attention for its dietary value and therapeutic benefits. In this study, a PEG6000-based method was developed to isolate LRM-ELNs. Response surface methodology (RSM) was used to optimize the extraction conditions to obtain the optimal extraction efficiency. When PEG6000 concentration was at 11.93%, relative centrifugal force was 9720 g, and incubation time was 21.12 h, the maximum LRM-ELN yield was 4.24 g/kg. This optimization process yielded LRM-ELNs with a particle size of 114.1 nm and a surface charge of −6.36 mV. Additionally, LRM-ELNs mitigated Aβ-induced apoptosis in HT22 cells by enhancing mitochondrial membrane potential (MMP), lowering the Bax/Bcl-2 ratio, and reducing Cleaved Caspase-3 expression. Furthermore, LRM-ELNs alleviated Aβ-induced oxidative stress in HT22 cells by promoting the nuclear translocation of Nrf2 and upregulating the expression of HO-1 and NQO1. These findings indicate that LRM-ELNs exert protective effects against Aβ-induced damage in HT22 cells and may be considered as a potential dietary supplement for Alzheimer's disease prevention. [ABSTRACT FROM AUTHOR]

The measurement of cardiac troponin I (cTnI) is of vital importance for the early diagnosis of acute myocardial infarction. In this study, an enhanced electrochemiluminescent immunoassay for the highly sensitive and precise determination of cTnI was reported. A biomimetic chip with nepenthes peristome surface microstructures to achieve single-layer microbead arrays and integrated microelectrode arrays (MEAs) for ECL detection was microfabricated. Ru@SiO2 nanoparticles were prepared as signal amplificators labeling immunomagnetic beads. Dendrimer-encapsulated platinum nanoparticles (Pt DENs) were electrochemically modified on ITO MEAs. The resulting Pt DEN-modified ITO MEAs preserved good optical transparency and exhibited an approximately 20-fold ECL signal amplification compared to that obtained from bare ITO. The method made full use of the biomimetic chip with Pt DENs to develop single-layer immunomagnetic bead arrays with increasingly catalyzed electrochemical oxidation of the [Ru(bpy)3]2+–TPA system. Consequently, a limit of detection calculated as 0.38 pg/mL (S/N = 3) was obtained with excellent selectivity, demonstrating significant potential for the detection of cTnI in clinical diagnostics. [ABSTRACT FROM AUTHOR]

Volatile organic compounds (VOCs) produced by Bacillus species exhibit biocontrol activity against fungal pathogens of fruits and vegetables. However, research on the effect of VOCs on Aspergillus flavus in stored grains is limited. This study aimed to investigate the effects of VOCs extracted from the strain R2, which was isolated from unhulled rice and identified as Bacillus paramycoides on A. flavus in vitro and unhulled rice. R2 VOCs effectively inhibited conidial germination and the hyphal growth of A. flavus in vitro. Moreover, R2 VOCs reduced the fungal population, aflatoxin B1 (AFB1) levels, and free fatty acid (FFA) value by 90.8%, 67%, and 38.7%, respectively, in unhulled rice. Eighteen R2 VOCs were identified using headspace solid-phase micro-extraction gas chromatography–mass spectrometry, and the individual activity of the VOCs against A. flavus was tested in vitro. Benzaldehyde (Ben) and 3,7-dimethyl-1-octanol (Dmo) showed strong inhibitory activities against A. flavus on PDA plates, with inhibition rates of 100% and 91.2%, respectively, at a concentration of 20 μL/dish. Ben at the concentration of 0.09 mg/mL, Dmo at the concentration of 0.07 mg/mL, or a mixture of both at halved concentrations could reduce the fungal population, AFB1 levels, and FFA content in unhulled rice. Our findings suggest that R2 VOCs are good alternatives to traditional chemical fumigants for suppressing A. flavus in stored grains. However, further research is necessary to establish the optimal fumigation concentration of these two components in unhulled rice. The impact of their residues on grain quality should be explored through sensory evaluation and nutritional analysis, and their safety to the environment and human body should be evaluated through safety assessment. [ABSTRACT FROM AUTHOR]

The diversity of metabolites produced in fermented pine needles at different stages of fermentation has rarely been investigated. In the present study, untargeted metabolomic analysis using GC-MS and LC-MS was performed to detect metabolites in fermented pine needles at different fermentation stages. A total of 30 samples of pine needles fermented first with yeast (Saccharomyces cerevisiae) and then with a mixed bacterial culture of Lactobacillus fermentum CECT5716 and Bifidobacterium Breve M16V, were used to detect differential metabolites at different stages of fermentation. Pearson's correlation analysis was used to determine correlations between metabolites and key microbial communities. A total of 708 differential metabolites (430 from LC-MS and 278 from GC-MS analysis) were identified. The PCA and OPLS-DA revealed distinct differences between metabolites at different fermentation stages. Key differential metabolites identified through GC-MS analysis included; Phosphoric acid, D-Fructose, 2-O-alpha-mannosyl-D-glycerate, 1,3-dihydroxyacetone dimer, Galactosylglycerol, 2-Isopropylmalic acid, alpha-D-Galactose, Citrate, 4-Hydroxycinnamic acid, and Shikimate. Similarly, key differential metabolites identified through LC-MS included; 2-Phenlyethanol, Dimethlglycine, 2-Hydroxybenzaldehyde, 3-Aminoisobutanoic acid, p-Cresol, Triethylamine, 2-Ketobutyric acid, Cytosine, Benzaldehyde, and Creatinine. Annotation of differential metabolites to KEGG pathway enrichment analysis revealed the association of these metabolites with phenylpropanoid, flavonoid, and secondary metabolite biosynthesis. Furthermore, the results showed that three bacterial (Firmicutes, Actinobacteria, and Lactobacillus) and three fungal genera (Penicillium, Candida, and Basidiomycota) significantly correlated with differential metabolites showing synergistic effects. Our study reveals a comprehensive comparison of metabolites at different fermentation stages and provides practical insights into the mechanism of metabolite enrichment in fermented pine needles. [ABSTRACT FROM AUTHOR]

