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1.
Medicine (Baltimore) ; 103(16): e37848, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640332

RESUMO

OBJECTIVE: To investigate the clinical efficacy of fire acupuncture (FA) on plaque psoriasis (PP), exploring its suitable syndrome types, in order to achieve better therapeutic effects, accelerate the possibility of psoriasis skin lesion recovery, and provide assistance for clinical treatment. METHODS: A total of 8 patients with PP aged between 18 and 60 years were recruited and treated with FA once a week, and the lesion area and severity index (PASI), visual analog scale and pruritus were measured before, 2, 4 and 8 weeks after treatment and at the follow-up period (week 12), respectively. Visual analog scale, and dermoscopy were used for assessment. RESULTS: All patients showed improvement in pruritus after 1 FA treatment, and lesions were reduced to varying degrees after 2 weeks. Except for patients 5 and 8, who only achieved effective results due to severe disease, all other patients with psoriasis achieved significant results at 8 weeks after treatment. CONCLUSION: FA can significantly control the development of lesions, reduce the symptoms of PP lesions and pruritus, and help prevent psoriasis recurrence.


Assuntos
Terapia por Acupuntura , Psoríase , Humanos , Lactente , Psoríase/tratamento farmacológico , Resultado do Tratamento , Prurido/etiologia , Prurido/terapia , Pesquisa , Índice de Gravidade de Doença , Método Duplo-Cego
2.
Geohealth ; 8(4): e2024GH001040, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38651003

RESUMO

Animal experiments suggest that selenium (Se) may alleviate cadmium (Cd) toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. In black shale regions such as Enshi and Zhuxi County, residents who long-term consume local rice may surpass safe Se and Cd intake levels. Significantly high median blood Se (B-Se) and urine selenium (U-Se) levels were detected in these areas, measuring 416.977 µg/L and 352.690 µg/L and 104.527 µg/L and 51.820 µg/L, respectively. Additionally, the median blood Cd (B-Cd) and urine Cd (U-Cd) levels were markedly elevated at 4.821 µg/L and 3.848 µg/L and at 7.750 µg/L and 7.050 µg/L, respectively, indicating substantial Cd exposure. Nevertheless, sensitive liver and kidney biomarkers in these groups fall within healthy reference ranges, suggesting a potential antagonistic effect of Se on Cd in the human body. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. However, within the healthy ranges, residents in the Enshi study area had significantly greater median levels of serum creatinine and cystatin C, measuring 67.3 µmol/L and 0.92 mg/L, respectively, than those in Zhuxi did (53.6 µmol/L and 0.86 mg/L). In cases of excessive Se and Cd exposure, high Se and Cd levels impact the filtration function of the human kidney to some extent.

3.
Aging (Albany NY) ; 162024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38656888

RESUMO

BACKGROUND: Patients with gastric cancer respond poorly to immunotherapy. There are still unknowns about the biomarkers associated with immunotherapy sensitivity and their underlying molecular mechanisms. METHODS: Gene expression data for gastric cancer were gathered from TCGA and GEO databases. DEGs associated with immunotherapy response came from ICBatlas. KEGG and GO analyses investigated pathways. Hub genes identification employed multiple machine algorithms. Associations between hub genes and signaling pathways, disease genes, immune cell infiltration, drug sensitivity, and prognostic predictions were explored via multi-omics analysis. Hub gene expression was validated through HPA and CCLE. Multiple algorithms pinpointed Cancer-Associated Fibroblasts genes (CAFs), with ten machine-learning methods generating CAFs scores for prognosis. Model gene expression was validated at the single-cell level using the TISCH database. RESULTS: We identified 201 upregulated and 935 downregulated DEGs. Three hub genes, namely CDH6, EGFLAM, and RASGRF2, were unveiled. These genes are implicated in diverse disease-related signaling pathways. Additionally, they exhibited significant correlations with disease-associated gene expression, immune cell infiltration, and drug sensitivity. Exploration of the HPA and CCLE databases exposed substantial expression variations across patients and cell lines for these genes. Subsequently, we identified CAFs-associated genes and established a robust prognostic model. The analysis in the TISCH database showed that the genes in this model were highly expressed in CAFs. CONCLUSIONS: The results unveil an association between CDH6, EGFLAM, and RASGRF2 and the immunotherapeutic response in gastric cancer. These genes hold potential as predictive biomarkers for gastric cancer immunotherapy resistance and prognostic assessment.

