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Doping of perovskite semiconductors1 and passivation of their grain boundaries2 remain challenging but essential for advancing high-efficiency perovskite solar cells. Particularly, it is crucial to build perovskite/indium tin oxide (ITO) Schottky contact based inverted devices without predepositing a layer of hole-transport material3-5. Here we report a dimethylacridine-based molecular doping process used to construct a well-matched p-perovskite/ITO contact, along with all-round passivation of grain boundaries, achieving a certified power conversion efficiency (PCE) of 25.39%. The molecules are shown to be extruded from the precursor solution to the grain boundaries and the bottom of the film surface in the chlorobenzene-quenched crystallization process, which we call a molecule-extrusion process. The core coordination complex between the deprotonated phosphonic acid group of the molecule and lead polyiodide of perovskite is responsible for both mechanical absorption and electronic charge transfer, and leads to p-type doping of the perovskite film. We created an efficient device with a PCE of 25.86% (reverse scan) and that maintained 96.6% of initial PCE after 1,000 h of light soaking.
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Adhesion G-protein-coupled receptors (aGPCRs) are important for organogenesis, neurodevelopment, reproduction and other processes1-6. Many aGPCRs are activated by a conserved internal (tethered) agonist sequence known as the Stachel sequence7-12. Here, we report the cryogenic electron microscopy (cryo-EM) structures of two aGPCRs in complex with Gs: GPR133 and GPR114. The structures indicate that the Stachel sequences of both receptors assume an α-helical-bulge-ß-sheet structure and insert into a binding site formed by the transmembrane domain (TMD). A hydrophobic interaction motif (HIM) within the Stachel sequence mediates most of the intramolecular interactions with the TMD. Combined with the cryo-EM structures, biochemical characterization of the HIM motif provides insight into the cross-reactivity and selectivity of the Stachel sequences. Two interconnected mechanisms, the sensing of Stachel sequences by the conserved 'toggle switch' W6.53 and the constitution of a hydrogen-bond network formed by Q7.49/Y7.49 and the P6.47/V6.47φφG6.50 motif (φ indicates a hydrophobic residue), are important in Stachel sequence-mediated receptor activation and Gs coupling. Notably, this network stabilizes kink formation in TM helices 6 and 7 (TM6 and TM7, respectively). A common Gs-binding interface is observed between the two aGPCRs, and GPR114 has an extended TM7 that forms unique interactions with Gs. Our structures reveal the detailed mechanisms of aGPCR activation by Stachel sequences and their Gs coupling.
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Peptídeos , Receptores Acoplados a Proteínas G , Sítios de Ligação , Microscopia Crioeletrônica , Domínios Proteicos , Estrutura Secundária de Proteína , Receptores Acoplados a Proteínas G/metabolismo , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Prostaglandin I2 synthesized by endothelial COX (cyclooxygenase) evokes potent vasodilation in some blood vessels but is paradoxically responsible for endothelium-dependent constriction (EDC) in others. Prostaglandin I2 production and EDC may be enhanced in diseases such as hypertension. However, how PGIS (prostaglandin I2 synthase) deficiency affects EDC and how this is implicated in the consequent cardiovascular pathologies remain largely unknown. METHODS: Experiments were performed with wild-type, Pgis knockout (Pgis-/-) and Pgis/thromboxane-prostanoid receptor gene (Tp) double knockout (Pgis-/-Tp-/-) mice and Pgis-/- mice transplanted with unfractionated wild-type or Cox-1-/- bone marrow cells, as well as human umbilical arteries. COX-derived prostanoids were measured by high-performance liquid chromatography-mass spectrometry. Vasomotor responses of distinct types of arteries were assessed by isometric force measurement. Parameters of hypertension, vascular remodeling, and cardiac hypertrophy in mice at different ages were monitored. RESULTS: PGF2α, PGE2, and a trace amount of PGD2, but not thromboxane A2 (TxA2), were produced in response to acetylcholine in Pgis-/- or PGIS-inhibited arteries. PGIS deficiency resulted in exacerbation or occurrence of EDC ex vivo and in vivo. Endothelium-dependent hyperpolarization was unchanged, but phosphorylation levels of eNOS (endothelial nitric oxide synthase) at Ser1177 and Thr495 were altered and NO production and the NO-dependent relaxation evoked by acetylcholine were remarkably reduced in Pgis-/- aortas. Pgis-/- mice developed high blood pressure and vascular remodeling at 16 to 17 weeks and subsequently cardiac hypertrophy at 24 to 26 weeks. Meanwhile, blood pressure and cardiac parameters remained normal at 8 to 10 weeks. Additional ablation of TP (TxA2 receptor) not only restrained EDC and the downregulation of NO signaling in Pgis-/- mice but also ameliorated the cardiovascular abnormalities. Stimulation of Pgis-/- vessels with acetylcholine in the presence of platelets led to increased TxA2 generation. COX-1 disruption in bone marrow-derived cells failed to affect the development of high blood pressure and vascular remodeling in Pgis-/- mice though it largely suppressed the increase of plasma TxB2 (TxA2 metabolite) level. CONCLUSIONS: Our study demonstrates that the non-TxA2 prostanoids/TP axis plays an essential role in mediating the augmentation of EDC and cardiovascular disorders when PGIS is deficient, suggesting TP as a promising therapeutic target in diseases associated with PGIS insufficiency.
