Quality control of traditional Chinese medicine (TCM) is the basis of clinical efficacy. Due to the complexity of TCM, it is difficult to unify the quality control, and hinders the further ...implementation of the quality standardization of TCM. As a new concept, quality-marker (Q-marker) plays a powerful role in promoting the standardization of quality control system of TCM.
The present review aims to provide reference and scientific basis for further development of Q-marker and assist standardization of quality control of TCM.
Extensive search of various documents and electronic databases such as Pubmed, Royal Society of Chemistry, Science Direct, Springer, Web of Science, and Wiley, etc., were used to search scientific contributions. Other online academic libraries, e.g. Google Scholars, Scopus and national pharmacology literature were also been employed to learn more relevant information about Q-marker.
Q-markers play vital role in promoting the standardization of quality control of TCM. The factors that affect the quality of TCM, the advantages and disadvantages of the analytical techniques commonly used in Q-marker research were reviewed, as well as the systematic research strategies, which were verified by practices.
The proposal of Q-marker not only provided a new perspective to break through the bottleneck of current quality control, but also can be used in the evaluation of pharmacological efficiency, therapeutic discovery, toxicology, etc. In addition, the Q-marker analysis strategies summarized in this paper is helpful to standardize the quality control of TCM and promote the internationalization of TCM.
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FUN14 domain-containing protein 1 (Fundc1)-dependent mitophagy, mainly activated by ischemic/hypoxic preconditioning, benefits acute myocardial reperfusion injury and chronic metabolic syndrome via ...sustaining mitochondrial homeostasis. Mitochondrial fission plays a pathogenic role in ischemic acute kidney injury (AKI) through perturbation of mitochondrial quality and activation of mitochondrial apoptosis. The aim of our study was to explore the role of Fundc1 mitophagy in ischemia preconditioning (IPC)-mediated renoprotection. Proximal tubule-specific Fundc1 knockout (Fundc1PTKO) mice were subjected to ischemia reperfusion injury (IRI) and IPC prior to assessment of renal function, mitophagy, mitochondrial quality control, and Drp1-related mitochondrial fission. Following exposure to IPC, Fundc1 mitophagy was activated through post-transcriptional phosphorylation at Ser17. Interestingly, IRI-mediated renal injury, inflammation, and tubule cell death were mitigated by IPC whereas proximal tubule-specific Fundc1 knockout (Fundc1PTKO) mice abolished IPC-offered renoprotection. Mechanistically, IRI-evoked mitochondrial damage was improved by IPC whereas Fundc1 deficiency provoked mitochondrial abnormality, manifested by impaired mitochondrial quality and hyperactivated Drp1-dependent mitochondrial fission. Interestingly, Fundc1 deficiency-associated mitochondrial dysfunction was reversed by pharmacological inhibition of mitochondrial fission. In vivo, Fundc1 deletion-caused renal injury, severe pro-inflammatory response, and tubule cell death could be nullified by way of knockout Drp1 on Fundc1PTKO background. Finally, we also revealed that IPC triggered Fundc1 mitophagy activation through UNC-51-like kinase 1 (Ulk1) and Ulk1 ablation interrupted IPC-mediated Fundc1 activation and thus attenuated IPC-induced renoprotection. Fundc1 mitophagy, primarily driven by IPC, confers resistance to AKI through reconciliation of mitochondrial fission, implicating the therapeutic potential of targeting mitochondrial homeostasis for AKI.
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Complex industrial production processes often involve multiple product quality indicators that are interrelated. There exists a complex nonlinear mapping relationship between the operational input ...feature variables and multiple output target quality variables, making it difficult to accurately model through first-principle models. In order to fully capture the complex relationship between measurable variables and difficult-to-measure quality variables, and achieve accurate prediction of multiple output variables to meet the needs of practical industrial sites, this paper proposes a broad random forest-based multi-output soft sensor modeling method based on the idea of attention mechanism derived from the concept of broad learning systems. This method comprehensively considers the dynamic impact of different feature variables on the target quality indicators in actual production processes. The attention mechanism assists the soft sensor model in capturing contextual information better when dealing with long sequences, with a focus on the relevant parts related to the current task. Additionally, the interpretable random forest algorithm is employed as the weight estimator for the basic feature learning unit of Broad-based learning, enabling regression modeling of multiple target quality variables. The use of Broad-based random forest improves the model’s learning ability, interpretability, and generalization capability. To validate the reliability of the proposed method, it was applied to real industrial cases. The results demonstrated that the multi-output quality variable prediction performance of the proposed soft sensor outperforms existing soft sensors in terms of prediction accuracy. This indicates promising industrial application prospects for the proposed method.
