Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 471
Filtrar
1.
BMC Vet Res ; 20(1): 411, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39272157

RESUMO

BACKGROUND: Sepsis, defined as a dysregulated inflammatory response to infection inducing organ dysfunction, is a common cause of mortality in both humans and animals. Early detection and treatment is essential for survival, but accurate diagnosis is challenging due to the lack of specific biomarkers for sepsis. This study explored the potential of the keratinocyte-derived chemokine (KC)-like protein in dogs as a biomarker of sepsis in dogs with bacterial uterine infection (pyometra). The aim was to compare KC-like concentrations in dogs with pyometra with or without sepsis and to assess associations between KC-like and clinical variables, including days of hospitalization as an outcome. RESULTS: A mouse KC ELISA was validated and used to determine the concentrations of KC-like in serum from 34 dogs with pyometra and 18 healthy controls. Dogs with pyometra were classified as having sepsis based on two different criteria for systemic inflammatory response syndrome (SIRS), resulting in 74% and 30% sepsis-positive, respectively. The concentration of KC-like protein was higher in pyometra dogs with sepsis than in pyometra dogs without sepsis (p < 0.05) and in healthy controls (p < 0.0001) when using either of the two SIRS criteria. Moreover, KC-like was slightly increased in dogs with pyometra without sepsis compared with healthy controls when using the more stringent SIRS criteria (p < 0.05). Analyses of all dogs showed that KC-like concentrations correlated positively with hospitalization days, C-reactive protein (CRP) concentrations, white blood cells, and percentage of band neutrophils; however, KC-like correlated negatively with hemoglobin and did not correlate with circulating creatinine. CONCLUSIONS: Our results suggest that circulating KC-like protein increases in dogs with sepsis in pyometra and that KC-like is associated with more severe clinical illness. These findings support a potential role of KC-like as a biomarker of sepsis; however, the true identity of KC-like in dogs has yet to be uncovered.


Assuntos
Biomarcadores , Doenças do Cão , Piometra , Sepse , Animais , Cães , Piometra/veterinária , Piometra/sangue , Piometra/complicações , Feminino , Doenças do Cão/sangue , Biomarcadores/sangue , Sepse/veterinária , Sepse/sangue , Quimiocinas/sangue , Ensaio de Imunoadsorção Enzimática/veterinária , Síndrome de Resposta Inflamatória Sistêmica/veterinária , Síndrome de Resposta Inflamatória Sistêmica/sangue
2.
Future Oncol ; : 1-12, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39155836

RESUMO

Aim: To evaluate real-world treatment patterns, survival and healthcare-resource utilization in US patients with advanced biliary tract cancers (BTC) receiving systemic therapy.Patients & methods: This study used claims data from the Healthcare Integrated Research Database (HIRD®) linked to clinical data from the Cancer Care Quality Program (January 1, 2015-September 30, 2020).Results: Of 413 patients, 84.5% received gemcitabine-based first-line (1L) treatment, 46% received second-line treatment, and 16.5% received third-line (3L) treatment. All-cause mortality was 53% and approximately 70% of patients had ≥1 inpatient visit. The total mean per-patient-per-month all-cause costs were $19,589 for 1L and $33,534 for 3L treatment.Conclusion: Results showed poor survival, significant resource use and high costs as treatment line progresses for patients with advanced BTC.


Our research explored which treatments US patients with advanced biliary tract cancers (BTC) received and how long they lived for. We analyzed information from a US database, called the Healthcare Integrated Research Database (HIRD®), which holds information related to healthcare insurance claims. Out of 413 patients in the database, 84.5% were initially given a combination treatment involving a chemotherapy called gemcitabine. We also found that 46% of patients received a type of second treatment (also known as second-line therapy), and 16.5% received a third treatment (third-line therapy). During treatment, around 70% of patients needed to stay in hospital at least once. The cost of healthcare was more expensive for patients receiving later lines of therapy, with the average monthly cost per patient for first-line treatment being $19,589 and third-line treatment being $33,534. Furthermore, just over half of the 413 patients died from any causes, showing the poor outlook these patients face. This information is important for understanding the real-world management of patients with BTC, so that their care can be improved in the future.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39181741

