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1.
Chem Sci ; 15(18): 6833-6841, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38725503

RESUMO

The understanding of electron transfer pathways and orbital interactions between analytes and adsorption sites in gas-sensitive studies, especially at the atomic level, is currently limited. Herein, we have designed eight isoreticular catechol-metalloporphyrin scaffolds, FeTCP-M and InTCP-M (TCP = 5,10,15,20-tetrakis-catechol-porphyrin, M = Fe, Co, Ni and Zn) with adjustable charge transfer schemes in the coordination microenvironment and precise tuning of orbital interactions between analytes and adsorption sites, which can be used as models for exploring the influence of these factors on gas sensing. Our experimental findings indicate that the sensitivity and selectivity can be modulated using the type of metals in the metal-catechol chains (which regulate the electron transfer routes) and the metalloporphyrin rings (which fine-tune the orbital interactions between analytes and adsorption sites). Among the isostructures, InTCP-Co demonstrates the highest response and selectivity to NO2 under visible light irradiation, which could be attributed to the more favorable transfer pathway of charge carriers in the coordination microenvironment under visible light illumination, as well as the better electron spin state compatibility, higher orbital overlap and orbital symmetry matching between the N-2s2pz hybrid orbital of NO2 and the Co-3dz2 orbital of InTCP-Co.

2.
Water Res ; 257: 121693, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38728785

RESUMO

Cyanobacterial harmful algal blooms (cyanoHABs) are becoming increasingly common in aquatic ecosystems worldwide. However, their heterogeneous distributions make it difficult to accurately estimate the total algae biomass and forecast the occurrence of surface cyanoHABs by using traditional monitoring methods. Although various optical instruments and remote sensing methods have been employed to monitor the dynamics of cyanoHABs at the water surface (i.e., bloom area, chlorophyll a), there is no effective in-situ methodology to monitor the dynamic change of cell density and integrated biovolume of algae throughout the water column. In this study, we propose a quantitative protocol for simultaneously measurements of multiple indicators (i.e., biovolume concentration, size distribution, cell density, and column-integrated biovolume) of cyanoHABs in water bodies by using the laser in-situ scattering and transmissometry (LISST) instrument. The accuracy of measurements of the biovolume and colony size of algae was evaluated and exceeded 95% when the water bloom was dominated by cyanobacteria. Furthermore, the cell density of cyanobacteria was well estimated based on total biovolume and mean cell volume measured by the instrument. Therefore, this methodology has the potential to be used for broader applications, not only to monitor the spatial and temporal distribution of algal biovolume concentration but also monitor the vertical distribution of cell density, biomass and their relationship with size distribution patterns. This provides new technical means for the monitoring and analysis of algae migration and early warning of the formation of cyanoHABs in lakes and reservoirs.

3.
Sci Rep ; 14(1): 10945, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740919

RESUMO

To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6-48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.


Assuntos
Artéria Carótida Interna , Estenose das Carótidas , Endarterectomia das Carótidas , Placa Aterosclerótica , Humanos , Masculino , Feminino , Idoso , Placa Aterosclerótica/cirurgia , Placa Aterosclerótica/patologia , Placa Aterosclerótica/complicações , Artéria Carótida Interna/cirurgia , Artéria Carótida Interna/patologia , Pessoa de Meia-Idade , Estenose das Carótidas/cirurgia , Estenose das Carótidas/patologia , Estenose das Carótidas/complicações , Endarterectomia das Carótidas/métodos , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Idoso de 80 Anos ou mais , Fatores de Risco
4.
BMC Cancer ; 24(1): 558, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702621

