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Extracellular vesicles (EVs), secreted by most cells, act as natural cell-derived carriers for delivering proteins, nucleic acids, and organelles between cells. Mitochondria are highly dynamic organelles responsible for energy production and cellular physiological processes. Recent evidence has highlighted the pivotal role of EVs in intercellular mitochondrial content transfer, including mitochondrial DNA (mtDNA), proteins, and intact mitochondria. Intriguingly, mitochondria are crucial mediators of EVs release, suggesting an interplay between EVs and mitochondria and their potential implications in physiology and pathology. However, in this expanding field, much remains unknown regarding the function and mechanism of crosstalk between EVs and mitochondria and the transport of mitochondrial EVs. Herein, we shed light on the physiological and pathological functions of EVs and mitochondria, potential mechanisms underlying their interactions, delivery of mitochondria-rich EVs, and their clinical applications in regenerative medicine.
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Vesículas Extracelulares , Mitocôndrias , Medicina Regenerativa , Humanos , Vesículas Extracelulares/metabolismo , Medicina Regenerativa/métodos , Mitocôndrias/metabolismo , AnimaisRESUMO
Excessive acetaminophen (APAP) can induce neutrophil activation and hepatocyte death. Along with hepatocyte dysfunction and death, NETosis (a form of neutrophil-associated inflammation) plays a vital role in the progression of acute liver injury (ALI) induced by APAP overdose. It has been shown that activated neutrophils tend to migrate towards the site of injury and participate in inflammatory processes via formation of neutrophil extracellular traps (NETs). In this study we investigated whether NETs were involved in hepatocyte injury and contributed to APAP-induced ALI progression. ALI mouse model was established by injecting overdose (350 mg/kg) of APAP. After 24 h, blood and livers were harvested for analyses. We showed that excessive APAP induced multiple programmed cell deaths of hepatocytes including pyroptosis, apoptosis and necroptosis, accompanied by significantly increased NETs markers (MPO, citH3) in the liver tissue and serum. Preinjection of DNase1 (10 U, i.p.) for two consecutive days significantly inhibited NETs formation, reduced PANoptosis and consequently alleviated excessive APAP-induced ALI. In order to clarify the communication between hepatocytes and neutrophils, we induced NETs formation in isolated neutrophils, and treated HepaRG cells with NETs. We found that NETs treatment markedly increased the activation of GSDMD, caspase-3 and MLKL, while pre-treatment with DNase1 down-regulated the expression of these proteins. Knockdown of AIM2 (a cytosolic innate immune receptor) abolished NETs-induced PANoptosis in HepaRG cells. Furthermore, excessive APAP-associated ALI was significantly attenuated in AIM2KO mice, and PANoptosis occurred less frequently. Upon restoring AIM2 expression in AIM2KO mice using AAV9 virus, both hepatic injury and PANoptosis was aggravated. In addition, we demonstrated that excessive APAP stimulated mtROS production and mitochondrial DNA (mtDNA) leakage, and mtDNA activated the TLR9 pathway to promote NETs formation. Our results uncover a novel mechanism of NETs and PANoptosis in APAP-associated ALI, which might serve as a therapeutic target.
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Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Proteínas de Ligação a DNA , Armadilhas Extracelulares , Hepatócitos , Camundongos Endogâmicos C57BL , Neutrófilos , Animais , Acetaminofen/toxicidade , Acetaminofen/efeitos adversos , Armadilhas Extracelulares/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Camundongos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Humanos , Camundongos Knockout , Piroptose/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Analgésicos não Narcóticos/toxicidadeRESUMO
In this paper, we present a high-precision optical frequency noise detection and comparison technique using a two-way transfer method over a 260 km field fiber link. This method allows for the comparison of optical frequencies between remote optical references without the need for data transfer through communication. We extend a previously established two-way comparison technique to obtain all data at the local site. Two optical carrier signals are injected into the bidirectional fiber from both ends, and one carrier is reflected back from the remote end. This enables the phase comparison of the two carrier signals at a single site without the need to transmit experimental data. The common-mode frequency noise induced by the bidirectional fiber link is detected and effectively suppressed without the need for sophisticated active fiber noise control. Our demonstration system, which uses a 260 km field fiber link and a common laser source, achieves a fractional instability of 2.5×10-17 at 1 s averaging time and scales down to 3.5×10-21 at 8000 s. This scheme offers the distinct advantage of completing the comparison at a single site, eliminating the need for remote data transfer via communication. This method is expected to enhance reliability for high-precision frequency comparisons between remote optical clocks and advanced atomic clocks.
