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1.
Front Immunol ; 15: 1382449, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745657

RESUMO

Background: Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Methods: Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. Results: The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFß signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to B-cell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. Conclusion: This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies.


Assuntos
Lesão Pulmonar Aguda , Comunicação Celular , Perfilação da Expressão Gênica , Animais , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/imunologia , Camundongos , Humanos , Comunicação Celular/imunologia , Transcriptoma , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/genética , Modelos Animais de Doenças , Análise de Célula Única , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Neutrófilos/metabolismo , COVID-19/imunologia , COVID-19/genética , Transdução de Sinais , Masculino , Macrófagos/imunologia , Macrófagos/metabolismo
2.
Food Res Int ; 183: 114202, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38760133

RESUMO

Pixian broad bean paste is a renowned fermented seasoning. The fermentation of broad bean is the most important process of Pixian broad bean paste. To enhance the flavor of tank-fermented broad bean paste, salt-tolerant Bacillus amyloliquefaciens strain was inoculated, resulting in an increase in total amount of volatile compounds, potentially leading to different flavor characteristics. To investigate the fermentation mechanism, monoculture simulated fermentation systems were designed. Metabolomics and transcriptomics were used to explore Bacillus amyloliquefaciens' transcriptional response to salt stress and potential aroma production mechanisms. The results highlighted different metabolite profiles under salt stress, and the crucial roles of energy metabolism, amino acid metabolism, reaction system, transportation system in Bacillus amyloliquefaciens' hypersaline stress response. This study provides a scientific basis for the industrial application of Bacillus amyloliquefaciens and new insights into addressing the challenges of poor flavor quality in tank fermentation products.


Assuntos
Bacillus amyloliquefaciens , Fermentação , Metabolômica , Bacillus amyloliquefaciens/metabolismo , Bacillus amyloliquefaciens/genética , Transcriptoma , Microbiologia de Alimentos , Alimentos Fermentados/microbiologia , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/metabolismo , Perfilação da Expressão Gênica , Paladar , Fabaceae/microbiologia
3.
Sensors (Basel) ; 24(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38794032

RESUMO

Control design for the nonlinear cascaded system is challenging due to its complicated system dynamics and system uncertainty, both of which can be considered some kind of system nonlinearity. In this paper, we propose a novel nonlinearity approximation scheme with a simplified structure, where the system nonlinearity is approximated by a steady component and an alternating component using only local tracking errors. The nonlinearity of each subsystem is estimated independently. On this basis, a model-free adaptive control for a class of nonlinear cascaded systems is proposed. A squared-error correction procedure is introduced to regulate the weight coefficients of the approximation components, which makes the whole adaptive system stable even with the unmodeled uncertainties. The effectiveness of the proposed controller is validated on a flexible joint system through numerical simulations and experiments. Simulation and experimental results show that the proposed controller can achieve better control performance than the radial basis function network control. Due to its simplicity and robustness, this method is suitable for engineering applications.

4.
Eur J Oncol Nurs ; 70: 102608, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38795445

RESUMO

PURPOSE: To support colorectal cancer couples cope with cancer, we developed a couple-based unmet supportive care needs intervention program guided by the Supportive Care Needs Framework and examined the feasibility, acceptability, and initial effects of the unmet supportive care needs program. METHODS: The design of a pre-and post-intervention study was conducted among Chinese colorectal cancer couples. The intervention was delivered in five sessions through in-person and telephone interventions combined. To measure program feasibility through recruitment and retention rates, and to test program acceptability through quantitative and qualitative post-intervention program assessments. The complete data (N = 20 pairs) were used to calculate effect sizes to assess the initial intervention effect. RESULTS: There was evidence of the feasibility of the intervention program in terms of recruitment (66.7%) and retention (83.3%) rates. Participants' satisfaction with the program also attested to its acceptability. The intervention (Cohen's = 0.15-0.56) had a small-moderate effect size in improving unmet supportive care needs and most cancer-adapted outcomes for colorectal cancer couples, validating the initial effect of the program. CONCLUSIONS: The unmet supportive care needs program is feasible, acceptable, and preliminarily effective in supporting Chinese colorectal cancer couples to improve unmet supportive care needs and cancer adaptability, as provided by this study.

