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OBJECTIVE: Segmentectomy has been widely performed in clinical practice, which required a comprehensive understanding of anatomical structure. In right lower lobe, studies of superior segment (S6) were relatively small-sized. And only one study focusing on subsuperior segment (S∗) was published, which showed different results with previous ones. As the close relationship between S6 and S∗, variation types and their prevalence rate were reported, aiming to providing larger-size study of S6 and showing new evidence on anatomical structure of S∗. METHODS: 800 CT imaging data were collected from patients in our hospital. Three-dimensional reconstruction was performed after quality check. All images were screened according to the definition of corresponding segment and anatomical variations were analyzed. RESULTS: The proportion of S6 variation types in the largest scale (718 patients) was reported with no significant difference compared to previous studies and newly classified subtypes of two-stem V6. The prevalence rate for S∗ in right lower lobe reached 28.3 % (203/718) with similar proportion of three types. Variation types and origins of pulmonary artery were analyzed in detail, finding two-stem A∗ only be observed in type III B∗. CONCLUSIONS: Through this study, the variation types and incidence rate of S6 were confirmed, and a different result of S∗ has been provided as well. The feasibility of the current classification standards and proposed new subclassifications were verified. The results would be a supplement to lung segmental anatomy and could advance researches in the future.
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The resected pâ ¢A-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.
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The advancement in electrocatalysis, particularly in the development of efficient catalysts for hydrogen and oxygen evolution reactions (HER and OER), is crucial for sustainable energy generation through processes like overall water splitting. A notable bifunctional electrocatalyst, CoFe2O4/Co7Fe3, has been engineered to facilitate both OER and HER concurrently, aiming to reduce overpotentials. In the pursuit of further enhancing catalytic efficiency, a morphological transformation has been achieved by introducing a sulphur source and multi-walled carbon nanotubes (MWCNTs) into the catalyst system, resulting in S-CoFe2O4/Co7Fe3/MWCNTs. This modification has significantly improved the activity for both OER and HER. An onset overpotential of 250 mV@10 mAcm-2 for the OER and 270 mV@50 mAcm-2 for the HER, indicating efficient catalytic activity at relatively low overpotentials. S-CoFe2O4/Co7Fe3/MWCNTs display an outstanding long-term stability in alkaline electrolytes, with minimal Tafel slopes of 77 mV/dec for the OER and 70 mV/dec for the HER, suggesting sustained catalytic performance over extended periods. Furthermore, when employed as both the cathode and anode in the context of complete water splitting, S-CoFe2O4/Co7Fe3/MWCNTs demonstrate an impressive cell voltage of 1.52 V at a current density of 10 mA cm-2 in a 1 M KOH solution, showcasing its viability for practical applications. Given its cost-effectiveness and superior activity, S-CoFe2O4/Co7Fe3/MWCNTs hold significant promise for widespread applications in overall water splitting electrocatalysis, contributing to the advancement of cleaner and sustainable fuel generation technologies.
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Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4â¯O and +5â¯O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ.
Subject(s)
Drugs, Chinese Herbal , Rats, Sprague-Dawley , Sesquiterpenes, Germacrane , Animals , Sesquiterpenes, Germacrane/metabolism , Rats , Drugs, Chinese Herbal/pharmacokinetics , Drugs, Chinese Herbal/metabolism , Drugs, Chinese Herbal/administration & dosage , Male , Chromatography, High Pressure Liquid/methods , Tissue Distribution , Administration, Oral , Feces/chemistryABSTRACT
Photo-thermal co-catalytic reduction of CO2 to synthesize value-added chemicals presents a promising approach to addressing environmental issues. Nevertheless, traditional catalysts exhibit low light utilization efficiency, leading to the generation of a reduced number of electron-hole pairs and rapid recombination, thereby limiting catalytic performance enhancement. Herein, a Mott-Schottky heterojunction catalyst was developed by incorporating nitrogen-doped carbon coated TiO2 supported nickel (Ni) nanometallic particles (Ni/x-TiO2@NC). The optimal Ni/0.5-TiO2@NC sample displayed a conversion rate of 71.6 % and a methane (CH4) production rate of 65.3 mmol/(gcat·h) during photo-thermal co-catalytic CO2 methanation under full-spectrum illumination, with a CH4 selectivity exceeding 99.6 %. The catalyst demonstrates good stability as it shows no decay after two reaction cycles. The Mott-Schottky heterojunction catalysts display excellent efficiency in separating photo-generated electron-hole pairs and elevate the catalysts' temperature, thus accelerating the reaction rate. The in-situ experiments revealed that light-induced electron transfer effectively facilitates H2 dissociation and enhances surface defects, thereby promoting CO2 adsorption. This study introduces a novel approach for developing photo-thermal catalysts for CO2 reduction, aiming to enhance solar energy utilization and facilitate interface electron transfer.
