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1.
Front Pharmacol ; 15: 1353662, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576488

RESUMO

Purpose: This study aimed to assess the efficacy and safety of Panax notoginseng saponin (PNS) injection, when combined with conventional treatment (CT), for acute myocardial infarction (AMI). Methods: Comprehensive searches were conducted in seven databases from inception until 28 September 2023. The search aimed to identify relevant randomized controlled trials (RCTs) focusing on PNS injection in the context of AMI. This meta-analysis adhered to the PRISMA 2020 guidelines, and its protocol was registered with PROSPERO (number: CRD42023480131). Result: Twenty RCTs involving 1,881 patients were included. The meta-analysis revealed that PNS injection, used adjunctively with CT, significantly improved treatment outcomes compared to CT alone, as evidenced by the following points: (1) enhanced total effective rate [OR = 3.09, p < 0.05]; (2) decreased incidence of major adverse cardiac events [OR = 0.32, p < 0.05]; (3) reduction in myocardial infarct size [MD = -6.53, p < 0.05]; (4) lower ST segment elevation amplitude [MD = -0.48, p < 0.05]; (5) mitigated myocardial injury as indicated by decreased levels of creatine kinase isoenzymes [MD = -11.19, p < 0.05], cardiac troponin T [MD = -3.01, p < 0.05], and cardiac troponin I [MD = -10.72, p < 0.05]; (6) enhanced cardiac function, reflected in improved brain natriuretic peptide [MD = -91.57, p < 0.05], left ventricular ejection fraction [MD = 5.91, p < 0.05], left ventricular end-diastolic dimension [MD = -3.08, p < 0.05], and cardiac output [MD = 0.53, p < 0.05]; (7) reduced inflammatory response, as shown by lower levels of C-reactive protein [MD = -2.99, p < 0.05], tumor necrosis factor-α [MD = -6.47, p < 0.05], interleukin-6 [MD = -24.46, p < 0.05], and pentraxin-3 [MD = -2.26, p < 0.05]; (8) improved vascular endothelial function, demonstrated by decreased endothelin-1 [MD = -20.56, p < 0.05] and increased nitric oxide [MD = 1.33, p < 0.05]; (9) alleviated oxidative stress, evidenced by increased superoxide dismutase levels [MD = 25.84, p < 0.05]; (10) no significant difference in adverse events [OR = 1.00, p = 1.00]. Conclusion: This study highlighted the efficacy and safety of adjunctive PNS injections in enhancing AMI patient outcomes beyond CT alone. Future RCTs need to solidify these findings through rigorous methods. Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/), identifier (CRD42023480131).

2.
J Nanobiotechnology ; 22(1): 163, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600506

RESUMO

Photothermal immunotherapy is regarded as the ideal cancer therapeutic modality to against malignant solid tumors; however, its therapeutic benefits are often modest and require improvement. In this study, a thermoresponsive nanoparticle (BTN@LND) composed of a photothermal agent (PTA) and pyroptosis inducer (lonidamine) were developed to enhance immunotherapy applications. Specifically, our "two-step" donor engineering strategy produced the strong NIR-II-absorbing organic small-molecule PTA (BTN) that exhibited high NIR-II photothermal performance (ε1064 = 1.51 × 104 M-1 cm-1, η = 75.8%), and this facilitates the diagnosis and treatment of deep tumor tissue. Moreover, the fabricated thermally responsive lipid nanoplatform based on BTN efficiently delivered lonidamine to the tumor site and achieved spatiotemporal release triggered by the NIR-II photothermal effect. In vitro and in vivo experiments demonstrated that the NIR-II photothermal therapy (PTT)-mediated on-demand release of cargo effectively faciliated tumor cell pyroptosis, thereby intensifying the immunogenic cell death (ICD) process to promote antitumor immunotherapy. As a result, this intelligent component bearing photothermal and chemotherapy can maximally suppress the growth of tumors, thus providing a promising approach for pyroptosis/NIR-II PTT synergistic therapy against tumors.