RESUMO

This study aimed to evaluate the relationship between the precise three-dimensional location of the third molar (M3) and mandibular angle fracture (MAF) patterns and to assess the effect of the volume ratio occupied by M3 in the mandibular angle on fracture patterns. The location of M3 was assessed in 218 patients with MAF using computed tomography reconstruction. The bone volume of the mandibular angle and the bone volume occupied by M3 were measured to calculate the volume ratio of M3 to the mandibular angle (M3/MA). MAF patterns were categorized into simple fracture (Type I), displaced fracture (Type II), and comminuted fracture (Type III) based on fracture severity. The results showed that the location of M3 significantly influenced MAF patterns (vertical position: P = .001; horizontal position: P = .002; angulation: P = .027, respectively) and the volume ratio of M3/MA was significantly higher for Type III fracture than Types I and II (P < .001). Regression analysis showed that the horizontal position and angulation of M3 and the volume ratio of M3/MA were the main predictors for comminuted MAF. A larger volume ratio (odds ratio [OR], 1.201; 95% confidence interval [CI], 1.037-1.391; P < .014), Class III position (OR, 7.978; 95% CI, 1.275-49.910; P < .026), and horizontal angulation (OR, 7.212; 95% CI, 1.028-50.581; P < .047) of the M3 were more prone to comminuted MAF than simple fracture. Our findings indicate that the location of M3 significantly affects MAF patterns, and that M3 may weaken the mandibular angle by occupying more bone space, thereby increasing the risk of a comminuted fracture.

4.
NAR Genom Bioinform ; 6(3): lqae097, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39131819

RESUMO

Sorghum bicolor (L.) Moench is a significant grass crop globally, known for its genetic diversity. High quality genome sequences are needed to capture the diversity. We constructed high-quality, chromosome-level genome assemblies for two vital sorghum inbred lines, Tx2783 and RTx436. Through advanced single-molecule techniques, long-read sequencing and optical maps, we improved average sequence continuity 19-fold and 11-fold higher compared to existing Btx623 v3.0 reference genome and obtained 19 and 18 scaffolds (N50 of 25.6 and 14.4) for Tx2783 and RTx436, respectively. Our gene annotation efforts resulted in 29 612 protein-coding genes for the Tx2783 genome and 29 265 protein-coding genes for the RTx436 genome. Comparative analyses with 26 plant genomes which included 18 sorghum genomes and 8 outgroup species identified around 31 210 protein-coding gene families, with about 13 956 specific to sorghum. Using representative models from gene trees across the 18 sorghum genomes, a total of 72 579 pan-genes were identified, with 14% core, 60% softcore and 26% shell genes. We identified 99 genes in Tx2783 and 107 genes in RTx436 that showed functional enrichment specifically in binding and metabolic processes, as revealed by the GO enrichment Pearson Chi-Square test. We detected 36 potential large inversions in the comparison between the BTx623 Bionano map and the BTx623 v3.1 reference sequence. Strikingly, these inversions were notably absent when comparing Tx2783 or RTx436 with the BTx623 Bionano map. These inversion were mostly in the pericentromeric region which is known to have low complexity regions and harder to assemble and suggests the presence of potential artifacts in the public BTx623 reference assembly. Furthermore, in comparison to Tx2783, RTx436 exhibited 324 883 additional Single Nucleotide Polymorphisms (SNPs) and 16 506 more Insertions/Deletions (INDELs) when using BTx623 as the reference genome. We also characterized approximately 348 nucleotide-binding leucine-rich repeat (NLR) disease resistance genes in the two genomes. These high-quality genomes serve as valuable resources for discovering agronomic traits and structural variation studies.

