Chemical constituents from uncaria laevigata and their vasodilatory activities in vitro and action mechanism.

A new triterpenoid compound 1* (scandine A1) was obtained from 95% ethanol extract of Uncaria laevigata. Meanwhile, eleven described compounds were also isolated for the first time from Uncaria laevigata. Herein, compound 2 exhibited strong diastolic cardio-cerebrovascular activity (EC50BA = 9.22 µM and EC50CA = 14.65 µM), which was not been previously described. Compound 1* also showed certain diastolic cardio-cerebrovasculary activity. Network pharmacology indicated that the diastolic cardio-cerebrovascular activity of compound 2 was most correlated with the Ras signalling pathway. Molecular docking confirmed that it exhibited strong binding activity with target protein (matrix metalloproteinase inhibitor-1). Moreover, compound 2 demonstrated significant potential on cardio-cerebrovascular activity in vitro. Overall, compounds 1* and 2 with good diastolic cardio-cerebrovascular activity were discovered in this work.

Distinguishable Magnetic Reporter Coordination with Buoyancy-Magnetism Separation for Immobilization-Free Dual-Target Electrochemical Immunosensing.

Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.

Quantitative Measurement of Plasma Membrane Protein Internalisation and Recycling in Heterogenous Cellular Samples by Flow Cytometry.

Plasma membrane proteins mediate important aspects of physiology, including nutrient acquisition, cell-cell interactions, and monitoring homeostasis. The trafficking of these proteins, involving internalisation from and/or recycling back to the cell surface, is often critical to their functions. These processes can vary among different proteins and cell types and states and are still being elucidated. Current strategies to measure surface protein internalisation and recycling are typically microscopy or biochemical assays; these are accurate but generally limited to analysing a homogenous cell population and are often low throughput. Here, we present flow cytometry-based methods involving probe-conjugated antibodies that enable quantification of internalisation or recycling rates at the single-cell level in complex samples. To measure internalisation, we detail an assay where the protein of interest is labelled with a specific antibody conjugated to a fluorescent oligonucleotide-labelled probe. To measure recycling, a specific antibody conjugated to a cleavable biotin group is employed. These probes permit the differentiation of molecules that have been internalised or recycled from those that have not. When combined with cell-specific marker panels, these methods allow the quantitative study of plasma membrane protein trafficking dynamics in a heterogenous cell mixture at the single-cell level. Key features • These assays allow sensitive quantification of internalised or recycled surface molecules using oligonucleotide or cleavable biotin-conjugated probes, respectively, and detected by flow cytometry. • They can be adapted to any membrane protein that transits via the cell surface and for which a specific purified antibody is available. • The dynamics of a cell surface protein can be measured in heterogenous cell populations simultaneously, including various cellular activation states. • The internalisation assay builds upon the method developed by Liu et al. [1,2] and extends its application to heterogenous human peripheral blood mononuclear cells. • These assays have been extensively used on suspension cells but have not been tested on adherent cells.

Effects of age-based stereotype threat on time-based prospective memory.

The present study aimed to investigate the effect of a blatant activation of age-based stereotype threats (ABST) on time-based prospective memory (TBPM) in older adults. A sample of 74 adults from Hong Kong was randomly assigned to one of the two experimental conditions: the stereotyped condition (n = 36) or the neutral condition (n = 38). Participants were asked to read fictitious news reports related to dementia (stereotyped condition) or the importance of English oral skills (neutral condition). After, all participants performed a TBPM task using the Chinese lexical decision task as an ongoing task block. The results indicate a main effect of ABST on TBPM accuracy. Specifically, older adults under a blatant activation of ABST demonstrated lower TBPM accuracy (p < 0.05, ηp2 = 0.08). Further analyses based on age groups demonstrated that TBPM accuracy was only impaired in older participants (aged 70-80 years) (p < 0.05, ηp2 = 0.19). The study, for the first time, provides evidence that ABST can disrupt TBPM performance in older adults, especially when cues are blatantly activated.

Microbial community dynamics and functional potentials in the conversion of oil palm wastes into biomethane.

Oil palm processing generates substantial waste materials rich in organic content, posing various environmental challenges. Anaerobic digestion (AD), particularly for palm oil mill effluent (POME), offers a sustainable solution, by converting waste into valuable biomethane for thermal energy or electricity generation. The synergistic activities of the AD microbiota directly affect the biomethane production, and the microbial community involved in biomethane production in POME anaerobic digestion has been reported. The composition of bacterial and archaeal communities varies under different substrate and physicochemical conditions. This review discusses the characteristics of POME, explores the microbial members engaged in each stage of AD, and elucidates the impacts of substrate and physicochemical conditions on the microbial community dynamics, with a specific focus on POME. Finally, the review outlines current research needs and provides future perspectives on optimizing the microbial communities for enhanced biomethane production from oil palm wastes.

