Amino acid application inhibits root-to-shoot cadmium translocation in Chinese cabbage by modulating pectin methyl-esterification.

The exogenous application of amino acids (AAs) generally alleviates cadmium (Cd) toxicity in plants by altering their subcellular distribution. However, the physiological mechanisms underlying AA-mediated cell wall (CW) sequestration of Cd in Chinese cabbage remain unclear. Using two genotypes of Chinses cabbage, Jingcui 60 (Cd-tolerant) and 16-7 (Cd-sensitive), we characterized the root structure, subcellular distribution of Cd, CW component, and related gene expression under the Cd stress. Cysteine (Cys) supplementation led to a reduction in the Cd concentration in the shoots of Jingcui 60 and 16-7 by 65.09 % and 64.03 %, respectively. Addition of Cys alleviated leaf chlorosis in both cultivars by increasing Cd chelation in the root CW and reducing its distribution in the cytoplasm and organelles. We further demonstrated that Cys supplementation mediated the downregulation of PMEI1 expression and improving the activity of pectin methyl-esterase (PME) by 17.98 % and 25.52 % in both cultivars, respectively, compared to the Cd treatment, resulting in an approximate 12.00 %-14.70 % increase in Cd retention in pectin. In contrast, threonine (Thr) application did not significantly alter Cd distribution in the shoots of either cultivar. Taken together, our results suggest that Cys application reduces Cd root-to-shoot translocation by increasing Cd sequestration in the root CW through the downregulation of pectin methyl-esterification.

Comparison of Direct Pars Repair Techniques for Spondylolysis in Young Patients: Pedicle Screw Hook System versus Pedicle Screw Rod.

Background: Lumbar spondylolysis (LS) poses a potential threat, and there is a need to evaluate and compare the effectiveness of direct pars repair techniques. Objective: To assess and compare the clinical and radiographic outcomes of direct pars repair techniques using the pedicle screw hook system (PSHS) and the pedicle screw rod system (PSRS) in young symptomatic patients with lumbar spondylolysis. Methods: A retrospective study was conducted to compare clinical and radiological data in young symptomatic LS patients after surgery. Records of 45 post-surgery LS patients with a minimum 24-month follow-up (January 2014 to June 2019) were reviewed. A total of 26 patients underwent PSHS, and 19 had PSRS. Treatment outcomes were analyzed using the visual analog pain scale (VAS), Oswestry disability index (ODI), MacNab criteria, lumbar fusion status, and Pfirrmann grading standards. Patient baseline characteristics were also compared between the two groups. Results: No disc degeneration was observed in either PSHS or PSRS groups at 24 months postoperatively, according to the Pfirrmann grading scale. The PSRS group outperformed the PSHS group in operative time, intraoperative blood loss, postoperative drainage, length of hospital stays, ODI, VAS values at 3 months postoperatively, and fusion status at 6 months postoperatively. No notable differences were observed in other parameters during the 24-month follow-up period, and no significant surgical complications were recorded. Conclusions: Direct pars repair techniques using PSHS and PSRS yielded satisfactory clinical and radiographic results in young patients with symptomatic LS. PSRS, compared to PSHS, demonstrated greater effectiveness in young individuals with LS and promoted early recovery.

Co-delivery of indomethacin and uricase as a new strategy for inflammatory diseases associated with high uric acid.

