Hydrophobic TPU/CNTs-ILs Ionogel as a Reliable Multimode and Flexible Wearable Sensor for Motion Monitoring, Information Transfer, and Underwater Sensing.

Ionogel-based sensors have gained widespread attention in recent years due to their excellent flexibility, biocompatibility, and multifunctionality. However, the adaptation of ionogel-based sensors in extreme environments (such as humid, acidic, alkaline, and salt environments) has rarely been studied. Here, thermoplastic polyurethane/carbon nanotubes-ionic liquids (TPU/CNTs-ILs) ionogels with a complementary sandpaper morphology on the surface were prepared by a solution-casting method with a simple sandpaper as the template, and the hydrophobic flexible TPU/CNTs-ILs ionogel-based sensor was obtained by modification using nanoparticles modified with cetyltrimethoxysilane. The hydrophobicity improves the environmental resistance of the sensor. The ionogel-based sensor exhibits multimode sensing performance and can accurately detect response signals from strain (0-150%), pressure (0.1-1 kPa), and temperature (30-100 °C) stimuli. Most importantly, the hydrophobic TPU/CNTs-ILs ionogel-based sensors can be used not only as wearable strain sensors to monitor human motion signals but also for information transfer, writing recognition systems, and underwater activity monitoring. Thus, the hydrophobic TPU/CNTs-ILs ionogel-based sensor offers a new strategy for wearable electronics, especially for applications in extreme environments.

Advanced nanomedicines and immunotherapeutics to treat respiratory diseases especially COVID-19 induced thrombosis.

Immunotherapy and associated immune regulation strategies gained huge attraction in order to be utilized for treatment and prevention of respiratory diseases. Engineering specifically nanomedicines can be used to regulate host immunity in lungs in the case of respiratory diseases including coronavirus disease 2019 (COVID-19) infection. COVID-19 causes pulmonary embolisms, thus new therapeutic options are required to target thrombosis, as conventional treatment options are either not effective due to the complexity of the immune-thrombosis pathophysiology. In this review, we discuss regulation of immune response in respiratory diseases especially COVID-19. We further discuss thrombosis and provide an overview of some antithrombotic nanoparticles, which can be used to develop nanomedicine against thrombo-inflammation induced by COVID-19 and other respiratory infectious diseases. We also elaborate the importance of immunomodulatory nanomedicines that can block pro-inflammatory signalling pathways, and thus can be recommended to treat respiratory infectious diseases.

Self-Assembly of Amphiphilic PDI and NDI Derivatives with Opposite Thermoresponsive Fluorescent Behaviors in Aqueous Solution.

This work presents a study of the thermally induced aggregation of perylene diimide (PDI) and naphthalene diimide (NDI) derivatives modified with oligo ethylene glycol (OEG) chains in aqueous solution. Water-soluble and flexible OEG side chains were introduced into the π-core of glutamate-modified NDI and PDI structures, and the aggregation process was modulated by heating or cooling in water. Interestingly, a rare opposite temperature response of fluorescent behavior from the two amphiphilic chromophores was revealed, in which the PDI exhibited fluorescent enhancement, while fluorescent quenching upon temperature increase was observed from the NDI assembly. The mechanism of thermally induced aggregation is clearly explained by studies with various spectroscopic techniques including UV-visible, fluorescence, 1H NMR, 2D NMR spectroscopy, and SEM observation as well as control experiments operated in DMSO solution. It is found that although similar J-aggregates were formed by both amphiphilic chromophores in aqueous solution, the temperature response of the aggregates to temperature was opposite. The degree of PDI aggregation decreased, while that of NDI increased upon temperature rising. This research paves a valuable way for understanding the complicated supramolecular behaviors of amphiphilic chromophores.

Generation of induced pluripotent stem cells (ZZUCSBi001-A) from skin fibroblasts of a healthy donor.

Fibroblasts were extracted from the scalp of a healthy 55-year-old male and subsequently transformed into pluripotent stem cells by introducing episomal plasmids harboring essential reprogramming factors. These induced pluripotent stem cells exhibited a normal karyotype and demonstrated the capacity to differentiate into all three germ layers, as confirmed through teratoma assays. This specific cell line serves as a valuable reference for comparative investigations alongside other induced pluripotent stem cell lines generated from somatic cells of patients afflicted by genetic neurodegenerative disorders.

