Overcoming the adhesion paradox and switchability conflict on rough surfaces with shape-memory polymers.

Smart adhesives that can be applied and removed on demand play an important role in modern life and manufacturing. However, current smart adhesives made of elastomers suffer from the long-standing challenges of the adhesion paradox (rapid decrease in adhesion strength on rough surfaces despite adhesive molecular interactions) and the switchability conflict (trade-off between adhesion strength and easy detachment). Here, we report the use of shape-memory polymers (SMPs) to overcome the adhesion paradox and switchability conflict on rough surfaces. Utilizing the rubbery-glassy phase transition in SMPs, we demonstrate, through mechanical testing and mechanics modeling, that the conformal contact in the rubbery state followed by the shape-locking effect in the glassy state results in the so-called rubber-to-glass (R2G) adhesion (defined as making contact in the rubbery state to a certain indentation depth followed by detachment in the glassy state), with extraordinary adhesion strength (>1 MPa) proportional to the true surface area of a rough surface, overcoming the classic adhesion paradox. Furthermore, upon transitioning back to the rubbery state, the SMP adhesives can detach easily due to the shape-memory effect, leading to a simultaneous improvement in adhesion switchability (up to 103, defined as the ratio of the SMP R2G adhesion to its rubbery-state adhesion) as the surface roughness increases. The working principle and the mechanics model of R2G adhesion provide guidelines for developing stronger and more switchable adhesives adaptable to rough surfaces, thereby enhancing the capabilities of smart adhesives, and impacting various fields such as adhesive grippers and climbing robots.

Rolling Circle Amplification-Based Self-Assembly to Form a "GPS-Nanoconveyor" for In Vitro Targeted Imaging and Enhanced Gene/Chemo (CRISPR/DOX) Synergistic Therapy.

The GPS-Nanoconveyor (MA-NV@DOX-Cas13a) is a targeted nanoplatform designed for the imaging and gene/chemotherapy synergistic treatment of melanoma. It utilizes rolling circle amplification (RCA) products as a scaffold to construct a DNA "Nanoconveyor" (NV), which incorporates a multivalent aptamer (MA) as a "GPS", encapsulates doxorubicin (DOX) in the transporter, and equips it with CRISPR/Cas13a ribonucleoproteins (Cas13a RNP). Carrying MA enhances the ability to recognize the overexpressed receptor nucleolin on B16 cells, enabling targeted imaging and precise delivery of MA-NV@DOX-Cas13a through receptor-mediated endocytosis. The activation of signal transducer and activator of transcription 3 (STAT3) in cancer cells triggers cis-cleavage of CRISPR/Cas13a, initiating its trans-cleavage function. Additionally, deoxyribonuclease I (DNase I) degrades MA-NV, releasing DOX for intracellular imaging and as a chemotherapeutic agent. Experiments demonstrate the superior capabilities of this versatile nanoplatform for cellular imaging and co-treatment while highlighting the advantages of these nanodrug delivery systems in mitigating DOX side effects.

Comprehensive transcriptomic and metabolomic insights into simultaneous CO2 sequestration and nitrate removal by the Chlorella vulgaris and Pseudomonas sp. consortium.

Simultaneous CO2 sequestration and nitrate removal can be achieved by co-cultivation of Chlorella vulgaris with Pseudomonas sp. However, a comprehensive understanding of the synergistic mechanism between C. vulgaris and Pseudomonas sp. remains unknown. In this study, transcriptomics and metabolomics analysis were employed to elucidate the synergistic mechanism of C. vulgaris and Pseudomonas sp. Transcriptomic and metabolomic analyses identified 3664 differentially expressed genes and 314 metabolites. Transcriptome analysis revealed that co-culture with Pseudomonas sp. promoted the photosynthesis of C. vulgaris by promoting the synthesis of photosynthetic pigments and photosynthesis-antenna proteins. Furthermore, it stimulated pathways associated with energy metabolism from carbon sources, such as the Calvin cycle, glycolytic pathway, and TCA cycle. Additionally, Pseudomonas sp. reduced nitrate levels in the co-culture system by denitrification, and microalgae regulated nitrate uptake by down-regulating the transcript levels of nitrate transporter genes. Metabolomic analysis indicated that nutrient exchange was conducted between algae and bacteria, and amino acids, phytohormones, and organic heterocyclic compounds secreted by the bacteria promoted the growth metabolism of microalgae. After supplementation with differential metabolites, the carbon fixation rate and nitrate removal rate of the co-culture system reached 0.549 g L-1 d-1 and 135.4 mg L-1 d-1, which were increased by 20% and 8%, respectively. This study provides a theoretical insight into microalgae-bacteria interaction and its practical application, as well as a novel perspective on flue gas treatment management.