Sensitive detection and precise quantitation of trace-level crucial biomarkers in a complex sample matrix has become an important area of research. For example, the detection of high-sensitivity cardiac troponin I (hs-cTnI) is strongly recommended in clinical guidelines for early diagnosis of acute myocardial infarction. Based on the use of an electrode modified by single-walled carbon nanotubes (SWCNTs) and a Ru(bpy)32+-doped silica nanoparticle (Ru@SiO2)/tripropylamine (TPA) system, a novel type of electrochemiluminescent (ECL) magneto-immunosensor is developed for ultrasensitive detection of hs-cTnI. In this approach, a large amount of [Ru(bpy)3]2+ is loaded in SiO2 (silica nanoparticles) as luminophores with high luminescent efficiency and SWCNTs as electrode surface modification material with excellent electrooxidation ability for TPA. Subsequently, a hierarchical micropillar array of microstructures is fabricated with a magnet placed at each end to efficiently confine a single layer of immunomagnetic microbeads on the surface of the electrode and enable 7.5-fold signal enhancement. In particular, the use of transparent SWCNTs to modify a transparent ITO electrode provides a two-order-of-magnitude ECL signal amplification. A good linear calibration curve is developed for hs-cTnI concentrations over a wide range from 10 fg/ml to 10 ng/ml, with the limit of detection calculated as 8.720 fg/ml (S/N = 3). This ultrasensitive immunosensor exhibits superior detection performance with remarkable stability, reproducibility, and selectivity. Satisfactory recoveries are obtained in the detection of hs-cTnI in human serum, providing a potential analysis protocol for clinical applications. HIGHLIGHTS: • An integrated microfluidic chip is fabricated to confine immunomagnetic beads at the electrode surface, leading to improved electrochemiluminescent efficiency and increased sensitivity in electrochemiluminescent immunoassays. • The combination of single-walled carbon nanotubes with the excellent electrooxidation ability of TPA and SiO2 nanoparticles as carriers loading a large amount of [Ru(bpy)3]2+ enables a sensitivity improvement of at least two orders of magnitude. • The electrochemiluminescent magneto-immunosensor exhibits an ultralow detection limit of 8.72 fg/ml, excellent selectivity and reproducibility, and satisfactory recoveries in human serum. [ABSTRACT FROM AUTHOR]

Rationale: Clinical and preclinical studies have demonstrated that estradiol withdrawal after delivery is one of important factors involved in the pathogenesis of postpartum depression (PPD). The infralimbic cortex (IL) is related to anxiety and mood disorders. Whether IL neurons mediate PPD is still unclear. Objectives: This study was to observe the antidepressant effect and expression of BDNF and β-catenin in IL by allopregnanolone (ALLO) treatment or the selective activation or inhibition of IL neurons using a chemogenetic approach in a pseudopregnancy model of PPD. Methods: Administration of estradiol combined with progesterone and the abrupt withdrawal of estradiol simulated the pregnancy and early postpartum periods to induce depression in ovariectomized rats. The relative expression levels of β-catenin and BDNF were observed by western blotting. Results: Immobility time was significantly increased in the forced swim test and open-arm movement was reduced in the elevated plus maze test in the estradiol-withdrawn rats. After ALLO treatment, the immobility time were lower and open-arm traveling times higher than those of the estradiol-withdrawn rats. Meanwhile, the expression level of BDNF or β-catenin in the IL was reduced significantly in estradiol-withdrawn rats, which was prevented by treatment with ALLO. The hM3Dq chemogenetic activation of pyramidal neurons in the IL reversed the immobility and open-arm travel time trends in the estradiol-withdrawal rat model, but chemogenetic inhibition of IL neurons failed to affect this. Upregulated BDNF and β-catenin expression and increased c-Fos in the basolateral amygdala were found following IL neuron excitation in model rats. Conclusions: Our results demonstrated that pseudopregnancy and estradiol withdrawal produced depressive-like behavior and anxiety. ALLO treatment or specific excitement of IL pyramidal neurons relieved abnormal behaviors and upregulated BDNF and β-catenin expression in the IL in the PPD model, suggesting that hypofunction of IL neurons may be involved in the pathogenesis of PPD. [ABSTRACT FROM AUTHOR]

Objective: Gastroesophageal reflux disease (GERD) and migraine are public health concerns worldwide. No observational study has conclusively elucidated the causal relationship between these two conditions. We employed Mendelian randomization (MR) methods to explore the potential causal links between GERD and migraine. Methods: Genome-wide association studies were subjected to MR to infer the causality between GERD and migraine. Bidirectional two-sample MR was performed to establish causal relationships. Multivariable MR analysis was conducted to adjust potential confounding factors, and mediation MR analysis was utilized to assess the role of depression between GERD and migraine as a mediator. We primarily utilized the inverse variance weighted method (IVW) and sensitivity analysis methods, including MR-Egger, weighted median, and leave-one-out methods. We assessed heterogeneity and pleiotropy to ensure the reliability of the results. Results: Bidirectional two-sample MR revealed a positive causal effect of GERD on migraine (IVW: OR = 1.49, 95% CI: 1.34–1.66, p = 3.70E-13). Migraine did not increase the risk of GERD (IVW: OR = 1.07, 95% CI: 0.98–1.17, p = 0.1139). Multivariable MR indicated that the positive causal effect of GERD on migraine remained after adjustment for factors, such as smoking, alcohol consumption, obesity, type 2 diabetes, and depression. Mediation MR revealed that depression mediated 28.72% of GERD's effect on migraine. MR analysis was supported by all sensitivity analyses and was replicated and validated in another independent dataset on migraine. Conclusion: Our findings elucidate the positive causal effect of GERD on migraine and underscores the mediating role of depression in increasing the risk of migraine due to GERD. Effective control of GERD, particularly interventions targeting depression, may aid in preventing the occurrence of migraine. Future research should delve deeper into the specific pathophysiological mechanisms through which GERD affects migraine risk, facilitating the development of more effective drug targets or disease management strategies. [ABSTRACT FROM AUTHOR]

Synthetic cathinones, derived from cathinone found in the plant Catha edulis, represent the second largest and most frequently seized group of new psychoactive substances. They are considered as β-keto analogs of amphetamine, sharing pharmacological effects with amphetamine and cocaine. This review describes the neurotoxic properties of synthetic cathinones, encompassing their capacity to induce neuroinflammation, dysregulate neurotransmitter systems, and alter monoamine transporters and receptors. Additionally, it discusses the rewarding and abuse potential of synthetic cathinones drawing from findings obtained through various preclinical animal models, contextualized with other classical psychostimulants. The review also offers an overview of current abuse trends of synthetic cathinones on the illicit drug market, specifying the aspects covered, and underscores the risks they pose to public health. Finally, the review discusses public health initiatives and efforts to reduce the hazards of synthetic cathinones, including harm reduction methods, education, and current clinical management strategies. [ABSTRACT FROM AUTHOR]

N‐Isopropylbenzylamine (N‐ipb), a chain isomer of methamphetamine (METH) with similar physical properties, has been used as a substitute for METH in seized drug samples. However, the abuse potential of N‐ipb remains unclear. Therefore, this study aimed to evaluate the abuse potential of N‐ipb in comparison to METH, by using conditioned place preference (CPP), locomotor sensitization and intravenous self‐administration tests. The results showed that N‐ipb at a dose of 3 mg·kg−1 significantly induced CPP in mice, which was comparable to the effect of METH at 1 mg·kg−1. Either acute or repeated N‐ipb injections (1 or 3 mg·kg−1) failed to raise the locomotor activity. However, acute treatment with 10 mg·kg−1N‐ipb elevated the locomotor activity compared with saline, while chronic injection of 10 mg·kg−1N‐ipb induced a delayed and attenuated sensitization compared with 1 mg·kg−1 METH. Rats could acquire N‐ipb self‐administration at a dose of 1 mg·kg−1·infusion−1, and a typical inverted U‐shaped dose–response curve was obtained for N‐ipb. The mean dose of N‐ipb that maintained the maximum response was greater than that of METH, indicating that N‐ipb is less potent for reinforcement than METH. In the economic behavioural analysis, comparison of essential values derived from the demand elasticity revealed that N‐ipb is less efficacy as a reinforcer than METH. The present data demonstrate that N‐ipb functions as a reinforcer and has a potential for abuse. However, the potency of psychomotor stimulation and the reinforcing effectiveness of N‐ipb are lower than those of METH. [ABSTRACT FROM AUTHOR]

