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Background: Zhiqiao Gancao decoction (ZQGCD) was created by Professor Gong Zhengfeng, a renowned Chinese medicine expert. Clinical studies have shown its efficacy in alleviating pain and enhancing lumbar function in intervertebral disc degeneration (IDD) patients. However, the precise mechanism of ZQGCD in treating IDD remains unclear., Methods: The active components of ZQGCD were identified using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). A rat model of intervertebral disc degeneration was established, and rats in each group received ZQGCD for three weeks. Assessment parameters included hyperalgesia status, observation of intervertebral disc tissue degeneration and macrophage infiltration, and analysis of JAK2/STAT3 pathway protein expression in the intervertebral disc. Primary macrophage M1 polarization was induced using LPS, with cells treated using the JAK2 inhibitor (AZD1480) and ZQGCD to evaluate macrophage polarization, cellular supernatant inflammatory factors, and JAK2/STAT3 pathway expression. Macrophage supernatant served as a conditioned medium to observe its effects on the proliferation of nucleus pulposus cells (NPCs) and the expression of collagen II and MMP3 proteins., Results: A total of 81 active components were identified in ZQGCD. Following ZQGCD treatment, infiltrating macrophages in intervertebral disc tissues of model rats decreased, the content of M1 macrophages decreased, while the content of M2 macrophages increased, the expression of proinflammatory factors and pain-inducing factors in serum decreased, and the expression of substance P in intervertebral disc tissue decreased. Consequently, the intervertebral disc degeneration and hyperalgesia of rats were improved. In vitro studies revealed that LPS induced M1 macrophage polarization. By inhibiting the JAK2/STAT3 pathway, both JAK2 inhibitors and ZQGCD effectively suppressed M1 polarization, resulting in decreased levels of IL-1β, IL-6, TNF-α, and various other inflammatory factors. Consequently, this inhibition led to a delay in the degeneration of NPCs., Conclusion: There is macrophage infiltration in the intervertebral disc tissue of IDD rats, and JAK2/STAT3 pathway is activated, macrophages are polarized to M1 type, resulting in inflammatory microenvironment, leading to intervertebral disc degeneration and hyperalgesia. ZQGCD exhibited a delaying effect on IDD and improved hyperalgesia by inhibiting the JAK2/STAT3/macrophage M1 polarization pathway., Competing Interests: The authors declare that they have no conflicts of interest to disclose., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Inflammation and immune factors are the core of intervertebral disc degeneration (IDD), but the immune environment and epigenetic regulation process of IDD remain unclear. This study aims to identify immune-related diagnostic candidate genes for IDD, and search for potential pathogenesis and therapeutic targets for IDD., Methods: Gene expression datasets were obtained from the Gene Expression Omnibus (GEO). Differential expression immune genes (Imm-DEGs) were identified through weighted gene correlation network analysis (WGCNA) and linear models for microarray data analysis (Limma). LASSO algorithm was used to identify feature genes related to IDD, which were compared with core node genes in PPI network to obtain hub genes. Based on the coefficients of hub genes, a risk model was constructed, and the diagnostic value of hub genes was further evaluated through receiver operating characteristic (ROC) analysis. Xcell, an immunocyte analysis tool, was used to estimate the infiltration of immune cells. Finally, nucleus pulposus cells were co-cultured with macrophages to create an M1 macrophage immune inflammatory environment, and the changes of hub genes were verified., Results: Combined with the results of WGCNA and Limma gene differential analysis, a total of 30 Imm-DEGs were identified. Imm-DEGs enriched in multiple pathways related to immunity and inflammation. LASSO algorithm identified 10 feature genes from Imm-DEGs that significantly affected IDD, and after comparison with core node genes in the PPI network of Imm-DEGs, 6 hub genes (NR1H3, SORT1, PTGDS, AGT, IRF1, TGFB2) were determined. Results of ROC curves and external dataset validation showed that the risk model constructed with the 6 hub genes had high diagnostic value for IDD. Immunocyte infiltration analysis showed the presence of various dysregulated immune cells in the degenerative nucleus pulposus tissue. In vitro experimental results showed that the gene expression of NR1H3, SORT1, PTGDS, IRF1, and TGFB2 in nucleus pulposus cells in the immune inflammatory environment was up-regulated, but the change of AGT was not significant., Conclusions: The hub genes NR1H3, SORT1, PTGDS, IRF1, and TGFB2 can be used as immunorelated biomarkers for IDD, and may be potential targets for immune regulation therapy for IDD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Gynostemma pentaphyllum (Thunb.) Makino is an important producer of dammarene-type triterpenoid saponins. These saponins (gypenosides) exhibit diverse pharmacological benefits such as anticancer, antidiabetic, and immunomodulatory effects, and have major potential in the pharmaceutical and health care industries. Here, we employed single-cell RNA sequencing (scRNA-seq) to profile the transcriptomes of more than 50,000 cells derived from G. pentaphyllum shoot apexes and leaves. Following cell clustering and annotation, we identified five major cell types in shoot apexes and four in leaves. Each cell type displayed substantial transcriptomic heterogeneity both within and between tissues. Examining gene expression patterns across various cell types revealed that gypenoside biosynthesis predominantly occurred in mesophyll cells, with heightened activity observed in shoot apexes compared to leaves. Furthermore, we explored the impact of transposable elements (TEs) on G. pentaphyllum transcriptomic landscapes. Our findings the highlighted the unbalanced expression of certain TE families across different cell types in shoot apexes and leaves, marking the first investigation of TE expression at the single-cell level in plants. Additionally, we observed dynamic expression of genes involved in gypenoside biosynthesis and specific TE families during epidermal and vascular cell development. The involvement of TE expression in regulating cell differentiation and gypenoside biosynthesis warrant further exploration. Overall, this study not only provides new insights into the spatiotemporal organization of gypenoside biosynthesis and TE activity in G. pentaphyllum shoot apexes and leaves but also offers valuable cellular and genetic resources for a deeper understanding of developmental and physiological processes at single-cell resolution in this species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Du, Zhang, Shen, Yun, Wang, Li, Sun, Wei, Li, Guo and Sun.)

