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1.
Cancer Immunol Immunother ; 73(6): 111, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38668781

RESUMO

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.


Assuntos
Neoplasias Pulmonares , Mutação , Neoplasias Primárias Múltiplas , Receptores de Antígenos de Linfócitos T , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Neoplasias Primárias Múltiplas/imunologia , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso
2.
Cancer Lett ; 588: 216655, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38460724

RESUMO

Cancer remains a major burden globally and the critical role of early diagnosis is self-evident. Although various miRNA-based signatures have been developed in past decades, clinical utilization is limited due to a lack of precise cutoff value. Here, we innovatively developed a signature based on pairwise expression of miRNAs (miRPs) for pan-cancer diagnosis using machine learning approach. We analyzed miRNA spectrum of 15832 patients, who were divided into training, validation, test, and external test sets, with 13 different cancers from 10 cohorts. Five different machine-learning (ML) algorithms (XGBoost, SVM, RandomForest, LASSO, and Logistic) were adopted for signature construction. The best ML algorithm and the optimal number of miRPs included were identified using area under the curve (AUC) and youden index in validation set. The AUC of the best model was compared to previously published 25 signatures. Overall, Random Forest approach including 31 miRPs (31-miRP) was developed, proving highly efficient in cancer diagnosis across different datasets and cancer types (AUC range: 0.980-1.000). Regarding diagnosis of cancers at early stage, 31-miRP also exhibited high capacities, with AUC ranging from 0.961 to 0.998. Moreover, 31-miRP exhibited advantages in differentiating cancers from normal tissues (AUC range: 0.976-0.998) as well as differentiating cancers from corresponding benign lesions. Encouragingly, comparing to previously published 25 different signatures, 31-miRP also demonstrated clear advantages. In conclusion, 31-miRP acts as a powerful model for cancer diagnosis, characterized by high specificity and sensitivity as well as a clear cutoff value, thereby holding potential as a reliable tool for cancer diagnosis at early stage.


Assuntos
MicroRNA Circulante , MicroRNAs , Neoplasias , Humanos , MicroRNA Circulante/genética , Neoplasias/diagnóstico , Neoplasias/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Algoritmos , Diagnóstico Precoce
3.
Eur J Med Chem ; 269: 116326, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38513340

RESUMO

Bacterial infections cause a variety of life-threatening diseases, and the continuous evolution of drug-resistant bacteria poses an increasing threat to current antimicrobial regimens. Gram-positive bacteria (GPB) have a wide range of genetic capabilities that allow them to adapt to and develop resistance to practically all existing antibiotics. Oxazolidinones, a class of potent bacterial protein synthesis inhibitors with a unique mechanism of action involving inhibition of bacterial ribosomal translation, has emerged as the antibiotics of choice for the treatment of drug-resistant GPB infections. In this review, we discussed the oxazolidinone antibiotics that are currently on the market and in clinical development, as well as an updated synopsis of current advances on their analogues, with an emphasis on innovative strategies for structural optimization of linezolid, structure-activity relationship (SAR), and safety properties. We also discussed recent efforts aimed at extending the activity of oxazolidinones to gram-negative bacteria (GNB), antitumor, and coagulation factor Xa. Oxazolidinone antibiotics can accumulate in GNB by a conjugation to siderophore-mediated ß-lactamase-triggered release, making them effective against GNB.


Assuntos
Anti-Infecciosos , Oxazolidinonas , Antibacterianos/química , Oxazolidinonas/farmacologia , Oxazolidinonas/química , Linezolida/farmacologia , Relação Estrutura-Atividade , Anti-Infecciosos/farmacologia , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana
4.
Eur J Med Chem ; 268: 116293, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38447461

