ABSTRACT
Effective antitumour immunity depends on the orchestration of potent T cell responses against malignancies1. Regression of human cancers has been induced by immune checkpoint inhibitors, T cell engagers or chimeric antigen receptor T cell therapies2-4. Although CD8 T cells function as key effectors of these responses, the role of CD4 T cells beyond their helper function has not been defined. Here we demonstrate that a trispecific antibody to HER2, CD3 and CD28 stimulates regression of breast cancers in a humanized mouse model through a mechanism involving CD4-dependent inhibition of tumour cell cycle progression. Although CD8 T cells directly mediated tumour lysis in vitro, CD4 T cells exerted antiproliferative effects by blocking cancer cell cycle progression at G1/S. Furthermore, when T cell subsets were adoptively transferred into a humanized breast cancer tumour mouse model, CD4 T cells alone inhibited HER2+ breast cancer growth in vivo. RNA microarray analysis revealed that CD4 T cells markedly decreased tumour cell cycle progression and proliferation, and also increased pro-inflammatory signalling pathways. Collectively, the trispecific antibody to HER2 induced T cell-dependent tumour regression through direct antitumour and indirect pro-inflammatory/immune effects driven by CD4 T cells.
Subject(s)
Breast Neoplasms , Animals , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , CD28 Antigens/metabolism , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Female , Humans , Mice , Receptor, ErbB-2/geneticsABSTRACT
BACKGROUND: Bone morphogenetic protein 9 (BMP9) is a hepatokine that plays a pivotal role in the progression of liver diseases. Moreover, an increasing number of studies have shown that BMP9 is associated with hepatopulmonary syndrome (HPS), but its role in HPS is unclear. Here, we evaluated the influence of CBDL on BMP9 expression and investigated potential mechanisms of BMP9 signalling in HPS. METHODS: We profiled the circulating BMP9 levels in common bile duct ligation-induced HPS rat model, and then investigated the effects and mechanisms of HPS rat serum on pulmonary vascular endothelial dysfunction in rat model, as well as in primarily cultured rat pulmonary microvascular endothelial cells. RESULTS: Our data revealed that circulating BMP9 levels were significantly increased in the HPS rats compared to control group. Besides, the elevated BMP9 in HPS rat serum was not only crucial for promoting endothelial cell proliferation and tube formation through the activin receptor-like kinase1 (ALK1)-Endoglin-Smad1/5/9 pathway, but also important for accumulation of monocytes. Treatments with ALK1-Fc or silencing ALK1 expression to inhibit the BMP9 signalling pathway effectively eliminated these effects. In agreement with these observations, increased circulating BMP9 was associated with an increase in lung vessel density and accumulation of pro-angiogenic monocytes in the microvasculature in HPS rats. CONCLUSIONS: This study provided evidence that elevated circulating BMP9, secreted from the liver, promote pulmonary angiogenesis in HPS rats via ALK1-Endoglin-Smad1/5/9 pathway. In addition, BMP9-regulated pathways are also involved in accumulation of pro-angiogenic monocytes in the pulmonary microvasculature in HPS rats.
Subject(s)
Activin Receptors, Type II , Endoglin , Growth Differentiation Factor 2 , Hepatopulmonary Syndrome , Lung , Neovascularization, Pathologic , Signal Transduction , Smad1 Protein , Animals , Hepatopulmonary Syndrome/metabolism , Growth Differentiation Factor 2/metabolism , Rats , Activin Receptors, Type II/metabolism , Lung/metabolism , Male , Smad1 Protein/metabolism , Endoglin/metabolism , Neovascularization, Pathologic/metabolism , Endothelial Cells/metabolism , Disease Models, Animal , Smad5 Protein/metabolism , Rats, Sprague-Dawley , Cell Proliferation , Common Bile Duct , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Monocytes/metabolism , Angiogenesis , Activin ReceptorsABSTRACT
In this Letter, we report continuous-wave (CW) lasers with wavelengths beyond 3â µm in homemade Ho3+/Pr3+ co-doped AlF3-based glass fibers. The laser cavity was established through the integration of a dichroic mirror (DM, HR@3-3.1â µm) positioned at the pump end and a partial reflectivity (PR) fiber Bragg grating (FBG) situated at the laser emission end. The FBGs in AlF3-based glass fibers were fabricated by a fs laser direct-writing method, and the resonant wavelengths were 3.009, 3.036, and 3.064â µm, respectively. Under the pump of 1.15â µm laser, a maximum unsaturated output power of 1.014â W was obtained at 3.009â µm with an overall laser efficiency of 11.8% and FWHM bandwidth of 0.88â nm. Furthermore, in order to enhance the optical-thermal stability, the FBG was heat-treated at 200°C for 30â min, and a higher output power of 1081â mW (348â mW without heat treatment) at 3.036â µm was achieved. To the best of our knowledge, this is the first demonstration of 3-3.1â µm lasers by using FBGs in Ho3+/Pr3+ co-doped AlF3-based fibers.