RESUMO

BACKGROUND: Portal hypertension (PHT) has been proven to be closely related to the development of hepatocellular carcinoma (HCC). Whether PHT before liver transplantation (LT) will affect the recurrence of HCC is not clear. METHODS: 110 patients with depressurization of the portal vein (DPV) operations (Transjugular Intrahepatic Portosystemic Shunt-TIPS, surgical portosystemic shunt or/and splenectomy) before LT from a HCC LT cohort, matched with 330 preoperative non-DPV patients; this constituted a nested case-control study. Subgroup analysis was based on the order of DPV before or after the occurrence of HCC. RESULTS: The incidence of acute kidney injury and intra-abdominal bleeding after LT in the DPV group was significantly higher than that in non-DPV group. The 5-year survival rates in the DPV and non-DPV group were 83.4% and 82.7% respectively (P = 0.930). In subgroup analysis, patients in the DPV prior to HCC subgroup may have a lower recurrence rate (4.7% vs.16.8%, P = 0.045) and a higher tumor free survival rate (88.9% vs.74.4%, P = 0.044) after LT under the up-to-date TNMI-II stage, while in TNM III stage, there was no difference for DPV prior to HCC subgroup compared with the DPV after HCC subgroup or the non-DPV group. CONCLUSION: Compared with DPV after HCC, DPV treatment before HCC can reduce the recurrence rate of HCC after early transplantation (TNM I-II). DPV before LT can reduce the recurrence of early HCC.


Assuntos
Carcinoma Hepatocelular , Hipertensão Portal , Neoplasias Hepáticas , Transplante de Fígado , Recidiva Local de Neoplasia , Veia Porta , Humanos , Transplante de Fígado/efeitos adversos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Masculino , Feminino , Veia Porta/patologia , Veia Porta/cirurgia , Pessoa de Meia-Idade , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Estudos de Casos e Controles , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Hipertensão Portal/cirurgia , Hipertensão Portal/complicações , Idoso , Adulto
5.
Skeletal Radiol ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695874

RESUMO

OBJECTIVE: To determine which bones and which grades had the highest inter-rater variability when employing the Tanner-Whitehouse (T-W) method. MATERIALS AND METHODS: Twenty-four radiologists were recruited and trained in the T-W classification of skeletal development. The consistency and skill of the radiologists in determining bone development status were assessed using 20 pediatric hand radiographs of children aged 1 to 18 years old. Four radiologists had a poor concordance rate and were excluded. The remaining 20 radiologists undertook a repeat reading of the radiographs, and their results were analyzed by comparing them with the mean assessment of two senior experts as the reference standard. Concordance rate, scoring, and Kendall's W were calculated to evaluate accuracy and consistency. RESULTS: Both the radius, ulna, and short finger (RUS) system (Kendall's W = 0.833) and the carpal (C) system (Kendall's W = 0.944) had excellent consistency, with the RUS system outperforming the C system in terms of scores. The repeatability analysis showed that the second rating test, performed after 2 months of further bone age assessment (BAA) practice, was more consistent and accurate than the first. The capitate had the lowest average concordance rate and scoring, as well as the lowest overall concordance rate for its D classification. Moreover, the G classifications of the seven carpal bones all had a concordance rate less than 0.6. The bones with lower Kendall's W were likewise those with lower scores and concordance rates. CONCLUSION: The D grade of the capitate showed the highest variation, and the use of the Tanner-Whitehouse 3rd edition (T-W3) to determine bone age (BA) was frequently inconsistent. A more comprehensive description with a focus on inaccuracy bones or ratings and a modification to the T-W3 approach would significantly advance BAA.

6.
Clin Chim Acta ; 559: 117887, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38643818

RESUMO

A crucial step in the design of a diagnostic test is determining the cutoff point, the threshold which separates a negative measurement from a positive one. The results of a diagnostic test have clinical consequences: only when disease is accurately detected, proper treatments be administered, and vice versa. Benefit-Risk (BR) analysis should be used to determine the optimal cutoff point that optimizes the consequence. Quantitative BR analysis requires measurable benefit and risk and a function, e.g., linear or ratio, to combine all the components. When BR corresponding to the four possible diagnostic test outcomes are all scaled in units of risk resulting from an untreated disease, we propose a net BR (linear BR) equation as a function of diagnostic parameters, disease prevalence, benefit of correct diagnosis and risk of false diagnostic results. Optimal cutoff of a diagnostic test can be obtained using this function. Comparison of diagnostic tests based on their benefit and risk of tests is also discussed. Use of this function is illustrated with a biosensor rapid antigen test for SARS-CoV-2.