Assuntos
Indazóis , Nanopartículas , Neoplasias , Humanos , Fototerapia , Piroptose , Neoplasias/tratamento farmacológico , Imunoterapia , Linhagem Celular Tumoral
3.
Sci Total Environ ; 927: 172262, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38583605

RESUMO

South and Southeast Asia (SSA) emitted black carbon (BC) exerts potential effects on glacier and snow melting and regional climate change in the Tibetan Plateau. In this study, online BC measurements were conducted for 1 year at a remote village located at the terminus of the Mingyong Glacier below the Meili Snow Mountains. The Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) was used to investigate the contribution and potential effect of SSA-emitted BC. In addition, variations in the light absorption characteristics of BC and brown carbon (BrC) were examined. The results indicated that the annual mean concentration of BC was 415 ± 372 ngm-3, with the highest concentration observed in April (monthly mean: 930 ± 484 ngm-3). BC exhibited a similar diurnal variation throughout the year, with two peaks observed in the morning (from 8:00 to 9:00 AM) and in the afternoon (from 4:00 to 5:00 PM), with even lower values at nighttime. At a short wavelength of 370 nm, the absorption coefficient (babs) reached its maximum value, and the majority of babs values were < 20 Mm-1, indicating that the atmosphere was not overloaded with BC. At the same wavelength, BrC substantially contributed to babs, with an annual mean of 25.2 % ± 12.8 %. SSA was the largest contributor of BC (annual mean: 51.1 %) in the study area, particularly in spring (65.6 %). However, its contributions reached 20.2 % in summer, indicating non-negligible emissions from activities in other regions. In the atmosphere, the SSA BC-induced radiative forcing (RF) over the study region was positive. While at the near surface, the RF exhibited a significant seasonal variation, with the larger RF values occurring in winter and spring. Overall, our findings highlight the importance of controlling BC emissions from SSA to protect the Tibetan Plateau against pollution-related glacier and snow cover melting.

4.
J Int Med Res ; 52(4): 3000605241238134, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38630560

RESUMO

OBJECTIVE: We explored whether changes in clinical parameters and inflammatory markers can facilitate early identification of positive blood culture in adult patients with COVID-19 and clinically suspected bloodstream infection (BSI). METHODS: This single-center retrospective study enrolled 20 adult patients with COVID-19 admitted to the intensive care unit who underwent blood culture for clinically suspected BSI (February 2020-November 2021). We divided patients into positive (Pos) and negative blood culture groups. Clinical parameters and inflammatory markers were obtained from medical records between blood culture collection and the first positive or negative result and compared between groups on different days. RESULTS: Patients in the positive culture group had significantly older age and higher D-dimer, immunoglobulin 6 (IL-6), and Sequential Organ Failure Assessment score as well as lower albumin (ALB). The area under the receiver operating characteristic curve (AUC) was 0.865 for IL-6, D-dimer and ALB on the first day after blood culture collection; the AUC was 0.979 for IL-6, IL-10, D-dimer, and C-reactive protein on the second day after blood culture collection. CONCLUSION: Changes in clinical parameters and inflammatory markers after blood culture collection may facilitate early identification of positive culture in adult patients with COVID-19 and clinically suspected BSI.


Assuntos
COVID-19 , Sepse , Adulto , Humanos , Estudos Retrospectivos , Hemocultura , Interleucina-6
5.
Nat Nanotechnol ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499860

RESUMO

Bone is the most common site of metastasis, and although low proliferation and immunoediting at the early stage make existing treatment modalities less effective, the microenvironment-inducing behaviour could be a target for early intervention. Here we report on a spatiotemporal coupling interaction between tumour cells and osteoclasts, and named the tumour-associated osteoclast 'tumasteoclast'-a subtype of osteoclasts in bone metastases induced by tumour-migrasome-mediated cytoplasmic transfer. We subsequently propose an in situ decoupling-killing strategy in which tetracycline-modified nanoliposomes encapsulating sodium bicarbonate and sodium hydrogen phosphate are designed to specifically release high concentrations of hydrogen phosphate ions triggered by tumasteoclasts, which depletes calcium ions and forms calcium-phosphorus crystals. This can inhibit the formation of migrasomes for decoupling and disrupt cell membrane for killing, thereby achieving early prevention of bone metastasis. This study provides a research model for exploring tumour cell behaviour in detail and a proof-of-concept for behaviour-targeting strategy.