4.
Heliyon ; 10(7): e28897, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596102

RESUMO

Although considerable research has been devoted to improving safety in university laboratories, accidents, in that environment, have still occurred frequently at the cost of serious injury or even death of laboratory personnel. Currently, few Human Reliability Analyses (HRA) have been conducted with respect to a university laboratory. The aim of the research was to conduct a reliability study relating to human behaviour in a university laboratory to explore quantitatively the causes and influencing factors relating to the frequency of laboratory accidents. Improved Cognitive Reliability and Error Analysis Method (CREAM) and improved Standardized Plant Analysis Risk HRA (SPAR-H) were employed to assess Human Error Probability (HEP) of 23 subjects. The HEP calculated through improved CREAM proved more accurate than results obtained through improved SPAR-H. Unexpectedly, the results demonstrated that under similar environmental conditions, the HEP of subjects did not decrease with an increase in educational background, including additional experimental time and experience. Moreover, environmental conditions exerted greater impact on personnel reliability than Human Inherent Factors (HIFs) in laboratories. It is anticipated that the study would provide valuable insights, in respect of research methods, and to serve as a practical basis for lowering the accident rate in university laboratories.

5.
Am J Cancer Res ; 14(3): 1121-1138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590396

RESUMO

Autophagy, a highly regulated lysosome-dependent catabolic pathway, has garnered increasing attention because of its role in leukemia resistance. Among the S100 family of small calcium-binding proteins, S100P is differentially expressed in various tumor cell lines, thereby influencing tumor occurrence, invasion, metastasis, and drug resistance. However, the relationship between S100P and autophagy in determining chemosensitivity in leukemia cells remains unexplored. Our investigation revealed a negative correlation between S100P expression and the clinical status in childhood leukemia, with its presence observed in HL-60 and Jurkat cell lines. Suppression of S100P expression resulted in increased cell proliferation and decreased chemosensitivity in leukemia cells, whereas enhancement of S100P expression inhibited cell proliferation and increased chemosensitivity. Additionally, S100P knockdown drastically promoted autophagy, which was subsequently suppressed by S100P upregulation. Moreover, the p53/AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway was found to be functionally associated with S100P-mediated autophagy. Knockdown of S100P expression led to a decrease in p53 and p-mTOR levels and an increase in p-AMPK expression, ultimately promoting autophagy. This effect was reversed by administration of Tenovin-6 (a p53 activator) and Compound C (an AMPK inhibitor). The findings of our in vivo experiments provide additional evidence supporting the aforementioned data. Specifically, S100P inhibition significantly enhanced the growth of HL-60 tumor xenografts and increased the expression of microtubule-associated protein 1 light chain 3 and p-AMPK in nude mice. Consequently, it can be concluded that S100P plays a regulatory role in the chemosensitivity of leukemia cells by modulating the p53/AMPK/mTOR pathway, which controls autophagy in leukemia cells.