Uric acid is the final metabolite in humans. High level of uric acid chronically induces urate deposition, aggravates kidney damage, and concomitantly causes an increase in inflammatory factors. Alleviating acute inflammation and decreasing uric acid levels are the key points in the treatment of inflammatory diseases associated with high uric acid. However, a drug delivery system that combines anti-inflammatory and uric acid reduction functions at the same time remains a challenge to be settled. Here, we designed a nanocrystal-based co-delivery platform, IND Nplex, characterized by loading of indomethacin (IND) and uricase. Compared with free IND or uricase, IND Nplex possessed a better anti-inflammatory effect by restraining the release of inflammation-related factors in vitro. In addition, pharmacokinetic and biodistribution studies revealed that IND Nplex significantly prolonged the retention time in vivo and was more concentrated in the kidney. In acute gouty arthritis model rats, IND Nplex markedly relieved ankle joint swelling and mitigated synovial inflammation. In acute kidney injury model rats, IND Nplex indicated better biocompatibility and significant amelioration of renal fibrosis. Moreover, IND Nplex showed the effect of anti-inflammatory and improved renal function via determination of inflammatory factors and biochemical markers in the serum and kidney. In conclusion, these results indicate that IND Nplex exerts anti-inflammatory activity and uric acid-lowering effect and could become a promising candidate for the treatment of uric acid-related diseases. In this study, a stable neutral co-delivery platform (IND Nplex) was fabricated by using a co-delivery strategy, allowing for a combination of the anti-inflammation drug IND and the metabolic enzyme uricase. IND Nplex showed a good therapeutic effect on rats with acute gouty arthritis or acute kidney injury due to the dual effects of anti-inflammatory and uric acid lowering. This platform provided a novel strategy for high uric acid-related illnesses.

Effect of shaking manners on floral aroma quality and identification of key floral-aroma-active compounds in Hunan black tea.

Shaking is a key process effecting the floral aroma of Hunan black tea (HBT). In this study, the aroma composition of HBTs shaken in the early withering stage (ES1, ES1 + LS1, and ES2), shaken in the late withering stage (LS1), and not shaken (NS), and the identification of main floral aroma compounds were analyzed using sensory evaluation combined with gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), and aroma recombination experiments. Sensory evaluation results showed that the floral aroma of HBT shaken in the early withering stage was with high intensity, whereas HBT shaken in the late withering stage had low-intensity floral aroma. GC-MS identified a total number of 81 differential volatile compounds in HBT, including 30 esters, 18 aldehydes, 15 alcohols, 12 terpenes, 4 ketones, and 2 nitrogen-containing compounds. Further screening of important floral aroma differential compounds was performed using sensory-guided, odor activity value (OAV), and GC-O analysis, which identified three critical floral aroma differential compounds. Eventually, absolute quantification analysis and aroma recombination experiments confirmed that indole and methyl jasmonate were the most critical compounds of HBT determining floral aroma intensity. The findings of this study provide valuable guidance for the production of HBT with rich floral aroma attributes.

Exogenous IL-25 ameliorates airway neutrophilia via suppressing macrophage M1 polarization and the expression of IL-12 and IL-23 in asthma.

BACKGROUND: Severe asthma is associated with substantial mortality and has unmet therapeutic need. A subset of severe asthma is characterized by neutrophilic airway inflammation. Classically activated (or M1) macrophages which express IL-12 and IL-23 are associated with airway neutrophilia in asthma. Exogenous IL-25 was reported to suppress intestinal inflammation in animal models of inflammatory bowel diseases via suppressing IL-12 and IL-23 production. We hypothesize that IL-25 ameliorates airway neutrophilia via inhibiting macrophage M1 polarization and the expression of IL-12 and IL-23 in asthma. METHODS: In a mouse model of neutrophil-dominant allergic airway inflammation, the effect of mouse recombinant IL-25 on airway inflammation were assessed by H&E staining and bronchoalveolar lavage (BAL) cell counting. The percentage of M1 macrophages in lung tissue and BAL cells were analyzed by flow cytometry. Quantitative PCR and immunostaining were performed to measure the expression of Il12, Il23, and inflammatory cytokines. Mechanistic experiments were performed in primary culture of macrophages from mouse lungs. The expression of IL-12, IL-23 and IL-25 in sputum was analyzed in a cohort of severe asthma and subjects with eosinophilic or non-eosinophilic asthma. RESULTS: Intranasal administration of IL-25 markedly decreased the number of neutrophils in BAL cells in a murine model of neutrophil-dominant allergic airway inflammation. Moreover, exogenous IL-25 decreased the number of M1 macrophages, and reduced the expression of IL-12, IL-23 in the lungs of the mouse model. Exogenous IL-25 also inhibited the expression of inflammatory cytokines IL-1ß, IFN-γ, TNF-α and IL-17 A. In vitro, IL-25 suppressed IL-12 and IL-23 expression in lipopolysaccharide (LPS)-stimulated primary culture of mouse pulmonary macrophages. Mechanistically, IL-25 inhibited LPS-induced c-Rel translocation to nucleus via STAT3-dependent signaling. In a cohort of severe asthma, IL-25 protein levels in sputum were significantly lower than control subjects. The transcript levels of IL-12 and IL-23 were increased whereas IL-25 transcripts were decreased in sputum cells from subjects with non-eosinophilic asthma compared to eosinophilic asthma. CONCLUSIONS: IL-25 expression is downregulated in subjects with severe or non-eosinophilic asthma. Exogenous IL-25 ameliorates airway neutrophilia, at least in part, via inhibiting macrophage M1 polarization and the expression of IL-12 and IL-23.