RESUMO

Global public health is facing a serious problem as a result of the rise in antibiotic resistance and the decline in the discovery of new antibiotics. In this study, two series of amphiphilic-cephalosporins were designed and synthesized, several of which showed good antibacterial activity against both Gram-positive and Gram-negative bacteria. Structure-activity relationships indicated that the length of the hydrophobic alkyl chain significantly affects the antibacterial activity against Gram-negative bacteria. The best compound 2d showed high activity against drug-susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) with MICs of 0.5 and 2-4 µg/mL, respectively. Furthermore, 2d remained active in complex mammalian body fluids and had a longer post-antibiotic effect (PAE) than vancomycin. Mechanism studies indicated that compound 2d lacks membrane-damaging properties and can target penicillin-binding proteins to disrupt bacterial cell wall structure, inhibit the metabolic activity and induce the accumulation of reactive oxygen species (ROS) in bacteria. Compound 2d showed minimal drug resistance and was nontoxic to HUVEC and HBZY-1 cells with CC50 > 128 µg/mL. These findings suggest that 2d is a promising drug candidate for treating bacterial infections.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Antibacterianos/química , Cefalosporinas/farmacologia , Bactérias Gram-Positivas , Bactérias Gram-Negativas , Monobactamas/farmacologia , Testes de Sensibilidade Microbiana , Mamíferos
5.
Opt Express ; 32(3): 2906-2915, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297527

RESUMO

We present a novel micro-fabrication technique for creating concave surfaces on the endfacets of photonic crystal fibers. A fiber fusion splicer is used to generate arc discharges to melt and reshape the fiber endfacet. This technique can produce large spherical concave surfaces with roughness as low as 0.12 nm in various types of photonic crystal fibers. The deviation of fabricated surface and a spherical profile in the region of 70 µm in diameter is less than 50 nm. The center of the concave surface and the fiber mode field are highly coincident with a deviation less than 500 nm. Finesse measurements have shown that a Fabry-Pérot cavity composed of the fiber fabricated using this method and a plane mirror maintains finesse of 20000. This method is easy to replicate, making it a practical and efficient approach to fabricate concave surface on fibers for open-access fiber Fabry-Pérot cavities.

6.
Plants (Basel) ; 13(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38337916

RESUMO

Melatonin plays a vital role in plant growth and development. In this study, we treated hydroponically grown tomato roots with various concentrations of exogenous melatonin (0, 10, 30, and 50 µmol·L-1). We utilized root scanning and microscopy to examine alterations in root morphology and cell differentiation and elucidated the mechanism by which melatonin regulates these changes through the interplay with endogenous hormones and relevant genes. The results showed that for melatonin at concentrations ranging between 10 and 30 µmol·L-1, the development of lateral roots were significantly stimulated, the root hair growth was enhanced, and biomass accumulation and root activity were increased. Furthermore, we elucidated that melatonin acts as a mediator for the expression of genes, such as SlCDKA1, SlCYCA3;1, SlARF2, SlF3H, and SlKT1, which are involved in the regulation of root morphology changes. Additionally, we observed that melatonin influences the levels of endogenous hormones, including ZT, GA3, IAA, ABA, and BR, which subsequently impact the root morphology development of tomato roots. In summary, this study shows that tomato root morphology can be promoted by the optimal concentration of exogenous melatonin (10-30 µmol·L-1).

7.
China CDC Wkly ; 6(6): 100-104, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38406636

RESUMO

What is already known about this topic?: Echinococcosis is classified as a Class C infectious disease in China. It is endemic in 370 counties located in the agricultural and pastoral regions of western China. What is added by this report?: This report provides a comprehensive overview of the cases of echinococcosis reported in China in 2022. Following a thorough evaluation conducted by provincial CDCs, it was identified that 105 new cases were not reported through the National Notifiable Disease Reporting System. Furthermore, there were 1,051 cases that were reported among patients who had been previously diagnosed with echinococcosis. What are the implications for public health practice?: The reported cases of echinococcosis in non-endemic counties of provincial-level administrative divisions where the disease is endemic need to be given more attention, as there is a potential risk of it spreading within the non-endemic areas. Inadequate reporting practices by clinical medical institutions are hindering the subsequent investigations carried out by CDCs. It is important to implement enhanced health promotion efforts that focus on high-risk populations to address unhealthy lifestyles.