ABSTRACT
N-acetylcysteine (NAC) positively contributes to enhancing animal health, regulating inflammation and reducing stress by participating in the synthesis of cysteine, glutathione, and taurine in the body. The present study aims to investigate the effects of dietary different levels of NAC on the morphology, function and physiological state of hepatopancreas in juvenile common carp (Cyprinus carpio). 450 common carps were randomly divided into 5 groups: N1 (basal diet), N2 (1.5 g/kg NAC diet), N3 (3.0 g/kg NAC diet), N4 (4.5 g/kg NAC diet) and N5 (6.0 g/kg NAC diet), and fed for 8 weeks. The results indicated that dietary 3.0-6.0 g/kg NAC reduced hepatopancreas lipid vacuoles and nuclear translocation, and inhibited apoptosis in common carp. Simultaneously, the activities of hepatopancreas alanine aminotransferase and aspartate aminotransferase progressively increased with rising dietary NAC levels. Dietary NAC enhanced the non-specific immune function of common carp, and exerted anti-inflammatory effects by inhibiting the MAPK/NF-κB signaling pathway. Additionally, dietary 3.0-6.0 g/kg NAC significantly improved the antioxidant capacity of common carp, which was associated with enhanced glutathione metabolism, clearance of ROS and the activation of Nrf2 signaling pathway. In summary, NAC has the potential to alleviate inflammation, mitigate oxidative stress and inhibit apoptosis via the MAPK/NF-κB/Nrf2 signaling pathway, thereby improving hepatopancreas function and health of common carp. The current findings provide a theoretical basis for promoting the application of NAC in aquaculture and ecological cultivation of aquatic animals.
Subject(s)
Antioxidants , Carps , Animals , Antioxidants/metabolism , NF-kappa B/metabolism , Acetylcysteine/pharmacology , Carps/metabolism , NF-E2-Related Factor 2/metabolism , Hepatopancreas/metabolism , Signal Transduction , Diet/veterinary , Inflammation/veterinary , Glutathione , Dietary SupplementsABSTRACT
As mimetic compounds of the natural alkaloid mackinazolinone, forty pyrido[1,2-a]thiazolo[5,4-d] pyrimidinone were designed and synthesized from a bioisosterism approach. The structure of these compounds was confirmed through analysis using 1H NMR, 13C NMR, and HRMS techniques. All the compounds were evaluated for their anticholinesterase activities and cytotoxicity on normal cells (293 T) by the Ellman method and methyl thiazolyl tetrazolium (MTT) method in vitro. and the structure-activity relationships (SARs) were summarized. The results showed that most of the compounds effectively inhibited acetylcholinesterase (AChE) in the micromolar range with weak cytotoxicity. Compound 7o exhibited the best inhibitory activity against AChE, displaying an IC50 values of 1.67 ± 0.09 µM and an inhibitory constant Ki of 11.31 µM as a competitive inhibitor to AChE. Molecular docking indicated that compound 7o may bind to AChE via hydrogen bond and π-π stacking. Further molecular dynamics (MD) simulations indicated a relatively low binding free energy (- 27.91 kJ·mol-1) of compound 7o with AChE. In summary, the collective findings suggested that 7o was promising as a potential novel drug candidate worthy of further investigation for the treatment of Alzheimer's disease.