Investigating the antidepressant effect of Ziyan green tea on chronic unpredictable mild stress mice through fecal metabolomics.

Introduction: Some studies have shown the effectiveness of tea in reducing depression. Gut flora dysfunction is strongly associated with depression. The mechanism by which Ziyan green tea ameliorates depression is not clear. Methods: In this study, we examined the impact of Ziyan green tea on mice exhibiting symptoms similar to depression. We specifically focused on the role of intestinal flora and its metabolites. We first established a chronic unpredictable mild stress (CUMS) mouse model to induce depressive symptoms and conducted behavioural tests, biochemical tests, and pathological tissue analysis. We also investigated gut microbiota changes by 16S rRNA sequencing and measured faecal metabolites in mice using UHPLC-MS/MS. Results: The results showed that Ziyan green tea intervention improved depression-like behaviour, neurobiochemical factors, and reduced levels of pro-inflammatory factors in CUMS mice. Spearman's correlation analysis showed that different microbial communities (Corynebacterium, Faecalibaculum, Enterorhabdus, Desulfovibrio) correlation with differential metabolites (Cholic acid, Deoxycholic acid, etc.) and depression-related biochemical indicators (5-HT, DA, BDNF, IL-6, and TNF-α). Discussion: In conclusion, our findings suggest that both low and high-dose interventions of Ziyan green tea have positive preventive effects on CUMS mice without dose dependence, partly because they mainly affect intestinal Purine Metabolism, Bile Acid Biosynthesis and Cysteine Metabolism in CUMS mice, thus stimulating brain 5-HT, DA and BDNF, and decreasing the inflammatory factors IL-6, TNF-α, activate the composition of intestinal flora, improve the intestinal flora environment and thus promote the production of intestinal metabolites, which can be used for depression treatment. It is suggested that Ziyan green tea may achieve an antidepressant effect through the gut-microbiota-brain axis.

Mitigation of soil N2O emissions by decomposed straw based on changes in dissolved organic matter and denitrifying bacteria.

The return of decomposed straw represents a less explored potential option for reducing N2O emissions. However, the mechanisms underlying the effects of decomposed straw return on soil N2O mitigation are still not fully clear. Therefore, we used a helium atmosphere robotized continuous flow incubation system to compare the soil N2O and N2 emissions from four treatments: CK (control: no straw), WS (wheat straw), IWS (wheat straw decomposed with Irpex lacteus), and PWS (wheat straw decomposed with Phanerochaete chrysosporium). All the treatments have been fertilized with the same amount of KNO3. Furthermore, we also analyzed i) the chemodiversity of soil dissolved organic matter (DOM), ii) the nirS, nirK, and nosZ gene copies and relative abundances of denitrifying bacterial communities (DBCs), and iii) the specific linkages between N2O emissions and DOM and DBC. The results showed that the WS, IWS and PWS treatments increased N2O emissions compared to the CK treatment. However, applying decomposed straw to soil, especially straw treated with P. chrysosporium, effectively decreased the soil N2O and increased N2 emissions compared to WS and IWS. Moreover, the IWS and PWS treatments increased the CHO composition, but they decreased the CHON and CHOS compositions of heteroatomic compounds of DOM compared with the WS and CK treatments. Furthermore, the WS, IWS and PWS treatments all significantly increased the nirS and nosZ gene copies compared with the CK treatment. Additionally, compared with the other treatments, the PWS treatment significantly shaped the DBC and led to a higher relative abundance of Pseudomonas with nirS and nosZ genes. Meanwhile, Network analysis showed that the mitigation of N2O was closely related to particular DOM molecules, and specific DBC taxa. These results highlight the potential for decomposed straw amendments to mitigate of soil N2O emissions not only by changing soil DOM but also mediating the soil DBC.

