The tonoplast-localized OsTIP2;1 is involved in aluminum detoxification in rice.

Aluminum (Al) stress is a significant issue in acidic soils, severely affecting crop growth and yield. Rice is notably resilient to Al toxicity, yet the internal tolerance mechanisms remain inadequately addressed. Here, we examined the role of OsTIP2;1, a tonoplast-bound intrinsic protein (TIP), in rice's internal Al detoxification. Our findings reveal that OsTIP2;1 expression was quickly and explicitly activated by Al ions in roots but not in shoots. The OsTIP2;1-GFP protein localizes to the tonoplast in plant and yeast cells. Non-functional ostip2;1 rice mutants were more vulnerable to Al toxicity. In the roots, the ostip2;1 mutants exhibited considerably lower levels of Al in the cell sap, primarily the vacuolar contents, than in the wild-type plant. Moreover, the ostip2;1 mutants showed reduced Al accumulation in the roots but increased translocation to the shoots. Heterologous expression of tonoplast-localized OsTIP2;1 in yeast led to enhanced Al tolerance, suggesting that OsTIP2;1 facilitates Al sequestration to the vacuole. These findings indicate that OsTIP2;1 mediates internal detoxification by transporting Al into the vacuole in the root and restricting its transport to above-ground tissues, thus contributing to Al resistance in rice.

Patient-derived ovarian cancer organoid carries immune microenvironment and blood vessel keeping high response to cisplatin.

Ovarian cancer is high recurrence and mortality malignant tumor. The most common ovarian cancer was High-Grade Serous Ovarian Cancer. However, High-Grade Serous Ovarian Cancer organoid is rare, which organoid with patient immune microenvironment and blood vessels even absence. Here, we report a novel High-Grade Serous Ovarian Cancer organoid system derived from patient ovarian cancer samples. These organoids recapitulate High-Grade Serous Ovarian Cancer organoids' histological and molecular heterogeneity while preserving the critical immune microenvironment and blood vessels, as evidenced by the presence of CD34 + endothelial cells. Whole exome sequencing identifies key mutations (CSMD3, TP53, GABRA6). Organoids show promise in testing cisplatin sensitivity for patients resistant to carboplatin and paclitaxel, with notable responses in cancer proteoglycans and p53 (TP53) signaling, like ACTG/ACTB1/AKT2 genes and BBC3/MDM2/PERP. Integration of immune microenvironment and blood vessels enhances potential for novel therapies like immunotherapies and angiogenesis inhibitors. Our work may provide a new detection system and theoretical basis for ovarian cancer research and individual therapy.

Investigating the molecular mechanism of vitexin targeting CDK1 to inhibit colon cancer cell proliferation via GEO chip data mining, computer simulation, and biological activity verification.

The objective of this study is to explore the antiproliferative activity of the traditional Chinese medicine monomer vitexin on colon cancer HCT-116 cells and its underlying mechanism. The in vitro antiproliferative activity of vitexin on colon cancer HCT-116 cells was evaluated using the CCK-8 assay. Potential drug targets for colon cancer were identified through GEO chip data mining, and molecular docking using Schrödinger software was conducted. Molecular dynamics simulations were employed to deeply analyze the interaction between candidate compounds and target proteins. Flow cytometry was employed to examine the cell cycle. The impact of vitexin on the expression of CDK1/cyclinB proteins in HCT-116 cells was assessed through Western blot analysis, immunofluorescence, and CDK inhibition assay. Vitexin exhibited inhibitory effects on colon cancer HCT-116 cells, with a half inhibitory concentration (IC50) value of 203.27 ± 9.85 µmol/L. The analysis of differential gene expression in GEO and TCGA datasets, along with the GENECARD dataset of related disease genes, identified 91 disease targets, including "CDK1." Vitexin induced cell cycle arrest in the G2/M phase of HCT-116 cells. Molecular docking revealed a strong interaction between Vitexin and CDK1 (Docking score - 9.497), with molecular dynamics simulations confirming the stability of the Vitexin-CDK1 complex and comparable inhibitory effects to Flavopiridol. Vitexin can inhibit the expression of CDK1/cyclin B proteins in HCT-116 cells, with an IC50 of 58.06 ± 3.07 µmol/L. Vitexin may inhibit colon cancer HCT-116 cell proliferation by suppressing CDK1/cyclin B expression, leading to cell cycle arrest in the G2/M phase.

