Integrated metabolomic and transcriptomic analyses provide insights into regulation mechanisms during bulbous stem development in the Chinese medicinal herb plant, Stephania kwangsiensis.

BACKGROUND: Stephania kwangsiensis Lo (Menispermaceae) is a well-known Chinese herbal medicine, and its bulbous stems are used medicinally. The storage stem of S. kwangsiensis originated from the hypocotyls. To date, there are no reports on the growth and development of S. kwangsiensis storage stems. RESULTS: The bulbous stem of S. kwangsiensis, the starch diameter was larger at the stable expanding stage (S3T) than at the unexpanded stage (S1T) or the rapidly expanding stage (S2T) at the three different time points. We used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and Illumina sequencing to identify key genes involved in bulbous stem development. A large number of differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) were identified. Based on the differential expression profiles of the metabolites, alkaloids, lipids, and phenolic acids were the top three differentially expressed classes. Compared with S2T, significant changes in plant signal transduction and isoquinoline alkaloid biosynthesis pathways occurred at both the transcriptional and metabolic levels in S1T. In S2T compared with S3T, several metabolites involved in tyrosine metabolism were decreased. Temporal analysis of S1T to S3T indicated the downregulation of phenylpropanoid biosynthesis, including lignin biosynthesis. The annotation of key pathways showed an up-down trend for genes and metabolites involved in isoquinoline alkaloid biosynthesis, whereas phenylpropanoid biosynthesis was not completely consistent. CONCLUSIONS: Downregulation of the phenylpropanoid biosynthesis pathway may be the result of carbon flow into alkaloid synthesis and storage of lipids and starch during the development of S. kwangsiensis bulbous stems. A decrease in the number of metabolites involved in tyrosine metabolism may also lead to a decrease in the upstream substrates of phenylpropane biosynthesis. Downregulation of lignin synthesis during phenylpropanoid biosynthesis may loosen restrictions on bulbous stem expansion. This study provides the first comprehensive analysis of the metabolome and transcriptome profiles of S. kwangsiensis bulbous stems. These data provide guidance for the cultivation, breeding, and harvesting of S. kwangsiensis.

Establishment of diabetes mellitus model using Bombyx mori silkworms in a low-temperature environment.

Due to the high prevalence of diabetes mellitus, researchers have conducted numerous experimental animal studies. However, the mammalian diabetes model is cumbersome and expensive to operate, while the cheap and simple common silkworm diabetes model has the disadvantage of a short cycle time. Since the growth of silkworms is greatly affected by environmental factors, we extended the five-age cycle of silkworms by lowering the ambient temperature to establish a novel low-temperature silkworm diabetes model. Our goal was to determine whether the low-temperature feeding of a high-sugar diet to silkworms could serve as an effective animal model for diabetes. Also, we aimed to resolve certain issues concerning the normal temperature silkworm diabetes model, such as the short time frame for experiments and erratic fluctuations in blood sugar levels. Silkworms weighing between 0.9 and 1.0 g at the beginning of the fifth instar were selected, and we created diabetic silkworms by feeding mulberry leaves containing 4% glucose daily in a 16-20°C environment. When the silkworms were kept at a cooler temperature, the fifth instar stage lasted for an additional 9-11 days. In the model group, 83.3% of the silkworms had blood glucose levels greater than 7.8 mmol/L, while the total prevalence of diabetic silkworms was 89.8%. Moreover, JNK phosphorylation expression rose in the model group, while PI3K expression fell. Additionally, the JNK and PI3K signaling pathway expressions matched diabetic signals. Therefore, using silkworms to create a diabetes model in a cool environment is a straightforward and cost-effective approach to studying diabetes in animals.