Stereoselective Synthesis of Xylodonin A and 22-Hydroxyxylodonin A and Discovery of Analogues with Cytotoxic Activity.

The first and stereoselective synthesis of xylodonin A and 22-hydroxyxylodonin A, two drimane-type sesquiterpenoid natural products, was developed from the readily available (+)-sclareolide. This route features an allylic oxidation and acid-promoted dehydration for construction of the key intermediate 6-hydroxyisodrimenin. Representative analogues were synthesized, and their previously unknown bioactivities were revealed after biological evaluation. The analogue 19a exhibited cytotoxic activity against liver cancer HepG2 cells (IC50: 8.8 vs 5.9 µM) that was comparable to that of the clinical anticancer drug etoposide with lower toxicity to normal liver HL7702 cells (IC50 > 100 µM).

Molecular and cellular pruritus mechanisms in the host skin.

Pruritus, also known as itching, is a complex sensation that involves the activation of specific physiological and cellular receptors. The skin is innervated with sensory nerves as well as some receptors for various sensations, and its immune system has prominent neurological connections. Sensory neurons have a considerable impact on the sensation of itching. However, immune cells also play a role in this process, as they release pruritogens. Disruption of the dermal barrier activates an immune response, initiating a series of chemical, physical, and cellular reactions. These reactions involve various cell types, including keratinocytes, as well as immune cells involved in innate and adaptive immunity. Collective activation of these immune responses confers protection against potential pathogens. Thus, understanding the molecular and cellular mechanisms that contribute to pruritus in host skin is crucial for the advancement of effective treatment approaches. This review provides a comprehensive analysis of the present knowledge concerning the molecular and cellular mechanisms underlying itching signaling in the skin. Additionally, this review explored the integration of these mechanisms with the broader context of itch mediators and the expression of their receptors in the skin.

Integrated BSA-seq and RNA-seq analysis to identify candidate genes associated with nitrogen utilization efficiency (NUtE) in rapeseed (Brassica napus L.).

Rapeseed (Brassica napus L.) is one of the important oil crops, with a high demand for nitrogen (N). It is essential to explore the potential of rapeseed to improve nitrogen utilization efficiency (NUtE). Rapeseed is an allotetraploid crop with a relatively large and complex genome, and there are few studies on the mapping of genes related to NUtE regulation. In this study, we used the combination of bulk segregant analysis sequencing (BSA-Seq) and RNA sequencing (RNA-Seq) to analyze the N-efficient genotype 'Zheyou 18' and N-inefficient genotype 'Sollux', to identify the genetic regulatory mechanisms. Several candidate genes were screened, such as the high-affinity nitrate transporter gene NRT2.1 (BnaC08g43370D) and the abscisic acid (ABA) signal transduction-related genes (BnaC02g14540D, BnaA03g20760D, and BnaA05g01330D). BnaA05g01330D was annotated as ABA-INDUCIBLE bHLH-TYPE TRANSCRIPTION FACTOR (AIB/bHLH17), which was highly expressed in the root. The results showed that the primary root length of the ataib mutant was significantly longer than that of the wild type under low N conditions. Overexpression of BnaA5.AIB could reduce the NUtE under low N levels in Arabidopsis (Arabidopsis thaliana). Candidate genes identified in this study may be involved in the regulation of NUtE in rapeseed, and new functions of AIB in orchestrating N uptake and utilization have been revealed. It is indicated that BnaA5.AIB may be the key factor that links ABA to N signaling and a negative regulator of NUtE. It will provide a theoretical basis and application prospect for resource conservation, environmental protection, and sustainable agricultural development.

The application of P-modified biochar in wastewater remediation: A state-of-the-art review.