Surface enhanced Raman spectroscopy (SERS) is a unique analytical technique with excellent performance in terms of sensitivity, non-destructive detection and resolution. However, due to the randomness and poor repeatability of hot spot distribution, SERS quantitative analysis is still challenging. Meanwhile, snus is a type of tobacco product that can release nicotine and other components in the mouth without burning, and the rapid detection technique based on SERS can reliably evaluate the amount of nicotine released from snus, which is of great significance for understanding its characteristics and regulating its components. Herein, the strategy was proposed to solve the feasibility of SERS quantitative detection based on self-assembled core-shell nanoparticles with embedded internal standards (EIS) due to EIS signal can effectively correct SERS signal fluctuations caused by different aggregation states and measurement conditions, thus allowing reliable quantitative SERS analysis of targets with different surface affinity. By means of process control, after the Au nanoparticles (Au NPs) were modified with 4-Mercaptobenzonitrile (4-MBN) as internal standard molecules, Ag shell with a certain thickness was grown on the surface of the AuNP@4-MBN, and then the Au@4-MBN@Ag NPs were used to regulate and control the assembly of liquid-liquid interface. The high-density nano-arrays assembled at the liquid-liquid interface ensure high reproducibility as SERS substrates, and which could be used for SERS detection of nicotine released from snus products. In addition, time-mapping research shows that this method can also be used to dynamically monitor the release of nicotine. Moreover, such destruction-free evaluation of the release of nicotine from snus products opens up new perspectives for further research about the impact of nicotinoids-related health programs., Competing Interests: Authors YT, XS, SS, GD, and DZ were employed by Technology Center of China Tobacco Yunnan Industrial Co., Ltd. Author YP was employed by Hongta Tobacco (Group) Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Zhao, Shen, Shang, Pan, Dong, Huo, Zhu and Tang.)

Background: Closed reduction is the preferred treatment for distal radius fractures. However, it requires a multiple experienced medical staff and manually maintaining stable traction is difficult. Additionally, doctors cannot assess the reduction status of a fracture in real-time through radiographic images, which may lead to improper reduction. Furthermore, post-fracture complications such as joint adhesion, stiffness, and impaired mobility pose a challenge for the doctors. So it is necessary to optimize the treatment process of the distal radius fracture through technological means. Methods: A robot-assisted closed reduction and rehabilitation system, which could assist doctors throughout the entire process of reduction, fixation, and rehabilitation of distal radius fractures, was developed. A mechanical system, composed of two grippers and a cooperative robotic arm, was used to grasp and tract the affected limb. A doctor controlled the robot through a joystick console and Windows application program. A biplane radiographic device was integrated into the system, which is not only convenient for doctors to view radiographic images of the fracture at any time but also for them to select the rotation axis of the wrist on the images before reduction and rehabilitation. Important information including the anteroposterior and lateral radiographic data and force and position parameters during the reduction and rehabilitation process were displayed on a graphic user interface. Results: Experimental results showed that the proposed robotic system can meet the technical requirements for the reduction and rehabilitation of distal radius fractures, all the rotation angles could be achieved, a maximum force of more than 50 N could be achieved in all traction directions, and the error in selecting the wrist joint rotation axis line using radiographic images was less than 5 mm. Conclusion: The developed robot-assisted system was shown to be suitable for closed reduction and rehabilitation of distal radius fractures, contributing a potential improvement in the quality of the procedures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zha, Xu, Yang, Zhang, Cai, Zhang, Liu, Shen and Li.)

Tissue regeneration/fibrosis after injury is intricately regulated by the immune cascade reaction and extracellular matrix (ECM). Dysregulated cascade signal could jeopardize tissue homeostasis leading to fibrosis. Bioactive scaffolds mimicking natural ECM microstructure and chemistry could regulate the cascade reaction to achieve tissue regeneration. The current study constructed an ECM-engineered micro/nanofibrous scaffold using self-assembled nanofibrous collagen and decorin (DCN)-loaded microfibers to regulate the immune cascade reaction. The ECM-engineered scaffold promoted anti-inflammatory and pro-regenerative effects, M2 polarization of macrophages, by nanofibrous collagen. The ECM-engineered scaffold could release DCN to inhibit inflammation-associated fibrous angiogenesis. Yet, to prevent excessive M2 activity leading to tissue fibrosis, controlled release of DCN was expected to elicit M1 activity and achieve M1/M2 balance in the repair process. Regulated cascade reaction guided favorable crosstalk between macrophages, endothelial cells and fibroblasts by proximity. Additionally, decorin could also antagonize TGF-β1 via TGF-β/Smad3 pathway to suppress fibrotic activity of fibroblasts. Hence, ECM-engineered scaffolds could exert effective regulation of the immune cascade reaction by microstructure and DCN release and achieve the balance between tissue fibrosis and regeneration. STATEMENT OF SIGNIFICANCE: With the incidence of up to 74.6%, failed back surgery syndrome (FBSS) has been a lingering issue in spine surgery, which poses a heavy socio-economic burden to society. Epidural fibrosis is believed to be responsible for the onset of FBSS. Current biomaterial-based strategies treating epidural fibrosis mainly rely on physical barriers and unidirectional suppression of inflammation. Regulation of the immune cascade reaction for inhibiting fibrosis has not been widely studied. Based on the simultaneous regulation of M1/M2 polarization and intercellular crosstalk, the ECM-engineered micro/nanofibrous scaffolds constructed in the current study could exert an immune cascade effect to coordinate tissue regeneration and inhibit fibrosis. This finding makes a significant contribution in the development of a treatment for epidural fibrosis and FBSS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Distal radius fractures are a common type of fracture. For patients treated with closed reduction with splinting, a period of rehabilitation is still required after the removal of the splint. However, there is a general lack of attention and low compliance to rehabilitation training during this period, so it is necessary to build a rehabilitation training monitoring system to improve the efficiency of patients' rehabilitation., Methods: A wearable rehabilitation training wristband was proposed, which could be used in the patient's daily rehabilitation training scenario and could recognize four common wrist rehabilitation actions in real-time by using three thin film pressure sensors to detect the pressure change curve at three points on the wrist. An algorithmic framework for classifying rehabilitation training actions was proposed. In our framework, an action pre-detection strategy was designed to exclude false detections caused by switching initial gestures during rehabilitation training and wait for the arrival of the complete signal. To classify the action signals into four categories, firstly an autoencoder was used to downscale the original signal. Six SVMs were then used for evaluation and voting, and the final action with the highest number of votes would be used as the prediction result., Results: Experimental results showed that the proposed algorithmic framework achieved an average recognition accuracy of 89.62%, an average recognition recall of 88.93%, and an f1 score of 89.27% on the four rehabilitation training actions., Conclusion: The developed device has the advantages of being small size and easy to wear, which can quickly and accurately identify and classify four common rehabilitation training actions. It can easily be combined with peripheral devices and technologies (e.g., cell phones, computers, Internet) to build different rehabilitation training scenarios, making it worthwhile to use and promote in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zha, Xu, Cai, Zhang and Shen.)