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Postconsumer plastics are generally perceived as valueless with only a small portion of plastic waste being closed-loop recycled into similar products while most of them are discarded in landfills. Depositing plastic waste in landfills not only harms the environment but also signifies a substantial economic loss. Alternatively, constructing value-added chemical feedstocks via mining the waste-derived intermediate species as a carbon (C) source under mild electrochemical conditions is a sustainable strategy to realize the circular economy. This proof-of-concept work provides an attractive "turning trash to treasure" strategy by integrating electrocatalytic polyethylene terephthalate (PET) plastic upcycling with a chemical C-S coupling reaction to synthesize organosulfur compounds, hydroxymethanesulfonate (HMS). HMS can be produced efficiently (Faradaic efficiency, FE of â¼70%) via deliberately capturing electrophilic intermediates generated in the PET monomer (ethylene glycol, EG) upcycling process, followed by coupling them with nucleophilic sulfur (S) species (i.e., SO32- and HSO3-). Unlike many previous studies conducted under alkaline conditions, PET upcycling was performed over an amorphous MnO2 catalyst under near-neutral conditions, allowing for the stabilization of electrophilic intermediates. The compatibility of this strategy was further investigated by employing biomass-derived compounds as substrates. Moreover, comparable HMS yields can be achieved with real-world PET plastics, showing its enormous potential in practical application. Lastly, Density function theory (DFT) calculation reveals that the C-C cleavage step of EG is the rate-determining step (RDS), and amorphous MnO2 significantly decreases the energy barriers for both RDS and C-S coupling when compared to the crystalline counterpart.
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The progression and the metastatic potential of colorectal cancer (CRC) are intricately linked to the epithelial-mesenchymal transition (EMT) process. The present study harnesses the power of machine learning combined with multi-omics data to develop a risk stratification model anchored on EMT-associated genes. The aim is to facilitate personalized prognostic assessments in CRC. We utilized publicly accessible gene expression datasets to pinpoint EMT-associated genes, employing a CoxBoost algorithm to sift through these genes for prognostic significance. The resultant model, predicated on gene expression levels, underwent rigorous independent validation across various datasets. Our model demonstrated a robust capacity to segregate CRC patients into distinct high- and low-risk categories, each correlating with markedly different survival probabilities. Notably, the risk score emerged as an independent prognostic indicator for CRC. High-risk patients were characterized by an immunosuppressive tumor milieu and a heightened responsiveness to certain chemotherapeutic agents, underlining the model's potential in steering tailored oncological therapies. Moreover, our research unearthed a putative repressive interaction between the long non-coding RNA PVT1 and the EMT-associated genes TIMP1 and MMP1, offering new insights into the molecular intricacies of CRC. In essence, our research introduces a sophisticated risk model, leveraging machine learning and multi-omics insights, which accurately prognosticates outcomes for CRC patients, paving the way for more individualized and effective oncological treatment paradigms.