6.
J Transl Med ; 22(1): 266, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468254

RESUMO

BACKGROUND: The clinical routine test of HBV-specific T cell reactivity is still limited due to the high polymorphisms of human leukocyte antigens (HLA) in patient cohort and the lack of universal detection kit, thus the clinical implication remains disputed. METHODS: A broad-spectrum peptide library, which consists of 103 functionally validated CD8+ T-cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins and fits to the HLA polymorphisms of Chinese and Northeast Asian populations, was grouped into eight peptide pools and was used to establish an ELISpot assay for enumerating the reactive HBV-specific T cells in PBMCs. Totally 294 HBV-infected patients including 203 ones with chronic hepatitis B (CHB), 13 ones in acute resolved stage (R), 52 ones with liver cirrhosis (LC) and 26 ones with hepatocellular carcinoma (HCC) were detected, and 33 CHB patients were longitudinally monitored for 3 times with an interval of 3-5 months. RESULTS: The numbers of reactive HBV-specific T cells were significantly correlated with ALT level, HBsAg level, and disease stage (R, CHB, LC and HCC), and R patients displayed the strongest HBV-specific T cell reactivity while CHB patients showed the weakest one. For 203 CHB patients, the numbers of reactive HBV-specific T cells presented a significantly declined trend when the serum viral DNA load, HBsAg, HBeAg or ALT level gradually increased, but only a very low negative correlation coefficient was defined (r = - 0.21, - 0.21, - 0.27, - 0.079, respectively). Different Nucleotide Analogs (NUCs) did not bring difference on HBV-specific T cell reactivity in the same duration of treatment. NUCs/pegIFN-α combination led to much more reactive HBV-specific T cells than NUCs monotherapy. The dynamic numbers of reactive HBV-specific T cells were obviously increasing in most CHB patients undergoing routine treatment, and the longitudinal trend possess a high predictive power for the hepatitis progression 6 or 12 months later. CONCLUSION: The presented method could be developed into an efficient reference method for the clinical evaluation of cellular immunity. The CHB patients presenting low reactivity of HBV-specific T cells have a worse prognosis for hepatitis progression and should be treated using pegIFN-α to improve host T-cell immunity.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Biblioteca de Peptídeos , Epitopos de Linfócito T/uso terapêutico , Cirrose Hepática , DNA Viral
7.
Nat Commun ; 15(1): 2599, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521768

RESUMO

The effectiveness of poly (ADP-ribose) polymerase inhibitors (PARPi) in creating single-stranded DNA gaps and inducing sensitivity requires the FANCJ DNA helicase. Yet, how FANCJ relates to PARP1 inhibition or trapping, which contribute to PARPi toxicity, remains unclear. Here, we find PARPi effectiveness hinges on S-phase PARP1 activity, which is reduced in FANCJ deficient cells as G-quadruplexes sequester PARP1 and MSH2. Additionally, loss of the FANCJ-MLH1 interaction diminishes PARP1 activity; however, depleting MSH2 reinstates PARPi sensitivity and gaps. Indicating sequestered and trapped PARP1 are distinct, FANCJ loss increases PARPi resistance in cells susceptible to PARP1 trapping. However, with BRCA1 deficiency, the loss of FANCJ mirrors PARP1 loss or inhibition, with the detrimental commonality being loss of S-phase PARP1 activity. These insights underline the crucial role of PARP1 activity during DNA replication in BRCA1 deficient cells and emphasize the importance of understanding drug mechanisms for enhancing therapeutic response.


Assuntos
DNA Helicases , Replicação do DNA , Proteínas de Grupos de Complementação da Anemia de Fanconi , Poli(ADP-Ribose) Polimerase-1 , Linhagem Celular Tumoral , DNA Helicases/genética , Reparo do DNA , Proteína 2 Homóloga a MutS/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Fase S , Humanos , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética
8.
J Exp Med ; 221(5)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38530240

RESUMO

Long-term antitumor efficacy of chimeric antigen receptor (CAR) T cells depends on their functional persistence in vivo. T cells with stem-like properties show better persistence, but factors conferring bona fide stemness to T cells remain to be determined. Here, we demonstrate the induction of CAR T cells into an immortal-like and functional state, termed TIF. The induction of CARTIF cells depends on the repression of two factors, BCOR and ZC3H12A, and requires antigen or CAR tonic signaling. Reprogrammed CARTIF cells possess almost infinite stemness, similar to induced pluripotent stem cells while retaining the functionality of mature T cells, resulting in superior antitumor effects. Following the elimination of target cells, CARTIF cells enter a metabolically dormant state, persisting in vivo with a saturable niche and providing memory protection. TIF represents a novel state of T cells with unprecedented stemness, which confers long-term functional persistence of CAR T cells in vivo and holds broad potential in T cell therapies.


