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1.
Nat Chem ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744914

RESUMO

Membrane-bound styrene oxide isomerase (SOI) catalyses the Meinwald rearrangement-a Lewis-acid-catalysed isomerization of an epoxide to a carbonyl compound-and has been used in single and cascade reactions. However, the structural information that explains its reaction mechanism has remained elusive. Here we determine cryo-electron microscopy (cryo-EM) structures of SOI bound to a single-domain antibody with and without the competitive inhibitor benzylamine, and elucidate the catalytic mechanism using electron paramagnetic resonance spectroscopy, functional assays, biophysical methods and docking experiments. We find ferric haem b bound at the subunit interface of the trimeric enzyme through H58, where Fe(III) acts as the Lewis acid by binding to the epoxide oxygen. Y103 and N64 and a hydrophobic pocket binding the oxygen of the epoxide and the aryl group, respectively, position substrates in a manner that explains the high regio-selectivity and stereo-specificity of SOI. Our findings can support extending the range of epoxide substrates and be used to potentially repurpose SOI for the catalysis of new-to-nature Fe-based chemical reactions.

2.
J Anim Sci ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727196

RESUMO

Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), a significant member of the conserved RNA-binding protein family, plays various roles in numerous physiological and pathological processes. However, the specific function of IGF2BP2 in regulating endometrial function in sheep remains largely unknown. In this study, we observed a significant upregulation in IGF2BP2 mRNA abundance in the endometrium during the luteal phase (LP) compared to the follicular phase (FP) in Hu sheep. The knockdown of IGF2BP2 resulted in accelerated cell proliferation and migration of Hu sheep endometrial stromal cells (ESCs). Moreover, RNA sequencing analysis revealed that genes with significantly altered expression in IGF2BP2 knockdown cells were predominantly enriched in endometrial receptivity-related signaling pathways, such as cytokine-cytokine receptor interaction, NOD-like receptor, PI3K-AKT, and JAK-STAT signaling pathway. Additionally, the knockdown of IGF2BP2 significantly increased the expression of matrix metalloprotein 9 (MMP9), vascular endothelial growth factor (VEGF), and prolactin (PRL) in ESCs. The knockdown of IGF2BP2 was also observed to stimulate the PI3K/AKT/mTOR pathway by upregulating integrin ß4 (ITGB4) expression. Notably, the downregulation of ITGB4 attenuates IGF2BP2 knockdown-induced facilitation of proliferation and migration of Hu sheep ESCs by inhibiting the PI3K/AKT/mTOR pathway. Collectively, these findings highlight the important role of IGF2BP2 in regulating endometrial function, particularly through the modulation of ESC proliferation and migration via the PI3K/AKT/mTOR pathway.

3.
ACS Infect Dis ; 10(5): 1576-1589, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38581387

RESUMO

Exploring novel antimicrobial drugs and strategies has become essential to the fight MRSA-associated infections. Herein, we found that membrane-disrupted repurposed antibiotic salifungin had excellent bactericidal activity against MRSA, with limited development of drug resistance. Furthermore, adding salifungin effectively decreased the minimum inhibitory concentrations of clinical antibiotics against Staphylococcus aureus. Evaluations of the mechanism demonstrated that salifungin disrupted the level of H+ and K+ ions using hydrophilic and lipophilic groups to interact with bacterial membranes, causing the disruption of bacterial proton motive force followed by impacting on bacterial the function of the respiratory chain and adenosine 5'-triphosphate, thereby inhibiting phosphatidic acid biosynthesis. Moreover, salifungin also significantly inhibited the formation of bacterial biofilms and eliminated established bacterial biofilms by interfering with bacterial membrane potential and inhibiting biofilm-associated gene expression, which was even better than clinical antibiotics. Finally, salifungin exhibited efficacy comparable to or even better than that of vancomycin in the MRSA-infected animal models. In conclusion, these results indicate that salifungin can be a potential drug for treating MRSA-associated infections.


Assuntos
Antibacterianos , Biofilmes , Reposicionamento de Medicamentos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Animais , Camundongos , Farmacorresistência Bacteriana/efeitos dos fármacos
4.
Heliyon ; 10(8): e29643, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38655343

RESUMO

Chitin is a polysaccharide similar to cellulose that contains abundant hydrogen bonds. Expansin-like proteins disrupt hydrogen bond networks, causing cellulose to swell and accelerating its degradation. We examined the effects of pretreatment with two expansin-like proteins, CxEXL22 (Arthrobotrys sp. CX1) and HcEXL (Hahella chejuensis), on chitin depolymerisation and enzymatic degradation. The efficiency of chitin degradation increased more than two-fold after pretreatment with expansin-like proteins. Following pretreatment with expansin-like proteins, chitin had a lower crystallinity index, greater d-spacing and crystallite size, and weaker hydrogen bonds, and the loosened porous microfibrils were more exposed than in untreated chitin. The rupture characterisation of crystalline chitin indicated that expansin-like proteins loosened the hydrogen bonds of the chitin polysaccharide chains, causing significant depolymerisation to expose more porous structures and enhance chitin accessibility.