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Neoplasias Colorretais , Multiômica , Humanos , Prognóstico , Transição Epitelial-Mesenquimal/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Aprendizado de MáquinaRESUMO
Ferroptosis is associated with the occurrence and development of many diseases, which is the result of an imbalance in cellular metabolism and oxidation-reduction balance. Therefore, it is an effective therapeutic strategy that simultaneously regulating the intracellular oxidation-reduction system. Herein, a click reaction of alkynylamide with thiol groups in the presence of amine or in PBS (pH = 7.4) is developed, which can react efficiently with thiol substances, such as cysteine (Cys), glutathione (GSH), and bovine serum albumin (BSA). Notably, MBTB-PA, an aggregation-induced emission (AIE) photosensitizer with an alkynylamide unit, is synthesized and its intracellular behavior is visualized in situ by fluorescence imaging, demonstrating its excellent ability to target the endoplasmic reticulum. Furthermore, MBTB-PA reacted with proteins in tumor cells, consumed reducing substances, and triggered intracellular oxidative stress, resulting in cell death. Based on this reaction therapy strategy, click reaction is combined with photodynamic therapy to achieve effective killing of tumor cells by simultaneously raising the intracellular oxidative state and reducing the reductive state. This work not only develops an application of click reaction of alkynamide with thiol in bioconjugation and anti-tumor therapy, but also provides feasible ideas for organic reactions in the exploration of organisms.
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Química Click , Compostos de Sulfidrila , Compostos de Sulfidrila/química , Humanos , Linhagem Celular Tumoral , Animais , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
BACKGROUND AND AIMS: The Zhongshan colorectal endoscopic submucosal dissection (CR-ESD) score model was proposed to grade the technical difficulty of CR-ESD. The objective of this study was to prospectively validate and update the score model. METHODS: A multicenter prospective cohort analysis of CR-ESD was conducted. Individual data on patients, lesions, and outcomes of CR-ESD were used to validate the original model and further refine the difficulty of the prediction model. Data were randomly divided into discovery and internal validation cohorts. A multivariate Cox regression analysis was conducted on the discovery cohort to develop an updated risk-scoring system, which was then validated. RESULTS: Five hundred forty-eight patients with 565 colorectal lesions treated by ESD from 4 hospitals were included. In the prospective validation cohort, the area under the receiver-operating characteristic (ROC) curve for the original model was .707. Six risk factors were identified and assigned point values: tumor size (2 points for 30-50 mm, 3 points for ≥50 mm), at least two-thirds circumference of the lesion (3 points), tumor location in the cecum (2 points) or flexure (2 points), laterally spreading tumor-nongranular lesions (1 point), preceding biopsy sampling (1 point), and NBI International Colorectal Endoscopic type 3 (3 points). The updated model had an area under the ROC curve of .738 in the discovery cohort and of .782 in the validation cohort. Cases were categorized into easy (score = 0-1), intermediate (score = 2-3), difficult (score = 4-6), and very difficult (score ≥7) groups. Satisfactory discrimination and calibration were observed. CONCLUSIONS: The original model achieved an acceptable level of prediction in the prospective cohort. The updated model exhibited superior performance and can be used in place of the previous version. (Clinical trial registration number: ChiCTR2100047087.).
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Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Ressecção Endoscópica de Mucosa/efeitos adversos , Neoplasias Colorretais/patologia , Estudos Prospectivos , Estudos Retrospectivos , Estudos de Coortes , Resultado do TratamentoRESUMO
Spinal cord injury (SCI) is a complex problem in modern medicine. Fibroblast activation and fibroscarring after SCI impede nerve recovery. Non-coding RNA plays an important role in the progression of many diseases, but the study of its role in the progression of spinal fibrosis is still emerging. Here, we investigated the function of circular RNAs, specifically antisense to the cerebellar degeneration-related protein 1 (CDR1as), in spinal fibrosis and characterized its molecular mechanism and pathophysiology. The presence of CDR1as in the spinal cord was verified by sequencing and RNA expression assays. The effects of inhibition of CDR1as on scar formation, inflammation and nerve regeneration after spinal cord injury were investigated in vivo and in vitro. Further, gene expression of miR-7a-5p and protein expression of transforming Growth Factor Beta Receptor II (TGF-ßR2) were measured to evaluate their predicted interactions with CDR1as. The regulatory effects and activation pathways were subsequently verified by miR-7a-5p inhibitor and siCDR1as. These results indicate that CDR1as/miR-7a-5p/TGF-ßR2 interactions may exert scars and nerves functions and suggest potential therapeutic targets for treating spinal fibrotic diseases.