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AIM: The aryl hydrocarbon receptor (AhR)-ligand axis has been shown to be involved in inflammatory diseases and bone homeostasis. However, the activation of AhR signalling pathway and the possible functions of AhR ligands in periodontitis are underexplored. This study investigated the expression of the AhR target gene cytochrome P450 subfamily B member 1 (CYP1B1) and the functions and mechanisms of the AhR ligand 6 formylindolo[3,2-b]carbazole (FICZ) in periodontitis. MATERIALS AND METHODS: CYP1B1 expression was detected in human periodontitis samples, mice with ligature-induced periodontitis and lipopolysaccharide (LPS)-induced inflammation in periodontal ligament cells (PDLCs) in vitro. FICZ was administered topically or systemically. The therapeutic functions of FICZ were detected via qPCR, micro-computed tomography and immunohistochemistry. Finally, the mechanisms of AhR signalling in periodontitis were investigated by cell assays. RESULTS: CYP1B1 expression was downregulated in periodontitis. FICZ rescued the alveolar bone loss and mitigated the inflammatory cytokines in periodontitis mice. In vitro, FICZ pre-treatment reduced the LPS-induced inflammation in PDLCs via the increased phosphorylation of STAT3. Additionally, FICZ prompted the mineralization of PDLCs via activation of the Wnt/ß-catenin signalling pathway. CONCLUSION: AhR signalling pathway is suppressed in periodontitis and the AhR ligand FICZ can prevent periodontitis.
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Perda do Osso Alveolar , Periodontite , Animais , Humanos , Inflamação , Camundongos , Receptores de Hidrocarboneto Arílico , Microtomografia por Raio-XRESUMO
BACKGROUND/AIMS: Pancreatic cancer is an aggressive malignancy as a result of highly metastatic potential. The current study was carried out to alter the expression of LINC01121 in pancreatic cancer, with the aim of elucidating its effects on the biological processes of cell proliferation, migration, invasion, and apoptosis. We hypothesized that both the GLP1R gene and cAMP/PKA signaling pathway participate in the aforementioned process. METHODS: Microarray data (GSE14245, GSE27890 and GSE16515) and annotating probe files linked to pancreatic cancer were downloaded through the GEO database. The Multi Experiment Matrix (MEM) site was used to predict the target gene of lncRNA. Both pancreatic cancer tissues (n = 56) and paracancerous tissues (n = 45) were collected from patients diagnosed with pancreatic cancer. Immunohistochemistry was applied to identify the positive expression rate of GLP1R protein. Isolated pancreatic cancer cells and PANC-1 cells were independently classified into the blank, negative control (NC), LINC01121 vector, siRNA-LINC01121, siRNA-GLP1R and siRNA-LINC01121 + siRNA-GLP1R groups. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were applied to detect the expressions of LINC01121, GLP1R, cAMP, PKA, CREB, Bcl-2, Bad and PCNA. Cell proliferation, migration, invasion, cycle progression, and apoptosis were examined by MTT assay, scratch test, Transwell assay and flow cytometry analyses of Annexin V-FITC/PI staining. RESULTS: Observations were made indicating that LINC01121 was highly expressed, while low expressions of GLP1R in pancreatic cancer were detected based on microarray data, which was largely in consistent with the data collected of LINC01121 and GLP1R within the tissues. The target prediction program and luciferase activity analysis was testament to the notion suggesting that GLP1R was indeed a target of LINC01121. In contrast to the blank and NC groups, the LINC01121 vector group exhibited increased expressions of LINC01121; decreased mRNA and protein levels of GLP1R, Bad, cAMP, and PKA; increased protein levels of CREB, Bcl-2, PCNA, p-PKA and p-CREB; increased cell proliferation, migration and invasion; and decreased cell apoptosis. There was no significant difference detected among the blank, NC, and siRNA-LINC01121 + siRNA-GLP1R groups, except that decreased LINC01121 expression was determined in the siRNA-LINC01121 + siRNA-GLP1R group. Parallel data were observed in the pancreatic cancer cells and PANC-1 cells. CONCLUSION: The current study presents evidence indicating that LINC01121 might inhibit apoptosis while acting to promote proliferation, migration, and invasion of pancreatic cancer cells, supplementing the stance held that LINC01121 functions as a tumor promoter by means of its involvement in the process of translational repression of the GLP1R and inhibition of the cAMP/PKA signaling pathway.