The photothermal performance of black phosphorus (BP) in the near infrared (NIR)‐II bio‐window (1000–1500 nm) is low, which limits its biomedical applications. Herein, ultrasmall nickel phosphide quantum dots (Ni2P QDs) are synthesized with BP quantum dots (BPQDs) as the template by topochemical transformation. The size of Ni2P QDs is ≈3.5 nm, similar to that of BPQDs, whereas the absorption and photothermal conversion efficiency of Ni2P QDs at 1064 nm (43.5%) are significantly improved compared with those of BPQDs. To facilitate in vivo applications, an Ni2P QDs‐based liposomal nano‐platform (Ni2P‐DOX@Lipo‐cRGD) is designed by incorporation of Ni2P QDs and doxorubicin (DOX) into liposomal bilayers and the interior, respectively. The encapsulated DOX is responsively released from liposomes upon 1064‐nm laser irradiation owing to the photothermal effect of Ni2P QDs, and the drug release rate and amount are controlled by the light intensity and exposure time. In vivo, experiments show that Ni2P‐DOX@Lipo‐cRGD has excellent tumor target capability and biocompatibility, as well as complete tumor ablation through the combination of photothermal therapy and chemotherapy. The work provides a new paradigm for the NIR‐II transformation of nano‐materials and may shed light on the construction of multifunctional nano‐platforms for cancer treatment. [ABSTRACT FROM AUTHOR]

Electro‐chemically reducing CO2 in a highly acidic medium is promising for addressing the issue of carbonate accumulation. However, the hydrogen evolution reaction (HER) typically dominates the acidic CO2 reduction. Herein, we construct an efficient electro‐catalyst for CO formation based on a core‐shell structure, where nitrogen‐doped Ni nanoparticles coexist with nitrogen‐coordinated Ni single atoms. The optimal catalyst demonstrates a significantly improved CO faradaic efficiency (FE) of 96.7 % in the acidic electrolyte (pH=1) at an industrial‐scale current density of 500 mA cm−2. Notably, the optimal catalyst maintains a high FE of CO exceeding 90 % (current density=500 mA cm−2) in the electrolyte with a wide pH range from 0.67 to 14. In‐situ spectroscopic characterization and density functional theory calculations show that the local electron density of Ni‐N‐C sites is enhanced by N‐doped Ni particles, which facilitates the formation of *COOH intermediate and the adsorption of *CO. This study demonstrates the potential of a hybrid metal/Ni‐N‐C interface in boosting acidic CO2 electro‐reduction. [ABSTRACT FROM AUTHOR]

As a common tumor with high incidence, osteosarcoma possesses extremely poor prognosis and high mortality. Improving the survival of osteosarcoma patients is still a great challenge due to the precipice of advancement in treatment. In this study, a combination strategy of gene therapy and photothermal therapy (PTT) is developed for efficient treatment of osteosarcoma. Two-dimensional (2D) FePS3 nanosheets are synthesized and functionalized by poly-L-lysine-PEG-folic acid (PPF) to fabricate a multifunctional nanoplatform (FePS@PPF) for further loading microRNAs inhibitor, miR-19a inhibitor (anti-miR-19a). The photothermal conversion efficiency of FePS@PPF is up to 47.1% under irradiation by 1064 nm laser. In vitro study shows that anti-miR-19a can be efficiently internalized into osteosarcoma cells through the protection and delivery of FePS@PPF nanaocarrier, which induces up-regulation of PTEN protein and down-regulation p-AKT protein. After intravenous injection, the FePS@PPF nanoplatform specifically accumulates to tumor site of osteosarcoma-bearing mice. The in vitro and in vivo investigations reveal that the combined PTT-gene therapy displays most significant tumor ablation compared with monotherapy. More importantly, the good biodegradability promotes FePS@PPF to be cleared from body avoiding potential toxicity of long-term retention. Our work not only develops a combined strategy of NIR-II PTT and gene therapy mediated by anti-miR-19a/FePS@PPF but also provides insights into the design and applications of other nanotherapeutic platforms. [ABSTRACT FROM AUTHOR]

The kinetics and mechanisms of selective maltose hydrogenation over Raney Ni remain poorly understood, which hinders the industrial advancement of maltitol production for biorefining. Herein, the impact of hydrogenation conditions and in‐depth mechanistic characterizations were carefully investigated in this research. Optimization of reaction conditions illustrated that maltitol formation was favored by moderate reaction temperatures (≤130°C), high hydrogen pressures (>7 MPa), and near‐neutral sodium phosphate buffer (pH = 6.47). Kinetic studies demonstrated the Ea of 45.5 kJ/mol for the hydrogenation of maltose. The in situ IR revealed that the hydrogenation of maltose over Raney Ni occurs in the order of ring opening and adsorption via CO of the aldose form followed by hydrogenation. The UV–vis spectra demonstrated the near‐neutral setting (pH = 6.47) promoted the production of open‐chain aldose conformation and selective CO hydrogenation to the corresponding alcohols. The present study on concentrated‐maltose hydrogenation paves the way for the industrial development of maltitol manufacturing. [ABSTRACT FROM AUTHOR]

In this study, the flavor compounds of Camellia seed oils obtained by four processes were characterized by headspace solid phase microextraction/gas chromatography/mass spectrometry (HS-SPME/GC/MS). A variety of about 76 volatile flavor compounds were identified from all the oil samples. Of the four processing processes, the pressing process can retain a lot of volatile components. Among these, compounds nonanal and 2-undecenal were predominantly in the majority of the samples. Meanwhile, other compounds such as octyl ester formic acid, octanal and 2-nonenal (E), 3-acetyldihydro 2(3H)-furanone, (E)-2-decenal, dihydro-5-penty 2(3H)-furanone, nonanoic acid, and dodecane were also among the most consistently found compounds among the oil samples analyzed. The principal component analysis carried out to categorize the data produced seven clusters of the total oil samples based on the number of flavor compounds obtained in each sample. This categorization would lead to understanding the components which highly contributed to the characteristic volatile flavor and build up the flavor profile of Camellia seed oil. [ABSTRACT FROM AUTHOR]

Harnessing the physiochemical properties and enzymatic activities of nanozymes will provide new insights for disease theranostics. Herein, a novel carbon dot (C‐dot) superoxide dismutase (SOD) nanozyme that exhibits red fluorescence with emission wavelength of 683 nm and shows high SOD‐like activity of >4000 U mg−1 is reported, which presents the great potential for imaging the biodistribution of nanozyme itself in vivo and ameliorating acute lung injury. Through surface modifications, the mechanism of C‐dot SOD nanozyme activity is revealed to be relied on their surface functional groups which bind with superoxide radicals, promote the electron transfer between C‐dots and superoxide radicals, and finally accelerate the dismutation of superoxide radicals. The absolute quantum yield of ≈14% of red fluorescence C‐dot nanozyme endow it bioimaging in vitro and in vivo. Moreover, the C‐dot nanozyme effectively enters the cells, accumulates at mitochondria, and protects living cells from oxidative damage by scavenging reactive oxygen species (ROS) and reducing the levels of pro‐inflammatory factors. Importantly, in vivo animal experiments demonstrate the accumulation of C‐dots in injure lung and therapeutic effect of C‐dot nanozyme toward acute lung injury in mice. The red fluorescent C‐dot SOD nanozyme shows great potential for in vivo bioimaging and management of ROS‐related diseases. [ABSTRACT FROM AUTHOR]

