Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.615
Filtrar
1.
Int J Gen Med ; 17: 1193-1211, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559590

RESUMO

Background: Esophageal squamous cell carcinoma (ESCC) is an aggressive and fatal malignancy that leads to epithelial cancer. The association between epithelial cell heterogeneity, prognosis, and immune response in this cancer remains uncertain. This study aimed to investigate epithelial cell heterogeneity in ESCC and develop a predictive risk model using the identified cell types. Methods: Single-cell RNA sequencing (scRNA-seq) and differential ESCC gene data were accessed from the Gene Expression Omnibus. Functional enrichment analysis, inferCNV, cell development trajectories, and intercellular communication were analyzed following epithelial cell characterization. Differentially expressed ESCC (n = 773) and epithelial cell marker genes (n = 3407) were intersected to obtain core genes, and epithelial cell-related prognostic genes were identified. LASSO regression analysis was used to construct a prognostic model. The external dataset GSE53624 was used to further validate the stability of the model. Drug sensitivity predictions, and immune cell infiltration were analyzed. Molecular docking clarified the possible therapeutic role of ß-sitosterol in ESCC. Finally, wound healing assay, cell colony, and transwell assay were constructed to detect the effects of the core gene PDLIM2 on ESCC cell proliferation, invasion, and migration. Results: Eight cell clusters were identified, and epithelial cells were categorized into tumor and paratumor groups. The tumor group possessed more chromosomal variants than the paratumor group. Epithelial cells were associated with multiple cell types and significantly correlated with the Wnt, transforming growth factor, and epidermal growth factor signaling pathways. From 231 intersected genes, five core genes were screened for use in the risk model: CTSL, LAPTM4B, MYO10, NCF2, and PDLIM2. These genes may contribute to the cancerous transformation of normal esophageal epithelial cells and thereby act as biomarkers and potential therapeutic targets in patients with ESCC. ß-Sitosterol furthermore displayed excellent docking potential with these genes. Meanwhile, further experiments demonstrated that the gene PDLIM2 plays a major role in the progression of oesophageal squamous carcinoma. Conclusion: We successfully developed a risk model for the prognosis of ESCC based on epithelial cells that addresses the response of ESCC to immunotherapy and offers novel cancer treatment options.

3.
Front Pediatr ; 12: 1327648, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562135

RESUMO

Background: The data report of a large sample, dynamic epidemiology, and characteristic analysis of pediatric tuberculosis (TB) in Southwest China is not clear. Herein, we conducted descriptive dynamic epidemiology, characteristic analysis and geographical distribution study of pediatric TB inpatients in Southwest China for more than 20 years. Methods: Patients with pediatric TB were recruited from October 2002 to September 2022 in Southwest of China based on etiology or clinical confirmation. Extract hospitalization medical record information for each patient. The geographical distribution chart of cases is used to display the trend of case flow segmented every 5 years. Results: Among 3,024 pediatric TB patients with an average age of 9.11 ± 4.39, 17.49% (529) had pulmonary tuberculosis (PTB), 9.06% (274) had extrapulmonary tuberculosis (EPTB), and 73.45% (2,221) had combined TB. The most common form of EPTB is disseminated TB (28.98%), followed by TB lymphadenitis (20.56%), pleural TB (19.72%), and TB meningitis (19.68%). Children aged 0-4 years had a high risk of TB meningitis and a severe symptoms, while children in the elderly age group had a high risk of pleural TB. In the past 20 years, hospitalized TB pediatric cases mainly came from Sichuan, Tibet, Qinghai, Yunnan and other places. The number of patients from ethnic minorities, especially Tibetans, showed an upward trend on a yearly basis (χ2 = 401.43, P < 0.001). Conclusions: Public health investment and effective management in pediatric TB should be further strengthened.

