Intrinsically unidirectional chemically fuelled rotary molecular motors.

Biological systems mainly utilize chemical energy to fuel autonomous molecular motors, enabling the system to be driven out of equilibrium1. Taking inspiration from rotary motors such as the bacterial flagellar motor2 and adenosine triphosphate synthase3, and building on the success of light-powered unidirectional rotary molecular motors4-6, scientists have pursued the design of synthetic molecular motors solely driven by chemical energy7-13. However, designing artificial rotary molecular motors operating autonomously using a chemical fuel and simultaneously featuring the intrinsic structural design elements to allow full 360° unidirectional rotary motion like adenosine triphosphate synthase remains challenging. Here we show that a homochiral biaryl Motor-3, with three distinct stereochemical elements, is a rotary motor that undergoes repetitive and unidirectional 360° rotation of the two aryl groups around a single-bond axle driven by a chemical fuel. It undergoes sequential ester cyclization, helix inversion and ring opening, and up to 99% unidirectionality is realized over the autonomous rotary cycle. The molecular rotary motor can be operated in two modes: synchronized motion with pulses of a chemical fuel and acid-base oscillations; and autonomous motion in the presence of a chemical fuel under slightly basic aqueous conditions. This rotary motor design with intrinsic control over the direction of rotation, simple chemical fuelling for autonomous motion and near-perfect unidirectionality illustrates the potential for future generations of multicomponent machines to perform mechanical functions.

Kcnma1 is involved in mitochondrial homeostasis in diabetes-related skeletal muscle atrophy.

Uncontrolled diabetes causes a catabolic state with multi-organic complications, of which impairment on skeletal muscle contributes to the damaged mobility. Kcnma1 gene encodes the pore-forming α-subunit of Ca2+ - and voltage-gated K+ channels of large conductance (BK channels), and loss-of-function mutations in Kcnma1 are in regards to impaired myogenesis. Herein, we observed a time-course reduction of Kcnma1 expression in the tibialis anterior muscles of leptin receptor-deficient (db/db) diabetic mice. To investigate the role of Kcnma1 in diabetic muscle atrophy, muscle-specific knockdown of Kcnma1 was achieved by mice receiving intravenous injection of adeno-associated virus-9 (AAV9)-encoding shRNA against Kcnma1 under the muscle creatine kinase (MCK) promoter. Impairment on muscle mass and myogenesis were observed in m/m mice with AAV9-shKcnma1 intervention, while this impairment was more obvious in diabetic db/db mice. Simultaneously, damaged mitochondrial dynamics and biogenesis showed much severer in db/db mice with AAV9-shKcnma1 intervention. RNA sequencing revealed the large transcriptomic changes resulted by Kcnma1 knockdown, and changes in mitochondrial homeostasis-related genes were validated. Besides, the artificial alteration of Kcnma1 in mouse C2C12 myoblasts was achieved with an adenovirus vector. Consistent results were demonstrated by Kcnma1 knockdown in palmitate-treated cells, whereas opposite results were exhibited by Kcnma1 overexpression. Collectively, we document Kcnma1 as a potential keeper of mitochondrial homeostasis, and the loss of Kcnma1 is a critical event in priming skeletal muscle loss in diabetes.

Targeting epigenetic and post-translational modifications regulating pyroptosis for the treatment of inflammatory diseases.