Irisin inhibits microglial senescence via TFAM-mediated mitochondrial metabolism in a mouse model of tauopathy.

BACKGROUND: The accumulation of senescent microglia has been highlighted as a critical contributor to the progression of tauopathies. Irisin, a muscle-derived hormone produced by the proteolytic cleavage of Fibronectin-domain III containing 5 (FNDC5), mediates the pleiotropic effects of exercise on the physical body. Herein, we investigate the potential role of irisin in microglial senescence in tauopathies. METHODS: To model tauopathies both in vivo and in vitro, we utilized P301S tau transgenic mice and tau K18 fibril-treated microglia BV2 cells, respectively. We first examined the expression of the irisin expression and senescence phenotypes of microglia in tauopathies. Subsequently, we investigated the impact of irisin on microglial senescence and its underlying molecular mechanisms. RESULT: We observed a reduction in irisin levels and an onset of premature microglial senescence both in vivo and in vitro. Irisin administration was found to counteract microglial senescence and ameliorate cognitive decline in P301S mice. Mechanistically, irisin effectively inhibited microglial senescence by stimulating the expression of mitochondrial transcription factor A (TFAM), a master regulator of mitochondrial respiratory chain biogenesis, thereby enhancing mitochondrial oxidative phosphorylation (OXPHOS). Silencing TFAM eliminated the inhibitory effect of irisin on microglial senescence as well as the restorative effect of irisin on mitochondrial OXPHOS. Furthermore, the SIRT1/PGC1α signaling pathway appeared to be implicated in irisin-mediated upregulation of TFAM. CONCLUSION: Taken together, our study revealed that irisin mitigated microglial senescence via TFAM-driven mitochondrial biogenesis, suggesting a promising new avenue for therapeutic strategies targeting tauopathies.

Dual-mode fluorescent and colorimetric sensing of thiourea and aluminum ion in natural water based on CuO nanoparticles.

CuO nanoparticles with good water solubility and uniform particle size were successfully prepared. Interestingly, the oxidase-like activity of CuO NPs was continuously enhanced by the addition of thiourea (TU), and the enzyme activity was further enhanced by the addition of aluminum ion (Al3+). By systematically exploring and optimizing the experimental conditions, including the key parameters such as temperature, reaction time, and pH, a fluorescence-colorimetric dual-mode sensing system based on CuO nanoparticles was constructed. The detection range of TU and Al3+ were 1-100 µM and 1-100 µM, respectively, and the selectivity and precision of detection were further improved. In addition, the catalytic mechanism of CuO NPs as oxidase-like catalysts and the specific process in the reaction were investigated. Finally, the nano-sensing system was successfully applied to the analysis of three real environmental samples, namely, tap water, lake water and river water, which provided an effective new strategy for the future development of nano-sensing technology for TU and Al3+.

A Deep Learning Method for Bearing Cross-Domain Fault Diagnostics Based on the Standard Envelope Spectrum.