4.
Appl Opt ; 63(8): 1962-1970, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38568636

RESUMO

In this paper, a dual-band terahertz metamaterial sensor based on aluminum and silicon is proposed and simulated. The aluminum surface, which is deposited on a silicon substrate, is made of a C-shaped frame resonator, a rectangular beam, and a cross. The device is insensitive to the change of incident angle in the range of 0°-30°, which shows the great transmission stability of the sensor. By examining the resonance frequency shift, it is shown that 98.3 and 237.5 GHz/RIU refractive index sensitivity can be obtained near 1.76 and 2.404 THz transmission dips of the proposed structure, respectively. The two dips can be used to sense analytes in different refractive index ranges, respectively. For Dip 1 at 1.76 THz, the range is 1.0-1.6. For Dip 2 at 2.404 THz, the range is 1.6-2.0. Different from traditional multi-band metamaterial sensors, two dips generated by the proposed device can measure continuous and non-multiplexed refractive index ranges, respectively. Because the resonance frequencies of matters are different, such a characteristic enables the device to measure different types of analyte using the appropriate resonant peak. A central-relief design is then proposed based on perturbation theory to further improve its sensing performance. The aluminum cross is covered by polyimide, which can interfere with the scattering field on the metal surface and affect the transmission results. For both transmission dips, the optimized structure realizes higher sensitivities of 111.7 GHz/RIU and 262.5 GHz/RIU, respectively. More significantly, the optimized structure also has the characteristic of a wide and non-multiplexed refractive index range. In addition, the effects of analyte thickness and polyimide layer thickness on sensor performance are also discussed. The proposed structure opens up new prospects in the design of multiple-band terahertz metamaterial sensors. It can also meet the sensing needs of biomedical, environmental monitoring, and industrial manufacturing.

6.
bioRxiv ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38559100

RESUMO

MYC-driven medulloblastoma (MB) is a highly aggressive cancer type with poor prognosis and limited treatment options. Through CRISPR-Cas9 screening across MB cell lines, we identified the Mediator-associated kinase CDK8 as the top dependence for MYC-driven MB. Loss of CDK8 markedly reduces MYC expression and impedes MB growth. Mechanistically, we demonstrate that CDK8 depletion suppresses ribosome biogenesis and mRNA translation. CDK8 regulates occupancy of phospho-Polymerase II at specific chromatin loci facilitating an epigenetic alteration that promotes transcriptional regulation of ribosome biogenesis. Additionally, CDK8-mediated phosphorylation of 4EBP1 plays a crucial role in initiating eIF4E-dependent translation. Targeting CDK8 effectively suppresses cancer stem and progenitor cells, characterized by increased ribosome biogenesis activity. We also report the synergistic inhibition of CDK8 and mTOR in vivo and in vitro . Overall, our findings establish a connection between transcription and translation regulation, suggesting a promising therapeutic approach targets multiple points in the protein synthesis network for MYC-driven MB.

7.
J Cardiothorac Surg ; 19(1): 171, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566106

RESUMO

BACKGROUND: Acute Type A aortic dissection (ATAAD) is a life-threatening cardiovascular disease associated with high mortality rates, where surgical intervention remains the primary life-saving treatment. However, the mortality rate for ATAAD operations continues to be alarmingly high. To address this critical issue, our study aimed to assess the correlation between preoperative laboratory examination, clinical imaging data, and postoperative mortality in ATAAD patients. Additionally, we sought to establish a reliable prediction model for evaluating the risk of postoperative death. METHODS: In this study, a total of 384 patients with acute type A aortic dissection (ATAAD) who were admitted to the emergency department for surgical treatment were included. Based on preoperative laboratory examination and clinical imaging data of ATAAD patients, logistic analysis was used to obtain independent risk factors for postoperative in-hospital death. The survival prediction model was based on cox regression analysis and displayed as a nomogram. RESULTS: Logistic analysis identified several independent risk factors for postoperative in-hospital death, including Marfan syndrome, previous cardiac surgery history, previous renal dialysis history, direct bilirubin, serum phosphorus, D-dimer, white blood cell, multiple aortic ruptures and age. A survival prediction model based on cox regression analysis was established and presented as a nomogram. The model exhibited good discrimination and significantly improved the prediction of death risk in ATAAD patients. CONCLUSIONS: In this study, we developed a novel survival prediction model for acute type A aortic dissection based on preoperative clinical features. The model demonstrated good discriminatory power and improved accuracy in predicting the risk of death in ATAAD patients undergoing open surgery.


Assuntos
Dissecção Aórtica , Síndrome de Marfan , Humanos , Mortalidade Hospitalar , Estudos Retrospectivos , Dissecção Aórtica/cirurgia , Fatores de Risco
8.
Artigo em Inglês | MEDLINE | ID: mdl-38598680