5.
Mol Genet Genomic Med ; 12(7): e2492, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39007454

RESUMO

BACKGROUND: Synonymous variants are non-pathogenic due to non-substitution of amino acids. However, synonymous exonic terminal nucleotide substitutions may affect splicing. Splicing variants are easily analyzed at RNA level for genes expressed in blood cells. Minigene analysis provides another method for splicing variant analysis of genes that are poorly or not expressed in peripheral blood. METHODS: Whole exome sequencing was performed to screen for potential pathogenic mutations in the proband, which were validated within the family by Sanger sequencing. The pathogenicity of the synonymous mutation was analyzed using the minigene technology. RESULTS: The proband harbored the compound heterogeneous variants c. [291G >A; 572-50C >T] and c.681 + 1G >T in F7, of which the synonymous variant c.291G >A was located at the terminal position of exon 3. Minigene analysis revealed exon3 skipping due to this mutation, which may have subsequently affected protein sequence, structure, and function. CONCLUSION: Our finding confirmed the pathogenicity of c.291G >A, thus extending the pathogenic mutation spectrum of F7, and providing insights for effective reproductive counseling.


Assuntos
Éxons , Fator VII , Splicing de RNA , Mutação Silenciosa , Adulto , Feminino , Humanos , Masculino , Linhagem , Fator VII/genética
6.
iScience ; 27(7): 110273, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39040056

RESUMO

Liver sinusoidal endothelial cells (LSECs) have a unique morphological structure known as "fenestra" that plays a crucial role in liver substance exchange and homeostasis maintenance. In this study, we demonstrate that ADAMTS18 protease is primarily secreted by fetal liver endothelial cells. ADAMTS18 deficiency leads to enlarged fenestrae and increased porosity of LSECs, microthrombus formation in liver vessels, and an imbalance of liver oxidative stress. These defects worsen carbon tetrachloride (CCl4)-induced liver fibrosis and diethylnitrosamine (DEN)/high-fat-induced hepatocellular carcinoma (HCC) in adult Adamts18-deficient mice. Mechanically, ADAMTS18 functions as a modifier of fibronectin (FN) to regulate the morphological acquisition of LSECs via the vascular endothelial growth factor A (VEGFA) signaling pathways. Collectively, a mechanism is proposed for LSEC morphogenesis and liver homeostasis maintenance via ADAMTS18-FN-VEGFA niches.

7.
Heliyon ; 10(12): e32671, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975126

RESUMO

Microbially induced nitrogen (N2) gas bubbles can desaturate subsurface areas and thus have been considered as an alternative ground improvement technique for mitigating soil liquefaction potential caused by earthquakes. However, the detailed mechanisms of subsurface N2 bubbles are not well understood and remain a subject of ongoing research. In this study, a transparent microfluidic device was utilized to mimic biological N2 gas bubble formation by nitrate-reducing bacteria and to visually characterize the entire process. During N2 gas formation, a limited number of bubble nucleation sites were identified, which gradually expanded upward through the preferential pore channels. N2 gas bubbles tended to create interconnected gas pockets rather than existing as evenly distributed small gas cavities. The degree of water saturation gradually reduced over a week as the bubbles were produced. The gas ganglia repeatedly grew until they reached the top boundary, which triggered a drastic expulsion of bubbles by ebullition. Despite fluctuations in saturation level, the residual saturation was maintained at around 73 %. Comparative experimental case studies of CO2 gas bubble formation were conducted to identify contrasting gas formation mechanisms. CO2 gas bubbles were generated via the abiotic decompression of a supersaturated CO2 solution under two distinct rates of pressure reduction. Rapid CO2 bubble formation led to uniform nucleation and 41 % residual saturation, while slower formation yielded 35 % due to stable liquid displacement by the gas front. This study highlights the potential of the microfluidic device as an experimental tool for visualizing subsurface gas formation mechanisms. The insights gained could further enhance and optimize geotechnical applications involving gas formation in highly saturated soils.

