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1.
Proc Natl Acad Sci U S A ; 120(1): e2209760120, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36574658

RESUMO

Using hydrogen as a fuel is an effective way to combat energy crisis and at the same time reduce greenhouse gas emission. Alkaline hydrogen evolution reaction (HER) is one important way to obtain green hydrogen, which however is energy intensive and is difficult to obtain high efficiencies even when using state-of-the-art noble metal catalysts. Here, we report a three-component catalytic system using only non-noble elements, consisting of cobalt oxide clusters and single molybdenum atoms supported on oxyanion-terminated two-dimensional MXene, which enabled the unusual generation of hydrogen by a kinetically fast Volmer-Tafel process in an alkaline electrolyte. The key feature of this catalyst is that the three components are connected by bridging oxygen, which serves to immediately adsorb H* produced during water dissociation on cobalt oxide and relay it to the molybdenum single-atom catalyst. On the Mo atom, due to this unique coordination environment, the relayed H* intermediates directly combine and desorb, realizing H2 generation through an unusual Tafel pathway. The presence of bridging oxygen increases the acidity of the catalyst as Brønsted acid with the reversible adsorption and donation of a proton, thus eliminating the need for acid addition and ensuring excellent and sustainable alkaline HER performance. The performance of our catalyst is comparable to that of the commercial noble metal catalyst PtRu/C. Our work makes a significant contribution to designing efficient non-noble catalysts for alkaline HER electrocatalysis.

2.
Chem Soc Rev ; 53(18): 9254-9305, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39143899

RESUMO

With the increasing demand for energy and the climate challenges caused by the consumption of traditional fuels, there is an urgent need to accelerate the adoption of green and sustainable energy conversion and storage technologies. The integration of flexible thermoelectrics with other various energy conversion technologies plays a crucial role, enabling the conversion of multiple forms of energy such as temperature differentials, solar energy, mechanical force, and humidity into electricity. The development of these technologies lays the foundation for sustainable power solutions and promotes research progress in energy conversion. Given the complexity and rapid development of this field, this review provides a detailed overview of the progress of multifunctional integrated energy conversion and storage technologies based on thermoelectric conversion. The focus is on improving material performance, optimizing the design of integrated device structures, and achieving device flexibility to expand their application scenarios, particularly the integration and multi-functionalization of wearable energy conversion technologies. Additionally, we discuss the current development bottlenecks and future directions to facilitate the continuous advancement of this field.

3.
J Am Chem Soc ; 146(2): 1681-1689, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38178655

RESUMO

The coupled relationship between carrier and phonon scattering severely limits the thermoelectric performance of n-type GeTe materials. Here, we provide an efficient strategy to enlarge grains and induce vacancy clusters for decoupling carrier-phonon scattering through the annealing optimization of n-type GeTe-based materials. Specifically, boundary migration is used to enlarge grains by optimizing the annealing time, while vacancy clusters are induced through the aggregation of Ge vacancies during annealing. Such enlarged grains can weaken carrier scattering, while vacancy clusters can strengthen phonon scattering, leading to decoupled carrier-phonon scattering. As a result, a ratio between carrier mobility and lattice thermal conductivity of ∼492.8 cm3 V-1 s-1 W-1 K and a peak ZT of ∼0.4 at 473 K are achieved in Ge0.67Pb0.13Bi0.2Te. This work reveals the critical roles of enlarged grains and induced vacancy clusters in decoupling carrier-phonon scattering and demonstrates the viability of fabricating high-performance n-type GeTe materials via annealing optimization.