RESUMO

Flexible foam-based sensors have attracted substantial interest due to their high specific surface area, light weight, superior deformability, and ease of manufacture. However, it is still a challenge to integrate multimodal stimuli-responsiveness, high sensitivity, reliable stability, and good biocompatibility into a single foam sensor. To achieve this, a magnetoresistive foam sensor was fabricated by an in situ freezing-polymerization strategy based on the interpenetrating networks of sodium alginate, poly(vinyl alcohol) in conjunction with glycerol, and physical reinforcement of core-shell bidisperse magnetic particles. The assembled sensor exhibited preferable magnetic/strain-sensing capability (GF ≈ 0.41 T-1 for magnetic field, 4.305 for tension, -0.735 for bending, and -1.345 for pressing), quick response time, and reliable durability up to 6000 cycles under external stimuli. Importantly, a machine learning algorithm was developed to identify the encryption information, enabling high recognition accuracies of 99.22% and 99.34%. Moreover, they could be employed as health systems to detect human physiological motion and integrated as smart sensor arrays to perceive external pressure/magnetic field distributions. This work provides a simple and ecofriendly strategy to fabricate biocompatible foam-based multimodal sensors with potential applications in next-generation soft electronics.

9.
J Am Chem Soc ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598684

RESUMO

Cross-coupling reactions represent an indispensable tool in chemical synthesis. An intriguing challenge in this field is to achieve selective cross-coupling between two precursors with similar reactivity or, to the limit, the identical molecules. Here we report an unexpected dehydrobrominative cross-coupling between 1,3,5-tris(2-bromophenyl)benzene molecules on silver surfaces. Using scanning tunneling microscopy, we examine the reaction process at the single-molecular level, quantify the selectivity of the dehydrobrominative cross-coupling, and reveal the modulation of selectivity by substrate lattice-related catalytic activity or molecular assembly effect. Theoretical calculations indicate that the dehydrobrominative cross-coupling proceeds via regioselective C-H bond activation of debrominated TBPB and subsequent highly selective C-C coupling of the radical-based intermediates. The reaction kinetics plays an important role in the selectivity for the cross-coupling. This work not only expands the toolbox for chemical synthesis but also provides important mechanistic insights into the selectivity of coupling reactions on the surface.

11.
Small ; : e2309756, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602191

RESUMO

Control over particle size and shape heterogeneity is highly relevant to the design of photonic coatings and supracolloidal assemblies. Most developments in the area have relied on mineral and petroleum-derived polymers that achieve well-defined chemical and dimensional characteristics. Unfortunately, it is challenging to attain such control when considering renewable nanoparticles. Herein, a pathway toward selectable biobased particle size and physicochemical profiles is proposed. Specifically, lignin is fractionated, a widely available heterogeneous polymer that can be dissolved in aqueous solution, to obtain a variety of monodispersed particle fractions. A two-stage cascade and density gradient centrifugation that relieves the need for solvent pre-extraction or other pretreatments but achieves particle bins of uniform size (~60 to 860 nm and polydispersity, PDI<0.06, dynamic light scattering) along with characteristic surface chemical features is introduced. It is found that the properties and associated colloidal behavior of the particles are suitably classified in distinctive size populations, namely, i) nanoscale (50-100 nm), ii) photonic (100-300 nm) and iii) near-micron (300-1000 nm). The strong correlation that exists between size and physicochemical characteristics (molar mass, surface charge, bonding and functional groups, among others) is introduced as a powerful pathway to identify nanotechnological uses that benefit from the functionality and cost-effectiveness of biogenic particles.

12.
Phys Med Biol ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593821

RESUMO

OBJECTIVE: The textures and detailed structures in computed tomography (CT) images are highly desirable for clinical diagnosis. This study aims to expand the current body of work on textures and details preserving convolutional neural networks for low-dose CT (LDCT) image denoising task. APPROACH: This study proposed a novel Multi-scale Feature Aggregation and Fusion network (MFAF-net) for LDCT image denoising. Specifically, we proposed a Multi-scale Residual Feature Aggregation Module (MRFAM) to characterize multi-scale structural information in CT images, which captures regional-specific inter-scale variations using learned weights. We further proposed a Cross-level Feature Fusion Module (CFFM) to integrate cross-level features, which adaptively weights the contributions of features from encoder to decoder by using a Spatial Pyramid Attention (SPA) mechanism. Moreover, we proposed a Self-supervised Multi-level Perceptual Loss Module (SMPLM) to generate multi-level auxiliary perceptual supervision for recovery of salient textures and structures of tissues and lesions in CT images, which takes advantage of abundant semantic information at various levels. We introduced parameters for the perceptual loss to adaptively weight the contributions of auxiliary features of different levels and we also introduced an automatic parameter tuning strategy for these parameters. MAIN RESULTS: Extensive experimental studies were performed to validate the effectiveness of the proposed method. Experimental results demonstrate that the proposed method can achieve better performance on both fine textures preservation and noise suppression for CT image denoising task compared with other competitive CNN based methods. SIGNIFICANCE: The proposed MFAF-net takes advantage of multi-scale receptive fields, cross-level features integration and self-supervised multi-level perceptual loss, enabling more effective recovering of fine textures and detailed structures of tissues and lesions in CT images.

