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1.
Plant J ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39239888

RESUMO

Structural variations (SVs) pervade plant genomes and contribute substantially to the phenotypic diversity. However, most SVs were ineffectively assayed due to their complex nature and the limitations of early genomic technologies. By applying the PacBio high-fidelity (HiFi) sequencing for wheat genomes, we performed a comprehensive evaluation of mainstream long-read aligners and SV callers in SV detection. The results indicated that the accuracy of deletion discovery is markedly influenced by callers, accounting for 87.73% of the variance, whereas both aligners (38.25%) and callers (49.32%) contributed substantially to the accuracy variance for insertions. Among the aligners, Winnowmap2 and NGMLR excelled in detecting deletions and insertions, respectively. For SV callers, SVIM achieved the best performance. We demonstrated that combining the aligners and callers mentioned above is optimal for SV detection. Furthermore, we evaluated the effect of sequencing depth on the accuracy of SV detection, revealing that low-coverage HiFi sequencing is sufficiently robust for high-quality SV discovery. This study thoroughly evaluated SV discovery approaches and established optimal workflows for investigating structural variations using low-coverage HiFi sequencing in the wheat genome, which will advance SV discovery and decipher the biological functions of SVs in wheat and many other plants.

2.
J Biol Chem ; 299(1): 102787, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36509141

RESUMO

Chemoresistance remains a major challenge in the current treatment of acute myeloid leukemia (AML). The bone marrow microenvironment (BMM) plays a complex role in protecting leukemia cells from chemotherapeutics, and the mechanisms involved are not fully understood. Antileukemia drugs kill AML cells directly but also damage the BMM. Here, we determined antileukemia drugs induce DNA damage in bone marrow stromal cells (BMSCs), resulting in resistance of AML cell lines to adriamycin and idarubicin killing. Damaged BMSCs induced an inflammatory microenvironment through NF-κB; suppressing NF-κB with small molecule inhibitor Bay11-7082 attenuated the prosurvival effects of BMSCs on AML cell lines. Furthermore, we used an ex vivo functional screen of 507 chemokines and cytokines to identify 44 proteins secreted from damaged BMSCs. Fibroblast growth factor-10 (FGF10) was most strongly associated with chemoresistance in AML cell lines. Additionally, expression of FGF10 and its receptors, FGFR1 and FGFR2, was increased in AML patients after chemotherapy. FGFR1 and FGFR2 were also widely expressed by AML cell lines. FGF10-induced FGFR2 activation in AML cell lines operates by increasing P38 MAPK, AKT, ERK1/2, and STAT3 phosphorylation. FGFR2 inhibition with small molecules or gene silencing of FGFR2 inhibited proliferation and reverses drug resistance of AML cells by inhibiting P38 MAPK, AKT, and ERK1/2 signaling pathways. Finally, release of FGF10 was mediated by ß-catenin signaling in damaged BMSCs. Our data indicate FGF10-FGFR2 signaling acts as an effector of damaged BMSC-mediated chemoresistance in AML cells, and FGFR2 inhibition can reverse stromal protection and AML cell chemoresistance in the BMM.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda , Células-Tronco Mesenquimais , Humanos , Células da Medula Óssea/metabolismo , Dano ao DNA , Fator 10 de Crescimento de Fibroblastos/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Células-Tronco Mesenquimais/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Células Estromais/metabolismo , Microambiente Tumoral , Comunicação Parácrina
3.
J Biol Chem ; 299(9): 105126, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37543362