Identification of Characteristic Genes and Immune Cell Infiltration Signatures in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a lung disease caused by limited airflow that leads to difficulty breathing. It is a major chronic disease that affects human quality of life and even endangers life. However, the exact cause of COPD is still unclear. The present study aimed to identify characteristic genes in COPD, assess the level of immune cell infiltration in COPD samples, and explore the association between characteristic genes and infiltrating immune cells. In this paper, we used dataset GSE76925 to identify 452 differentially expressed genes (DEGs) (including 407 downregulated and 45 upregulated DEGs). Gene Ontology (GO) enrichment analysis showed that the functions mainly include leukocyte migration, protein folding, negative regulation of cell activation, transcription regulator complex, collagen-containing extracellular matrix, RNA polymerase II transcription regulator complex, guanyl nucleotide binding, guanyl ribonucleotide binding, ubiquitin protein ligase binding, etc. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, pathways identified by DEGs mainly focused on Basal transcription factors, Arachidonic acid metabolism, Nucleocytoplasmic transport, Glutamatergic synapse, Ether lipid metabolism, alpha-Linolenic acid metabolism, etc. Next, we constructed a weighted gene co-expression network, identified six gene modules, found that the module with the highest correlation was the MEturquoise, and obtained 51 hub module genes. Further, 43 overlapping genes were obtained after the intersection of 452 DEGs and 51 hub genes in MEturquoise module, and seven characteristic DEGs (C-DEGs) (LOC649214, LOC440563, LOC643431, LOC642585, KRT18P17, LOC648057 and UBASH3B) were identified by the Least absolute shrinkage and selection operator (LASSO) regression method. In addition, we assessed the infiltration of 28 immune cells in 111 COPD samples and 40 NC samples, calculated and visualized the correlation between the expression of 7 C-DEGs and the infiltration level of 28 immune cells. These results will contribute to our further understanding of the molecular immunopathogenesis of COPD and have potential reference value for the development of molecular drug targets in the future.

[Effects of propiconazole on physiological and biochemical properties of Panax notoginseng and dietary risk assessment].

To study the residue and dietary risk of propiconazole in Panax notoginseng and the effects on physiological and bioche-mical properties of P. notoginseng, we conducted foliar spraying of propiconazole on P. notoginseng in pot experiments. The physiolo-gical and biochemical properties studied included leaf damage, osmoregulatory substance content, antioxidant enzyme system, non-enzymatic system, and saponin content in the main root. The results showed that at the same application concentration, the residual amount of propiconazole in each part of P. notoginseng increased with the increase in the times of application and decreased with the extension of harvest interval. After one-time application of propiconazole according to the recommended dose(132 g·hm~(-2)) for P. ginseng, the half-life was 11.37-13.67 days. After 1-2 times of application in P. notoginseng, propiconazole had a low risk of dietary intake and safety threat to the population. The propiconazole treatment at the recommended concentration and above significantly increased the malondialdehyde(MDA) content, relative conductivity, and osmoregulatory substances and caused the accumulation of reactive oxygen species in P. notoginseng leaves. The propiconazole treatment at half(66 g·hm~(-2)) of the recommended dose for P. ginseng significantly increased the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) in P. notoginseng leaves. The propiconazole treatment at 132 g·hm~(-2) above inhibited the activities of glutathione reductase(GR) and glutathione S-transferase(GST), thereby reducing glutathione(GSH) content. Proconazole treatment changed the proportion of 5 main saponins in the main root of P. notoginseng. The treatment with 66 g·hm~(-2) propiconazole promoted the accumulation of saponins, while that with 132 g·hm~(-2) and above propiconazole significantly inhibited the accumulation of saponins. In summary, using propiconazole at 132 g·hm~(-2) to prevent and treat P. notoginseng diseases will cause stress on P. notoginseng, while propiconazole treatment at 66 g·hm~(-2) will not cause stress on P. notoginseng but promote the accumulation of saponins. The effect of propiconazole on P. notoginseng diseases remains to be studied.

Rapid determination and dietary intake risk assessment of 249 pesticide residues in Panax notoginseng.

UPLC-MS/MS and GC-MS/MS were used to establish a method to simultaneously determine various pesticide residues in Panax notoginseng. Results showed that the limits of detection of 249 pesticides were all 5-10 µg/kg. The detection rate of pesticides in 121 P. notoginseng samples was 93.39%, and 19 pesticides were detected. According to the US Code of Federal Regulations, the Chinese Pharmacopoeia recommended algorithm, and the Japanese "positive list system", the pass rates of pesticide residues were 100%, 99.17%, and 89.26%, respectively. The chronic risk quotient (ADI%) and acute risk quotient (ARfD%) of P. notoginseng were 0.00-0.12% and 0.00-0.15%, respectively. In summary, the detection method established in this study can be used for routine analysis of various P. notoginseng pesticide residues. The pesticide residues in the main root samples of P. notoginseng were at a safe level and unlikely pose health risks to consumers.