8.
Mol Cancer ; 23(1): 31, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347558

RESUMO

Minimally invasive testing is essential for early cancer detection, impacting patient survival rates significantly. Our study aimed to establish a pioneering cell-free immune-related miRNAs (cf-IRmiRNAs) signature for early cancer detection. We analyzed circulating miRNA profiles from 15,832 participants, including individuals with 13 types of cancer and control. The data was randomly divided into training, validation, and test sets (7:2:1), with an additional external test set of 684 participants. In the discovery phase, we identified 100 differentially expressed cf-IRmiRNAs between the malignant and non-malignant, retaining 39 using the least absolute shrinkage and selection operator (LASSO) method. Five machine learning algorithms were adopted to construct cf-IRmiRNAs signature, and the diagnostic classifies based on XGBoost algorithm showed the excellent performance for cancer detection in the validation set (AUC: 0.984, CI: 0.980-0.989), determined through 5-fold cross-validation and grid search. Further evaluation in the test and external test sets confirmed the reliability and efficacy of the classifier (AUC: 0.980 to 1.000). The classifier successfully detected early-stage cancers, particularly lung, prostate, and gastric cancers. It also distinguished between benign and malignant tumors. This study represents the largest and most comprehensive pan-cancer analysis on cf-IRmiRNAs, offering a promising non-invasive diagnostic biomarker for early cancer detection and potential impact on clinical practice.


Assuntos
MicroRNAs , Neoplasias Gástricas , Masculino , Humanos , MicroRNAs/genética , Reprodutibilidade dos Testes , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer/métodos , Neoplasias Gástricas/diagnóstico
9.
Eur J Med Chem ; 267: 116215, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38354522

RESUMO

With the widespread use of antibiotics, bacterial resistance has developed rapidly. To make matters worse, infections caused by persistent bacteria and biofilms often cannot be completely eliminated, which brings great difficulties to clinical medication. In this work, three series of quinolone pyridinium quaternary ammonium small molecules were designed and synthesized. Most of the compounds showed good antibacterial activity against Gram-positive bacteria (S. aureus and E. faecalis) and Gram-negative bacteria (E. coli and S. maltophilia). The activity of the para-pyridine quaternary ammonium salt was better than that of the meta-pyridine. 3f was the optimal compound with good stability in body fluids and was unlikely to induce bacterial resistance. The hemolysis rate of erythrocytes at 1280 µg/mL for 3f was only 5.1%. Encouragingly, 3f rapidly killed bacteria within 4 h at 4 × MIC concentration and was effective in killing persistent bacteria in biofilms. The antibacterial mechanism experiments showed that 3f could cause disorder of bacterial membrane potential, increase bacterial membrane permeability, dissolve and destroy the membrane. Incomplete bacterial membranes lead to leakage of bacterial genetic material, concomitant production of ROS, and bacterial death due to these multiple effects.


Assuntos
Compostos de Amônio , Infecções Bacterianas , Humanos , Antibacterianos/farmacologia , Ciprofloxacina , Staphylococcus aureus , Escherichia coli , Hemólise , Bactérias , Piridinas , Testes de Sensibilidade Microbiana
10.
Int J Biol Macromol ; 261(Pt 2): 129718, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38296129