Fuzhuan brick tea ameliorates hepatic steatosis and steatohepatitis through gut microbiota-derived aryl hydrocarbon receptor ligands in high-fat diet-induced obese mice.

High-fat diet (HFD) induced obesity and its associated conditions, such as hepatic steatosis and steatohepatitis, are major health concerns worldwide. Previous studies have reported the excellent efficiency of Fuzhuan brick tea (FBT) in attenuating HFD-induced obesity and metabolic disorders. In this study, we investigated the effects of FBT on hepatic steatosis and simple steatohepatitis in HFD-induced obese mice, as well as the metabolic function of the gut microbiome using metagenomics and metabolomics. The results showed that FBT ameliorated dyslipidemia, hepatic steatosis and steatohepatitis in HFD-induced obese mice by normalizing the gut microbiota structure and tryptophan metabolism. FBT increased the cecal abundance of aryl hydrocarbon receptor (AhR)-ligand producing bacteria such as Lactobacillus_reuteri and Lactobacillus_johnsonii, at the expense of AhR-ligand consuming bacteria, such as Faecalibaculum_rodentium and Escherichia_coli, and elevated the cecal contents of AhR-ligands such as IAA, IPA, and KYNA. Furthermore, FBT regulated the expressions of AhR and its targeted lipometabolic genes such as Pemt, Fasn, and SREBP-1c, as well as other inflammatory genes including TNF-α, IL-6, and IL-1ß in the liver of mice. Overall, these findings highlight the beneficial effects of FBT on obesity-related hepatic steatosis and steatohepatitis via microbiota-derived AhR signaling.

Comprehensive metabolic analyses provide new insights into primary and secondary metabolites in different tissues of Jianghua Kucha tea (Camellia sinensis var. assamica cv. Jianghua).

Background: Jianghua Kucha (JHKC) is a special tea germplasm with enriched specialized secondary metabolites, including theacrine, non-epimeric flavanols and methylated flavanols. Moreover, primary metabolites provide precursors and energy for the production of secondary metabolites. However, the accumulation patterns of primary and secondary metabolites in different tissues of JHKC are unclear. Methods: The changes of primary and secondary metabolites and related metabolic pathways (primary and secondary metabolism) in different JHKC tissues (the bud, 1st-4th leaves, and new stem) were investigated via metabolomics analysis with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Results: Significant differences were observed in 68 primary and 51 secondary metabolites mainly related with the pathways of starch and sucrose, amino acids, caffeine, and flavanols metabolism and TCA cycle. The bud exhibited higher levels of glucose-6-phosphate, citric acid, most amino acids, theobromine, catechin-gallate, epicatechin-gallate, procyanidins, and theasinensins; the 1st leaf showed higher levels of caffeine and epigallocatechin-3-gallate; and the 4th leaf contained higher levels of most monosaccharides, theacrine, and epigallocatechin-3-O-(3"-O-methyl)-gallate. In addition, primary metabolites and important secondary metabolites had certain correlations. Conclusion: This study provides comprehensive insight into primary and secondary metabolites in JHKC and offers guidelines for efficiently utilizing specialized metabolites of JHKC in the future.

Shading-guided Manga Screening from Reference.