RESUMO

Oxidative stress triggered by aging, radiation, or inflammation impairs ovarian function by inducing granulosa cell (GC) apoptosis. However, the mechanism inducing GC apoptosis has not been characterized. Here, we found that ovarian GCs from aging patients showed increased oxidative stress, enhanced reactive oxygen species activity, and significantly decreased expression of the known antiapoptotic factor sphingosine-1-phosphate/sphingosine kinase 1 (SPHK1) in GCs. Interestingly, the expression of Krüppel-like factor 12 (KLF12) was significantly increased in the ovarian GCs of aging patients. Furthermore, we determined that KLF12 was significantly upregulated in hydrogen peroxide-treated GCs and a 3-nitropropionic acid-induced in vivo model of ovarian oxidative stress. This phenotype was further confirmed to result from inhibition of SPHK1 by KLF12. Interestingly, when endogenous KLF12 was knocked down, it rescued oxidative stress-induced apoptosis. Meanwhile, supplementation with SPHK1 partially reversed oxidative stress-induced apoptosis. However, this function was lost in SPHK1 with deletion of the binding region to the KLF12 promoter. SPHK1 reversed apoptosis caused by hydrogen peroxide-KLF12 overexpression, a result further confirmed in an in vitro ovarian culture model and an in vivo 3-nitropropionic acid-induced ovarian oxidative stress model. Overall, our study reveals that KLF12 is involved in regulating apoptosis induced by oxidative stress in aging ovarian GCs and that sphingosine-1-phosphate/SPHK1 can rescue GC apoptosis by interacting with KLF12 in negative feedback.


Assuntos
Envelhecimento , Apoptose , Células da Granulosa , Peróxido de Hidrogênio , Fatores de Transcrição Kruppel-Like , Lisofosfolipídeos , Fosfotransferases (Aceptor do Grupo Álcool) , Esfingosina , Feminino , Humanos , Envelhecimento/metabolismo , Retroalimentação Fisiológica , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Peróxido de Hidrogênio/farmacologia , Técnicas In Vitro , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Fatores de Transcrição Kruppel-Like/biossíntese , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Lisofosfolipídeos/biossíntese , Lisofosfolipídeos/metabolismo , Técnicas de Cultura de Órgãos , Estresse Oxidativo/efeitos dos fármacos , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Regiões Promotoras Genéticas , Esfingosina/biossíntese , Esfingosina/metabolismo , Espécies Reativas de Oxigênio/metabolismo
4.
J Am Chem Soc ; 146(1): 1081-1088, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38113465

RESUMO

The first asymmetric total synthesis of the hexacyclic veatchine-type C20-diterpenoid alkaloid (-)-garryine is presented. Key steps include a Pd-catalyzed enantioselective Heck reaction, a radical cyclization, and a photoinduced C-H activation/oxazolidine formation sequence. Of note, a highly enantioselective Heck reaction developed in this work provides efficient access to 6/6/6 tricyclic compounds, in particular, containing a C19-functionalitiy, which is useful for diverse transformations.

5.
Microcirculation ; 31(5): e12854, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38690631

RESUMO

OBJECTIVE: Designing physiologically adequate microvascular trees is of crucial relevance for bioengineering functional tissues and organs. Yet, currently available methods are poorly suited to replicate the morphological and topological heterogeneity of real microvascular trees because the parameters used to control tree generation are too simplistic to mimic results of the complex angiogenetic and structural adaptation processes in vivo. METHODS: We propose a method to overcome this limitation by integrating a conditional deep convolutional generative adversarial network (cDCGAN) with a local fractal dimension-oriented constrained constructive optimization (LFDO-CCO) strategy. The cDCGAN learns the patterns of real microvascular bifurcations allowing for their artificial replication. The LFDO-CCO strategy connects the generated bifurcations hierarchically to form microvascular trees with a vessel density corresponding to that observed in healthy tissues. RESULTS: The generated artificial microvascular trees are consistent with real microvascular trees regarding characteristics such as fractal dimension, vascular density, and coefficient of variation of diameter, length, and tortuosity. CONCLUSIONS: These results support the adoption of the proposed strategy for the generation of artificial microvascular trees in tissue engineering as well as for computational modeling and simulations of microcirculatory physiology.