RESUMO

Recently, conductive hydrogels have shown great promise in flexible electronics and are ideal materials for the preparation of wearable strain sensors. However, developing a simple method to produce conductive hydrogels with excellent mechanical properties, self-adhesion, transparency, anti-freezing, and UV resistance remains a significant challenge. A novel sodium lignosulfonate/xanthan gum/sodium alginate/polyacrylamide/Zn2+/DMSO (SLS/XG/SA/PAM/Zn2+/DMSO) ionic conductive hydrogel was developed using a one-pot method. The resulting ionic conductive hydrogels have excellent mechanical properties (stress: 0.13 MPa, strain: 1629 %), high anti-fatigue properties, self-adhesion properties (iron: 7.37 kPa, pigskin: 4.74 kPa), anti-freezing (freezing point: -33.49 °C) and UV resistance by constructing a chemical and physical hybrid cross-linking network. In particular, the conductivity of G hydrogel reached 6.02 S/m at room temperature and 5.52 S/m at -20 °C. Thus, the hydrogel was assembled into a flexible sensor that could distinguish a variety of large and small scales human movements, such as joint bending, swallowing and speaking in real time with high stability and sensitivity. Moreover, the hydrogel could be used as electronic skin just like human skin and touch screen pen to write.


Assuntos
Resinas Acrílicas , Alginatos , Dimetil Sulfóxido , Lignina/análogos & derivados , Polissacarídeos Bacterianos , Humanos , Condutividade Elétrica , Hidrogéis , Íons , Sódio
11.
Biomacromolecules ; 25(2): 614-625, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38241010

RESUMO

Conductive hydrogels integrate the conductive performance and soft nature, which is like that of human skin. Thus, they are more suitable for the preparation of wearable human-motion sensors. Nevertheless, the integration of outstanding multiple functionalities, such as stretchability, toughness, biocompatibility, self-healing, adhesion, strain sensitivity, and durability, by a simple way is still a huge challenge. Herein, we have developed a multifunctional chitosan/oxidized hyaluronic acid/hydroxypropyl methylcellulose/poly(acrylic acid)/tannic acid/Al3+ hydrogel (CS/OHA/HPMC/PAA/TA/Al3+) by using a two-step method with hydroxypropyl methylcellulose (HPMC), acrylic acid (AA), tannic acid (TA), chitosan (CS), oxidized hyaluronic acid (OHA), and aluminum chloride hexahydrate (AlCl3·6H2O). Due to the synergistic effect of dynamic imine bonds between CS and OHA, dynamic metal coordination bonds between Al3+ and -COOH and/or TA as well as reversible hydrogen, the hydrogel showed excellent tensile property (elongation at break of 3168%) and desirable toughness (0.79 MJ/m3). The mechanical self-healing efficiency can reach 95.5% at 30 min, and the conductivity can recover in 5.2 s at room temperature without stimulation. The favorable attribute of high transparency (98.5% transmittance) facilitates the transmission of the optical signal and enables visualization of the sensor. It also shows good adhesiveness to various materials and is easy to peel off without residue. The resistance of the hydrogel-based sensors shows good electrical conductivity (2.33 S m-1), good durability, high sensing sensitivity (GF value of 4.12 under 1600% strain), low detection limit (less than 1%), and short response/recovery time (0.54/0.31 s). It adhered to human skin and monitored human movements such as the bending movements of joints, swallowing, and speaking successfully. Therefore, the obtained multifunctional conductive hydrogel has great potential applications in wearable strain sensors.


Assuntos
Quitosana , Polifenóis , Dispositivos Eletrônicos Vestíveis , Humanos , Adesivos , Ácido Hialurônico , Derivados da Hipromelose , Cimentos de Resina , Condutividade Elétrica , Hidrogéis , Íons
12.
Phys Chem Chem Phys ; 26(6): 5558-5568, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38284214

RESUMO

Rare base-pairs consists of guanine (G) paired with rare bases, such as 5-methylcytosine (5-meCyt), 5-hydroxymethylcytosine (5-hmCyt), 5-carboxylcytosine (5-caCyt), and 5-formylcytosine (5-fCyt), have become the focus of epigenetic research because they can be used as markers to detect some chronic diseases and cancers. However, the correlation detection of these rare base-pairs is limited, which in turn limits the development of diagnostic tests and devices. Herein, the interaction of rare base-pairs adsorbed on pure and B/N-doped γ-graphyne (γ-GY) nanosheets was explored using the density functional theory. The calculated adsorption energy showed that the system of rare base-pairs on B-doped γ-GY is more stable than that on pure γ-GY or N-doped γ-GY. Translocation time values indicate that rare base-pairs can be successfully distinguished as the difference in their translocation times is very large for pure and B/N-doped γ-GY nanosheets. Meanwhile, sensing response values illustrated that pure and B-doped γ-GY are the best for G-5-hmCyt adsorption, while the N-doped γ-GY is the best for G-Cyt adsorption. The findings indicate that translocation times and sensing response can be used as detection indexes for pure and B/N doped γ-GY, which will provide a new way for experimental scientists to develop the biosensor components.