Irisin attenuates vascular remodeling in hypertensive mice induced by Ang II by suppressing Ca2+-dependent endoplasmic reticulum stress in VSMCs.

Vascular remodeling plays a vital role in hypertensive diseases and is an important target for hypertension treatment. Irisin, a newly discovered myokine and adipokine, has been found to have beneficial effects on various cardiovascular diseases. However, the pharmacological effect of irisin in antagonizing hypertension-induced vascular remodeling is not well understood. In the present study, we investigated the protection and mechanisms of irisin against hypertension and vascular remodeling induced by angiotensin II (Ang II). Adult male mice of wild-type, FNDC5 (irisin-precursor) knockout, and FNDC5 overexpression were used to develop hypertension by challenging them with Ang II subcutaneously in the back using a microosmotic pump for 4 weeks. Similar to the attenuation of irisin on Ang II-induced VSMCs remodeling, endogenous FNDC5 ablation exacerbated, and exogenous FNDC5 overexpression alleviated Ang II-induced hypertension and vascular remodeling. Aortic RNA sequencing showed that irisin deficiency exacerbated intracellular calcium imbalance and increased vasoconstriction, which was parallel to the deterioration in both ER calcium dysmetabolism and ER stress. FNDC5 overexpression/exogenous irisin supplementation protected VSMCs from Ang II-induced remodeling by improving endoplasmic reticulum (ER) homeostasis. This improvement includes inhibiting Ca2+ release from the ER and promoting the re-absorption of Ca2+ into the ER, thus relieving Ca2+-dependent ER stress. Furthermore, irisin was confirmed to bind to its receptors, αV/ß5 integrins, to further activate the AMPK pathway and inhibit the p38 pathway, leading to vasoprotection in Ang II-insulted VSMCs. These results indicate that irisin protects against hypertension and vascular remodeling in Ang II-challenged mice by restoring calcium homeostasis and attenuating ER stress in VSMCs via activating AMPK and suppressing p38 signaling.

Moutai Distiller's grains Polyphenol extracts and rutin alleviate DSS-induced colitis in mice: Modulation of gut microbiota and intestinal barrier function （R2）.

Distiller's grains, byproducts of the brewing process, represent a valuable resource for extracting natural phenolic compounds due to their significant global production. This study presents the first evidence of the protective effects of Moutai distiller's grain polyphenol extract (MDGP) on dextran sulfate sodium (DSS)-induced colitis in mice. These protective effects manifest predominantly through the amelioration of general colitis indices and histopathological improvements. Utilizing liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), the main components of MDGP were identified as rutin, quercetin, naringenin, and dihydroquercetin. Moreover, a novel mechanism was elucidated by which rutin, the primary active component of MDGP, alleviates DSS-induced colitis. Assessment of intestinal barrier function, microbial sequencing, fecal transplantation, and antibiotic depletion experiments revealed that rutin suppresses the abundance of pathogenic bacteria (Helicobacter, Klebsiella, and Veillonella) while promoting the proliferation of beneficial bacteria (Ruminococcus_torques_group, Lachnoclostridium, and norank_f__Muribaculaceae). This modulation culminates in elevated butyric acid concentrations within short-chain fatty acids (SCFAs), amplified integrity of tight (ZO-1, occludin) and adherent (E-cadherin, ß-catenin) junctional complexes, fortified intestinal barrier function, and diminished intestinal inflammation.This investigation accentuates the innovative therapeutic potential of MDGP and its main active component, rutin, in assuaging DSS-induced intestinal inflammation and fortifying the intestinal barrier through a mechanism predominantly mediated by the intestinal microbiota. Such insights potentially elevate the prominence of distiller's grains in the realm of functional food development.

Humidity-Resistant, Conductive Fabric-Based Triboelectric Nanogenerator for Efficient Energy Harvesting and Human-Machine Interaction Sensing.