Main Conclusion: The hierarchical architecture of chromatins affects the gene expression level of glandular secreting trichomes and the artemisinin biosynthetic pathway-related genes, consequently bringing on huge differences in the content of artemisinin and its derivatives of A. annua. The plant of traditional Chinese medicine "Qinghao" is called Artemisia annua L. in Chinese Pharmacopoeia. High content and the total amount of artemisinin is the main goal of A. annua breeding, nevertheless, the change of chromatin organization during the artemisinin synthesis process has not been discovered yet. This study intended to find the roles of chromatin structure in the production of artemisinin through bioinformatics and experimental validation. Chromosome conformation capture analysis was used to scrutinize the interactions among chromosomes and categorize various scales of chromatin during artemisinin synthesis in A. annua. To confirm the effect of the changes in chromatin structure, Hi-C and RNA-sequencing were performed on two different strains to find the correlation between chromatin structure and gene expression levels on artemisinin synthesis progress and regulation. Our results revealed that the frequency of intra-chromosomal interactions was higher in the inter-chromosomal interactions between the root and leaves on a high artemisinin production strain (HAP) compared to a low artemisinin production strain (LAP). We found that compartmental transition was connected with interactions among different chromatins. Interestingly, glandular secreting trichomes (GSTs) and the artemisinin biosynthetic pathway (ABP) related genes were enriched in the areas which have the compartmental transition, reflecting the regulation of artemisinin synthesis. Topologically associated domain boundaries were associated with various distributions of genes and expression levels. Genes associated with ABP and GST in the adjacent loop were highly expressed, suggesting that epigenetic regulation plays an important role during artemisinin synthesis and glandular secreting trichomes production process. Chromatin structure could show an important status in the mechanisms of artemisinin synthesis process in A. annua., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Surface enhanced Raman spectroscopy (SERS) is a highly sensitive analytical detection technique that provides unique chemical and structural information on target molecules. Snus is a type of tobacco product that can release nicotine and other components under certain humidity and temperature without burning, and the evaluation of its nicotine release under different storage conditions is very important for understanding its characteristics, regulating its components, and setting reasonable storage conditions. Herein, by means of an artificial climate box and suction extraction device, the volatile release evaluations of nicotine from snus products under different storage conditions were performed based on Fe 3 O 4 microparticles coated with Au nanorods and Au nanoparticles (Fe 3 O 4 @AuNRsNPs) as SERS substrates combined with a capillary. The Fe 3 O 4 @AuNRsNPs assemblies can be fixed in the inner wall of the capillary with the aid of an external magnetic field, which improved the maneuverability of the SERS substrates. By comparing the intensities of the spectral peaks of the symmetrical breathing of the pyridine moiety of nicotine molecules with increasing temperature and humidity, which could significantly accelerate the volatile release of a small amount of nicotine, the nicotine release under different conditions could be evaluated. Based on this strategy, it was possible to obtain the storage or placement conditions of the product. The results of this study provide a reference to clarify the volatile release of nicotine under various storage conditions, which is helpful for better regulation of the levels of nicotine in snus. Moreover, such destruction-free evaluation of the volatile release of nicotine from snus products under different storage conditions opens up new perspectives for further research about the impact of nicotinoids on smokers' health and cessation programs., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: The aim of this study was to investigate the effect of Zhiqiao Gancao decoction (ZQGCD) on hyperalgesia in lumbar disc herniation (LDH) and its mechanism., Methods: The potential mechanism of ZQGCD's therapeutic effect on LDH was investigated through network pharmacology, which involved screening the targets of eight components that were absorbed into the bloodstream. The effects of CCR2 inhibitors and ZQGCD-containing serum on the excitability of the CCL2/CCR2 signaling pathway and dorsal root ganglion neurons (DRGn) were investigated in vitro. The effects of CCR2 inhibitors and ZQGCD on the expression of the CCL2/CCR2 signaling pathway and ASIC3 in the rat intervertebral disc and dorsal root ganglion (DRG), the degree of disc degeneration, the threshold of foot retreat, and the latency of foot retreat in LDH rats were examined in vivo. The binding affinities and interaction modes between CCR2 and the components absorbed into the blood were analyzed using the AutodockVina 1.2.2 software., Results: Network pharmacology revealed that ZQGCD could treat LDH through a mechanism involving the chemokine signaling pathway. It was observed that the CCR2 inhibitor and ZQGCD-containing serum downregulated CCR2 and ASIC3 expression and decreased cell excitability in DRGn. The CCL2/CCR2 signaling pathway was activated in the degenerated intervertebral disc and DRG of LDH rats, increased the expression of ASIC3, and decreased the mechanical allodynia domain and thermal hyperalgesia domain. However, a CCR2 inhibitor or ZQGCD could ameliorate the above changes in LDH rats. The target proteins, CCL2 and CCR2, exhibited a robust affinity for the eight components that were absorbed into the bloodstream., Conclusion: The CCL2/CCR2 pathway was activated in the intervertebral disc and DRG of LDH rats. This was accompanied by upregulation of ASIC3 expression, increased excitability of DRGn, and the occurrence of hyperalgesia. ZQGCD improves hyperalgesia in LDH rats by inhibiting the CCL2/CCR2 pathway and downregulating ASIC3 expression., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Huang et al.)