Charged Gold Nanoparticles for Target Identification-Alignment and Automatic Segmentation of CT Image-Guided Adaptive Radiotherapy in Small Hepatocellular Carcinoma.

Because of the challenges posed by anatomical uncertainties and the low resolution of plain computed tomography (CT) scans, implementing adaptive radiotherapy (ART) for small hepatocellular carcinoma (sHCC) using artificial intelligence (AI) faces obstacles in tumor identification-alignment and automatic segmentation. The current study aims to improve sHCC imaging for ART using a gold nanoparticle (Au NP)-based CT contrast agent to enhance AI-driven automated image processing. The synthesized charged Au NPs demonstrated notable in vitro aggregation, low cytotoxicity, and minimal organ toxicity. Over time, an in situ sHCC mouse model was established for in vivo CT imaging at multiple time points. The enhanced CT images processed using 3D U-Net and 3D Trans U-Net AI models demonstrated high geometric and dosimetric accuracy. Therefore, charged Au NPs enable accurate and automatic sHCC segmentation in CT images using classical AI models, potentially addressing the technical challenges related to tumor identification, alignment, and automatic segmentation in CT-guided online ART.

Landscape of human organoids: Ideal model in clinics and research.

In the last decade, organoid research has entered a golden era, signifying a pivotal shift in the biomedical landscape. The year 2023 marked a milestone with the publication of thousands of papers in this arena, reflecting exponential growth. However, amid this burgeoning expansion, a comprehensive and accurate overview of the field has been conspicuously absent. Our review is intended to bridge this gap, providing a panoramic view of the rapidly evolving organoid landscape. We meticulously analyze the organoid field from eight distinctive vantage points, harnessing our rich experience in academic research, industrial application, and clinical practice. We present a deep exploration of the advances in organoid technology, underpinned by our long-standing involvement in this arena. Our narrative traverses the historical genesis of organoids and their transformative impact across various biomedical sectors, including oncology, toxicology, and drug development. We delve into the synergy between organoids and avant-garde technologies such as synthetic biology and single-cell omics and discuss their pivotal role in tailoring personalized medicine, enhancing high-throughput drug screening, and constructing physiologically pertinent disease models. Our comprehensive analysis and reflective discourse provide a deep dive into the existing landscape and emerging trends in organoid technology. We spotlight technological innovations, methodological evolution, and the broadening spectrum of applications, emphasizing the revolutionary influence of organoids in personalized medicine, oncology, drug discovery, and other fields. Looking ahead, we cautiously anticipate future developments in the field of organoid research, especially its potential implications for personalized patient care, new avenues of drug discovery, and clinical research. We trust that our comprehensive review will be an asset for researchers, clinicians, and patients with keen interest in personalized medical strategies. We offer a broad view of the present and prospective capabilities of organoid technology, encompassing a wide range of current and future applications. In summary, in this review we attempt a comprehensive exploration of the organoid field. We offer reflections, summaries, and projections that might be useful for current researchers and clinicians, and we hope to contribute to shaping the evolving trajectory of this dynamic and rapidly advancing field.

Revealing the active ingredients and mechanism of P. sibiricumm in non-small-cell lung cancer based on UPLC-Q-TOF-MS/MS, network pharmacology, and molecular docking.