13.
Chemistry ; : e202400629, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594211

RESUMO

Herein, we synthesized two donor-acceptor (D-A) type small organic molecules with self-assembly properties, namely MPA-BT-BA and MPA-2FBT-BA, both containing a low acidity anchoring group, benzoic acid. After systematically investigation, it is found that, with the fluorination, the MPA-2FBT-BA demonstrates a lower highest occupied molecular orbital (HOMO) energy level, higher hole mobility, higher hydrophobicity and stronger interaction with the perovskite layer than that of MPA-BT-BA. As a result, the device based-on MPA-2FBT-BA displays a better crystallization and morphology of perovskite layer with larger grain size and less non-radiative recombination. Consequently, the device using MPA-2FBT-BA as hole transport material achieved the power conversion efficiency (PCE) of 20.32% and remarkable stability. After being kept in an N2 glove box for 116 days, the unsealed PSCs' device retained 93% of its initial PCE. Even exposed to air with a relative humidity range of 30±5% for 43 days, its PCE remained above 91% of its initial condition. This study highlights the vital importance of the fluorination strategy combined with a low acidity anchoring group in SAMs, offering a pathway to achieve efficient and stable PSCs.

14.
Nat Commun ; 15(1): 3001, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589388

RESUMO

Designing two-dimensional halide perovskites for high-performance optoelectronic applications requires deep understanding of the structure-property relationship that governs their excitonic behaviors. However, a design framework that considers both intra and interlayer structures modified by the A-site and spacer cations, respectively, has not been developed. Here, we use pressure to synergistically tune the intra and interlayer structures and uncover the structural modulations that result in improved optoelectronic performance. Under applied pressure, (BA)2(GA)Pb2I7 exhibits a 72-fold boost of photoluminescence and 10-fold increase of photoconductivity. Based on the observed structural change, we introduce a structural descriptor χ that describes both the intra and interlayer characteristics and establish a general quantitative relationship between χ and photoluminescence quantum yield: smaller χ correlates with minimized trapped excitons and more efficient emission from free excitons. Building on this principle, we design a perovskite (CMA)2(FA)Pb2I7 that exhibits a small χ and an impressive photoluminescence quantum yield of 59.3%.

15.
BMC Nephrol ; 25(1): 125, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589792

RESUMO

BACKGROUND: Sepsis and acute kidney injury (AKI) are common severe diseases in the intensive care unit (ICU). This study aimed to estimate the attributable mortality of AKI among critically ill patients with sepsis and to assess whether AKI was an independent risk factor for 30-day mortality. METHODS: The information we used was derived from a multicenter prospective cohort study conducted in 18 Chinese ICUs, focusing on septic patients post ICU admission. The patients were categorized into two groups: those who developed AKI (AKI group) within seven days following a sepsis diagnosis and those who did not develop AKI (non-AKI group). Using propensity score matching (PSM), patients were matched 1:1 as AKI and non-AKI groups. We then calculated the mortality rate attributable to AKI in septic patients. Furthermore, a survival analysis was conducted comparing the matched AKI and non-AKI septic patients. The primary outcome of interest was the 30-day mortality rate following the diagnosis of sepsis. RESULTS: Out of the 2175 eligible septic patients, 61.7% developed AKI. After the application of PSM, a total of 784 septic patients who developed AKI were matched in a 1:1 ratio with 784 septic patients who did not develop AKI. The overall 30-day attributable mortality of AKI was 6.6% (95% CI 2.3 ∼ 10.9%, p = 0.002). A subgroup analysis revealed that the 30-day attributable mortality rates for stage 1, stage 2, and stage 3 AKI were 0.6% (95% CI -5.9 ∼ 7.2%, p = 0.846), 4.7% (95% CI -3.1 ∼ 12.4%, p = 0.221) and 16.8% (95% CI 8.1 ∼ 25.2%, p < 0.001), respectively. Particularly noteworthy was that stage 3 AKI emerged as an independent risk factor for 30-day mortality, possessing an adjusted hazard ratio of 1.80 (95% CI 1.31 ∼ 2.47, p < 0.001). CONCLUSIONS: The overall 30-day attributable mortality of AKI among critically ill patients with sepsis was 6.6%. Stage 3 AKI had the most significant contribution to 30-day mortality, while stage 1 and stage 2 AKI did not increase excess mortality.