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Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .
Subject(s)
Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Psychological Distress , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Female , Male , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Middle Aged , Aged , Prospective Studies , Depression/drug therapy , Anxiety/drug therapy , Treatment Outcome , Progression-Free Survival , Adult , Aged, 80 and overABSTRACT
The brain presents age-related structural and functional changes in the human life, with different extends between subjects and groups. Brain age prediction can be used to evaluate the development and aging of human brain, as well as providing valuable information for neurodevelopment and disease diagnosis. Many contributions have been made for this purpose, resorting to different machine learning methods. To solve this task and reduce memory resource consumption, we develop a mini architecture of only 10 layers by modifying the deep residual neural network (ResNet), named ResNet mini architecture. To support the ResNet mini architecture in brain age prediction, the brain age dataset (OpenNeuro #ds000228) that consists of 155 study participants (three classes) and the Alzheimer MRI preprocessed dataset that consists of 6400 images (four classes) are employed. We compared the performance of the ResNet mini architecture with other popular networks using the two considered datasets. Experimental results show that the proposed architecture exhibits generality and robustness with high accuracy and less parameter number.
Subject(s)
Aging , Brain , Magnetic Resonance Imaging , Neural Networks, Computer , Humans , Brain/diagnostic imaging , Brain/physiology , Aging/physiology , Magnetic Resonance Imaging/methods , Deep Learning , Aged , Alzheimer Disease/diagnostic imaging , Machine Learning , Female , Aged, 80 and over , Male , Middle AgedABSTRACT
Correlated noise across multiple qubits poses a significant challenge for achieving scalable and fault-tolerant quantum processors. Despite recent experimental efforts to quantify this noise in various qubit architectures, a comprehensive understanding of its role in qubit dynamics remains elusive. Here, we present an analytical study of the dynamics of driven qubits under spatially correlated noise, including both Markovian and non-Markovian noise. Surprisingly, we find that by operating the qubit system at low temperatures, where correlated quantum noise plays an important role, significant long-lived entanglement between qubits can be generated. Importantly, this generation process can be controlled on-demand by turning the qubit driving on and off. On the other hand, we demonstrate that by operating the system at a higher temperature, the crosstalk between qubits induced by the correlated noise is unexpectedly suppressed. We finally reveal the impact of spatio-temporally correlated 1/f noise on the decoherence rate, and how its temporal correlations restore lost entanglement. Our findings provide critical insights into not only suppressing crosstalk between qubits caused by correlated noise but also in effectively leveraging such noise as a beneficial resource for controlled entanglement generation.
ABSTRACT
The weak adsorption of oxygen on transition metal oxide catalysts limits the improvement of their electrocatalytic oxygen reduction reaction (ORR) performance. Herein, a dopamine-assisted method is developed to prepare Mn-doped ceria supported on nitrogen-doped carbon nanotubes (Mn-Ce-NCNTs). The morphology, dispersion of Mn-doped ceria, composition, and oxygen vacancies of the as-prepared catalysts were analyzed using various technologies. The results show that Mn-doped ceria was formed and highly dispersed on NCNTs, on which oxygen vacancies are abundant. The as-prepared Mn-Ce-NCNTs exhibit a high ORR performance, on which the average electron transfer number is 3.86 and the current density is 24.4% higher than that of commercial 20 wt % Pt/C. The peak power density of Mn-Ce-NCNTs is 68.1 mW cm-2 at the current density of 138.9 mA cm-2 for a Zn-air battery, which is close to that of 20 wt % Pt/C (69.4 mW cm-2 at 106.1 mA cm-2). Density functional theory (DFT) calculations show that the oxygen vacancy formation energies of Mn-doped CeO2(111) and pure CeO2(111) are -0.55 and 2.14 eV, respectively. Meanwhile, compared with undoped CeO2(111) (-0.02 eV), Mn-doped CeO2(111) easily adsorbs oxygen with the oxygen adsorption energy of only -0.68 eV. This work provides insights into the synergetic effect of Mn-doped ceria for facilitating oxygen adsorption and enhancing ORR performance.