Brain white matter (WM) networks have been widely studied in neuropsychiatric disorders. However, few studies have evaluated alterations in WM network topological organization in patients with methamphetamine (MA) dependence. Therefore, using machine learning classification methods to analyze WM network topological attributes may give new insights into patients with MA dependence. In the study, diffusion tensor imaging-based probabilistic tractography was used to map the weighted WM networks in 46 MA-dependent patients and 46 control subjects. Using graph-theoretical analyses, the global and regional topological attributes of WM networks for both groups were calculated and compared to determine inter-group differences using a permutation-based general linear model. In addition, the study used a support vector machine (SVM) learning approach to construct a classifier for discriminating subjects with MA dependence from control subjects. Relative to the control group, the MA-dependent group exhibited abnormal topological organization, as evidenced by decreased small-worldness and modularity, and increased nodal efficiency in the right medial superior temporal gyrus, right pallidum, and right ventromedial putamen; the MA-dependent group had the higher hubness scores in 25 regions, which were mainly located in the default mode network. An SVM trained with topological attributes achieved classification accuracy, sensitivity, specificity, and kappa values of 98.09% ± 2.59%, 98.24% ± 4.00%, 97.94% ± 4.26%, and 96.18% ± 5.19% for patients with MA dependence. Our results may suggest altered global WM structural networks in MA-dependent patients. Furthermore, the abnormal WM network topological attributes may provide promising features for the construction of high-efficacy classification models. [ABSTRACT FROM AUTHOR]

Background: The survival rate of patients with diabetes mellitus (DM) and end‐stage renal disease (ESRD) undergoing maintenance dialysis, including hemodialysis (HD) and peritoneal dialysis (PD), is markedly lower than that observed in patients with ESRD without DM. Methods: We used propensity score matching to balance the clinical characteristics of patients from the HD and PD groups. We compared the survival rate between HD or PD, followed by Cox regression analyses accounting for age, Charlson comorbidity index (CCI), body mass index (BMI), and serum albumin levels to examine the outcome influence of dialysis modalities. Results: During follow‐up, there were 19 (18.1%) and 18 (17.1%) deaths among patients who underwent HD and PD, respectively (P = 0.856). Kaplan–Meier survival analyses showed no significant difference in overall survival between patients in the HD and PD groups. Cox regression analyses stratified based on age, CCI, BMI, and serum albumin demonstrated that the choice of HD over PD did not influence survival. Conclusions: Regardless of age, CCI, BMI, and albumin level, patients with DM and ESRD had similar survival rates whether they received HD or PD in China. The choice of dialysis modality should be individualized according to patients' physical status and local practices for patients with DM and ESRD. [ABSTRACT FROM AUTHOR]

This paper investigated the effects of different particle sizes and addition levels of purple sweet potato flour (PSPF) on the rheological properties and moisture states of wheat dough. There was deterioration in the pasting and mixing properties of the dough, due to the addition of PSPF (0~20% substitution), which was reduced by decreasing the particle size of the PSPF (260~59 μm). Dynamic rheology results showed that PSPF enhanced the elasticity of the dough, providing it solid-like processability. PSPF promoted the binding of gluten proteins and starch in the dough, resulting in a denser microstructure. Differential scanning calorimetry and low-field nuclear magnetic resonance showed that PSPF converted immobilized water and freezable water to bound water and non-freezable water in the dough, making the dough more stable, and that the reduction in PSPF particle size facilitated these processes. Our results provide evidence for the great application potential of purple sweet potatoes for use in flour-based products. [ABSTRACT FROM AUTHOR]

To improve the quality and organoleptic properties of fermented pine needle, the physiological parameters and microbial communities must be explored. In this study, high-throughput sequencing was used to explore bacterial and fungal communities during the fermentation process of pine needle after adding starter culture of 0.8% activated dry yeast and Lactobacillus fermentum CECT5716 and Bifidobacterium Breve M-16 V. During the fermentation, the total flavonoid (from 0.049 to 111.404 mg/L) and polyphenol (from 19.412 to 183.399 mg/L) contents increased rapidly from 0 to 15 days. The total sugar increased from 0 to 3 days fermentation with a range from 3.359 mg/mL to 45.502 mg/mL in yeast fermentation stage, and reached the maximum value on day 3. The content of total acid (39.167 g/L) and amino acid nitrogen (1.185 g/L) gradually increased during the entire fermentation process and reached a maximum on day 7 of bacterial fermentation. Firmicutes and Proteobacteria phyla were the predominant bacteria in all time periods. At the genus level, well-known Lactobacillus was the most abundant bacterial strain on day 3, followed by Gluconobacter. The Acetobacter constituted more than 50% of the total bacterial abundance on day 1, but it decreased with the fermentation process. Exploration of fermented pine needle microbial community structure will expand the knowledge about their microbiota to manipulate the microbial community and improve their quality and organoleptic properties using different microbial recipes. [ABSTRACT FROM AUTHOR]

Urgent start peritoneal dialysis (USPD) is an effective therapeutic method for end-stage renal disease (ESRD). However, whether it is safe to initiate peritoneal dialysis (PD) within 24 h unclear. We examined the short-term outcomes of a break-in period (BI) of 24 h for patients undergoing USPD. This real-world, multicenter, retrospective cohort study evaluated USPD patients from five centers from January 2013 to August 2020. Patients were divided into BI ≤ 24 h or BI > 24 h groups. The Primary outcomes included incidence of mechanical and infectious complications. The secondary outcome was technique failure. Moreover, we presented a subgroup analysis for patients who did not receive temporary hemodialysis (HD). A total of 871 USPD patients were included: 470 in the BI ≤ 24 h and 401 in the BI > 24 h groups. Mechanical and infectious complications did not differ between the two groups across the follow-up timepoints (2 weeks, 1 month, 3 months, and 6 months) (p > 0.05). Multiple logistic regression analysis revealed that BI ≤ 24 h was not an independent risk factor for mechanical complications, catheter migration, or infectious complications (p > 0.05). A BI ≤ 24 h was not an independent significant risk factor for technique failure by multivariate Cox regression analysis (p > 0.05). The subgroup analysis of patients who did not receive temporary HD returned the same results. Initiating PD within 24 h of catheter insertion was not associated with increased mechanical complications, infectious complications, or technique failures. [ABSTRACT FROM AUTHOR]

The article in Advanced Science discusses the modular fabrication of a graphene field-effect transistor biosensor for detecting nucleic acids with high sensitivity and specificity. The method allows for the customization of microfluidic electronic devices for various applications. The research was conducted by a team of authors led by Zhen Zhao and Jiahong Wang, providing valuable insights into biosensing technology. [Extracted from the article]