6.
Chemosphere ; 354: 141667, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38485002

RESUMO

The rapid development of the economy has led to an increase in the sulfur and nitrogen load in surface water, which has the potential to cause river eutrophication and the emission of malodorous gases. A lab-scale sediment microbial fuel cell coupled with Vallisneria natans (P-SMFC) was designed for surface water remediation. The enhancement of pollutant removal performance of P-SMFC was evaluated in contrast to the SMFC system without plants (SMFC), the open-circuit control system with plants (C-P), and the open-circuit control system without plants (C-S), while illustrating the mechanisms of the sulfur and nitrogen transformation process. The results demonstrated that the effluent and sediment of P-SMFC had lower concentrations of sulfide compared to other systems. Furthermore, P-SMFC exhibited higher removal efficiency for COD (73.1 ± 8.7%), NH4+-N (80.5 ± 19.8%), and NO3--N (88.5 ± 11.8%) compared to other systems. The closed-circuit conditions and growth of Vallisneria natans create a favorable ecological niche for functional microorganisms involved in power generation, sulfur oxidation, and nitrogen transformation. Additionally, metagenomic analysis revealed that multifunctional bacteria possessing both denitrification and sulfur oxidation genes, such as Thiobacillus, Dechloromonas, and Bacillus, may play simultaneous roles in metabolizing sulfur and nitrogen, thus serving as integral factors in maintaining the performance of P-SMFC. In summary, these findings provide a theoretical reference for the concurrent enhancement of sulfur and nitrogen pollutants removal in P-SMFC and will facilitate its practical application in the remediation of contaminated surface water.


Assuntos
Fontes de Energia Bioelétrica , Microbiota , Nitrogênio/metabolismo , Sedimentos Geológicos/química , Água/química , Enxofre , Desnitrificação
7.
Int J Biol Macromol ; 264(Pt 1): 130551, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431010

RESUMO

Achieving the controllable detachment of polysaccharide-based wound dressings is challenging. In this study, a novel, photodetachable salecan-based hydrogel dressing with injectable, self-healing, antibacterial, and wound healing properties was developed using a green and facile approach. A salecan hydrogel with a uniform porous structure and water content of 90.4 % was prepared by simply mixing salecan and an Fe3+-citric acid complexing solution in an acidic D-(+)-glucono-1,5-lactone environment. Metal coordinate interactions were formed between the released Fe3+ ions and carboxyl groups on the salecan polysaccharide, inducing homogeneous gelation. Benefiting from this dynamic and reversible crosslinking, the salecan hydrogel exhibited self-healing and injectable behavior, facilitating the formation of the desired shapes in situ. The exposure of Fe3+-citric acid to UV light (365 nm) resulted in the reduction of Fe3+ to Fe2+ through photochemical reactions, enabling phototriggered detachment. Moreover, the hydrogel exhibited excellent biocompatibility and satisfactory antibacterial efficacy against Escherichia coli and Staphylococcus aureus of 72.5 % and 85.3 %, respectively. The adhesive strength of the salecan hydrogel to porcine skin was 1.06 ± 0.12 kPa. In vivo wound healing experiments further highlighted the advantages of the prepared hydrogel in alleviating the degree of wound inflammation and promoting tissue regeneration within 12 days.