The alcohol extraction of P. sibiricum has exhibited significant inhibitory effects on the production of free radicals and the proliferation of non-small-cell lung carcinoma (NSCLC) A549 cells. Despite the diverse components found in alcohol extraction of P. sibiricum and its multiple targets, the active components and associated targets remain largely unidentified. Hence, there is a need for additional investigation into the pharmacodynamic elements and mechanisms of action. This study aimed to analyze and identify the components responsible for the anti-tumor activity of alcohol extraction from P. sibiricum using UPLC-Q-TOF-MS/MS for the first time. Subsequently, the targets of the active components were predicted using the SwissTargetPrediction database, whereas the targets for NSCLC were sourced from the Online Mendelian Inheritance in Man database (OMIM) and the GeneCards database. Next, the targets of chemical composition were integrated with disease targets via Venny online. GO and KEGG pathway enrichment analyses were performed utilizing DAVID. Subsequently, a network analysis of "components-targets-pathways" was established using Cytoscape 3.8.2 and assessed with the "network analyzer" plug-in. Molecular docking was conducted utilizing Autodock 1.5.6. The study aimed to examine the anti-proliferative impacts and underlying mechanisms of alcohol extraction from P. sibiricum on NSCLC through in vivo and in vitro investigations utilizing an animal model of transplanted tumor, CCK8 assay, cell scratch test, RT-qPCR, and western blotting. The study unveiled that 17 active components extracted from P. sibiricum alcohol demonstrated anti-non-small cell lung cancer (NSCLC) effects through the modulation of 191 targets and various significant signaling pathways. These pathways include Endocrine resistance, PI3K/AKT, Chemical carcinogenesis-receptor activation, Proteoglycans in cancer, EGFR tyrosine kinase inhibitor resistance, AMPK signaling pathway, and other related signaling pathways. Network analysis and molecular docking results indicated that specific compounds such as (25S)-26-O-(ß-d-glucopyranosyl)-furost-5-en3ß,22α,26-triol3-O-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranosyl-(1→4)-ß-d-glucopyranoside, Timosaponin H1, Deapi-platycodin D3, (3R)-5,7-dihydroxy-6,8-dimethyl-3-(4'-hydroxybenzyl)-chroman-4-one, Disporopsin, Funkioside F, Kingianoside E, Parisyunnanoside H, and Sibiricoside B primarily targeted 17 key proteins (BCL2, EGFR, ESR1, ESR2, GRB2, IGF1R, JUN, MAP2K1, MAPK14, MAPK8, MDM2, MMP9, mTOR, PIK3CA, RAF1, RPS6KB1, and SRC) collectively. In conclusion, the alcohol extraction of P. sibiricum demonstrated inhibitory effects on cell proliferation, induction of apoptosis, and inhibition of metastasis through various pathways.

Understanding Sorafenib-Induced Cardiovascular Toxicity: Mechanisms and Treatment Implications.

Tyrosine kinase inhibitors (TKIs) have been recognized as crucial agents for treating various tumors, and one of their key targets is the intracellular site of the vascular endothelial growth factor receptor (VEGFR). While TKIs have demonstrated their effectiveness in solid tumor patients and increased life expectancy, they can also lead to adverse cardiovascular effects including hypertension, thromboembolism, cardiac ischemia, and left ventricular dysfunction. Among the TKIs, sorafenib was the first approved agent and it exerts anti-tumor effects on hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) by inhibiting angiogenesis and tumor cell proliferation through targeting VEGFR and RAF. Unfortunately, the adverse cardiovascular effects caused by sorafenib not only affect solid tumor patients but also limit its application in curing other diseases. This review explores the mechanisms underlying sorafenib-induced cardiovascular adverse effects, including endothelial dysfunction, mitochondrial dysfunction, endoplasmic reticulum stress, dysregulated autophagy, and ferroptosis. It also discusses potential treatment strategies, such as antioxidants and renin-angiotensin system inhibitors, and highlights the association between sorafenib-induced hypertension and treatment efficacy in cancer patients. Furthermore, emerging research suggests a link between sorafenib-induced glycolysis, drug resistance, and cardiovascular toxicity, necessitating further investigation. Overall, understanding these mechanisms is crucial for optimizing sorafenib therapy and minimizing cardiovascular risks in cancer patients.