Inflammatory diseases, including infectious diseases, diabetes-related diseases, arthritis-related diseases, neurological diseases, digestive diseases, and tumor, continue to threaten human health and impose a significant financial burden despite advancements in clinical treatment. Pyroptosis, a pro-inflammatory programmed cell death pathway, plays an important role in the regulation of inflammation. Moderate pyroptosis contributes to the activation of native immunity, whereas excessive pyroptosis is associated with the occurrence and progression of inflammation. Pyroptosis is complicated and tightly controlled by various factors. Accumulating evidence has confirmed that epigenetic modifications and post-translational modifications (PTMs) play vital roles in the regulation of pyroptosis. Epigenetic modifications, which include DNA methylation and histone modifications (such as methylation and acetylation), and post-translational modifications (such as ubiquitination, phosphorylation, and acetylation) precisely manipulate gene expression and protein functions at the transcriptional and post-translational levels, respectively. In this review, we summarize the major pathways of pyroptosis and focus on the regulatory roles and mechanisms of epigenetic and post-translational modifications of pyroptotic components. We also illustrate these within pyroptosis-associated inflammatory diseases. In addition, we discuss the effects of novel therapeutic strategies targeting epigenetic and post-translational modifications on pyroptosis, and provide prospective insight into the regulation of pyroptosis for the treatment of inflammatory diseases.

Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo Study.

Background: Rheumatoid arthritis (RA) remains one of the most prevalent chronic joint diseases. However, due to the heterogeneity among RA patients, there are still no robust diagnostic and therapeutic biomarkers for the diagnosis and treatment of RA. Methods: We retrieved RA-related and pan-cancer information datasets from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. Six gene expression profiles and corresponding clinical information of GSE12021, GSE29746, GSE55235, GSE55457, GSE77298, and GSE89408 were adopted to perform differential expression gene analysis, enrichment, and immune component difference analyses of RA. Four machine learning algorithms, including LASSO, RF, XGBoost, and SVM, were used to identify RA-related biomarkers. Unsupervised cluster analysis was also used to decipher the heterogeneity of RA. A four-signature-based nomogram was constructed and verified to specifically diagnose RA and osteoarthritis (OA) from normal tissues. Consequently, RA-HFLS cell was utilized to investigate the biological role of CRTAM in RA. In addition, comparisons of diagnostic efficacy and biological roles among CRTAM and other classic biomarkers of RA were also performed. Results: Immune and stromal components were highly enriched in RA. Chemokine- and Th cell-related signatures were significantly activated in RA tissues. Four promising and novel biomarkers, including CRTAM, PTTG1IP, ITGB2, and MMP13, were identified and verified, which could be treated as novel treatment and diagnostic targets for RA. Nomograms based on the four signatures might aid in distinguishing and diagnosing RA, which reached a satisfactory performance in both training (AUC = 0.894) and testing (AUC = 0.843) cohorts. Two distinct subtypes of RA patients were identified, which further verified that these four signatures might be involved in the immune infiltration process. Furthermore, knockdown of CRTAM could significantly suppress the proliferation and invasion ability of RA cell line and thus could be treated as a novel therapeutic target. CRTAM owned a great diagnostic performance for RA than previous biomarkers including MMP3, S100A8, S100A9, IL6, COMP, LAG3, and ENTPD1. Mechanically, CRTAM could also be involved in the progression through immune dysfunction, fatty acid metabolism, and genomic instability across several cancer subtypes. Conclusion: CRTAM, PTTG1IP, ITGB2, and MMP13 were highly expressed in RA tissues and might function as pivotal diagnostic and treatment targets by deteriorating the immune dysfunction state. In addition, CRTAM might fuel cancer progression through immune signals, especially among RA patients.

Comparative transcriptome analysis reveals the molecular mechanism of sterility induced by irradiation of Plutella xylostella (Linnaeus).

Plutella xylostella (Linnaeus) is an important pest of cruciferous plants, which is harmful all over the world, causing serious economic losses, and its drug resistance is increasing rapidly. The sterile insect technique (SIT) is a green control method and does not cause resistance. In this study, transcriptomics and bioinformatics were used to explore the effects of irradiation on the reproductive function of Plutella xylostella, and the response mechanism of sterility under irradiation was initially revealed. We identified 3342 (1682 up-regulated, 1660 down-regulated), 1963 (1042 up-regulated, 921 down-regulated) and 1531 (721 up-regulated, 810 down-regulated) differentially expressed genes (DEGs) in the 200 Gy vs CK (Control Check), 400 Gy vs CK and 400 Gy vs 200 Gy groups, respectively. GO and KEGG analyses were performed for DEGs in each group. The results showed that 200 Gy activated the downstream phosphorylation pathway and inhibited the cytochrome p450 immune response mechanism. 400 Gy promoted protein decomposition and absorption pathways, autophagy pathways, etc. Down-regulated genes were concentrated in the transformation process of energy metabolizing substances such as ATP, phosphorylation signaling pathway, and insulin, while up-regulated genes were concentrated in biological regulation and metabolic processes. Eight genes in the phosphorylation pathway were selected for qRT-PCR verification, and the results showed that the phosphorylation of different dose groups was regulated in different ways. 400 Gy used positive feedback regulation, while the phosphorylation of F1 used negative feedback regulation.