5.
Polymers (Basel) ; 16(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38611189

RESUMO

Vaccines typically work by eliciting an immune response against larger antigens like polysaccharides or proteins. Small molecules like nicotine, on their own, usually cannot elicit a strong immune response. To overcome this, anti-nicotine vaccines often conjugate nicotine molecules to a carrier protein by carbodiimide crosslinking chemistry to make them polymeric and more immunogenic. The reaction is sensitive to conditions such as pH, temperature, and the concentration of reactants. Scaling up the reaction from laboratory to industrial scales while maintaining consistency and yield can be challenging. Despite various approaches, no licensed anti-nicotine vaccine has been approved so far due to the susboptimal antibody titers. Here, we report a novel approach to conjugate maleimide-modified nicotine hapten with a disulfide bond-reduced carrier protein in an organic solvent. It has two advantages compared with other approaches: (1) The protein was unfolded to make the peptide conformation more flexible and expose more conjugation sites; (2) thiol-maleimide "click" chemistry was utilized to conjugate the disulfide bond-reduced protein and maleimide-modified nicotine due to its availability, fast kinetics, and bio-orthogonality. Various nicotine conjugate vaccines were prepared via this strategy, and their immunology effects were investigated by using MPL and QS-21 as adjuvants. The in vivo study in mice showed that the nicotine-BSA conjugate vaccines induced high anti-nicotine IgG antibody titers, compared with vaccines prepared by using traditional condensation methods, indicating the success of the current strategy for further anti-nicotine or other small-molecule vaccine studies. The enhancement was more significant by using MPL and QS-21 than that of traditional aluminum adjuvants.

6.
J Magn Reson Imaging ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587265

RESUMO

BACKGROUND: Cardiac diffusion-weighted imaging (DWI) using second-order motion-compensated spin echo (M2C) can provide noninvasive in-vivo microstructural assessment, but limited by relatively low signal-to-noise ratio (SNR). Echo-planar imaging (EPI) with compressed sensitivity encoding (EPICS) could address these issues. PURPOSE: To combine M2C DWI and EPCIS (M2C EPICS DWI), and compare image quality for M2C DWI. STUDY TYPE: Prospective. POPULATION: Ten ex-vivo hearts, 10 healthy volunteers (females, 5 [50%]; mean ± SD of age, 25 ± 4 years), and 12 patients with diseased hearts (female, 1 [8.3%]; mean ± SD of age, 44 ± 16 years; including coronary artery heart disease, congenital heart disease, dilated cardiomyopathy, amyloidosis, and myocarditis). FIELD STRENGTH/SEQUENCE: 3-T, M2C EPICS DWI, and M2C DWI. ASSESSMENT: The apparent SNR (aSNR) and the rating scores were used to evaluate and compared image quality of all three groups. The aSNR was calculated using aSNR = Mean intensity myocardium / Standard deviation myocardium $$ \mathrm{aSNR}={\mathrm{Mean}\ \mathrm{intensity}}_{\mathrm{myocardium}}/{\mathrm{Standard}\ \mathrm{deviation}}_{\mathrm{myocardium}} $$ , and the myocardium was segmented manually. Three observers independently rated subjective image quality using a 5-point Likert scale. STATISTICAL TESTS: Bland-Altman analysis and paired t-tests. The threshold for statistical significance was set at P < 0.05. RESULTS: In healthy volunteers, the aSNR with a b-value of 450 s/mm2 acquired by M2C EPICS DWI was significantly higher than M2C DWI at in-plane resolutions of 3.0 × 3.0, 2.5 × 2.5, and 2.0 × 2.0 mm2. In patients with diseased hearts, the aSNR ofM2C EPICS DWI was also significantly higher than that for M2C DWI (bias of M2C EPICS-M2C = 1.999, 95% limits of agreement, 0.362 to 3.636; mean ± SD, 7.80 ± 1.37 vs. 5.80 ± 0.81). The ADC values of M2C EPICS was significantly higher than M2C DWI in in-vivo hearts. Over 80% of the images with rating scores for M2C EPICS DWI were higher than M2C DWI in in-vivo hearts. DATA CONCLUSION: Cardiac imaging by M2C EPICS DWI may demonstrate better overall image quality and higher aSNR than M2C DWI. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