With the rapid development of triboelectric nanogenerators (TENGs), the exploration of self-powered, flexible, and wearable electronic devices has attracted widespread attention. However, the choice of tribomaterials and high humidity environment have a significant impact on the triboelectricity of TENG. Therefore, we prepared a composite fabric (HPC) with superhydrophobic and conductive properties, which was used simultaneously as a tribopositive material and electrode for the construction of promising wearable TENGs. Specifically, the loading of polydopamine, carbon nanotubes, and polypyrrole on the surface of the cotton fabric makes it have not only conductivity but also enhanced tribopositive polarity. Then, cetyltrimethoxysilane was selected to modify it to obtain superhydrophobicity. Compared with the common TENGs with a separate tribolayer and electrode, the integrated HPC-TENG shows the advantages of simpler structure and lighter wear. Moreover, compared with the unmodified fabric-based TENG, the performance of the proposed HPC-TENG is improved by nearly 7.2 times, and the maximum power density can reach 2.6 W m-2. This remarkable output can be attributed to the combination of strong electron-giving groups, high electrical conductivity, and abundant micro- and nanorough structure of the HPC fabric. More importantly, due to the water repellency of the fabric surface, the high output performance can be maintained under high humidity conditions. In addition, HPC-TENG has potential applications as pressure sensors for human motion status monitoring and multichannel sensing for smart game blanket entertainment. The newly designed HPC-TENG offers a new strategy for the development of superhydrophobic fabrics with an electrical conductivity, energy harvesting, and self-powered sensor.

Bidirectional associations between maladaptive cognitions and emotional symptoms, and their mediating role on the quality of life in adults with ADHD: a mediation model.

Background/objectives: Adults with attention-deficit/hyperactivity disorder (ADHD) have more maladaptive cognitions, emotional problems and a poorer quality of life (QoL). A verification of the psychological model in clinical samples is needed for a better understanding of the mechanisms of ADHD diagnosis on QoL via maladaptive cognitions, emotional symptoms, and their interactions. Methods: 299 ADHD participants and 122 healthy controls were recruited. ADHD core symptoms, maladaptive cognitions, emotional symptoms and psychological QoL were rated. Pearson's correlation and structural equation modeling were analyzed to explore the relationship and influence of ADHD diagnosis on QoL. Results: More maladaptive cognitions, emotional symptoms, and poorer QoL were found in the ADHD group, and the dysfunctional attitudes were on par between ADHD with or without medication (p = 0.368). Moderate to strong correlations were found between emotional symptoms, maladaptive cognitions and QoL, and ADHD core symptoms presented correlations among the above scores (r = 0.157 ~ 0.416, p < 0.01) in ADHD participants. The influence of ADHD diagnosis on QoL was mediated through maladaptive cognitions, emotional symptoms, and their bidirectional interactions (p < 0.05), especially those with stable medication. Conclusion: Our study is the first to verify the psychological model in adults with ADHD in China. The findings determined the direct influence of ADHD diagnosis on QoL and the indirect influence through maladaptive cognitions, emotional symptoms, and their interactions, emphasizing the importance of interventions for emotional symptoms and maladaptive cognitions for ADHD patients both with or without medication for a better QoL outcome.

Multi-Functional Janus Hollow Solar Evaporator Based on Copper Foam for Non-Contact High-Efficiency Solar Interfacial Distillation.

As a sustainable, clean, and friendly technology with a minimal carbon footprint when treating seawater or wastewater, interfacial solar vapor generation (ISVG) technology is a great alternative to traditional desalination and water purification methods (e.g., reverse osmosis and ultrafiltration). So far, it presents tremendous potential for applications in realizing desalination of seawater or brine, wastewater treatment, and so forth. However, the precipitated salt particles during conventional ISVG inevitably block the evaporator surface, resulting in the degradation of photothermal conversion and decrease of evaporation rate. Herein, a multi-functional non-contact Janus hollow evaporator based on copper foam was prepared, which was assembled by a hydrophobic light-to-heat conversion layer and a hydrophilic interfacial water evaporation layer as two separate parts. Accordingly, the precipitated salt in the ISVG system does not block the photothermal interface, increasing the stability of solar capture and reusability of the evaporator. Notably, the hollow structure of the evaporator has a local interfacial heating effect, endowing the evaporation system with a high seawater evaporation rate of 2.249 kg m-2 h-1. The evaporator is capable of stable operation for 10 h under 1 sun illumination even when evaporating concentrated brine (15 wt %). Moreover, the evaporation rate of water under one sun irradiation reached 2.284 kg m-2 h-1 and the solar-to-vapor efficiency reached 96.6%. Not only that, the evaporator was able to successfully purify wastewater containing dyes and heavy metal ions. The multi-functional Janus hollow interfacial solar evaporator will provide inspiration for upcoming research on the production of safety water.