8.
Hum Genomics ; 18(1): 79, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010135

RESUMO

The analysis of genomic variations in offspring after implantation has been infrequently studied. In this study, we aim to investigate the extent of de novo mutations in humans from developing fetus to birth. Using high-depth whole-genome sequencing, 443 parent-offspring trios were studied to compare the results of de novo mutations (DNMs) between different groups. The focus was on fetuses and newborns, with DNA samples obtained from the families' blood and the aspirated embryonic tissues subjected to deep sequencing. It was observed that the average number of total DNMs in the newborns group was 56.26 (54.17-58.35), which appeared to be lower than that the multifetal reduction group, which was 76.05 (69.70-82.40) (F = 2.42, P = 0.12). However, after adjusting for parental age and maternal pre-pregnancy body mass index (BMI), significant differences were found between the two groups. The analysis was further divided into single nucleotide variants (SNVs) and insertion/deletion of a small number of bases (indels), and it was discovered that the average number of de novo SNVs associated with the multifetal reduction group and the newborn group was 49.89 (45.59-54.20) and 51.09 (49.22-52.96), respectively. No significant differences were noted between the groups (F = 1.01, P = 0.32). However, a significant difference was observed for de novo indels, with a higher average number found in the multifetal reduction group compared to the newborn group (F = 194.17, P < 0.001). The average number of de novo indels among the multifetal reduction group and the newborn group was 26.26 (23.27-29.05) and 5.17 (4.82-5.52), respectively. To conclude, it has been observed that the quantity of de novo indels in the newborns experiences a significant decrease when compared to that in the aspirated embryonic tissues (7-9 weeks). This phenomenon is evident across all genomic regions, highlighting the adverse effects of de novo indels on the fetus and emphasizing the significance of embryonic implantation and intrauterine growth in human genetic selection mechanisms.


Assuntos
Feto , Humanos , Feminino , Gravidez , Recém-Nascido , Masculino , Adulto , Polimorfismo de Nucleotídeo Único/genética , Implantação do Embrião/genética , Genoma Humano/genética , Mutação INDEL/genética , Genômica , Sequenciamento Completo do Genoma , Sequenciamento de Nucleotídeos em Larga Escala , Mutação/genética , Desenvolvimento Fetal/genética
9.
Reprod Toxicol ; 128: 108648, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38909692

RESUMO

Previous retrospective cohort studies have found that, compared with oxygen tension in the uterus and fallopian tubes (2 %-8 %), exposure of pre-implantation embryos to atmospheric oxygen tension (AtmO2, 20 %) during assisted reproductive technology(ART) can affect embryo quality, pregnancy outcomes and offspring health. However, current research on the effects and mechanisms of AtmO2 on the development of embryos and offspring is mainly limited to animal experiments. Human embryonic stem cells (hESCs) play a special and irreplaceable role in the study of early human embryonic development. In this study, we used hESCs as a model to elucidate the possible effects and mechanisms of AtmO2 exposure on human embryonic development. We found that exposure to AtmO2 can reduce cell viability, produce oxidative stress, increase DNA damage, initiate DNA repair, activate autophagy, and increase cell apoptosis. We also noticed that approximately 50 % of hESCs survived, adapted and proliferated through high expression of self-renewal and pluripotency regulatory factors, and affected embryoid body differentiation. These data indicate that hESCs experience oxidative stress, accumulation of DNA damage, and activate DNA damage response under the selective pressure of AtmO2.Some hESCs undergo cell death, whereas other hESCs adapt and proliferate through increased expression of self-renewal genes. The current findings provide in vitro evidence that exposure to AtmO2 during the early preimplantation stage negatively affects hESCs.