ABSTRACT
Dual-atom site catalysts (DASCs) have sparked considerable interest in heterogeneous photocatalysis as they possess the advantages of excellent photoelectronic activity, photostability, and high carrier separation efficiency and mobility. The DASCs involved in these important photocatalytic processes, especially in the photocatalytic hydrogen evolution reaction (HER), CO2 reduction reaction (CO2RR), N2/nitrate reduction, etc., have been extensively investigated in the past few years. In this review, we highlight the recent progress in DASCs that provides fundamental insights into the photocatalytic conversion of small molecules. The controllable preparation and characterization methods of various DASCs are discussed. Subsequently, the reaction mechanisms of the formation of several important molecules (hydrogen, hydrocarbons and ammonia) on DASCs are introduced in detail, in order to probe the relationship between DASCs's structure and photocatalytic activity. Finally, some challenges and outlooks of DASCs in the photocatalytic conversion of small molecules are summarized and prospected. We hope that this review can provide guidance for in-depth understanding and aid in the design of efficient DASCs for photocatalysis.
ABSTRACT
Single-site Fe-N-C catalysts are the most promising Pt-group catalyst alternatives for the oxygen reduction reaction, but their application is impeded by their relatively low activity and unsatisfactory stability as well as production costs. Here, cobalt atoms are introduced into an Fe-N-C catalyst to enhance its catalytic activity by utilizing the synergistic effect between Fe and Co atoms. Meanwhile, phenanthroline is employed as the ligand, which favours stable pyridinic N-coordinated Fe-Co sites. The obtained catalysts exhibit excellent ORR performance with a half-wave potential of 0.892 V and good stability under alkaline conditions. In addition, the excellent ORR activity and durability of FeCo-N-C enabled the constructed zinc-air battery to exhibit a high power density of 247.93 mW cm-2 and a high capacity of 768.59 mA h gZn-1. Moreover, the AEMFC based on FeCo-N-C also achieved a high open circuit voltage (0.95 V) and rated power density (444.7 mW cm-2), surpassing those of many currently reported transition metal-based cathodes. This work emphasizes the feasibility of this non-precious metal catalyst preparation strategy and its practical applicability in fuel cells and metal-air batteries.
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RATIONALE: Guidewire fracture is one of the biggest risks of percutaneous coronary intervention, twisting wire technique is very useful for retrieving the fractured wire, but the potential risks have been inadequately reported. Herein, we present a case of retrieval of guidewire fragments using the twisting wire technique that causes coronary perfusion. PATIENT CONCERNS: A 37-year-old male patient was admitted to our hospital for elective percutaneous coronary intervention of the left circumflex coronary artery. CLINICAL FINDINGS: For chronic total occlusion of the distal left circumflex coronary artery, antegrade recanalization by wire escalation, and parallel wire techniques were attempted. However, we shockingly found that the BMW guidewire, anchored in the right coronary artery, spontaneously fractured from the proximal right coronary artery, and a lengthy fragment of the guidewire remained in the coronary. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Many attempts were made to retrieve the remnant guidewire including the twisting wire technique, which leads to the perforation of the coronary. OUTCOMES: Finally, percutaneous retrieving procedures were stopped in favor of surgical extraction via a small coronary arteriotomy. This procedure was successful. LESSONS: To the best of our knowledge, the present case is the first reported spontaneous fracture of the guidewire. Leaving such a lengthy remnant guidewire in the artery, or leaving stenting over the wire, would impose a high risk of coronary thrombosis, perforation, and embolization. Yet, the perforation of the artery that occurred in this case, which could have had life-threatening consequences, resulted from our attempts to retrieve the guidewire using the twisting wire technique.