Intelligent fault diagnostics based on deep learning provides a favorable guarantee for the reliable operation of equipment, but a trained deep learning model generally has low prediction accuracy in cross-domain diagnostics. To solve this problem, a deep learning fault diagnosis method based on the reconstructed envelope spectrum is proposed to improve the ability of rolling bearing cross-domain fault diagnostics in this paper. First, based on the envelope spectrum morphology of rolling bearing failures, a standard envelope spectrum is constructed that reveals the unique characteristics of different bearing health states and eliminates the differences between domains due to different bearing speeds and bearing models. Then, a fault diagnosis model was constructed using a convolutional neural network to learn features and complete fault classification. Finally, using two publicly available bearing data sets and one bearing data set obtained by self-experimentation, the proposed method is applied to the data of the fault diagnostics of rolling bearings under different rotational speeds and different bearing types. The experimental results show that, compared with some popular feature extraction methods, the proposed method can achieve high diagnostic accuracy with data at different rotational speeds and different bearing types, and it is an effective method for solving the problem with cross-domain fault diagnostics for rolling bearings.

Risk factors of electrical status epilepticus during sleep in children with benign childhood epilepsy with centro-temporal spikes.

Objective: To explore risk factors of electrical status epilepticus during sleep in children with benign childhood epilepsy with centro-temporal spikes (BECT). Methods: This is a clinical comparative study. The subjects of study were 67 children with BECT from the Outpatient Department of Pediatric Neurology in Xingtai People's Hospital from January 2019 to January 2022. According to the occurrence of ESES, the enrolled children were divided into control group which included BECT children without ESES and the observation group which included BECT children with ESES. Compared differences of the two groups in the age of first seizure, the frequency of seizures before treatment, the classification of treatment drugs, cranial MRI, and discharge side of electroencephalogram (EEG). Results: There was no statistical difference between the two groups in the frequency of seizures before treatment, the classification of treatment drugs, cranial MRI, and the distribution of EEG discharges in the left and right cerebral areas(P>0.05). Statistical differences were observed in the age of the first seizure, whether the seizures occurred after treatment, and EEG discharges in unilateral/bilateral cerebral areas (P<0.05). Furthermore, the collinearity test and Logistic regression analysis showed that the age of the first seizure, the frequency of seizures before treatment, and whether the seizures occurred after treatment were independent risk factors for the occurrence of ESES in BECT (P<0.05). Conclusion: Clinically, the occurrence of ESES in children with BECT may be related to the younger age of the first seizure, higher frequency of seizures before treatment, and the occurrence of seizures after treatment.

Rolling Circle Amplification-Based DNA Nano-Assembly for Targeted Drug Delivery and Gene Therapy.

Combining the killing ability of chemotherapy drugs on tumor cells with the inhibiting ability of genetic drugs on tumor cell growth, a dual drug delivery system loaded with therapy drugs and siRNA has gradually received more and more research and extensive attention. In this paper, we designed a DNA nano-assembly based on rolling circle amplification that can co-deliver doxorubicin (Dox) and siRNA simultaneously. In order to fully exploit the potential of the dual loading system in cancer treatment, we selected STAT3 gene as a target and used siRNA to target STAT3 of mRNA and reduce the STAT3 expression in mouse melanoma cell line (B16); meanwhile, Dox as a chemotherapy drug was combined with multivalent aptamers specifically targeting B16 to achieve efficient delivery of siRNA and Dox. The results showed that the synergistic delivery system could achieve high efficiency in targeting and inhibiting proliferation in mouse melanoma cells. In addition, the synergistic effect of the dual delivery system on apoptosis of cancer cells was significantly better than that of single drug delivery systems.

A nucleolin-activated polyvalent aptamer nanoprobe for the detection of cancer cells.

Sensitive detection of cancer cells plays a critical role in early cancer diagnosis. Nucleolin, overexpressed on the surface of cancer cells, is regarded as a candidate biomarker for cancer diagnosis. Thus, cancer cells can be detected through the detection of membrane nucleolin. Herein, we designed a nucleolin-activated polyvalent aptamer nanoprobe (PAN) to detect cancer cells. In brief, a long single-stranded DNA with many repeated sequences was synthesized through rolling circle amplification (RCA). Then the RCA product acted as a scaffold chain to combine with multiple AS1411 sequences, which was doubly modified with fluorophore and quenching group, respectively. The fluorescence of PAN was initially quenched. Upon binding to target protein, the conformation of PAN changed, leading to the recovery of fluorescence. The fluorescence signal of cancer cells treated with PAN was much brighter compared with that of monovalent aptamer nanoprobes (MAN) at the same concentration. Furthermore, the binding affinity of PAN to B16 cells was proved to be 30 times higher than that of MAN by calculating the dissociation constants. The results indicated that PAN could specifically detect target cells, and this design concept has potential to become promising in cancer diagnosis.