Camptotheca acuminata Decne., the main source of camptothecin (CPT), has received increasing attention for its remarkable antitumor activity. Many CPT derivatives are clinically used as effective anticancer agents worldwide. However, their biosynthesis mechanism remains unclear, and uncovering this pathway would greatly facilitate development of alternative CPT production methods to replace current inefficient plant-derived ones. The expression of >30,000 genes was accurately quantified using unique molecular identifier RNA sequencing in 10 C. acuminata tissues, and 7854 proteins from five tissues were quantified with label-free quantitative proteomics. Fifteen full-length transcriptomes were sequenced with long-read Oxford Nanopore Technologies, and 5692 alternative splicing events were discovered among 4746 genes. Integrated transcriptome and proteome analysis provided novel insights into CPT biosynthesis and its hierarchical regulation. Five cytochrome P450s and three O-methyltransferases were considered as candidates involved in the biosynthesis of CPT and its derivatives, while 15 transcription factors potentially regulating CPT biosynthesis were screened. These findings provide important clues for elucidating the biosynthetic mechanisms of CPT and its derivatives and substantially contribute to the future production of these anticancer agents with synthetic biology. The generated large-scale multiomics data also provide valuable resources for investigating the functional genomics of the most important CPT-producing plant species-C. acuminata., (© 2023 Scandinavian Plant Physiology Society.)

The solvated structure of a highly concentrated hybrid tetraglyme (G4)-water electrolyte was studied for an increasing cycle stability and performance of a KS6 used dual-ion battery. Hybrid solvent of G4 and water with a weight ratio of 2 to 8 was able to dissolve 9LiFSI-1LiTFSI supporting salts up to 37 mol kg -1 (37 mol kg -1 G2W8). In spite of such high concentration of supporting salts, reasonable charge and discharge performance of dual-ion battery (discharge capacity of ≈40 mAh g -1 and coulombic efficiency of 90 %) were exhibited over 300 cycles. This was attributed to the decreased hydrogen evolution reaction (HER) potential to -1.05 V vs. Ag/AgCl by addition of G4. From Fourier-transform infrared, nuclear magnetic resonance, and Raman spectroscopies, G4 molecules were more strongly coordinated to Li + to form ion pairs of [Li(G4) x (H 2 O) y ] + complex in hybrid G4-water electrolyte. Co-intercalation of bis(trifluoromethanesulfonyl)imide (TFSI - ) and bis(fluorosulfonyl)imide (FSI - ) into graphitic carbon KS6 cathode was confirmed in hybrid aqueous electrolyte., (© 2022 Wiley-VCH GmbH.)

Monoterpenoid indole alkaloids (MIAs) are among the most diverse specialized metabolites in plants and are of great pharmaceutical importance. We leveraged single-cell transcriptomics to explore the spatial organization of MIA metabolism in Catharanthus roseus leaves, and the transcripts of 20 MIA genes were first localized, updating the model of MIA biosynthesis. The MIA pathway was partitioned into three cell types, consistent with the results from RNA in situ hybridization experiments. Several candidate transporters were predicted to be essential players shuttling MIA intermediates between inter- and intracellular compartments, supplying potential targets to increase the overall yields of desirable MIAs in native plants or heterologous hosts through metabolic engineering and synthetic biology. This work provides not only a universal roadmap for elucidating the spatiotemporal distribution of biological processes at single-cell resolution, but also abundant cellular and genetic resources for further investigation of the higher-order organization of MIA biosynthesis, transport and storage., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The stepped-frequency (SF) waveform is highly sensitive to the target motion, which induces range shift and echo spread in a high-range-resolution profile (HRRP). This paper proposes a method based on a cross-transmitted double-stepped frequency (DSF) waveform and the phase-cancellation technique. The proposed method obtains the stationary HRRP of the moving targets according to the inverse discrete Fourier transform (IDFT) and complex multiplication. The results also show that the proposed method eliminates the generated false peaks from the existing methods. As a result, the obtained signal-to-noise ratio (SNR) of the HRRP using the proposed method is improved. Due to the cross-transmitted DSF waveform application, the proposed method adapts to higher speed targets. The analysis and simulation results validate the effectiveness of the proposed approach.

Artemisia annua is the major natural source of artemisinin, an anti-malarial medicine commonly used worldwide. Here, we present chromosome-level haploid maps for two A. annua strains with different artemisinin contents to explore the relationships between genomic organization and artemisinin production. High-fidelity sequencing, optical mapping, and chromatin conformation capture sequencing were used to assemble the heterogeneous and repetitive genome and resolve the haplotypes of A. annua. Approximately 50,000 genes were annotated for each haplotype genome, and a triplication event that occurred approximately 58.12 million years ago was examined for the first time in this species. A total of 3,903,467-5,193,414 variants (SNPs, indels, and structural variants) were identified in the 1.5-Gb genome during pairwise comparison between haplotypes, consistent with the high heterozygosity of this species. Genomic analyses revealed a correlation between artemisinin concents and the copy number of amorpha-4,11-diene synthase genes. This correlation was further confirmed by resequencing of 36 A. annua samples with varied artemisinin contents. Circular consensus sequencing of transcripts facilitated the detection of paralog expression. Collectively, our study provides chromosome-level allele-aware genome assemblies for two A. annua strains and new insights into the biosynthesis of artemisinin and its regulation, which will contribute to conquering malaria worldwide., (Copyright © 2022 The Author. Published by Elsevier Inc. All rights reserved.)