4.
Mol Med ; 30(1): 53, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649840

RESUMO

OBJECTIVE: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with significant mortality rates. The role of Fcgr2b in the pathogenesis of ALI/ARDS is not fully elucidated. This study aimed to investigate the functions of Fcgr2b in ALI/ARDS and explore its underlying mechanisms. METHODS: Methods: In this study, rat models of ARDS and pulmonary microvascular endothelial cell (PMVEC) injury models were established through the administration of lipopolysaccharide (LPS). The expression levels of Fcgr2b and Elk1 were quantified in both LPS-induced ARDS rats and PMVECs. Subsequent gain- and loss-of-function experiments were conducted, followed by comprehensive assessments of lung tissue for pathomorphological changes, edema, glycogen storage, fibrosis, and infiltration of inflammatory cells. Additionally, bronchoalveolar lavage fluid was analyzed for T-helper 17 (Th17) cell infiltration, inflammatory response, and microvascular permeability to evaluate lung injury severity in ARDS models. Furthermore, the activity, cytotoxicity, apoptosis, and angiogenic potential of PMVECs were assessed to gauge cell injury. The interaction between Elk1 and Fcgr2b was also examined to confirm their regulatory relationship. RESULTS: In the context of LPS-induced ARDS and PMVEC injury, Fcgr2b expression was markedly reduced, whereas Elk1 expression was elevated. Overexpression of Fcgr2b led to a decrease in Th17 cell infiltration and mitigated lung tissue damage in ARDS models, in addition to reducing LPS-induced injury in PMVECs. Elk1 was found to suppress Fcgr2b transcription through the recruitment of histone 3 lysine 9 trimethylation (H3K9me3). Knockdown of Elk1 diminished Th17 cell infiltration and lung tissue damage in ARDS models, and alleviated LPS-induced injury in PMVECs, effects that were reversed upon Fcgr2b upregulation. CONCLUSION: Elk1 negatively regulates Fcgr2b transcription, thereby augmenting the inflammatory response and exacerbating lung injury in LPS-induced ALI/ARDS.


Assuntos
Lesão Pulmonar Aguda , Modelos Animais de Doenças , Células Endoteliais , Lipopolissacarídeos , Receptores de IgG , Síndrome do Desconforto Respiratório , Proteínas Elk-1 do Domínio ets , Animais , Masculino , Ratos , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/etiologia , Células Endoteliais/metabolismo , Proteínas Elk-1 do Domínio ets/metabolismo , Proteínas Elk-1 do Domínio ets/genética , Pulmão/patologia , Pulmão/metabolismo , Ratos Wistar , Receptores de IgG/metabolismo , Receptores de IgG/genética , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/genética , Células Th17/metabolismo , Células Th17/imunologia , Transcrição Gênica
5.
J Gene Med ; 26(1): e3572, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37525871

RESUMO

BACKGROUND: The physiological and immunological characteristics of the tumor microenvironment (TME) have a profound impact on the effectiveness of immunotherapy. The present study aimed to define the TME subtype of osteosarcoma according to the signatures representing the global TME of the tumor, as well as create a new prognostic assessment tool to monitor the prognosis, TME activity and immunotherapy response of patients with osteosarcoma. METHODS: The enrichment scores of 29 functional gene expression signatures in osteosarcoma samples were calculated by single sample gene set enrichment analysis (ssGSEA). TME classification of osteosarcoma was performed and a prognostic assessment tool was created based on 29 ssGSEA scores to comprehensively correlate them with TME components, immunotherapy efficacy and prognosis of osteosarcoma. RESULTS: Three TME subtypes were generated that differed in survival, TME activity and immunotherapeutic response. Four differentially expressed genes between TME subtypes were involved in the development of prognostic assessment tools. The established prognosis assessment tool had strong performance in both training and verification cohorts, could be effectively applied to the survival prediction of samples of different ages, genders and transfer states, and could well distinguish the TME status of different samples. CONCLUSIONS: The present study describes three different TME phenotypes in osteosarcoma, provides a risk stratification tool for osteosarcoma prognosis and TME status assessment, and provides additional information for clinical decision-making of immunotherapy.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Feminino , Masculino , Prognóstico , Microambiente Tumoral/genética , Osteossarcoma/diagnóstico , Osteossarcoma/genética , Osteossarcoma/terapia , Fenótipo , Imunoterapia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia
6.
Small ; 20(36): e2401931, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38708707

RESUMO

Chemodynamic therapy (CDT) is a non-invasive strategy for generating reactive oxygen species (ROS) and is promising for cancer treatment. However, increasing ROS in tumor therapy remains challenging. Therefore, exogenous excitation and inhibition of electron-hole pair recombination are attractive for modulating ROS storms in tumors. Herein, a Ce-doped BiFeO3 (CBFO) piezoelectric sonosensitizer to modulate ROS generation and realize a synergistic mechanism of CDT/sonodynamic therapy and piezodynamic therapy (PzDT) is proposed. The mixed Fe2+ and Ce3+ can implement a circular Fenton/Fenton-like reaction in the tumor microenvironment. Abundant ·OH can be generated by ultrasound (US) stimulation to enhance CDT efficacy. As a typical piezoelectric sonosensitizer, CBFO can produce O2 - owing to the enhanced polarization by the US, resulting in the motion of charge carriers. In addition, CBFO can produce a piezoresponse irradiated upon US, which accelerates the migration rate of electrons/holes in opposite directions and results in energy band bending, further achieving toxic ROS production and realizing PzDT. Density functional theory calculations confirmed that Ce doping shortens the diffusion of electrons and improves the conductivity and catalytic activity of CBFO. This distinct US-enhanced strategy emphasizes the effects of doping engineering and piezoelectric-optimized therapy and shows great potential for the treatment of malignant tumors.