Assuntos
Células-Tronco Pluripotentes Induzidas , Transdução de Sinais
9.
Nat Ecol Evol ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519631

RESUMO

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

10.
Respir Med ; 226: 107613, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38548141

RESUMO

BACKGROUND: Patients with microscopic polyangiitis (MPA) and positive myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) may present with various abnormalities in chest computed tomography (CT). This study aimed to identify subphenotypes using latent class analysis (LCA) and to explore the relationship between the subphenotypes and clinical patterns, as well as compare the clinical characteristics of these subphenotypes in patients with MPO-ANCA-positive MPA (MPO-MPA). METHODS: The study identified subphenotypes using LCA based on chest CT findings in 178 patients with MPO-MPA and pulmonary involvement from June 2014 to August 2022. RESULTS: LCA identified 27 participants (15.2%) in class 1, 43 (24.1%) in class 2, 35 (19.7%) in class 3, and 73 (41.0%) in class 4. Class 1 was characterized by prominent inflammatory exudation, class 2 by fibrosis and architectural distortion, class 3 by predominantly bronchiectasis, and class 4 by lesions mixed with inflammation and fibrosis. Class 1 had the highest level of extrapulmonary disease activity, with 77.8% of patients experiencing diffuse alveolar hemorrhage. Class 2 had the lowest level of extrapulmonary disease activity, with 41.9% of patients showing usual interstitial pneumonia. Class 3 patients were more likely to have complications involving the ear, nose, and throat, as well as pulmonary infections before treatment, and they exhibited the best outcomes. The characteristics and outcomes of class 4 were intermediate among the four classes. CONCLUSIONS: These findings suggest that bronchiectasis may represent a unique pattern of pulmonary involvement in MPO-MPA, highlighting the importance of screening for bronchiectasis in MPO-MPA and identifying optimal management strategies.

12.
PeerJ ; 12: e16819, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38317842

RESUMO

Hepatocellular carcinoma (HCC) stands as the prevailing manifestation of primary liver cancer and continues to pose a formidable challenge to human well-being and longevity, owing to its elevated incidence and mortality rates. Nevertheless, the quest for reliable predictive biomarkers for HCC remains ongoing. Recent research has demonstrated a close correlation between ferroptosis and disulfidptosis, two cellular processes, and cancer prognosis, suggesting their potential as predictive factors for HCC. In this study, we employed a combination of bioinformatics algorithms and machine learning techniques, leveraging RNA sequencing data, mutation profiles, and clinical data from HCC samples in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the International Cancer Genome Consortium (ICGC) databases, to develop a risk prognosis model based on genes associated with ferroptosis and disulfidptosis. We conducted an unsupervised clustering analysis, calculating a risk score (RS) to predict the prognosis of HCC using these genes. Clustering analysis revealed two distinct HCC clusters, each characterized by significantly different prognostic and immune features. The median RS stratified HCC samples in the TCGA, GEO, and ICGC cohorts into high-and low-risk groups. Importantly, RS emerged as an independent prognostic factor in all three cohorts, with the high-risk group demonstrating poorer prognosis and a more active immunosuppressive microenvironment. Additionally, the high-risk group exhibited higher expression levels of tumor mutation burden (TMB), immune checkpoints (ICs), and human leukocyte antigen (HLA), suggesting a heightened responsiveness to immunotherapy. A cancer stem cell infiltration analysis revealed a higher similarity between tumor cells and stem cells in the high-risk group. Furthermore, drug sensitivity analysis highlighted significant differences in response to antitumor drugs between the two risk groups. In summary, our risk prognostic model, constructed based on ferroptosis-related genes associated with disulfidptosis, effectively predicts HCC prognosis. These findings hold potential implications for patient stratification and clinical decision-making, offering valuable theoretical insights in this field.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Ferroptose/genética , Neoplasias Hepáticas/genética , Algoritmos , Tomada de Decisão Clínica , Microambiente Tumoral
14.
Medicine (Baltimore) ; 103(5): e37109, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306530