A study integrated metabolomics and network pharmacology to investigate the effects of Shicao in alleviating acute liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Shicao is the aerial part of Achillea alpina L., a common herb found mainly in Europe, Asia, and North America. Traditional Chinese medicine has a history of thousands of years and is widely used to treat various diseases. AIM OF STUDY: To explore the hepatoprotective effects of Shicao on CCl4-induced acute liver injury. METHODS: A rat model of acute liver injury was established and liver function indices were assessed to evaluate the protective effect of Shicao on the liver. Untargeted metabolomics of the serum and liver tissues was conducted using UPLC-Q-TOF/MS to identify differential metabolites related to acute liver injury. A network of metabolite-reaction-enzyme-gene constituents was constructed using network pharmacology. Hub targets and key components of the effect of Shicao on acute liver injury were screened from the network. RESULTS: Compared to the model group, Shicao improved the degree of liver damage through the assessment of the liver index, ALT and AST levels, and hepatic pathology slices, demonstrating its hepatoprotective effect against acute liver injury in rats. 10 and 38 differential metabolites involved in acute liver injury were identified in serum and liver tissues, respectively. Most of these were regulated or restored following treatment with Shicao, which mainly consisted of bile acids, lipids, and nucleotides such as taurocholic acid, LysoPC (17:0), and adenosine diphosphate ribose. Through the network of metabolite-reaction-enzyme-gene-constituents, 10 key components and 5 hub genes, along with 7 crucial differential metabolites, were mainly involved in glycerophospholipid metabolism, purine metabolism, biosynthesis of unsaturated fatty acids, and primary bile acid biosynthesis, which may play important roles in the prevention of acute liver injury by Shicao. CONCLUSION: This study revealed that Shicao had protective effects against CCl4-induced liver injury in rats. It was speculated that the ingredients of Shicao might be closely related to the hub targets, thereby regulating the levels of key metabolites, affecting inflammatory response and oxidative stress and attenuate the liver injury consequently. This study provides a basis for further investigation of its therapeutic potential and the mechanism of action.

Immune pathway activation in neurons triggers neural damage after stroke.

Ischemic brain injury is a severe medical condition with high incidences in elderly people without effective treatment for the resulting neural damages. Using a unilateral mouse stroke model, we analyze single-cell transcriptomes of ipsilateral and contralateral cortical penumbra regions to objectively reveal molecular events with single-cell resolution at 4 h and 1, 3, and 7 days post-injury. Here, we report that neurons are among the first cells that sense the lack of blood supplies by elevated expression of CCAAT/enhancer-binding protein ß (C/EBPß). To our surprise, the canonical inflammatory cytokine gene targets for C/EBPß, including interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α), are subsequently induced also in neuronal cells. Neuronal-specific silencing of C/EBPß or IL-1ß and TNF-α substantially alleviates downstream inflammatory injury responses and is profoundly neural protective. Taken together, our findings reveal a neuronal inflammatory mechanism underlying early pathological triggers of ischemic brain injury.

Low-density polyethylene microplastics and biochar interactively affect greenhouse gas emissions and microbial community structure and function in paddy soil.

Paddy soils are susceptible to microplastics (MPs) contamination. As a common soil amendment, biochar (BC) has been extensively applied in paddy fields. The co-occurrence of MPs and BC may cause interactive effects on soil biogeochemical processes, which has yet been well studied. In this study, a 41-days of microcosm experiment was conducted using paddy soil added with 0.5-1.5 wt% of low-density polyethylene (LDPE) and 5 wt% of BC individually or jointly. Application of BC, LDPE, or their mixture into soil significantly increased the emission of methane (CH4), but suppressed the emission of carbon dioxide (CO2). LDPE addition lowered soil nitrous oxide (N2O) emissions, while BC exerted an opposite effect. Proteobacteria was the most dominant phylum with a relative abundance range of 35.1-51.0%, followed by Actinobacteria (19.3-30.9%) and Acidobacteria (7.5-23.5%). The abundances of the mcrA gene and pH values were increased in soils added with BC or/and LDPE, which were the possible reasons for the higher CH4 emissions in these treatments. The emission of N2O was positively related to the abundances of norB and narG genes, suggesting denitrification was a major pathway to produce N2O. Results of structural equation modeling demonstrated that addition of BC or/and LDPE MPs could affect greenhouse gas emissions from paddy soil by altering soil chemical properties, microbial community structure, and functional gene abundances.

Integrating Network Pharmacology and Experimental Verification to Investigate the Mechanisms of Shuangshi Tonglin Capsule to Treat Chronic Prostatitis.