Assuntos
Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Humanos , Neoplasias/terapia , Animais , Linhagem Celular Tumoral , Camundongos , Terapia Combinada , Cério/química , Microambiente Tumoral
7.
Small ; 20(26): e2310829, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38258407

RESUMO

The pursuit of highly-active and stable catalysts in anodic oxygen evolution reaction (OER) is desirable for high-current-density water electrolysis toward industrial hydrogen production. Herein, a straightforward yet feasible method to prepare WFeRu ternary alloying catalyst on nickel foam is demonstrated, whereby the foreign W, Fe, and Ru metal atoms diffuse into the Ni foam resulting in the formation of inner immobilized ternary alloy. Thanks to the synergistic impact of foreign metal atoms and structural robustness of inner immobilized alloying catalyst, the well-designed WFeRu@NF self-standing anode exhibits superior OER activities. It only requires overpotentials of 245 and 346 mV to attain current densities of 20 and 500 mA cm-2, respectively. Moreover, the as-prepared ternary alloying catalyst also exhibits a long-term stability at a high-current-density of 500 mA cm-2 for over 45 h, evidencing the inner-immobilization strategy is promising for the development of highly active and stable metal-based catalysts for high-density-current water oxidation process.

8.
Opt Express ; 32(12): 20862-20865, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859456

RESUMO

This joint issue of Optics Express and Optical Materials Express showcases 29 articles that report the latest advancements in nonlinear optics. These articles include contributions from authors who participated in the Optica Nonlinear Optics Topical Meeting, which took place in Honolulu, Hawaii, from July 10th to July 14th, 2023. The conference was organized by Optica (formerly known as OSA). As an introduction, the editors provide a summary of these articles, which cover a broad range of topics in nonlinear optics, spanning from fundamental nonlinear optical concepts to novel nonlinear effects, and from innovative nonlinear materials to topics such as ultrafast optics, machine learning empowered nonlinear optics, and unconventional applications. This diverse array of contributions reflects the dynamic and interdisciplinary nature of contemporary research in the field of nonlinear optics while showcasing some of the most recent developments.

9.
Opt Express ; 32(4): 5760-5769, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439294

RESUMO

Heme is the prosthetic group for cytochrome that exists in nearly all living organisms and serves as a vital component of human red blood cells (RBCs). Tunable optical nonlinearity in suspensions of RBCs has been demonstrated previously, however, the nonlinear optical response of a pure heme (without membrane structure) solution has not been studied to our knowledge. In this work, we show optical nonlinearity in two common kinds of heme (i.e., hemin and hematin) solutions by a series of experiments and numerical simulations. We find that the mechanism of nonlinearity in heme solutions is distinct from that observed in the RBC suspensions where the nonlinearity can be easily tuned through optical power, concentration, and the solution properties. In particular, we observe an unusual phenomenon wherein the heme solution exhibits negative optical nonlinearity and render self-collimation of a focused beam at specific optical powers, enabling shape-preserving propagation of light to long distances. Our results may have potential applications in optical imaging and medical diagnosis through blood.


Assuntos
Eritrócitos , Heme , Humanos , Imagem Óptica
10.
Opt Lett ; 49(17): 4811-4814, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39207970

RESUMO

We recently introduced a new class of optical beams with a Bessel-like transverse profile and increasing beam width during propagation, akin to an "inverted pin." Owing to their specially engineered distribution, these beams have shown remarkable performance in atmospheric turbulence. Specifically, inverted pin beams (PBs) were found to have a reduced scintillation index as compared to collimated or focused Gaussian beams as well as other types of pin beams especially in moderate to strong turbulence. In this work, we demonstrate that inverted pin beams carrying orbital angular momentum (OAM) can further suppress intensity scintillations in moderate to strong irradiance fluctuation conditions. Our results can be useful in improving the performance and link availability of free-space optical communication systems.