Assuntos
Diferenciação Celular , Sobrevivência Celular , Dano ao DNA , Desenvolvimento Embrionário , Células-Tronco Embrionárias Humanas , Estresse Oxidativo , Oxigênio , Humanos , Diferenciação Celular/efeitos dos fármacos , Oxigênio/toxicidade , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Células-Tronco Embrionárias Humanas/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Reparo do DNA , Autofagia/efeitos dos fármacos , Linhagem Celular
10.
Comput Inform Nurs ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934788

RESUMO

BACKGROUND AND OBJECTIVES: Mental health disorders, including anxiety and depression, are the leading causes of global health-related burden and have increased dramatically since the 1990s. Delivering mental healthcare using artificial intelligence chatbots may be one option for closing the gaps in mental healthcare access. The overall aim of this scoping review was to describe the use, efficacy, and advantages/disadvantages of using an artificial intelligence chatbot for mental healthcare (stress, anxiety, depression). METHODS: PubMed, PsycINFO, CINAHL, and Web of Science databases were searched. When possible, Medical Subject Headings terms were searched in combination with keywords. Two independent reviewers reviewed a total of 5768 abstracts. RESULTS: Fifty-four articles were chosen for further review, with 10 articles included in the final analysis. Regarding quality assessment, the overall quality of the evidence was lower than expected. Overall, most studies showed positive trends in improving anxiety, stress, and depression. DISCUSSION: Overall, using an artificial intelligence chatbot for mental health has some promising effects. However, many studies were done using rudimentary versions of artificial intelligence chatbots. In addition, lack of guardrails and privacy issues were identified. More research is needed to determine the effectiveness of artificial intelligence chatbots and to describe undesirable effects.

11.
Small ; : e2403781, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850188

RESUMO

The delayed healing of infected wounds can be attributed to the increased production of reactive oxygen species (ROS) and consequent damages to vascellum and tissue, resulting in a hypoxic wound environment that further exacerbates inflammation. Current clinical treatments including hyperbaric oxygen therapy and antibiotic treatment fail to provide sustained oxygenation and drug-free resistance to infection. To propose a dynamic oxygen regulation strategy, this study develops a composite hydrogel with ROS-scavenging system and oxygen-releasing microspheres in the wound dressing. The hydrogel itself reduces cellular damage by removing ROS derived from immune cells. Simultaneously, the sustained release of oxygen from microspheres improves cell survival and migration in hypoxic environments, promoting angiogenesis and collagen regeneration. The combination of ROS scavenging and oxygenation enables the wound dressing to achieve drug-free anti-infection through activating immune modulation, inhibiting the secretion of pro-inflammatory cytokines interleukin-6, and promoting tissue regeneration in both acute and infected wounds of rat skins. Thus, the composite hydrogel dressing proposed in this work shows great potential for dynamic redox regulation of infected wounds and accelerates wound healing without drugs.

12.
Heliyon ; 10(11): e32114, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38882369

RESUMO

Background: Cervical intraepithelial neoplasia (CIN) encompasses a range of cervical lesions that are closely linked to cervical invasive carcinoma. Early detection and timely treatment of CIN are crucial for preventing the progression of the disease. However, no bibliometric analysis has been conducted in this area. This research aimed to employ bibliometric analysis to summarize the current research hotspots and estimate future research trends in the CIN field. Methods: Publications related to CIN (2013-2023) were retrieved from the Science-Citation-Index-Expanded-of-Web-of-Science-Core-Collection. CiteSpace, VOSviewer, and the bibliometric-Online-Analysis-Platform-of-Literature-Metrology were employed to analyze the yearly research output, collaborating institutions or countries, leading researchers, principal journals, co-referenced sources, and emerging keywords. Results: In total, 4677 articles on CIN that were published from 2013 to 2023 and met our criteria were extracted. Major publishing platforms were predominantly USA until 2017 when China emerged as the leading source of publications about CIN. The USA was the leading nation in international collaborations. The National-Cancer-Institute (NCI) was the institution with the most publications. Schiffman Mark produced the highest number of articles, with a total of 92. Ten major clusters were identified through co-cited keyword clustering, including prevalence, human papillomavirus, DNA methylation, p16, methylation, conization, HPV genotyping tests (VALGENT), deep learning, vaginal microbiome, and immunohistochemistry. Keyword burst analysis showed that photodynamic therapy and deep learning emerged as prominent research focal points with significant impact in resent three years. Conclusion: Global publications on CIN research showed a relatively stable trend over the past eleven years. Current research hotspots are deep learning and photodynamic therapy. This research offered organized data and insightful guidance for future studies, which may help better prevent, screen, and treat CIN.