ABSTRACT
In recent years, there has been an increasing demand for a multiple degrees of freedom (DOF) measurement system with high performance and high integration. Here, we report a 3DOF displacement sensor based on the self-imaging effect of optical micro-gratings. The optical field distribution behind a micro-grating with a period of 3 µm is analyzed theoretically. The transmission properties of a double-grating structure are investigated in theory. In the experiment, 3DOF displacement measurement within a range of 1 mm is demonstrated. Using an interpolation circuit with a subdividing factor of 1000, displacement measurement with a theoretical resolution of 3 nm is realized. The experimental resolution is â¼8n m. An error within 2 µm is obtained experimentally within a range of 1 mm for 3DOF measurement. With a few optical components such as a beam splitter prism and beam expanders, the sensor shows potential in developing ultra-compact multi-DOF displacement measuring systems. Together with a nanometric resolution, the 3DOF displacement sensor has shown great potential in applications such as high-precision mechanical engineering and semiconductor processing.
ABSTRACT
This publisher's note reports a correction in Appl. Opt.63, 1153 (2024)APOPAI0003-693510.1364/AO.513837.
ABSTRACT
A single-double-band switchable circular polarization filter based on surface plasmon resonance exhibits significant potential for applications in fields such as communication and sensing due to its adjustable, low-cost, and easy integration features. In this study, we propose a bi-layer rod nanostructure and use FEM simulation to study the transmission spectra of the structure. The results demonstrate that the structure exhibits both single- and double-band circular polarization filtering effects, which can be switched by varying geometric parameters such as the distance between the two layers and the width of nanorods. Furthermore, the filtering effects of both single- and double-band are highly dependent on the length of the nanorods, with average extinction rates reaching 486 and 2020/129, respectively; the operating bandwidths (defined as extinction ratio >10) can reach 170 nm and 35 nm/70 nm, respectively. The underlying physical mechanisms are clarified by analyzing the electric dipole, magnetic dipole resonance modes, and induced chiral fields on nanostructures.
ABSTRACT
Small-cell neuroendocrine carcinoma of the cervix (SCNCC) is a rare and aggressive tumor with a poor prognosis. Surgical resection followed by adjuvant therapy is the standard treatment for early-stage disease but the influence of different neo/adjuvant treatment approaches remains unclear. Retrospectively, we collected patients' characteristics and treatments in two medical centers. Disease status and survival outcomes were renewed through follow-up. Statistics analysis mainly included Kaplan-Meier methods for survival curve estimation, log-rank test for survival curve comparison, and Cox proportional hazards models for independent prognostic factors prediction. Finally, 51 patients treated by radical surgery between January 2010 and April 2020 were enrolled with a median age of 50 years (range: 32-68). 12 (23.5%) patients were at stage IIIC1 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging systems and the rest were at the early stage. The mean tumor size was 3.6±1.3 cm. Pathological examination found 24 cases with pure SCNCC and 27 cases with admixed SCCC. 29 (56.9%) patients had deep stromal infiltration and 19 (37.3%) patients had lymphovascular space invasion. 34 (66.7%) patients received neo/adjuvant chemotherapy and pelvic radiation was conducted in 41 (80.39%) patients with a median dose of 46 Gy (range: 40-50.4 Gy). The median follow-up time was 25.0 months. The median disease-free survival (DFS) time was 23.0 months. 27 (52.9%) patients developed distant metastasis and 14 (27.5%) experienced local failure. The median overall survival (OS) was 32.0 months. Univariate and multivariate analysis showed neoadjuvant chemotherapy as negative (HR=2.081, 95% CI 1.030-4.203, p=0.041) and adjuvant chemotherapy (HR=0.409, 95% CI 0.213-0.784, p=0.020) as positive independent prognostic factor for DFS. For OS, only lymph node metastasis was confirmed as an independent prognostic factor in both univariate analysis (HR=1.528, 95% CI 1.011-2.308, p=0.044) and multivariate analysis (HR=1.697, 95% CI 1.041-2.768, p=0.034). In conclusion, for surgically treated SCNCC, adjuvant chemotherapy showed a positive influence on DFS while neoadjuvant chemotherapy harmed DFS. OS was unaffected by either treatment choice.