11.
Phys Rev Lett ; 132(6): 066602, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38394559

RESUMO

It is commonly believed that topologically nontrivial one-dimensional systems support edge states rather than bulk states at zero energy. In this work, we find an unanticipated case of topological Anderson insulator (TAI) phase where two bulk modes are degenerate at zero energy, in addition to degenerate edge modes. We term this "ungapped TAI" to distinguish it from the previously known gapped TAIs. Our experimental realization of both gapped and ungapped TAIs relies on coupled photonic resonators, in which the disorder in coupling is judiciously engineered by adjusting the spacing between the resonators. By measuring the local density of states both in the bulk and at the edges, we demonstrate the existence of these two types of TAIs, together forming a TAI plateau in the phase diagram. Our experimental findings are well supported by theoretical analysis. In the ungapped TAI phase, we observe stable coexistence of topological edge states and localized bulk states at zero energy, highlighting the distinction between TAIs and traditional topological insulators.

12.
BMC Cancer ; 24(1): 1187, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334021

RESUMO

N6-methyladenosine (m6A) is a prevalent mRNA modification known for its implications in various cancer types, yet its role in chromophobe renal cell carcinoma (chRCC) remains largely unexplored. In this study, we performed m6A-SEAL-seq and RNA-seq analyses on tissues from three chRCC subjects, aiming to uncover m6A alterations in chRCC. Our findings revealed reduced expression levels of four m6A regulators in chRCC tissues and highlighted differences in m6A levels compared to normal tissues. Furthermore, we identified specific genes and cancer-related pathways affected by these differences, including notable candidates like NOTCH1 and FGFR1, implicated in chRCC development. Additionally, we developed a predictive model based on the expression level of m6A associated genes, demonstrating promising prognostic capabilities for patient survival prediction. Overall, our study provides valuable insights into the role of m6A in chRCC and its potential as a prognostic indicator.


Assuntos
Adenosina , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Masculino , Feminino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Perfilação da Expressão Gênica
13.
Hum Genomics ; 17(1): 77, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37592328

RESUMO

BACKGROUND: Thalassemia is an extremely prevalent monogenic inherited blood disorder in southern China. It is important to comprehensively understand the molecular spectrum of thalassemia in an area with such a high prevalence of thalassemia before taking appropriate actions for the prevention and treatment of this disorder. Herein, we explored the clinical feasibility of using next-generation sequencing (NGS) for large-scale population screening to illustrate the prevalence and spectrum of thalassemia in Southern Jiangxi. METHODS: Blood samples collected from 136,312 residents of reproductive age in Southern Jiangxi were characterized for thalassemia by NGS. A retrospective analysis was then conducted on blood samples determined to be positive for thalassemia. RESULTS: In total, 19,827 (14.545%) subjects were diagnosed as thalassemia carriers, and the thalassemia prevalence rate significantly varied by geographical region (p < 0.001). A total of 40 α-thalassemia genotypes including 21 rare genotypes were identified, with -@-SEA/αα being the most prevalent genotype. 42 ß-thalassemia genotypes including 27 rare genotypes were identified, with the most common mutation IVS II-654 C > T accounting for 35.257% of these ß-thalassemia genotypes. Furthermore, 74 genotypes were identified among 608 individuals with combined α- and ß-thalassemia. Notably, most individuals with rare thalassemia mutations had mildly abnormal hematologic parameters including microcytic hypochromia. CONCLUSIONS: Our findings demonstrate the great heterogeneity and diverse spectrum of thalassemia in Southern Jiangxi, emphasizing the importance and necessity of persistent prevention and control of thalassemia in this region. Additionally, our findings further suggest that NGS can effectively identify rare mutations and reduce the misdiagnosis rate of thalassemia.


Assuntos
Talassemia alfa , Talassemia beta , Humanos , Talassemia beta/epidemiologia , Talassemia beta/genética , Estudos Retrospectivos , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Sequenciamento de Nucleotídeos em Larga Escala , China/epidemiologia
14.
Hum Genomics ; 17(1): 33, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-37004060