Locality sensitive hashing (LSH), one of the most popular hashing techniques, has attracted considerable attention for nearest neighbor search in the field of image retrieval. It can achieve promising performance only if the number of the generated hash bits is large enough. However, more hash bits assembled to the binary codes contain massive redundant information and require more time cost and storage spaces. To alleviate this limitation, we propose a novel bit selection framework to pick important bits out of the hash bits generated by hashing techniques. Within the bit selection framework, we further exploit eleven evaluation criteria to measure the importance and similarity of each bit generated by LSH, so that the bits with high importance and less similarity are selected to assemble new binary codes. To demonstrate the effectiveness of the proposed framework of bit selection, we evaluated the proposed framework with the evaluation criteria on five commonly used data sets. Experimental results show the proposed bit selection framework works effectively in different cases, and the performance of LSH has not been degraded significantly after redundant hash bits reduced by the evaluation criteria. [ABSTRACT FROM AUTHOR]

Background: As one of the most widely planted fruit trees in southern China, citrus occupies an important position in the agriculture field and forestry economy in China. There are many kinds of citrus diseases. If citrus infected with diseases cannot be controlled in time, it easily seriously affects citrus production and causes large economic losses. Timely monitoring of disease characteristics in the citrus growth process is important for implementing timely control measures. Citrus images are easily disturbed by environmental factors such as dust, low light, clouds or leaf shadows. This makes it easy for some disease spot features in citrus pictures to be obscured. Occluded lesions cannot be effectively extracted and recognized. Second, similar characteristics of different diseases also make it difficult to distinguish the different types of diseases. However, the existing machine vision technology for identifying citrus diseases still has some difficulties in dealing with the above problems. Results: This paper proposes a new citrus disease identification framework. First, a citrus image enhancement algorithm based on the MSR-AMSR algorithm is proposed, which can enhance the image and highlight the disease characteristic information. The AMSR algorithm can also greatly alleviate the interference of clouds and low light on image lesions, making the image features clearer. Second, an MF-RANet network is proposed to recognize citrus disease images. MF-RANet is composed of a main feature frame and a detail feature frame. The main feature frame uses the cross stacking structure of ResNet50 and RAM to extract the main features in the citrus image dataset. RAM is used to extract the attention weight in the feature layer, which enables RAM to give higher weight to disease features. The detailed feature frame path uses AugFPN to extract features from multiple scales and fuse the main feature frame path. AugFPN enables the network to retain more detailed features, so it can effectively distinguish similar features in different diseases. In addition, we use the ELU activation function not only to solve the problem of gradient explosion and gradient disappearance but also to effectively use the negative input of the network. Finally, we use the label smoothing regularization method to prevent overfitting the network in the classification process. Finally, the experimental results show that the highest detection accuracy of the network for Huanglong disease, Corynespora blight of citrus, fat spot macular disease, citrus scab, citrus canker and healthy citrus is 96.77%, 96.22%, 95.96%, 95.93%, 94.04% and 97.55%, respectively. Conclusions: The citrus disease algorithm based on AMSR and MF-RANet can effectively perform the disease detection function. It has a high recognition rate for different kinds of citrus diseases. With the addition of AMSR preprocessing, RAM, AugFPN, ELU activation function and other structures, the MF-RANet network performance improves. [ABSTRACT FROM AUTHOR]

Rationale: Following the emergence of methylone as one of the most popular synthetic cathinones, this group of novel psychoactive substance with names ending in "-lone," such as dibutylone, ethylone, and N-ethylpentylone, appeared on the recreational drug market. The pharmacological mechanisms of dibutylone, ethylone, and N-ethylpentylone are well understood; however, to date, the reinforcing effects of dibutylone, ethylone, and N-ethylpentylone are still unclear. Objectives: This study aimed to examine the self-administration of dibutylone, ethylone, and N-ethylpentylone relative to methamphetamine (METH) and to quantify their relative reinforcing effectiveness using behavioral economic analysis. Methods: Male Sprague–Dawley rats were trained to self-administer METH (0.05 mg/kg) under a fixed-ratio 1 (FR1) schedule. Following the training, dose substitution was used to generate full dose–response curves for METH and the three synthetic cathinones. According to the first doses on the descending limb of the dose–response curves, rats were trained to self-administer METH (0.05 mg/kg), dibutylone (0.1 mg·kg−1·infusion−1), ethylone (0.4 mg·kg−1·infusion−1), or N-ethylpentylone (0.1 mg·kg−1·infusion−1) under an FR1 schedule, and a behavioral economic evaluation of their reinforcing effectiveness was then performed. Results: Dibutylone, ethylone, and N-ethylpentylone functioned as reinforcers, and the inverted U-shaped dose–response curves were obtained. The rank order of reinforcing potency in this procedure was METH > N-ethylpentylone ≈ dibutylone > ethylone. In the economic analysis, the comparisons of the essential value (EV) transformed from demand elasticity (α) indicated that the rank order of efficacy as reinforcers was METH (EV = 7.93) ≈ dibutylone (EV = 7.81) > N-ethylpentylone (EV = 5.21) ≈ ethylone (EV = 4.19). Conclusions: These findings demonstrated that dibutylone, ethylone, and N-ethylpentylone function as reinforcers and have addictive potential, suggesting that the modification of α-alkyl and N-alkyl side chains may affect their reinforcing efficacy. [ABSTRACT FROM AUTHOR]

Oxidative stress in the brain is highly related to the pathogenesis of Alzheimer's disease (AD). It could be induced by the overproduction of reactive oxygen species (ROS), produced by the amyloid beta (Aβ) peptide and excess copper (Cu) in senile plaques and cellular species, such as ascorbic acid (AA) and O2. In this study, the protective effect of 5-hydroxy-7-(4′-hydroxy-3′-methoxyphenyl)-1-phenyl-3-heptanone (DHPA) on Aβ(1–42)/Cu2+/AA mixture-treated SH-SY5Y cells was investigated via in vitro and in silico studies. The results showed that DHPA could inhibit Aβ/Cu2+/AA-induced SH-SY5Y apoptosis, OH· production, intracellular ROS accumulation, and malondialdehyde (MDA) production. Further research demonstrated that DHPA could decrease the ratio of Bax/Bcl-2 and repress the increase of mitochondrial membrane potential (MMP) of SH-SY5Y cells, to further suppress the activation of caspase-3, and inhibit cell apoptosis. Meanwhile, DHPA could inhibit the Aβ/Cu2+/AA-induced phosphorylation of Erk1/2 and P38 in SH-SY5Y cells, and increase the expression of P-AKT. Furthermore, DHPA could bind to Keap1 to promote the separation of Nrf2 to Keap1 and activate the Keap1/Nrf2/HO-1 signaling pathway to increase the expression of heme oxygenase-1 (HO-1), quinone oxidoreductase-1 (NQO1), glutathione (GSH), and superoxide dismutase (SOD). Thus, our results demonstrated that DHPA could inhibit Aβ/Cu2+/AA-induced SH-SY5Y apoptosis via scavenging OH·, inhibit mitochondria apoptosis, and activate the Keap1/Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