6.
Plants (Basel) ; 13(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732469

RESUMO

During the period preceding the vegetation growing season (GS), temperature emerges as the pivotal factor determining phenology in northern terrestrial ecosystems. Despite extensive research on the impact of daily mean temperature (Tmean) during the preseason period, the influence of diurnal temperature range (DTR) on vegetation photosynthetic phenology (i.e., the impact of the plant photosynthetic cycle on seasonal time scale) has largely been neglected. Using a long-term vegetation photosynthetic phenology dataset and historical climate data, we examine vegetation photosynthetic phenology dynamics and responses to climate change across the mid-high latitudes of the Northern Hemisphere from 2001 to 2020. Our data reveal an advancing trend in the start of the GS (SOS) by -0.15 days per year (days yr-1), affecting 72.1% of the studied area. This is particularly pronounced in western Canada, Alaska, eastern Asia, and latitudes north of 60°N. Conversely, the end of the GS (EOS) displays a delaying trend of 0.17 days yr-1, impacting 62.4% of the studied area, especially northern North America and northern Eurasia. The collective influence of an earlier SOS and a delayed EOS has resulted in the notably prolonged length of the GS (LOS) by 0.32 days yr-1 in the last two decades, affecting 70.9% of the studied area, with Eurasia and western North America being particularly noteworthy. Partial correlation coefficients of the SOS with preseason Tmean, DTR, and accumulated precipitation exhibited negative values in 98.4%, 93.0%, and 39.2% of the study area, respectively. However, there were distinct regional variations in the influence of climate factors on the EOS. The partial correlation coefficients of the EOS with preseason Tmean, DTR, and precipitation were positive in 58.6%, 50.1%, and 36.3% of the region, respectively. Our findings unveil the intricate mechanisms influencing vegetation photosynthetic phenology, holding crucial significance in understanding the dynamics of carbon sequestration within terrestrial ecosystems amidst climate change.

7.
ACS Appl Mater Interfaces ; 16(19): 25246-25255, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38696547

RESUMO

Ion transportation via the mixed mechanisms of hydrogels underpins ultrafast biological signal transmission in nature, and its application to the rapid and sensitive sensing detection of human specific ions is of great interest for the field of medical science. However, current research efforts are still unable to achieve transmission results that are comparable to those of bioelectric signals. Herein, 3D interconnected nanochannels based on poly(pyrrole-co-dopamine)/poly(vinyl alcohol) (P(Py-co-DA)/PVA) supernetwork conductive hydrogels are designed and fabricated as stimuli-responsive structures for K+ ions. Distinct from conventional configurations, which exhibit rapid electron transfer and permeability to biosubstrates, interconnected nanofluidic nanochannels collaborated with the P(Py-co-DA) conductive polymer in the supernetwork conductive hydrogel significantly improve conductivity (88.3 mS/cm), ion transport time (0.1 s), and ion sensitivity (74.6 mV/dec). The faster ion response time is attributed to the synergism of excellent conductivity originating from the P(Py-co-DA) polymer and the electronic effect in the interconnected nanofluidic channels. Furthermore, the supernetwork conductive hydrogel demonstrates K+ ion selectivity relative to other cations in biofluids such as Na+, Mg2+, and Ca2+. The DFT calculation indicates that the small solvation energy and low chemical transfer resistance are the main reasons for the excellent K+ ion selectivity. Finite element analysis (FEA) simulations further support these experimental results. Consequently, the P(Py-co-DA)/PVA supernetwork conductive hydrogels enriched with the 3D interconnected nanofluidic channels developed in this work possess excellent sensing of K+ ions. This strategy provides great insight into efficient ion sensing in traditional biomedical sensing that has not been explored by previous researchers.