Effects of Jatrorrhizine on inflammatory response induced by H2O2 in microglia by regulating the MAPK/NF-κB/NLRP3 signaling pathway.

Microglia-induced neuroinflammation is a contributing factor to neurodegenerative diseases. Jatrorrhizine (JAT), an alkaloid isolated from Huanglian, has been shown to have neuroprotective effects against various neurodegenerative diseases, but its impact on microglia-induced neuroinflammation remains unclear. In this study, we investigated the role of JAT in MAPK/NF-κB/NLRP3 signaling pathway in an H2O2-induced oxidative stress model using microglia (N9 cells). We divided cells into six groups, including control, JAT, H2O2, H2O2 + 5 µmol/L JAT, H2O2 + 10 µmol/L JAT, and H2O2 + 20 µmol/L minocycline groups. Cell viability was measured using MTT assay and TNF-α levels were detected with an ELISA Kit. Western blot was used to detect NLRP3, HMGB1, NF-κB, p-NF-κB, ERK, p-ERK, p38, p-p38, p-JNK, JNK, IL-1ß, and IL-18 expressions. Our results showed that JAT intervention improved H2O2-induced cytotoxicity in N9 cells and reduced the elevated expression of TNF-α, IL-1ß, IL-18, p-ERK/ERK, p-p38/p38, p-JNK/JNK, p-p65/p65, NLRP3, and HMGB1 in H2O2 group. Furthermore, treatment with ERK inhibitor SCH772984 specifically blocked ERK phosphorylation, resulting in decreased protein levels of p-NF-κB, NLRP3, IL-1ß, and IL-18 in H2O2 group. These results suggest that the MAPK/NF-κB signaling pathway may regulate the protein levels of NLRP3. Overall, our study indicates that JAT may have a protective effect on H2O2-treated microglia via inhibition the MAPK/NF-κB/NLRP3 pathway and could be a potential therapeutic approach for neurodegenerative diseases.

[Molecular mechanism of resveratrol combined with irinotecan in treatment of colorectal cancer].

This study aimed to investigate the mechanism of resveratrol(RES) combined with irinotecan(IRI) in the treatment of colorectal cancer(CRC). The targets of RES, IRI, and CRC were obtained from databases, and the targets of RES combined with IRI in the treatment of CRC were acquired by Venn diagram. The protein functional cluster analysis, GO and KEGG enrichment analyses were performed. In addition, the protein-protein interaction(PPI) network was constructed. The core target genes were screened out and the target-signaling pathway network was set up. IGEMDOCK was used to dock the core target gene molecules. Besides, the relationship between the expression level of key target genes and the prognosis and immune infiltration of CRC was analyzed. Based on the in vitro cell experiment, the molecular mechanism of RES combined with IRI in the treatment of CRC was explored and analyzed. According to the results, 63 potential targets of RES combined with IRI were obtained for CRC treatment. Furthermore, cluster analysis revealed that protein functions included 23% transmembrane signal receptors, 22% protein modifying enzymes, and 14% metabolite converting enzymes. GO analysis indicated that BPs were mainly concentrated in protein autophosphorylation, CCs in receptor complex and plasma membrane, and MFs in transmembrane receptor protein tyrosine kinase activity. Moreover, KEGG signaling pathways were mainly enriched in central carbon metabolism in cancer. The key targets of RES combined with IRI in the treatment of CRC were PIK3CA, EGFR, and IGF1R, all of which were significantly positively correlated with the immune infiltration of CRC. As shown by the molecular docking results, PIK3CA had the most stable binding with RES and IRI. Compared with the results in the control group, the proliferation ability and EGFR protein expression of CRC cells in the RES-treated group, the IRI-treated group, and the RES+IRI treated group significantly decreased. Moreover, the cell proliferation ability and EGFR protein expression level of CRC cells in the RES+IRI treated group were remarkably lower than those in the IRI-treated group. In conclusion, PIK3CA, EGFR, and IGF1R are the key targets of RES combined with IRI in CRC treatment. In addition, RES can inhibit the proliferation of CRC cells and improve IRI chemoresistance by downregulating the EGFR signaling pathway.