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Apoptose , Movimento Celular , Proliferação de Células , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Sistemas do Segundo Mensageiro , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/patologiaRESUMO
Three new sesquiterpenes of canusesnol K (1), canusesnol L (2) and 12, 15-dihydroxycurcumene (3), along with five known ones (4-8), were isolated from the heartwood extract of Pterocarpus santalinus. Their structures were established by extensive analyses of 1D and 2D NMR spectroscopy, including 1H NMR, 13C NMR, HSQC, HMBC and NOESY, and HRESI-MS. The absolute configurations of the new compounds were established with Modified Mosher's method. The cytotoxic activities of all these compounds against HepG2 (human liver cancer), MCF-7 (human breast cancer), MDA-MB-231 (human breast cancer), and Hela (human cervical carcinoma) cancer cell lines were evaluated. Compound 1 exhibited moderate cytotoxic activity toward MDA-MB-231 cell lines.
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Antineoplásicos Fitogênicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Pterocarpus/química , Sesquiterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células HeLa , Células Hep G2 , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Background: Bladder cancer is a common urinary tract malignancy. Minimally invasive radical cystectomy has shown oncological outcomes comparable to the conventional open surgery and with advantages over the open procedure. However, outcomes of the two main minimally invasive procedures, robot-assisted and pure laparoscopic, have yet to be compared. This study aimed to compare in-hospital outcomes between these two techniques performed for patients with bladder cancer. Methods: This population-based, retrospective study included hospitalized patients aged ≥ 50 years with a primary diagnosis of bladder cancer who underwent robot-assisted or pure laparoscopic radical cystectomy. All patient data were extracted from the US National Inpatient Sample (NIS) database 2008-2018 and were analyzed retrospectively. Primary outcomes were in-hospital mortality, prolonged length of stay (LOS), and postoperative complications. Results: The data of 3284 inpatients (representing 16,288 US inpatients) were analyzed. After adjusting for confounders, multivariable analysis revealed that patients who underwent robot-assisted radical cystectomy had a significantly lower risk of in-hospital mortality (adjusted OR [aOR], 0.50, 95% CI: 0.28-0.90) and prolonged LOS (aOR, 0.63, 95% CI: 0.49-0.80) than those undergoing pure laparoscopic cystectomy. Patients who underwent robot-assisted radical cystectomy had a lower risk of postoperative complications (aOR, 0.69, 95% CI: 0.54-0.88), including bleeding (aOR, 0.73, 95% CI: 0.54-0.99), pneumonia (aOR, 0.49, 95% CI: 0.28-0.86), infection (aOR, 0.55, 95% CI: 0.36-0.85), wound complications (aOR, 0.33, 95% CI: 0.20-0.54), and sepsis (aOR, 0.49, 95% CI: 0.34-0.69) compared to those receiving pure laparoscopic radical cystectomy. Conclusions: Patients with bladder cancer, robot-assisted radical cystectomy is associated with a reduced risk of unfavorable short-term outcomes, including in-hospital mortality, prolonged LOS, and postoperative complications compared to pure laparoscopic radical cystectomy.