The roots of Salvia miltiorrhiza Bunge. are commonly used in the treatment of cardiovascular diseases, and tanshinones and salvianolic acids are its main active ingredients. However, the composition and content of active ingredients of S. miltiorrhiza planted in different regions of the soil environment are also quite different, which adds new difficulties to the large-scale and standardization of artificial cultivation. Therefore, in this study, we measured the active ingredients in the roots of S. miltiorrhiza and the contents of rhizosphere soil elements from 25 production areas in eight provinces in China, and used the data to develop a prediction model based on BP (back propagation) neural network. The results showed that the active ingredients had different degrees of correlation with soil macronutrients and trace elements, the prediction model had the best performance (MSE = 0.0203, 0.0164; R 2 = 0.93, 0.94). The artificial neural network model was shown to be a method that can be used to screen the suitable cultivation sites and proper fertilization. It can also be used to optimize the fertilizer application at specific sites. It also suggested that soil testing formula fertilization should be carried out for medicinal plants like S. miltiorrhiza , which is grown in multiple origins, rather than promoting the use of "special fertilizer" on a large scale. Therefore, the model is helpful for efficient, rational, and scientific guidance of fertilization management in the cultivation of S. miltiorrhiza ., Competing Interests: The authors declare there are no competing interests., (©2022 Liu et al.)

Background: Stem cells intra-articular injection stagey indicated a potential therapeutic effect on improving the pathological progress of osteoarthritis (OA). However, the long-term effect of stem cells intra-articular injection on the cartilage regeneration remains unclear. miR-29a-3p is predicted to be a critical target for inhibiting insulin-like growth factor-1 expression and may aggravate the progression of OA., Methods: In this study, we investigated the therapeutic efficacy of intra-articular injection of bone marrow mesenchymal stem cells (BMSCs) transfected with miR-29a-3p inhibitor in OA., Results: miR-29a-3p inhibitor transfection did not influence cell viability of BMSCs, while the chondrogenic differentiation potential of BMSCs was significantly improved. Interestingly, intra-articular injection of BMSCs with miR-29a-3p inhibition significantly prevented articular cartilage degeneration by up-regulating the expression of Sox 9, Col-2a1, aggrecan and down-regulating the expression of matrix metalloproteinase, as well as relieved pain in OA., Conclusion: The double effects on cartilage protection and pain relief indicated a great potential of intra-articular injection of miR-29a-3p inhibitor-transfected BMSCs for the treatment of OA., (© 2021. The Korean Tissue Engineering and Regenerative Medicine Society.)

The development of easily recyclable non-noble metal plasmonic photocatalysts with high performance is highly desired for the removal of Cr(VI). Herein, the in-situ growth of plasmonic-bismuth (Bi) combined with magnetic ferroferric (Fe 3 O 4 ) nanoparticles on biochar (BC) was realized by a facile high temperature calcination. BC/Bi/Fe 3 O 4 exhibits broad photoabsorption from 200 to 2000 nm. The weaker photoluminescence (PL) spectrum or stronger photocurrent density confirmed its higher separation efficiency of photogenerated carriers than that of BC or Bi/Fe 3 O 4 . Under visible light irradiation, BC/Bi/Fe 3 O 4 exhibits excellent adsorption-photocatalytic performance for Cr(VI) (95%) in 180 min. With BC/Bi/Fe 3 O 4 as a working electrode, the higher removal efficiency (97%) was achieved than that using BC/Bi (65%), BC/Fe 3 O 4 (79%) or Bi/Fe 3 O 4 (66%) after 160 min under visible light irradiation, rooting from wide spectral absorption and efficient separation of photogenerated carriers. BC/Bi/Fe 3 O 4 can be easily recycled by magnetism with good stability. This work not only provides ideas for the preparation of surface plasma resonance (SPR) semiconductor photocatalyst for removing heavy metal, but also realizes the resource utilization of agricultural and forestry waste., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Bone is the most common late metastasis of breast cancer. Bone metastasis causes not only severe bone pain, but also bone-related diseases such as pathological fractures, which are closely related to osteoclasts. The effects of demethoxycurcumin (DMC) on osteoclast biology has not been investigated. In this study, we explored the effects of DMC on MDA-MB-231 cells, MCF-7 cells, and osteoclasts induced by RANKL in vitro, as well as the protective effect on bone destruction of tumor bone metastasis in vivo. DMC showed inhibitory effect on the migration and promotes the apoptosis of MDA-MB-231 and MCF-7 cells. At the same time, DMC inhibited osteoclast maturation and mature osteoclast bone resorption in a dose-dependent manner, and suppressed the expression of osteoclast marker genes TRAP, CTSK, MMP9, V-ATPase-d2 and DC-STAMP significantly. Biochemical data showed that DMC inhibited tumor cells and osteoclasts by inhibiting the early activation of ERK and JNK MAPK pathway. Consistent with the results in vitro, we confirmed that DMC protects bone destruction caused by tumor metastasis in vivo. In short, our study confirmed that DMC could be used as a potential drug for the treatment of tumor bone destruction.

In this study, the chloroplast genome sequencing of the Achyranthes longifolia, Achyranthes bidentata and Achyranthes aspera were performed by Next-generation sequencing technology. The results revealed that there were a length of 151,520 bp (A. longifolia), 151,284 bp (A. bidentata), 151,486 bp (A. aspera), respectively. These chloroplast genome have a highly conserved structure with a pair of inverted repeat (IR) regions (25,150 bp; 25,145 bp; 25,150 bp), a large single copy (LSC) regions (83,732 bp; 83,933 bp; 83,966 bp) and a small single copy (SSC) regions (17,252 bp; 17,263 bp; 17,254 bp) in A. bidentate, A. aspera and A. longifolia. There were 127 genes were annotated, which including 8 rRNA genes, 37 tRNA genes and 82 functional genes. The phylogenetic analysis strongly revealed that Achyranthes is monophyletic, and A. bidentata was the closest relationship with A. aspera and A. longifolia. A. bidentata and A. longifolia were clustered together, the three Achyranthes species had the same origin, then the gunes of Achyranthes is the closest relative to Alternanthera, and that forms a group with Alternanthera philoxeroides. The research laid a foundation and provided relevant basis for the identification of germplasm resources in the future.