A Recursive Non-Uniform Sampling Estimator for Asynchronous Nonlinear Systems.

In this paper, we consider the problem of asynchronous estimation in the presence of packet losses for the randomly sampling nonlinear system. Packet losses occur at the control input and at the measurement side. Firstly, the synchronization of the asynchronous sampling system is realized by weighting the state of the adjacent state update points. Secondly, the projection theorem is used to estimate the system state at the sampling time. Due to modeling errors and unmodeled dynamics, obtaining an accurate dynamic model is challenging. Therefore, observation inference based on interpolation techniques is proposed to solve the asynchronous estimation problem. Furthermore, the algorithm is extended to multi-sensor systems to obtain a distributed fusion estimator. Finally, simulation experiments are conducted to validate the effectiveness of the algorithm.

Enhanced Cr(VI) removal and stabilization from bioleached wastewater by zero-valent iron coupled with hetero and autotrophic bacteria.

Zero-valent iron (Fe0) usually suffers from organic acid complexation and ferrochrome layer passivation in Cr(VI) removal from bioleached wastewater of Cr slag. In this work, a synergetic system combined Fe0 and mixed hetero/autotrophic bacteria was established to reduce and stabilize Cr(VI) from bioleached wastewater. Due to bacterial consumption of organic acid and hydrogen, severe iron corrosion and structured-Fe(II) mineral generation (e.g., magnetite and green rust) occurred on biotic Fe0 surface in terms of solid-phase characterization, which was crucial for Cr(VI) adsorption and reduction. Therefore, compared with the abiotic Fe0 system, this integrated system exhibited a 6.1-fold increase in Cr(VI) removal, with heterotrophic reduction contributing 3.4-fold and abiotic part promoted by hydrogen-autotrophic bacteria enhancing 2.7-fold. After reaction, the Cr valence distribution and X-ray photoelectron spectroscopy indicated that most Cr(VI) was converted into immobilized products such as FexCr1-x(OH)3, Cr2O3, and FeCr2O4 by biotic Fe0. Reoxidation experiment revealed that these products exhibited superior stability to the immobilized products generated by Fe0 or bacteria. Additionally, organic acid concentration and Fe0 dosage showed significantly positive correlation with Cr(VI) removal within the range of biological adaptation, which emphasized that heterotrophic and autotrophic bacteria acted essential roles in Cr(VI) removal. This work highlighted the enhanced effect of heterotrophic and autotrophic activities on Cr(VI) reduction and stabilization by Fe0 and offered a promising approach for bioleached wastewater treatment.

Roles of protein post-translational modifications in glucose and lipid metabolism: mechanisms and perspectives.

The metabolism of glucose and lipids is essential for energy production in the body, and dysregulation of the metabolic pathways of these molecules is implicated in various acute and chronic diseases, such as type 2 diabetes, Alzheimer's disease, atherosclerosis (AS), obesity, tumor, and sepsis. Post-translational modifications (PTMs) of proteins, which involve the addition or removal of covalent functional groups, play a crucial role in regulating protein structure, localization function, and activity. Common PTMs include phosphorylation, acetylation, ubiquitination, methylation, and glycosylation. Emerging evidence indicates that PTMs are significant in modulating glucose and lipid metabolism by modifying key enzymes or proteins. In this review, we summarize the current understanding of the role and regulatory mechanisms of PTMs in glucose and lipid metabolism, with a focus on their involvement in disease progression associated with aberrant metabolism. Furthermore, we discuss the future prospects of PTMs, highlighting their potential for gaining deeper insights into glucose and lipid metabolism and related diseases.