Assuntos
Adsorção , Pareamento de Bases
13.
Medicine (Baltimore) ; 103(4): e37116, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277512

RESUMO

The aim of this study was to explore the impact of female body mass index (BMI) on cumulative live birth rates (CLBR) in patients treated with in vitro fertilization (IVF) and embryo transfer. A total of 2377 patients who visited the Reproductive Medical Center, Luoyang Maternal and Child Health Hospital from January 2015 to December 2021. The patients underwent the first IVF cycles. According to female BMI, patients were divided into 3 groups, group A: BMI ≤ 18.5 kg/m2 (underweight), group B: BMI: 18.5 to 24.0 kg/m2 (normal), group C: BMI ≥ 24.0 kg/m2 (overweight/obesity). Patient basic parameters and clinical outcomes were compared among these 3 groups. Multivariate logistic regression analysis was used to explore the impact of BMI on CLBR. In all treatment cycles, patients' basic parameters were significantly different among 3 BMI groups. Age of underweight patient was younger than patients in the other 2 groups (28.45 ±â€…5.32 vs 29.89 ±â€…5.00 vs 30.74 ±â€…5.40; P = .000). In addition, number of oocytes retrieved was also significantly higher in group A (11.25 ±â€…5.97 vs 11.07 ±â€…5.49 vs 10.52 ±â€…5.02; P = .000). CLBR in these 3 groups were 66.40%, 65.98%, and 59.14%, respectively. In logistic analysis, overweight/obesity was associated with CLBR in young patients (aOR = 0.822, 95% CI: 0.817-0.957, P = .000). However, in the cycles of older patients, the effect of overweight/obesity on the CLBR was not significant (aOR = 0.986, 95% CI: 0.903-1.027, P > .05). Overweight/obesity is a predictor for CLBR in younger patients (<35 years old), but not in advanced age patients undergoing their first IVF/intracytoplasmic sperm injection treatment cycles.


Assuntos
Coeficiente de Natalidade , Sobrepeso , Masculino , Gravidez , Criança , Feminino , Humanos , Adulto , Índice de Massa Corporal , Sobrepeso/epidemiologia , Magreza/epidemiologia , Nascido Vivo/epidemiologia , Estudos Retrospectivos , Sêmen , Fertilização In Vitro , Obesidade , Taxa de Gravidez , Indução da Ovulação
14.
Reprod Domest Anim ; 59(1): e14497, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37917556