Surface Wettability for Skin-Interfaced Sensors and Devices.

The practical applications of skin-interfaced sensors and devices in daily life hinge on the rational design of surface wettability to maintain device integrity and achieve improved sensing performance under complex hydrated conditions. Various bio-inspired strategies have been implemented to engineer desired surface wettability for varying hydrated conditions. Although the bodily fluids can negatively affect the device performance, they also provide a rich reservoir of health-relevant information and sustained energy for next-generation stretchable self-powered devices. As a result, the design and manipulation of the surface wettability are critical to effectively control the liquid behavior on the device surface for enhanced performance. The sensors and devices with engineered surface wettability can collect and analyze health biomarkers while being minimally affected by bodily fluids or ambient humid environments. The energy harvesters also benefit from surface wettability design to achieve enhanced performance for powering on-body electronics. In this review, we first summarize the commonly used approaches to tune the surface wettability for target applications toward stretchable self-powered devices. By considering the existing challenges, we also discuss the opportunities as a small fraction of potential future developments, which can lead to a new class of skin-interfaced devices for use in digital health and personalized medicine.

Precision therapy with quinidine of KCNT1-related epileptic disorders: A systematic review.

AIMS: Despite numerous studies on quinidine therapies for epilepsies associated with KCNT1 gene mutations, there is no consensus on its clinical utility. Thus, we reviewed studies evaluating the efficacy and safety of quinidine in KCNT1-related epileptic disorders. METHODS: Electronic databases were queried for in vivo and in vitro studies on quinidine therapy in KCNT1-related epilepsies published on or before 1 May 2022. The evaluation of evidence was done as per the American Academy of Neurology's classification scheme. Identification of significant factors that possibly influenced therapeutic effects of quinidine were performed using χ2 tests. RESULTS: Twenty-seven studies containing 82 patient records were reviewed. Records of 80 patients with 33 KCNT1 mutations were analysed, of which 20 patients had gained ≥50% seizure reduction due to quinidine therapy. However, quinidine therapy often had different effects on patients with the same KCNT1 mutation. Age, genotypes of KCNT1 mutations, seizure types and brain MRI did not significantly influence the therapeutic effect of quinidine. Prolonged QTc was the most common among all adverse events with quinidine. Notably, results of in vitro quinidine tests did not correspond with in vivo tests. CONCLUSIONS: Therapeutic effects of quinidine on KCNT1-related epilepsies remained indefinite as contradictory results were detected in similar patients. Age, seizure types, genotypes of KCNT1 mutations and brain MRI did not influence the therapeutic effects of quinidine. Insensitivity to quinidine by a certain Kcnt1 genotype in molecular tests is predictive of its inefficacy in human populations of the respective mutation.

Moisture-resistant MXene-sodium alginate sponges with sustained superhydrophobicity for monitoring human activities.

Wearable mechanical sensors are easily influenced by moisture resulting in inaccuracy for monitoring human health and body motions. Though the superhydrophobic barrier has been extensively explored as passive water repel strategy on the sensor surface, the dense superhydrophobic surface not only limits the sensor working under large deformations but also inevitable degradation in high humidity or saturation water vapor environments. This work reports a superhydrophobic MXene-sodium alginate sponge (SMSS) pressure sensor with a low voltage Joule heating effect to provide sustain moisture-insensitive property for both sensing performance and superhydrophobicity by heating-driven water molecules away. Because of the positive temperature coefficient under pressure applied, the Joule heating can provides a stable temperature to the moisture-insensitivity property during the whole dynamic pressure cycled. Therefore, the pressure sensor with a simple spray-coating superhydrophobic coating on the outer layer demonstrates key capabilities even in extreme use scenarios with high humidity or water vapor and also provides stable and reliable bio-signal monitoring.