Assuntos
Hidrogéis , Prunella , beta-Glucanas , Suínos , Animais , Hidrogéis/farmacologia , Bandagens , Antibacterianos/farmacologia , Ácido Cítrico , Escherichia coli , Metais , Polissacarídeos
8.
Int Immunopharmacol ; 130: 111728, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38430801

RESUMO

The treatment of hepatocellular carcinoma (HCC) remains a major challenge in the medical field. Lenvatinib, a multi-target tyrosine kinase inhibitor, has demonstrated anti-HCC effects by targeting and inhibiting pathways such as vascular endothelial growth factor receptor 1-3 (VEGFR1-3). However, the therapeutic efficacy of Lenvatinib is subject to various influences, with the hypoxic microenvironment of the tumor being a pivotal factor. Consequently, altering the hypoxic milieu of the tumor emerges as a viable strategy to augment the efficacy of Lenvatinib. Hypoxia-inducible factor-1α (HIF-1α), synthesized by tumor cells in response to oxygen-deprived conditions, regulates the expression of resistance genes, promotes tumor angiogenesis and cell proliferation, enhances tumor cell invasion, and confers resistance to radiotherapy and chemotherapy. Thus, we constructed a self-designed siRNA targeting HIF-1α to suppress its expression and improve the efficacy of Lenvatinib in treating HCC. The therapeutic efficacy of siRNA-HIF-1α in combination with Lenvatinib on HCC were evaluated through in vivo and in vitro experiments. The results showed that the recombinant Salmonella delivering siRNA-HIF-1α in combination with Lenvatinib effectively inhibited tumor growth and prolonged the survival of tumor-bearing mice. This treatment approach reduced cell proliferation and angiogenesis in HCC tissues while promoting tumor cell apoptosis. Additionally, this combined therapy significantly increased the infiltration of T lymphocytes and M1 macrophages within the tumor microenvironment, as well as elevated the proportion of immune cells in the spleen, thereby potentiating the host's immune response against the tumor.


Assuntos
Carcinoma Hepatocelular , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , RNA Interferente Pequeno , Terapêutica com RNAi , Salmonella , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/uso terapêutico , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Terapia Combinada , Terapêutica com RNAi/métodos
9.
Chemosphere ; 357: 141854, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38556181

RESUMO

This study investigates the nitrogen removal efficacy and microbial community dynamics in seawater aquaculture effluent treatment using three different substrate combinations of microscale laboratory aerated filters (MFs) - MF1 (LECA), MF2 (LECA/Fe-C), and MF3 (LECA/Pyrite). The findings indicated that the COD removal exceeded 95% across all MFs, with higher removal efficiencies in MF2 and MF3. In terms of nitrogen removal performance, MF2 exhibited the highest average nitrogen removal of 93.17%, achieving a 12.35% and 3.56% increase compared to MF1 (80.82%) and MF3 (89.61%), respectively. High-throughput sequencing analysis revealed that the Fe-C substrate significantly enhanced the diversity of the microbial community. Notably, in MF2, the salinophilic denitrifying bacterium Halomonas was significantly enriched, accounting for 42.6% of the total microbial community, which was beneficial for nitrogen removal. Moreover, an in-depth analysis of nitrogen metabolic pathways and microbial enzymes indicated that MF2 and MF3 possessed a high abundance of nitrification and denitrification enzymes, related to the high removal rates of NH4+-N and NO3--N. Therefore, the combination of LECA with iron-based materials significantly enhances the nitrogen removal efficiency from mariculture wastewater.