RESUMO

RATIONALE: This report describes a unique case of a combination transhepatic and transsplenic recanalization of chronic splenic vein occlusion to treat left-sided portal hypertension (LSPH). PATIENT CONCERNS: In this case report, we report a 49-year-old male who was admitted due to LSPH causing black stools for 2 days and vomiting blood for 1 hour. DIAGNOSES: The patient has a history of multiple episodes of pancreatitis in the past. After admission, abdominal contrast-enhanced CT scan showed the appearance of pancreatitis, with extensive splenic vein occlusion and accompanied by gastric varicose veins, indicating the formation of LSPH. INTERVENTION: The patient received treatment with a combination of splenic and hepatic splenic venoplasty. OUTCOMES: Follow up for 1 year, CT and gastroscopy showed disappearance of gastric varices. LESSONS: Splenic venoplasty is an effective method for treating LSPH. When it is difficult to pass through the occluded segment of the splenic vein through a single approach, percutaneous double approach splenic venoplasty can be attempted for treatment.


Assuntos
Varizes Esofágicas e Gástricas , Pancreatite , Hipertensão Portal Segmentar , Masculino , Humanos , Pessoa de Meia-Idade , Veia Esplênica/diagnóstico por imagem , Abdome , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/cirurgia , Veia Porta
15.
Int J Biol Macromol ; 262(Pt 2): 129984, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342260

RESUMO

The ATP-binding cassette (ABC) transporters have crucial roles in various biological processes such as growth, development and immune defense in eukaryotes. However, the roles of ABC transporters in the immune system of crustaceans remain elusive. In this study, 38 ABC genes were systematically identified and characterized in Penaeus vannamei. Bioinformation analysis revealed that PvABC genes were categorized into ABC A-H eight subfamilies with 17 full-transporters, 11 half transporters and 10 soluble proteins, and multiple immunity-related cis-elements were found in gene promoter regions. Expression analysis showed that most PvABC genes were widely and highly expressed in immune-related tissues and responded to the stimulation of Vibrio parahaemolyticus. To investigate whether PvABC genes mediated innate immunity, PvABCC5, PvABCF1 and PvABCB4 were selected for dsRNA interference experiment. Knockdown of PvABCF1 and PvABCC5 not PvABCB4 increased the cumulative mortality of P. vannamei and bacterial loads in hepatopancreas after infection with V. parahaemolyticus. Further analysis showed that the PvABCF1 and PvABCC5 knockdown decreased expression levels of NF-κB pathway genes and antimicrobial peptides (AMPs). Collectively, these findings indicated that PvABCF1 and PvABCC5 might restrict V. parahaemolyticus challenge by positively regulating NF-κB pathway and then promoting the expression of AMPs, which would contribute to overall understand the function of ABC genes in innate immunity of invertebrates.


Assuntos
Penaeidae , Vibrio parahaemolyticus , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Vibrio parahaemolyticus/genética , Penaeidae/genética , Penaeidae/microbiologia , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteínas de Artrópodes/genética , Transdução de Sinais , Imunidade Inata/genética , Trifosfato de Adenosina/metabolismo
16.
Nat Commun ; 15(1): 966, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302493