7.
Eur J Clin Invest ; : e14233, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38666585

RESUMO

BACKGROUND: Studies on the predictive ability of disease-specific health quality of life (QoL) in patients with heart failure (HF) have produced conflicting results. To address these gaps in knowledge, we conducted a meta-analysis to evaluate the predictive value of QoL measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with HF. MATERIALS AND METHODS: We searched PubMed, and Embase databases to identify studies investigating the predictive utility of baseline QoL measured by the KCCQ in HF patients. The outcome measures were all-cause mortality and HF hospitalisation. The predictive value of QoL was expressed by pooling the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the bottom versus the top category of KCCQ score or for per 10-point KCCQ score decrease. RESULTS: Twelve studies reporting on 11 articles with a total of 34,927 HF patients were identified. Comparison of the bottom with the top KCCQ score, the pooled adjusted HR was 2.34 (95% CI 2.10-2.60) and 2.53 (95% CI 2.23-2.88) for all-cause mortality and HF hospitalisation, respectively. Additionally, a 10-point decrease in KCCQ score was associated with a 12% (95% CI 7%-16%) increased risk of all-cause mortality and a 14% (95% CI 13%-15%) increased risk of HF hospitalisation. CONCLUSIONS: Poor health-related QoL as determined by the lower KCCQ score, was associated with an increased risk of all-cause mortality and HF hospitalisation in patients with HF. Measuring disease-specific health-related QoL using the KCCQ score may provide valuable predictive information for HF patients.

8.
BMC Genomics ; 25(1): 379, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632516

RESUMO

BACKGROUND: Tumor cells exhibit a heightened susceptibility to lysosomal-dependent cell death (LCD) compared to normal cells. However, the role of LCD-related genes (LCD-RGs) in Osteosarcoma (OS) remains unelucidated. This study aimed to elucidate the role of LCD-RGs and their mechanisms in OS using several existing OS related datasets, including TCGA-OS, GSE16088, GSE14359, GSE21257 and GSE162454. RESULTS: Analysis identified a total of 8,629 DEGs1, 2,777 DEGs2 and 21 intersection genes. Importantly, two biomarkers (ATP6V0D1 and HDAC6) linked to OS prognosis were identified to establish the prognostic model. Significant differences in risk scores for OS survival were observed between high and low-risk cohorts. Additionally, scores of dendritic cells (DC), immature DCs and γδT cells differed significantly between the two risk cohorts. Cell annotations from GSE162454 encompassed eight types (myeloid cells, osteoblastic OS cells and plasma cells). ATP6V0D1 was found to be significantly over-expressed in myeloid cells and osteoclasts, while HDAC6 was under-expressed across all cell types. Moreover, single-cell trajectory mapping revealed that myeloid cells and osteoclasts differentiated first, underscoring their pivotal role in patients with OS. Furthermore, ATP6V0D1 expression progressively decreased with time. CONCLUSIONS: A new prognostic model for OS, associated with LCD-RGs, was developed and validated, offering a fresh perspective for exploring the association between LCD and OS.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Prognóstico , Análise de Sequência de RNA , Morte Celular , Lisossomos , RNA
9.
Bioresour Bioprocess ; 11(1): 26, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38647789

RESUMO

The use of enzymes to catalyze Henry reaction has advantages of mild reaction conditions and low contamination, but low enzyme activity of promiscuous catalysis limits its application. Here, rational design was first performed to identify the key amino acid residues in Henry reaction catalyzed by Lactococcal multidrug resistance Regulator (LmrR). Further, non-canonical amino acids were introduced into LmrR, successfully obtaining variants that enhanced the catalytic activity of LmrR. The best variant, V15CNF, showed a 184% increase in enzyme activity compared to the wild type, and was 1.92 times more effective than the optimal natural amino acid variant, V15F. Additionally, this variant had a broad substrate spectrum, capable of catalyzing reactions between various aromatic aldehydes and nitromethane, with product yielded ranging from 55 to 99%. This study improved enzymatic catalytic activity by enhancing affinity between the enzyme and substrates, while breaking limited types of natural amino acid residues by introducing non-canonical amino acids into the enzyme, providing strategies for molecular modifications.