Assuntos
Simulação por Computador , Microcirculação , Microvasos , Microvasos/fisiologia , Microvasos/anatomia & histologia , Humanos , Microcirculação/fisiologia , Modelos Cardiovasculares , Fractais
6.
Small ; 20(29): e2311578, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38363013

RESUMO

Charging LiCoO2 to high voltages yields alluring specific capacities, yet the deleterious phase-transitions lead to significant capacity degradation. Herein, this study demonstrates a novel strategy to stabilize LiCoO2 at 4.6 V by doping with Er and Mg at the Li-site and Co-site, respectively, which is different from the traditional method of doping foreign elements solely at the Co-site. Theoretical calculations and experiments jointly reveal that the inclusion of Mg2+-dopants at the Co-site curbs the hexagonal-monoclinic phase transitions ≈4.2 V. However, this unintentionally compromises the stability of lattice oxygen in LiCoO2, exacerbating the undesired phase transition (O3 to H1-3) above 4.45 V. Fascinatingly, the introduction of Er3+-dopants into Li-sites enhances the stability of lattice oxygen in LiCoO2, effectively mitigating phase transitions above 4.45 V. Therefore, the Er, Mg co-doped LiCoO2 exhibits high stability over 500 cycles when tested in a half-cell with a cut-off voltage of 4.6 V. Furthermore, the Er, Mg-doped LiCoO2//graphite pouch-type full cell demonstrates a high energy density of 310.8 Wh kg-1, preserving 91.3% of its energy over 100 cycles.

7.
Small ; : e2405187, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39206605

RESUMO

Traditional PEO electrolyte has high crystallinity which hinders the transmission of Li+, resulting in poor ion conductivity and complicated processing technology. Herein, a polymer electrolyte (p-electrolyte) with a wide electrochemical window and high ionic conductivity is designed, which possesses an amorphous condensed structure. The amorphous structure provides fast transport channels for Li+, so the p-electrolyte possesses an electrochemical window of 4.2 V, and high ionic conductivity of 1.58 × 10-5 S cm-1 at room temperature, which is 1-2 orders of magnitude higher than that of traditional PEO electrolyte. By using the designed polymer electrolyte as the foundation, an in situ curable composite polymer electrolyte (CPE-L) with multiple Li+ transport channels is elaborately constructed. The Cu-BTC MOF stores abundant Li+, which is introduced into the p-electrolyte. The rich unsaturated Cu2+ coordination sites of Cu-BTC can anchor TFSI- to release Li+, and the pore structure of Cu-BTC MOF cooperates with LLZTO nanoparticles to provide multiple fast transport channel for Li+, resulting in remarkable ionic conductivity (1.02 × 10-3 S cm-1) and Li+ transference number (0.58). The Li||CPE-L||Li symmetric battery cycles stably for more than 700 h at 0.1 mA cm-2, while the specific capacity of full battery is ≈153 mAh g-1 (RT, 0.2 C).

8.
Bioconjug Chem ; 35(6): 737-743, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38738511

RESUMO

Radiation therapy is one of the most common treatments for cancer. However, enhancing tumors' radiation sensitivity and overcoming tolerance remain a challenge. Previous studies have shown that the Ras signaling pathway directly influences tumor radiation sensitivity. Herein, we designed a series of Ras-targeting stabilized peptides, with satisfactory binding affinity (KD = 0.13 µM with HRas) and good cellular uptake. Peptide H5 inhibited downstream phosphorylation of ERK and increased radio-sensitivity in HeLa cells, resulting in significantly reduced clonogenic survival. The stabilized peptides, designed with an N-terminal nucleation strategy, acted as potential radio-sensitizers and broadened the applications of this kind of molecule. This is the first report of using stabilized peptides as radio-sensitizers, broadening the applications of this kind of molecule.