Subject(s)
Carcinoma, Neuroendocrine , Carcinoma, Small Cell , Uterine Cervical Neoplasms , Female , Humans , Adult , Middle Aged , Aged , Treatment Outcome , Cervix Uteri/pathology , Retrospective Studies , Neoplasm Staging , Prognosis , Carcinoma, Small Cell/surgery , Carcinoma, Small Cell/drug therapy , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/drug therapy , Chemotherapy, Adjuvant , Carcinoma, Neuroendocrine/surgery , Carcinoma, Neuroendocrine/drug therapyABSTRACT
BACKGROUND: Cardio-cerebrovascular diseases constitute a major global public health burden. Volatile organic compounds (VOCs) exposure has become progressively severe, endangering human health and becoming one of the main concerns in environmental pollution. The associations of VOCs exposure with nonfatal cardio-cerebrovascular events have not been identified in observational study with a large sample size, so we aim to examine the association in US adult population. METHODS: Adults aged > 18 years with complete data regarding selected blood levels of VOCs (including benzene, ethylbenzene, o-xylene, and m-/p-xylene) and nonfatal cardio-cerebrovascular events were included in the analysis (n = 3,968, National Health and Nutrition Examination Survey, NHANES, 2013-2018 survey cycle). Participants were classified into low- and high-exposure based on whether above selected VOCs low limit detect concentration or median value. Weighted multivariate logistic analyses and subgroup analyses were used to detect the association between selected VOCs exposure and nonfatal cardio-cerebrovascular events in US adults. RESULTS: Weighted multivariate logistic analyses showed that the high-VOCs exposure group had an increased risk of nonfatal cardio-cerebrovascular events compared with the low-VOCs exposure group; the adjusted odds ratios (OR) and 95% confidence intervals (CI) of nonfatal cardio-cerebrovascular events for the high-VOCs exposure group were 1.41 (0.91, 2.19), 1.37 (0.96, 1.95), 1.32 (0.96, 1.82), and 1.17 (0.82, 1.67) for benzene, ethylbenzene, o-xylene, and m-/p-xylene, respectively, which was not significant assuming statistical significance at a 0.05 significance level (95% CI) for a two-tailed test. Lastly, we found high-VOCs exposure was associated with increased incidence of nonfatal cardio-cerebrovascular events in both daily smokers an non-daily smokers (p-interaction > 0.01), but the association was not statistically significant in non-daily smokers. CONCLUSIONS: This study found that VOCs (benzene, ethylbenzene, o-xylene, and m-/p-xylene) exposure was associated with increased incidence of nonfatal cardio-cerebrovascular events in US adults, and the results need to be confirmed by larger cohort studies.
Subject(s)
Air Pollutants , Benzene Derivatives , Volatile Organic Compounds , Xylenes , Adult , Humans , Volatile Organic Compounds/adverse effects , Nutrition Surveys , Benzene , Air Pollutants/analysis , Environmental Monitoring/methodsABSTRACT
Visual Simultaneous Localization and Mapping (VSLAM) estimates the robot's pose in three-dimensional space by analyzing the depth variations of inter-frame feature points. Inter-frame feature point mismatches can lead to tracking failure, impacting the accuracy of the mobile robot's self-localization and mapping. This paper proposes a method for removing mismatches of image features in dynamic scenes in visual SLAM. First, the Grid-based Motion Statistics (GMS) method was introduced for fast coarse screening of mismatched image features. Second, an Adaptive Error Threshold RANSAC (ATRANSAC) method, determined by the internal matching rate, was proposed to improve the accuracy of removing mismatched image features in dynamic and static scenes. Third, the GMS-ATRANSAC method was tested for removing mismatched image features, and experimental results showed that GMS-ATRANSAC can remove mismatches of image features on moving objects. It achieved an average error reduction of 29.4% and 32.9% compared to RANSAC and GMS-RANSAC, with a corresponding reduction in error variance of 63.9% and 58.0%, respectively. The processing time was reduced by 78.3% and 38%, respectively. Finally, the effectiveness of inter-frame feature mismatch removal in the initialization thread of ORB-SLAM2 and the tracking thread of ORB-SLAM3 was verified for the proposed algorithm.
ABSTRACT
Nitrogenase MoFe protein can be coupled with CdS nanocrystals (NCs) to enable photocatalytic N2 reduction. The nature of interactions that support complex formation is of paramount importance in intermolecular electron transfer that supports catalysis. In this work we have employed microscale thermophoresis to examine binding interactions between 3-mercaptopropionate capped CdS quantum dots (QDs) and MoFe protein over a range of QD diameters (3.4-4.3 nm). The results indicate that the interactions are largely electrostatic, with the strength of interactions similar to that observed for the physiological electron donor. In addition, the strength of interactions is sensitive to the QD diameter, and the binding interactions are significantly stronger for QDs with smaller diameters. The ability to quantitatively assess NC protein interactions in biohybrid systems supports strategies for understanding properties and reaction parameters that are important for obtaining optimal rates of catalysis in biohybrid systems.
