RESUMO
High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.
Assuntos
Genoma de Planta , Seleção Genética , Adaptação Fisiológica/genética , AltitudeRESUMO
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/diagnósticoRESUMO
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 , IdosoRESUMO
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.
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 , ÍonsRESUMO
OBJECTIVE: Our study aimed to investigate the effects of different extracorporeal membrane oxygenation (ECMO) blood flow rates on lung perfusion assessment using the saline bolus-based electrical impedance tomography (EIT) technique in patients on veno-venous (VV) ECMO. METHODS: In this single-centered prospective physiological study, patients on VV ECMO who met the ECMO weaning criteria were assessed for lung perfusion using saline bolus-based EIT at various ECMO blood flow rates (gradually decreased from 4.5 L/min to 3.5 L/min, 2.5 L/min, 1.5 L/min, and finally to 0 L/min). Lung perfusion distribution, dead space, shunt, ventilation/perfusion matching, and recirculation fraction at different flow rates were compared. RESULTS: Fifteen patients were included. As the ECMO blood flow rate decreased from 4.5 L/min to 0 L/min, the recirculation fraction decreased significantly. The main EIT-based findings were as follows. (1) Median lung perfusion significantly increased in region-of-interest (ROI) 2 and the ventral region [38.21 (34.93-42.16)% to 41.29 (35.32-43.75)%, p = 0.003, and 48.86 (45.53-58.96)% to 54.12 (45.07-61.16)%, p = 0.037, respectively], whereas it significantly decreased in ROI 4 and the dorsal region [7.87 (5.42-9.78)% to 6.08 (5.27-9.34)%, p = 0.049, and 51.14 (41.04-54.47)% to 45.88 (38.84-54.93)%, p = 0.037, respectively]. (2) Dead space significantly decreased, and ventilation/perfusion matching significantly increased in both the ventral and global regions. (3) No significant variations were observed in regional and global shunt. CONCLUSIONS: During VV ECMO, the ECMO blood flow rate, closely linked to recirculation fraction, could affect the accuracy of lung perfusion assessment using hypertonic saline bolus-based EIT.
Assuntos
Impedância Elétrica , Oxigenação por Membrana Extracorpórea , Pulmão , Tomografia , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Masculino , Feminino , Estudos Prospectivos , Impedância Elétrica/uso terapêutico , Pessoa de Meia-Idade , Adulto , Tomografia/métodos , Pulmão/irrigação sanguínea , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Solução Salina Hipertônica/uso terapêutico , Idoso , Velocidade do Fluxo Sanguíneo/fisiologiaRESUMO
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 BasesRESUMO
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: BMIâ ≤â 18.5 kg/m2 (underweight), group B: BMI: 18.5 to 24.0 kg/m2 (normal), group C: BMIâ ≥â 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 (28.45â ±â 5.32 vs 29.89â ±â 5.00 vs 30.74â ±â 5.40; Pâ =â .000). In addition, number of oocytes retrieved was also significantly higher in group A (11.25â ±â 5.97 vs 11.07â ±â 5.49 vs 10.52â ±â 5.02; Pâ =â .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 (aORâ =â 0.822, 95% CI: 0.817-0.957, Pâ =â .000). However, in the cycles of older patients, the effect of overweight/obesity on the CLBR was not significant (aORâ =â 0.986, 95% CI: 0.903-1.027, Pâ >â .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 OvulaçãoRESUMO
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 , SódioRESUMO
Corporate governance plays an important role in achieving high-quality economic development and sustainable corporate development. In recent years, as listed companies face increasing challenges in social responsibility issues such as environmental pollution and financial fraud, corporate governance has received widespread attention from academics and practitioners. In particular, technological innovation has attracted much attention to the development of enterprises. This paper also explores the intermediary mechanism of technological innovation based on the output measurement method of technological innovation. This study selected data from companies listed on the A-share main board of the Shanghai and Shenzhen Stock Exchanges in China from 2012 to 2022, aiming to explore the relationship between corporate governance and corporate performance. At the same time, we further analyzed the impact of corporate governance on corporate performance based on the mediating role of technological innovation. The research results show that equity balance degree, board size, and executive incentives all have a positive impact on corporate performance. Technological innovation has a certain mediating effect on independent variables (equity balance degree, board size, and executive incentives) and corporate performance. This study clarifies the controversy about the relationship between corporate governance and corporate performance and deepens the understanding of this relationship. It also provides empirical support for listed companies to pay attention to and improve corporate governance levels and enhance innovation capabilities. By exploring the interplay between governance mechanisms, innovation processes, and performance outcomes, researchers can gain a deeper understanding of how organizations can leverage governance practices to drive innovation-led growth and sustainable success.