BACKGROUND AND OBJECTIVE: Chronic prostatitis (CP) is one of the most common diseases in young and middle-aged men but lacks effective treatment. Shuangshi Tonglin Capsule (SSTLC) is a clinical drug for the treatment of chronic prostatitis. However, the underlying molecular mechanisms of SSTLC in treating CP are still unclear. In this study, we researched the underlying mechanisms of SSTLC in treating chronic prostatitis. METHODS: The ingredients of SSTLC were received from the TCMSP and BATMAN databases, and the CP targets were collected based on GeneCards and OMIM. Then, the PPI network and the "drug-ingredient-target" network map were constructed. GO and KEGG enrichment analyses by using DAVID. Molecular docking was performed by using AutoDock 4.2 and PyMol. And using animal experiments to verify the potential effect of SSTLC in CP. RESULTS: SSTLC contained 10 herbs, 158 chemical ingredients and 277 targets, 2002, diseaserelated targets were obtained. Network analysis outcomes indicated that VEGFA, TNF, MAPK1, EGFR, and MAPK8 are the key targets of SSTLC in treating chronic prostatitis. Furthermore, molecular docking revealed that quercetin, luteolin, and kaempferol exhibited a strong binding effect. Animal experimental indicated that SSTLC can reduce the pathological damage to prostate tissue. And, we found that high-dose SSTLC significantly reduced the level of TNF-α and downregulated the expression of EGFR, p-p38 and p-ERK1/2 (P<0.05). CONCLUSION: This study determined the pharmacological effects of SSTLC and the potential mechanism of action on SSTLC to treat CP, it provides a new idea for traditional Chinese medicine to treat chronic prostatitis.

Iron counteracts zinc-induced toxicity in soybeans.

Zinc (Zn) and iron (Fe) are essential micronutrients for all living organisms and the major targets for crop biofortification. However, when acquired in excess quantities, Zn and Fe can be toxic to plants. In this study, we examined the interaction between Zn and Fe in soybean plants under various Zn and Fe treatments. While the level of Zn accumulation increased with increasing Zn supplies, Zn content greatly decreased with rising Fe supplies. Moreover, Zn uptake rates were negatively correlated with Fe supplies. However, Fe accumulation was not greatly affected by elevating Zn supplies. Excess Zn supplies were found to induce typical Fe deficiency symptoms under low Fe conditions, which can be counteracted by increasing Fe supplies. Interestingly, leaf chlorosis caused by excess Zn and low Fe supplies was not directly associated with reduced total Fe content but likely associated with deleterious effects of excess Zn. The combination of high Zn and low Fe greatly activates FRO2 and FIT1 gene expression in soybean roots. Besides, Zn-Fe interaction influences the activities of antioxidative enzymes as well as the uptake, accumulation, and homeostasis of other essential micronutrients, such as copper and manganese in soybean plants. These findings provide new perspectives on Zn and Fe interaction and on heavy metal-induced Fe deficiency-like symptoms.

Identification of circRNA-miRNA-mRNA networks to explore the molecular mechanism and immune regulation of postoperative neurocognitive disorder.

Postoperative neurocognitive disorder (PND) is a common complication in older patients. However, its pathogenesis has still remained elusive. Recent studies have shown that circular RNA (circRNA) plays an important role in the development of neurodegenerative diseases, such as PND after surgery. CircRNA, as a competitive endogenous RNA (ceRNA), mainly acts as a molecular sponge for miRNA to "adsorb" microRNA (miRNA) and to reduce the inhibitory effects of miRNAs on target mRNA. The sequencing data of circRNA were obtained from the Gene Expression Omnibus (GEO) database. By bioinformatic methods, circAtlas, miRDB, miRTarBase and miRwalk databases were applied to construct circRNA-miRNA-mRNA networks and screen differentially expressed mRNAs. To improve the accuracy of the data, we randomly divided aging mice into control (non-PND group) and PND groups, and used high-throughput sequencing to analyze their brain hippocampal tissue for analysis. Three key genes were cross-detected in the data of both groups, which were Unc13c, Tbx20 and St8sia2 (as hub genes), providing new targets for PND treatment. According to the results of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, immune cell infiltration analysis, gene set enrichment analysis (GSEA), Connectivity Map (CMap) analysis, quantitative real-time polymerase chain reaction (qRT-PCR), the genes that were not related to the central nervous system were removed, and finally, mmu_circ_0000331/miR-1224-3p/Unc13c and mmu_circ_0000406/miR-24-3p/St8sia2 ceRNA networks were identified. In addition, the CMap method was used to select the top 4 active compounds with the largest negative correlation absolute values, including cimaterol, Rucaparib, FG-7142, and Hydrocortisone.