10.
Molecules ; 29(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38398606

RESUMO

Organic dyes in natural waters jeopardize human health. Whether semiconductor materials can effectively degrade dyes has become a challenge for scientific research. Based on this, this study rationally prepared different nanocomposites to remove organic dyes effectively. Pure SnO2 quantum dots, ZnO nanosheets, and SnO2/ZnO (ZS) binary nanocomposites are prepared using the hydrothermal method. Subsequently, SnO2/ZnO@GO (ZSG) ternary composites containing different amounts of GO, i.e., ZSG-5, ZSG-15, and ZSG-25, are synthesized by an ultrasonic water bath method, in which ZS was coupled with GO to form Z-type heterojunctions. The ZSG-15 ternary composites exhibited excellent photocatalytic activity for the degradation of rhodamine B by simulating sunlight. The test results show that the degradation rate of ZSG-15 is about 7.6 times higher than ZnO. The increase in photocatalytic activity is attributed to the synergistic effect of SnO2 and GO to improve the separation efficiency of photogenerated carriers in ZnO. Notably, the large specific surface area of GO increases the reactive sites. Compared with binary nanocomposites, ZSG-15 broadens the response range to light while further accelerating the electron transport rate and improving the photoelectric stability.

11.
J Sci Food Agric ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38348948

RESUMO

BACKGROUND: Obesity has been demonstrated as a risk factor that seriously affects health. Insoluble dietary fiber (IDF), as a major component of dietary fiber, has positive effects on obesity, inflammation and diabetes. RESULTS: In this study, complex IDF was prepared using 50% enoki mushroom IDF, 40% carrot IDF, and 10% oat IDF. The effects and potential mechanism of complex IDF on obesity were investigated in C57BL/6 mice fed a high-fat diet. The results showed that feeding diets containing 5% complex IDF for 8 weeks significantly reduced mouse body weight, epididymal lipid index, and ectopic fat deposition, and improved mouse liver lipotoxicity (reduced serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), fatty liver, and short-chain fatty acid composition. High-throughput sequencing of 16S rRNA and analysis of fecal metabolomics showed that the intervention with complex IDF reversed the high-fat-diet-induced dysbiosis of gut microbiota, which is associated with obesity and intestinal inflammation, and affected metabolic pathways, such as primary bile acid biosynthesis, related to fat digestion and absorption. CONCLUSION: Composite IDF intervention can effectively inhibit high-fat-diet-induced obesity and related symptoms and affect the gut microbiota and related metabolic pathways in obesity. Complex IDF has potential value in the prevention of obesity and metabolic syndrome. © 2024 Society of Chemical Industry.

12.
Sci Total Environ ; 922: 171321, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38423306

RESUMO

Carbonaceous particles play a crucial role in atmospheric radiative forcing. However, our understanding of the behavior and sources of carbonaceous particles in remote regions remains limited. The Tibetan Plateau (TP) is a typical remote region that receives long-range transport of carbonaceous particles from severely polluted areas such as South Asia. Based on carbon isotopic compositions (Δ14C/δ13C) of water-insoluble particulate carbon (IPC) in total suspended particle (TSP), PM2.5, and precipitation samples collected during 2020-22 at the Nam Co Station, a remote site in the inner TP, the following results were achieved: First, fossil fuel contributions (ffossil) to IPC in TSP samples (28.60 ± 9.52 %) were higher than that of precipitation samples (23.11 ± 8.60 %), and it is estimated that the scavenging ratio of IPC from non-fossil fuel sources was around 2 times that from fossil fuel combustion during the monsoon season. The ffossil of IPC in both TSP and PM2.5 samples peaked during the monsoon season. Because heavy precipitation during the monsoon season scavenges large amounts of long-range transported carbonaceous particles, the contribution of local emissions from the TP largely outweighs that from South Asia during this season. The results of the IPC source apportionment based on Δ14C and δ13C in PM2.5 samples showed that the highest contribution of liquid fossil fuel combustion also occurred in the monsoon season, reflecting increased human activities (e.g., tourism) on the TP during this period. The results of this study highlight the longer lifetime of fossil fuel-sourced IPC in the atmosphere than that of non-fossil fuel sources in the inner TP and the importance of local emissions from the TP during the monsoon season. The findings provide new knowledge for model improvement and mitigation of carbonaceous particles.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38306258