RESUMO
BACKGROUND AND OBJECTIVE: Endometriosis and adenomyosis are two common diseases that impair women's health, and dienogest is one of the pharmacologic treatments which is the first-line therapeutic option for patients with pelvic pain and individuals who have no desire for immediate pregnancy. The goal of this study was to summarize the current evidence of adverse events associated with dienogest as well as the prevalence of these adverse events during treatment with dienogest. METHODS: Several databases (PubMed, Embase, Cochrane Central and Clinicaltrials.gov, etc.) and the US FDA Adverse Event Reporting System (FAERS) Public Dashboard were searched on May 31, 2023, using the topic words alongside free words of dienogest and "adverse reaction". Studies were incorporated into this research if they reported or assessed safety issues or adverse reactions of dienogest during the period of endometriosis treatment or adenomyosis therapy. The extracted information comprised trial design, dienogest and control group demographics, as well as reported side effects. RESULTS: This systematic review comprehended 39 publications in total. The mean age of patients in the included studies was 34.43 years. The follow-up duration varied from 3 to 60 months. Most adverse reactions were common and not serious, and the most common adverse reactions during dienogest medication were abnormal uterine bleeding (55%, 95% CI 37-73%), amenorrhea (17%, 95% CI 2-42%) and swelling (13%, 95% CI 3-28%). Uncommon adverse reactions included dysmenorrhea (0.2%, n = 1), dyspepsia (0.4%, n = 1), and (lower) abdominal pain (1%, 95% CI 0-3%), urticaria (1%, 95% CI 0-3%) and peritonitis (1%, n = 1). Serious adverse reactions including decreased lumbar spine Bone Mineral Density (BMD), depression, peritonitis and so on have been reported. Heterogeneity assessment revealed that patient number and study design are influencing factors to adverse reaction prevalence. Moreover, abdominal pain, diarrhea, nausea and vomiting, back pain and anemia are side effects reported both in the FAERS database and in the systematic review. CONCLUSIONS: Dienogest's most frequent side effects were not severe. Dienogest is generally safe for treating endometriosis and adenomyosis. Nevertheless, people should be aware of serious adverse reactions, such as decreased lumbar spine BMD and hemorrhagic shock.
Assuntos
Teorema de Bayes , Endometriose , Nandrolona , Humanos , Nandrolona/análogos & derivados , Nandrolona/efeitos adversos , Nandrolona/uso terapêutico , Feminino , Endometriose/tratamento farmacológico , Adenomiose/tratamento farmacológico , Antagonistas de Hormônios/efeitos adversos , Antagonistas de Hormônios/uso terapêuticoRESUMO
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).
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 MicrobianaRESUMO
A thermoelectric generator (TEG) is one of the important energy harvesting sources for wearable electronic devices, which converts waste heat into electrical energy without any external stimuli, such as light or mechanical motion. However, the poor flexibility of traditional TEGs (e.g., Si-based TE devices) causes the limitations in practical applications. Flexible paper substrates are becoming increasingly attractive in wearable electronic technology owing to their usability, environmental friendliness (disposable, biodegradable, and renewable materials), and foldability. The high water-absorbing quality of paper restricts its scope of application due to water failure. Therefore, we propose a high-performance flexible waterproof paper-based thermoelectric generator (WPTEG). A modification method that infiltrates TE materials into cellulose paper through vacuum filtration is used to prepare the TE modules. By connecting the TE-modified paper with Al tape, as well as a superhydrophobic layer encapsulation, the WPTEG is fabricated. The WPTEG with three P-N modules can generate an output voltage of up to 235 mV at a temperature difference of 50 K, which can provide power to portable electronic devices such as diodes, clocks, and calculators in hot water. With the waterproof property, the WPTEG paves the way for achieving multi-scenario applications in humid environments on human skin.