RESUMO

The tumor microenvironment is reprogrammed by cancer cells and participates in all stages of tumor progression. Neutral ceramidase is a key regulator of ceramide, the central intermediate in sphingolipid metabolism. The contribution of neutral ceramidase to the reprogramming of the tumor microenvironment is not well understood. Here, we find that deletion of neutral ceramidase in multiple breast cancer models in female mice accelerates tumor growth. Our result show that Ly6C+CD39+ tumor-infiltrating CD8 T cells are enriched in the tumor microenvironment and display an exhausted phenotype. Deletion of myeloid neutral ceramidase in vivo and in vitro induces exhaustion in tumor-infiltrating Ly6C+CD39+CD8+ T cells. Mechanistically, myeloid neutral ceramidase is required for the generation of lipid droplets and for the induction of lipolysis, which generate fatty acids for fatty-acid oxidation and orchestrate macrophage metabolism. Metabolite ceramide leads to reprogramming of macrophages toward immune suppressive TREM2+ tumor associated macrophages, which promote CD8 T cells exhaustion.


Assuntos
Neoplasias , Ceramidase Neutra , Animais , Feminino , Camundongos , Linfócitos T CD8-Positivos/metabolismo , Ceramidas/metabolismo , Macrófagos/metabolismo , 60645 , Ceramidase Neutra/metabolismo , Microambiente Tumoral
17.
Chem Sci ; 15(8): 2954-2962, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38404390

RESUMO

Materials with two or more fluorescence features under different excitation sources have great potential in optical applications, but luminous materials with three emission characteristics have been largely undeveloped. Here, we report a novel zero-dimensional (0D) organic-inorganic hybrid ((C2H5)4N)2ZrCl6 perovskite with multiple emissions. The zirconium-based perovskite exhibits a red emission around 620 nm, a green emission at 527 nm, and a blue emission around 500 nm. The red and green emissions come from self-trapped excitons (STEs) and the d-d transitions of Zr(iv), respectively, which are caused by distortion of the [ZrCl6]2- octahedra. The blue emission is caused by thermally activated delayed fluorescence (TADF), which is similar to that of Cs2ZrCl6. The absolute photoluminescence quantum yield (PLQY) of the red and blue double emission is up to 83% and the PLQY of the green emission is 27%. With different combinations of ((C2H5)4N)2ZrCl6 samples, we achieve a variety of applications, including a two-color luminescent anti-counterfeiting device, a white light-emitting diode (WLED) with a color rendering index (CRI) of 95 and information encryption with different excitations. We also synthesize other hybrid zirconium perovskites with tri-luminescence through a similar method. Our work provides a potential set of excitation-dependent luminescent materials and is expected to expand the basic research and practical applications of multi-luminescence materials.

18.
Poult Sci ; 103(3): 103376, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38228059

RESUMO

Wenchang chicken, a prized local breed in Hainan Province of China renowned for its exceptional adaptability to tropical environments and good meat quality, is deeply favored by the public. However, an insufficient understanding of its population architecture and the unclear genetic basis that governs its typical attributes have posed challenges in the protection and breeding of this precious breed. To address these gaps, we conducted whole-genome resequencing on 200 Wenchang chicken samples derived from 10 distinct strains, and we gathered data on an array of 21 phenotype traits. Population genomics analysis unveiled distinctive population structures in Wenchang chickens, primarily attributed to strong artificial selection for different feather colors. Selection sweep analysis identified a group of candidate genes, including PCDH9, DPF3, CDIN1, and SUGCT, closely linked to adaptations that enhance resilience in tropical island habitats. Genome-wide association studies (GWAS) highlighted potential candidate genes associated with diverse feather color traits, encompassing TYR, RAB38, TRPM1, GABARAPL2, CDH1, ZMIZ1, LYST, MC1R, and SASH1. Through the comprehensive analysis of high-quality genomic and phenotypic data across diverse Wenchang chicken resource groups, this study unveils the intricate genetic backgrounds and population structures of Wenchang chickens. Additionally, it identifies multiple candidate genes linked to environmental adaptation, feather color variations, and production traits. These insights not only provide genetic reference for the purification and breeding of Wenchang chickens but also broaden our understanding of the genetic basis of phenotypic diversity in chickens.