Assuntos
Peptídeos , Tolerância a Radiação , Proteínas ras , Humanos , Peptídeos/química , Peptídeos/farmacologia , Células HeLa , Tolerância a Radiação/efeitos dos fármacos , Proteínas ras/metabolismo , Radiossensibilizantes/farmacologia , Radiossensibilizantes/química , Sobrevivência Celular/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/radioterapia
9.
Glob Chang Biol ; 30(5): e17303, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38741339

RESUMO

Nitrous oxide (N2O) emissions from livestock manure contribute significantly to the growth of atmospheric N2O, a powerful greenhouse gas and dominant ozone-depleting substance. Here, we estimate global N2O emissions from livestock manure during 1890-2020 using the tier 2 approach of the 2019 Refinement to the 2006 IPCC Guidelines. Global N2O emissions from livestock manure increased by ~350% from 451 [368-556] Gg N year-1 in 1890 to 2042 [1677-2514] Gg N year-1 in 2020. These emissions contributed ~30% to the global anthropogenic N2O emissions in the decade 2010-2019. Cattle contributed the most (60%) to the increase, followed by poultry (19%), pigs (15%), and sheep and goats (6%). Regionally, South Asia, Africa, and Latin America dominated the growth in global emissions since the 1990s. Nationally, the largest emissions were found in India (329 Gg N year-1), followed by China (267 Gg N year-1), the United States (163 Gg N year-1), Brazil (129 Gg N year-1) and Pakistan (102 Gg N year-1) in the 2010s. We found a substantial impact of livestock productivity, specifically animal body weight and milk yield, on the emission trends. Furthermore, a large spread existed among different methodologies in estimates of global N2O emission from livestock manure, with our results 20%-25% lower than those based on the 2006 IPCC Guidelines. This study highlights the need for robust time-variant model parameterization and continuous improvement of emissions factors to enhance the precision of emission inventories. Additionally, urgent mitigation is required, as all available inventories indicate a rapid increase in global N2O emissions from livestock manure in recent decades.


Assuntos
Gado , Esterco , Óxido Nitroso , Óxido Nitroso/análise , Esterco/análise , Animais , Poluentes Atmosféricos/análise
10.
BMC Cancer ; 24(1): 682, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38835015

RESUMO

BACKGROUND: Astragaloside IV (AS-IV) is one of the basic components of Astragali radix, that has been shown to have preventive effects against various diseases, including cancers. This study aimed to explore the role of AS-IV in hepatocellular carcinoma (HCC) and its underlying mechanism. METHODS: The cell viability, glucose consumption, lactate production, and extracellular acidification rate (ECAR) in SNU-182 and Huh7 cell lines were detected by specific commercial kits. Western blot was performed to analyze the succinylation level in SNU-182 and Huh7 cell lines. The interaction between lysine acetyltransferase (KAT) 2 A and phosphoglycerate mutase 1 (PGAM1) was evaluated by co-immunoprecipitation and immunofluorescence assays. The role of KAT2A in vivo was explored using a xenografted tumor model. RESULTS: The results indicated that AS-IV treatment downregulated the protein levels of succinylation and KAT2A in SNU-182 and Huh7 cell lines. The cell viability, glucose consumption, lactate production, ECAR, and succinylation levels were decreased in AS-IV-treated SNU-182 and Huh7 cell lines, and the results were reversed after KAT2A overexpression. KAT2A interacted with PGAM1 to promote the succinylation of PGAM1 at K161 site. KAT2A overexpression promoted the viability and glycolysis of SNU-182 and Huh7 cell lines, which were partly blocked following PGAM1 inhibition. In tumor-bearing mice, AS-IV suppressed tumor growth though inhibiting KAT2A-mediated succinylation of PGAM1. CONCLUSION: AS-IV inhibited cell viability and glycolysis in HCC by regulating KAT2A-mediated succinylation of PGAM1, suggesting that AS-IV might be a potential and suitable therapeutic agent for treating HCC.