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BACKGROUND: To explore the role of leukemia inhibitory factor (LIF) in periodontitis via in vivo and in vitro experiments. METHODS: The second upper molar of LIF knockout mice and their wild-type littermates were ligated for 8 days. Micro-computed tomography (micro-CT), histological analysis, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. The expression levels of proinflammatory cytokines were examined in mouse bone marrow derived macrophages and human periodontal ligament fibroblasts (HPDLFs) after lipopolysaccharide (LPS) treatment. RESULTS: LIF deficiency promoted alveolar bone loss, inflammatory cells infiltration, osteoclasts formation and collagen fiber degradation in ligature-induced mouse, along with higher expressions of proinflammatory cytokines, including interleukin-6 (IL6), IL-1ß (IL1B), tumor necrosis factor-α (TNFA), matrix metalloproteinase 13 (MMP13), and RANKL/OPG ratio. Additionally, LIF deletion led to higher expression levels of these proinflammatory cytokines in mouse bone marrow-derived macrophages from both femur and alveolar bone and HPDLFs when treated with LPS. Administration of recombined LIF attenuated TNFA, IL1B, and RANKL/OPG ratio in HPDLFs. CONCLUSIONS: These findings indicate that LIF deficiency promotes the progress of periodontitis via modulating immuno-inflammatory responses of macrophages and periodontal ligament fibroblasts, and the application of LIF may be an adjunctive treatment for periodontitis to resolute inflammation.
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Lithium ion capacitors (LICs) are a new generation of energy storage devices that combine the super energy storage capability of lithium ion batteries with the satisfactory power density of supercapacitors. The development of high-performance LICs still faces great challenges due to the unbalanced reaction kinetics at the anode and cathode. Therefore, it is an inevitable need to enhance the electron/ion transfer capability of the anode materials. In this paper, to obtain a superior-rate and high-capacity Ni3S2-based anode, highly conductive Ti3C2Tx MXene sheets were introduced to sever as the carrier of Ni3S2 nanoparticles and simultaneously an amorphous carbon layer which coats onto the surface of Ni3S2 nanoparticles was in-situ generated by the carbonization of dopamine reactant. The as-synthesized Ni3S2/Ti3C2Tx/C composite exhibits a high specific surface area (112.6 m2/g) because of the addition of Ti3C2Tx that can reduce the aggregation of Ni3S2 nanoparticles and the in-situ generated amorphous carbon layer that can suppress the growth of Ni3S2 nanoparticles. The Ni3S2/Ti3C2Tx/C anode possesses a remarkable reversible discharge specific capacity (626.0 mAh/g under 0.2 A/g current density), which increases to 1150.8 mAh/g after 400-cycle charge/discharge measurement at the same measurement condition indicating eminent cyclability, along with superior rate capability. To construct a superior-performance LIC device, a sterculiae lychnophorae derived porous carbon (SLPC) cathode with an average discharge specific capacity of 73.4 mAh/g@0.1A/g was prepared. The Ni3S2/Ti3C2Tx/C//SLPC LIC device with optimal cathode/anode mass ratio has a satisfactory energy density ranging from 32.8 to 119.1 Wh kg-1 at the corresponding power density of 8799.4 to 157.5 W kg-1, together with a prominent capacity retention (95.5 %@1 A/g after 10,000 cycles).
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OBJECTIVES: Bone marrow-derived mesenchymal stem cells (BMSCs) - based tissue engineering is an important strategy for treatment of bone defects. However, the ischemia environment limits the survival and biological functions of BMSCs. The present study aimed to investigate the effect of leukemia inhibitory factor (LIF) on the apoptosis of BMSCs induced by hypoxia and serum-deprivation (H&SD) as well as the underlying pathway mechanism. METHODS: Mitochondrial membrane potential (MMP) was determined by flow cytometry. The apoptotic phenomenon of nuclear morphology was detected by fluorescence microscope. The ratio of apoptotic BMSCs was investigated by Annexin V/propidium iodide (PI) double staining and flow cytometric analysis. The expression of apoptosis-related molecules was detected by quantitative polymerase chain reaction (qPCR) and western blotting. RESULTS: H&SD treatment induced a series of apoptotic phenotypes, including the downregulation of MMP, the apoptotic phenomenon of nuclear morphology, the increased rate of BMSCs at early and late apoptotic stage, and the reduced B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X (Bax) ratio. Administration of recombinant LIF alleviated the apoptosis of BMSCs induced by H&SD, which was reflected in recovery of MMP, morphology of nuclei, rate of apoptotic cells and inhibition of cleaved Caspase-3. The results of western blot demonstrated that phosphorylation of janus kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3 was inhibited by H&SD treatment, which was upregulated by LIF administration. JAK1-specific inhibitor GLPG0634 or STAT3-specific inhibitor S3I-201 eliminated the protective effects of LIF on the apoptosis of BMSCs. CONCLUSION: These data indicated that LIF played a protective role in apoptosis of BMSCs induced by ischemia via activating JAK1/STAT3 signaling pathway.