On-surface synthesis of Au-C4 and Au-O4 alternately arranged organometallic coordination networks via selective aromatic C-H bond activation.

Selective activation of the C-H bond of aromatic hydrocarbons is significant in synthetic chemistry. However, achieving oriented C-H activation remains challenging due to the poor selectivity of aromatic C-H bonds. Herein, we successfully constructed alternately arranged Au-C4 and Au-O4 organometallic coordination networks through selective aromatic C-H bond activation on Au(111) substrate. The stepwise reaction process of the 5, 12-dibromopyrene 3,4,9, 10-tetracarboxylic dianhydride precursor is monitored by high-resolution scanning tunneling microscopy. Our results show that the gold atoms in C-Au-C organometallic chains play a crucial role in promoting the selective ortho C-H bonds activation and forming Au-C4 coordination structure, which is further demonstrated by a comparative experiment of PTCDA precursor on Au(111). Furthermore, our experiment of 2Br-PTCDA precursor on Cu(111) substrate confirms that copper atoms in C-Cu-C organometallic chains can also assist the formation of Cu-C4 coordination structure. Our results reveal the vital effect of organometallic coordination on selective C-H bond activation of reactants, which holds promising implications for controllable on-surface synthesis.

Exosome-derived circ_0001785 delays atherogenesis through the ceRNA network mechanism of miR-513a-5p/TGFBR3.

PURPOSE: Endothelial cell dysfunction is a major cause of early atherosclerosis. Although the role of extracellular vesicles in stabilizing atherosclerotic plaques is well established, the effect of circulating exosomes on plaque formation is still unknown. Here, we explored the effect of exosomes on atherosclerosis based on the function that exosomes can act on intercellular communication. PATIENTS AND METHODS: We extracted serum exosomes from the blood of CHD patients (CHD-Exo) and healthy individuals (Con-Exo). The obtained exosomes were co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro. In addition, we determined that circ_0001785 functions as a competing endogenous RNA (ceRNAs) in coronary artery disease by dual luciferase reporter gene analysis. The protective effect of circ_0001785 against endothelial cell injury was also verified using over-expression lentiviral transfection functional assays. In vivo experiments, we injected over-expressed circ_0001785 lentivirus into the tail vein of mice to observe its therapeutic effect on a mouse model of atherosclerosis. RESULTS: The vitro co-cultured results showed that the amount of plasma-derived exosomes have an increase in patients with coronary artery disease, and the inflammation and apoptosis of endothelial cells were exacerbated. Over-expression of circ_0001785 reduced endothelial cell injury through the ceRNA network pathway of miR-513a-5p/TGFBR3. Quantitative reverse transcription-polymerase chain reaction identified that the expressed amount of circ_0001785 was reduced in the circulating peripheral blood of CHD patients and increased within human and mouse atherosclerotic plaque tissue. The results of in vivo experiments showed that circ_0001785 reduced aortic endothelial cell injury and the formation of intraplaque neo-vascularization, and enhanced left ventricular diastolic function, thereby delaying the development of atherosclerosis in mice. CONCLUSION: Our results demonstrated a new biomarker, exosome-derived circ_0001785, for atherogenesis, which can reduce endothelial cell injury and thus delay atherogenesis through the miR-513a-5p/TGFBR3 ceRNA network mechanism, providing an exosome-based intervention strategy for atherosclerosis.

PNANet: Probabilistic Two-Stage Detector Using Pyramid Non-Local Attention.