•A broad learning-based method for multi-output soft sensor modeling in industrial production processes.•The RF algorithm is employed to capture the weights of the basic feature learning units in the Broad Learning model.•The dynamic impact of different feature variables on the target quality indicator is taken into consideration.•The developed and tested soft measurement method is based on industrial process data.
In this paper, we have developed a simple, fast, convenient and sensitive method for determination of organophosphorus pesticides in real samples based on inhibition mechanism of acetylcholinesterase ...(AChE). The biosensor is composed of enzymes (AChE and ChOx (choline oxidase)), QDs and acetylcholine (ACh), without any complex process of assembly for biosensor. After the experimental conditions are optimized, the limit of detection (LOD) for dichlorvos (DDVP) is found to be 4.49nM. Two linear ranges allow a wide determination of DDVP concentration from 4.49nM to 6780nM. Furthermore, a possible mechanism is put forward to explain the fluorescence quenching of CdTe QDs in the presence of H2O2. More importantly, the obtained biosensor is proven to be suitable for the detection of residues of organophosphorus pesticides (OPs) in real examples. The excellent performance of this biosensor will facilitate future development of rapid and high-throughput detection of organophosphorus pesticides.
•A simple and fast biosensor for detection of OPs was proposed.•The biosensor does not need any complex process of assembly and pretreatment.•A possible mechanism is put forward on the fluorescence quenching of CdTe QDs.•The biosensor is suitable for the detection of residues of OPs in real examples.
Alcoholic cardiomyopathy is manifested as cardiac hypertrophy, disrupted contractile function and myofibrillary architecture. An ample amount of clinical and experimental evidence has depicted a ...pivotal role for alcohol metabolism especially the main alcohol metabolic product acetaldehyde, in the pathogenesis of this myopathic state. Findings from our group and others have revealed that the mitochondrial isoform of aldehyde dehydrogenase (ALDH2), which metabolizes acetaldehyde, governs the detoxification of acetaldehyde formed following alcohol consumption and the ultimate elimination of alcohol from the body. The ALDH2 enzymatic cascade may evolve as a unique detoxification mechanism for environmental alcohols and aldehydes to alleviate the undesired cardiac anomalies in ischemia-reperfusion and alcoholism. Polymorphic variants of the ALDH2 gene encode enzymes with altered pharmacokinetic properties and a significantly higher prevalence of cardiovascular diseases associated with alcoholism. The pathophysiological effects of ALDH2 polymorphism may be mediated by accumulation of acetaldehyde and other reactive aldehydes. Inheritance of the inactive ALDH2*2 gene product is associated with a decreased risk of alcoholism but an increased risk of alcoholic complications. This association is influenced by gene-environment interactions such as those associated with religion and national origin. The purpose of this review is to recapitulate the pathogenesis of alcoholic cardiomyopathy with a special focus on ALDH2 enzymatic metabolism. It will be important to dissect the links between ALDH2 polymorphism and prevalence of alcoholic cardiomyopathy, in order to determine the mechanisms underlying such associations. The therapeutic value of ALDH2 as both target and tool in the management of alcoholic tissue damage will be discussed.
Cluster materials have attracted much attention because of their unique chemical and physical properties, hitherto unseen in bulk materials. Inspired by the lipid self‐assembly principle, a series of ...heterocluster Janus molecules (HCJMs) with atomic precision have been rationally designed and synthesized by connecting different clusters via covalent bonds for the construction of nanomaterials and nano‐objects. Due to their amphiphilicity, HCJMs self‐assemble into cluster‐containing nanomaterials or nano‐objects with versatile ordered structures beyond those observed in conventional crystals. Their hybrid composition and nanoscale size are also greatly advantageous in the study of their fine structure by electron microscopy techniques, and enable their formation mechanisms to be unraveled. Finally, the influence of the characteristics of the HCJMs on the structure and properties of the self‐assembled nano‐objects are explored comprehensively. This synthesis strategy will promote further development of cluster materials with advanced functions via rational molecular design toward the construction of hierarchical nanostructures via molecular self‐assembly.
Inspired by lipid self‐assembly and nanocluster functionalities, the design and subsequent creation of a series of heterocluster Janus molecules (HCJMs) are pioneered. Owing to efficient shape control, HCJMs self‐assemble into nanostructures that can go beyond those of predicated nanoaggregates of traditional amphiphiles. Thus, an efficient strategy for bridging the gap between clusters and cluster materials is established.