DMSO-soluble smoking particles up-regulate the vascular endothelin receptors through AMPK-SIRT1 and MAPK pathways.

Smoking is a well-known risk factor for cardiovascular diseases. However, the mechanisms behind how smoking leads to vasospasm are not fully elucidated. Endothelin receptors are involved in the pathogenesis of cardiovascular diseases. This study examined whether cigarette smoke could induce up-regulation of vascular endothelin receptors through AMPK-SIRT1 and MAPK pathways. The results show that DMSO-soluble smoking particles (DSP) up-regulated the protein expressions of endothelin receptors and the contractile responses. Furthermore, the inhibition of MAPK or activation of AMPK-SIRT1 markedly attenuated DSP-enhanced vasoconstriction and the protein expression of endothelin receptors. The in vivo study showed that cigarette smoke increased the blood pressure of the rats and down-regulated p-AMPKα, SIRT1, and up-regulated endothelin receptors, p-ERK1/2, and p-P38 protein expressions. However, treatment with resveratrol attenuated vasoconstriction, endothelin receptor proteins expression, and blood pressure in vivo. In conclusion, this suggests that cigarette smoke up-regulates the vascular endothelin receptors through AMPK-SIRT1 and MAPK pathways.

The plasma membrane-localized OsNIP1;2 mediates internal aluminum detoxification in rice.

Aluminum (Al) toxicity significantly restricts crop production on acidic soils. Although rice is highly resistant to Al stress, the underlying resistant mechanisms are not fully understood. Here, we characterized the function of OsNIP1;2, a plasma membrane-localized nodulin 26-like intrinsic protein (NIP) in rice. Aluminum stress specifically and quickly induced OsNIP1;2 expression in the root. Functional mutations of OsNIP1;2 in two independent rice lines led to significantly enhanced sensitivity to Al but not other metals. Moreover, the Osnip1;2 mutants had considerably more Al accumulated in the root cell wall but less in the cytosol than the wild-type rice. In addition, compared with the wild-type rice plants, the Osnip1;2 mutants contained more Al in the root but less in the shoot. When expressed in yeast, OsNIP1;2 led to enhanced Al accumulation in the cells and enhanced sensitivity to Al stress, suggesting that OsNIP1;2 facilitated Al uptake in yeast. These results suggest that OsNIP1;2 confers internal Al detoxification via taking out the root cell wall's Al, sequestering it to the root cell's vacuole, and re-distributing it to the above-ground tissues.

Total flavonoids of sea buckthorn (Hippophae rhamnoides L.) improve MC903-induced atopic dermatitis-like lesions.