The coupling of acetonitrile into succinonitrile, an important terminal dinitrile for value-added nylon production, via a dehydrogenative route is highly attractive, as it combines the valuable chemical synthesis with the production of green hydrogen energy. Here, we demonstrate that it is possible to achieve a highly selective light driven dehydrogenative coupling of acetonitrile molecules to synthesize succinonitrile using anatase TiO2 based photocatalysts in aqueous medium under mild conditions. Under optimized conditions, the formation rate of succinonitrile reaches 6.55 mmol/(gcat*h), with over 97.5% selectivity to target product. Mechanism studies reveal that water acts as cocatalyst in the reaction. The excited hole of anatase semiconductor oxidizes water forming hydroxyl radical, which subsequently assists the cleavage of sp3 C-H bond of acetonitrile to generate ·CH2CN radical for further C-C coupling. The synergy between TiO2 and Pt cocatalyst is important to enhance the succinonitrile selectivity and prevent undesirable over-oxidation and hydrolysis. This work offers an alternative route to prepare succinonitrile based on renewable energy under mild conditions and avoid the use of toxic reagents and stoichiometric oxidative radical initiators. The coupling of acetonitrile into succinonitrile via a dehydrogenative route is highly attractive in terms of valuable chemical synthesis and green hydrogen energy production. Here, the authors report succinonitrile synthesis with high selectivity and rate via a light driven dehydrogenative coupling reaction of CH3CN over the anatase TiO2 supported Pt catalyst. [ABSTRACT FROM AUTHOR]

Wholewheat sourdough products are becoming increasingly more popular, and Staphylococcus aureus is a common opportunistic pathogen in dough products. The effects of S. aureus contamination (102 cfu/g) on metabolites as well as titratable acidity (TTA), pH, and microbial diversity of sourdough were investigated. S. aureus contamination significantly decreased the content of mannose while increasing the sorbitol in sourdough (p < 0.05). The S. aureus contamination significantly reduced the number of lactic acid bacteria (LAB), such as Lactobacillus curvatus, and the TTA values (p < 0.05). Furthermore, S. aureus contamination significantly reduced the content of most esters and acid flavor compounds while significantly increasing the content of 2,4-decadienal (p < 0.05), which is a compound that could have a negative impact on the flavor of sourdough. The PCA model developed based on volatile metabolites data could be used to distinguish contamination of S. aureus in sourdough cultured for 4 h. Sorbitol, 2,3-dimethylundecane, 1-pentanol, and 3-methylbutanoic acid were newly found to be the characteristic metabolites in S. aureus-contaminated sourdough. [ABSTRACT FROM AUTHOR]

Grape cracking is a common phenomenon that can reach more than 50% in some varieties and can cause enormous economic losses. "Li Xiu" grapes in different developmental stages were treated with calcium chloride (5 g/L), and the cracking rate and related biochemical and genetic indices were measured in the fruit ripening stage. The results showed that calcium treatment during the flowering period could significantly reduce grape cracking. Based on the experimental results, there are several reasons as follows: first, calcium spraying during the flowering period was more favorable to calcium absorption in grapes, and the increased calcium content in the peels helped to improve the mechanical properties of the peels, thus increasing crack resistance; second, calcium treatment reduced the expression levels of genes related to glucose metabolism, which in turn reduced PG and cellulase activities, delaying the degradation of pectin and cellulose and resulting in more structural integrity of the peels; third, calcium treatment increased fruit hardness and reduced fruit ventral pressure by decreasing the expression levels of ABA-related genes and synthesis of endogenous abscisic acid (ABA), soluble sugars (SSs), and total soluble solids (TSSs). [ABSTRACT FROM AUTHOR]

With the world's energy resources decreasing, ethanol/acetone/ethyl acetate mixed fuel has the potential as a fossil fuel alternative or oxygenated fuel additive. In this work, the burning characteristics of ethanol/acetone/ethyl acetate mixed fuels including 3 pure fuels, 9 binary fuels, and 7 ternary fuels were studied at a temperature of 358 K, the pressure of 1 bar, and the equivalence ratios of 0.7 to 1.4 in the constant volume combustion chamber (CVCC). The burning velocities of the ternary fuels were compared at ϕ = 0.8, 1.0, and 1.4. The results show that the laminar burning velocities of the mixed fuels are affected by the contents of ethanol, acetone, and ethyl acetate. The Markstein length, Markstein number, and burning flux were also analyzed in this paper. Furthermore, a detailed chemical mechanism comprising 506 species and 2809 reactions was reduced to a skeletal mechanism including 98 species and 642 reactions, using the directed relation graph with error propagation (DRGEP). The experimental and the simulated laminar burning velocities were compared. The results of laminar burning velocities show that the relative deviation of ETEAAC 112 is approximately 17.5%. The sensitivity coefficients, flame structure, and reaction paths of ethyl acetate were investigated with the skeletal and the detailed mechanisms. It is found that the key reaction path is retained in the skeletal mechanism. [ABSTRACT FROM AUTHOR]

2-Fluorodeschloroketamine (2-FDCK) as a substitute for ketamine has emerged among drug abusers in recent years. However, 2-FDCK has not been controlled or regulated in many countries, which may be partly related to the lack of evidence on its abuse potential. In this study, we evaluated the abuse potential of 2-FDCK via the tests of the conditioned place preference (CPP), locomotor sensitization, drug self-administration and drug discrimination using ketamine as a reference. 2-FDCK induced significant CPP at a minimum dose of 3 mg/kg in mice, an effect comparable with that of ketamine (3 mg/kg). Acute injections of 2-FDCK or ketamine at 30 mg/kg enhanced locomotor activity. Repeated treatments with this dose of 2-FDCK and ketamine induced locomotor sensitization after withdrawal. 2-FDCK readily induced self-administration with 0.5 mg/kg/infusion, the same dose for ketamine, and induced the highest seeking response at 1 mg/kg. Drug discrimination test showed that 2-FDCK dose-dependently substitute for ketamine with comparable ED50 to ketamine in substitution testing. Taken together, these results strongly suggested that 2-FDCK has an abuse potential comparable with ketamine. [ABSTRACT FROM AUTHOR]

Botryosphaeria dothidea is a main post‐harvest pathogen of kiwifruit, causing fruit decay and health problems. In this study, the effect of Chinese herbal extract compound (CHEC) on the antifungal assay, the SEM (scanning electron microscope) observation, fluorescence microscopy observation, transcriptional profile, and physiological characters of B. dothidea was measured. CHEC (0.6 to 0.8 mg/ml) significantly inhibited mycelium growth, reduced the formation and germination of spores, and decreased the content of sugar and protein in the mycelium. The activity of SOD, CAT, POD, NADP‐malate dehydrogenase, succinate dehydrogenase, cellulase, and glucanase was significantly reduced, while the content of malondialdehyde in the mycelium was significantly increased. In addition, there was a significant decrease in DNA content and mitochondrial membrane potential and a significant increase in ROS. The mycelium appeared thicker, the top of the mycelium was significantly larger, the cell membrane of spores began to contract and bend, and the nucleus gradually disappeared. Transcriptome data showed that a total of 20,510 differentially expressed genes (DEGs) were obtained, including 19,139 down‐regulated and 1371 up‐regulated genes. Both RNA‐seq data and qRT‐PCR showed that the genes of remarkable down‐regulation were included in the membrane pathway, cell pathway, oxidoreductase activity pathway, transport and catabolism, and carbohydrate metabolism. Practical applications: CHEC is a mixture of several extracts with strong antifungal effects. It is a green and safe antifungal agent. CHEC has a strong antifungal effect by destroying mycelial cell structure, inhibiting gene expression and mycelial growth and metabolism. These findings provided additional useful information on the antifungal mechanism of CHEC at the molecular and genetic levels, and suggested that CHEC was a potential candidate to control B. dothidea. Moreover, our data provided novel insights into the green and safe preservation of kiwifruit. [ABSTRACT FROM AUTHOR]