Background: Studies have shown the efficacy of norepinephrine in the treatment of maternal hypotension during cesarean section by comparing it to treatment with phenylephrine. However, few studies have compared the efficacy of norepinephrine to ephedrine., Methods: Ninety-seven women undergoing elective cesarean section were administered norepinephrine at 4 μg/minute (group N; n = 48) or ephedrine at 4 mg/minute (group E; n = 49) immediately postspinal anesthesia, with an on-off titration to maintain systolic blood pressure (SBP) at 80% to 120% of baseline. A rescue bolus of 8 μg norepinephrine was given whenever SBP reached the predefined lower limit. Our primary outcome was the incidence of tachycardia. Secondary outcomes included the incidence of bradycardia, hypertension, hypotension, severe hypotension, hypotensive episodes, number of rescue top-ups, hemodynamic performance error including median performance error (MDPE), and median absolute performance error (MDAPE). Neonatal Apgar scores and umbilical arterial (UA) blood gas data were also collected., Results: Women in group N experienced fewer cases of tachycardia (4.2% vs 30.6%, P = .002, odds ratio: 0.11 [95% confidence interval, CI: 0.02-0.47]), a lower standardized heart rate (HR) (70.3 ± 11 vs 75 ± 11, P = .04, difference: 4.7 ± 2.2 [95% CI: 0.24-9.1]), and a lower MDPE for HR (1.3 ± 9.6 vs 8.4 ± 13.5 bpm, P = .003, difference: 3.1 ± 1.8 [95% CI: -0.6-6.7]). In addition, the lowest or the highest HR was lower in group N compared to group E (both P < .05). Meanwhile, the standardized SBP in group N was lower than that in group E (P = .04). For neonates, the UA blood gas showed a higher base excess (BE) and a lower lactate level in group N compared to E (both P < .001). Other hemodynamic variables, maternal, and neonatal outcomes were similar., Conclusion: Infusion of 4 μg/minute norepinephrine presented fewer cases of tachycardia, less fluctuation and a lower HR compared to baseline values, as well as a less stressed fetal status compared to ephedrine infusion at 4 mg/minute. In addition, norepinephrine infusion presented a lower standardized SBP compared to ephedrine.

From the prehistoric era until the publishing of the Compendium of Materia Medica and the first scientific Nobel Prize in the Chinese mainland for Tu's discovery on anti-malarial tablets, each milestone and stepping stone in the developmental history of herbal medicine involved intrepid exploration, bold hypothesis formulation, and cautious verification. After thousands of years of discovery and development, herbal research has entered a new era-the era of herbgenomics. Herbgenomics combines herbal and genomic research, bridging the gap between traditional herbal medicine and cutting-edge omics studies. Therefore, it provides a general picture of the genetic background of traditional herbs, enabling researchers to investigate the mechanisms underlying the prevention and treatment of human diseases from an omics perspective.

C 3 N 4 -decorated carbon-fiber (CF) cloth has been demonstrated as flexible filter-membrane-shaped photocatalyst for degrading the flowing wastewater, but its photocatalytic activity should be further improved. To enhance the separation efficiency of photogenerated carrier, herein we inserted TiO 2 between C 3 N 4 and CF. With CF cloth as the substrate, the in-situ growth of TiO 2 nanoparticles (diameter: 100-200 nm) was realized by a dip-coating/hydrothermal method; and C 3 N 4 nanosheets (thickness: 30-50 nm) were prepared on their surface by thermal polymerization. CF/TiO 2 /C 3 N 4 cloth shows excellent visible photoabsorption (edge: ∼450 nm). Under visible light irradiation, CF/TiO 2 /C 3 N 4 cloth exhibits improved photocurrent and photocatalytic activity for degrading various organic pollutants (methylene blue, acid orange 7, 4-chloprophenol, tetracycline hydrochloride (TC)) and reducing heavy-metal ions (Cr(VI)), compared with CF/C 3 N 4 and CF/TiO 2 cloth. Especially, when CF/TiO 2 /C 3 N 4 cloth is used as filter-membrane to photo-degrade the flowing wastewater (rate: 1.5 L h -1 ), the removal efficiency of TC and Cr(VI) reaches 87% and 88% after 7 grade, higher than that by CF/C 3 N 4 cloth (60% TC, 28% Cr(VI)) and CF/TiO 2 cloth (8% TC, 7% Cr(VI)). Therefore, CF/TiO 2 /C 3 N 4 cloth can be used as efficient filter-membrane-shaped photocatalyst for removing various organic pollutants and heavy metal in the flowing wastewater., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study evaluated the efficacy and safety of dexmedetomidine in intravenous patient-controlled analgesia (PCA) after cesarean delivery. This multicenter study enrolled 208 subjects who were scheduled for selective cesarean delivery from 9 research centers. Patients received 0.5 ug/kg dexmedetomidine (study group) or normal saline (control group) after delivery and an intravenous PCA pump after surgery (100 μg sufentanil +300 μg dexmedetomidine for the study group, 100 μg sufentanil for the control group, background infusion: 1 ml/h, bolus dose: 2 ml and lock time: 8 min). The sufentanil consumption, pain scores, rescue analgesia, sedation scores, analgesic satisfaction, the incidence of postoperative nausea and vomiting (PONV) and the first passage of flatus were recorded within 24 h after surgery. The sufentanil consumption in the study group was significantly lower than that in the control group (p = 0.004). Compared with the control group, the study group had lower pain scores (p < 0.01), higher analgesic satisfaction degree [p < 0.001, odd ratio 4.28 and 95% CI (2.46, 7.46)], less requirement of rescue analgesia (p = 0.003), lower incidence of PONV (p = 0.005 and p < 0.001, respectively), and shorter time to first passage of flatus (p = 0.007). Dexmedetomidine added to sufentanil intravenous PCA significantly enhanced the analgesic effects, improved analgesic satisfaction, and had the potential benefits of reducing PONV and the recovery of intestinal functions after cesarean section.