Assuntos
Carcinoma Hepatocelular , Sobrevivência Celular , Glicólise , Neoplasias Hepáticas , Fosfoglicerato Mutase , Saponinas , Triterpenos , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Animais , Fosfoglicerato Mutase/metabolismo , Camundongos , Glicólise/efeitos dos fármacos , Triterpenos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Saponinas/farmacologia , Linhagem Celular Tumoral , Histona Acetiltransferases/metabolismo , Camundongos Nus , Proliferação de Células/efeitos dos fármacos
11.
Cell Commun Signal ; 22(1): 227, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38610001

RESUMO

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck. Vasculogenic mimicry (VM) is crucial for tumor growth and metastasis and refers to the formation of fluid channels by invasive tumor cells rather than endothelial cells. However, the regulatory mechanisms underlying VM during the malignant progression of LSCC remain largely unknown. METHODS: Gene expression and clinical data for LSCC were obtained from the TCGA and Gene GEO (GSE27020) databases. A risk prediction model associated with VM was established using LASSO and Cox regression analyses. Based on their risk scores, patients with LSCC were categorized into high- and low-risk groups. The disparities in immune infiltration, tumor mutational burden (TMB), and functional enrichment between these two groups were examined. The core genes in LSCC were identified using the machine learning (SVM-RFE) and WGCNA algorithms. Subsequently, the involvement of bone morphogenetic protein 2 (BMP2) in VM and metastasis was investigated both in vitro and in vivo. To elucidate the downstream signaling pathways regulated by BMP2, western blotting was performed. Additionally, ChIP experiments were employed to identify the key transcription factors responsible for modulating the expression of BMP2. RESULTS: We established a new precise prognostic model for LSCC related to VM based on three genes: BMP2, EPO, and AGPS. The ROC curves from both TCGA and GSE27020 validation cohorts demonstrated precision survival prediction capabilities, with the nomogram showing some net clinical benefit. Multiple algorithm analyses indicated BMP2 as a potential core gene. Further experiments suggested that BMP2 promotes VM and metastasis in LSCC. The malignant progression of LSCC is promoted by BMP2 via the activation of the PI3K-AKT signaling pathway, with the high expression of BMP2 in LSCC resulting from its transcriptional activation by runt-related transcription factor 1 (RUNX1). CONCLUSION: BMP2 predicts poor prognosis in LSCC, promotes LSCC VM and metastasis through the PI3K-AKT signaling pathway, and is transcriptionally regulated by RUNX1. BMP2 may be a novel, precise, diagnostic, and therapeutic biomarker of LSCC.


Assuntos
Proteína Morfogenética Óssea 2 , Neoplasias de Cabeça e Pescoço , Humanos , Subunidade alfa 2 de Fator de Ligação ao Core , Células Endoteliais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Transdução de Sinais
12.
Langmuir ; 40(1): 696-703, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38103257

RESUMO

The development of electrochemically inexpensive, durable, and active electrocatalysts for the oxygen evolution reaction (OER) is attracting considerable attention. The heterogeneous interfacing might regulate the electronic structure and further improve the electrochemical activity. Herein, a Ce(OH)3 nanoparticle-interfaced Fe-doped nickel sulfide (Ce(OH)3@Fe-Ni3S2) electrocatalyst was prepared to improve the OER performance. The fabricated electrocatalyst displayed excellent intrinsic activity and long-term stability in 1 M KOH for the OER. The catalyst shows an ultralow overpotential of 195 mV at a current density of 10 mA cm-2 and a Tafel slope of 52 mV dec-1, which are remarkably smaller than those of the control samples. This excellent electrocatalytic activity is attributed to the incorporation of Ce(OH)3 nanoparticles on the surface of the Fe-Ni3S2 nanosheet, which increases the electrochemical activity and enlarges the active surface area of the catalyst. In comparison to previous nonprecious OER electrocatalysts, the prepared Ce(OH)3@Fe-Ni3S2 exhibits greater electrocatalytic activity and longer durability, allowing for the selection of new electrocatalysts for practical applications.