Living on a high-fat, high-calorie, and high-protein diet for a long period may compromise human immunity due to the long-term accumulation of free radicals and plasma lipids. The antioxidant and lipid-lowering compounds (ie polyphenols and vitamin E) in Camellia oil help to decrease the risk of numerous ailments, including cardiovascular disease (CVD), and obesity. The aims of this study were to study the hypolipidemic and antioxidant effects of Camellia oil in high-fat-fed rats and to promote the high-value use of camellia resources. The high-fat-fed rats were administrated with 2.5, 7.5, and 15 mL/kg BW Camellia oil (Camellia oil group), and 10 mg/kg BW atorvastatin (atorvastatin group), respectively, and compared with a model group (only fed with high fat) and a control group (fed with basal diet). Several parameters were measured, including (1) body weight (BW), liver-to-BW ratio; (2) plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C); and (3) alanine aminotransferase (ALT), alanine aminotransferase (AST), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity, model driven architecture (MDA) content, lipid metabolism-related genes, and antioxidant-related genes in liver tissue. Compared with the model group, the high-fat-fed rats in the Camellia oil and atorvastatin group had significantly lower BW and liver-to-BW ratio (P <.01), plasma TC, TG, and LDL-C levels and ALT and AST activities, but higher HDL-C levels. The relative expressions of ACAT1, DGAT2, FAS, and SREBP genes were significantly reduced in the Camellia oil and atorvastatin groups, while the relative expressions of LCAT, UCP2, MCD, and CPT-1 genes were significantly increased. The rats in the Camellia oil group showed significantly higher SOD and GSH-Px activities, significantly lower MDA content, and significantly higher relative expression of antioxidant genes (eg SOD1, GPx1, CAT, and Gclm). Thus, atorvastatin and Camellia oil exhibited significant hypolipidemic and antioxidant effects, which were better at a dose of 7.5 mL/kg (BW) of Camellia oil. Therefore, Camellia oil becomes a potential new natural resource for future research and development of antioxidant and hypolipidemic drugs, nutraceuticals, and additives. [ABSTRACT FROM AUTHOR]

This study aims to examine the effects of ambient pressure and injection parameters on the macro-characteristics of air-assisted diesel spray. To illustrate the morphological variation of spray and the formation of vortex ring, the spray diffusion angle was defined. The results indicate that high ambient pressure hinders the radial and axial development of spray and delays the formation of vortex ring. As the ambient pressure increased from 1 bar to 2 bar, the formation of vortex ring was delayed by approximately 0.5 ms. Extending fuel injection duration reduced the spray penetration and increased the far- and near-field spray angles; however, the spray diffusion angle decreased. Increasing fuel injection pressure produces more small-sized droplets owing to enhanced droplet breakup, which decreased the spray penetration and facilitated the lateral diffusion of droplets. Increasing mixture injection duration did not affect the spray penetration; however, the variation of the diffusion angle was slowed down after the mixture injection ended. The insufficient fuel-air interval cannot adequately decelerate the injected fuel droplets, resulting in large penetration and weak lateral diffusion. And there was a critical interval between 1.0 ms − 3.0 ms in this study, after which the fuel droplets could be decelerated sufficiently. [ABSTRACT FROM AUTHOR]

Propofol addiction has been detected in humans and rats, which may be facilitated by stress. Corticotropin-releasing factor acts through the corticotropin-releasing factor (CRF) receptor-1 (CRF1R) and CRF2 receptor-2 (CRF2R) and is a crucial candidate target for the interaction between stress and drug abuse, but its role on propofol addiction remains unknown. Tail clip stressful stimulation was performed in rats to test the stress on the establishment of the propofol self-administration behavioral model. Thereafter, the rats were pretreated before the testing session at the bilateral lateral ventricle with one of the doses of antalarmin (CRF1R antagonist, 100–500 ng/site), antisauvagine 30 (CRF2R antagonist, 100–500 ng/site), and RU486 (glucocorticoid receptor antagonist, 100–500 ng/site) or vehicle. The dopamine D1 receptor (D1R) in the nucleus accumbens (NAc) was detected to explore the underlying molecular mechanism. The sucrose self-administration establishment and maintenance, and locomotor activities were also examined to determine the specificity. We found that the establishment of propofol self-administration was promoted in the tail clip treated group (the stress group), which was inhibited by antalarmin at the dose of 100–500 ng/site but was not by antisauvagine 30 or RU486. Accordingly, the expression of D1R in the NAc was attenuated by antalarmin, dose-dependently. Moreover, pretreatments fail to change sucrose self-administration behavior or locomotor activities. This study supports the role of CRF1R in the brain in mediating the central reward processing through D1R in the NAc and provided a possibility that CRF1R antagonist may be a new therapeutic approach for the treatment of propofol addiction. [ABSTRACT FROM AUTHOR]

The isolation of proanthocyanidins from raspberries and their antioxidant activity remains an ongoing challenge. Optimization of ultrasound-assisted extraction method of raspberry proanthocyanidins by response surface analysis. Assessment of the effect of AB-8 macroporous adsorption on obtaining proanthocyanidin monomers of different composition and evaluation of their antioxidant activity. Determination of protective effects of proanthocyanidins by cell proliferation assay. Under the optimized extraction conditions of 60% ethanol, material-to-liquid ratio of 1:30, ultrasonic extraction temperature of 44°C, time of 2 h, and power of 450 watts (W), the yield of proanthocyanidins was 0.914%. The four separated proanthocyanidins, D1, D2, D3, D4, showed dose-dependent antioxidant activities, with D2 having the best antioxidant effect. 100 μg/ml of D2 could scavenge above 90% free radicals and achieve above 85% of human cell survival rate. The identified extraction conditions and antioxidant activities may drive the development of potential health-promoting ingredients. [ABSTRACT FROM AUTHOR]