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Fibrose , MicroRNAs , RNA Circular , RNA Longo não Codificante , Transdução de Sinais , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/fisiopatologia , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Medula Espinal/metabolismo , Medula Espinal/patologia , Proteínas Smad/metabolismo , Proteínas Smad/genética , Regeneração Nervosa , Feminino , Masculino , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Camundongos Endogâmicos C57BL , Camundongos , Recuperação de Função FisiológicaRESUMO
PREMISE: Previous work searching for sexual dimorphism has largely relied on the comparison of trait mean vectors between sexes in dioecious plants. Whether trait scaling (i.e., the ratio of proportional changes in covarying traits) differs between sexes, along with its functional significance, remains unclear. METHODS: We measured 10 vegetative traits pertaining to carbon, water, and nutrient economics across 337 individuals (157 males and 180 females) of the diocious species Eurya japonica during the fruiting season in eastern China. Piecewise structural equation modeling was employed to reveal the scaling relationships of multiple interacting traits, and multivariate analysis of (co)variance was conducted to test for intersexual differences. RESULTS: There was no sexual dimorphism in terms of trait mean vectors across the 10 vegetative traits in E. japonica. Moreover, most relationships for covarying trait pairs (17 out of 19) exhibited common scaling slopes between sexes. However, the scaling slopes for leaf phosphorus (P) vs. nitrogen (N) differed between sexes, with 5.6- and 3.0-fold increases of P coinciding with a 10-fold increase of N in male and female plants, respectively. CONCLUSIONS: The lower ratio of proportional changes in P vs. N for females likely reflects stronger P limitation for their vegetative growth, as they require greater P investments in fruiting. Therefore, P vs. N scaling can be a key avenue allowing for sex-specific strategic optimization under unequal reproductive requirements. This study uncovers a hidden aspect of secondary sex character in dioecious plants, and highlights the use of trait scaling to understand sex-defined economic strategies.
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Nitrogênio , Fósforo , Folhas de Planta , Reprodução , Fósforo/metabolismo , Fósforo/análise , Nitrogênio/metabolismo , Folhas de Planta/fisiologia , Folhas de Planta/crescimento & desenvolvimento , China , Cyperaceae/fisiologia , Cyperaceae/crescimento & desenvolvimentoRESUMO
Experimental and numerical studies were performed on the vibrational energy relaxation in shock-heated CO/N2/Ar mixtures. A laser absorption technique was applied to the time-dependent rovibrational temperature time-history measurements. The vibrational relaxation data of reflected-shock-heated CO were summarized at 1720-3230 K. In shock-tube experiments, the rotational temperature of CO quickly reached equilibrium, whereas a relaxation process was found in the time-dependent vibrational temperature. For the mixture with 1.0% CO and 10.0% N2, the vibrational excitation caused a decrease in the macroscopic thermodynamic temperature of the test gas. In the simulations, the state-to-state (StS) approach was employed, where the vibrational energy levels of CO and N2 are treated as pseudo-species. The vibrational state-specific inelastic rate coefficients of N2-Ar collisions were calculated using the mixed quantum-classical method based on a newly developed three-dimensional potential energy surface. The StS predictions agreed well with the measurements, whereas deviations were found between the Schwartz-Slawsky-Herzfeld formula predictions and the measurements. The Millikan-White vibrational relaxation data of the N2-Ar system were found to have the most significant impact on the model predictions via sensitivity analysis. The vibrational relaxation data of the N2-Ar system were then modified according to the experimental data and StS results, providing an indirect way to optimize the vibrational relaxation data of a specific system. Moreover, the vibrational distribution functions of CO and N2 and the effects of the vibration-vibration-translation energy transfer path on the thermal nonequilibrium behaviors were highlighted.
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Citronella and Nutmeg are two common spices used for seasoning and medicinal purposes, both of which have significant economic value. This study aimed to investigate whether Citronella essential oil and Nutmeg essential oil (NEO) can ameliorate monosodium urate (MSU)-induced gouty arthritis in rats and the potential mechanisms. The results showed that CEO and NEO reduced swelling and redness at joint sites, inhibited neutrophil infiltration, and limited proinflammatory mediator secretion in mice with MSU-induced gouty arthritis. Based on the results of network pharmacology, molecular docking, and western blotting, CEO and NEO may exert anti-gouty arthritis effects by reducing the expression of reactive oxygen species and oxidative stress and downregulating the phosphorylation of the PI3K/AKT/mTOR signaling pathway, thereby inhibiting the production of the NLRP3 inflammasome and inhibiting the production of inflammatory cytokines. Therefore, these two essential oils show potential for use as adjuvant treatments for gouty arthritis in specific aromatherapy products or food seasonings.