RESUMO

Point-based object localization (POL), which pursues high-performance object sensing under low-cost data annotation, has attracted increased attention. However, the point annotation mode inevitably introduces semantic variance due to the inconsistency of annotated points. Existing POL heavily rely on strict annotation rules, which are difficult to define and apply, to handle the problem. In this study, we propose coarse point refinement (CPR), which to our best knowledge is the first attempt to alleviate semantic variance from an algorithmic perspective. CPR reduces the semantic variance by selecting a semantic centre point in a neighbourhood region to replace the initial annotated point. We further integrate a variance regularization into the structure to concentrate the predicted scores, yielding CPR++. We observe that CPR++ can obtain scale information and further reduce the semantic variance in a global region, thus guaranteeing high-performance object localization. Extensive experiments on four challenging datasets validate the effectiveness of both CPR and CPR++. We hope our work can inspire more research on designing algorithms rather than annotation rules to address the semantic variance problem in POL. The dataset and code will be public at github.com/ucas-vg/PointTinyBenchmark.

14.
PLoS One ; 19(2): e0296087, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38300965

RESUMO

In order to analyze the differences between the master curves of relaxation modulus E(t) and creep compliance J(t) obtained from discrete and continuous spectrum models, and to comprehensively evaluate the effect of basalt fiber content on the viscoelastic behavior of asphalt mixtures, complex modulus tests were conducted for asphalt mixtures with fiber content of 0%, 0.1%, 0.2% and 0.3%, respectively. Consequently, the master curves of Viscoelastic Parameters of asphalt mixtures were constructed according to the generalized Sigmoidal model(GSM) and the approximate Kramers-Kronig (K-K) relationship. Then, transformation of master curves using discrete and continuous spectrum models to obtain the models of E(t) and J(t) containing all viscoelastic information. Also, the accuracy of the models of E(t) and J(t) was evaluated. The results show that the addition of basalt fibers improves the strength, stress relaxation and deformation resistance of asphalt mixtures. It is worth noting that basalt fibers achieve the improvement of asphalt mixtures by changing their internal structure. Considering the different viscoelastic master curves at four dosages, the optimum fiber dosage was 0.2%. In addition, both discrete and continuous model conversion methods can obtain high accuracy conversion results.


Assuntos
Gastrópodes , Silicatos , Animais , Hidrocarbonetos , Relaxamento
15.
Bioelectrochemistry ; 157: 108639, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38199185

RESUMO

Recently, high-entropy alloys have superior physicochemical properties as compared to conventional alloys for their glamorous "cocktail effect". Nevertheless, they are scarcely applied to electrochemical immunoassays until now. Herein, uniform PtRhMoCoFe high-entropy alloyed nanodendrites (HEANDs) were synthesized by a wet-chemical co-reduction method, where glucose and oleylamine behaved as the co-reducing agents. Then, a series of characterizations were conducted to illustrate the synergistic effect among multiple metals and fascinating structural characteristics of PtRhMoCoFe HEANDs. The obtained high-entropy alloy was adopted to build a electrochemical label-free biosensor for ultrasensitive bioassay of biomarker cTnI. In the optimized analytical system, the resultant sensor exhibited a dynamic linear range of 0.0001-200 ng mL-1 and a low detection limit of 0.0095 pg mL-1 (S/N = 3). Eventually, this sensing platform was further explored in serum samples with satisfied recovery (102.0 %). This research renders some constructive insights for synthesis of high-entropy alloys and their expanded applications in bioassays and bio-devices.