RESUMO

Milk production traits as the most important economic traits of dairy cows, they directly reflect the benefits of breeding and the economic benefits of pasture. In this study, A disintegrin and metalloproteinase-12 (ADAM12), Parkinson's disease gene 2 (PRKN) and dipeptidyl peptidase-like protein subtype 6 (DPP6) polymorphism in 384 Chinese Holstein cows were detected by time-of-flight mass spectrometry and through statistical analysis using software such as Popgene 32, SAS 9.4 and Origin 2022, the relationship between single nucleotide polymorphisms (SNPs) of three genes with four milk production traits such as daily milk yield (DMY), milk fat percentage (MFP), milk protein percentage (MPP) and somatic cell score (SCS) was verified at molecular level. The results showed that four polymorphic loci (116,467,133, 116,604,487, 116,618,268 and 116,835,111) of DPP6 gene, two polymorphic loci (97,665,052 and 97,159,837) of PRKN gene and two polymorphic loci (45,542,714 and 45,553,888) of ADAM12 gene were detected. PRKN-97665052, DPP6-116467133, ADAM12-45553888, DPP6-116604487 and DPP6-116835111 were all in Hardy-Weinberg equilibrium state (p > .05). ADAM12-45542714, PRKN-97159837 and PRKN-97665052 were moderately polymorphic (0.25 ≤ PIC <0.50) in Holstein. It is evident that the selection potential and genetic variation of these five loci are relatively large, and the genetic richness is relatively high. The correlation analysis of different genotypes between these eight loci and milk production traits of Holstein showed that ADAM12-45542714 and DPP6-116835111 (p < .01) had an extremely significant effects on the DMY of Chinese Holstein in Ningxia, while PRKN-97665052 had an extremely significant effect on MFP (p < .01). The effect of PRKN-97665052 and DPP6-116467133 on MPP of Holstein were extremely significant (p < .01). DPP6-116618268 had an extremely significant effect on the SCS of Holstein in Ningxia (p < .01), and AA genotype individuals showed a higher SCS than GG genotype individuals; the other two loci (ADAM12-45553888 and DPP6-116604487) had no significant effects on milk production traits of Holstein (p > .05). In addition, through the joint analysis of DPP6, PRKN and ADAM12 gene loci, it was found that the interaction effect between the three gene loci could significantly affect the DMY, SCS (p < .01) and MPP (p < .05). In conclusion, several different loci of DPP6, PRKN and ADAM12 genes can affect the milk production traits of Holstein to different degrees. PRKN, DPP6 and ADAM12 genes can be used as potential candidate genes for milk production traits of Holstein for marker-assisted selection, providing theoretical basis for breeding of Holstein.


Assuntos
Lactação , Leite , Polimorfismo de Nucleotídeo Único , Animais , Bovinos/genética , Feminino , Humanos , Proteína ADAM12/genética , Proteína ADAM12/metabolismo , Dipeptidil Peptidases e Tripeptidil Peptidases/análise , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Genótipo , Lactação/genética , Leite/química , Proteínas do Leite , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fenótipo , Canais de Potássio/análise , Canais de Potássio/genética , Canais de Potássio/metabolismo , Proteínas/metabolismo , Ubiquitina-Proteína Ligases/genética
15.
Int J Biol Macromol ; 257(Pt 2): 128613, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070814

RESUMO

Circular RNAs (circRNA) are a kind of endogenous biological macromolecules that play significant roles in many biological processes, including adipogenesis, a precisely orchestrated process that is mediated by a large number of factors. Among them, peroxisome proliferator-activated receptor gamma (PPARG), is undoubtedly the most important regulator of adipocyte development in all types of adipose tissue. The formation of intramuscular fat (IMF), is a key factor that influences the meat quality in livestock animals. PPARG has been demonstrated to show a positive correlation with IMF deposition although the regulatory mechanism involved is not known. This study demonstrates that PPARG mediates IMF deposition by producing multiple exonic circRNAs (circPPARGs). Three circPPARGs promote adipogenic differentiation and inhibit the proliferation of intramuscular preadipocytes and these effects are conserved across several species including buffaloes, cattle and mice. Notably, circPPARG1 interacts with PPARG protein to inhibit the transcription of hormone sensitive lipase (HSL) involved in lipolysis. In addition, the positive effects of circPPARG1 on IMF deposition were identified in mice in vivo. Thus, PPARG drives IMF deposition, not only through the common transcription factor pathway, but also by producing circRNAs. This study provides new insights into our understanding of the regulatory mechanisms of PPARG in IMF deposition.