8.
Angew Chem Int Ed Engl ; : e202404816, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38788189

RESUMO

Room-temperature sodium-sulfur (RT Na-S) batteries, noted for their low material costs and high energy density, are emerging as a promising alternative to LIBs in various applications including power grids and standalone renewable energy systems. These batteries are commonly assembled with glass fiber membranes, which face significant challenges like the dissolution of polysulfides, sluggish sulfur conversion kinetics, and the dendrites growth. Here, we develop an amorphous FeSnOx nanosheet with hierarchical vacancies, including abundant oxygen vacancies (Ovs) and nano-sized perforations, that can be assembled into a multifunctional layer overlaying commercial separators for RT Na-S batteries. The Ovs offer strong adsorption and abundant catalytic sites for polysulfides, while the defect concentration is finely tuned to elucidate the polysulfides conversion mechanisms. The nano-sized perforations aid in regulating Na ions transport, resulting in uniform Na deposition. Moreover, the strategic addition of trace amounts of Ti3C2 forms an amorphous/crystalline interface that significantly improves the mechanical properties of the separator and suppresses dendrite growth. As a result, the task-specific layer achieves ultra-light (~0.1mg cm-2), ultra-thin (~200nm), and ultra-robust (modulus = 4.9GPa) characteristics. Consequently, the RT Na-S battery maintained a high capacity of 610.3mAh g-1 and an average Coulombic efficiency of 99.9% after 400 cycles at 0.5C.

9.
Biomed Pharmacother ; 175: 116800, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38788547

RESUMO

The limited expansion ability and functional inactivation of T cells within the solid tumor microenvironment are major problems faced during in the application of using tumor-infiltrating lymphocytes (TILs) in vivo. We sought to determine whether TILs carrying a PD-1-CD28-enhanced receptor and CD19 CAR could overcome this limitation and mediate tumor regression. First, anti-tumor effects of PD-1-CD28-enhanced receptor or CD19 CAR modified NY-ESO-1-TCR-T cells to mimic the TILs function (hereafter "PD-1-CD28-TCR-T" or "CD19 CAR-TCR-T" cells, respectively) were tested using the NY-ESO-1 over-expressed tumor cell line in vitro and in a tumor-bearing model. Furthermore, the safety and anti-tumor ability of S-TILs (TILs modified through transduction with a plasmid encoding the PD-1-CD28-T2A-CD19 CAR) were evaluated in vivo. PD-1-CD28-TCR-T cells showed a formidable anti-tumor ability that was not subject to PD-1/PD-L1 signaling in vivo. CD19 CAR-TCR-T cells stimulated with CD19+ B cells exhibited powerful expansion and anti-tumor abilities both in vitro and in vivo. Three patients with refractory solid tumors received S-TILs infusion. No treatment-related mortality was observed, and none of the patients experienced serious side effects. One patient with melanoma achieved a partial response, and two patients with colon or kidney cancer achieved long-term stable disease following S-TILs therapy. To the best of our knowledge, this is the first study describing the safety and efficacy of the adoptive transfer of autologous S-TILs to control disease in patients with advanced cancers, suggesting that S-TILs may be a promising alternative therapy for cancer.

10.
J Ethnopharmacol ; 331: 118327, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750987

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Rohdea pachynema F.T.Wang & Tang (R. pachynema), is a traditional folk medicine used for the treatment of stomach pain, stomach ulcers, bruises, and skin infections in China. Some of the diseases may relate to microbial infections in traditional applications. However few reports on its antimicrobial properties and bioactive components. AIM OF THE STUDY: To identify its bioactive constituents against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, and its mechanism. MATERIALS AND METHODS: The anti-MRSA ingredient 6α-O-[ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-quinovopyranosyl]-(25S)-5α-spirostan-3ß-ol (XQS) was obtained from R. pachynema by phytochemical isolation. Subsequently, XQS underwent screening using the broth microdilution method and growth inhibition curves to assess its antibacterial activity. The mechanism of XQS was evaluated by multigeneration induction, biofilm resistance assay, scanning electron microscopy, transmission electron microscopy, and metabolomics. Additionally, a mouse skin infection model was established in vivo. RESULTS: 26 compounds were identified from the R. pachynema, in which anti-MRSA spirostane saponin (XQS) was reported for the first time with a minimum inhibitory concentration (MIC) of 8 µg/mL. XQS might bind to peptidoglycan (PGN) of the cell wall, phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) of the cell membrane, then destroying the cell wall and the cell membrane, resulting in reduced membrane fluidity and membrane depolarization. Furthermore, XQS affected MRSA lipid metabolism, amino acid metabolism, and ABC transporters by metabolomics analysis, which targeted cell walls and membranes causing less susceptibility to drug resistance. Furthermore, XQS (8 mg/kg) recovered skin wounds in mice infected by MRSA effectively, superior to vancomycin (8 mg/kg). CONCLUSIONS: XQS showed anti-MRSA bioactivity in vitro and in vivo, and its mechanism association with cell walls and membranes was reported for the first, which supported the traditional uses of R. pachynema and explained its sensitivity to MRSA.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Saponinas , Animais , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação , Camundongos , Saponinas/farmacologia , Saponinas/isolamento & purificação , Espirostanos/farmacologia , Espirostanos/isolamento & purificação , Biofilmes/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Feminino , Peixes , Masculino
11.
Pathol Res Pract ; 258: 155330, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38733868