Manga screening is a critical process in manga production, which still requires intensive labor and cost. Existing manga screening methods either generate simple dotted screentones only or rely on color information and manual hints during screentone selection. Due to the large domain gap between line drawings and screened manga, and the difficulties in generating high-quality, properly selected and shaded screentones, even state-of-the-art deep learning methods cannot convert line drawings to screened manga well. Besides, ambiguity exists in the screening process since different artists may screen differently for the same line drawing. In this paper, we propose to introduce shaded line drawing as the intermediate counterpart of the screened manga so that the manga screening task can be decomposed into two sub-tasks, generating shading from a line drawing and replacing shading with proper screentones. The reference image is adopted to resolve the ambiguity issue and provides options and controls on the generated screened manga. We proposed a reference-based shading generation network and a reference-based screentone generation module to achieve the two sub-tasks individually. We conduct extensive visual and quantitative experiments to verify the effectiveness of our system. Results and statistics show that our method outperforms existing methods on the manga screening task.

Visible trephine-based foraminoplasty in PTED leads to asymmetrical stress changes and instability in the surgical and adjacent segments: a finite element analysis.

This study aimed to construct a multi-segment lumbar finite element model (FEM) of PTED surgery to analyze the changes in stress and ROM after visible trephine-based foraminoplasty. The CT scans of a 35-year-old healthy male were used to develop a multi-segment lumbar FEM with Mimic, Geomagic Studio, Hypermesh and MSC.Patran. Different foraminoplasty was performed on the model, and these were grouped into normal group (A), the ventral resection group (B), the apex resection group (C), the ventral + apex + isthmus resection group (D), and the SAP + isthmus + lateral recess resection group (E). A vertical load of 500N and a torque of 10N·M were applied to the upper surface of the L3 vertebral body to simulate the biomechanical characteristics under the motion of flexion, extension, lateral bending, and rotation. The von Mises stress maps of the intervertebral f, vertebral body, facet joints, and the ROM of the L3-S1 intervertebral disk were calculated and analyzed. The changes of peak stress on the vertebral body for each group were not significant in the same motion state. Significant stress differences were observed in the L4/5 intervertebral disks, while no obvious stress changes were observed for the L3/4 and L5/S1 intervertebral disks. The stress of the L3/4 and L5/S1 facet joints decreased after L4/5 foraminoplasty, while the stress of L4/5 facet joints displayed an overall increasing trend. Significant asymmetrical stress changes of bilateral facet joints were observed in all three segments, particularly during bilateral rotation movements. The ROM of L3-S1 gradually increased from Group A to Group E, especially during flexion, left lateral bending, and right rotation, with the highest elevation observed for the L45 ROM. Our FEM indicated that enlarged resection and exposure of the articular surface could lead to significant asymmetrical stress changes in the bilateral facet joints and ROM instability of the surgical and adjacent segments. These findings suggested that unnecessary and excessive resection should be avoided in PTED to reduce the incidence of low back pain and the risk of postsurgical degeneration.

Special tea products featuring functional components: Health benefits and processing strategies.

The functional components in tea confer various potential health benefits to humans. To date, several special tea products featuring functional components (STPFCs) have been successfully developed, such as O-methylated catechin-rich tea, γ-aminobutyric acid-rich tea, low-caffeine tea, and selenium-rich tea products. STPFCs have some unique and enhanced health benefits when compared with conventional tea products, which can meet the specific needs and preferences of different groups and have huge market potential. The processing strategies to improve the health benefits of tea products by regulating the functional component content have been an active area of research in food science. The fresh leaves of some specific tea varieties rich in functional components are used as raw materials, and special processing technologies are employed to prepare STPFCs. Huge progress has been achieved in the research and development of these STPFCs. However, the current status of these STPFCs has not yet been systematically reviewed. Here, studies on STPFCs have been comprehensively reviewed with a focus on their potential health benefits and processing strategies. Additionally, other chemical components with the potential to be developed into special teas and the application of tea functional components in the food industry have been discussed. Finally, suggestions on the promises and challenges for the future study of these STPFCs have been provided. This paper might shed light on the current status of the research and development of these STPFCs. Future studies on STPFCs should focus on screening specific tea varieties, identifying new functional components, evaluating health-promoting effects, improving flavor quality, and elucidating the interactions between functional components.