Subject(s)
Molybdoferredoxin , Quantum Dots , Molybdoferredoxin/chemistry , Molybdoferredoxin/metabolism , Static Electricity , Nitrogenase/chemistry , Nitrogenase/metabolism , Electron TransportABSTRACT
In this work, the conformational behaviors of ring polyelectrolyte in tetravalent salt solutions are discussed in detail through molecular dynamics simulation. For simplification, here we have neglected the effect of the twisting interaction, although it has been well known that both bending and twisting interactions play a deterministic in the steric conformation of a semiflexible ring polymer. The salt concentration CS and the bending energy b take a decisive role in the conformation of the ring polyelectrolyte (PE). Throughout our calculations, the b varies from b = 0 (freely joint chain) to b = 120. The salt concentration CS changes in the range of 3.56 × 10-4 M ≤ CS ≤ 2.49 × 10-1 M. Upon the addition of salt, ring PE contracts at first, subsequently re-expands. More abundant conformations are observed for a semiflexible ring PE. For b = 10, the conformation of semiflexible ring PE shifts from the loop to two-racquet-head spindle, then it condenses into toroid, finally arranges into coil with the increase of CS. As b increases further, four phase transitions are observed. The latter two phase transitions are different. The semiflexible ring PE experiences transformation from toroid to two racquet head spindle, finally to loop in the latter two phase transitions. Its conformation is determined by the competition among the bending energy, cation-bridge, and entropy. Combined, our findings indicate that the conformations of semiflexible ring PE can be controlled by changing the salt concentration and chain stiffness.
Subject(s)
Molecular Conformation , Molecular Dynamics Simulation , Polyelectrolytes , Salts , Polyelectrolytes/chemistry , Salts/chemistry , SolutionsABSTRACT
Investigated mitigating effects of sodium butyrate (SB) on the inflammatory response, oxidative stress, and growth inhibition of common carp (Cyprinus carpio) (2.94 ± 0.2 g) are caused by glycinin. Six isonitrogenous and isoenergetic diets were prepared, in which the basal diet was the control diet and the Gly group diet contained 80 g/kg glycinin, while the remaining 4 diets were supplemented with 0.75, 1.50, 2.25, and 3.00 g/kg SB, respectively. The feeding trial lasted for 8 weeks, and the results indicated that supplementing the diet with 1.50-2.25 g/kg of SB significantly improved feed efficiency and alleviated the growth inhibition induced by glycinin. Hepatopancreas and intestinal protease activities and the content of muscle crude protein were significantly decreased by dietary glycinin, but supplement 1.50-2.25 g/kg SB partially reversed this result. SB (1.50-2.25 g/kg) increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the hepatopancreas and reduced the activities of AST and ALT in the serum. Glycinin significantly reduced immune and antioxidant enzyme activities, whereas 1.50-2.25 g/kg SB reversed these adverse effects. Furthermore, compared with the Gly group, supplement 1.50-2.25 g/kg SB eminently up-regulated the TGF-ß and IL-10 mRNA, and down-regulated the IL-1ß, TNF-α, and NF-κB mRNA in hepatopancreas, mid-intestine (MI), and distal intestine (DI). Meanwhile, supplement 1.50-2.25 g/kg SB activated the Keap1-Nrf2-ARE signaling pathway and upregulate CAT, SOD, and HO-1 mRNA expression in hepatopancreas, MI, and DI. Summarily, glycinin induced inflammatory response, and oxidative stress of common carp ultimately decreased the digestive function and growth performance. SB partially mitigated these adverse effects by activating the Keap1-Nrf2-ARE signaling pathway and inhibiting the NF-κB signaling pathway.