[Hydroxysafflor yellow A inhibits proliferation, migration, and chemoresistance of colorectal cancer cells through Akt/mTOR-autophagy pathway].

In recent years, the clinical treatment of colorectal cancer(CRC) has made great progress, but chemoresistance is still one of the main reasons for reducing the survival rate of patients with colorectal cancer. Therefore, ameliorating chemotherapy resis-tance is an urgent problem to be solved. The purpose of this study was to investigate the regulatory role and related molecular mechanisms of hydroxysafflor yellow A(HSYA) in colorectal cancer cell proliferation, migration, and 5-fluorouracil(5-FU) chemoresistance. In this study, HCT116 and HT-29 cells were used as research subjects. Firstly, methyl thiazolyl tetrazolium(MTT) assay and colony formation assay were used to detect and analyze the effect of HSYA on the proliferation of CRC cells. Secondly, the effect of HSYA on the cell cycle in CRC cells was analyzed by cell cycle assay. Furthermore, the effect of HSYA on the migration of CRC cells was analyzed by wound-healing assay and Transwell assay. Based on the above, the influences of HSYA on 5-FU chemoresistance of CRC cells and related molecular mechanisms were explored and analyzed. The results showed that HSYA significantly inhibited the proliferation and migration of CRC cells, and arrested the cell cycle in G_0/G_1 phase. In addition, HSYA significantly ameliorated the chemoresistance of CRC cells to 5-FU. The results of acridine orange staining and Western blot showed that the autophagy activity of CRC cells in the HSYA and 5-FU combined treatment group was significantly higher than that in the 5-FU single drug treatment group. As compared with the 5-FU single drug treatment group, the phosphorylation levels of protein kinase B(Akt) and mammalian target of rapamycin(mTOR) in the HSYA and 5-FU combined treatment group were significantly reduced, indicating that the Akt/mTOR signaling pathway in the combined treatment group was down-regulated in CRC cells. In conclusion, HSYA may upregulate autophagy activity through the Akt/mTOR signaling pathway, thereby inhibiting the proliferation and migration of CRC cells and ameliorating the chemoresistance to 5-FU.

Nuclear access of DNlg3 c-terminal fragment and its function in regulating innate immune response genes.

Neuroligins (NLGNs) are one of the autism susceptibility genes, however, the mechanism that how dysfunction of NLGNs leads to Autism remains unclear. More and more studies have shown that the transcriptome alteration may be one of the important factors to generate Autism. Therefore, we are very concerned about whether Neuroligins would affect transcriptional regulation, which may at last lead to Autism. As a single-transmembrane receptor, proteolytic cleavage is one of the most important posttranslational modifications of NLGN proteins. In this study, we demonstrated the existence of DNlg3 C-terminal fragment. Studies in the S2 cells and HEK293T cells showed the evidence for nuclear access of the DNlg3 C-terminal fragment. Then we identified the possible targets of DNlg3 C-terminal fragment after its nuclear access by RNA-seq. The bioinformatics analysis indicated the transcriptome alteration between dnlg3 null flies and wild type flies focused on genes for the innate immune responses. These results were consistent with the infection hypotheses for autism. Our study revealed the nuclear access ability of DNlg3 c-terminal fragment and its possible function in transcriptional regulation of the innate immune response genes. This work provides the new links between synaptic adhesion molecule NLGNs and immune activation, which may help us to get a deeper understanding on the relationship between NLGNs and Autism.

The novel HLA-C*01:02:89 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*01:02:89 differs from HLA-C*01:02:01:01 by one nucleotide in exon 2.