Application of Parameter Optimization Methods Based on Kalman Formula to the Soil-Crop System Model.

Soil-crop system models are effective tools for optimizing water and nitrogen application schemes, saving resources and protecting the environment. To guarantee model prediction accuracy, we must apply parameter optimization methods for model calibration. The performance of two different parameter optimization methods based on the Kalman formula are evaluated for a parameter identification of the soil Water Heat Carbon Nitrogen Simulator (WHCNS) model using mean bias error (ME), root-mean-square error (RMSE) and an index of agreement (IA). One is the iterative local updating ensemble smoother (ILUES), and the other is the DiffeRential Evolution Adaptive Metropolis with Kalman-inspired proposal distribution (DREAMkzs). Our main results are as follows: (1) Both ILUES and DREAMkzs algorithms performed well in model parameter calibration with the RMSE_Maximum a posteriori (RMSE_MAP) values were 0.0255 and 0.0253, respectively; (2) ILUES significantly accelerated the process to the reference values in the artificial case, while outperforming in the calibration of multimodal parameter distribution in the practical case; and (3) the DREAMkzs algorithm considerably accelerated the burn-in process compared with the original algorithm without Kalman-formula-based sampling for parameter optimization of the WHCNS model. In conclusion, ILUES and DREAMkzs can be applied to a parameter identification of the WHCNS model for more accurate prediction results and faster simulation efficiency, contributing to the popularization of the model.

Ortho-silicic Acid Plays a Protective Role in Glucocorticoid-Induced Osteoporosis via the Akt/Bad Signal Pathway In Vitro and In Vivo.

Glucocorticoid-induced osteoporosis (GIOP) has been the most common form of secondary osteoporosis. Glucocorticoids (GCs) can induce osteocyte and osteoblast apoptosis. Plenty of research has verified that silicon intake would positively affect bone. However, the effects of silicon on GIOP are not investigated. In this study, we assessed the impact of ortho-silicic acid (OSA) on Dex-induced apoptosis of osteocytes by cell apoptosis assays. The apoptosis-related genes, cleaved-caspase-3, Bcl-2, and Bax, were detected by western blotting. Then, we evaluated the possible role of OSA on osteogenesis and osteoclastogenesis with Dex using Alizarin red staining and tartrate-resistant acid phosphatase (TRAP) staining. We also detected the related genes by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting. We then established the GIOP mouse model to evaluate the potential role of OSA in vivo. We found that OSA showed no cytotoxic on osteocytes below 50 µM and prevented MLO-Y4 from Dex-induced apoptosis. We also found that OSA promoted osteogenesis and inhibited osteoclastogenesis with Dex. OSA had a protective effect on GIOP mice via the Akt signal pathway in vivo. In the end, we verified the Akt/Bad signal pathway in vitro, which showed the same results. Our finding demonstrated that OSA could protect osteocytes from apoptosis induced by GCs both in vitro and in vivo. Also, it promoted osteogenesis and inhibited osteoclastogenesis with the exitance of Dex. In conclusion, OSA has the potential value as a therapeutic agent for GIOP.