10.
Endosc Int Open ; 12(4): E513-E519, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628387

RESUMO

Background and study aims Symptomatic simple hepatic cysts require treatment, with several guidelines recommending laparoscopic deroofing. However, cysts located in the posterosuperior segments are considered poor candidates for this procedure. Gastrointestinal endoscopes are more flexible and able to reach less accessible areas than laparoscopes. This study aimed to evaluate the utility of endoscopic transgastric hepatic cyst deroofing (ETGHCD) for treatment of simple hepatic cysts. Patients and methods Seven patients with simple hepatic cysts were evaluated between June 2021 and October 2023. The success rate, procedure time, post-procedure length of hospital stays, complications, pathologic diagnosis, and efficacy were recorded. Results Eleven cysts in seven patients (5 men; mean age 65.5 (standard deviation [SD] 8.5) years) were successfully treated without any complications. The mean procedure time was 65.6 minutes (SD 17.2). Mean post-procedure hospitalization was 4.4 days (SD 1.0). The pathologic diagnosis of 11 cysts showed simple hepatic cysts. The size of the cysts was significantly decreased from 337.0 cm 3 (SD 528.8) to 5.2 cm 3 (SD 6.3) 1 month after ETGHCD. During the median 12.7-month follow-up in seven patients, the cysts showed a 99.6% reduction with no recurrence. Conclusions ETGHCD provided a feasible, safe, effective, and minimal invasive alternative approach for the treatment of simple hepatic cysts.

11.
High Alt Med Biol ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38647652

RESUMO

Li, Xiaoxu, Zhijun Pu, Gang Xu, Yidong Yang, Yu Cui, Xiaoying Zhou, Chenyuan Wang, Zhifeng Zhong, Simin Zhou, Jun Yin, Fabo Shan, Chengzhong Yang, Li Jiao, Dewei Chen, and Jian Huang. Hypoxia-induced myocardial hypertrophy companies with apoptosis enhancement and p38-MAPK pathway activation. High Alt Med Biol. 00:00-00, 2024. Background: Right ventricular function and remodeling are closely associated with symptom severity and patient survival in hypoxic pulmonary hypertension. However, the detailed molecular mechanisms underlying hypoxia-induced myocardial hypertrophy remain unclear. Methods: In Sprague-Dawley rats, hemodynamics were assessed under both normoxia and hypobaric hypoxia at intervals of 7 (H7), 14 (H14), and 28 (H28) days. Morphological changes in myocardial tissue were examined using hematoxylin and eosin (HE) staining, while myocardial hypertrophy was evaluated with wheat germ agglutinin (WGA) staining. Apoptosis was determined through TUNEL assays. To further understand the mechanism of myocardial hypertrophy, RNA sequencing was conducted, with findings validated via Western blot analysis. Results: The study demonstrated increased hypoxic pulmonary hypertension and improved right ventricular diastolic and systolic function in the rat models. Significant elevations in pulmonary arterial systolic pressure (PASP), mean pulmonary arterial pressure (mPAP), right ventricular mean pressure (RVMP), and the absolute value of +dp/dtmax were observed in the H14 and H28 groups compared with controls. In addition, right ventricular systolic pressure (RVSP), -dp/dtmax, and the mean dp/dt during isovolumetric relaxation period were notably higher in the H28 group. Heart rate increased in the H14 group, whereas the time constant of right ventricular isovolumic relaxation (tau) was reduced in both H14 and H28 groups. Both the right heart hypertrophy index and the heart weight/body weight ratio (HW/BW) were elevated in the H14 and H28 groups. Myocardial cell cross-sectional area also increased, as shown by HE and WGA staining. Western blot results revealed upregulated HIF-1α levels and enhanced HIF-2α expression in the H7 group. In addition, phosphorylation of p38 and c-fos was augmented in the H28 group. The H28 group showed elevated levels of Cytochrome C (Cyto C), whereas the H14 and H28 groups exhibited increased levels of Cleaved Caspase-3 and the Bax/Bcl-2 ratio. TUNEL analysis revealed a rise in apoptosis with the extension of hypoxia duration in the right ventricle. Conclusions: The study established a link between apoptosis and p38-MAPK pathway activation in hypoxia-induced myocardial hypertrophy, suggesting their significant roles in this pathological process.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38652239