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Ternary metal sulfides employed in supercapacitors exhibit better electrochemical performances than their counterpart oxides due to their superior conductivity. However, the insertion/extraction of electrolyte ions can lead to a significant volume change in electrode materials, which can result in poor cycling stability. Herein, novel amorphous Co-Mo-S nanospheres were fabricated through a facile room-temperature vulcanization method. It involves the conversion of crystalline CoMoO4 by reacting it with Na2S at room temperature. In addition to the conversion of the crystalline state into an amorphous structure with more grain boundaries, which is beneficial for the transport of electron/ion and can accommodate the volume change generated by the insertion/extraction of electrolyte ions, the production of more pores led to an increased specific surface area. The electrochemical results indicate that the as-prepared amorphous Co-Mo-S nanospheres had a specific capacitance of up to 2049.7F/g@1 A/g together with good rate capability. The amorphous Co-Mo-S nanospheres can be used as the cathode of supercapacitors and assembled with an activated carbon anode into an asymmetric supercapacitor possessing a satisfactory energy density of 47.6 Wh kg-1@1012.9 W kg-1. One of the prominent features exhibited by this asymmetric device is its remarkable cyclic stability, with a capacitance retention of 107% after 10,000 cycles.
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Lamellar bone, compactly and ingeniously organized in the hierarchical pattern with 6 ordered scales, is the structural motif of mature bone. Each hierarchical scale exerts an essential role in determining physiological behavior and osteogenic bioactivity of bone. Engineering lamellar bone with full-scale hierarchy remains a longstanding challenge. Herein, using bioskiving and mineralization, we attempt to engineer compact constructs resembling full-scale hierarchy of lamellar bone. Through systematically investigating the effect of mineralization on physicochemical properties and bioactivities of multi-sheeted collagen matrix fabricated by bioskiving, the hierarchical mimicry and hierarchy-property relationship are elucidated. With prolongation of mineralization, hierarchical mimicry and osteogenic bioactivity of constructs are performed in a bidirectional manner, i.e. first rising and then descending, which is supposed to be related with transformation of mineralization mechanism from nonclassical to classical crystallization. Construct mineralized 9 days can accurately mimic each hierarchical scale and efficiently promote osteogenesis. Bioinformatic analysis further reveals that this construct potently activates integrin α5-PI3K/AKT signaling pathway through mechanical and biophysical cues, and thereby repairing critical-sized bone defect. The present study provides a bioinspired strategy for completely resembling complex hierarchy of compact mineralized tissue, and offers a critical research model for in-depth studying the structure-function relationship of bone.
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BACKGROUND: The aim of this study is to evaluate the impact of intraoperative allograft vascular flow on early kidney graft function. METHODS: A total of 159 patients underwent kidney transplantation from January 2017 to March 2022 at Linkou Chang Gung Memorial Hospital. Graft arterial and venous blood flow was measured separately with a transient time flowmeter (Transonic HT353; Transonic Systems, Inc, Ithaca, NY, United States) after ureteroneocystostomy. The early outcomes, including the postoperative creatinine level, were analyzed accordingly. RESULTS: There were 83 males and 76 females, with a mean age of 44.5 years. The mean graft arterial flow measured was 480.6 mL/min, and the mean venous flow was 506.2 mL/min. Delayed graft function (DGF) incidence was 36.5%, 32.5%, and 40.8% in total, living, and deceased donor groups, respectively. Living donor and deceased donor kidney transplantation were analyzed separately. In the DGF subgroup, there were lower graft venous flows, higher body mass index (BMI), and more male patients in the living kidney transplant group. Similarly, the deceased donor kidney transplantation group with delayed graft function tended to have higher body height, higher body weight, higher BMI, and more diabetes mellitus. The multivariate analysis showed that lower graft venous blood flow (odds ratio [OR] = 0.995, P = .008) and higher BMI (OR = 1.144, P = .042) were significantly correlated with delayed graft function in living donor kidney transplantations. In the deceased donor group, a multivariate analysis of risk factors showed that BMI had a significant correlation with delayed graft function (OR = 1.41, P = .039). CONCLUSIONS: Graft venous blood flow was significantly associated with delayed graft function in living donor kidney transplantation, and high BMI was correlated with DGF in all patients receiving kidney transplantation.