RESUMO

Mitochondrial DNA (mtDNA) is a circular double-stranded genome that exists independently of the nucleus. In recent years, research on mtDNA has significantly increased, leading to a gradual increase in understanding of its physiological and pathological characteristics. Reactive oxygen species (ROS) and other factors can damage mtDNA. This damaged mtDNA can escape from the mitochondria to the cytoplasm or extracellular space, subsequently activating immune signaling pathways, such as NLR family pyrin domain protein 3 (NLRP3), and triggering inflammatory responses. Numerous studies have demonstrated the involvement of mtDNA damage and leakage in the pathological mechanisms underlying various diseases including infectious diseases, metabolic inflammation, and immune disorders. Consequently, comprehensive investigation of mtDNA can elucidate the pathological mechanisms underlying numerous diseases. The prevention of mtDNA damage and leakage has emerged as a novel approach to disease treatment, and mtDNA has emerged as a promising target for drug development. This article provides a comprehensive review of the mechanisms underlying mtDNA-induced inflammation, its association with various diseases, and the methods used for its detection.


Assuntos
DNA Mitocondrial , Inflamação , Humanos , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Inflamação/metabolismo , Inflamação/genética , Animais , Dano ao DNA , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
12.
Mol Med Rep ; 30(1)2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38757304

RESUMO

Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote the gut microbiota homeostasis; however, its role in renoprotection remains unknown. The present study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8­week 2% NaCl­feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, The medium and high doses of PLR significantly alleviated CKD­associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and downregulating the canonical Wnt/ß­catenin pathway. Furthermore, PLR rescued the gut microbiota dysbiosis and protected against high salt­induced gut barrier dysfunction. Enrichment of Akkermansia and Bifidobacterium was found after PLR intervention, the relative abundances of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was, at least partially, exerted through gut microbiota reestablishment and downregulation of the Wnt/ß­catenin pathway. The present study provided evidence for a new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.


Assuntos
Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Pueraria , Insuficiência Renal Crônica , Via de Sinalização Wnt , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Pueraria/química , Modelos Animais de Doenças , Disbiose/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Camundongos Endogâmicos C57BL , Transplante de Microbiota Fecal
13.
Free Radic Biol Med ; 220: 56-66, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38697489

RESUMO

Apart from dopaminergic neurotoxicity, exposure to rotenone, a commonly used insecticide in agriculture, also adversely affects hippocampal and cortical neurons, resulting in cognitive impairments in mice. We recently established a role of microglia-mediated neuroinflammation in rotenone-elicited deficits of cognition, yet the mechanisms remain elusive. Here, we investigated the involvement of NADPH oxidase 2 (NOX2) catalytic subunit gp91phox in rotenone-induced cognitive deficits and the associated mechanisms. Our study demonstrated that rotenone exposure elevated expression of gp91phox and phosphorylation of the NOX2 cytosolic subunit p47phox, along with NADPH depletion in the hippocampus and cortex of mice, indicating NOX2 activation. Specific knockdown of gp91phox in microglia via adeno-associated virus delivery resulted in reduced microglial activation, proinflammatory gene expression and improved learning and memory capacity in rotenone-intoxicated mice. Genetic deletion of gp91phox also reversed rotenone-elicited cognitive dysfunction in mice. Furthermore, microglial gp91phox knockdown attenuated neuronal damage and synaptic loss in mice. This intervention also suppressed iron accumulation, disruption of iron-metabolism proteins and iron-dependent lipid peroxidation and restored the balance of ferroptosis-related parameters, including GPX4, SLC711, PTGS2, and ACSL4 in rotenone-lesioned mice. Intriguingly, pharmacological inhibition of ferroptosis with liproxstatin-1 conferred protection against rotenone-induced neurodegeneration and cognitive dysfunction in mice. In summary, our findings underscored the contribution of microglial gp91phox-dependent neuroinflammation and ferroptosis to learning and memory dysfunction in rotenone-lesioned mice. These results provided valuable insights into the pathogenesis of cognitive deficits associated with pesticide-induced Parkinsonism, suggesting potential therapeutic avenues for intervention.