RESUMO

BACKGROUND: Hypoglycemic pharmacotherapy interventions for alleviating the risk of dementia remains controversial, particularly about dipeptidyl peptidase 4 (DPP4) inhibitors versus metformin. Our objective was to investigate whether the initiation of DPP4 inhibitors, as opposed to metformin, was linked to a reduced risk of dementia. METHODS: We included individuals with type 2 diabetes over 40 years old who were new users of DPP4 inhibitors or metformin in the Chinese Renal Disease Data System (CRDS) database between 2009 and 2020. The study employed Kaplan-Meier and Cox regression for survival analysis and the Fine and Gray model for the competing risk of death. RESULTS: Following a 1:1 propensity score matching, the analysis included 3626 DPP4 inhibitor new users and an equal number of metformin new users. After adjusting for potential confounders, the utilization of DPP4 inhibitors was associated with a decreased risk of all-cause dementia compared to metformin (hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.45-0.89). Subgroup analysis revealed that the utilization of DPP4 inhibitors was associated with a reduced incidence of dementia in individuals who initiated drug therapy at the age of 60 years or older (HR 0.69, 95% CI 0.48-0.98), those without baseline macrovascular complications (HR 0.62, 95% CI 0.41-0.96), and those without baseline microvascular complications (HR 0.67, 95% CI 0.47-0.98). CONCLUSION: In this real-world study, we found that DPP4 inhibitors presented an association with a lower risk of dementia in individuals with type 2 diabetes than metformin, particularly in older people and those without diabetes-related comorbidities.

13.
Structure ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38657613

RESUMO

Accurate protein side-chain modeling is crucial for protein folding and design. This is particularly true for molecular docking as ligands primarily interact with side chains. In this study, we introduce a two-stage side-chain modeling approach called OPUS-Rota5. It leverages a modified 3D-Unet to capture the local environmental features, including ligand information of each residue, and then employs the RotaFormer module to aggregate various types of features. Evaluation on three test sets, including recently released targets from CAMEO and CASP15, shows that OPUS-Rota5 significantly outperforms some other leading side-chain modeling methods. We also employ OPUS-Rota5 to refine the side chains of 25 G protein-coupled receptor targets predicted by AlphaFold2 and achieve a significantly improved success rate in a subsequent "back" docking of their natural ligands. Therefore, OPUS-Rota5 is a useful and effective tool for molecular docking, particularly for targets with relatively accurate predicted backbones but not side chains such as high-homology targets.

14.
Cell Biochem Biophys ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619643

RESUMO

Multiple RNAs have been involved in the progress of heart failure. However, the role of miR-1268a in heart failure is still unclear. The differentially expressed miRNAs in heart failure was analyzed based on GEO dataset GSE104150. AC16 cells were treated with Angiotensin II (Ang II) to explore the role of miR-1268a in heart failure. The web tool miRWalk was used to analyze the targets of miR-1268a. miR-1268a was up-regulated in Ang II-treated AC16 cells. Ang II treatment markedly inhibited cell proliferation, ATP production, fatty acid (FA) uptake and enhanced levels of HF markers BNP and ST2, and oxidative stress of AC16 cells. Notably, inhibition of miR-1268a eliminated the inhibiting effect of Ang II on cell proliferation, ATP production, FA uptake and decreased levels of BNP an ST2, and oxidative stress on AC16 cells. Furthermore, CD36 was a target of miR-1268a and the CD36 level was decreased by miR-1268a mimics but increased by miR-1268a inhibitor in AC16 cells. miR-1268a regulates FA metabolism and oxidative stress in myocardial cells by targeting CD36 in heart failure.