Assuntos
Injúria Renal Aguda , Sepse , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Estado Terminal , Injúria Renal Aguda/diagnóstico , Unidades de Terapia Intensiva , Sepse/complicações
16.
Materials (Basel) ; 17(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38591485

RESUMO

This paper presents an investigation on the forming characteristics of the tailor rolled blank of an aluminum alloy (Al-TRB) during three-point bending at room temperature through experiments and finite element simulations. The strain distribution, spring-back characteristics, and metal flow law of 6000 series Al-TRB during three-point bending are explored. The prepared Al-TRB has good bending properties, and no surface cracks appear in the bending region of the Al-TRB when bent to 180°. Surface roughening occurs on the outside of the bending region. Since the strain in the thick zone is greater than that in the thin zone, the surface roughening in the thick zone is more obvious than that in the thin zone. The spring-back angle in the thin zone is higher than that in the thick zone after three-point bending, and the overall spring-back angle of Al-TRB becomes larger with an increasing bending angle. When the transition zone of Al-TRB is centered and the length of the transition zone is certain, as the length of the equal-thickness zone increases, the spring-back angle of the thin zone is larger, while the spring-back angle of the thick zone is smaller. Under the premise of a certain total length of Al-TRB and the length of the transition zone, the larger the length proportion of the thin zone, the larger the overall spring-back angle of Al-TRB, and the larger the length proportion of the thick zone, the smaller the overall spring-back angle of Al-TRB. In addition, a slight metal flow phenomenon exists during three-point bending, which shows that the metal in the bending region will flow to the thick zone, and the metal at the edge will flow to the thin zone. At the same time, there are localized thickening and thinning phenomena in Al-TRB. This study is helpful because it provides theoretical guidance for designing molds for the actual production of Al-TRB parts for automotives.

17.
Medicine (Baltimore) ; 103(16): e37884, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640323

RESUMO

INTRODUCTION: Trigeminal herpes zoster, which comprises 10% to 20% of cases of herpes zoster, often leads to severe pain in the ophthalmic branches. Current treatments, including drug therapy and minimally invasive interventions, have limitations; accordingly, there is a need to explore alternative approaches. This study aimed to evaluate the efficacy and safety of computerized tomography (CT)-guided pulsed radiofrequency of the sphenopalatine ganglion in patients with intractable trigeminal herpetic pain. PATIENT CONCERNS: Three patients with intractable trigeminal ophthalmic zoster neuralgia were studied. All patients complained of bursts of headache, which occurred at least 10 times a day, usually in the periorbital and frontal regions. Conventional treatments, including oral medications and radiofrequency therapy targeting the trigeminal-semilunar ganglion and supraorbital nerve, could not sufficiently provide relief. DIAGNOSIS: Two patients were diagnosed with herpes zoster in the ocular branch of the trigeminal nerve with conjunctivitis, while one patient was diagnosed with postherpetic neuralgia in the ocular branch of the trigeminal nerve. INTERVENTIONS: This study employed a novel approach that involved CT-guided radiofrequency regulation of the pterygopalatine fossa sphenopalatine ganglion. OUTCOMES: In all three patients, pain relief was achieved within 1 to 3 days after treatment. During the follow-up, one patient had pain recurrence; however, its severity was ≈ 40% lower than the pretreatment pain severity. The second patient had sustained and effective pain relief. However, the pain of the third patient worsened again after 2 months. The average follow-up duration was 3 months. None of the enrolled patients showed treatment-related adverse reactions or complications. CONCLUSION: Our findings indicated that CT-guided radiofrequency regulation of the pterygopalatine fossa sphenopalatine ganglion was a safe and effective intervention for pain in patients with trigeminal ophthalmic zoster neuralgia, suggesting that it may be a therapeutic option if other treatments fail.