Assuntos
Galinhas , Estudo de Associação Genômica Ampla , Animais , Galinhas/genética , Estudo de Associação Genômica Ampla/veterinária , Genômica , Fenótipo , Sorogrupo
19.
bioRxiv ; 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38260529

RESUMO

Single-stranded DNA gaps are postulated to be fundamental to the mechanism of anti-cancer drugs. Gaining insights into their induction could therefore be pivotal for advancing therapeutic strategies. For poly (ADP-ribose) polymerase inhibitors (PARPi) to be effective, the presence of FANCJ helicase is required. However, the relationship between FANCJ dependent gaps and PARP1 catalytic inhibition or trapping-both linked to PARPi toxicity in BRCA deficient cells-is yet to be elucidated. Here, we find that the efficacy of PARPi is contingent on S-phase PARP1 activity, which is compromised in FANCJ deficient cells because PARP1, along with MSH2, is "sequestered" by G-quadruplexes. PARP1's replication activity is also diminished in cells missing a FANCJ-MLH1 interaction, but in such cells, depleting MSH2 can release sequestered PARP1, restoring PARPi-induced gaps and sensitivity. Our observations indicate that sequestered and trapped PARP1 are different chromatin-bound forms, with FANCJ loss increasing PARPi resistance in cells susceptible to canonical PARP1 trapping. However, in BRCA1 null cells, the loss of FANCJ mirrors the effects of PARP1 loss or inhibition, with the common detrimental factor being the loss of PARP1 activity during DNA replication, not trapping. These insights underline the crucial role of PARP1 activity during DNA replication in BRCA deficient cells and emphasize the importance of understanding drug mechanisms for enhancing precision medicine.

20.
Neuroradiology ; 66(3): 399-407, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38183425

RESUMO

PURPOSE: The optimal primary recanalization strategy for intracranial atherosclerosis-related emergent large vessel occlusion (ICAS-ELVO) remains controversial. We aimed to explore the safety and efficacy of balloon angioplasty as the first-choice recanalization strategy for ICAS-ELVO with small clot burden. METHODS: Consecutive ICAS-ELVO patients presenting with microcatheter "first-pass effect" during endovascular treatment (EVT) were retrospectively analyzed. Patients were divided into preferred balloon angioplasty (PBA) and preferred mechanical thrombectomy (PMT) groups based on the first-choice recanalization strategy. The reperfusion and clinical outcomes between the two groups were compared. RESULTS: Seventy-six patients with ICAS-ELVO involving the microcatheter "first-pass effect" during EVT were enrolled. Compared with patients in the PMT group, those in the PBA group were associated with (i) a higher rate of first-pass recanalization (54.0% vs. 28.9%, p = .010) and complete reperfusion (expanded thrombolysis in cerebral ischemia ≥ 2c; 76.0% vs. 53.8%, p = .049), (ii) shorter puncture-to-recanalization time (49.5 min vs. 89.0 min, p < .001), (iii) lower operation costs (¥48,499.5 vs. ¥ 99,086.0, p < .001), and (iv) better 90-day functional outcomes (modified Rankin scale:0-1; 44.0% vs. 19.2%, p = .032). Logistic regression analysis revealed that balloon angioplasty as the first-choice recanalization strategy was an independent predictor of 90-day excellent functional outcomes for ICAS-ELVO patients with microcatheter "first-pass effect" (adjusted odds ratio = 6.01, 95% confidence interval: 1.15-31.51, p = .034). CONCLUSION: Direct balloon angioplasty potentially improves 90-day functional outcomes for ICAS-ELVO patients with small clot burden, and may be a more appropriate first-choice recanalization strategy than mechanical thrombectomy for these patients.


Assuntos
Angioplastia com Balão , Arteriosclerose Intracraniana , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/cirurgia , Estudos Retrospectivos , Trombectomia , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/terapia , Arteriosclerose Intracraniana/complicações , Resultado do Tratamento
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