Progress in pH-Sensitive sensors: essential tools for organelle pH detection, spotlighting mitochondrion and diverse applications.

pH-sensitive fluorescent proteins have revolutionized the field of cellular imaging and physiology, offering insight into the dynamic pH changes that underlie fundamental cellular processes. This comprehensive review explores the diverse applications and recent advances in the use of pH-sensitive fluorescent proteins. These remarkable tools enable researchers to visualize and monitor pH variations within subcellular compartments, especially mitochondria, shedding light on organelle-specific pH regulation. They play pivotal roles in visualizing exocytosis and endocytosis events in synaptic transmission, monitoring cell death and apoptosis, and understanding drug effects and disease progression. Recent advancements have led to improved photostability, pH specificity, and subcellular targeting, enhancing their utility. Techniques for multiplexed imaging, three-dimensional visualization, and super-resolution microscopy are expanding the horizon of pH-sensitive protein applications. The future holds promise for their integration into optogenetics and drug discovery. With their ever-evolving capabilities, pH-sensitive fluorescent proteins remain indispensable tools for unravelling cellular dynamics and driving breakthroughs in biological research. This review serves as a comprehensive resource for researchers seeking to harness the potential of pH-sensitive fluorescent proteins.

Wheat TaMYB1A Negatively Regulates the Phenylpropanoid Pathway and Plant Height / 中国生物化学与分子生物学报

The phenylpropanoid pathway is one of the important pathways for synthesizing plant secondary metabolites, which can produce lignin, flavonoid, and sinapoylmalate. These compounds can not only affect the plant growth, development, and stress response, but also be used to produce perfume, pesticide, dye, medicine, feed, and biomass energy. R2R3-MYBs play important roles in regulating plant secondary metabolism, organ development, and in responding to environmental stresses. Wheat (Triticum aestivum L.) is an important food crop, but lots of straw will be produced accompanied by grain yields. Therefore, elucidating the function and regulatory mechanism of R2R3 MYBs of wheat is crucial for the effective utilization of the wheat straw. RT-PCR results showed that TaMYB1A was highly expressed in the wheat stems, and the GFP-TaMYB1A fusion protein was mainly localized in the nucleus of the N. benthamiana epidermal cells. TaMYB1A has transcriptional repressive activity in yeast cells. In this study, TaMYB1A-overexpressed transgenic Arabidopsis lines were generated to elucidate the effect of overexpression of TaMYB1A on the biosynthesis of lignin and flavonoid. Our results suggested that overexpression of TaMYB1A inhibited the plant height (P < 0. 05) and decreased the lignin (P < 0. 05) and flavonoid (P < 0. 05) biosynthesis of the transgenic Arabidopsis plants significantly. TaMYB1A could bind to the promoters of the Arabidopsis At4CL1, AtC4H, AtC3H, and AtCHS as well as the wheat Ta4CL1 and TaC4H1 revealed by yeast one-hybrid (Y1H) assasy, the transcriptional repressive effect of TaMYB1A on At4CL1, AtC4H, AtC3H, and AtCHS was confirmed by dual-luciferase reporter systems and also on Ta4CL1 and TaC4H1 by a genetic approach. Gene chip and quantitative RT-PCR (qRT-PCR) results showed that overexpression of TaMYB1A down-regulated the expression of most of the key genes involved in the phenylpropanoid metabolism and decreased the 4CL activity (P < 0. 05) of the transgenic Arabidopsis plants significantly. As suggested above, the wheat TaMYB1A belongs to the subgroup 4 R2R3 MYB transcription factors. TaMYB1A could bind to the promoters of the key genes involved in phenylpropanoid metabolism, repress their expression and negatively regulate the phenylpropanoid metabolism pathway and plant height.

Molecular mechanism of resveratrol combined with irinotecan in treatment of colorectal cancer / 中国中药杂志