Assuntos
Ferroptose , Transtornos da Memória , Microglia , NADPH Oxidase 2 , Doenças Neuroinflamatórias , Rotenona , Animais , Camundongos , NADPH Oxidase 2/metabolismo , NADPH Oxidase 2/genética , Microglia/metabolismo , Microglia/patologia , Microglia/efeitos dos fármacos , Rotenona/toxicidade , Ferroptose/efeitos dos fármacos , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/induzido quimicamente , Doenças Neuroinflamatórias/genética , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Transtornos da Memória/genética , Transtornos da Memória/patologia , Masculino , Camundongos Endogâmicos C57BL , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Neurônios/metabolismo , Neurônios/patologia , Neurônios/efeitos dos fármacos , Camundongos Knockout
14.
Pharm Biol ; 62(1): 404-422, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38739082

RESUMO

CONTEXT: Traditional Chinese medicines (TCMs) have emerged as potential adjuvant therapies to treat non-small cell lung cancer. More direct comparative studies must be conducted among various oral TCMs. OBJECTIVE: This network meta-analysis evaluates the efficacy and safety of seven oral TCMs combined with chemotherapy in treating NSCLC. METHODS: The analysis included Zilongjin, Banmao, Hongdoushan, Huachansu, Kanglaite, Xihuang, and Pingxiao TCMs. Randomized-controlled trials (RCTs) were identified from the following databases: China National Infrastructure, Wanfang, PubMed, Embase, and the Cochrane Library up to April 2023. Two researchers independently extracted data. RESULTS: Sixty-eight RCTs (5,099 patients) were included. Compared to chemotherapy, Banmao capsules [odds ratio (OR) = 2.69, 95% confidence interval (CI) 1.96-3.69)] and Huachansu tablets [OR = 2.35, 95%CI (1.81, 3.05)] ranked in the top two in terms of increasing disease control rate. The two main TCMs to improve the objective response rate were Banmao capsules [OR = 3.49, 95%CI (2.17, 5.60)] and Zilongjin tablets [OR = 2.62, 95%CI (1.92, 3.57)]. Zilongjin tablets [OR = 3.47, 95%CI (2.14, 5.63)] and Huachansu tablets [OR = 3.30, 95%CI (1.65, 6.60)] were ranked as the top two in improving Karnofsky performance status. Hongdoushan capsules (SUCRA = 18.8%) and Banmao capsules (SUCRA = 19.8%) were the top two in reducing gastrointestinal toxicity. Zilongjin tablets (SUCRA = 18.9%) and Banmao capsules (SUCRA = 26.6%) were the top two to reduce liver and kidney toxicity. Hongdoushan capsules (SUCRA = 15.7%) and Huachansu tablets (SUCRA = 16.8%) ranked the top two in reducing thrombocytopenia. Banmao capsules (SUCRA = 14.3%) and Zilongjin tablets (SUCRA = 26.3%) were the top two decreasing leukopenia. CONCLUSIONS: Combining oral TCMs with platinum-based chemotherapy has shown superior efficacy compared to platinum-based chemotherapy alone in treating NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Medicina Tradicional Chinesa , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Administração Oral , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Resultado do Tratamento
15.
Nat Commun ; 15(1): 4406, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782991

RESUMO

The photoinduced non-thermalized hot electrons at an interface play a pivotal role in determining plasmonic driven chemical events. However, understanding non-thermalized electron dynamics, which precedes electron thermalization (~125 fs), remains a grand challenge. Herein, we simultaneously captured the dynamics of both molecules and non-thermalized electrons in the MXene/molecule complexes by femtosecond time-resolved spectroscopy. The real-time observation allows for distinguishing non-thermalized and thermalized electron responses. Differing from the thermalized electron/heat transfer, our results reveal two non-thermalized electron dynamical pathways: (i) the non-thermalized electrons directly transfer to attached molecules at an interface within 50 fs; (ii) the non-thermalized electrons scatter at the interface within 125 fs, inducing adsorbed molecules heating. These two distinctive pathways are dependent on the irradiating wavelength and the energy difference between MXene and adsorbed molecules. This research sheds light on the fundamental mechanism and opens opportunities in photocatalysis and interfacial heat transfer theory.