Aim: This study determined if gene variants in the GABA receptor delta subunit (GABRD) are associated with treatment response and dose in methadone maintenance treatment (MMT) for heroin addiction. Materials & methods: A total of 286 MMT patients were recruited and divided into response and nonresponse groups based on retention time in therapy. A total of 177 responders were classified into low dose and high dose subgroups according to the stabilized methadone dose. Four (single nucleotide polymorphisms) SNPs (rs13303344, rs4481796, rs2376805 and rs2229110) in GABRD were genotyped using the TaqMan SNP assay. Logistic regression was used to assess the genetic effects of the SNPs in MMT. Results: No significant associations were observed between the SNPs and treatment response or dose, except the frequency of haplotype ACGC at the four SNPs significantly differed between responders and nonresponders. Conclusion: The results indicated that GABRD variants may play a small role in modulating methadone treatment response. This study determined if gene variants in the GABA receptor delta subunit (GABRD) are associated with treatment response and dose in methadone maintenance treatment (MMT) for heroin addiction. A total of 286 MMT patients were recruited and divided into response and nonresponse groups. A total of 177 responders were classified into low and high dose subgroups. Four single nucleotide polymorphisms (SNPs) (rs13303344, rs4481796, rs2376805 and rs2229110) in GABRD were genotyped and assessed the genetic effects of the SNPs in MMT. No significant associations were observed between the SNPs and treatment response or dose, except the frequency of haplotype ACGC significantly differed between responders and nonresponders. The results indicated that GABRD variants may play a small role in MMT, which may help provide a foundation for personalized solutions for MMT. [ABSTRACT FROM AUTHOR]

Akt is initially identified as one of the downstream targets of phosphatidylinositol‐3 kinase (PI3K) and is involved in morphine reward and tolerance. However, whether phospholyration of Akt (p‐Akt) mediates heroin relapse remains unclear. Here, we aimed to explore the role of p‐Akt in the nucleus accumbens (NAc) in cue‐induced heroin‐seeking behaviors after withdrawal. First, rats were trained to self‐administer heroin for 14 days, after which we assessed heroin‐seeking behaviors induced by a context cue (CC) or by discrete conditioned cues (CS) after 1 day or 14 days of withdrawal. We found that the active responses induced by CC or CS after 14 days of withdrawal were higher than those after 1 day of withdrawal. Meanwhile, the expression of p‐Akt in the NAc was also greatest when rats were exposed to the CS after 14 days of withdrawal. Additionally, a microinjection of LY294002, an inhibitor of PI3K, into the NAc inhibited the CS‐induced heroin‐seeking behaviors after 14 days of withdrawal, paralleling the decreased levels of p‐Akt in the NAc. Finally, Akt1 or β‐arrestin 2 was downregulated via a lentiviral injection to assess the effect on heroin seeking after 14 days of withdrawal. CS‐induced heroin‐seeking behavior was inhibited by downregulation of Akt1, but not β‐arrestin 2, in the NAc. These data demonstrate that Akt phosphorylation in the NAc may play an important role in the incubation of heroin‐seeking behavior, suggesting that the PI3K/Akt pathways may be involved in the process of heroin relapse and addiction. [ABSTRACT FROM AUTHOR]

Rationale: Epigenetic regulation has been implicated in the incubation of drug craving (the time-dependent increase in drug seeking after prolonged withdrawal from drug self-administration). There is little information available on the role of microRNAs in incubation of heroin craving. Objective: This study aimed to investigate the roles and mechanisms of miR-181a and methyl CpG binding protein 2 (MeCP2) in the nucleus accumbens (NAc) in incubation of heroin seeking. Methods: MiRNA sequencing was used to predict potential miRNAs, and miRNA profiles were performed in the NAc after 1 day or 14 days after withdrawal from heroin self-administration. Following 14 days of heroin self-administration, rats were injected of lentiviral vectors into the NAc and evaluated for the effects of overexpression of miR-181a or knockdown of MeCP2 on non-reinforced heroin seeking after 14 withdrawal days. Results: Lever presses during the heroin-seeking tests were higher after 14 withdrawal days than after 1 day (incubation of heroin craving). miR-181a expression in NAc was lower after 14 withdrawal days than after 1 day, and meCP2 expression in NAc was higher after 14 days than after 1 day. Luciferase activity assay showed that the 3′UTR of MeCP2 is directly regulated by miR-181a. Overexpression of miR-181a in NAc decreased heroin seeking after 14 withdrawal days and decreased MeCP2 mRNA and protein expression. Knockdown of MeCP2 expression in NAc by LV-siRNA-MeCP2 also decreased heroin seeking after 14 withdrawal days. Conclusions: Results indicate that incubation of heroin craving is mediated in part by time-dependent decreases in NAc miR181a expression that leads to time-dependent increases in MeCP2 expression. Our data suggest that NAc miR-181a and MeCP2 contribute to incubation of heroin craving. [ABSTRACT FROM AUTHOR]

Heroin use disorder is a chronic and relapsing disease that induces persistent changes in the brain. The diagnoses of heroin use disorders are mainly based on subjective reports and no valid biomarkers available. Recent researches have revealed that circulating miRNAs are useful non-invasive biomarkers for diagnosing brain diseases such as Alzheimer's disease, multiple sclerosis, schizophrenia, and bipolar disorder. However, studies on circulating miRNAs for the diagnosis of heroin use disorders are rarely reported. In this study, we investigated the differential expression of plasma miRNAs in 57 heroin-dependent patients. Based on literature research and microarray analysis, two candidate miRNAs, miR-320a and let-7b-5p, were selected and analyzed by quantitative real-time RT-PCR. The results showed miR-320a and let-7b were significantly upregulated in plasma of the heroin-dependent patients compared to that in healthy controls. The area under curves (AUCs) of receiver operating characteristic (ROC) curves of miR-320a and let-7b-5p were 0.748 and 0.758, respectively. The sensitivities of miR-320a and let-7b-5p were 71.9 and 70.2%, while the specificities of miR-320a and let-7b-5p were 76.1 and 78.3%, respectively. The combination of these two miRNAs predicted heron dependence with an AUC of 0.782 (95% CI 0.687–0.876), with 73.7% sensitivity and 82.6% specificity. Our findings suggest a potential use for circulating miRNAs as biomarkers for the diagnosis of heroin abuse. [ABSTRACT FROM AUTHOR]

Testing for high risk human papillomavirus (HR-HPV) status is standard of care in squamous cell carcinomas of the oropharynx as well as cervical lymph node squamous cell carcinomas of unknown primary origin. DNA or RNA in-situ hybridization (ISH) and p16 immunohistochemistry, widely used currently for HPV detection are operator-dependent. In addition, DNA ISH has a relatively low sensitivity, and p16 is not entirely specific for HR-HPV infection. In this study, we examined the performance of the cobas® HPV genotyping assay in formalin-fixed, paraffin-embedded (FFPE) samples of head and neck squamous cell carcinoma. FFPE samples from head neck and other anatomic sites tested by ISH and p16 for HR-HPV at ARUP Laboratories were selected for this study. Samples were deparaffinized, stained and micro-dissected for tumor contents followed by tissue lysis, then tested with cobas® for HR-HPV. All the samples were also tested by HPV Linear Array for confirmation. All (N = 18) high risk HPV positive specimens tested by cobas® were confirmed as positive by the Linear Array test. All the specimens tested as negative by cobas® were tested as negative (N = 5) or positive only for low risk HPV (N = 3) by Linear Array, as cobas® only detects HR HPV. Limits of detection for HPV16 and 18 were established at 160–320 and 320–1600 copies, respectively. Our data suggest that cobas® HR-HPV genotyping is a viable option for detection of HR-HPV in formalin-fixed, paraffin-embedded samples from head and neck and other anatomic sites and has been validated for clinical use. [ABSTRACT FROM AUTHOR]