Subject(s)
Carps , Globulins , Soybean Proteins , Animals , Carps/metabolism , Butyric Acid/pharmacology , Kelch-Like ECH-Associated Protein 1/metabolism , NF-kappa B/metabolism , NF-E2-Related Factor 2/metabolism , Dietary Supplements , Diet/veterinary , Antioxidants/pharmacology , Antioxidants/metabolism , Oxidative Stress , RNA, Messenger/metabolism , Animal Feed/analysisABSTRACT
The Jiamusi section of the Songhua River is one of the first 17 model river construction sections in China. The implementation of river health assessments can determine the health dynamics of rivers and test the management's effectiveness. Targeting seven rivers, this study conducted river zoning and monitoring point deployment to conduct sufficient field research and monitoring. The authors selected hydrological and water resources, physical structure, water quality, aquatic life, social service functions, and management as guideline layers and 15 indicator layers. Subsequently, the authors established an evaluation index system to evaluate and analyze the ecological status and social service status of each river. The results showed that the Yindamu, Alingda, and Gejie rivers scored well as healthy rivers, with health evaluation scores of 78.98, 76.06, and 75.83, respectively. The Wangsanwu, Lujiagang, and Lingdangmai rivers are generally sub-healthy rivers with scores of 71.55, 67.97, and 60.7, respectively. The Yinggetu River has a score of 54.52 and is therefore assessed as unhealthy. Based on the scientific evaluation index method, this study analyses the current river health state in Jiamusi City to provide the basis for the evaluation of the river chief's work and future river management.
Subject(s)
Environmental Monitoring , Rivers , China , Environmental Monitoring/methods , Water Quality , CitiesABSTRACT
Organic ultra-long room-temperature phosphorescence (RTP) materials in the amorphous state have attracted widespread attention due to their simple preparation and flexibility to adopt various forms in sensors, bioimaging, and encryption applications. However, the amorphous molecular host for the host-guest RTP systems is highly demanded but limited. Here, a universal molecular host (DPOBP-Br) has been designed by integration of an amorphous moiety of diphenylphosphine oxide (DPO) and an intersystem crossing (ISC) group of 4-bromo-benzophenone (BP-Br). Various commercial fluorescence dyes were doped into the tight and transparent DPOBP-Br film, respectively, resulting in amorphous host-guest systems with ultra-long RTP colors from green to red. It was found that DPOBP-Br acted as a universal "triplet exciton pump" for promoting the generation of triplet excitons in the guest, through energy transfer processes and external heavy-atom effect based on DPOBP-Br. Interestingly, dynamic RTP was achieved by controlling residual oxygen concentration in the amorphous matrix by UV irradiation. Therefore, multi-dimensional anti-counterfeiting coatings were realized even on curved surfaces, simultaneously exhibiting spatial and 2D-time dependence. This work provides a strategy to design new amorphous molecular hosts for RTP systems and demonstrates the advanced information encryption with tempo-spatial resolution based on the dynamic ultra-long RTP of an amorphous system.
ABSTRACT
A central feature of the current understanding of dinitrogen (N2) reduction by the enzyme nitrogenase is the proposed coupling of the hydrolysis of two ATP, forming two ADP and two Pi, to the transfer of one electron from the Fe protein component to the MoFe protein component, where substrates are reduced. A redox-active [4Fe-4S] cluster associated with the Fe protein is the agent of electron delivery, and it is well known to have a capacity to cycle between a one-electron-reduced [4Fe-4S]1+ state and an oxidized [4Fe-4S]2+ state. Recently, however, it has been shown that certain reducing agents can be used to further reduce the Fe protein [4Fe-4S] cluster to a super-reduced, all-ferrous [4Fe-4S]0 state that can be either diamagnetic (S = 0) or paramagnetic (S = 4). It has been proposed that the super-reduced state might fundamentally alter the existing model for nitrogenase energy utilization by the transfer of two electrons per Fe protein cycle linked to hydrolysis of only two ATP molecules. Here, we measure the number of ATP consumed for each electron transfer under steady-state catalysis while the Fe protein cluster is in the [4Fe-4S]1+ state and when it is in the [4Fe-4S]0 state. Both oxidation states of the Fe protein are found to operate by hydrolyzing two ATP for each single-electron transfer event. Thus, regardless of its initial redox state, the Fe protein transfers only one electron at a time to the MoFe protein in a process that requires the hydrolysis of two ATP.