Specific immunity proteomic profile of the skin mucus of Antarctic fish Chionodraco hamatus and Notothenia coriiceps.

The white-blooded Antarctic icefish is the only known vertebrate lacking oxygen-transporting haemoglobins. Fish skin mucus, as the first line of defence against pathogens, can reflect fish welfare. In this study, we analysed the skin mucus proteome profiles of the two Antarctic fish species, the white-blooded Antarctic icefish, Chionodraco hamatus, and the red-blooded Antarctic fish, Notothenia coriiceps, unfolding the different proteins by liquid chromatography coupled with tandem mass spectrometry isobaric tags for relative and absolute quantitation (iTRAQ) technology. Of the 4444 totally identified proteins, 227 differentially expressed proteins (DEPs) were found in the comparison between C. hamatus and N. coriiceps, of which 121 were upregulated and 106 were downregulated in the icefish. In the Kyoto Encyclopedia of Genes and Genomes pathway annotation, we found two pathways "Legionellosis" and "Complement and coagulation cascades" were significantly enriched, among of which innate immune candidate proteins such as C3, CASP1, ASC, F3 and C9 were significantly upregulated, suggesting their important roles in C. hamatus immune system. Additionally, the DEP protein-protein interaction network analysis and "Response to stress" GO category provided candidate biomarkers for deep understanding of the distinct immune response of the two Antarctic fish underlying the cold adaptation.

Mechanistic Insight into the Chemiluminescent Decomposition of Cypridina Dioxetanone and the Chemiluminescent, Fluorescent Properties of the Light Emitter of Cypridina Bioluminescence.

Cypridina bioluminescence has been increasingly used in bioimaging, bioanalysis, and biomedicine, due to high quantum yield and high signal-to-noise ratio. However, there is still no consensus regarding different aspects of the chemiluminescent mechanism of this system, which impairs the development of new applications. Herein, we have used a theoretical DFT and TD-DFT approach to (i) determine the identity of the dioxetanone species responsible for efficient chemiexcitation and (ii) identify the bioluminescent emitter and determine if light-emission occurs from the fluorescent or chemiluminescent state. Our results demonstrate that upon oxygenation of the imidazopyrazinone scaffold, a dioxetanone with a neutral amide group and a cationic guanidinopropyl group is formed. This species is efficiently chemiexcited (with no obvious charge transfer step) to the corresponding oxyluciferin with a neutral amide and cationic guanidinopropyl groups. After the "dark" chemiluminescent state, this oxyluciferin species is converted into a bright blue-emitting fluorescent state.

A Computational Investigation of the Equilibrium Constants for the Fluorescent and Chemiluminescent States of Coelenteramide.

In spite of recent advances in understanding the mechanism of coelenterate bioluminescence, there is no consensus about which coelenteramide specie and/or state are the light emitter. In this study, a systematic investigation of the geometries and spectra of all possible light emitters has been performed at the TD ωB97XD/6-31+G(d) level of theory, including various fluorescent and chemiluminescent states in vacuum, in a hydrophobic environment and in aqueous solution. To deduce the most probable form of the fluorescent and chemiluminescent coelenteramide emitter, the equilibrium constants for the fluorescent and chemiluminescent states connecting the various species have been calculated. ωB97XD gives a qualitatively good description of fluorescent and chemiluminescent structures. Coelenteramide is formed in a "dark" chemiluminescent state and must evolve to a bright fluorescent state. Moreover, the photoacidity of the phenol group is significantly higher in the fluorescent state than in the chemiluminescent state, which allows the formation of phenolate coelenteramide and clarifies its role as the bioluminescent emitter.

Analgesic effect of flurbiprofen axetil in treatment of single hole thoracoscopic surgery for pneumothorax.