MicroRNA-93 Blocks Signal Transducers and Activator of Transcription 3 to Reduce Neuronal Damage in Parkinson's Disease.

MicroRNA-93 (miR-93) is an oncogene that promotes tumor growth and angiogenesis. However, its role in Parkinson's disease (PD) remains unknown. This study aimed at investigating the role of miR-93 in PD and the molecular mechanisms involved. 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mouse model and lipopolysaccharide (LPS)-exposed BV2 cells were constructed. Real-time quantitative PCR was used to detect the mRNA expression of miR-93, iNOS, IL-6, IL-10, TNF-α and TGF-ß1. Bioinformatics analysis and luciferase reporter assay were used to predict and confirm the interaction between miR-93 and STAT3. Flow cytometry was used to detect cell apoptosis. Western blotting was used to detect the protein expression of STAT3. Immunohistochemistry was used to analyze the Iba1-positive and TH positive cells. It was found that the expression of miR-93 was down-regulated in LPS-exposed BV2 cells. Overexpression of miR-93 inhibited the expression of iNOS, IL-6 and TNF-α, while enhanced the expression of TGF-ß1 and IL-10. The expression of transcriptional activator 3 (STAT3) was found to be up-regulated in LPS-exposed BV2 cells. Knockdown of STAT3 inhibited the expression of iNOS, IL-6 and TNF-α, while enhanced the expression of TGF-ß1 and IL-10. Moreover, STAT3 was found to be a direct target of miR-93, and miR-93 overexpression inhibited the expression of STAT3. Furthermore, both miR-93 overexpression and STAT3 knockdown reduced LPS-induced BV2 cell apoptosis, whereas STAT3 overexpression eliminated the inhibitory effect of miR-93 on LPS-induced BV2 cell apoptosis. In addition, miR-93 overexpression inhibited MPTP-induced STAT3 expression, microglial activation and inflammatory reaction and reduced the loss of tyrosine hydroxylase in the substantia nigra of mice. In conclusion, we demonstrate that miR-93 may be involved in PD by regulating the expression of STAT3.

Construction of Aptamer-Based Molecular Beacons with Varied Blocked Structures and Targeted Detection of Thrombin.

A kind of blocked aptamer-functionalized molecular beacon (MB) was designed as fluorescence sensors to detect thrombins by binding-induced "turn on" structural transformation. Three MBs named MB(8 + 8), MB(15 + 8), and MB(15 + 6) consisted of two single-stranded oligonucleotides. One long single-stranded oligonucleotide (abbreviated as SS) contained a thrombin aptamer sequence and was modified with a fluorescence group and quenching group on each end side. Another short single-stranded oligonucleotide (written as cDNA) was partially complementary to the long SS. It was interesting to find that the complementary sequence length of cDNA greatly influenced the structure of the MBs. The construction of MB experiments proved that MB(8 + 8) and MB(15 + 8) could form the quenching MBs but MB(15 + 6) could not. MB(8 + 8) was composed of a SS strand paired with a complementary cDNA(8 + 8), which was called one-to-one combination, while MB(15 + 8) was two-to-two combination and MB(15 + 6) was one-to-two combination. When the ratio of SS and cDNA (15 + 8) was 1:1, the quenching efficiency reached maximum. But with the molar ratio of SS and cDNA(8 + 8) increasing, the quenching efficiency increased continuously. Under the optimal conditions that we studied, the detection limit of thrombin by MB(8 + 8) and MB(15 + 8) was 0.19 and 1.2 nM, respectively. In addition, the assay proved to be selective, and the average recovery of thrombin detected by MB(8 + 8) and MB(15 + 8) in diluted serum was 95.4 and 94.5%, respectively.

Cu2+doped TiO2-SiO2with photonic crystal structure for synergistic enhancement of photocatalytic degradation under visible light irradiation.