13.
J Org Chem ; 89(4): 2807-2811, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38324536

RESUMO

A new asymmetric synthesis of the A/E-ring fragment of C18-diterpenoid alkaloids is described. The crucial contiguous stereogenic centers at C4, C5, and C11 were established through an asymmetric Michael addition/allylation sequence. The unique azabicyclo[3.3.1]nonane motif (A/E rings) was assembled by employing ring-closing metathesis and Mitsunobu reaction as key strategies.

14.
Org Biomol Chem ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39290038

RESUMO

The metal-free BF3-catalyzed hydroamination of silylynamides with amines allows facile and efficient synthesis of α-silylmethylamidines in moderate to excellent yields (up to 99%) with a broad substrate scope and excellent functional group compatibility under mild reaction conditions. This protocol offers the first synthetic route to silyl-incorporated amidine compounds, which features the use of Lewis acid BF3 as the catalyst and easily available silylynamides as the silicon source. Considering the biological importance of amidine scaffolds and silyl groups, the easy incorporation of these two structural units should make great sense for medicinal chemistry. Notably, with this strategy, the installation of amidine scaffolds to drug-like molecules celecoxib and estrone is realized for the first time. A plausible mechanism involves the formation of vinyl-boron intermediates from BF3-activated ynamides, which after protodeboronation and tautomerization afford the desired products.

15.
Phys Chem Chem Phys ; 26(35): 22832-22845, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39177483

RESUMO

Porous liquids (PLs) are the combination of porous solid material and flowing liquid, which provides alternative options to solve difficulties in the development of porous solids. With the booming development of PLs since 2015, plenty of syntheses and applications have been reported with a specific focus on gas adsorption. Given the lack of a comprehensive review, this paper reviews the application of PLs in CO2 capture. To start with, ground-breaking case studies are reviewed to help understand the progress of PLs research. Then, as a major part of this paper, studies of PLs for CO2 capture are reviewed separately. Moreover, five basic properties of porous liquids, including stability, viscosity, selectivity, porosity, capacity, and the influencing factors are systemically reviewed respectively. Furthermore, gas storage and release mechanisms in PLs are briefly outlined, and potential processing methods of PLs used for CO2 capture are discussed.

16.
Nature ; 555(7697): 520-523, 2018 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-29539638

RESUMO

Here we report a multi-tissue gene expression resource that represents the genotypic and phenotypic diversity of modern inbred maize, and includes transcriptomes in an average of 255 lines in seven tissues. We mapped expression quantitative trait loci and characterized the contribution of rare genetic variants to extremes in gene expression. Some of the new mutations that arise in the maize genome can be deleterious; although selection acts to keep deleterious variants rare, their complete removal is impeded by genetic linkage to favourable loci and by finite population size. Modern maize breeders have systematically reduced the effects of this constant mutational pressure through artificial selection and self-fertilization, which have exposed rare recessive variants in elite inbred lines. However, the ongoing effect of these rare alleles on modern inbred maize is unknown. By analysing this gene expression resource and exploiting the extreme diversity and rapid linkage disequilibrium decay of maize, we characterize the effect of rare alleles and evolutionary history on the regulation of expression. Rare alleles are associated with the dysregulation of expression, and we correlate this dysregulation to seed-weight fitness. We find enrichment of ancestral rare variants among expression quantitative trait loci mapped in modern inbred lines, which suggests that historic bottlenecks have shaped regulation. Our results suggest that one path for further genetic improvement in agricultural species lies in purging the rare deleterious variants that have been associated with crop fitness.


Assuntos
Alelos , Regulação da Expressão Gênica de Plantas/genética , Aptidão Genética/genética , Zea mays/genética , Produtos Agrícolas/genética , Variação Genética/genética , Genoma de Planta/genética , Genótipo , Desequilíbrio de Ligação , Fenótipo , Densidade Demográfica , Locos de Características Quantitativas/genética , RNA de Plantas/genética , Sementes/genética , Análise de Sequência de RNA
17.
BMC Public Health ; 24(1): 538, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383355