Assuntos
PPAR gama , RNA Circular , Bovinos , Animais , Camundongos , RNA Circular/genética , PPAR gama/genética , PPAR gama/metabolismo , Esterol Esterase/genética , Adipogenia/genética , Tecido Adiposo/metabolismo
16.
BMJ Paediatr Open ; 7(1)2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38114241

RESUMO

BACKGROUND: Antibacterial therapy plays a crucial role in neonatal infections. The efficacy of antibacterial agents is closely related to the actual dose given to neonates. So we evaluated factors potentially affecting the actual dose of intravenous antibiotics during dispensing process in neonates. METHODS: Meropenem, cefoperazone/sulbactam and piperacillin/tazobactam with two strengths were used to evaluate three methods. Method A (MA) was diluted once and the volumes of 5% glucose for MA were meropenem 4.00 mL, cefoperazone/sulbactam 3.00 mL, piperacillin/tazobactam 9.00 mL. Method B (MB) differed by doubling the volume of 5% glucose. The difference in method C (MC) involved diluting with 5% glucose twice. The concentrations were measured by high-performance liquid chromatography. Relative error (RE) was used to evaluate the preparation accuracy. RESULTS: The RE values using MA/MB/MC were: (1) meropenem 0.5 g: 15.1%, 8.0%, 10.4%; 0.25 g: 7.8%, 3.1%, 6.0%; (2) cefoperazone/sulbactam 1.5 g: 13.6%, 4.2%, 3.4%; 0.75 g: 8.8%, 3.5%, 4.0%; (3) piperacillin/tazobactam 4.5 g: 18.2%, 8.7%, 6.3%; 562.5 mg: 8.1%, 2.8%, 6.1%. MB was better than MA in all three drugs. No difference in RE values was found between single and double dilution, except meropenem with 0.25 g. Using MB, meropenem and piperacillin/tazobactam with small drug strength had higher accuracy in preparation. CONCLUSIONS: MB was suitable for neonatal drug dispensing because of its high accuracy and simple operation. Drugs with small strength were promoted due to the high accuracy.


Assuntos
Antibacterianos , Cefoperazona , Recém-Nascido , Humanos , Antibacterianos/uso terapêutico , Meropeném , Cefoperazona/uso terapêutico , Sulbactam , Piperacilina , Combinação Piperacilina e Tazobactam/uso terapêutico , Glucose
17.
Plants (Basel) ; 12(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38140502

RESUMO

Optimal plant growth in many species is achieved when the two major forms of N are supplied at a particular ratio. This study investigated optimal nitrogen forms and ratios for tomato growth using the 'Jingfan 502' tomato variety. Thirteen treatments were applied with varying proportions of nitrate nitrogen (NN), ammonium nitrogen (AN), and urea nitrogen (UN). Results revealed that the combination of AN and UN inhibited tomato growth and photosynthetic capacity. Conversely, the joint application of NN and UN or NN and AN led to a significant enhancement in tomato plant growth. Notably, the T12 (75%UN:25%NN) and T4 (75%NN:25%AN) treatments significantly increased the gas exchange and chlorophyll fluorescence parameters, thereby promoting the accumulation of photosynthetic products. The contents of fructose, glucose, and sucrose were significantly increased by 121.07%, 206.26%, and 94.64% and by 104.39%, 156.42%, and 61.40%, respectively, compared with those in the control. Additionally, AN favored starch accumulation, while NN and UN favored fructose, sucrose, and glucose accumulation. Gene expression related to nitrogen and sugar metabolism increased significantly in T12 and T4, with T12 showing greater upregulation. Key enzyme activity in metabolism also increased notably. In summary, T12 enhanced tomato growth by upregulating gene expression, increasing enzyme activity, and boosting photosynthesis and sugar accumulation. Growers should consider using NN and UN to reduce AN application in tomato fertilization.