The development of visible light photocatalysts with the ability to efficiently degrade pollutants is an important measure to solve environmental problems. In this paper, Cu2+doped TiO2-SiO2(CTS) with photonic crystal structure composite was successfully synthesized via sol-gel strategy and template method. The prepared materials have abundant pore structure and uniform pore diameter, and the pores were arranged in a periodically hexagonal structure. It showed enhancing synergistic effect of adsorption-photodegradation ability for removing Rhodamine B (RhB). The brilliant adsorption capability of the catalyst is not only due to the addition of silica which can increase surface area that results the increase in adsorption ability, but also related to the rich and ordered porous structure provided by the photonic crystal. The catalyst has a narrow band gap ∼2.92 eV which exhibits the excellent photocatalytic activity for RhB degradation (>95% at 30 min) under visible light irradiation, and possesses higher photocatalytic reaction apparent rate constants (k) which is 7 folds higher than that of pure TiO2. The excellent photocatalytic performance is attributed to the Cu2+doping that narrows the band gap, increases light absorption, and promotes charge separation. Besides, the constructed photonic crystal structure not only further enhances charge transport but also provides more surface activity sites for photocatalytic reactions. More importantly, the ordered pore structure-photonic crystal can prolong the interaction time between light and catalyst through the slow photon effect and the porous scattering effect. Eventually, the photocatalytic degradation efficiency of the catalyst was significantly improved by the synergistic effect of the above mechanisms.

Hard template synthesis of 2D porous Co3O4 nanosheets with graphene oxide for H2O2 sensing.

In this work, we used graphene oxide (GO) as a template that was removed by calcination to finally successfully prepare Co3O4 with 2D porous nanostructure. The results show that 2D porous structure Co3O4 nanosheets were only prepared at pH = 2. After electrochemical tests, the as-prepared Co3O4 nanosheets showed electrochemical properties that are highly suitable for H2O2 detection, such as high current response, short response time (less than 3 s), wide linear range (0.388-44.156 mM), low limit of detection (2.33 µM) and high sensitivity (0.0891 mA mM-1 cm-2). These excellent properties are mainly due to GO, as a 2D template, which connects Co3O4 nanoparticles to each other on a 2D plane, preventing the agglomeration of Co3O4 nanoparticles. The abundant pores between Co3O4 nanoparticles can greatly increase the reaction between the nanoparticles and H2O2 molecules.

Relation between blood pressure and pulse wave velocity for human arteries.

Continuous monitoring of blood pressure, an essential measure of health status, typically requires complex, costly, and invasive techniques that can expose patients to risks of complications. Continuous, cuffless, and noninvasive blood pressure monitoring methods that correlate measured pulse wave velocity (PWV) to the blood pressure via the Moens-Korteweg (MK) and Hughes Equations, offer promising alternatives. The MK Equation, however, involves two assumptions that do not hold for human arteries, and the Hughes Equation is empirical, without any theoretical basis. The results presented here establish a relation between the blood pressure P and PWV that does not rely on the Hughes Equation nor on the assumptions used in the MK Equation. This relation degenerates to the MK Equation under extremely low blood pressures, and it accurately captures the results of in vitro experiments using artificial blood vessels at comparatively high pressures. For human arteries, which are well characterized by the Fung hyperelastic model, a simple formula between P and PWV is established within the range of human blood pressures. This formula is validated by literature data as well as by experiments on human subjects, with applicability in the determination of blood pressure from PWV in continuous, cuffless, and noninvasive blood pressure monitoring systems.

Large-Scale DNA Nanoarrays with a Controllable Fluorescence Switch Constructed by RCA Simplified Origami.

The manufacture of large-scale and highly ordered fluorescent assemblies has received more and more scientific attention in recent years. An ingenious and low-cost strategy for constructing large-scale DNA nanoarrays by rolling circle amplification (RCA) and a simplified DNA origami technique is proposed in this study. Thrombins are used to trigger the excitation of the fluorescent groups modified on the aptamer staple strands of nanoladders, which leads to the delicate construction of millimeter large-scale fluorescent nanoarrays, whose fluorescence intensity could be effectively regulated by the concentration of thrombin. The above fluorescent nanoarrays will generate a potential application value in the fields of biosensors, super-resolution imaging, and novel light-emitting devices.