13.
Brain Res Bull ; 211: 110937, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38570077

RESUMO

Adult survivors of childhood brain tumors often present with cognitive deficits that affect their quality of life. Studying brain structure and function in brain tumor survivors can help understand the underlying mechanisms of their cognitive deficits to improve long-term prognosis of these patients. This study analyzed voxel-based morphometry (VBM) derived from T1-weighted MRI and the amplitude of low-frequency fluctuation (ALFF) from resting-state functional magnetic resonance imaging (rs-fMRI) to examine the structural and functional alterations in 35 brain tumor survivors using 35 matching healthy individuals as controls. Compared with healthy controls, brain tumor survivors had decreased gray matter volumes (GMV) in the thalamus and increased GMV in the superior frontal gyrus. Functionally, brain tumor survivors had lower ALFF values in the inferior temporal gyrus and medial prefrontal area and higher ALFF values in the thalamus. Importantly, we found concurrent but negatively correlated structural and functional alterations in the thalamus based on observed significant differences in GMV and ALFF values. These findings on concurrent brain structural and functional alterations provide new insights towards a better understanding of the cognitive deficits in brain tumor survivors.


Assuntos
Neoplasias Encefálicas , Sobreviventes de Câncer , Imageamento por Ressonância Magnética , Tálamo , Humanos , Masculino , Feminino , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética/métodos , Tálamo/diagnóstico por imagem , Tálamo/patologia , Adulto , Adulto Jovem , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Imagem Multimodal/métodos , Criança , Sobreviventes
14.
Comput Methods Programs Biomed ; 249: 108159, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583291

RESUMO

BACKGROUND AND OBJECTIVE: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. The accurate survival prediction for CRC patients plays a significant role in the formulation of treatment strategies. Recently, machine learning and deep learning approaches have been increasingly applied in cancer survival prediction. However, most existing methods inadequately represent and leverage the dependencies among features and fail to sufficiently mine and utilize the comorbidity patterns of CRC. To address these issues, we propose a self-attention-based graph learning (SAGL) framework to improve the postoperative cancer-specific survival prediction for CRC patients. METHODS: We present a novel method for constructing dependency graph (DG) to reflect two types of dependencies including comorbidity-comorbidity dependencies and the dependencies between features related to patient characteristics and cancer treatments. This graph is subsequently refined by a disease comorbidity network, which offers a holistic view of comorbidity patterns of CRC. A DG-guided self-attention mechanism is proposed to unearth novel dependencies beyond what DG offers, thus augmenting CRC survival prediction. Finally, each patient will be represented, and these representations will be used for survival prediction. RESULTS: The experimental results show that SAGL outperforms state-of-the-art methods on a real-world dataset, with the receiver operating characteristic curve for 3- and 5-year survival prediction achieving 0.849±0.002 and 0.895±0.005, respectively. In addition, the comparison results with different graph neural network-based variants demonstrate the advantages of our DG-guided self-attention graph learning framework. CONCLUSIONS: Our study reveals that the potential of the DG-guided self-attention in optimizing feature graph learning which can improve the performance of CRC survival prediction.