Objective: To evaluate whether maintaining a motor-sparing epidural analgesia infusion affects the duration of the second stage of labor in nulliparous parturients compared with a placebo control., Methods: We conducted a double-blind, randomized, placebo-controlled trial involving nulliparous women with term cephalic singleton pregnancies who requested epidural analgesia. All women received epidural analgesia for the first stage of labor using 0.08% ropivacaine with 0.4 micrograms/mL sufentanil with patient-controlled epidural analgesia. At the onset of the second stage of labor, women were randomized to receive a blinded infusion of the same solution or placebo saline infusion. The primary outcome was the duration of the second stage of labor. A sample size of 200 per group (400 total) was planned to identify at least a 15% difference in duration., Results: Between March 2015 and September 2015, 560 patients were screened and 400 patients (200 in each group) completed the study. Using an intention-to-treat analysis, the duration of the second stage was similar between groups (epidural 52±27 minutes compared with saline 51±25 minutes, P=.52). The spontaneous vaginal delivery rate was also similar (epidural 193 [96.5%] compared with saline 198 [99%], P=.17). Pain scores were similar between groups at each measurement during the second stage. More women who received placebo reported satisfaction scores of 8 or less (epidural 32 [16%] compared with saline 61 [30.5%], P=.001)., Conclusion: Maintaining the infusion of epidural medication had no effect on the duration of the second stage of labor compared with a placebo infusion. Maternal and neonatal outcomes were similar. A low concentration of epidural local anesthetic does not affect the duration of the second stage of labor., Clinical Trial Registration: Chinese Clinical Trial Register, http://www.chictr.org.cn/enindex.aspx, ChiCTR-IOR-15005875.

Bone tissue engineering by using osteoinductive scaffolds seeded with stem cells to promote bone extracellular matrix (ECM) production and remodeling has evolved into a promising approach for bone repair and regeneration. In order to mimic the ECM of bone tissue structurally and compositionally, nanofibrous silk fibroin (SF) scaffolds containing hydroxyapatite (HAP) nanoparticles and bone morphogenetic protein 2 (BMP-2) were fabricated in this study using electrospinning technique. The microstructure, mechanical property, biocompatibility, and osteogenic characteristics were examined. It was found that the HAP nanoparticles were successfully incorporated in the SF nanofibers (diameter, 200-500 nm). The mechanical properties of SF/HAP/BMP-2 composite scaffolds increased with HAP content when it was less than 20 wt%, after which the mechanical properties dropped as HAP content increased. Cell culture tests using bone marrow mesenchymal stem cells (BMSCs) showed that the scaffolds had good biocompatibility and promoted the osteogenic differentiation of BMSCs. Therefore, the electrospun SF/HAP/BMP-2 scaffolds may serve as a promising biomaterial for bone tissue engineering.

Postoperative cognitive dysfunction (POCD) is a subtle disorder of thought processes, which may influence isolated domains of cognition and has a significant impact on patient health. The reported incidence of POCD varies enormously due to lack of formal criteria for the assessment and diagnosis of POCD. The significant risk factors of developing POCD mainly include larger and more invasive operations, duration of anesthesia, advanced age, history of alcohol abuse, use of anticholinergic medications, and other factors. The release of cytokines due to the systemic stress response caused by anesthesia and surgical procedures might induce the changes of brain function and be involved in the development of postoperative cognitive dysfunction. The strategies for management of POCD should be a multimodal approach involving close cooperation between the anesthesiologist, surgeon, geriatricians, and family members to promote early rehabilitation and avoid loss of independence in these patients.

The endothelium performs a crucial role in maintaining vascular integrity leading to whole organ metabolic homeostasis. Endothelial dysfunction represents a key etiological factor leading to moderate to severe vasculopathies observed in both Type 2 diabetic and Alzheimer's Disease (AD) patients. Accordingly, evidence-based epidemiological factors support a compelling hypothesis stating that metabolic rundown encountered in Type 2 diabetes engenders severe cerebral vascular insufficiencies that are causally linked to long term neural degenerative processes in AD. Of mechanistic importance, Type 2 diabetes engenders an immunologically mediated chronic pro-inflammatory state involving interactive deleterious effects of leukocyte-derived cytokines and endothelial-derived chemotactic agents leading to vascular and whole organ dysfunction. The long term negative consequences of vascular pro-inflammatory processes on the integrity of CNS basal forebrain neuronal populations mediating complex cognitive functions establish a striking temporal comorbidity of AD with Type 2 diabetes. Extensive biomedical evidence supports the pivotal multi-functional role of constitutive nitric oxide (NO) production and release as a critical vasodilatory, anti-inflammatory, and anti-oxidant, mechanism within the vascular endothelium. Within this context, we currently review the functional contributions of dysregulated endothelial NO expression to the etiology and persistence of Type 2 diabetes-related and co morbid AD-related vasculopathies. Additionally, we provide up-to-date perspectives on critical areas of AD research with special reference to common NO-related etiological factors linking Type 2 diabetes to the pathogenesis of AD.

Background and Objectives: Spinal anesthesia-associated maternal hypotension in Cesarean delivery is the most frequent and troublesome complication, posing serious risks to mothers and compromising neonatal well-being. The effective volume of intravenous crystalloid as the preventive strategy in this context has not been estimated., Methods: Eighty-five parturients with ASA physical status I/II undergoing elective Cesarean delivery were screened and 67 eligible women were assigned to receive pre-spinal crystalloid loading. Hyperbaric 0.5% bupivacaine 2mL (10mg) plus morphine 50μg was given to all patients. The volume of crystalloid was determined by an up-and-down sequential method. The crystalloid was infused at a rate of 100-150mL.min(-1) prior to the spinal anesthetic injection. The initial volume of crystalloid was 5mL.kg(-1). Volume-effect data were fitted to a sigmoidal maximum efficacy model and the median effective volume (EV(50)) and corresponding 95% confidence interval (95% CI) were estimated using maximum likelihood estimation and logistic regression with Firth's correction., Results: A total of 67 subjects completed the study and were analyzed. Twenty-eight (41.8%) patients developed hypotension with their systolic blood pressure (SBP) decreasing > 20% of baseline. The EV(50) of crystalloid were 12.6mL.kg(-1) (95% CI, 11.6 to 14.8mL.kg(-1)). With Firth's correction, the pooled probability of an effective preventive volume of crystalloid at 13mL.kg(-1) was 50.2% (95% CI, 30% to 83.1%)., Conclusions: The estimated EV(50) of the preloaded crystalloid required to prevent spinal anesthesia-induced hypotension in a Cesarean section is, approximately, 13mL.kg(-1). However, prophylactic or therapeutic vasoconstrictors should also be prepared and administered at an appropriate time., (Copyright © 2012 Elsevier Editora Ltda. All rights reserved.)