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Função Retardada do Enxerto , Sobrevivência de Enxerto , Feminino , Humanos , Masculino , Adulto , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/epidemiologia , Rejeição de Enxerto/epidemiologia , Estudos Retrospectivos , Doadores de Tecidos , Doadores Vivos , Fatores de RiscoRESUMO
Background: Standard treatments for nonparasitic hepatic cysts (NPHCs) include laparoscopic deroofing (LD), percutaneous aspiration, and alcohol sclerotherapy. However, these treatments have limitations. LD and alcohol sclerotherapy, for example, fail to prevent NPHC recurrences, although alcohol sclerotherapy is satisfactorily effective in treating small cysts (diameter <5 cm), which do not usually need treatment. The present study introduces a novel surgical procedure, laparoscopic enucleation with intact cyst (LEIC), which may prevent postoperative cyst recurrence. Materials and Methods: In this study, we enrolled 14 patients, with NPHCs larger than 9 cm in diameter, who underwent LEIC. Dissection and coagulation were performed using the harmonic shear enucleation and bipolar coagulation techniques. We attempted to completely remove the cysts intact. Results: For all patients, symptoms disappeared after complete elimination of the cyst capsule. No complications (hemorrhage or bile leakage) were found during the perioperative period. The mean follow-up period was 19.3 months (range 10-38 months), during which no recurrences or complications were noted. Conclusions: LEIC is a novel surgical approach that shows satisfactory efficacy and safety in patients with large, surficial, and symptomatic NPHCs. LEIC's main advantage is that it can efficiently prevent cyst recurrence and decrease postoperative morbidity. However, its long-term efficacy and safety require further verification, especially with huge cysts.
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Cistos/cirurgia , Laparoscopia/métodos , Hepatopatias/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
In the title coordination polymer, [La(2)(C(8)H(4)O(4))(3)(H(2)O)(2)](n), there are two independent La(III) atoms which are coordinated differently in slightly distorted penta-gonal-bipyramidal and slightly disorted bicapped trigonal-prismatic environments. The La(III) ions are bridged by µ(4)-isophthalate ligands, forming two-dimensional layers. In the crystal structure, these layers are connected by inter-molecular O-Hâ¯O hydrogen bonds into a three-dimensional network.
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In the title compound, {[Ag(2)Gd(C(6)H(4)NO(2))(4)(H(2)O)(2)]NO(3)·H(2)O}(n), the Gd(III) ion is coordinated by eight O atoms from six isonicotinate ligands and two water mol-ecules in a distorted square anti-prismatic geometry. Two Ag(I) ions are each bonded to two N atoms from two isonicotinate ligands in a linear or bow-like fashion [N-Ag-N angles = 178.6â (2) and 147.1â (2)°]. These metal ions are connected by the isonicotin-ate ligands into a layer parallel to (010). O-Hâ¯O hydrogen bonds donated by the coordinated and uncoordinated water mol-ecules and intra-layer π-π stacking inter-actions between the pyridine rings [centroid-centroid distances = 3.551â (4) and 3.555â (4)â Å] are observed. The layers inter-act with each other by inter-layer Agâ¯O(aqua) contacts [2.731â (4)â Å] and π-π stacking inter-actions between the pyridine rings [centroid-centroid distances = 3.466â (3) and 3.516â (3)â Å], resulting in the formation of a three-dimensional supra-molecular structure.
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China is now the largest and only producer of avermectin in the world. However, its current yield is still lower than other similar antibiotics. Therefore, we studied the effect of nitrogen on the growth and the synthesis ability of B1a to improve the overall yield. Nitrogen had significant effects on the cell activity, PMV of Streptomyces avermitilis and the synthesis of B1a in the middle and later phase of fermentation. Additional feeding yeast powder based on carbon-dioxide evolution rate in a 100-L bioreactor significantly improved the synthesis of B1a. The production of avermectin reached 8 697 mg/L, 26.9% higher than the original process. In short, this study will serve in production enhancement of avermectin at industrial production.