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Artrite Gotosa , Proteína 3 que Contém Domínio de Pirina da Família NLR , Óleos Voláteis , Estresse Oxidativo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/metabolismo , Ratos , Masculino , Myristica/química , Ácido Úrico/metabolismo , Simulação de Acoplamento Molecular , Ratos Sprague-DawleyRESUMO
BACKGROUND: Pediatric patients undergoing liver transplantation are particularly susceptible to complications arising from intraoperative fluid management strategies. Conventional liberal fluid administration has been challenged due to its association with increased perioperative morbidity. This study aimed to assess the impact of intraoperative high-volume fluid therapy on pediatric patients who are undergoing living donor liver transplantation (LDLT). METHODS: Conducted at the Children's Hospital of Chongqing Medical University from March 2018 to April 2021, this retrospective study involved 90 pediatric patients divided into high-volume and non-high-volume fluid administration groups based on the 80th percentile of fluid administered. We collected the perioperative parameters and postoperative information of two groups. Multivariable logistic regression was utilized to assess the association between estimated blood loss (EBL) and high-volume FA. Kaplan-Meier survival analysis was used to compare patient survival after pediatric LDLT. RESULTS: Patients in the high-volume FA group received a higher EBL and longer length of stay than that in the non-high-volume FA group. Multivariate logistic regression analysis indicated that hours of maintenance fluids and fresh frozen plasma were significantly associated risk factors for the occurrence of EBL during pediatric LDLT. In addition, survival analysis showed no significant differences in one-year mortality between the groups. CONCLUSIONS: High-volume fluid administration during LDLT is linked with poorer intraoperative and postoperative outcomes among pediatric patients. These findings underscore the need for more conservative fluid management strategies in pediatric liver transplantations to enhance recovery and reduce complications.
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Hidratação , Cuidados Intraoperatórios , Transplante de Fígado , Doadores Vivos , Humanos , Masculino , Feminino , Hidratação/métodos , Estudos Retrospectivos , Pré-Escolar , Criança , Cuidados Intraoperatórios/métodos , Lactente , Resultado do Tratamento , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , AdolescenteRESUMO
Excessive ammonia nitrogen can potentially compromise the safety of drinking water. Therefore, developing a rapid and simple detection method for ammonia nitrogen in drinking water is of great importance. Nickel-copper hydroxides exhibit strong catalytic capabilities and are widely applied in ammonia nitrogen oxidation. In this study, a self-supported electrode made of nickel-copper carbonate hydroxide was synthesized on a carbon cloth collector via a straightforward one-step hydrothermal method for rapid ammonia nitrogen detection in water. It exhibits sensitivities of 3.9 µA µM-1 cm-2 and 3.13 µA µM-1 cm-2 within linear ranges of 1 µM to 100 µM and 100 µM to 400 µM, respectively, using a simple and rapid i-t method. The detection limit is as low as 0.62 µM, highlighting its excellent anti-interference properties against various anions and cations. The methodology's simplicity and effectiveness suggest broad applicability in water quality monitoring and environmental protection, particularly due to its significant cost-effectiveness.
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Pt-based electrochemical ammonia-nitrogen sensors played a significance role in real-time monitoring the ammonia-nitrogen concentration. The alloying of Pt and transition metals was one of the effective ways to increase the detectability of the sensitive electrode. In this paper, a self-supported electrochemical electrode for the detection of ammonia nitrogen was obtained by the electrodeposition of PtNi alloy nanoleaves on a carbon cloth (PtNi-CC). Experimental results showed that the PtNi-CC electrode exhibited enhanced detection performance with a wide linear range from 0.5 to 500 µM, high sensitivity (7.83 µA µM-1 cm-2 from 0.5 to 150 µM and 0.945 µA µM-1 cm-2 from 150 to 500 µM) and lower detection limit (24 nM). The synergistic effect between Pt and Ni and the smaller lattice spacing of the PtNi alloy were the main reasons for the excellent performance of the electrode. This work showed the great potential of Pt-based alloy electrodes for the detection of ammonia-nitrogen.