Background and Objectives: Local anesthetics are used broadly to prevent or reverse acute pain and treat symptoms of chronic pain. Local anesthetic-induced cardiotoxic reaction has been considered the accidental event without currently effective therapeutic drugs except for recently reported intralipid infusion whose possible mechanism of action is not well known., Contents: Cardiolipin, an anionic phospholipid, plays a key role in determining mitochondrial respiratory reaction, fatty acid metabolism and cellular apoptosis. Mitochondrial energy metabolism dysfunction is suggested as associated with local anesthetic cardiotoxicity, from an in vitro study report that the local anesthetic cardiotoxicity may be due to the strong electrostatic interaction of local anesthetics and cardiolipin in the mitochondria membrane, although there is a lack for experimental evidence. Herein we hypothesized that local anesthetic-cardiolipin interactions were the major determinant of local anesthetic-associated cardiotoxic reaction, established by means of theoretic and structural biological methods. This interacting model would give an insight on the underlying mechanism of local anesthetic cardiotoxicity and provide clues for further in depth research on designing preventive drugs for such inadvertent accidence in routine clinical practice., Conclusions: The interaction between local anesthetic and mitochondrial cardiolipin may be the underlying mechanism for cardiotoxicity affecting its energy metabolism and electrostatic status., (Copyright 2010 Elsevier Editora Ltda. All rights reserved.)

Background: The optimal timing of epidural analgesia has been a controversial issue, and how early women can benefit from epidural analgesia is still debated. The objective of this trial was to test the hypothesis that patient-controlled epidural analgesia given at cervical dilation of 1.0 cm or more does not increase the risk of prolonged labor or Cesarean delivery., Methods: After institutional review board approval and patient consent, 12,793 nulliparous patients requesting neuraxial analgesia were enrolled and randomized to an early epidural (cervical dilation at least 1.0 cm) or delayed epidural (cervical dilation at least 4.0 cm) group. A 15-ml epidural analgesic mixture consisting of 0.125% (1.25 mg/ml) ropivacaine plus 0.3 microg/ml sufentanil was given in a single bolus, followed by patient-controlled pump with a 10-ml bolus without background infusion. Repeatable meperidine (25 mg) was prescribed as being the rescue analgesic to patients in the delayed epidural group. The primary outcome was the rate of Cesarean section., Results: The median diameters of cervical dilation were 1.6 cm and 5.1 cm in the early and delayed epidural groups, respectively (P < 0.0001). The duration of labor from analgesia request to vaginal delivery was equal in both groups (11.3 +/- 4.5 h for early epidural and 11.8 +/- 4.9 h for delayed epidural group women, P = 0.90). No statistically significant difference in the rate of Cesarean section was observed between the two groups on the intention-to-treat analysis (23.2% vs. 22.8% in the early and delayed epidural groups, respectively; P = 0.51)., Conclusions: Epidural analgesia in the latent phase of labor at cervical dilation of 1.0 cm or more does not prolong the progression of labor and does not increase the rate of Cesarean in nulliparous women compared with the delayed analgesia at the cervical dilation of 4.0 cm or more.

The aim of this study was to investigate the analgesic efficacy of tramadol administrated preemptively or preventively in the earlier period of lumpectomy. Four hundred American Society of Anesthesiologists (ASA) physical status I-II patients, undergoing lumpectomy, were screened and 317 were randomly assigned into one of two groups. In the preemptive tramadol (n = 158) group, patients received an iv injection of tramadol 100 mg 15 min before operation. The preventive group (n = 159) received the same dose of tramadol 15 min before the end of the operation. Pain intensity at rest, overall satisfaction score, morphine consumption and side effects were recorded. A total of 299 patients completed the study. Preemptive and preventive subjects experienced similar analgesic effect and feeling of satisfaction at the first 24 h after surgeries. The similar amount of additional morphine was consumed [4.6 mg (95% CI 1.5-7.2) vs. 4.1 mg (95% CI 1.2-6.3), p = 0.811]. No intergroup difference was observed in the incidence of side effects. In conclusion, preemptive and preventive administration of tramadol expressed analgesia of similar efficacy up to 24 h after lumpectomy. The additional morphine requirement, the overall satisfaction and the frequency of side effects all did not display significant difference between the two groups. This implies that the administration of tramadol either before the start or before the end of the surgical procedures all can produce effective postoperative analgesia.

The new biodegradable chitosan graft copolymer, chitosan-g-polycaprolactone, was synthesized by the ring-opening graft copolymerization of epsilon-caprolactone onto phthaloyl-protected chitosan (PHCS) at the hydroxyl group in the presence of tin(II) 2-ethylhexanoate catalyst via a protection-graft-deprotection procedure. Toluene acted as a swelling agent in this heterogeneous system. The grafting reactions were conducted with various PHCS/monomer/toluene feed ratios to obtain chitosan-g-polycaprolactone copolymers with various polycaprolactone contents. The chemical structure of the chitosan-g-polycaprolactone was characterized by Fourier transform infrared and one- and two-dimensional NMR spectroscopy. After deprotection, the phthaloyl group was removed and the amino group was regenerated. Thus the obtained chitosan-g-polycaprolactone was an amphoteric hybrid with a large amount of free amino groups and hydrophobic polycaprolactone side chains. Some properties of the final product were also investigated, such as crystallinity, thermal property, and solubility., ((c) 2005 Wiley Periodicals, Inc.)