15.
BMC Genomics ; 25(1): 328, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38566015

RESUMO

BACKGROUND: Whole-genome duplication and long terminal repeat retrotransposons (LTR-RTs) amplification in organisms are essential factors that affect speciation, local adaptation, and diversification of organisms. Understanding the karyotype projection and LTR-RTs amplification could contribute to untangling evolutionary history. This study compared the karyotype and LTR-RTs evolution in the genomes of eight oaks, a dominant lineage in Northern Hemisphere forests. RESULTS: Karyotype projections showed that chromosomal evolution was relatively conservative in oaks, especially on chromosomes 1 and 7. Modern oak chromosomes formed through multiple fusions, fissions, and rearrangements after an ancestral triplication event. Species-specific chromosomal rearrangements revealed fragments preserved through natural selection and adaptive evolution. A total of 441,449 full-length LTR-RTs were identified from eight oak genomes, and the number of LTR-RTs for oaks from section Cyclobalanopsis was larger than in other sections. Recent amplification of the species-specific LTR-RTs lineages resulted in significant variation in the abundance and composition of LTR-RTs among oaks. The LTR-RTs insertion suppresses gene expression, and the suppressed intensity in gene regions was larger than in promoter regions. Some centromere and rearrangement regions indicated high-density peaks of LTR/Copia and LTR/Gypsy. Different centromeric regional repeat units (32, 78, 79 bp) were detected on different Q. glauca chromosomes. CONCLUSION: Chromosome fusions and arm exchanges contribute to the formation of oak karyotypes. The composition and abundance of LTR-RTs are affected by its recent amplification. LTR-RTs random retrotransposition suppresses gene expression and is enriched in centromere and chromosomal rearrangement regions. This study provides novel insights into the evolutionary history of oak karyotypes and the organization, amplification, and function of LTR-RTs.


Assuntos
Quercus , Retroelementos , Quercus/genética , Genoma de Planta , Cariótipo , Sequências Repetidas Terminais/genética , Evolução Molecular , Filogenia
16.
Ann Appl Stat ; 18(1): 487-505, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38577266

RESUMO

Many genetic studies contain rich information on longitudinal phenotypes that require powerful analytical tools for optimal analysis. Genetic analysis of longitudinal data that incorporates temporal variation is important for understanding the genetic architecture and biological variation of complex diseases. Most of the existing methods assume that the contribution of genetic variants is constant over time and fail to capture the dynamic pattern of disease progression. However, the relative influence of genetic variants on complex traits fluctuates over time. In this study, we propose a retrospective varying coefficient mixed model association test, RVMMAT, to detect time-varying genetic effect on longitudinal binary traits. We model dynamic genetic effect using smoothing splines, estimate model parameters by maximizing a double penalized quasi-likelihood function, design a joint test using a Cauchy combination method, and evaluate statistical significance via a retrospective approach to achieve robustness to model misspecification. Through simulations we illustrated that the retrospective varying-coefficient test was robust to model misspecification under different ascertainment schemes and gained power over the association methods assuming constant genetic effect. We applied RVMMAT to a genome-wide association analysis of longitudinal measure of hypertension in the Multi-Ethnic Study of Atherosclerosis. Pathway analysis identified two important pathways related to G-protein signaling and DNA damage. Our results demonstrated that RVMMAT could detect biologically relevant loci and pathways in a genome scan and provided insight into the genetic architecture of hypertension.