The stress response induced by surgery and anesthesia can inhibit the immune function of the body. Studies have shown that pain can inhibit the proliferation of T cells and weaken the activity of NK cells, resulting in immunosuppression. In this study, flurbiprofen axetil was used for drug intervention. The results showed that flurbiprofen can make the serum TNF- and IL-6 levels significantly reduce, illustrate the application of flurbiprofen axetil can promote the inflammatory balance, inhibit excessive stress reaction, thus contributing to the clinical curative effect and postoperative recovery of patients. The authors have also analyzed treatment of primary spontaneous pneumothorax by using single port thoracoscopy. Based on the analysis of the effect of single hole thoracoscopic surgery, it shows that the average time of single hole thoracoscopic surgery group (49±12.34) min, intraoperative blood loss (32.5±7.32) ml, there was no significant difference between the two groups. The result proved that the technique of single hole thoracoscopic surgery can reduce the injury of the chest wall and the hemostasis time, and reduce the incision scar.

[Change of Volume and Mechanical Properties of Femoral Bone in Rabbits at Different Ages with Knee Osteoarthritis under Sand-therapy].

The present paper is aimed to study the effect of sand-therapy with Uyghur medicine on biomechanical properties and femoral bone volume of the femur of osteoarthritis (OA) rabbits at two different ages. In the experiments, we injected Papain through the joint space of right knees into the bodies of New Zealand rabbits (16 in the growing group, and 16 in the mature group), and established an OA model. The 16 rabbits in the mature group were divided randomly into 2 sub-groups: 8 in control group (no sand therapy), and 8 sand-therapy group. The 16 rabbits in the growing group were divided randomly into 2 groups as well: 8 in the control group (no sand therapy), and 8 in the sand-therapy group. We carried out CT scanning four times (1 day before, 13th, 27th and 41st days after the establishment of the model, respectively). After importing the CT data to MIMICS, the different volumes of each sclerotin were recorded and change of the percentage of each sclerotins in total femur bone volume were analyzed. Finally the rabbit femurs were given three-point bending test, the elastic load and the elastic deflection were obtained and the inertia of the section, the maximum bending stresses, the bending modulus of elasticity and the structural rigidity were calculated. The experimental results showed that (1) Compared with 1 day before and 13th day after establishment of model at maturity, the cancellous bone volume increased and cortical bone volume decreased (P < 0.05), but compared with those in the control group, the cancellous bone volume of femurs decrease and cortical bone volume increased under sand-therapy (P < 0.05). Compared with those in the control group, there were no significant changes in the deflection and cross-sectional moment of inertia in the sand-therapy group (P > 0.05), but the maximum bending normal stress, maximum load, elastic modulus, and structural stiffness (P < 0.05) in the sand therapy group were larger than those in the control group. The study showed that sand-therapy in Uyghur medicine has benign effect on bone volume of the OA rabbit femur in two ages and the mechanical properties of the OA rabbit femur at the two ages induced by sand-therapy in Uyghur medicine have been improved.

Role of ERCC1 variants in response to chemotherapy and clinical outcome of advanced non-small cell lung cancer.

Excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum-F (XPF) in the nucleotide excision repair pathway have been effectively repairing DNA damage induced by chemotherapeutic agents. We conducted a cohort study to assess the associations of ERCC1 and XPF polymorphisms with response to platinum-based chemotherapy and clinical outcome of non-small-cell lung cancer (NSCLC). One hundred eighty-seven NSCLC cases treated with platinum-based chemotherapy were prospectively analyzed. The predictive value of four SNPs in ERCC1 and two SNPs in XPF in patient's response and survival related to platinum-based chemotherapy were analyzed using χ(2) tests, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. The overall chemotherapy response rate for treatment was 51.18%. One hundred eighty-seven patients were followed up, and the median survival time is 17.6 months (ranged from 1 to 50 months). A total of 106 patients (56.68%) died from NSCLC during the follow-up period. Carriers of the rs3212986 AA and A allele had a borderline significantly lower response rate to the chemotherapy. In the Cox proportional hazards model, patients carrying the ERCC1 rs3212986 AA genotype were significantly associated with increased risk of death from NSCLC when compared with those with CC genotype as a reference variable. This study reported that variants in ERCC1 can be used as a prognostic maker to platinum-based chemotherapy in NSCLC patients.