Object detection algorithms require compact structures, reasonable probability interpretability, and strong detection ability for small targets. However, mainstream second-order object detectors lack reasonable probability interpretability, have structural redundancy, and cannot fully utilize information from each branch of the first stage. Non-local attention can improve sensitivity to small targets, but most of them are limited to a single scale. To address these issues, we propose PNANet, a two-stage object detector with a probability interpretable framework. We propose a robust proposal generator as the first stage of the network and use cascade RCNN as the second stage. We also propose a pyramid non-local attention module that breaks the scale constraint and improves overall performance, especially in small target detection. Our algorithm can be used for instance segmentation after adding a simple segmentation head. Testing on COCO and Pascal VOC datasets as well as practical applications demonstrated good results in both object detection and instance segmentation tasks.

Muti-objective optimization on energy consumption, CO2 emission and production cost for iron and steel industry.

Due to high material density, high energy consumption density and CO2 emission density, it is not only difficult but significant to clarify the relationship between energy consumption, the CO2 emission and the production cost in different conditions. However, the previous researches rarely refer how to balance the energy consumption, the CO2 emission and the production cost after the fluctuation of material, energy and carbon price as well as what will happen to them if production structure changes. Therefore, based on the conservation law of mass and energy, to study iron and steel manufacturing process (ISMP), this paper, taking carbon price into consideration, establishes a muti-optimization model of energy consumption, CO2 emission and cost. After optimization with different objectives, the production cost per tonne of crude steel is reduced by 192.03 CNY (7.71%), the CO2 emission per tonne of crude steel is reduced by 224.22 kg (13.37%), and the energy consumption per tonne of steel is reduced by 51.20 kgce (9.10%). Moreover, based on the optimization results under different objectives, it is ironmaking process (coal ratio and ore ratio) and steelmaking process (amount of scrap steel) that has more impact on three above as well as ore blending and coal blending have a great influence on production cost but little effect on energy consumption and CO2 emission.

Water-Accelerated Photooxidation of CH3NH3PbI3 Perovskite.

Halide perovskites have the potential to disrupt the photovoltaics market based on their high performance and low cost. However, the decomposition of perovskites under moisture, oxygen, and light raises concerns about service lifetime, especially because degradation mechanisms and the corresponding rate laws that fit the observed data have thus far eluded researchers. Here, we report a water-accelerated photooxidation mechanism dominating the degradation kinetics of archetypal perovskite CH3NH3PbI3 in air under >1% relative humidity at 25 °C. From this mechanism, we develop a kinetic model that quantitatively predicts the degradation rate as a function of temperature, ambient O2 and H2O levels, and illumination. Because water is a possible product of dry photooxidation, these results highlight the need for encapsulation schemes that rigorously block oxygen ingress, as product water may accumulate beneath the encapsulant and initiate the more rapid water-accelerated photooxidative decomposition.

Preparation and properties of environmentally benign waterborne polyurethane composites from sodium-alginate-modified nano calcium carbonate.

Well-dispersed inorganic nanoparticles in organic polymers are critical in the preparation of high-performance nanocomposites. This study prepared a series of waterborne polyurethane (WPU)/calcium carbonate nanocomposites using the solution blending method. Next, FT-IR, TG-DTG and XRD tests were carried out to confirm that the biopolymer sodium alginate (SA) was successfully encapsulated on the surface of the calcium carbonate nanoparticles, and that SA achieved satisfactory surface modification of the calcium carbonate nanoparticles. The Zeta and ultraviolet (UV) absorbance test results reveal that SA-modified nano calcium carbonate (MCC) had good dispersion stability in water. The effects of the MCC dosage on the composite mechanical properties, thermal stability, and cross-sectional morphology observed by scanning electron microscopy, and the water resistance of the nanocomposite were investigated. The results reveal that the incorporation of 3wt% of MCC in WPU had stable distribution, which led to a 54% increase in the tensile strength of the nanocomposite, while maintaining excellent elongation at break (2187%) and increasing the maximum decomposition temperature to 419.6 °C. Importantly, the improved water resistance facilitates the application of this environmentally benign composite material in humid environments.

Dietary Corn Starch Levels Regulated Insulin-Mediated Glycemic Responses and Glucose Homeostasis in Swimming Crab (Portunus trituberculatus).