18.
Sci Data ; 10(1): 832, 2023 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-38007506

RESUMO

Mahogany species (family Meliaceae) are highly valued for their aesthetic and durable wood. Despite their economic and ecological importance, genomic resources for mahogany species are limited, hindering genetic improvement and conservation efforts. Here we perform chromosome-scale genome assemblies of two commercially important mahogany species: Swietenia macrophylla and Khaya senegalensis. By combining 10X sequencing and Hi-C data, we assemble high-quality genomes of 274.49 Mb (S. macrophylla) and 406.50 Mb (K. senegalensis), with scaffold N50 lengths of 8.51 Mb and 7.85 Mb, respectively. A total of 99.38% and 98.05% of the assembled sequences are anchored to 28 pseudo-chromosomes in S. macrophylla and K. senegalensis, respectively. We predict 34,129 and 31,908 protein-coding genes in S. macrophylla and K. senegalensis, respectively, of which 97.44% and 98.49% are functionally annotated. The chromosome-scale genome assemblies of these mahogany species could serve as a vital genetic resource, especially in understanding the properties of non-model woody plants. These high-quality genomes could support the development of molecular markers for breeding programs, conservation efforts, and the sustainable management of these valuable forest resources.


Assuntos
Genoma de Planta , Meliaceae , Cromossomos , Meliaceae/genética
19.
Toxicon ; 235: 107326, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37871760

RESUMO

Food-borne botulism is a rare but potentially fatal illness. Its management depends on rapid diagnosis and prompt antitoxin administration. However, diagnosing food-borne botulism can be challenging at an early stage. Here, we report a 62-year-old male with food-borne botulism. The patient presented with extremity muscle weakness, dyspnea, bilateral droopy eyelids (more significant on the right side), dysarthria, and progressive dysphagia. The electromyography indicated presynaptic membrane abnormalities. The toxicology screen reported a positive result for botulinum toxin type A. He received plasma exchange, botulism antitoxin, and supportive care. However, he had a cardiac arrest six days later. Spontaneous circulation was restored after immediate cardiopulmonary resuscitation. The patient gradually recovered his muscle strength and could have complete eyelid elevation. A detailed interview revealed that six family members developed similar symptoms. All of them consumed a homemade sauce prepared three years ago. They all tested positive for botulinum toxin type A. Two of them had cardiac arrests. Therefore, family aggregation could happen to botulism. Careful interviews, early diagnosis, and timely administration of botulism antitoxin are the keys to saving lives. Special attentions should be given to the cardiac evaluations since botulism can cause cardiac arrest and death.


Assuntos
Toxinas Botulínicas Tipo A , Botulismo , Parada Cardíaca , Masculino , Humanos , Pessoa de Meia-Idade , Botulismo/diagnóstico , Botulismo/etiologia , Antitoxina Botulínica , Parada Cardíaca/induzido quimicamente , Parada Cardíaca/complicações
20.
Sci Data ; 10(1): 710, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848504

RESUMO

The Legume family (Leguminosae or Fabaceae), is one of the largest and economically important flowering plants. Heartwood, the core of a tree trunk or branch, is a valuable and renewable resource employed for centuries in constructing sturdy and sustainable structures. Hongmu refers to a category of precious timber trees in China, encompassing 29 woody species, primarily from the legume genus. Due to the lack of genome data, detailed studies on their economic and ecological importance are limited. Therefore, this study generates chromosome-scale assemblies of five Hongmu species in Leguminosae: Pterocarpus santalinus, Pterocarpus macrocarpus, Dalbergia cochinchinensis, Dalbergia cultrata, and Senna siamea, using a combination of short-reads, long-read nanopore, and Hi-C data. We obtained 623.86 Mb, 634.58 Mb, 700.60 Mb, 645.98 Mb, and 437.29 Mb of pseudochromosome level assemblies with the scaffold N50 lengths of 63.1 Mb, 63.7 Mb, 70.4 Mb, 61.1 Mb and 32.2 Mb for P. santalinus, P. macrocarpus, D. cochinchinensis, D. cultrata and S. siamea, respectively. These genome data will serve as a valuable resource for studying crucial traits, like wood quality, disease resistance, and environmental adaptation in Hongmu.


Assuntos
Fabaceae , Genoma de Planta , Pterocarpus , Cromossomos , Fabaceae/genética , Filogenia , Pterocarpus/química , Pterocarpus/genética
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