16.
Angew Chem Int Ed Engl ; : e202405449, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781085

RESUMO

Accessing versatile C(sp3)-C(sp3) bond through cross-electrophile coupling of two distinct etheric C-O bonds is crucial in organic synthesis but remains barely explored. Herein, we report an innovative photoinduced low-valent zirconocene catalysis enabling the reductive coupling of ethers with high activity and cross-selectivity. Mechanistic investigation suggests that photo-excitation of low-valent zirconocene facilitates the C(sp3)-O bond scission of benzylic ethers, leading to the benzylic radical intermediate via a single electron reduction pathway. The subsequent recombination of this benzylic radical to Zr center followed by carbomagnesiation generates benzylic Grignard reagents for down-stream coupling with aliphatic ethers through a SN2-like mechanism. In application, a wide range of ethers readily in-situ derived from aldehydes and ketones becomes feasible with high functional group compatibility as well as excellent cross-selectivity.

17.
Biosensors (Basel) ; 14(5)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38785687

RESUMO

The Wearable Robotic Limb (WRL) is a type of robotic arm worn on the human body, aiming to enhance the wearer's operational capabilities. However, proposing additional methods to control and perceive the WRL when human limbs are heavily occupied with primary tasks presents a challenge. Existing interactive methods, such as voice, gaze, and electromyography (EMG), have limitations in control precision and convenience. To address this, we have developed an interactive device that utilizes the mouth and tongue. This device is lightweight and compact, allowing wearers to achieve continuous motion and contact force control of the WRL. By using a tongue controller and mouth gas pressure sensor, wearers can control the WRL while also receiving sensitive contact feedback through changes in mouth pressure. To facilitate bidirectional interaction between the wearer and the WRL, we have devised an algorithm that divides WRL control into motion and force-position hybrid modes. In order to evaluate the performance of the device, we conducted an experiment with ten participants tasked with completing a pin-hole assembly task with the assistance of the WRL system. The results show that the device enables continuous control of the position and contact force of the WRL, with users perceiving feedback through mouth airflow resistance. However, the experiment also revealed some shortcomings of the device, including user fatigue and its impact on breathing. After experimental investigation, it was observed that fatigue levels can decrease with training. Experimental studies have revealed that fatigue levels can decrease with training. Furthermore, the limitations of the device have shown potential for improvement through structural enhancements. Overall, our mouth and tongue interactive device shows promising potential in controlling the WRL during tasks where human limbs are occupied.


Assuntos
Boca , Robótica , Língua , Dispositivos Eletrônicos Vestíveis , Humanos , Masculino , Adulto , Eletromiografia
18.
Eur Radiol ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780767

RESUMO

OBJECTIVE: To investigate the association of coronary plaque burden variables derived from coronary computed tomography angiography (CCTA) before patients underwent their first percutaneous coronary intervention (PCI) procedure and major adverse cardiovascular events (MACEs) after PCI. METHODS: Patients who underwent CCTA before their first PCI were included retrospectively. A radiologist and a cardiologist analyzed CCTA images on a dedicated workstation. The coronary plaque burden variables included total plaque volume, total percent atheroma volume, volumes and fractions of total low-attenuation plaque, total fibrous plaque, and total calcified plaque. The primary outcomes were MACEs, a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unscheduled coronary revascularization. RESULTS: A total of 230 patients were included in the final analysis. During a median follow-up of 4.8 years, 67 MACEs occurred. Total plaque volume, total percent atheroma volume, volumes of total low-attenuation plaque and total fibrous plaque but not their fractions were independent predictors for MACEs. Compared with the first tertiles, the hazard ratio of the third tertile of total plaque volume, total percent atheroma volume, total low-attenuation plaque volume, and total fibrous plaque volume were 2.06 (95% CI: 1.03-4.15), 2.15 (95% CI: 1.02-4.51), 3.04 (95% CI: 1.45-6.36), and 2.23 (95% CI: 1.11-4.46), respectively. Neither total calcified plaque volume nor fraction was associated with MACEs independently. CONCLUSION: Selected pre-PCI CCTA-derived variables, including total percent atheroma volume, volumes of total plaque, total low-attenuation plaque and total fibrous plaque, were significantly associated with MACEs after PCI, suggesting that CCTA before PCI reveals the residual risk after revascularization. CLINICAL RELEVANCE STATEMENT: The coronary plaque burden variables derived from coronary computed tomography angiography before percutaneous coronary intervention are independently associated with major adverse cardiovascular events, which could be instrumental in optimizing patient management. KEY POINTS: Coronary plaque burden is associated with cardiovascular events in patients with coronary artery disease. Selected total plaque burden variables derived from coronary computed tomography angiography before percutaneous coronary intervention were associated with poor prognosis. Routine coronary computed tomography angiography before percutaneous coronary intervention might be helpful in reducing future risks.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38769606