RESUMO

BACKGROUND: Large-scale outbreaks of scrub typhus combined with its emergence in new areas as a vector-borne rickettsiosis highlight the ongoing neglect of this disease. This study aims to explore the long-term changes and regional leading factors of scrub typhus in China, with the goal of providing valuable insights for disease prevention and control. METHODS: This study utilized a Bayesian space-time hierarchical model (BSTHM) to examine the spatiotemporal heterogeneity of scrub typhus and analyze the relationship between environmental factors and scrub typhus in southern and northern China from 2006 to 2018. Additionally, a GeoDetector model was employed to assess the predominant influences of geographical and socioeconomic factors in both regions. RESULTS: Scrub typhus exhibits a seasonal pattern, typically occurring during the summer and autumn months (June to November), with a peak in October. Geographically, the high-risk regions, or hot spots, are concentrated in the south, while the low-risk regions, or cold spots, are located in the north. Moreover, the distribution of scrub typhus is influenced by environment and socio-economic factors. In the north and south, the dominant factors are the monthly normalized vegetation index (NDVI) and temperature. An increase in NDVI per interquartile range (IQR) leads to a 7.580% decrease in scrub typhus risk in northern China, and a 19.180% increase in the southern. Similarly, of 1 IQR increase in temperature reduces the risk of scrub typhus by 10.720% in the north but increases it by 15.800% in the south. In terms of geographical and socio-economic factors, illiteracy rate and altitude are the key determinants in the respective areas, with q-values of 0.844 and 0.882. CONCLUSIONS: These results indicated that appropriate climate, environment, and social conditions would increase the risk of scrub typhus. This study provided helpful suggestions and a basis for reasonably allocating resources and controlling the occurrence of scrub typhus.


Assuntos
Tifo por Ácaros , Humanos , Tifo por Ácaros/epidemiologia , Teorema de Bayes , China/epidemiologia , Estações do Ano , Fatores Econômicos , Incidência
18.
BMC Musculoskelet Disord ; 25(1): 718, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242516

RESUMO

OBJECTIVE: To systematically review the clinical efficacy (pain, function, quality of life) and safety of platelet-rich plasma (PRP) in the treatment of frozen shoulder through meta-analysis, and provide evidence-based medical evidence for the effectiveness of PRP in the treatment of frozen shoulder. METHODS: A search was conducted on international databases (Pubmed, Web of science, Embase) and Chinese databases (CNKI, Wanfang, VIP) to search the clinical studies on the efficacy of platelet-rich plasma in treating frozen shoulder (adhesive capsulitis/periarthritis/50 shoulder) and their corresponding references published from inception until January 2024. Thoroughly excluded literature not meeting the predetermined inclusion criteria, extracted relevant data from the literature, and input it into RevMan5.4 for meta-analysis. RESULTS: This study ultimately included 14 RCTs, with a total of 1024 patients. The results showed that PRP has significant advantages compared with control groups in VAS (mean difference (MD) =-0.38, 95% confidence interval(CI)(-0.73, -0.03), P = 0.03), UCLA (MD = 3.31, 95% CI (1.02,5.60),P = 0.005), DASH (MD = -4.94,95% CI (-9.34, -0.53),P = 0.03), SPADI (SPADI Total: MD =-16.87, 95% CI (-22.84, -10.91), P < 0.00001; SPADI Pain: MD =-5.38, 95% CI (-7.80, -2.97), P < 0.0001; SPADI Disability: MD =-11.00, 95% CI (-13.61,-8.39), P < 0.00001), and the active and passive Range of Motion (active flexion: MD = 12.70, 95% CI (7.44, 17.95), P < 0.00001; passive flexion: MD = 9.47, 95% CI(3.80, 15.14), P = 0.001; active extension: MD = 3.45, 95% CI(2.39, 4.50), P < 0.00001; active abduction: MD = 13.54, 95% CI(8.42, 18.67), P < 0.00001; passive abduction: MD = 14.26, 95% CI (5.97, 22.56), P = 0.0008; active internal rotation: MD = 5.16, 95% CI (1.84, 8.48), P = 0.002; passive internal rotation: MD = 3.65, 95% CI(1.15, 6.15), P = 0.004; active external rotation: MD = 10.50, 95% CI(5.47, 15.53), P < 0.0001; passive external rotation: MD = 6.00, 95% CI (1.82, 10.19), P = 0.005) except passive extension (MD = 2.25, 95% CI (-0.77, 5.28), P = 0.14). In terms of safety, most studies reported no adverse effects, and only one study reported common complications of joint puncture such as swelling and pain after treatment in both PRP and control groups. Previous studies have shown a risk of osteonecrosis caused by corticosteroids. Therefore, the safety of PRP treatment is more reliable. CONCLUSION: The results showed that PRP was more durable and safer than corticosteroids and other control groups in the treatment of frozen shoulder. STUDY DESIGN: Systematic review. TRIAL REGISTRATION: PROSPERO CRD42022359444, date of registration: 22-09-2022.


Assuntos
Bursite , Plasma Rico em Plaquetas , Ensaios Clínicos Controlados Aleatórios como Assunto , Amplitude de Movimento Articular , Humanos , Bursite/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do Tratamento , Qualidade de Vida , Articulação do Ombro/fisiopatologia , Dor de Ombro/terapia , Medição da Dor
19.
BMC Surg ; 24(1): 233, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152385

RESUMO

OBJECTIVE: Achieving textbook outcome (TO) implies a smooth recovery post-operation without specified composite complications. This study aimed to evaluate TO in laparoscopic pancreaticoduodenectomy (LPD) and identify independent risk factors associated with achieving TO. METHODS: We conducted a retrospective analysis of data from a randomized controlled trial on LPD at West China Hospital (ChiCTR1900026653). Patients were categorized into the TO and non-TO groups. Perioperative variables were compared between these groups. Multivariate logistic regression was utilized to identify the risk factors. RESULTS: A total of 200 consecutive patients undergoing LPD were included in this study. TO was achieved in 82.5% (n = 165) of the patients. Female patients (OR: 2.877, 95% CI: 1.219-6.790; P = 0.016) and those with a hard pancreatic texture (OR: 2.435, 95% CI: 1.018-5.827; P = 0.046) were associated with an increased likelihood of achieving TO. CONCLUSIONS: TO can be achieved in more than 80% of patients in a high-volume LPD center. Independent risk factors associated with achieving TO included gender (male) and pancreatic texture (soft).


Assuntos
Laparoscopia , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/efeitos adversos , Feminino , Masculino , Laparoscopia/métodos , Pessoa de Meia-Idade , Fatores de Risco , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Estudos Prospectivos , China/epidemiologia , Adulto , Hospitais com Alto Volume de Atendimentos , Complicações Pós-Operatórias/epidemiologia
20.
Sensors (Basel) ; 24(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38931578

RESUMO

The railway fastener, as a crucial component of railway tracks, directly influences the safety and stability of a railway system. However, in practical operation, fasteners are often in low-light conditions, such as at nighttime or within tunnels, posing significant challenges to defect detection equipment and limiting its effectiveness in real-world scenarios. To address this issue, this study proposes an unsupervised low-light image enhancement algorithm, CES-GAN, which achieves the model's generalization and adaptability under different environmental conditions. The CES-GAN network architecture adopts a U-Net model with five layers of downsampling and upsampling structures as the generator, incorporating both global and local discriminators to help the generator to preserve image details and textures during the reconstruction process, thus enhancing the realism and intricacy of the enhanced images. The combination of the feature-consistency loss, contrastive learning loss, and illumination loss functions in the generator structure, along with the discriminator loss function in the discriminator structure, collectively promotes the clarity, realism, and illumination consistency of the images, thereby improving the quality and usability of low-light images. Through the CES-GAN algorithm, this study provides reliable visual support for railway construction sites and ensures the stable operation and accurate operation of fastener identification equipment in complex environments.

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