RESUMO

BACKGROUND: Super-enhancers (SEs), driving high-level expression of genes with tumor-promoting functions, have been investigated recently. However, the roles of super-enhancer-associated lncRNAs (SE-lncRNAs) in tumors remain undetermined, especially in gliomas. We here established a SE-lncRNAs expression-based prognostic signature to choose the effective treatment of glioma and identify a novel therapeutic target. METHODS: Combined analysis of RNA sequencing (RNA-seq) data and ChIP sequencing (ChIP-seq) data of glioma patient-derived glioma stem cells (GSCs) screened SE-lncRNAs. Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets served to construct and validate SE-lncRNA prognostic signature. The immune profiles and potential immuno- and chemotherapies response prediction value of the signature were also explored. Moreover, we verified the epigenetic activation mechanism of LINC00945 via the ChIP assay, and its effect on glioma was determined by performing the functional assay and a mouse xenograft model. RESULTS: 6 SE-lncRNAs were obtained and identified three subgroups of glioma patients with different prognostic and clinical features. A risk signature was further constructed and demonstrated to be an independent prognostic factor. The high-risk group exhibited an immunosuppressive microenvironment and was higher enrichment of M2 macrophage, regulatory T cells (Tregs), and Cancer-associated fibroblasts (CAFs). Patients in the high-risk group were better candidates for immunotherapy and chemotherapeutics. The SE of LINC00945 was further verified via ChIP assay. Mechanistically, BRD4 may mediate epigenetic activation of LINC00945. Additionally, overexpression of LINC00945 promoted glioma cell proliferation, EMT, migration, and invasion in vitro and xenograft tumor formation in vivo. CONCLUSION: Our study constructed the first prognostic SE-lncRNA signature with the ability to optimize the choice of patients receiving immuno- and chemotherapies and provided a potential therapeutic target for glioma.


Assuntos
Glioma , RNA Longo não Codificante , Humanos , Animais , Camundongos , Prognóstico , RNA Longo não Codificante/genética , Proteínas Nucleares , Fatores de Transcrição , Glioma/genética , Modelos Animais de Doenças , Microambiente Tumoral/genética , Proteínas de Ciclo Celular
15.
Genet Res (Camb) ; 2024: 9279653, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39185021

RESUMO

Backgroundsand Aims. Colorectal cancer (CRC) represents a major global health challenge, necessitating comprehensive investigations into its underlying molecular mechanisms to enhance diagnostic and therapeutic strategies. This study focuses on elucidating the oncogenic role of Membrane-Associated Ring-CH-Type Finger 9 (MARCHF9), a RING-Type E3 ubiquitin transferase, in CRC. We aim to assess MARCHF9's clinical significance, functional impact on CRC progression, and its potential as a prognostic biomarker. Methods. We leveraged data from the Cancer Genome Atlas (TCGA) cohort to evaluate MARCHF9 expression profiles in CRC. In vitro experiments involved siRNA-mediated MARCHF9 knockdown in COAD cell lines (SW480 and LoVo). Cell proliferation and invasion assays were conducted to investigate MARCHF9's functional relevance. Survival analyses were performed to assess its prognostic role. Results. Our analysis revealed significantly elevated MARCHF9 expression in CRC tissues compared to normal colorectal tissues (P < 0.05). High MARCHF9 expression correlated with advanced clinical stages, distant metastases, and the presence of residual tumors in CRC patients. Survival analyses demonstrated that high MARCHF9 expression predicted unfavorable overall and disease-free survival outcomes (P < 0.05). In vitro experiments further supported its oncogenic potential, with MARCHF9 knockdown inhibiting COAD cell proliferation and invasion. Conclusions. This study unveils the oncogenic role of MARCHF9 in CRC, highlighting its clinical relevance as a potential biomarker and therapeutic target. MARCHF9's association with adverse clinicopathological features and its functional impact on cancer cell behavior underscore its significance in CRC progression. Further research is essential to elucidate precise mechanisms by which MARCHF9 enhances tumorigenesis and to explore its therapeutic potential in CRC management.


Assuntos
Biomarcadores Tumorais , Proliferação de Células , Neoplasias Colorretais , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Prognóstico , Proliferação de Células/genética , Linhagem Celular Tumoral , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Masculino , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Carcinogênese/genética , Oncogenes/genética , Idoso
16.
J Med Primatol ; 53(5): e12734, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39245882

RESUMO

A captive 17-year-old male cynomolgus monkey (Macaca fascicularis) developed diffuse large B-cell lymphoma (DLBCL). This was the first report of DLBCL presenting with a mandible mass and violation of the paranasal sinus in a cynomolgus monkey. The neoplasm showed marked microscopical malignant aspects. Immunohistochemical staining showed strong positive expression of CD20. These features may contribute to the diagnosis and therapeutics of DLBCL in NHPs.