Assuntos
Ligas , Técnicas Biossensoriais , Entropia , Ligas/química , Biomarcadores , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos
16.
J Transl Med ; 22(1): 122, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297333

RESUMO

BACKGROUND: Emerging evidence suggests that Rho GTPases play a crucial role in tumorigenesis and metastasis, but their involvement in the tumor microenvironment (TME) and prognosis of hepatocellular carcinoma (HCC) is not well understood. METHODS: We aim to develop a tumor prognosis prediction system called the Rho GTPases-related gene score (RGPRG score) using Rho GTPase signaling genes and further bioinformatic analyses. RESULTS: Our work found that HCC patients with a high RGPRG score had significantly worse survival and increased immunosuppressive cell fractions compared to those with a low RGPRG score. Single-cell cohort analysis revealed an immune-active TME in patients with a low RGPRG score, with strengthened communication from T/NK cells to other cells through MIF signaling networks. Targeting these alterations in TME, the patients with high RGPRG score have worse immunotherapeutic outcomes and decreased survival time in the immunotherapy cohort. Moreover, the RGPRG score was found to be correlated with survival in 27 other cancers. In vitro experiments confirmed that knockdown of the key Rho GTPase-signaling biomarker SFN significantly inhibited HCC cell proliferation, invasion, and migration. CONCLUSIONS: This study provides new insight into the TME features and clinical use of Rho GTPase gene pattern at the bulk-seq and single-cell level, which may contribute to guiding personalized treatment and improving clinical outcome in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Carcinogênese , Linhagem Celular , Imunossupressores , Proteínas rho de Ligação ao GTP , Microambiente Tumoral
17.
Biol Trace Elem Res ; 202(2): 454-465, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37198357

RESUMO

The magnesium depletion score (MDS) is considered a new valuable and reliable predictor of body magnesium status. This study aimed to explore the association between MDS and congestive heart failure (CHF) among US adults. A total of 19,227 eligible participants from the 2007-2016 National Health and Nutrition Examination Survey were enrolled in this study and then divided into three groups according to the level of MDS (none to low: MDS=0-1, middle: MDS=2, high: MDS=3-5). Sample-weighted logistic regression models were applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) exploring the independent relationship between MDS and CHF. The estimated prevalence of CHF increased with the increasing level of MDS (none to low: 0.86%, middle: 4.06%, high: 13.52%; P < 0.001). Compared to those in the none-to-low group, participants in the middle and high groups were at significantly higher risk of CHF after adjusting for various covariates (model 3: OR=1.55, 95%CI: 1.05-2.30, P < 0.001; OR=3.20, 95%CI: 2.07-4.96, P < 0.001; respectively). Subgroup analyses indicated that adequate dietary magnesium intake could reduce the risk of CHF in participants who did not meet the recommended dietary allowance (RDA) for magnesium. Besides, there was an interaction between coronary artery disease and MDS on CHF (P for interaction < 0.001). These findings indicated that MDS, a novel indicator estimating magnesium deficiency, is associated with the risk of CHF in non-institutionalized US civilians. Participants whose dietary magnesium intake reaches the RDA might be at lower risk.


Assuntos
Insuficiência Cardíaca , Deficiência de Magnésio , Adulto , Humanos , Magnésio , Dieta , Inquéritos Nutricionais , Insuficiência Cardíaca/epidemiologia , Deficiência de Magnésio/complicações , Deficiência de Magnésio/epidemiologia , Fatores de Risco
18.
Eur Radiol ; 34(2): 1258-1267, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37581654