circ-Iqsec1 induces bone marrow-derived mesenchymal stem cell (BMSC) osteogenic differentiation through the miR-187-3p/Satb2 signaling pathway.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) are general progenitor cells of osteoblasts and adipocytes and they are characterized as a fundamental mediator for bone formation. The current research studied the molecular mechanisms underlying circRNA-regulated BMSC osteogenic differentiation. METHODS: Next-generation sequencing (NGS) was employed to study abnormal circRNA and mRNA expression in BMSCs before and after osteogenic differentiation induction. Bioinformatics analysis and luciferase reporting analysis were employed to confirm correlations among miRNA, circRNA, and mRNA. RT-qPCR, ALP staining, and alizarin red staining illustrated the osteogenic differentiation ability of BMSCs. RESULTS: Data showed that circ-Iqsec1 expression increased during BMSC osteogenic differentiation. circ-Iqsec1 downregulation reduced BMSC osteogenic differentiation ability. The present investigation discovered that Satb2 played a role during BMSC osteogenic differentiation. Satb2 downregulation decreased BMSC osteogenic differentiation ability. Bioinformatics and luciferase data showed that miR-187-3p linked circ-Iqsec1 and Satb2. miR-187-3p downregulation or Satb2 overexpression restored the osteogenic differentiation capability of BMSCs post silencing circ-Iqsec1 in in vivo and in vitro experiments. Satb2 upregulation restored osteogenic differentiation capability of BMSCs post miR-187-3p overexpression. CONCLUSION: Taken together, our study found that circ-Iqsec1 induced BMSC osteogenic differentiation through the miR-187-3p/Satb2 signaling pathway.

Study of Compound Sanqi Nanoparticles for Local Infection of Hydrocephalus Patients after Neurosurgery Medium Craniocerebral Injury.

Panax notoginseng is the dried root and rhizome of Panax notoginseng, which has the effect of lowering blood lipid, lowering blood pressure and promoting blood circulation to remove blood stasis. At present, the research on Panax notoginseng is mainly focused on its pharmacological action and its compound preparation, but the research on the granule of Panax notoginseng is less. This paper mainly studied the clinical study of compound notoginseng nanoparticles in the treatment of local infection in patients with hydrocephalus after medium craniocerebral injury in neurosurgery. The purpose of this article is to investigate the effects of compound notoginseng nanoparticles on serum TNF-α, IL-2 and IL-6 in rats with craniocerebral injury and to verify the protective effect of compound notoginseng nanoparticles on the body after craniocerebral injury. In this paper, 90 patients admitted to a hospital in this city were divided into a control group, model group and compound notoginseng nanoparticle group. According to the Zealonga method, the neurological function deficit score of experimental rats in each group was evaluated. The levels of TNF-α, IL-2 and IL-6 in the serum of the three groups were observed 1, 3 and 5 days after treatment. RESULTS: Compared with serum TNF-α, IL-2 and IL-6 of the three groups, there were significant differences in the main effects of time and intervention (P < 0.05). CONCLUSIONS: Compound notoginseng nanoparticles can reduce the contents of TNF-α and IL-6 in serum and increase the expression of IL-2 in rats with craniocerebral injury.

Cadherin-26 Amplifies Airway Epithelial IL-4 Receptor Signaling in Asthma.

Activation of IL-4R (IL-4 receptor) signaling in airway epithelial cells leads to airway hyperresponsiveness and mucus overproduction in asthma. CDH26 (cadherin-26), a cadherin implicated in the polarization of airway epithelial cells, is upregulated in asthma. However, the role of CDH26 in asthma remains unknown. In this study, we demonstrated that Cdh26 deficiency significantly reduced airway mucus overproduction, airway hyperresponsiveness, and airway eosinophilia in a murine model of allergic airway disease. Interestingly, allergen-induced Il-4Rα upregulation in airway epithelium was markedly reduced in Cdh26-/- mice. In cultured human bronchial epithelial cells, CDH26 knockdown inhibited IL-13, a ligand for IL-4R; induced IL-4Rα and IL-13Rα1 (IL-13 receptor α1) upregulation; and suppressed downstream Jak1 (Janus kinase 1) and Stat6 (signal transducer and activator of transcription 6) phosphorylation. Moreover, CDH26 knockdown inhibited IL-13-induced MUC5AC and eosinophilic chemokine expression. These results suggest that CDH26 plays a key role in epithelial IL-4R signaling activation and downstream effectors. In contrast, CDH26 overexpression amplified IL-13-activated IL-4R signaling in BEAS-2B cells. In the airway epithelium of patients with asthma, IL-4Rα expression was elevated, and CDH26 was the only cadherin that was upregulated among 11 cadherin family members. CDH26 expression was strongly correlated with epithelial IL-4Rα and MUC5AC expression, sputum eosinophilia, and fractional exhaled nitric oxide in patients with asthma. Taken together, we identified CDH26 as a key regulator of epithelial IL-4R signaling in asthma and a potential therapeutic target for IL-4R-mediated allergic diseases.