Carbohydrate is the cheapest source of energy among the three major nutrient groups, an appropriate amount of carbohydrates can reduce feed cost and improve growth performance, but carnivorous aquatic animals cannot effectively utilize carbohydrates. The objectives of the present study are aimed at exploring the effects of dietary corn starch levels on glucose loading capacity, insulin-mediated glycemic responses, and glucose homeostasis for Portunus trituberculatus. After two weeks of feeding trial, swimming crabs were starved and sampled at 0, 1, 2, 3, 4, 5, 6, 12, and 24 hours, respectively. The results indicated that crabs fed diet with 0% corn starch exhibited lower glucose concentration in hemolymph than those fed with the other diets, and glucose concentration in hemolymph remained low with the extension of sampling time. The glucose concentration in hemolymph of crabs fed with 6% and 12% corn starch diets reached the peak after 2 hours of feeding; however, the glucose concentration in hemolymph of crabs fed with 24% corn starch attained the highest value after 3 hours of feeding, and the hyperglycemia lasted for 3 hours and decreased rapidly after 6 hours of feeding. Enzyme activities in hemolymph related to glucose metabolism such as pyruvate kinase (PK), glucokinase (GK), and phosphoenolpyruvate carboxykinase (PEPCK) were significantly influenced by dietary corn starch levels and sampling time. Glycogen content in hepatopancreas of crabs fed with 6% and 12% corn starch first increased and then decreased; however, the glycogen content in hepatopancreas of crabs fed with 24% corn starch significantly increased with the prolongation of feeding time. In the 24% corn starch diet, insulin-like peptide (ILP) in hemolymph reached a peak after 1 hour of feeding and then significantly decreased, whereas crustacean hyperglycemia hormone (CHH) was not significantly influenced by dietary corn starch levels and sampling time. ATP content in hepatopancreas peaked at 1 h after feeding and then decreased significantly in different corn starch feeding groups, while the opposite trend was observed in NADH. The activities of mitochondrial respiratory chain complexes I, II, III, and V of crabs fed with different corn starch diets significantly increased first and then decreased. In addition, relative expressions of genes related to glycolysis, gluconeogenesis, glucose transport, glycogen synthesis, insulin signaling pathway, and energy metabolism were significantly affected by dietary corn starch levels and sampling time. In conclusion, the results of the present study reveal glucose metabolic responses were regulated by different corn starch levels at different time points and play an important role in clearing glucose through increased activity of insulin, glycolysis, and glycogenesis, along with gluconeogenesis suppression.

Benefits of and barriers to telehealth for the informal caregivers of elderly individuals in rural areas: A scoping review.

INTRODUCTION: Maintaining care for elderly individuals in rural areas is heavily dependent on support from informal caregivers. Many informal caregivers of the elderly in rural areas feel burdened and urgently require professional support. Interests in telehealth that can provide support irrespective of geographical location have been increasing. OBJECTIVE: To identify the benefits of and barriers in telehealth engagement for rural caregivers to provide evidence for service improvement. DESIGN: A scoping review method was used following PRISMA-ScR guidelines and Arksey and O'Malley's five-stage framework. Five databases were searched. The search terms were chosen based on the target intervention (i.e. telehealth), target population (caregivers of elderly individuals) and target context (rural areas). Two authors independently assessed the eligibility of studies and extracted data from eligible studies. FINDINGS: Of 4220 retrieved studies, 19 articles met the inclusion criteria. This study identified four benefits of and two barriers to telehealth for rural caregivers. Four subthemes were identified as the key benefits in using telehealth for caregivers: decrease in psychological distress, increase in care efficiency, increase in social support and increase in access to resources, while inadequate telehealth infrastructures and caregivers' own reasons were the primary barriers in using telehealth for those populations. CONCLUSIONS: Telehealth was shown to significantly benefit rural caregivers. Future research can be designed and conducted for overcoming the barriers to telehealth. Additionally, the benefits identified by this review need to be translated from research into practice for rural caregivers' care.