This study aimed to investigate the mechanism of resveratrol(RES) combined with irinotecan(IRI) in the treatment of colorectal cancer(CRC). The targets of RES, IRI, and CRC were obtained from databases, and the targets of RES combined with IRI in the treatment of CRC were acquired by Venn diagram. The protein functional cluster analysis, GO and KEGG enrichment analyses were performed. In addition, the protein-protein interaction(PPI) network was constructed. The core target genes were screened out and the target-signaling pathway network was set up. IGEMDOCK was used to dock the core target gene molecules. Besides, the relationship between the expression level of key target genes and the prognosis and immune infiltration of CRC was analyzed. Based on the in vitro cell experiment, the molecular mechanism of RES combined with IRI in the treatment of CRC was explored and analyzed. According to the results, 63 potential targets of RES combined with IRI were obtained for CRC treatment. Furthermore, cluster analysis revealed that protein functions included 23% transmembrane signal receptors, 22% protein modifying enzymes, and 14% metabolite converting enzymes. GO analysis indicated that BPs were mainly concentrated in protein autophosphorylation, CCs in receptor complex and plasma membrane, and MFs in transmembrane receptor protein tyrosine kinase activity. Moreover, KEGG signaling pathways were mainly enriched in central carbon metabolism in cancer. The key targets of RES combined with IRI in the treatment of CRC were PIK3CA, EGFR, and IGF1R, all of which were significantly positively correlated with the immune infiltration of CRC. As shown by the molecular docking results, PIK3CA had the most stable binding with RES and IRI. Compared with the results in the control group, the proliferation ability and EGFR protein expression of CRC cells in the RES-treated group, the IRI-treated group, and the RES+IRI treated group significantly decreased. Moreover, the cell proliferation ability and EGFR protein expression level of CRC cells in the RES+IRI treated group were remarkably lower than those in the IRI-treated group. In conclusion, PIK3CA, EGFR, and IGF1R are the key targets of RES combined with IRI in CRC treatment. In addition, RES can inhibit the proliferation of CRC cells and improve IRI chemoresistance by downregulating the EGFR signaling pathway.

Hydroxysafflor yellow A inhibits proliferation, migration, and chemoresistance of colorectal cancer cells through Akt/mTOR-autophagy pathway / 中国中药杂志

In recent years, the clinical treatment of colorectal cancer(CRC) has made great progress, but chemoresistance is still one of the main reasons for reducing the survival rate of patients with colorectal cancer. Therefore, ameliorating chemotherapy resis-tance is an urgent problem to be solved. The purpose of this study was to investigate the regulatory role and related molecular mechanisms of hydroxysafflor yellow A(HSYA) in colorectal cancer cell proliferation, migration, and 5-fluorouracil(5-FU) chemoresistance. In this study, HCT116 and HT-29 cells were used as research subjects. Firstly, methyl thiazolyl tetrazolium(MTT) assay and colony formation assay were used to detect and analyze the effect of HSYA on the proliferation of CRC cells. Secondly, the effect of HSYA on the cell cycle in CRC cells was analyzed by cell cycle assay. Furthermore, the effect of HSYA on the migration of CRC cells was analyzed by wound-healing assay and Transwell assay. Based on the above, the influences of HSYA on 5-FU chemoresistance of CRC cells and related molecular mechanisms were explored and analyzed. The results showed that HSYA significantly inhibited the proliferation and migration of CRC cells, and arrested the cell cycle in G_0/G_1 phase. In addition, HSYA significantly ameliorated the chemoresistance of CRC cells to 5-FU. The results of acridine orange staining and Western blot showed that the autophagy activity of CRC cells in the HSYA and 5-FU combined treatment group was significantly higher than that in the 5-FU single drug treatment group. As compared with the 5-FU single drug treatment group, the phosphorylation levels of protein kinase B(Akt) and mammalian target of rapamycin(mTOR) in the HSYA and 5-FU combined treatment group were significantly reduced, indicating that the Akt/mTOR signaling pathway in the combined treatment group was down-regulated in CRC cells. In conclusion, HSYA may upregulate autophagy activity through the Akt/mTOR signaling pathway, thereby inhibiting the proliferation and migration of CRC cells and ameliorating the chemoresistance to 5-FU.

Molecular Diversity and Evolutionary Relatedness of Paulownia Witches'-Broom Phytoplasma in Different Geographical Distributions in China.