Nontargeted and targeted metabolomics analysis provides novel insight into nonvolatile metabolites in Jianghua Kucha tea germplasm (Camellia sinensis var. Assamica cv. Jianghua).

Jianghua Kucha (JHKC) is a special tea germplasm with high bitterness growing in China; however, the chemical characteristics of JHKC are not completely understood. In this study, 61 differential metabolites were identified between 11 wild JHKC individuals and 3 control cultivars of Fudingdabai, Yunkang 10, and Zhuyeqi using comprehensive nontargeted and targeted metabolomics approach. The JHKC accessions mainly possessed significantly higher levels of purine alkaloids of theacrine (12.06 ± 5.23 mg/g) and 1,3,7-trimethyluric acid, non-epi-form flavanols (catechin, gallocatechin, catechin gallate, and gallocatechin gallate), and methylated flavanols of epigallocatechin-3-O-(3″-O-methyl)-gallate (4.79 ± 1.45 mg/g) and epicatechin-3-O-(3″-O-methyl)-gallate (1.02 ± 0.34 mg/g), as well as significantly lower levels of flavonol glycosides, which indicated that caffeine metabolism, flavonoid biosynthesis, and flavonol and flavone biosynthesis are mostly differential metabolic pathways. Our study demonstrated that JHKC germplasm is a promising resource for breeding novel tea cultivars with high contents of theacrine, non-epi-form flavanols, and methylated flavanols.

Lanthipeptides from the Same Core Sequence: Characterization of a Class II Lanthipeptide Synthetase from Microcystis aeruginosa NIES-88.

Class II lanthipeptide synthetases (LanMs) are relatively promiscuous to core peptide variations. Previous studies have shown that different LanMs catalyze identical reactions on the same core sequence fused to their respective cognate leaders. We characterized a new LanM enzyme from Microcystis aeruginosa NIES-88, MalM, and demonstrated that MalM and ProcM exhibited disparate dehydration and cyclization patterns on identical core peptides. Our study provided new insights into the regioselectivity of LanMs and showcased an appropriate strategy for lanthipeptide structural diversity engineering.

Identification of Key Signaling Pathways and Genes in Eosinophilic Asthma and Neutrophilic Asthma by Weighted Gene Co-Expression Network Analysis.

Background: Asthma is a heterogeneous disease with different subtypes including eosinophilic asthma (EA) and neutrophilic asthma (NA). However, the mechanisms underlying the difference between the two subtypes are not fully understood. Methods: Microarray datasets (GSE45111 and GSE137268) were acquired from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in induced sputum between EA (n = 24) and NA (n = 15) were identified by "Limma" package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and Gene set enrichment analysis (GSEA) were used to explore potential signaling pathways. Weighted gene co-expression network analysis (WGCNA) were performed to identify the key genes that were strongly associated with EA and NA. Results: A total of 282 DEGs were identified in induced sputum of NA patients compared with EA patients. In GO and KEGG pathway analyses, DEGs were enriched in positive regulation of cytokine production, and cytokine-cytokine receptor interaction. The results of GSEA showed that ribosome, Parkinson's disease, and oxidative phosphorylation were positively correlated with EA while toll-like receptor signaling pathway, primary immunodeficiency, and NOD-like receptor signaling pathway were positively correlated with NA. Using WGCNA analysis, we identified a set of genes significantly associated NA including IRFG, IRF1, STAT1, IFIH1, IFIT3, GBP1, GBP5, IFIT2, CXCL9, and CXCL11. Conclusion: We identified potential signaling pathways and key genes involved in the pathogenesis of the asthma subsets, especially in neutrophilic asthma.