Subject(s)
Molybdoferredoxin , Nitrogenase , Nitrogenase/chemistry , Molybdoferredoxin/chemistry , Electrons , Hydrolysis , Adenosine Triphosphate/chemistry , Oxidation-Reduction , Iron/metabolism , Catalysis , Electron Spin Resonance SpectroscopyABSTRACT
A critical step in the mechanism of N2 reduction to 2NH3 catalyzed by the enzyme nitrogenase is the reaction of the four-electron/four-proton reduced intermediate state of the active-site FeMo-cofactor (E4(4H)). This state is a junction in the catalytic mechanism, either relaxing by the reaction of a metal bound Fe-hydride with a proton forming H2 or going forward with N2 binding coupled to the reductive elimination (re) of two Fe-hydrides as H2 to form the E4(2N2H) state. E4(2N2H) can relax to E4(4H) by the oxidative addition (oa) of H2 and release of N2 or can be further reduced in a series of catalytic steps to release 2NH3. If the H2 re/oa mechanism is correct, it requires that oa of H2 be associative with E4(2N2H). In this report, we have taken advantage of CdS quantum dots in complex with MoFe protein to achieve photodriven electron delivery in the frozen state, with cryo-annealing in the dark, to reveal details of the E-state species and to test the stability of E4(2N2H). Illumination of frozen CdS:MoFe protein complexes led to formation of a population of reduced intermediates. Electron paramagnetic resonance spectroscopy identified E-state signals including E2 and E4(2N2H), as well as signals suggesting the formation of E6 or E8. It is shown that in the frozen state when pN2 is much greater than pH2, the E4(2N2H) state is kinetically stable, with very limited forward or reverse reaction rates. These results establish that the oa of H2 to the E4(2N2H) state follows an associative reaction mechanism.
ABSTRACT
BACKGROUND: Indocyanine green (ICG) fluorescence imaging technology is increasingly widely used in laparoscopic hepatectomy. However, whether it can provide long-term survival benefits to patients with liver malignancies remains unclear. This study investigated the clinical effect of laparoscopic hepatectomy for hepatocellular carcinoma (HCC) using ICG imaging technology. METHODS: We retrospectively analyzed HCC patients who underwent laparoscopic hepatectomy at Zhongnan Hospital of Wuhan University from January 2016 to December 2020. Propensity score matching (PSM) was used to match patients undergoing ICG fluorescence navigation laparoscopic hepatectomy (ICG-FNLH) with those undergoing conventional laparoscopic hepatectomy (CLH) in a 1:1 ratio to minimize the influence of confounding factors. We compared perioperative status and long-term prognosis between the two groups and performed multivariate analysis to identify risk factors associated with overall survival and recurrence-free survival. RESULTS: The original cohort consisted of 141 patients, with 50 patients in each group (100 patients in total) after PSM. The anatomical liver resection rate, R0 resection rate, and resection margin distance in the ICG-FNLH group were higher than those in the CLH group. The intraoperative blood loss was lower than that in the CLH group. The recurrence-free survival and overall survival of the ICG-FNLH group were better than those of the CLH group. ICG-FNLH improved the recurrence-free survival of HCC patients (hazard ratio [HR] = 2.165, 95% confidence interval [CI]: 1.136-4.127, P = 0.024). CONCLUSIONS: Compared with CLH, ICG-FNLH can improve the recurrence-free survival rate of patients with hepatocellular carcinoma and may help to improve the long-term prognosis of patients.
Subject(s)
Carcinoma, Hepatocellular , Laparoscopy , Liver Neoplasms , Humans , Liver Neoplasms/pathology , Retrospective Studies , Indocyanine Green , Cohort Studies , Hepatectomy/methods , Propensity Score , Laparoscopy/methodsABSTRACT
Most studies on the influence of lens parameters in polarization transmission have been carried out in the traditional geometric analysis method, which has the problems of low accuracy and complicated calculation. In this paper, taking the Galileo beam expanding system as an example, a matrix analysis method is proposed to characterize the process of polarization transmission, and derived the polarization azimuth deflection equation. The numerical simulations of the matrix analysis method and the geometric analysis method are compared with the Zemax simulations and the experiments. The variance of the matrix analysis method is compared with the geometric analysis method under four parameters of the lens. It turns out that the numerical simulation results of the two methods are consistent with the Zemax simulation and the experiments. The variance of the matrix analysis method is mostly smaller than that of the geometric analysis method, which further shows that the matrix analysis method is closer to the Zemax simulations and the experiments, and the accuracy is higher.