Subject(s)
Angioplasty, Balloon, Coronary , Percutaneous Coronary Intervention , Male , Humans , Adult , Angioplasty, Balloon, Coronary/methods , Coronary Angiography , Percutaneous Coronary Intervention/adverse effects , Coronary Vessels/diagnostic imaging , Coronary Vessels/surgery , Perfusion , Treatment OutcomeABSTRACT
BACKGROUND: The tumor microbiome has been characterized in several malignancies; however, no previous studies have investigated its role in intrahepatic cholangiocarcinoma (ICC). Hence, we explored the tumor microbiome and its association with prognosis in ICC. METHODS: One hundred and twenty-one ICC tumor samples and 89 adjacent normal tissues were profiled by 16S rRNA sequencing. Microbial differences between tumor and adjacent nontumoral liver tissues were assessed. Tumor microbial composition was then evaluated to detect its association with prognosis. Finally, a risk score calculated by the tumor microbiota was accessed by the least absolute shrinkage and selector operator method (Lasso) to predict prognosis of ICC. RESULTS: The tumor microbiome displayed a greater diversity than that in adjacent nontumoral liver tissues. Tumor samples were characterized by a higher abundance of Firmicutes, Actinobacteria, Bacteroidetes, and Acidobacteriota. Higher tumor microbial α diversity was associated with lymph node metastasis and predicted shortened overall survival (OS) and recurrence-free survival (RFS). A total of 11 bacteria were selected to generate the risk score by Lasso. This score showed potential in predicting OS, and was an independent risk factor for OS. CONCLUSION: In conclusion, our study characterized the tumor microbiome and revealed its role in predicting prognosis in ICC.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Humans , RNA, Ribosomal, 16S/genetics , Prognosis , Cholangiocarcinoma/pathology , Bile Ducts, Intrahepatic/pathology , Bile Duct Neoplasms/pathology , Retrospective StudiesABSTRACT
Benefiting from the unique photoluminescence behavior of the lanthanide(III) ions and organic ligands, a lanthanide(III) metal-organic framework (Ln-MOF) material can simultaneously demonstrate photoluminescence of lanthanide(III) cations and organic molecules and endow its superior applications of fluorescence sensing behaviors. Herein, we present a europium(III) MOF material {[Eu2(BPTA)·(CH3COO)2·3DMA]·0.5DMA·3H2O}n (1) (where H4BPTA is 3,3',5,5'-biphenyltetracarboxylic acid) for photoluminescence performance of quantitatively sensing the inflammatory marker neopterin (Neo). The obtained 1 comprises Eu2(COO)4 paddlewheel secondary building units, which could be bridged by BPTA4- ligands to extend a 2D framework. The fluorescence titration indicates 1 can achieve simultaneous fluorescence behavior of Eu3+ ions and Neo via on-off ratiometric effects and thus could be exploited as the ratiometric fluorescence sensor matrix. Such a fluorescence phenomenon of 1 as a ratiometric sensor for quantitative detection of Neo via an on-off ratiometric effect is never observed in MOF chemistry. Moreover, naked-eye visible color variations of the fluorescence for 1 could be observed from red to blue with increasing concentrations of Neo, confirmed by fluorescent test strips as well as portable fluorescent hydrogels. And 1 also shows a low detection limit of 15.11 nM. A synergetic contribution of the competitive absorption, fluorescence resonance energy-transfer, and photoinduced electron-transfer mechanisms between Neo and the framework of 1 realizes the on-off ratiometric fluorescence behavior for Neo detection, supported by the UV-vis spectral overlap experiment and DFT calculations.
ABSTRACT
Hydrogen peroxide (H2O2) is a highly value-added and environmental-friendly chemical with various applications. The production of H2O2 by electrocatalytic 2e- oxygen reduction reaction (ORR) has emerged as a promising alternative to the energy-intensive anthraquinone process. High selectivity Catalysts combining with superior activity are critical for the efficient electrosynthesis of H2O2. Earth-abundant transition metal selenides (TMSs) being discovered as a classic of stable, low-cost, highly active and selective catalysts for electrochemical 2e- ORR. These features come from the relatively large atomic radius of selenium element, the metal-like properties and the abundant reserves. Moreover, compared with the advanced noble metal or single-atom catalysts, the kinetic current density of TMSs for H2O2 generation is higher in acidic solution, which enable them to become suitable catalyst candidates. Herein, the recent progress of TMSs for ORR to H2O2 is systematically reviewed. The effects of TMSs electrocatalysts on the activity, selectivity and stability of ORR to H2O2 are summarized. It is intended to provide an insight from catalyst design and corresponding reaction mechanisms to the device setup, and to discuss the relationship between structure and activity.