Impaired cardiac microvascular function contributes to diabetic cardiovascular complications although effective therapy remains elusive. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) ...inhibitor recently approved for treatment of type 2 diabetes, promotes glycosuria excretion and offers cardioprotective actions beyond its glucose-lowering effects. This study was designed to evaluate the effect of empagliflozin on cardiac microvascular injury in diabetes and the underlying mechanism involved with a focus on mitochondria. Our data revealed that empagliflozin improved diabetic myocardial structure and function, preserved cardiac microvascular barrier function and integrity, sustained eNOS phosphorylation and endothelium-dependent relaxation, as well as improved microvessel density and perfusion. Further study suggested that empagliflozin exerted its effects through inhibition of mitochondrial fission in an adenosine monophosphate (AMP)-activated protein kinase (AMPK)-dependent manner. Empagliflozin restored AMP-to-ATP ratio to trigger AMPK activation, suppressed Drp1S616 phosphorylation, and increased Drp1S637 phosphorylation, ultimately leading to inhibition of mitochondrial fission. The empagliflozin-induced inhibition of mitochondrial fission preserved cardiac microvascular endothelial cell (CMEC) barrier function through suppressed mitochondrial reactive oxygen species (mtROS) production and subsequently oxidative stress to impede CMEC senescence. Empagliflozin-induced fission loss also favored angiogenesis by promoting CMEC migration through amelioration of F-actin depolymerization. Taken together, these results indicated the therapeutic promises of empagliflozin in the treatment of pathological microvascular changes in diabetes.
•Empagliflozin alleviates diabetes-induced cardiac microvascular dysfunction.•Hyperglycemia triggers CMEC dysfunction via mitochondrial fission.•Empagliflozin inhibits fission and delays CMEC senescence via suppressing mtROS oxidative stress.•Empagliflozin facilitates CMEC migration and neovascularization by preservation of F-actin homeostasis.
Pyroptosis is a newly discovered programmed cell death that is associated with tumor progression, prognosis, and treatment response. However, the potential roles of pyroptosis-related genes (PRGs) in ...the tumor microenvironment (TME) remain unclear. We described the alterations of PRGs in 1109 colorectal cancer (CRC) samples from genetic and transcriptional fields and evaluated their expression patterns from four independent datasets. We identified two distinct molecular subtypes and found that multi-layer PRG alterations were correlated with patient clinicopathological features, prognosis, and TME cell-infiltrating characteristics. Then, a PRG_score for predicting recurrence-free survival (RFS) was constructed and its predictive capability in CRC patients was validated. Consequently, we constructed a highly accurate nomogram for improving the clinical applicability of the PRG_score. A low PRG_score, characterized by increased microsatellite instability-high (MSI-H), mutation burden, and immunity activation, indicated favorable odds of RFS. Moreover, the PRG_score was significantly associated with the cancer stem cell (CSC) index and chemotherapeutic drug sensitivity. Our comprehensive analysis of PRGs in CRC demonstrated their potential roles in the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. These findings may improve our understanding of PRGs in CRC and pave a new path for the assessment of prognosis and the development of more effective immunotherapy strategies.
To investigate population structure, linkage disequilibrium (LD) pattern and selection signature at the genome level in Chinese and Western pigs, we genotyped 304 unrelated animals from 18 diverse ...populations using porcine 60 K SNP chips. We confirmed the divergent evolution between Chinese and Western pigs and showed distinct topological structures of the tested populations. We acquired the evidence for the introgression of Western pigs into two Chinese pig breeds. Analysis of runs of homozygosity revealed that historical inbreeding reduced genetic variability in several Chinese breeds. We found that intrapopulation LD extents are roughly comparable between Chinese and Western pigs. However, interpopulation LD is much longer in Western pigs compared with Chinese pigs with average r(2) (0.3) values of 125 kb for Western pigs and only 10.5 kb for Chinese pigs. The finding indicates that higher-density markers are required to capture LD with causal variants in genome-wide association studies and genomic selection on Chinese pigs. Further, we looked across the genome to identify candidate loci under selection using F(ST) outlier tests on two contrast samples: Tibetan pigs versus lowland pigs and belted pigs against non-belted pigs. Interestingly, we highlighted several genes including ADAMTS12, SIM1 and NOS1 that show signatures of natural selection in Tibetan pigs and are likely important for genetic adaptation to high altitude. Comparison of our findings with previous reports indicates that the underlying genetic basis for high-altitude adaptation in Tibetan pigs, Tibetan peoples and yaks is likely distinct from one another. Moreover, we identified the strongest signal of directional selection at the EDNRB loci in Chinese belted pigs, supporting EDNRB as a promising candidate gene for the white belt coat color in Chinese pigs. Altogether, our findings advance the understanding of the genome biology of Chinese and Western pigs.
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