Macrocyclic amine-linked oligocarbazole hollow microspheres: facile synthesis and efficient lead sorbents.

Novel macrocyclic amine-linked oligocarbazole hollow microspheres are synthesized via a one-step oxidative method in aqueous solution. Upon altering the oxidants and acidic media, the average diameters of the obtained hollow microspheres are tunable from 0.23 to 2.0 µm. With attractive amine and carbazole functionalities, exposed surface area, thermostability, and photoluminescent properties, the amine-linked oligocarbazole hollow microspheres are directly assembled to yield heavy metal sorbents with excellent selectivity and recyclability, shown to efficiently remove lead from contaminated water.

The cGAS-STING pathway in cardiovascular diseases: from basic research to clinical perspectives.

The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component of the innate immune system, is involved in the development of several diseases. Ectopic DNA-induced inflammatory responses are involved in several pathological processes. Repeated damage to tissues and metabolic organelles releases a large number of damage-associated molecular patterns (mitochondrial DNA, nuclear DNA, and exogenous DNA). The DNA fragments released into the cytoplasm are sensed by the sensor cGAS to initiate immune responses through the bridging protein STING. Many recent studies have revealed a regulatory role of the cGAS-STING signaling pathway in cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, and aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting the cGAS-STING signaling pathway can significantly inhibit myocardial hypertrophy and inflammatory cell infiltration. Therefore, this review is intended to identify risk factors for activating the cGAS-STING pathway to reduce risks and to simultaneously further elucidate the biological function of this pathway in the cardiovascular field, as well as its potential as a therapeutic target.

Poly(1-amino-5-chloroanthraquinone): highly selective and ultrasensitive fluorescent chemosensor for ferric ion.

Poly(1-amino-5-chloroanthraquinone) (PACA) was firstly synthesized by a chemically oxidative interfacial polymerization. The PACA has been developed as a fluorescent sensor for the determination of Fe(III) in semi-aqueous solution at pH 7.0. The sensor exhibited remarkably high sensitivity toward Fe(3+) since the fluorescence of the polymer could be significantly quenched even though trace Fe(3+) was added. The sensor showed a linear fluorescence emission response over a wide concentration range from 1.0 × 10(-10) to 1.0 × 10(-4) M, with an ultra-low detection limit of 2.0 × 10(-11) M. The quenching of the fluorescence was found to be static one due to the formation of non-fluorescent complex in the ground state.

Prognostic value of baseline C-reactive protein in diffuse large B-cell lymphoma: a systematic review and meta-analysis.

Background: C-reactive protein (CRP) is an inflammatory marker of great significance for progression and prognosis of diffuse large B-cell lymphoma (DLBCL). However, previous studies reported the inconsistent findings of the relationship between CRP levels and survival in DLBCL patients. This meta-analysis was performed to investigate the predictive value of baseline CRP in the prognosis of DLBCL. Methods: Relevant studies on baseline CRP and prognosis of DLBCL were searched from PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and other databases. The search time was from establishment of the database to December 2022. The studies that reported the baseline CRP level, DLBCL confirmed by pathology, data on the relationship between CRP and overall survival (OS) or progression-free survival (PFS), and published in English or Chinese were included in this meta-analysis. No evidence showed the risk of bias of the included studies. Random-effects meta-analysis were conducted to calculate hazard ratio (HR). Stata15.0 software was used for the meta-analysis. Results: A total of 11 studies with 2,314 patients were included. All included studies were of high quality. The result of prognosis in patients with CRP and DLBCL was HR =2.48 [95% confidence interval (CI): 1.52 to 4.07]. The subgroup analysis showed that the risk of death was higher in both groups (HR =2.58, 95% CI: 2.10 to 3.18, random effects model I2=39.7%). There was a significant difference between group 1 and group 2 (P=0.000). Conclusions: Current evidence suggests that baseline CRP is a potential predictor of DLBCL patients and has potential prognostic value in clinical practice, improving the survival rate and quality of life of DLBCL patients. Additionally, OS appears to be strongly influenced by potential country specific differences, which may be related to racial differences and specific lifestyles.