Early genetic screening uncovered a high prevalence of thalassemia among 18 309 neonates in Guizhou, China.

Thalassemia is a common monogenic disease in southwestern China, especially in Guizhou province. In this study, 18 309 neonates were examined for thalassemia. The thalassemia carrier rate was 12.90%, which is associated with geographical regions, with carrier frequencies significantly differing between regions (p < 0.0001). The carrier rates for α-thalassemia and ß-thalassemia were 8.91% and 3.36%, respectively. There are 22 genotypes identified among 1632 α-thalassemia cases, and 18 genotypes detected among 615 ß-thalassemia cases. The birthrates of individuals with intermediate thalassemia and ß-thalassemia major were 0.153% and 0.055%, respectively. Methodologically, NGS-Gap-PCR is superior to traditional detection methods, with 65 more cases detected by NGS-Gap-PCR. Since thalassemia-rich genotypes were highly prevalent in this region, early detection of thalassemia carriers would be meaningful for genetic counseling and prevention/treatment of thalassemia. NGS-Gap-PCR provides a powerful tool for neonate genetic testing and clinical diagnosis of thalassemia, especially in high-prevalence regions.

Simultaneous separation and determination of three huperzine alkaloids in Huperzia serrata and its preparations by cyclodextrin-modified mixed micellar electrokinetic capillary chromatography.

In this study, a simple and sensitive cyclodextrin-modified mixed micellar electrokinetic capillary chromatography (CD-MEKC) method has been developed for the simultaneous separation and determination of Huperzine A (HupA), Huperzine B (HupB) and Huperzine C (HupC) in Huperzia serrata (H. serrata). The optimal conditions (pH 9.3) were composed of 10 mM sodium tetraborate solution, 40 mM sodium dodecyl sulfate (SDS), 50 mM sodium cholate (SC) and 3.0 mM mono-(6-ethylenediamine-6-deoxy)-ß-cyclodextrin (ED-ß-CD). The separation and determination process were performed on a P/ACE MDQ capillary electrophoresis system, the separation voltage was 15 kV, the temperature was 25 °C and the detection wavelength was 308 nm. Under the optimum conditions, the migration time was less than 9 min. The LOD and LOQ were between 0.38 and 0.80 µg/mL and 1.2-2.3 µg/mL, respectively. The developed method, with excellent precision and accuracy, was applied for the determination of three alkaloids in H. serrata and its formulations.

MicroRNA-340-5p increases telomere length by targeting telomere protein POT1 to improve Alzheimer's disease in mice.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder which is the primary cause of dementia in the elderly. Telomere attrition has been proposed as a hallmark of aging. Our study aimed to explore the mechanism of the protection of telomere 1 (POT1) in regulating telomere length and affecting cellular senescence in AD. The AD mouse model was established by d-galactose and aluminum chloride, and the water maze test and dark avoidance test were used to detect the behaviors of mice and confirm the success of AD mouse model. AD cell model was established with HT22 cells induced by Aß42 oligomers. POT1 expression in the AD model was detected by quantitative real-time polymerase chain reaction. Cellular telomere length in hippocampal tissue was analyzed by telomere restriction fragment. Localization of intracellular POT1, telomerase, and telomeres was analyzed by immunofluorescence and fluorescence in situ hybridization. Dual-luciferase assay was used to validate the targeted binding relationship between microRNA-340-5p (miR-340-5p) and POT1. After inhibiting POT1 expression, the symptoms of AD in mice were improved. Aß1-42 deposition was reduced, whereas telomere length and telomerase activity was increased. Dual-luciferase assay verified the binding relationship between miR-340-5p and POT1. An increase in miR-340-5p expression could alleviate cellular senescence and AD symptoms. miR-340-5p increased cellular telomere length and delayed cell senescence by inhibiting POT1 expression to improve AD symptoms. This study made a conclusion that miR-340-5p increased cellular telomere length and delayed cell senescence by inhibiting POT1 expression to improve AD symptoms in mice.