RESUMO

OBJECTIVES: To determine the safety and efficacy of transcatheter arterial chemoembolization with CalliSpheres® beads loaded with arsenic trioxide (CBATO-TACE) in the first-line treatment of patients with large (5 cm ≤ maximum diameter < 10 cm) or huge (maximum diameter ≥ 10 cm) hepatocellular carcinoma (HCC). METHODS: Patients were randomly allocated to the CBATO-TACE group and the conventional transcatheter arterial chemoembolization (cTACE) group. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall survival (OS), treatment response, and treatment-related adverse events (TRAEs). The extrahepatic collateral arteries, liver function, and liver fibrosis after the first TACE were also evaluated. RESULTS: From September 2018 to September 2020, a total of 207 patients who underwent TACE were consecutively enrolled in this study. The median PFS was 9.5 months (range: 8.0 - 11.0) in the CBATO group, which was significantly longer than that in the cTACE group (6.0 months, range: 4.0-6.0) (p < 0.0001). Patients in the CBATO group had a median OS of 22 months (range: 20.0 - 27.0) compared with 16 months (range: 15.0 - 20.0) in the cTACE group (p = 0.0084). The most common TRAEs were fever (p = 0.043), and nausea and vomiting (p = 0.002), which were more observed in the cTACE group. In addition, the progressive disease time, pulmonary metastasis rate (p = 0.01), the mean number of extrahepatic collateral arteries (p = 0.01), and average number of TACE sessions (p = 0.025) were significantly decreased in the CBATO group. CONCLUSIONS: CBATO-TACE achieved better therapeutic outcomes and similar safety profile compared to cTACE in large or huge HCC patients. Furthermore, CBATO-TACE was able to reduce extrahepatic collateral arteries production and extrahepatic lung metastasis. CLINICAL RELEVANCE STATEMENT: Our study showed that CalliSpheres® beads loaded with arsenic trioxide (CBATO-TACE) were effective and safe for the treatment of large and giant HCC. In addition, CBATO-TACE can reduce lateral hepatic branch artery formation and extrahepatic pulmonary metastasis, which provides a new treatment approach for unresectable HCC. KEY POINTS: • We compare long-term efficacy and safety of transcatheter arterial chemoembolization with CalliSpheres® beads loaded with arsenic trioxide (CBATO-TACE) and conventional transcatheter arterial chemoembolization (cTACE) in patients with large (5 cm ≤ maximum diameter < 10 cm) or huge HCC (maximum diameter ≥ 10 cm). • Compared with cTACE, CBATO-TACE significantly improved therapeutic outcomes, overall survival, and progression-free survival in patients with large or huge HCC. The safety assessment suggested that CBATO-TACE is a safe treatment that improves the quality of life and has good treatment adherence.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Trióxido de Arsênio/efeitos adversos , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Artéria Hepática/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
19.
Chem Commun (Camb) ; 60(3): 332-335, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38073511

RESUMO

We propose a noncovalent backbone planarization strategy to fabricate a gas/phototheranostic nanocomposite (B-E-NO NPs) in the near-infrared-II (NIR-II, 1000-1700 nm) window by incorporating noncovalent conformational locks. B-E-NO NPs display a giant NIR-II extinction coefficient, realizing multimodal imaging-guided high-efficiency NIR-II photothermal therapy (η = 45.4%) and thermal-initiated nitric oxide combination therapy.

20.
Environ Sci Pollut Res Int ; 31(3): 3413-3424, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38114701

RESUMO

Tibetan Plateau (TP) is known as the water tower of Asia, and glaciers are solid reservoirs that can regulate the amount of water. Black carbon (BC), as one of the important factors accelerating glacier melting, is causing evident environmental effects in snow and ice. However, a systematical summary of the potential sources, analytical methods, distributions, and environmental effects of BC in snow and ice on the TP's glaciers is scarce. Therefore, this study drew upon existing research on snow and ice BC on glaciers of the TP to describe the detection methods and uncertainties associated with them to clarify the concentrations of BC in snow and ice and their climatic effects. The primary detection methods are the optical method, the thermal-optical method, the thermochemical method, and the single-particle soot photometer method. However, few studies have systematically compared the results of BC and this study found that concentrations of BC in different types of snow and ice varied by 1-3 orders of magnitude, which drastically affected the regional hydrologic process by potentially accelerating the ablation of glaciers by approximately 15% and reducing the duration of snow accumulation by 3-4 days. In general, results obtained from the various testing methods differ drastically, which limited the systematical discussion. Accordingly, a universal standard for the sampling and measurement should be considered in the future work, which will be beneficial to facilitate the comparison of the spatiotemporal features and to provide scientific data for the model-simulated climatic effects of BC.


Assuntos
Neve , Fuligem , Tibet , Monitoramento Ambiental/métodos , Camada de Gelo , Água , Carbono/análise
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