Assuntos
Herpes Zoster Oftálmico , Herpes Zoster , Neuralgia Pós-Herpética , Neuralgia , Dor Intratável , Tratamento por Radiofrequência Pulsada , Neuralgia do Trigêmeo , Humanos , Herpes Zoster Oftálmico/complicações , Herpes Zoster Oftálmico/terapia , Tratamento por Radiofrequência Pulsada/métodos , Neuralgia/etiologia , Neuralgia/terapia , Neuralgia Pós-Herpética/terapia , Neuralgia Pós-Herpética/complicações , Neuralgia do Trigêmeo/terapia , Neuralgia do Trigêmeo/complicações , Herpes Zoster/complicações , Resultado do Tratamento
18.
Sci Bull (Beijing) ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38644130

RESUMO

Colorectal cancer (CRC), a widespread malignancy, is closely associated with tumor microenvironmental hydrogen peroxide (H2O2) levels. Some clinical trials targeting H2O2 for cancer treatment have revealed its paradoxical role as a promoter of cancer progression. Investigating the dynamics of cancer cell H2O2 eustress at the single-cell level is crucial. In this study, non-contact hopping probe mode scanning ion conductance microscopy (HPICM) with high-sensitive Pt-functionalized nanoelectrodes was employed to measure dynamic extracellular to intracellular H2O2 gradients in individual colorectal cancer Caco-2 cells. We explored the relationship between cellular mechanical properties and H2O2 gradients. Exposure to 0.1 or 1 mmol/L H2O2 eustress increased the extracellular to intracellular H2O2 gradient from 0.3 to 1.91 or 3.04, respectively. Notably, cellular F-actin-dependent stiffness increased at 0.1 mmol/L but decreased at 1 mmol/L H2O2 eustress. This H2O2-induced stiffness modulated AKT activation positively and glutathione peroxidase 2 (GPX2) expression negatively. Our findings unveil the failure of some H2O2-targeted therapies due to their ineffectiveness in generating H2O2, which instead acts eustress to promote cancer cell survival. This research also reveals the complex interplay between physical properties and biochemical signaling in cancer cells' antioxidant defense, illuminating the exploitation of H2O2 eustress for survival at the single-cell level. Inhibiting GPX and/or catalase (CAT) enhances the cytotoxic activity of H2O2 eustress against CRC cells, which holds significant promise for developing innovative therapies targeting cancer and other H2O2-related inflammatory diseases.

19.
Chemistry ; : e202401218, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644346

RESUMO

High-valent Fe(IV)=O intermediates of metalloenzymes have inspired numerous efforts to generate synthetic analogs to mimic and understand their substrate oxidation reactivities. However, high-valent M(IV) complexes of late transition metals are rare. We have recently reported a novel Co(IV)-dinitrate complex (1-NO3) that activates sp3 C-H bonds up to 87 kcal/mol. In this work, we have shown that the nitrate ligands in 1-NO3 can be replaced by azide, a more basic coordinating base, resulting in the formation of a more potent Co(IV)-diazide species (1-N3) that reacts with substrates (hydrocarbons and phenols) at faster rate constants and activates stronger C-H bonds than the parent complex 1-NO3. We have characterized 1-N3 employing a combination of spectroscopic and computational approaches. Our results clearly show that the coordination of azide leads to the modulation of the Co(IV) electronic structure and the Co(IV/III) redox potential. Together with the higher basicity of azide, these thermodynamic parameters contribute to the higher driving forces of 1-N3 than 1-NO3 for C-H bond activation. Our discoveries are thus insightful for designing more reactive bio-inspired high-valent late transition metal complexes for activating inert aliphatic hydrocarbons.

20.
Expert Rev Anticancer Ther ; : 1-10, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623811

RESUMO

BACKGROUND: The effect of age, sex, and eastern cooperative oncology group performance status (ECOG PS) on the efficacy and safety of immune checkpoint inhibitor (ICI) therapy among hepatocellular carcinoma (HCC) patients remains elusive. Thus, a meta-analysis was conducted to evaluate whether such effects exist. RESEARCH DESIGN AND METHODS: Eligible studies in PubMed, Embase, and Cochrane Library databases were retrieved. RESULTS: One-hundred-and-eleven studies involving 14,768 HCC patients were included. The findings indicated that the ECOG PS didn't have a significant effect on the ORR and PFS in ICI-treated HCC patients (higher ECOG PS vs. lower ECOG PS: ORR: OR = 0.78, 95%CI = 0.55-1.10; PFS: HR = 1.15, 95%CI = 0.97-1.35), while those patients with a higher ECOG PS may have a worse OS (HR = 1.52, 95% CI = 1.26-1.84). There is no significant evidence of the effect of age (older vs. younger) or sex (males vs. females) on the efficacy of ICI therapy in HCC. CONCLUSION: ICI therapy in HCC should not be restricted strictly to certain patients in age or sex categories, while HCC patients with higher ECOG PS may require closer medication or follow-up strategy during ICI therapy. PROSPERO REGISTRATION: CRD42024518407.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA