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1.
J Food Sci ; 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39218817

RESUMO

Ingestion of perfluoroalkyl acids (PFAAs) via contaminated food contact materials (FCMs) is an important human exposure source. This study adopts a toxicity equivalent approach to evaluate the collective health risk of multiple PFAAs in FCMs. A comprehensive extraction and analysis of 21 PFAAs in FCMs was performed. Among the analyzed substances, 15 PFAAs were detected. Migration experiment using three food simulants revealed the migration range of seven PFAAs from FCMs into the simulant to be 0.47-46.7 ng/cm2. The hazard quotient results suggest minimal health risk, except for 9% of packaged samples where perfluorooctanoic acid (PFOA) poses a higher risk. Utilizing PFOA toxic equivalent concentrations, comprehensive risk calculations showed ∼77% of samples potentially posing elevated health risks due to PFAA exposure. This emphasizes the substantial contribution of PFAAs beyond PFOA and underscores the importance of considering them in related assessments. The aggregated risk assessment reflects actual exposure circumstances more accurately.

2.
Strahlenther Onkol ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39249499

RESUMO

PURPOSE: To construct a comprehensive model for predicting the prognosis of patients with glioblastoma (GB) using a radiomics method and integrating clinical risk factors, tumor microenvironment (TME), and imaging characteristics. MATERIALS AND METHODS: In this retrospective study, we included 148 patients (85 males and 63 females; median age 53 years) with isocitrate dehydrogenase-wildtype GB between January 2016 and April 2022. Patients were randomly divided into the training (n = 104) and test (n = 44) sets. The best feature combination related to GB overall survival (OS) was selected using LASSO Cox regression analyses. Clinical, radiomics, clinical-radiomics, clinical-TME, and clinical-radiomics-TME models were established. The models' concordance index (C-index) was evaluated. The survival curve was drawn using the Kaplan-Meier method, and the prognostic stratification ability of the model was tested. RESULTS: LASSO Cox analyses were used to screen the factors related to OS in patients with GB, including MGMT (hazard ratio [HR] = 0.642; 95% CI 0.414-0.997; P = 0.046), TERT (HR = 1.755; 95% CI 1.095-2.813; P = 0.019), peritumoral edema (HR = 1.013; 95% CI 0.999-1.027; P = 0.049), tumor purity (TP; HR = 0.982; 95% CI 0.964-1.000; P = 0.054), CD163 + tumor-associated macrophages (TAMs; HR = 1.049; 95% CI 1.021-1.078; P < 0.001), CD68 + TAMs (HR = 1.055; 95% CI 1.018-1.093; P = 0.004), and the six radiomics features. The clinical-radiomics-TME model had the best survival prediction ability, the C­index was 0.768 (0.717-0.819). The AUC of 1­, 2­, and 3­year OS prediction in the test set was 0.842, 0.844, and 0.795, respectively. CONCLUSION: The clinical-radiomics-TME model is the most effective for predicting the survival of patients with GB. Radiomics features, TP, and TAMs play important roles in the prognostic model.

3.
EPMA J ; 15(3): 511-524, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39239107

RESUMO

Background: Glaucoma is the leading cause of irreversible blindness worldwide. Normal tension glaucoma (NTG) is a distinct subtype characterized by intraocular pressures (IOP) within the normal range (< 21 mm Hg). Due to its insidious onset and optic nerve damage, patients often present with advanced conditions upon diagnosis. NTG poses an additional challenge as it is difficult to identify with normal IOP, complicating its prediction, prevention, and treatment. Observational studies suggest a potential association between NTG and abnormal lipid metabolism, yet conclusive evidence establishing a direct causal relationship is lacking. This study aims to explore the causal link between serum lipids and NTG, while identifying lipid-related therapeutic targets. From the perspective of predictive, preventive, and personalized medicine (PPPM), clarifying the role of dyslipidemia in the development of NTG could provide a new strategy for primary prediction, targeted prevention, and personalized treatment of the disease. Working hypothesis and methods: In our study, we hypothesized that individuals with dyslipidemia may be more susceptible to NTG due to a dysregulation of microvasculature in optic nerve head. To verify the working hypothesis, univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were utilized to estimate the causal effects of lipid traits on NTG. Drug target MR was used to explore possible target genes for NTG treatment. Genetic variants associated with lipid traits and variants of genes encoding seven lipid-related drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). GWAS data for NTG, primary open angle glaucoma (POAG), and suspected glaucoma (GLAUSUSP) were obtained from FinnGen Consortium. For apolipoproteins, we used summary statistics from a GWAS study by Kettunen et al. in 2016. For metabolic syndrome, summary statistics were extracted from UK Biobank participants. In the end, these findings could help identify individuals at risk of NTG by screening for lipid dyslipidemia, potentially leading to new targeted prevention and personalized treatment approaches. Results: Genetically assessed high-density cholesterol (HDL) was negatively associated with NTG risk (inverse-variance weighted [IVW] model: OR per SD change of HDL level = 0.64; 95% CI, 0.49-0.85; P = 1.84 × 10-3), and the causal effect was independent of apolipoproteins and metabolic syndrome (IVW model: OR = 0.29; 95% CI, 0.14-0.60; P = 0.001 adjusted by ApoB and ApoA1; OR = 0.70; 95% CI, 0.52-0.95; P = 0.023 adjusted by BMI, HTN, and T2DM). Triglyceride (TG) was positively associated with NTG risk (IVW model: OR = 1.62; 95% CI, 1.15-2.29; P = 6.31 × 10-3), and the causal effect was independent of metabolic syndrome (IVW model: OR = 1.66; 95% CI, 1.18-2.34; P = 0.003 adjusted by BMI, HTN, and T2DM), but not apolipoproteins (IVW model: OR = 1.71; 95% CI, 0.99-2.95; P = 0.050 adjusted by ApoB and ApoA1). Genetic mimicry of apolipoprotein B (APOB) enhancement was associated with lower NTG risks (IVW model: OR = 0.09; 95% CI, 0.03-0.26; P = 9.32 × 10-6). Conclusions: Our findings supported dyslipidemia as a predictive causal factor for NTG, independent of other factors such as metabolic comorbidities. Among seven lipid-related drug targets, APOB is a potential candidate drug target for preventing NTG. Personalized health profiles can be developed by integrating lipid metabolism with life styles, visual quality of life such as reading, driving, and walking. This comprehensive approach will aid in shifting from reactive medical services to PPPM in the management of NTG. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00373-5.

4.
Fish Shellfish Immunol ; : 109872, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39244075

RESUMO

Scylla paramamosain, an economically significant crab, is widely cultivated worldwide. In recent years, S. paramamosain has faced a serious threat from viral diseases due to the expansion of culture scale and increased culture density. Among these, mud crab dicistrovirus-1 (MCDV-1) stands out as highly pathogenic, presenting substantial challenges to the healthy development of mud crab aquaculture. Therefore, a comprehensive understanding of the mud crab immune response to MCDV-1 infection is imperative for devising effective disease prevention strategies. In this study, transcriptomic analyses were conducted on the hepatopancreas of mud crabs infected with MCDV-1. The findings revealed a total of 5,139 differentially expressed genes (DEGs) between healthy and MCDV-1 infected mud crabs, including 3,327 upregulated and 1,812 downregulated DEGs. Further analysis showed that mud crabs resist MCDV-1 infection by activating humoral immune-related pathways, including the MAPK signaling pathway, MAPK signaling pathway-fly, and Toll and Imd signaling pathway. In contrast, MCDV-1 infection triggers host metabolic disorders. Several immune-related vitamin metabolism pathways (ascorbate and aldarate metabolism, retinol metabolism, and nicotinate and nicotinamide metabolism) were significantly inhibited, which may create favorable conditions for the virus's self-replication. Notably, endocytosis emerged as significantly upregulated both in GO terms and KEGG pathways, with several viral endocytosis-related pathways showing significant activation. PPI network analysis identified 9 hub genes associated with viral endocytosis within the endocytosis. Subsequent GeneMANIA analysis confirmed the association of these hub genes with viral endocytosis. Both transcriptome data and qPCR analysis revealed a significant upregulation of these hub genes post MCDV-1 infection, suggesting MCDV-1 may use viral endocytosis to enter cells and facilitate replication. This study represents the first comprehensive report on the transcriptomic profile of mud crab hepatopancreas response to MCDV-1 infection. Future investigations should focus on elucidating the mechanisms through which MCDV-1 enters cells via endocytosis, as this may holds critical implications for the development of vaccine targets.

5.
Biol Direct ; 19(1): 71, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39175011

RESUMO

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) represents a significant proportion of renal cell carcinomas and is characterized by high aggressiveness and poor prognosis despite advancements in immunotherapy. Disulfidptosis, a novel cell death pathway, has emerged as a critical mechanism in various cellular processes, including cancer. This study leverages machine learning to identify disulfidptosis-related long noncoding RNAs (DRlncRNAs) as potential prognostic biomarkers in KIRC, offering new insights into tumor pathogenesis and treatment avenues. RESULTS: Our analysis of data from The Cancer Genome Atlas (TCGA) led to the identification of 431 DRlncRNAs correlated with disulfidptosis-related genes. Five key DRlncRNAs (SPINT1-AS1, AL161782.1, OVCH1-AS1, AC131009.3, and AC108673.3) were used to develop a prognostic model that effectively distinguished between low- and high-risk patients with significant differences in overall survival and progression-free survival. The low-risk group had a favorable prognosis associated with a protective immune microenvironment and a better response to targeted drugs. Conversely, the high-risk group displayed aggressive tumor features and poor immunotherapy outcomes. Validation through qRT‒PCR confirmed the differential expression of these DRlncRNAs in KIRC cells compared to normal kidney cells, underscoring their potential functional significance in tumor biology. CONCLUSIONS: This study established a robust link between disulfidptosis-related lncRNAs and patient prognosis in KIRC, underscoring their potential as prognostic biomarkers and therapeutic targets. The differential expression of these lncRNAs in tumor versus normal tissue further highlights their relevance in KIRC pathogenesis. The predictive model not only enhances our understanding of KIRC biology but also provides a novel stratification tool for precision medicine approaches, improving treatment personalization and outcomes in KIRC patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , RNA Longo não Codificante , RNA Longo não Codificante/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/imunologia , Humanos , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Masculino
6.
J Cell Physiol ; : e31423, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39188080

RESUMO

Bone marrow-derived mesenchymal stem cells (BMSC) are promising cellular reservoirs for treating degenerative diseases, tissue injuries, and immune system disorders. However, the stemness of BMSCs tends to decrease during in vitro cultivation, thereby restricting their efficacy in clinical applications. Consequently, investigating strategies that bolster the preservation of BMSC stemness and maximize therapeutic potential is necessary. Transcriptomic and single-cell sequencing methodologies were used to perform a comprehensive examination of BMSCs with the objective of substantiating the pivotal involvement of fibroblast growth factor 2 (FGF2) and integrin alpha 2 (ITGA2) in stemness regulation. To investigate the impact of these genes on the BMSC stemness in vitro, experimental approaches involving loss and gain of function were implemented. These approaches encompassed the modulation of FGF2 and ITGA2 expression levels via small interfering RNA and overexpression plasmids. Furthermore, we examined their influence on the proliferation and differentiation capacities of BMSCs, along with the expression of stemness markers, including octamer-binding transcription factor 4, Nanog homeobox, and sex determining region Y-box 2. Transcriptomic analyzes successfully identified FGF2 and ITGA2 as pivotal genes responsible for regulating the stemness of BMSCs. Subsequent single-cell sequencing revealed that elevated FGF2 and ITGA2 expression levels within specific stem cell subpopulations are closely associated with stemness maintenance. Moreover, additional in vitro experiments have convincingly demonstrated that FGF2 effectively enhances the BMSC stemness by upregulating ITGA2 expression, a process mediated by the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. This conclusion was supported by the observed upregulation of stemness markers following the induction of FGF2 and ITGA2. Moreover, administration of the BEZ235 pathway inhibitor resulted in the repression of stemness transcription factors, suggesting the substantial involvement of the PI3K/AKT pathway in stemness preservation facilitated by FGF2 and ITGA2. This study elucidates the involvement of FGF2 in augmenting BMSC stemness by modulating ITGA2 and activating the PI3K/AKT pathway. These findings offer valuable contributions to stem cell biology and emphasize the potential of manipulating FGF2 and ITGA2 to optimize BMSCs for therapeutic purposes.

7.
ACS Nano ; 18(34): 22978-22988, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39136625

RESUMO

Two-dimensional (2D) materials provide a versatile platform for the integration of diverse crystals, enabling the formation of heterostructures with intriguing functionalities. Coherently growing 2D heterostructures are highly desirable for property manipulation due to their strong interfacial interaction. In this work, we propose a general synthesis approach and provide insight into well-designed 2D binary-ternary magnetic heterostructures. Atomically sharp interfaces were achieved in typical lateral and vertical Cr1+mSe2(001)/CuCr2Se4(111) heterostructures owing to their similar lattice arrangement, with the observation of a significant enhancement of optical second-harmonic generation. Further magnetism measurements revealed a Curie temperature up to 360 K and thickness- and temperature-dependent magnetism in this heterostructure. Additionally, we synthesized three analogous 2D magnetic heterostructures in Fe-Cr-S, Co-Cr-S, and Cu-Cr-S systems, demonstrating the ubiquitous nature of the coherent heteroepitaxy. Our work involves the development of an innovative platform for investigating the underlying physics and potential applications of 2D binary-ternary heterostructures as well as the fabrication of associated functional devices.

8.
Nat Commun ; 15(1): 6544, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095338

RESUMO

Non-Hermitian physics has emerged as a new paradigm that profoundly changes our understanding of non-equilibrium systems, introducing novel concepts such as exceptional points, spectral topology, and non-Hermitian skin effects (NHSEs). Most existing studies focus on non-Hermitian eigenstates, whereas dynamic properties have been discussed only recently, and the dynamic NHSEs are not yet confirmed in experiments. Here, we report the experimental observation of non-Hermitian skin dynamics using tunable one-dimensional nonreciprocal double-chain mechanical systems with glide-time symmetry. Remarkably, dynamic NHSEs are observed with various behaviors in different dynamic phases, which can be understood via the generalized Brillouin zone and the related concepts. Moreover, the observed dynamic NHSEs, amplifications, bulk unidirectional wave propagation, and boundary wave trapping provide promising ways to manipulate waves in a controllable and robust way. Our findings open a new pathway toward non-Hermitian dynamics, which will fertilize the study of non-equilibrium phases of matter.

9.
J Pain Res ; 17: 2753-2765, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39206100

RESUMO

Purpose: This study aimed to explore the abnormal changes in short- and long-range functional connectivity density (FCD) in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN). Patients and Methods: Twenty HZ patients, 22 PHN patients, and 19 well-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scans. We used FCD mapping, a data-driven graph theory method, to investigate local and global functional connectivity patterns. Both short- and long-range FCD were calculated and compared among the PHN, HZ, and HC groups. Then, the abnormal regions were used to calculate seed-based functional connectivity. Finally, correlation analyses were performed between the altered FCD values and clinical datas. Results: Compared with HCs, HZ patients showed significantly increased long-range FCD of the bilateral cerebellum, thalamus, parahippocampal gyrus, superior temporal gyrus and lingual gyrus. HZ patients also displayed significantly decreased short-range FCD of the bilateral posterior cingulate gyrus, median cingulate/paracingulate gyri, and left precuneus. Compared with HCs, PHN patients displayed significantly decreased long-range FCD of the bilateral superior frontal gyrus and decreased short-range FCD in the bilateral posterior cingulate gyrus, median cingulate/paracingulate gyri, and precuneus. However, there was no significant difference in either long-range or short-range FCD between the PHN and HZ patients. Long-range FCD deficit areas and the right insula showed altered functional connectivity in PHN patients. Furthermore, pain duration in patients with PHN was correlated with abnormal long-range FCD. Conclusion: Herpes zoster pain widely affects intra- and inter-regional functional connectivity, leading to disrupted short-range FCD and increased long-range FCD during different stages of the disease. Long-term chronic pain in PHN patients may impair the pain emotion regulation pathway. These findings could improve our understanding of the pathophysiological mechanisms of HZ and PHN and offer neuroimaging markers for HZ and PHN.

10.
Org Biomol Chem ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39163001

RESUMO

A protein modification strategy was developed based on a thiol-yne click reaction using an electron-deficient yne reagent. This approach demonstrated exceptional selectivity towards thiols and exhibited rapid kinetics, resulting in conjugates with superior acid stability. The conjugation of IgG with an indole-derived fluorophore was achieved for the imaging of PD-L1 in cancer cells.

11.
Artigo em Chinês | MEDLINE | ID: mdl-39193745

RESUMO

Objective:To explore the safety and aesthetic effect of modified Z-shaped cosmetic incision in parotid benign tumor resection. Methods:A prospective study was conducted. A total of 44 patients with benign parotid tumor resection were randomly divided into experimental group(n=22) and control group(n=22). The experimental group underwent modified Z-shaped cosmetic incision, while the control group underwent the traditional S-shaped incision. The surgical duration, hospital stay, complications and maxillofacial aesthetics were compared between the two groups. Results:There was no significant difference in gender, age, surgical method, pathological type between the experimental group and the control group(P>0.05). The maxillofacial aesthetics and surgical duration of the two groups was statistically significant(P<0.05), while there was no statistically significant difference in terms of hospitalization days, surgical complications and Vancouver scar scale score (P>0.05). Conclusion:The modified Z-shaped cosmetic incision has a better effect on improving the maxillofacial aesthetics after benign parotid tumor resection, and compared with the traditional S-shaped incision, the safety is consistent, so it is worthy of clinical promotion and application.


Assuntos
Neoplasias Parotídeas , Humanos , Neoplasias Parotídeas/cirurgia , Estudos Prospectivos , Feminino , Masculino , Glândula Parótida/cirurgia , Estética , Pessoa de Meia-Idade , Cicatriz/prevenção & controle , Complicações Pós-Operatórias , Adulto , Ferida Cirúrgica , Procedimentos de Cirurgia Plástica/métodos , Tempo de Internação
12.
Animals (Basel) ; 14(16)2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39199918

RESUMO

A new Cyrtodactylus species, C. laevissp. nov., from the dry-hot valleys near the Yarlung Zangbo River in Re Village, Jindong Countryside, Lang County, Linzhi City, Xizang Autonomous Region, China, is described herein based upon the integrative taxonomic results combining molecular phylogenetic systematics and morphological characteristic comparisons. Our molecular phylogeny was inferred by combining three mitochondrial gene fragments (16S/CO1/ND2), and it indicated a distinct differentiation between the new species and C. tibetanus species complex, with obvious genetic distances (16S 9.9-11.8%/CO1 16.5-18.2%/ND2 16.6-18.5%) detected, supporting its validity. Morphologically, the new species can be easily distinguished from its congers by the following characters: (1) medium size (SVL 48.58-50.92 mm), (2) tubercles on dorsum sparse, (3) tail segments absent and tubercles on tails absent, (4) supralabials 10-12 and infralabials 8-10, (5) interorbital scales between anterior corners of the eyes 28-32, (6) scale rows at midbody 96-98, (7) ventral scales between mental and cloacal slit 145-153, (8) ventral scale rows 41-45, and (9) 4 to 5 white-yellow transverse bands with brown dots and black merges between the nape and sacrum. The description of C. laevissp. nov. increased the total species number of C. tibetanus group to three, and the total Cyrtodactylus species number in Xizang to six and in China to eleven. The new species is currently only known from the type locality with its extremely small populations and needs future surveys to reveal its distribution range, population status, natural history, and mechanisms so that the new species can coexist with Altiphylax medogense.

13.
J Integr Neurosci ; 23(8): 147, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39207073

RESUMO

BACKGROUND: Shingles can cause long-term pain and negative emotions, along with changes in brain function. In this study, Granger Causality Analysis (GCA) was used to compare herpes zoster (HZ) and postherpetic neuralgia (PHN) differences in effective connections within the "pain matrix" between patients and healthy controls to further understand patterns of interaction between brain regions and explore the relationship between changes in effective connections and clinical features. METHODS: Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 55 HZ; 55 PHN; and 50 age-, sex- matched healthy controls (HCs). The brain regions associated with the pain matrix are used as the seeds of effective connectivity. GCA was used to analyze effective connections in brain regions that differed significantly between groups. Then the correlation between GCA values and clinical indicators was studied. RESULTS: Compared with HC, GCA values between the thalamus and the amygdala, between the thalamus and the precentral gyrus, from the thalamus to the postcentral gyrus, and from the parahippocampal gyrus to the amygdala, anterior cingulate gyrus were significantly reduced in HZ patients. Compared with HC, GCA values between the insular and the postcentral gyrus, from the insular to the inferior parietal lobe, and from the postcentral gyrus to the amygdala were significantly reduced in PHN patients. Compared with HZ, GCA values between the inferior parietal lobe and the parahippocampal gyrus, between the inferior parietal lobe and the anterior cingulate gyrus, and from the anterior cingulate gyrus to the amygdala were significantly increased in PHN patients. The visual analogue scale (VAS) score of PHN patients was positively correlated with the GCA value from the central posterior lobe to the insula. CONCLUSIONS: PHN and HZ patients showed a broad reduction in effective connections, mainly reflected in abnormal pain pathway regulation, pain perception, negative emotion and memory production, providing new perspectives to understand the neuroimaging mechanisms of shingles.


Assuntos
Herpes Zoster , Imageamento por Ressonância Magnética , Neuralgia Pós-Herpética , Humanos , Neuralgia Pós-Herpética/diagnóstico por imagem , Neuralgia Pós-Herpética/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Herpes Zoster/diagnóstico por imagem , Herpes Zoster/complicações , Herpes Zoster/fisiopatologia , Idoso , Adulto , Conectoma , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia
14.
Int J Surg ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39166943

RESUMO

BACKGROUND: Mismatch-repair deficient (dMMR) and microsatellite instability-high (MSI-H) cancers are associated with an increased number of somatic mutations, which can render tumors more susceptible to immune checkpoint blockade. However, a comprehensive evaluation of the efficacy profile of immune checkpoint inhibitors in this patient population across multiple cancer types is lacking. This study aims to address this knowledge gap by synthesizing data from Phase I-III clinical trials. METHODS: A systematic search was conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials and Google Scholar from inception until June, 2024. Eligible studies included randomized controlled trials (RCTs), non-randomized comparative studies, and single-arm trials investigating immune checkpoint inhibitors in patients with dMMR/MSI-H advanced cancers. The primary outcome was objective response rate (ORR), and the secondary outcomes included disease control rate (DCR), 1-year, 2-year, and 3-year overall survival (OS) and progression-free survival (PFS) rates. Subgroup analyses were conducted for the primary outcome stratified by major study characteristics. RESULTS: Of the 10802 identified studies, 19 trials in 25 studies totaling 2052 participants met the inclusion criteria and were included in the meta-analysis. The pooled ORR was 41.7% (95% CI, 35.7%-47.7%). The pooled DCR was 68.9% (95% CI, 62.2%-75.7%). The pooled 12-month, 24-month and 36-month OS rates were 29.1% (95% CI, 19.9%-38.3%), 35.8% (95% CI, 23.6%-48.0%), and 35.8% (95% CI, 23.6%-48.0%), respectively. The pooled 12-month, 24-month and 36-month PFS rates were 46.4% (95% CI, 39.1%-53.8%), 67.0% (95% CI, 55.2%-78.8%), and 63.1% (95% CI, 37.3%-88.9%), respectively. CONCLUSIONS: The study establishes the therapeutic potential of immune checkpoint inhibitors in dMMR/MSI-H advanced cancers, highlighting the importance of MSI status in this context. Further head-to-head comparisons are needed to conclusively determine MSI's predictive power relative to proficient mismatch-repair/ microsatellite stable (pMMR/MSS) tumors.

15.
Environ Geochem Health ; 46(10): 379, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167328

RESUMO

In recent years, the prevalence and danger of organophosphorus flame retardants (OPFRs) have drawn attention from all around the world. This study examined twenty-five OPFRs observed in water and sediment samples from the Qiantang River in eastern China, as well as their occurrence, spatial distribution, possible origins, and ecological hazards. All the 25 OPFRs were detected in water and sediment samples. The levels of Σ25OPFRs in water and sediment were 35.5-192 ng/L and 8.84-48.5 ng/g dw, respectively. Chlorinated OPFRs were the main contributions in water, whereas alkyl-OPFRs were the most common congeners found in sediment. Spatial analysis revealed that sample locations in neighboring cities had somewhat higher water concentrations of OPFRs. Slowing down the river current and making the reservoir the main sink of OPFRs, the dam can prevent OPFRs from moving via the Qiantang River. Positive matrix factorization indicated that plasticizer in polyvinyl chloride, polyester resins, and polyurethane foam made the greatest contributions in water, whereas polyurethane foam and textile were the predominant source in sediment. Analysis of sediment-water exchange of OPFRs showed that twelve OPFRs in sediments can re-enter into the water body. The risk quotients showed the ecological risk was low to medium, but trixylyl phosphate exposures posed high ecological risk to aquatic organisms.


Assuntos
Monitoramento Ambiental , Retardadores de Chama , Sedimentos Geológicos , Compostos Organofosforados , Rios , Poluentes Químicos da Água , Retardadores de Chama/análise , China , Rios/química , Medição de Risco , Poluentes Químicos da Água/análise , Sedimentos Geológicos/química , Compostos Organofosforados/análise
16.
Phys Rev Lett ; 133(7): 073803, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39213563

RESUMO

Non-Hermitian physics has greatly enriched our understanding of nonequilibrium phenomena and uncovered novel effects such as the non-Hermitian skin effect (NHSE) that has profoundly revolutionized the field. NHSE has been predicted in systems with nonreciprocal couplings which, however, are challenging to realize in experiments. Without nonreciprocal couplings, the NHSE can also emerge in systems with coexisting gauge fields and loss or gain (e.g., in Floquet non-Hermitian systems). However, such Floquet NHSE remains largely unexplored in experiments. Here, we realize the Floquet NHSEs in periodically modulated optical waveguides integrated on a silicon photonic platform. By engineering the artificial gauge fields induced by the periodical modulation, we observe various Floquet NHSE phases and unveil their rich topological transitions. Remarkably, we discover the transitions between the unipolar NHSE phases and an unconventional bipolar NHSE phase, which is accompanied by the directional reversal of the NHSEs. The underlying physics is revealed by the band winding in complex quasienergy space which undergoes a topology change from isolated loops with the same winding to linked loops with opposite windings. Our work unfolds a new route toward Floquet NHSEs originating from the interplay between gauge fields and dissipation effects, and thus offers fundamentally new ways for steering light and other waves.

17.
Chembiochem ; : e202400516, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141545

RESUMO

The ability to precisely control the function of nucleic acids plays an important role in biosensing and biomedicine. In recent years, novel strategies employing biological, physical, and chemical triggers have been developed to modulate the function of nucleic acids spatiotemporally. These approaches commonly involve the incorporation of stimuli-responsive groups onto nucleic acids to block their functions until triggers-induced decaging restore activity. These inventive strategies deepen our comprehension of nucleic acid molecules' dynamic behavior and provide new techniques for precise disease diagnosis and treatment. Focusing on the spatiotemporal regulation of nucleic acid molecules through the chemical caging-decaging strategy, we here present an overview of the innovative triggered control mechanisms and accentuate their implications across the fields of chemical biology, biomedicine, and biosensing.

18.
Bioorg Chem ; 152: 107729, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39178703

RESUMO

This study describes the synthesis and characterization of a novel near-infrared (NIR) fluorescent probe RBNE based on a hybrid rhodamine dye, which shows excellent optical capability for detecting and imaging ONOO- in necrotizing enterocolitis (NEC) mouse model. The probe RBNE undergoes hydrazine redox-process, and subsequently the spirocyclic structure's opening, resulting in a turn-on fluorescence emission with the presence of ONOO-, which exhibits several excellent features, including a significant Stokes shift of 108 nm, near-infrared emission at 668 nm, a lower detection limit of 56 nM, low cytotoxicity, and excellent imaging ability for ONOO- both in vitro and in vivo. The presented study introduces a novel optical tool that has the potential to significantly advance our understanding of peroxynitrite (ONOO-) behaviors in necrotizing enterocolitis (NEC).


Assuntos
Enterocolite Necrosante , Corantes Fluorescentes , Hidrazinas , Ácido Peroxinitroso , Rodaminas , Ácido Peroxinitroso/análise , Ácido Peroxinitroso/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Enterocolite Necrosante/diagnóstico por imagem , Rodaminas/química , Rodaminas/síntese química , Animais , Camundongos , Hidrazinas/química , Hidrazinas/síntese química , Estrutura Molecular , Modelos Animais de Doenças , Humanos , Imagem Óptica
19.
Cell ; 187(18): 5064-5080.e14, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39089254

RESUMO

So far, biocomputation strictly follows traditional design principles of digital electronics, which could reach their limits when assembling gene circuits of higher complexity. Here, by creating genetic variants of tristate buffers instead of using conventional logic gates as basic signal processing units, we introduce a tristate-based logic synthesis (TriLoS) framework for resource-efficient design of multi-layered gene networks capable of performing complex Boolean calculus within single-cell populations. This sets the stage for simple, modular, and low-interference mapping of various arithmetic logics of interest and an effectively enlarged engineering space within single cells. We not only construct computational gene networks running full adder and full subtractor operations at a cellular level but also describe a treatment paradigm building on programmable cell-based therapeutics, allowing for adjustable and disease-specific drug secretion logics in vivo. This work could foster the evolution of modern biocomputers to progress toward unexplored applications in precision medicine.


Assuntos
Redes Reguladoras de Genes , Humanos , Lógica , Biologia Sintética/métodos , Engenharia Genética/métodos , Biologia Computacional/métodos , Animais
20.
Bioorg Chem ; 151: 107691, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39116524

RESUMO

Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed. Compounds 1, 2, 5, 6, 11, and 12 showed significant cardioprotective activities comparable to diltiazem against isoprenaline (ISO)-induced H9C2 cell damage in vitro. Compound 11 probably exerted heart-protective effect on ISO-induced H9C2 cells by modulating the PI3K-AKT-mTOR pathway, reducing excessive autophagy, and decreasing myocardial apoptosis.


Assuntos
Apoptose , Autofagia , Boraginaceae , Miócitos Cardíacos , Terpenos , Apoptose/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Autofagia/efeitos dos fármacos , Boraginaceae/química , Ratos , Terpenos/farmacologia , Terpenos/química , Terpenos/isolamento & purificação , Animais , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Insuficiência Cardíaca/tratamento farmacológico , Cardiotônicos/farmacologia , Cardiotônicos/química , Cardiotônicos/isolamento & purificação , Linhagem Celular
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