Phosphorus modified biochar (P-BC) is an effective adsorbent for wastewater remediation, which has attracted widespread attention due to its low cost, vast source, unique surface structure, and abundant functional groups. However, there is currently no comprehensive analysis and review of P-BC in wastewater remediation. In this study, a detailed introduction is given to the synthesis method of P-BC, as well as the effects of pyrolysis temperature and residence time on physical and chemical properties and adsorption performance of the material. Meanwhile, a comprehensive investigation and evaluation were conducted on the different biomass types and phosphorus sources used to synthesize P-BC. This article also systematically compared the adsorption efficiency differences between P-BC and raw biochar, and summarized the adsorption mechanism of P-BC in removing pollutants from wastewater. In addition, the effects of P-BC composite with other materials (element co-doping, polysaccharide stabilizers, microbial loading, etc.) on physical and chemical properties and pollutant adsorption capacity of the materials were investigated. Some emerging applications of P-BC were also introduced, including supercapacitors, CO2 adsorbents, carbon sequestration, soil heavy metal remediation, and soil fertility improvement. Finally, some valuable suggestions and prospects were proposed for the future research direction of P-BC to achieve the goal of multiple utilization.

Chemical constituents from Uncaria laevigata and their anti-inflammatory activities and action mechanism.

A new alkaloid 1* (scandine Z) and fourteen known natural products were isolated from 95% ethanol extract of Uncaria laevigata for the first time. Besides compound 1*, these fourteen compounds were firstly isolated from Uncaria laevigata. Excitedly, compound 4 exhibited strong anti-inflammatory activity (IC50 = 8.12 µmol/L), which wasn't described before. Moreover, compound 1* also de--monstrated certain anti-inflammatory activity (IC50 = 10.34 µmol/L). Network pharmacology suggested that compound 4 was involved in the IL-17 signalling pathway and the regulation of inflammation pathway. Molecular docking confirmed that it showed strong binding activity with the target protein (peroxisome proliferator-activated receptor γ, PPAR). Overall, compounds 1* and 4 exhibited strong anti-inflammatory activity and served as lead compounds and anti-inflammatory molecules for further study in vivo.

Co-encapsulation of curcumin and anthocyanins in bovine serum album-fucoidan nanocomplex with a two-step pH-driven method.

BACKGROUND: Curcumin (CUR) and anthocyanins (ACN) are recommended due to their bioactivities. However, their nutritional values and health benefits are limited by their low oral bioavailability. The incorporation of bioactive substances into polysaccharide-protein composite nanoparticles is an effective way to enhance their bioavailability. Accordingly, this study explored the fabrication of bovine serum albumin (BSA)-fucoidan (FUC) hybrid nanoparticles using a two-step pH-driven method for the delivery of CUR and ACN. RESULTS: Under a 1:1 weight ratio of BSA to FUC, the point of zero charge moved from pH ⁓ 4.7 for BSA to around 2.5 for FUC-coated BSA, and the formation of BSA-FUC nanocomplex was pH-dependent by showing the maximum CUR emission wavelength shifting from 546 nm (CUR-loaded BSA-FUC at pH 4.7) and 544 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 4.7) to 540 nm (CUR-loaded BSA-FUC at pH 6.0) and 539 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 6.0). Elevated concentrations of NaCl from 0 to 2.5 mol L-1 caused particle size increase from about 250 to about 800 nm, but showing no effect on the encapsulation efficiency of CUR. The CUR and ACN entrapped, respectively, in the inner and outer regions of the BSA-FUC nanocomplex were released at different rates. After incubation for 10 h, more than 80% of ACN was released, while less than 25% of CUR diffused into the receiving medium, which fitted well to Logistic and Weibull models. CONCLUSION: In summary, the BSA-FUC nanocomposites produced by a two-step pH-driven method could be used for the co-delivery of hydrophilic and hydrophobic nutraceuticals. © 2023 Society of Chemical Industry.

Can you accurately monitor your behaviors while multitasking? The effect of multitasking on metacognition.

With the pace of life accelerating, multitasking has become the norm in daily life. According to research, multiple cognitive processes, including numerical reasoning, comprehension, and writing, are negatively affected by multitasking. However, only a few studies have investigated the relationship between multitasking and metacognition. In this study, the effect of multitasking on metacognition was examined using a prospective monitoring paradigm (prediction of subsequent recall performance). In Experiment 1, the participants simultaneously studied word pairs (primary task) and differentiated between different sound pitches (secondary task) and then predicted their performance in a subsequent memory test for the studied word pairs (prospective metacognitive monitoring). The accuracy of metacognitive evaluation with multitasking was then compared with that without multitasking. In Experiment 2, sounds and icons of real-life applications were used to improve the ecological validity of the experiment in the secondary task. The results indicated that multitasking impaired metacognition in both artificial and real-life simulated scenarios. In addition, the participants who engaged in more media multitasking in their daily lives exhibited poorer metacognitive monitoring abilities in single tasks.

Associated factors of malnutrition status among children and adolescents living with HIV in Tanzania: Individual-level analysis and marginal effect estimation.

OBJECTIVES: This study aimed to identify individual-level factors that affect malnutrition outcomes among children and adolescents living with HIV/AIDS in Tanzania. METHODS: We used data from the National AIDS Control Programme. 70,102 participants aged 5 to 19 years attending care and treatment clinics between January to December 2021 were included. Nutritional assessments were performed by anthropometric measurement. Logistic regression models were used to evaluate risk factors. We further estimated marginal prevalence and adjusted predictions by marginal effects. Supplementary analysis assessed the accuracy of the final fitted model. RESULTS: Prevalence of malnutrition for stunting, underweight, wasting, and anthropometric failure (CIAF) were 36.0%, 28.9%, 13.0%, and 48.0%, respectively. Several individual-level factors were significant determinants of malnutrition. Boys, participants aged 15-19 years, those switched to second- or third-line antiretroviral therapy (ART), initiated ART at ages of 5-14 years, ART duration less than 3 years, and were in advanced stages of WHO HIV clinical status had increased adjusted odds ratios and marginal prevalence. The larger AUC values for all models implied importance of identified factors accounted for malnutrition. CONCLUSIONS: On long-term ART, nutritional interventions should be context-specific guidelines to improve growth, especially at ART initiation, ART regimen, and ART duration reckoning with age and sex.

Effects of bilateral repetitive transcranial magnetic stimulation on prospective memory in patients with schizophrenia: A double-blind randomized controlled clinical trial.

AIMS: To investigate effects of repetitive transcranial magnetic stimulation (rTMS) on the prospective memory (PM) in patients with schizophrenia (SCZ). METHODS: Fifty of 71 patients completed this double-blind placebo-controlled randomized trial and compared with 18 healthy controls' (HCs) PM outcomes. Bilateral 20 Hz rTMS to the dorsolateral prefrontal cortex at 90% RMT administered 5 weekdays for 4 weeks for a total of 20 treatments. The Positive and Negative Symptom Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), and PM test were assessed before and after treatment. RESULTS: Both Event-based PM (EBPM) and Time-based PM (TBPM) scores at baseline were significantly lower in patients with SCZ than that in HCs. After rTMS treatments, the scores of EBPM in patients with SCZ was significantly improved and had no differences from that in HCs, while the scores of TBPM did not improved. The negative symptom scores on PANSS and the scores of almost all subscales and total scores of SANS were significantly improved in both groups. CONCLUSIONS: Our findings indicated that bilateral high-frequency rTMS treatment can alleviate EBPM but not TBPM in patients with SCZ, as well as improve the negative symptoms. SIGNIFICANCE: Our results provide one therapeutic option for PM in patients with SCZ.

Recent development of carrier materials in anthocyanins encapsulation applications: A comprehensive literature review.

Anthocyanins are natural polyphenols belonging to the flavonoid family that possess a variety of putative health benefits when consumed in a balanced diet. However, applications of anthocyanins in, for example, functional foods are limited due to poor stability, degradation, and low transmembrane efficiency. To maintain bioactivities of anthocyanins and optimize their use, various carrier materials have been developed. Here, we reviewed the uses of the different carrier materials (organic/inorganic, micro/nano) for anthocyanin encapsulation and delivery over the past five years. The performance of different materials and interactions between anthocyanins and these materials are described. Lastly, we give our perspective on the future development trend of anthocyanin encapsulation strategies.

Green synthesis of silver nanoparticles using Phlebopus portentosus polysaccharide and their antioxidant, antidiabetic, anticancer, and antimicrobial activities.