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As a common water pollutant, ammonia nitrogen poses a serious risk to human health and the ecological environment. Therefore, it is important to develop a simple and efficient sensing scheme to achieve accurate detection of ammonia nitrogen. Here, we report a simple fabrication electrode for the electrochemical synthesis of platinum-zinc alloy nanoflowers (PtZn NFs) on the surface of carbon cloth. The obtained PtZn NFs/CC electrode was applied to the electrochemical detection of ammonia nitrogen by differential pulse voltammetry (DPV). The enhanced electrocatalytic activity of PtZn NFs and the larger electrochemical active area of the self-supported PtZn NFs/CC electrode are conducive to improving the ammonia nitrogen detection performance of the sensitive electrode. Under optimized conditions, the PtZn NFs/CC electrode exhibits excellent electrochemical performance with a wide linear range from 1 to 1000 µM, a sensitivity of 21.5 µA µM-1 (from 1 µM to 100 µM) and a lower detection limit of 27.81 nM, respectively. PtZn NFs/CC electrodes show excellent stability and anti-interference. In addition, the fabricated electrochemical sensor can be used to detect ammonia nitrogen in tap water and lake water samples.
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PURPOSE: Vibrio vulnificus (V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. METHODS: An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. RESULTS: In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival (p = 0.014), reduced the serum creatinine (p = 0.002), urea nitrogen (p = 0.030), aspartate aminotransferase (p = 0.029), and alanine aminotransferase (p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1ß: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1ß, IL-6, TNF-α in liver (IL-1ß: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1ß: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid (p = 0.225), liver (p = 0.186), or kidney (p = 0.637). CONCLUSION: Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.
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Chuanxiong Rhizoma is a well-known Sichuan-specific herbal medicine. Its original plant, Ligusticum chuanxiong, has been cultivated asexually for a long time. L. chuanxiong has sexual reproductive disorders, which restricts its germplasm innovation. However, there is little research on the reproductive system of L. chuanxiong. This study is based on a comparative anatomical research approach, using morphological dissection, paraffin sectioning, staining and compression, and combined with scanning electron microscopy technology, to observe and compare the flowers, fruits, and seeds at various stages of reproductive growth of L. chuanxiong and its wild relative L. sinense. The results showed that the meiosis of pollen mother cells is abnormal in L. chuanxiong anthers, and the size and number of microspores are uneven and inconsistent in the tetrad stage. tapetum cells are not completely degenerated during anther development. During the pollen ripening stage, there are fine cracks in the anther wall, while most anthers could not release pollen normally. The surface of mature pollen grains is concave and partially deformed, and the pollens are all inactive and cannot germinate in vitro. The starch, polysaccharides, and lipids in the pollen were insufficient. The filaments of L. chuanxiong are short at the flowering stage and recurved downward. Double-hanging fruits were observed in the fruiting stage, being wrinkled; with shriveled seeds. Compared with L. sinense at the same stage, the anthers of L. sinense developed normally, and the pollen grains are vigorous and can germinate in vitro. The double-hanging fruits of L. sinense are full and normal; at the flowering period, the filaments are long and erect, significantly higher than the stigma. Mature blastocysts are visible in the ovary of both L. chuanxiong and L. sinense, and there is no significant difference in stigmas. The conclusion is that during the development of L. chuanxiong stamens, the meiosis of pollen mother cells is abnormal, and tetrad, tapetum, filament and other pollen structures develop abnormally. L. chuanxiong has the characteristic of male infertility, which is an important reason for its sexual reproductive disorders.
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Ligusticum , Reprodução , Pólen , Flores , PolissacarídeosRESUMO
Necroinflammation plays an important role in disease settings such as acute kidney injury (AKI). We and others have elucidated that prostaglandins, which are critically involved in inflammation, may activate E-prostanoid 3 receptor (EP3) at low concentrations. However, how EP3 blockade interacts with regulated cell death and affects AKI remains unknown. In this study, AKI was induced by ischemia-reperfusion (30 minutes/24 hours) in Ep3 knockout (Ep3-/-), bone marrow chimeric, myeloid conditional EP3 knockout and corresponding control mice. The production of prostaglandins E2 and I2 was markedly increased after ischemia-reperfusion, and either abrogation or antagonism of EP3 ameliorated the injury. EP3 deficiency curbed inflammatory cytokine release, neutrophil infiltration and serum high-mobility group box 1 levels, but additional TLR4 inhibition with TAK-242 did not offer further protection against the injury and inflammation. The protection of Ep3-/- was predominantly mediated by suppressing Mixed Lineage Kinase domain-Like-dependent necroptosis, resulting from the inhibition of cytokine generation and the switching of cell death modality from necroptosis to apoptosis through caspase-8 up-regulation, in part due to the restraint of IL-6/JAK2/STAT3 signaling. EP3 deficiency failed to further alleviate the injury when necroptosis was inhibited. Ep3-/- in bone marrow-derived cells, particularly that in myeloid cells, protected kidneys to the same extent as that of global EP3 deletion. Thus, our results demonstrate that EP3 deficiency especially that on myeloid cells, ameliorates ischemic AKI via curbing inflammation and breaking the auto-amplification loop of necroinflammation. Hence, EP3 may be a promising target for the prevention and/or treatment of AKI.