RESUMO
Fruit size is a crucial agronomic trait in bottle gourd, impacting both yield and utility. Despite its significance, the regulatory mechanism governing fruit size in bottle gourd remains largely unknown. In this study, we used bottle gourd (small-fruited H28 and large-fruited H17) parent plants to measure the width and length of fruits at various developmental stages, revealing a single 'S' growth curve for fruit expansion. Paraffin section observations indicated that both cell number and size significantly influence bottle gourd fruit size. Through bulked segregant analysis and combined genotype-phenotype analysis, the candidate interval regulating fruit size was pinpointed to 17,747,353 bp-18,185,825 bp on chromosome 9, encompassing 0.44 Mb and including 44 genes. Parental fruits in the rapid expansion stage were subjected to RNA-seq, highlighting that differentially expressed genes were mainly enriched in pathways related to cell wall biosynthesis, sugar metabolism, and hormone signaling. Transcriptome and resequencing analysis, combined with gene function annotation, identified six genes within the localized region as potential regulators of fruit size. This study not only maps the candidate interval of genes influencing fruit size in bottle gourd through forward genetics, but also offers new insights into the potential molecular mechanisms underlying this trait through transcriptome analysis.
RESUMO
Natural pyrethrins (NPs) are insecticidal compounds isolated and extracted from pyrethrum flowers and are primarily use to control sanitary pests. The lungs become the main target after exposure, and its use may pose potential hazards to respiratory health. Therefore, in this paper, the toxic effects of NPs on human lung cells A549 were investigated and the risk of respiratory toxicity of NPs was studied using zebrafish swim bladder as a model. The results showed that NPs induced cytotoxicity, caused oxidative DNA damage and triggered mitochondria-mediated apoptosis. In addition, exposure to NPs decreased zebrafish embryo survival, hatchability, and heartbeat, and may inhibit normal swim bladder development by disrupting Wnt and Hedgehog signaling pathways. In conclusion, our results suggest that NPs can induce cytotoxicity in A549 in vitro and developmental toxicity in zebrafish in vivo. This study provides a conceptual basis for understanding the mechanisms of toxicity of NPs and assessing respiratory health risks in humans.
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 , MamíferosRESUMO
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 MicrobianaRESUMO
Intramuscular fat (IMF) is a crucial determinant of meat quality and is influenced by various regulatory factors. Despite the growing recognition of the important role of long noncoding RNAs (lncRNAs) in IMF deposition, the mechanisms underlying buffalo IMF deposition remain poorly understood. In this study, we identified and characterized a lncRNA, lncFABP4, which is transcribed from the antisense strand of fatty acid-binding protein 4 (FABP4). lncFABP4 inhibited cell proliferation in buffalo intramuscular preadipocytes. Moreover, lncFABP4 significantly increased intramuscular preadipocyte differentiation, as indicated by an increase in the expression of the adipogenic markers peroxisome proliferator-activated receptor gamma (PPARG), CCAAT enhancer binding protein alpha (C/EBPα), and FABP4. Mechanistically, lncFABP4 was found to have the potential to regulate downstream gene expression by participating in protein-protein interaction pathways. These findings contribute to further understanding of the intricate mechanisms through which lncRNAs modulate intramuscular adipogenesis in buffaloes.
Assuntos
Adipócitos , Adipogenia , Búfalos , Diferenciação Celular , Proliferação de Células , Proteínas de Ligação a Ácido Graxo , PPAR gama , RNA Longo não Codificante , Animais , Búfalos/genética , Búfalos/metabolismo , Adipogenia/genética , Adipócitos/metabolismo , Adipócitos/citologia , Proteínas de Ligação a Ácido Graxo/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Diferenciação Celular/genética , PPAR gama/metabolismo , PPAR gama/genética , Expressão Gênica , Células Cultivadas , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Qualidade dos AlimentosRESUMO
Dimefluthrin (DIM) is a commonly utilized sanitary insecticide, predominantly employed for indoor pest management within residential and public environments directly interacting with human habitation. However, the usage of DIM is escalating with increasing mosquito resistance, prompting concerns about its health risks. Here, using zebrafish as a research model, we systematically evaluated DIM's impact on human health. Findings revealed significant health hazards during embryonic development, including reduced hatching rates, shortened body lengths, and organ malformations, notably affecting the heart. It was explored the mechanism of DIM-induced cardiotoxicity in zebrafish, and histopathological analyses revealed that DIM resulted in ventricular linearization in zebrafish embryos. Antioxidant enzyme activities were reduced and cardiac reactive oxygen species (ROS) accumulated after DIM exposure, suggesting clear signs of oxidative stress. Additionally, acridine orange (AO) staining and caspase-3 immunofluorescence demonstrated cardiac apoptosis in Tg (kdrl: EGFP) zebrafish. qPCR analysis implied that DIM induced apoptosis via the p53/Caspase pathway by up-regulating the expression levels of p53, cytochrome C (cyto-C), caspase-9, and caspase-3. Together, our work provided a systematic perspective on the cardiotoxicity of sanitary pesticides, which could offer opportunities for future risk management.