Integrated Systems Pharmacology, Urinary Metabonomics, and Quantitative Real-Time PCR Analysis to Uncover Targets and Metabolic Pathways of the You-Gui Pill in Treating Kidney-Yang Deficiency Syndrome.

Kidney-yang deficiency syndrome (KYDS) is a metabolic disease caused by a neuro-endocrine disorder. The You-gui pill (YGP) is a classic traditional Chinese medicine (TCM) formula for the treatment of KYDS and has been widely used to warm and recuperate KYDS clinically for hundreds of years in China. However, it is unknown whetherthe corresponding targets and metabolic pathways can also be found via using metabonomics based on one platform (e.g., 1H NMR) to study different biological samples of KYDS. At the same time, relevant reports on further molecular verification (e.g., RT-qPCR analysis) of these targets associated with biomarkers and metabolic pathways have not yet, to our knowledge, been seen in KYDS's research. In the present study, a comprehensive strategy integrating systems pharmacology and 1H NMR-based urinary metabonomics analysis was proposed to identify the target proteins and metabolic pathways that YGP acts on KYDS. Thereafter, further validation of target proteins in kidney tissue was performed through quantitative real-time PCR analysis (RT-qPCR). Furthermore, biochemical parameters and histopathological analysis were studied. As a result, seven target proteins (L-serine dehydratase; phosphoenolpyruvate carboxykinase; spermidine synthase; tyrosyl-tRNA synthetase, glutamine synthetase; 3-hydroxyacyl-CoA dehydrogenase; glycine amidinotransferase) in YGP were discovered to play a therapeutic role in KYDS via affecting eight metabolic pathways (glycine, serine and threonine metabolism; butanoate metabolism; TCA cycle, etc.). Importantly, three target proteins (i.e., 3-hydroxyacyl-CoA dehydrogenase; glutamine synthetase; and glycine amidinotransferase) and two metabolic pathways (butanoate metabolism and dicarboxylate metabolism) related to KYDS, to our knowledge, had been newly discovered in our study. The mechanism of action mainly involved energy metabolism, oxidative stress, ammonia metabolism, amino acid metabolism, and fatty acid metabolism. In short, our study demonstrated that targets and metabolic pathways for the treatment of KYDS by YGP can be effectively found via combining with systems pharmacology and urinary metabonomics. In addition to this, common and specific targets and metabolic pathways of KYDS treated by YGP can be found effectively by integration with the analysis of different biological samples (e.g., serum, urine, feces, and tissue). It is; therefore, important that this laid the foundation for deeper mechanism research and drug-targeted therapy of KYDS in future.

Study on Hypoglycemic Effect of the Drug Pair of Astragalus Radix and Dioscoreae Rhizoma in T2DM Rats by Network Pharmacology and Metabonomics.

Type 2 diabetes mellitus (T2DM) is a metabolic disease accompanied by a series of diseases such as diabetic nephropathy. The drug pair (HS) of Astragalus Radix (HQ) and Dioscoreae Rhizoma (SY) was designed by Dr. Shi Jinmo to improve the treatment of T2DM. However, the exact mechanism involved requires further clarification. In this work, 1H-NMR-based metabonomics and network pharmacology were adopted. Metabolic profiling indicated that the metabolic perturbation was reduced after HS treatment. The results found 21 biomarkers. According to the network pharmacology, we found that the regulation of T2DM was primarily associated with 18 active compounds in HS. These active compounds mainly had an effect on 135 targets. Subsequently, combining network pharmacology and metabonomics, we found four target proteins, which indicated that HS has potential hypoglycemic effects through regulating monoamine oxidases B (MAOB), acetyl-CoA carboxylase 1 (ACACA), carbonic anhydrase 2 (CA2), and catalase (CAT). In conclusion, the result showed that these four targets might be the most relevant targets for the treatment of T2DM with HS. This study clarified the mechanism of HS in the treatment of T2DM and also confirmed the feasibility of combining metabonomics and network pharmacology to study the mechanisms of traditional Chinese medicine (TCM). In the future, this approach may be a potentially powerful tool to discovery active components of traditional Chinese medicines and elucidate their mechanisms.