Assuntos
Linfoma Difuso de Grandes Células B , Macaca fascicularis , Doenças dos Macacos , Animais , Masculino , Linfoma Difuso de Grandes Células B/veterinária , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Doenças dos Macacos/patologia , Doenças dos Macacos/diagnóstico
17.
Br J Anaesth ; 132(1): 45-52, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38007377

RESUMO

BACKGROUND: Preliminary clinical trials of adamgammadex, a new cyclodextrin-based selective reversal agent, have demonstrated its efficacy in reversing neuromuscular block by rocuronium. METHODS: This multicentre, randomised, double-blind, positive-controlled, non-inferiority phase III clinical trial compared the efficacy and safety of adamgammadex and sugammadex. We randomised 310 subjects to receive adamgammadex (4 mg kg-1) or sugammadex (2 mg kg-1) at reappearance of the second twitch of the train-of-four (TOF), and standard safety data were collected. RESULTS: For the primary outcome, the proportion of patients with TOF ratio ≥0.9 within 5 min was 98.7% in the adamgammadex group vs 100% in the sugammadex group, with a point estimate and 95% confidence interval (CI) of 1.3% (-4.6%, +1.3%); the lower limit was greater than the non-inferiority margin of -10%. For the key secondary outcome, the median (inter quartile range) time from the start of administration of adamgammadex or sugammadex to recovery of TOF ratio to 0.9 was 2.25 (1.75, 2.75) min and 1.75 (1.50, 2.00) min, respectively. The difference was 0.50 (95% CI: 0.25, 0.50); the upper limit was lower than the non-inferiority margin of 5 min. In addition, there were no inferior results observed in secondary outcomes. Adamgammadex had a lower incidence of adverse drug reactions compared with sugammadex (anaphylactic reaction, recurarisation, decreased heart rate, and laryngospasm; P=0.047). CONCLUSIONS: Adamgammadex was non-inferior to sugammadex with a possible lower incidence of adverse drug reactions compared with sugammadex. Adamgammadex may have a potential advantage in terms of its overall risk-benefit profile. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000039525. Registered October 30, 2020. https://www.chictr.org.cn/showproj.html?proj=56825.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Humanos , Sugammadex/efeitos adversos , Rocurônio , Bloqueio Neuromuscular/métodos , gama-Ciclodextrinas/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Androstanóis/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia
18.
Nature ; 624(7991): 260-261, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38092905
19.
Appl Opt ; 63(12): 3130-3137, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38856457

RESUMO

Numerous applications at the photon-starved regime require a free-space coupling single-photon detector with a large active area, low dark count rate (DCR), and superior time resolutions. Here, we developed a superconducting microstrip single-photon detector (SMSPD), with a large active area of 260 µm in diameter, a DCR of ∼5k c p s, and a low time jitter of ∼171p s, operated at a near-infrared of 1550 nm and a temperature of ∼2.0K. As a demonstration, we applied the detector to a single-pixel galvanometer scanning system and successfully reconstructed the object information in depth and intensity using a time-correlated photon counting technology.

20.
Biochem Genet ; 62(2): 1325-1346, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37603193

RESUMO

Osteosarcoma (OS) is a malignant bone tumor that most commonly occurs in children and adolescents. OS patients have a poor prognosis, and 5-year survival rates have rarely improved significantly over the past few decades. OS prognosis may be related to the infiltration of tumor-associated macrophages (TAMs). However, the role of proangiogenic macrophages, a subtype of TAMs, in OS prognosis has not been reported. In this study, seven subtypes of TAMs were identified from single-cell RNA sequencing (scRNA-seq) data that we propose defining as proangiogenic TAMs (Angio-TAMs), interferon-primed TAMs (IFN-TAMs), inflammatory cytokine-enriched TAMs (Inflam-TAMs), immune regulatory TAMs (Reg-TAMs), lipid-associated TAMs (LA-TAMs), and resident-tissue macrophages like TAMs (RTM-TAMs) (containing two subcellular types). In the survival analysis of each macrophage subtype, it was found that patients with Angio-TAMs had the most significant difference in survival. Eight genes associated with Angio-TAMs were obtained by differential expression analysis, and these genes were built into a prognostic model using the LASSO algorithm. Clinical OS case samples were categorized into high-risk and low-risk subgroups using median risk scores. In comparison to the low-risk subgroup, the survival time of the high-risk subgroup was much shorter. Additional studies on immune cell infiltration and immune checkpoint molecule expression in the two risk subgroups were carried out. In immunotherapy response prediction, the Angio-TAM-associated gene risk signature was found to be negatively correlated with immune checkpoint responses. In addition, the associated enriched GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were mainly involved in the malignant progression of tumors. As suggested by these findings, the Angio-TAM gene risk signature may be an underlying prognostic biomarker and novel therapeutic target for OS patients.Kindly check and confirm whether the ESM file is correctly identifiedWe have checked this file and confirmed that it can be correctly identified.

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