17.
Pest Manag Sci ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661024

RESUMO

BACKGROUND: Piriformospora indica is an endophytic fungus that can promote the growth and confer resistance against diverse stresses in host plants by root colonization. However, the effects of P. indica colonization on improving plant resistance to insect pests are still less explored. The brown planthopper (BPH) Nilaparvata lugens is a serious monophagous pest that causes extensive damage to rice plants. Here, we aimed to evaluate the effects of P. indica colonization on rice resistance against BPH. RESULTS: The colonization of P. indica in rice roots resisted damage from BPH. Age-stage, two-sex life table analyses showed that feeding on P. indica-colonized rice plants affected BPH's female adult longevity, oviposition period, fecundity, population parameters and population size. BPH female adults feeding on P. indica-colonized plants excreted less honeydew. P. indica colonization remarkably increased the duration of np, N2, and N3 waveform, as well as the occurrences of N1 and N2, and decreased the duration of N4-b for BPH on rice plants. Meanwhile, the weight of BPH on the colonized plants was significantly lower than the control. In addition, the feeding and oviposition preferences of BPH to P. indica-colonized plants were reduced. qRT-RCR analyses revealed that P. indica colonization induced the expressions of jasmonic acid (JA)- and salicylic acid (SA)-related genes in rice plants. CONCLUSION: P. indica colonization can reduce BPH performance on rice plants with potential inhibitory effects on population growth. Collectively, these results support the potential for endophytically colonized P. indica as an effective strategy to improve insect resistance of crops. © 2024 Society of Chemical Industry.

18.
J Environ Manage ; 358: 120837, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38593737

RESUMO

The virus that infects bacteria known as phage, plays a crucial role in the biogeochemical cycling of nutrients. However, the community structure and potential functions of phages in silage fermentation remain largely unexplored. In this study, we utilized viral metagenomics (viromics) to investigate the types, lifestyles, functions, and nutrient utilization patterns of phages in silage. Our findings indicated a high prevalence of annotated phages belonging to Caudovirales and Geplafuvirales, as well as unclassified phages in silage. The predominant host types for these phages were Campylobacterales and Enterobacterales. Virulent phages dominated the silage environment due to their broader range of hosts and enhanced survival capabilities. All identified phages present in silage were found to be non-pathogenic. Although temperate and virulent phages carried distinct genes associated with nutrient cycling processes, the shared genes (prsA) involved in carbon metabolism underscore the potential significance of phages in regulating carbon metabolism in silage. Overall, our findings provide a valuable foundation for further exploring the complex interactions between phages and microorganisms in regulating silage fermentation quality.


Assuntos
Bacteriófagos , Fermentação , Silagem , Metagenômica
19.
J Nephrol ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526665

RESUMO

BACKGROUND: Various immune cells, including T cells, B cells, macrophages, and neutrophils contribute to the development of crescentic glomerulonephritis. Previous animal studies have suggested that lymphangiogenesis is involved in the migration of inflammatory cells and the activation of adaptive immunity. However, the extent of the association between lymphatic vessels and crescentic glomerulonephritis severity and prognosis remains unknown. METHODS AND RESULTS: In this study, we assessed lymphatic vessel density in 71 patients with crescentic glomerulonephritis who underwent renal biopsies between June 2017 and June 2022. By immunohistochemistry and immunofluorescence, we identified increased lymphatic vessel density in the kidneys of patients with crescentic glomerulonephritis compared to controls. Lymphatic vessels were categorized as total, periglomerular, and interstitial. Spearman's rank correlation analysis showed a positive correlation between total and periglomerular lymphatic vessel density and glomerular crescent proportion. High lymphatic vessel density (total and periglomerular) correlated with declining kidney function, increased proteinuria, and severe glomerular and interstitial pathology. Interstitial lymphatic vessel density had minimal relationship with renal lesions. After a median duration of 13 months of follow-up, higher total and periglomerular lymphatic vessel density was associated with poorer prognosis. Transcriptomic analysis revealed increased immune cell activation and migration in crescentic glomerulonephritis patients compared to healthy controls. Periglomerular lymphatic vessels might play a significant role in immune cell infiltration and renal injury. CONCLUSION: Elevated lymphatic vessel density in patients with crescentic glomerulonephritis is associated with poor prognosis and may serve as a predictive factor for adverse outcomes in these patients.

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