Silver nanoparticles (AgNPs) by green synthesis from fungi polysaccharides are attracting increasing attention owing to their distinctive features and special applications in numerous fields. In this study, a cost-effective and environmentally friendly biosynthesizing AgNPs method with no toxic chemicals involved from the fruiting body polysaccharide of Phlebopus portentosus (PPP) was established and optimized by single factor experiment and response surface methodology. The optimum synthesis conditions of polysaccharide-AgNPs (PPP-AgNPs) were identified to be the reaction time of 140 min, reaction temperature of 94 °C, and the PPP: AgNO3 ratio of 1:11.5. Formation of PPP-AgNPs was indicated by visual detection of colour change from yellowish to yellowish brown. PPP-AgNPs were characterized by different methods and further evaluated for biological activities. That the Ultraviolet-visible (UV-Vis.) spectroscopy displayed a sharp absorption peak at 420 nm confirmed the formation of AgNPs. Fourier transform infrared (FTIR) analysis detected the presence of various functional groups. The lattice indices of (111), (200), (220), and (331), which indicated a faced-centered-cubic of the Ag crystal structure of PPP-AgNPs, was confirmed by X-ray diffraction (XRD) and the particles were found to be spherical through high resolution transmission electron microscopy (HRTEM). Energy dispersive X-ray spectroscopy (EDS) determined the presence of silver in PPP-AgNPs. The percentage relative composition of elements was determined as silver (Ag) 82.5 % and oxygen (O) 17.5 % for PPP-AgNPs, and did not exhibit any nitrogen peaks. The specific surface area of PPP-AgNPs was calculated to be 0.5750 m2/g with an average pore size of 24.33 nm by BET analysis. The zeta potential was -4.32 mV, which confirmed the stability and an average particle size of 64.5 nm was calculated through dynamic light scattering (DLS). PPP-AgNPs exhibited significant free radical scavenging activity against DPPH with an IC50 value of 0.1082 mg/mL. The MIC values of PPP-AgNPs for E. coli, S. aureus, C. albicans, C. glabrata, and C. parapsilosis are 0.05 mg/mL. The IC50 value of the inhibition of PPP-AgNPs against α-glucosidase was 11.1 µg/mL, while the IC50 values of PPP-AgNPs against HepG2 and MDA-MB-231 cell lines were calculated to be 14.36 ± 0.43 µg/mL and 40.05 ± 2.71 µg/mL, respectively. According to the evaluation, it can be concluded that these green-synthesized and eco-friendly PPP-AgNPs are helpful to improve therapeutics because of significant antioxidant, antimicrobial, antidiabetic, and anticancer properties to provide new possibilities for clinic applications.

Peer popularity and self-discipline as protective factors against depressive symptoms in Chinese adolescents: Do boys and girls benefit equally?

The current study examined the concurrent and longitudinal protective effects of peer popularity and self-discipline (control, planning, and the ability to prioritize important things) against depressive symptoms among adolescents. We used multilevel modeling to examine the data of 1676 adolescents aged 12-15 years from the China Family Panel Studies (CFPS) survey, a large-scale panel survey with a nationally representative sample. Results showed that both peer popularity and self-discipline predicted lower levels of depressive symptoms measured concurrently. The buffering effect of self-discipline against concurrent depressive symptoms was stronger for girls than for boys, especially in middle adolescence. Peer popularity additionally predicted lower levels of depressive symptoms 4 years later, and this effect was stronger for girls than for boys. These patterns of results were maintained after controlling for self-rated physical health and society-level factors. We discuss these findings against the background of distinct traditional gender roles.

α-Lipoic acid chemistry: the past 70 years.

α-Lipoic acid (ALA) is a naturally occurring sulfur-containing fatty acid with high antioxidant activity. It is also used to treat diabetes, nerve pain, weight loss, heart disease, and primary mitochondrial disorders. Moreover, numerous therapeutic agents have been studied for managing other clinical conditions, including for anticancer, anti-HIV, anti-inflammatory, and anti-AD treatments. The medicinal importance of ALA, especially its biologically active form (R-ALA), has attracted considerable attention from synthetic chemists in industrial and academic fields. In this review, we discuss synthetic approaches to ALA and R-ALA over the past 70 years (1952 to the present), which will help medicinal chemists further develop novel routes for their synthesis.

Antifouling and Self-Healing Performance of Marine Coatings Based on Hydrogen-Bond Interactions.

Biofouling is an urgent problem that has to be solved in marine industries. As the traditional antifouling coating loses its antifouling ability after being damaged, the introduction of self-healing performance into the antifouling coating becomes a high priority. Accordingly, we report here a self-healing and antifouling polyurethane composite coating (PCL/MPU-Si/M) with the use of its carbonyl groups as multiple hydrogen bond acceptors. Its fabrication is carried out under mild and solvent-free conditions, forming a "cross-linking" network structure composed of alternately strong and weak bonds based on multiple carbonyl groups. The self-healing efficiency of PCL/MPU-Si/M in tensile strength is 85% after 48 h at room temperature, and higher temperatures can accelerate this self-healing process. Lubricant polydimethylsiloxane and antifoulant medetomidine endow the material with antifouling properties. The maximum antibacterial ability and algae inhibition coverage ability are 91.7 and 90.9%, respectively. This work provides a possible perspective for the design of antifouling and self-healing marine coatings.