Assuntos
Neoplasias Colorretais , Aprendizado de Máquina , Humanos , Redes Neurais de Computação , Período Pós-Operatório , Curva ROC
15.
Artigo em Inglês | MEDLINE | ID: mdl-38518117

RESUMO

Drosophila has been used as an animal model to study pathogenic mechanism of neurological disorders. Thymidylate kinase (TMPK) is an essential enzyme in dTTP synthesis catalyzing the phosphorylation of dTMP to dTDP. Loss of function mutations in the DTYMK gene, coding for TMPK, cause severe microcephaly in human patients. In this study, Drosophila melanogaster TMPK (DmTMPK) was cloned, expressed, purified and characterized. Unlike human TMPK, DmTMPK phosphorylated not only dTMP and dUMP but also dGMP and dIMP although with low efficiency. ATP and dATP are the most efficient phosphate donor but at higher concentration (>1 mM) ATP inhibited DmTMPK activity. Sequence and structural model analysis explain why DmTMPK could phosphorylate purine nucleoside monophosphates. This study has laid a solid foundation for future study of TMPK function in Drosophila.

16.
Front Oncol ; 14: 1348045, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38390265

RESUMO

Introduction: The programmed death-1 (PD-1) immune checkpoint inhibitor pembrolizumab is currently approved in the US for the first-line (1L) treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), either alone or in combination with platinum and 5-fluorouracil (5-FU). However, the toxicity of 5-FU has motivated the study of alternate combinations that replace 5-FU with a taxane. The objective of the current study was to describe the baseline characteristics, treatment patterns and sequences, and real-world outcomes of individuals receiving pembrolizumab + platinum + taxane as 1L treatment for R/M HNSCC in the US. Methods: This was a retrospective study of US adults ≥18 years of age receiving pembrolizumab + platinum + taxane as 1L treatment for R/M HNSCC, using electronic health record data from a nationwide de-identified database. Real-world overall survival (rwOS), time on treatment (rwToT), and time to next treatment (rwTTNT) outcomes were assessed using Kaplan-Meier analysis. Results: The study population comprised 83 individuals (80.7% male) with a median age of 64 years. The most common tumor site was the oropharynx (48.2%); 70.0% of these tumors were HPV-positive. A total of 71.1% of the study population had an Eastern Cooperative Oncology Group performance status of 0-1 at index date, 71.8% had a combined positive score for programmed death ligand-1 (PD-L1) expression of ≥1, and 30.8% had a score of ≥20. The median (95% CI) rwOS was 14.9 (8.8-23.3) months, rwToT was 5.3 (4.0-8.2) months, and rwTTNT was 8.7 (6.8-12.3) months. Among the 24 individuals who received a subsequent therapy, the most common second-line therapies were cetuximab-based (n = 9) or pembrolizumab-containing (n = 8) regimens. Conclusions: The rwOS and other real-world outcomes observed for this study population further support pembrolizumab + platinum + taxane combination therapy as a potential 1L treatment option for R/M HNSCC.

17.
Nat Commun ; 15(1): 1843, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418496

RESUMO

The development of facile tailoring approach to adjust the intrinsic activity and stability of atomically-precise metal nanoclusters catalysts is of great interest but remians challenging. Herein, the well-defined Au8 nanoclusters modified by single-atom sites are rationally synthesized via a co-eletropolymerization strategy, in which uniformly dispersed metal nanocluster and single-atom co-entrenched on the poly-carbazole matrix. Systematic characterization and theoretical modeling reveal that functionalizing single-atoms enable altering the electronic structures of Au8 clusters, which amplifies their electrocatalytic reduction of CO2 to CO activity by ~18.07 fold compared to isolated Au8 metal clusters. The rearrangements of the electronic structure not only strengthen the adsorption of the key intermediates *COOH, but also establish a favorable reaction pathway for the CO2 reduction reaction. Moreover, this strategy fixing nanoclusters and single-atoms on cross-linked polymer networks efficiently deduce the performance deactivation caused by agglomeration during the catalytic process. This work contribute to explore the intrinsic activity and stability improvement of metal clusters.