Assuntos
Injúria Renal Aguda , Animais , Camundongos , Injúria Renal Aguda/genética , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/metabolismo , Apoptose/fisiologia , Isquemia/metabolismo , Rim/metabolismo , Prostaglandinas/metabolismo , Inflamação/metabolismo , Células Mieloides/metabolismo , Citocinas/metabolismo , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Arbuscular mycorrhizal fungi (AMF) form symbiotic relationships with various terrestrial plants and have attracted considerable interest as biofertilizers for improving the quality and yield of medicinal plants. Despite the widespread distribution of AMFs in Salvia miltiorrhiza Bunge's roots, research on the impact of multiple AMFs on biomass and active ingredient accumulations has not been conducted. In this study, the effects of five native AMFs (Glomus formosanum, Septoglomus constrictum, Rhizophagus manihotis, Acaulospora laevis, and Ambispora gerdemannii) and twenty-six communities on the root biomass and active ingredient concentrations of S. miltiorrhiza were assessed using the total factor design method. RESULTS: Thirty-one treatment groups formed symbiotic relationships with S. miltiorrhiza based on the pot culture results, and the colonization rate ranged from 54.83% to 89.97%. AMF communities had higher colonization rates and total phenolic acid concentration than single AMF, and communities also appeared to have higher root fresh weight, dry weight, and total phenolic acid concentration than single inoculations. As AMF richness increased, there was a rising trend in root biomass and total tanshinone accumulations (ATTS), while total phenolic acid accumulations (ATP) showed a decreasing trend. This suggests that plant productivity was influenced by the AMF richness, with higher inoculation benefits observed when the communities contained three or four AMFs. Additionally, the affinities of AMF members were also connected to plant productivity. The inoculation effect of closely related AMFs within the same family, such as G. formosanum, S. constrictum, and R. manihotis, consistently yielded lower than that of mono-inoculation when any combinations were applied. The co-inoculation of S. miltiorrhiza with nearby or distant AMFs from two families, such as G. formosanum, R. manihotis, and Ac. laevis or Am. gerdemannii resulted in an increase of ATP and ATTS by more than 50%. AMF communities appear to be more beneficial to the yield of bioactive constituents than the single AMF, but overall community inoculation effects are related to the composition of AMFs and the relationship between members. CONCLUSION: This study reveals that the AMF community has great potential to improve the productivity and the accumulation of bioactive constituents in S. miltiorrhiza, indicating that it is an effective way to achieve sustainable agricultural development through using the AMF community.
Assuntos
Micorrizas , Plantas Medicinais , Salvia miltiorrhiza , Humanos , Plantas Medicinais/microbiologia , Raízes de Plantas , Fungos , Trifosfato de AdenosinaRESUMO
The formation of nanoaggregates makes a great difference to the improvement of photodynamic therapy (PDT) performance to some extent, but constructing stable aggregates with a clear structure is simultaneously a big challenge for us. Herein, just by electrostatic interaction, cationic 2PAHs and anionic FBA351, regarded as acceptor (A) and donor (D), respectively, are utilized to prepare stable aggregate of ionic-bonds coupled polymer (ICP) with repeated "D-A" structure, which is fully characterized by nuclear magnetic resonance (NMR), time-of-flight mass spectrometry, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). Remarkably, aggregate ICP with multiple "D-A" structures showed enhanced photosensitization efficiency over its precursor 2PAHs and FBA351, which is in accord with the image-guided photodynamic anticancer therapy. Such results not only offer a simple way to obtain stable aggregate but also give us a guideline to design efficient photosensitizers.