IQGAP1 promotes mitochondrial damage and activation of the mtDNA sensor cGAS-STING pathway to induce endothelial cell pyroptosis leading to atherosclerosis.

Atherosclerosis (AS) is the most common cardiovascular disease and has limited therapeutic options. IQ motif-containing GTPase-activating protein 1 (IQGAP1) is an important scaffolding protein regulating mitochondrial function influencing endothelial cell activity. Evidence suggests that mitochondrial damage can lead to leakage of mtDNA into the cytoplasm to activate the DNA sensor cGAS-STING to mediate pyroptosis. However, whether IQGAP1 induces NLRP3-mediated endothelial cell pyroptosis by regulating mitochondrial function and activating the DNA sensor cGAS-STING, and its underlying mechanisms remain unclear. In vivo, ApoE-/- C57BL/J and Ldlr-/- C57BL/J mice were pre-injected with adeno-associated virus (AAV) by the tail vein to specifically silence IQGAP1 expression and were fed a high-fat diet (HFD) for 12 weeks. IQGAP1 knockdown reduced mtDNA release and decreased the expression of DNA receptors and pyroptosis-related molecules as determined by immunohistochemistry and immunofluorescence. In vitro, palmitic acid (0.3 mmol/L) was incubated with human umbilical vein endothelial cells (HUVECs) for 24 h. Overexpression of IQGAP1 in HUVECs, flow cytometry, and mitochondrial superoxide staining revealed increased levels of ROS. Moreover, the mitochondrial tracker with dsDNA co-localization showed the release of mtDNA into the cytoplasm increased, which activated the DNA receptor cGAS-STING. Protein blotting and TUNEL staining revealed that IQGAP1 promoted NLRP3-mediated pyroptosis. Furthermore, cGAS or STING small-molecule inhibitors RU.521 or C-176 reverse IQGAP1-promoted HUVECs from undergoing NLRP3-mediated pyroptosis. These results suggest that IQGAP1 promotes oxidative stress and mtDNA release, activates the DNA sensor cGAS-STING, and leads to NLRP3-mediated pyroptosis. The present study provides new insights into the mechanisms underlying AS and identifies new pharmacological targets for treatment.

Application of protein/polysaccharide aerogels in drug delivery system: A review.

Drug delivery systems have emerged as a prominent research focus in the field of drug development, offering enhanced stability and improved bioavailability. Among them, protein (silk, gelatin and whey) or polysaccharide (alginate, chitosan, cellulose, starch, pectin and carrageenan) aerogels derived from natural sources have gained increasing popularity due to their unique advantages, such as cost-effectiveness, flexible preparation, bioactivity, biocompatibility, and biodegradability. However, despite their growing significance, there remains a lack of comprehensive information and ongoing confusion regarding the application of protein/polysaccharide aerogels in drug delivery system. Hence, the objective of this review was to provide a comprehensive review of the research progress in protein/polysaccharide aerogels for drug delivery systems from the perspective of aerogels category, synthesis strategy, drug-loading method, performance characteristic and release mechanism. Furthermore, by consolidating the existing information, we aimed to present our own perspectives and insights on the future development of protein/polysaccharide aerogels in drug delivery system. In conclusion, this comprehensive review served as a valuable resource for researchers and scholars, addressing the current gaps in knowledge and clarifying the complex landscape of protein/polysaccharide aerogels in drug delivery system.

[Retracted] Study of miR-143 expression in stomach cancer.

[This retracts the article DOI: 10.3892/ol.2018.9173.].

The Surgical Strategy for Progressive Dilatation of Aortic Root and Aortic Regurgitation After Repaired Tetralogy of Fallot: A Case Report.

It has been found that postoperative progressive dilatation of aortic root is not rare for adult patients with repaired Tetralogy of Fallot (TOF), which leads to severe aortic regurgitation or even fatal dissection. Therefore, clinically, surgical treatment for both regurgitated aortic valve and dilated root is needed based on preoperative assessments and individual treatment strategies.