RESUMO

BACKGROUND: Antihypertensive drugs are known to lower cardiovascular mortality, but the role of different types of antihypertensive drugs in lifespan has not been clarified. Moreover, the underlying mechanisms remain unclear. METHODS: To minimize confounding, we used Mendelian randomization to assess the role of different antihypertensive drug classes in longevity and examined the pathways via proteins. Genetic variants associated with systolic blood pressure (SBP) corresponding to drug target genes were used as genetic instruments. The genetic associations with lifespan were obtained from a large genome-wide association study including 1 million European participants from UK Biobank and LifeGen. For significant antihypertensive drug classes, we performed sex-specific analysis, drug-target analysis and colocalization. To examine the mediation pathways, we assessed the associations of 2291 plasma proteins with lifespan, and examined the associations of drug classes with the proteins affecting lifespan. RESULTS: After correcting for multiple testing, genetically proxied beta-blockers (BBs), calcium channel blockers (CCBs) and vasodilators were related to longer life years (BBs: 2.03, 95% CI 0.78 to 3.28 per 5-mmHg reduction in SBP, CCBs: 3.40, 95% CI 1.47 to 5.33, and vasodilators: 2.92, 95% CI 1.08 to 4.77). The beneficial effects of BBs and CCBs were more obvious in men. ADRB1, CACNA2D2, CACNB3, CPT1A, CPT2, and EDNRA genes were related to extended lifespan with CPT2 further supported by colocalization evidence. 86 proteins were related to lifespan, of which 4 proteins were affected by CCBs. CDH1 may mediate the association between CCBs and lifespan. CONCLUSIONS: BBs, CCBs and vasodilators may prolong lifespan, with potential sex differences for BBs and CCBs. The role of CCBs in lifespan is partly mediated by CDH1. Prioritizing the potential protein targets can provide new insights into healthy aging.

20.
Med ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38781965

RESUMO

BACKGROUND: Predictive biomarkers and models of immune checkpoint inhibitors (ICIs) have been extensively studied in non-small cell lung cancer (NSCLC). However, evidence for many biomarkers remains inconclusive, and the opaqueness of machine learning models hinders practicality. We aimed to provide compelling evidence for biomarkers and develop a transparent decision tree model. METHODS: We consolidated data from 3,288 ICI-treated patients with NSCLC across real-world multicenter, public cohorts and the Choice-01 trial (ClinicalTrials.gov: NCT03856411). Over 50 features were examined for predicting durable clinical benefits (DCBs) from ICIs. Noteworthy biomarkers were identified to establish a decision tree model. Additionally, we explored the tumor microenvironment and peripheral CD8+ programmed death-1 (PD-1)+ T cell receptor (TCR) profiles. FINDINGS: Multivariate logistic regression analysis identified tumor histology, PD-ligand 1 (PD-L1) expression, tumor mutational burden, line, and regimen of ICI treatment as significant factors. Mutation subtypes of EGFR, KRAS, KEAP1, STK11, and disruptive TP53 mutations were associated with DCB. The decision tree (DT10) model, using the ten clinicopathological and genomic markers, showed superior performance in predicting DCB in the training set (area under the curve [AUC] = 0.82) and consistently outperformed other models in test sets. DT10-predicted-DCB patients manifested longer survival, an enriched inflamed tumor immune phenotype (67%), and higher peripheral TCR diversity, whereas the DT10-predicted-NDB (non-durable benefit) group showed an enriched desert immune phenotype (86%) and higher peripheral TCR clonality. CONCLUSIONS: The model effectively predicted DCB after front-/subsequent-line ICI treatment, with or without chemotherapy, for squamous and non-squamous lung cancer, offering clinicians valuable insights into efficacy prediction using cost-effective variables. FUNDING: This study was supported by the National Key R&D Program of China.

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