18.
PLoS Comput Biol ; 20(2): e1011270, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38324613

RESUMO

CyVerse, the largest publicly-funded open-source research cyberinfrastructure for life sciences, has played a crucial role in advancing data-driven research since the 2010s. As the technology landscape evolved with the emergence of cloud computing platforms, machine learning and artificial intelligence (AI) applications, CyVerse has enabled access by providing interfaces, Software as a Service (SaaS), and cloud-native Infrastructure as Code (IaC) to leverage new technologies. CyVerse services enable researchers to integrate institutional and private computational resources, custom software, perform analyses, and publish data in accordance with open science principles. Over the past 13 years, CyVerse has registered more than 124,000 verified accounts from 160 countries and was used for over 1,600 peer-reviewed publications. Since 2011, 45,000 students and researchers have been trained to use CyVerse. The platform has been replicated and deployed in three countries outside the US, with additional private deployments on commercial clouds for US government agencies and multinational corporations. In this manuscript, we present a strategic blueprint for creating and managing SaaS cyberinfrastructure and IaC as free and open-source software.


Assuntos
Inteligência Artificial , Software , Humanos , Computação em Nuvem , Editoração
19.
J Colloid Interface Sci ; 661: 207-218, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38301459

RESUMO

Solar energy-assisted hydrogen production technology is an essential tool for exploring hydrogen energy. To date, semiconductors have been used as the primary photocatalyst to generate hydrogen via photocatalytic water splitting. However, the high photogenerated electron-hole recombination rate of semiconductor photocatalysts results in a low hydrogen production rate. Herein, the synergistic effect of Mo-ion doping and the incorporation of Ni-based Hofmann-type coordination polymer (Ni-Ni HCP) on the photocatalytic performance of ZnIn2S4 (ZIS) is investigated. The hydrogen production rate of the prepared in-situ Mo doped ZnIn2S4 wrapped Ni-Ni HCP (Ni-Ni HCP/Mo-ZIS) sample under visible-light irradiation is 26.7 mmol g-1h-1, which is 10 times that of pure ZIS. Hydrogen production rate test, microscopic characterization, and density functional theory calculation confirm that the proposed dual modulation approach (combined ion doping and heterogeneous structure construction) could effectively increase the photocatalytic efficiency of ZIS. The stability of prepared samples is also examined by four-cycle photocatalytic hydrogen production tests. The proposed integrated method opens a new route for advancing renewable energy technology towards a sustainable future.

20.
Adv Mater ; 36(19): e2309972, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38324725

RESUMO

Current approaches to treating inflammatory bowel disease focus on the suppression of overactive immune responses, the removal of reactive intestinal oxygen species, and regulation of the intestinal flora. However, owing to the complex structure of the gastrointestinal tract and the influence of mucus, current small-molecule and biologic-based drugs for treating colitis cannot effectively act at the site of colon inflammation, and as a result, they tend to exhibit low efficacies and toxic side effects. In this study, nanogel-based multistage NO delivery microcapsules are developed to achieve NO release at the inflammation site by targeting the inflammatory tissues using the nanogel. Surprisingly, oral administration of the microcapsules suppresses the growth of pathogenic bacteria and increases the abundance of probiotic bacteria. Metabolomics further show that an increased abundance of intestinal probiotics promotes the production of metabolites, including short-chain fatty acids and indole derivatives, which modulate the intestinal immunity and restore the intestinal barrier via the interleukin-17 and PI3K-Akt signaling pathways. This work reveals that the developed gas therapy strategy based on multistage NO delivery microcapsules modulates the intestinal microbial balance, thereby reducing inflammation and promoting intestinal barrier repair, ultimately providing a new therapeutic approach for the clinical management of colitis.


Assuntos
Cápsulas , Colite , Microbioma Gastrointestinal , Nanogéis , Óxido Nítrico , Colite/tratamento farmacológico , Animais , Cápsulas/química , Camundongos , Nanogéis/química , Óxido Nítrico/metabolismo , Probióticos , Polietilenoimina/química , Gases/química , Camundongos Endogâmicos C57BL , Polietilenoglicóis
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...