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We propose an experimentally feasible dissipative spin-wave diode comprising two magnetic layers coupled via a nonmagnetic spacer. We theoretically demonstrate that the spacer mediates not only coherent interactions but also dissipative coupling. Interestingly, an appropriately engineered dissipation engenders a nonreciprocal device response, facilitating the realization of a spin-wave diode. This diode permits wave propagation in one direction alone, given that the coherent Dzyaloshinskii-Moriya (DM) interaction is balanced with the dissipative coupling. The polarity of the diode is determined by the sign of the DM interaction. Furthermore, we show that when the magnetic layers undergo incoherent pumping, the device operates as a unidirectional spin-wave amplifier. The amplifier gain is augmented by cascading multiple magnetic bilayers. By extending our model to a one-dimensional ring structure, we establish a connection between the physics of spin-wave amplification and non-Hermitian topology. Our proposal opens up a new avenue for harnessing inherent dissipation in spintronic applications.
ABSTRACT
Lignin is the main component of lignocellulose and the largest source of aromatic substances on the earth. Biofuel and bio-chemicals derived from lignin can reduce the use of petroleum products. Current advances in lignin catalysis conversion have facilitated many of progress, but understanding the principles of catalyst design is critical to moving the field forward. In this review, the factors affecting the catalysts (including the type of active metal, metal particle size, acidity, pore size, the nature of the oxide supports, and the synergistic effect of the metals) are systematically reviewed based on the three most commonly used supports (carbon, oxides, and zeolites) in lignin hydrogenolysis. The catalytic performance (selectivity and yield of products) is evaluated, and the emerging catalytic mechanisms are introduced to better understand the catalyst design guidelines. Finally, based on the progress of existing studies, future directions for catalyst design in the field of lignin depolymerization are proposed.
ABSTRACT
The development of highly active and low-cost oxygen reduction reaction (ORR) catalysts is crucial for the practical application of hydrogen fuel cells. However, the linear scaling relation (LSR) imposes an inherent Sabatier's limitation for most catalysts including the benchmark Pt with an insurmountable overpotential ceiling, impeding the development of efficient electrocatalysts. To avoid such a limitation, using earth-abundant metal oxides with different crystal phases as model materials, we propose an effective and dynamic reaction pathway through constructing spatially correlated Pt-Mn pair sites, achieving an excellent balance between high activity and low Pt loading. Experimental and theoretical calculations demonstrate that manipulating the intermetallic distance and charge distribution of Pt-Mn pairs can effectively promote O-O bond cleavage at these sites through a bridge configuration, circumventing the formation of *OOH intermediates. Meanwhile, the dynamic adsorption configuration transition from the bridge configuration of O2 to the end-on configuration of *OH improves *OH desorption at the Mn site within such pairs, thereby avoiding Sabatier's limitation. The well-designed Pt-Mn/ß-MnO2 exhibits outstanding ORR activity and stability with a half-wave potential of 0.93 V and barely any activity degradation for 70 h. When applied to the cathode of a H2-O2 anion-exchange membrane fuel cell, this catalyst demonstrates a high peak power density of 287 mW cm-2 and 500 h of stability under a cell voltage of 0.6 V. This work reveals the adaptive bonding interactions of atomic pair sites with multiple reactant/intermediates, offering a new avenue for rational design of highly efficient atomic-level dispersed ORR catalysts beyond the Sabatier optimum.
ABSTRACT
Immune checkpoint inhibitors (ICIs) have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment, while substantial patients remain unresponsive or develop resistance to ICIs as a single agent, which is traceable to cellular metabolic dysfunction. Although dysregulated metabolism has long been adjudged as a hallmark of tumor, it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of immunocytes. Correspondingly, people used to pay more attention to the effect of tumor cell metabolism on immunocytes, but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation, which opens up a whole new frontier called immunometabolism. The metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy, whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune response. Herein, we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes, and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.
Subject(s)
Neoplasms , Humans , Neoplasms/pathology , Immunotherapy/methods , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic useABSTRACT
The improvement of non-oxide ceramic plasticity while maintaining the high-temperature strength is a great challenge through the classical strategy, which generally includes decreasing grain size to several nanometers or adding ductile binder phase. Here, we report that the plasticity of fully dense boron carbide (B4C) is greatly enhanced due to the boundary non-stoichiometry induced by high-pressure sintering technology. The effect decreases the plastic deformation temperature of B4C by 200 °C compared to that of conventionally-sintered specimens. Promoted grain boundary diffusion is found to enhance grain boundary sliding, which dominate the lower-temperature plasticity. In addition, the as-produced specimen maintains extraordinary strength before the occurrence of plasticity. The study provides an efficient strategy by boundary chemical change to facilitate the plasticity of ceramic materials.