ETHNOPHARMACOLOGICAL RELEVANCE: Sea buckthorn (Hippophae rhamnoides L.) is popularly used as a herbal medicine and food additive in the world. Total flavonoids of Hippophae rhamnoides (TFH) are reported to have anti-inflammatory and immunomodulatory activities. AIM: The effects of TFH on atopic dermatitis (AD)-like lesions induced by MC903 in mice was elucidated in the study. METHODS: To induce AD-like lesions, MC903 was adopted to apply repeatedly on the left ear in C57BL/6 mice. After induction of AD-like lesions, 0.5% and 1% TFH cream was applied topically on ears of mice once a day for 8 days. The degree of skin lesions was evaluated by macroscopical and histological methods. Expressions of filaggrin (FLG) was evaluated by Western blotting. Real-time polymerase chain reaction (qPCR) was adopted to detect the mRNA expression of thymic stromal lymphopoietin (TSLP), interferon (IFN)-γ, interleukin (IL-4), tumor necrosis factor (TNF)-α in skin lesions. In vitro, Cytokine Antibody Arrays were performed to measure production of cytokines in IFN-γ/TNF-α-treated HaCaT cells, Western blotting was employed to detect the expressions of p-NF-κB, p-ERK and p-P38. RESULTS: Topical application of TFH significantly improved the severity of dermatitis by inhibiting the infiltration of mast cell, increasing expression of FLG, decreasing the expressions of TNF-α, IL-4, IFN-γ and TSLP in skin lesions. TFH decreased the levels of IL-1α, IL-1ß, IL-6, monocyte chemoattractant protein (MCP)-1, MCP-3, macrophage-derived chemokine (MDC), platelet-derived growth factor (PDGF)-BB, thymus and activation regulated chemokine (TARC) in the supernatants of the HaCaT cells treated by IFN-γ/TNF-α. Furthermore, expressions of p-NF-κB, p-ERK and p-P38 were also decreased by TFH administration with dose dependent manner in HaCaT cells treated by IFN-γ/TNF-α. CONCLUSIONS: Topical application of TFH improved AD-like lesions in mice induced by MC903. Which exerted the effects of anti-inflammation and repairing skin barrier by regulating Th1/Th2 balance. This finding indicates that TFH is a novel potential agent for the external treatment of AD.

The roles of selectivity filters in determining aluminum transport by AtNIP1;2.

Aquaporins (AQPs) are channel proteins involved in transporting a variety of substrates. It has been proposed that the constriction regions in the central pores of the AQP channels play a crucial role in determining transport substrates and activities of AQPs. Our previous results suggest that AtNIP1;2, a member of the AQP superfamily in Arabidopsis, facilitates aluminum transport across the plasma membrane. However, the functions of the constriction regions in AtNIP1;2-mediated transport activities are unclear. This study reports that residue substitutions of the constriction regions affect AtNIP1;2-mediated aluminum uptake, demonstrating the critical roles of the constriction regions for transport activities. Furthermore, a constriction region that partially or wholly mimics AtNIP5;1, a demonstrated boric-acid transporter, could not render the boric-acid transport activity to AtNIP1;2. Therefore, besides the constriction regions, other structural features are also involved in determining the nature of AtNIP1;2's transport activities.Abbreviations: AIAR: alanine-isoleucine-alanine-arginine; AIGR: alanine-isoleucine-glycine- arginine; AQP: aquaporin; Al-Mal: aluminum-malate; ar/R: aromatic/arginine; AVAR: alanine-valine-alanine-arginine; CK: control; H: helical domain; ICP-MS: inductively coupled plasma mass spectrometry; LA - LE: inter-helical loops A to E; NIP: nodulin 26-like intrinsic protein; NPA: asparagine-proline-alanine; NPG: asparagine-proline- glycine; NPS: asparagine-proline-Serine; NPV: asparagine-proline-valine; ORF: open reading frame; PIP: plasma membrane intrinsic proteins; SIP: small basic intrinsic proteins; TM: transmembrane helices; WIAR: tryptophan-isoleucine-alanine-arginine; WVAR: tryptophan-valine-alanine-arginine; WVGR: tryptophan-valine-glycine- arginine.

Synthesis of a Reactive Template-Induced Core-Shell PZS@ZIF-67 Composite Microspheres and Its Application in Epoxy Composites.

Developing superior properties of epoxy resin composites with high fire resistance, light smoke, and low toxicity has been the focus of the research in the flame-retardant field. In particular, it is essential to decrease the emissions of toxic gases and smoke particles generated during the thermal decomposition of epoxy resin (EP) to satisfy the industrial requirements for environmental protection and safety. Consequently, the PZS@ZIF-67 composite was designed and synthesized by employing the hydroxyl group-containing polyphosphazene (poly(cyclotriphosphazene-co-4,4'-dihydroxydiphenylsulfone), PZS) as both the interfacial compatibility and an in situ template and the ZIF-67 nanocrystal as a nanoscale coating and flame-retardant cooperative. ZIF-67 nanocrystal with multidimensional nanostructures was uniformly wrapped on the surface of PZS microspheres. Subsequently, the acquired PZS@ZIF-67 composite was incorporated into the epoxy resin to prepare composite samples for the study of their fire safety, toxicity suppression, and mechanical performance. Herein, the EP/5% PZS@ZIF-67 passed the V-0 rating in a UL-94 test with a 31.9% limit oxygen index value. More precisely, it is endowed with a decline of 51.08%, 28.26%, and 37.87% of the peak heat release rate, the total heat release, and the total smoke production, respectively. In addition, the unique structure of PZS@ZIF-67 microsphere presented a slight impact on the mechanical properties of EP composites at low loading. The PZS@ZIF-67 possible flame-retardant mechanism was speculated based on the analysis of the condensed phase and the gas phase of EP composites.