To reveal the distribution and transmission pathway of Paulownia witches'-broom (PaWB) disease, which is caused by phytoplasmas related to genetic variation, and the adaptability to the hosts and environments of the pathogenic population in different geographical regions in China, in this study, we used ten housekeeping gene fragments, including rp, fusA, secY, tuf, secA, dnaK, rpoB, pyrG, gyrB, and ipt, for multilocus sequence typing (MLST). A total of 142 PaWB phytoplasma strains were collected from 18 provinces or municipalities. The results showed that the genetic diversity was comparatively higher among the PaWB phytoplasma strains, and substantially different from that of the other 16SrI subgroup strains. The number of gene variation sites for different housekeeping genes in the PaWB phytoplasma strains ranged from 1 to 14 SNPs. Among them, rpoB (1.47%) and dnaK (1.12%) had higher genetic variation, and rp (0.20%) had the least genetic variation. The tuf and rpoB genes showed the fixation of positively selected beneficial mutations in the PaWB phytoplasma populations, and all housekeeping genes except tuf followed the neutral evolutionary model. We found an absence of recombination among PaWB phytoplasma sequence types (STs) for each housekeeping gene except dnaK, and no evidence for such recombination events for concatenated sequences of PaWB phytoplasma strains. The 22 sequence types were identified among the concatenated sequences of seven housekeeping genes (rp, fusA, secY, secA, tuf, dnaK, and rpoB) from 105 representative strains. We analyzed all 22 STs by goeBURST algorithm, forming two clonal complexes (CCs) and three singletons. Among them, ST1, as the primary founder of CC1, had the widest geographical distribution, accounting for 72.38% of all strains, with a high frequency of shared sequence type. The results of phylogenetic analysis of the concatenated sequences further revealed that the 105 strains were clustered into two representative lineages of PaWB phytoplasma, with obvious geographical differentiation. The ST1 strains of highly homogeneous lineage-1 were a widespread and predominant population in diseased areas. Lineage-2 contained strains from Jiangxi, Fujian, and Shaanxi provinces, highlighting the close genetic relatedness of the strains in these regions, which was also consistent with the results of most single-gene phylogenetic analysis of each gene. We also found that the variability in the northwest China population was higher than in other geographical populations; the range of genetic differentiation between the south of the Yangtze River population and the Huang-huai-hai Plain (or southwest China) population was relatively large. The achieved diversity and evolution data, as well as the MLST technique, are helpful for epidemiological studies and guiding PaWB disease control decisions.

Prim-O-glucosycimifugin attenuates liver injury in septic mice by inhibiting NLRP3 inflammasome/caspase-1 signaling cascades in macrophages.

BACKGROUND: Liver dysfunction and liver failure are serious complications of sepsis, directly leading to septic progression and death. Now, there is no specific therapeutics available for sepsis-related liver dysfunction. Prim-O-glucosylcimifugin (POG), a chromone richest in the roots of Saposhnikovia divaricata (Turcz.) Schischk, is usually used to treat headache, rheumatoid arthritis and tetanus. While, the underlying mechanisms of POG against sepsis-induced liver damage and dysfunction are still not clear. PURPOSE: To study the anti-sepsis effect of POG, and its pharmacological mechanism to protect liver injury by weakening the function of macrophages in septic livers through inhibiting NOD-like receptor protein 3 (NLRP3) inflammasome pathway. METHOD: In vivo experiments, septic mouse model was induced by cecal ligation and puncture (CLP), and then the mortality was detected, liver inflammatory damages and plasma biomarkers of liver injury were evaluated by histopathological staining and biochemical assays, respectively. In vitro experiments, mouse primary peritoneal macrophages were treated with lipopolysaccharide (LPS) and ATP, and then the activated-inflammasomes, macrophage migration and polarization were detected by ASC immunofluorescence staining, transwell and flow cytometry assays, respectively. NLRP3 inflammasome components NLRP3, caspase-1, IL-1ß and IL-18 protein expressions were detected using western blot assays, and the contents of IL-1ß and IL-18 were measured by ELISA assays. RESULTS: POG treatment significantly decreased the mortality, liver inflammatory damages, hepatocyte apoptosis and plasma biomarkers of liver injury in CLP-challenged male WT mice, which were comparable to those in ibuprofen (a putative anti-inflammatory drug)-supplemented septic male WT mice and septic NLRP3 deficient-male mice. POG supplementation significantly suppressed NLRP3 inflammasome activation in septic liver tissues and cultured macrophages, by significantly reducing NLRP3, cleaved-caspase-1, IL-1ß and IL-18 levels, the activated-inflammasome ASC specks, and macrophage infiltration and migration, as well as M1-like polarization, but significantly increasing M2-like polarization. These findings were similar to the pharmacological effects of ibuprofen, NLRP3 deficiency, and a special NLRP3 inhibitor, MCC950. CONCLUSION: POG protected against sepsis by inhibiting NLRP3 inflammasome-mediated macrophage activation in septic liver and attenuating liver inflammatory injury, indicating that it may be a potential anti-sepsis drug candidate.