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Fermentação , Carbono , Dióxido de Carbono , China , Ivermectina/análogos & derivados , NitrogênioRESUMO
BACKGROUND: Giant multilocular cystadenoma (GMC) of the prostate gland is a very rare benign tumor. Although the benign nature has been known, complete surgical excision is the major treatment consensus because of its high recurrence rate. We report a rare case of GMC with accompanying lower urinary tract symptoms and repeated urine retention initially thought to be symptoms of benign prostatic hyperplasia, which was treated with robot-assisted laparoscopic radical prostatectomy. CASE SUMMARY: A 65-year-old man presented with a 2-year history of lower urinary tract symptoms that had deteriorated gradually within the previous six months, even though he had received treatment with a selective alpha-blocking agent. He had undergone two transurethral resections of the prostate (TURP) at a local hospital during a 4-mo interval because initial ultrasound imaging and prostatic core needle biopsy showed benign prostate hyperplasia. Upon the third recurrence, the patient underwent TURP with a green-light laser at our institution. The diagnosis was a tumor composed of variously sized dilated glandular and cystic structures lined by blended prostatic type epithelia positive for prostate-specific antigen; the final diagnosis was giant multilocular cystadenoma. Magnetic resonance imaging showed a large multilocular retrovesical mass 8.0 cm × 7.3 cm × 6.4 cm, with heterogeneous enhancement. A coexisting malignant part could not be excluded. Considering the high recurrence rate, risk of coexisting malignancy, and possible sequelae of open surgery for radical excision, the patient decided to undergo robot-assisted radical prostatectomy, with good outcomes at the 2-year follow-up. CONCLUSION: Robot-assisted surgery for the treatment of prostate GMC provides another choice for simultaneous attention to disease-control and postoperative quality of life.
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Sympathetic outflow is increased in hypertension. The aim of the present study was to investigate whether the cardiac sympathetic afferent reflex (CSAR) is enhanced in two-kidney one-clip (2K1C) renovascular hypertensive rats, and whether the enhanced CSAR contributes, in part, to the increased sympathetic outflow. Furthermore, the role of central angiotensin II type 1 (AT(1)) receptors in mediating the CSAR was determined. Under urethane and alpha-chloralose anaesthesia, the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic denervated and cervical vagotomized rats. The CSAR was evaluated by the response of RSNA and MAP to epicardial application of 1.0 nmol of capsaicin. Compared with sham-operated rats, the CSAR, baseline RSNA and plasma noradrenaline level were significantly enhanced in 2K1C rats. Intrapericardial administration of resiniferatoxin, which abolishes the CSAR because of the desensitization of transient receptor potential vanilloid 1-containing cardiac afferent fibres, decreased the RSNA and MAP. The enhanced CSAR in 2K1C rats was normalized by intracerebroventricular administration of the AT(1) receptor antagonist losartan. Intracerebroventricular administration of angiotensin II further potentiated the enhanced CSAR in 2K1C rats, a response which was abolished by pretreatment with losartan. These results indicate that the CSAR is enhanced in 2K1C rats and the enhanced CSAR contributes, in part, to the sympathetic activation and hypertension. Central AT(1) receptors are involved in the enhanced CSAR in 2K1C rats.
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Reflexo/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Angiotensina II/fisiologia , Animais , Coartação Aórtica/fisiopatologia , Hipertensão Renovascular/fisiopatologia , Injeções Intravenosas , Injeções Intraventriculares , Losartan/administração & dosagem , Losartan/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/fisiologia , Reflexo/efeitos dos fármacosRESUMO
In the centrosymmetric dimeric title compound, [Cu(2)(C(3)H(6)NS(2))(4)], the Cu(II) atom is five-coordinate in a square-pyramidal environment. The basal coordination positions are occupied by four S atoms from two dimethyl-dithio-carbamate ligands and the apical coordination position is occupied by an S atom also bonded to the other Cu atom.