An Intelligent Fire-Protection Coating Based on Ammonium Polyphosphate/Epoxy Composites and Laser-Induced Graphene.

Fire-protection coatings with a self-monitoring ability play a critical role in safety and security. An intelligent fire-protection coating can protect humans from personal and property damage. In this work, we report the fabrication of a low-cost and facile intelligent fire coating based on a composite of ammonium polyphosphate and epoxy (APP/EP). The composite was processed using laser scribing, which led to a laser-induced graphene (LIG) layer on the APP/EP surface via a photothermal effect. The C-O, C=O, P-O, and N-C bonds in the flame-retardant APP/EP composite were broken during the laser scribing, while the remaining carbon atoms recombined to generate the graphene layer. A proof-of-concept was achieved by demonstrating the use of LIG in supercapacitors, as a temperature sensor, and as a hazard detection device based on the shape memory effect of the APP/EP composite. The intelligent flame protection coating had a high flame retardancy, which increased the time to ignition (TTI) from 21 s to 57 s, and the limiting oxygen index (LOI) value increased to 37%. The total amount of heat and smoke released during combustion was effectively suppressed by ≈ 71.1% and ≈ 74.1%, respectively. The maximum mass-specific supercapacitance could reach 245.6 F·g-1. The additional LIG layer enables applications of the device as a LIG-APP/EP temperature sensor and allows for monitoring of the deformation according to its shape memory effect. The direct laser scribing of graphene from APP/EP in an air atmosphere provides a convenient and practical approach for the fabrication of flame-retardant electronics.

Dose Comparison of Dexmedetomidine Sedation following Spinal Anesthesia: Parturient versus Nonpregnant Women-A Randomized Trial.

BACKGROUND: This study was designed to investigate and compare the effective doses of dexmedetomidine for sedation in parturient patients who underwent Cesarean section (CS) and nonpregnant women who underwent elective gynecologic surgery. METHODS: The study comprised 60 females aged between 25 and 35. They were divided into two groups. The parturient group received a bolus dose of dexmedetomidine over 15 min after the delivery of the fetus and placenta. In the nonpregnant women group, a bolus of dexmedetomidine was administered intravenously upon the completion of spinal anesthesia. The subsequent dose required by patients in each group was then determined through a modified two-stage Dixon up-and-down sequential method. Probit analysis was used to calculate the ED50 and the ED95 of dexmedetomidine for adequate sedation. RESULTS: The ED50 of dexmedetomidine for adequate sedation in parturient patients was 1.58 µg/kg (1.51-1.66 µg/kg); in nonpregnant women, it was 0.96 µg/kg (0.91-1.01 µg/kg) (95% CI). The ED95 of dexmedetomidine in parturients was 1.80 µg/kg (1.70-2.16) µg/kg and that of nonpregnant women was 1.10 µg/kg (1.04-1.30 µg/kg) (95% CI). The ED50 in parturients was significantly higher than that in nonpregnant women (P < 0.05). CONCLUSION: The ED50 of dexmedetomidine for target sedation in parturients who received spinal anesthesia for CS is greater than 1.5 times that in nonpregnant women who received spinal anesthesia for lower abdominal gynecologic surgery. This study postulates that the dose of dexmedetomidine required to achieve optimal sedation following spinal anesthesia is much higher in parturients than in nonpregnant women undergoing gynecologic surgeries. This trial is registered with NCT02111421.