7.
Biochemistry ; 63(9): 1225-1233, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38682295

RESUMO

As plant photoreceptors, phytochromes are capable of detecting red light and far-red light, thereby governing plant growth. All2699 is a photoreceptor found in Nostoc sp. PCC7120 that specifically responds to red light and far-red light. All2699g1g2 is a truncated protein carrying the first and second GAF (cGMP phosphodiesterase/adenylyl cyclase/FhlA) domains of All2699. In this study, we found that, upon exposure to red light, the protein underwent aggregation, resulting in the formation of protein aggregates. Conversely, under far-red light irradiation, these protein aggregates dissociated. We delved into the factors that impact the aggregation of All2699g1g2, focusing on the protein structure. Our findings showed that the GAF2 domain contains a low-complexity (LC) loop region, which plays a crucial role in mediating protein aggregation. Specifically, phenylalanine at position 239 within the LC loop region was identified as a key site for the aggregation process. Furthermore, our research revealed that various factors, including irradiation time, temperature, concentration, NaCl concentration, and pH value, can impact the aggregation of All2699g1g2. The aggregation led to variations in Pfr concentration depending on temperature, NaCl concentration, and pH value. In contrast, ΔLC did not aggregate and therefore lacked responses to these factors. Consequently, the LC loop region of All2699g1g2 extended and enhanced sensory properties.


Assuntos
Proteínas de Bactérias , Luz , Nostoc , Nostoc/metabolismo , Nostoc/química , Nostoc/efeitos da radiação , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Domínios Proteicos , Agregados Proteicos , Fotorreceptores Microbianos/química , Fotorreceptores Microbianos/metabolismo , Pigmentos Biliares/química , Pigmentos Biliares/metabolismo , Concentração de Íons de Hidrogênio , Fitocromo/química , Fitocromo/metabolismo
8.
ACS Sens ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687557

RESUMO

In this study, we demonstrate whole blood immunoassays using a microfluidic device optimized for conducting rapid and multiplexed fluorescence-linked immunoassays. The device is capable of handling whole blood samples without any preparatory treatment. The three-dimensional channels in poly(methyl methacrylate) are designed to passively load bodily fluids and, due to their linearly tapered profile, facilitate size-dependent immobilization of biofunctionalized particles. The channel geometry is optimized to allow for the unimpeded flow of cellular constituents such as red blood cells (RBCs). Additionally, to make the device easier to operate, the biofunctionalized particles are pretrapped in a first step, and the channel is dried under vacuum, after which it can be loaded with the biological sample. This novel approach and design eliminated the need for traditionally laborious steps such as filtering, incubation, and washing steps, thereby substantially simplifying the immunoassay procedures. Moreover, by leveraging the shallow device dimensions, we show that sample loading to read-out is possible within 5 min. Our results also show that the presence of RBCs does not compromise the sensitivity of the assays when compared to those performed in a pure buffer solution. This highlights the practical adaptability of the device for simple and rapid whole-blood assays. Lastly, we demonstrate the device's multiplexing capability by pretrapping particles of different sizes, each functionalized with a different antigen, thus enabling the performance of multiplexed on-chip whole-blood immunoassays, showcasing the device's versatility and effectiveness toward low-cost, simple, and multiplexed sensing of biomarkers and pathogens directly in whole blood.

9.
WIREs Mech Dis ; : e1644, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38508867

RESUMO

Solute carrier family 40 member 1 (SLC40A1) plays an essential role in transporting iron from intracellular to extracellular environments. When SLC40A1 expression is abnormal, cellular iron metabolism becomes dysregulated, resulting in an overload of intracellular iron, which induces cell ferroptosis. Numerous studies have confirmed that ferroptosis is closely associated with the development of many diseases. Here, we review recent findings on SLC40A1 in ferroptosis and its association with various diseases, intending to explore new directions for research on disease pathogenesis and new therapeutic targets for prevention and treatment. This article is categorized under: Cancer > Genetics/Genomics/Epigenetics Metabolic Diseases > Molecular and Cellular Physiology.

10.
J Cosmet Dermatol ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532267

RESUMO

OBJECTIVE: To investigate the histological properties of microplasma radiofrequency (MPRF) using a stationary tip in different treatment strategies on porcine skin. METHODS: Two Bama miniature pigs received MPRF treatment with two types of stationary tips in eight groups of parameters (power, duration, and pass) on dorsal skin. Skin samples were collected from each treatment zone immediately, at 1 week and 1, 3, and 6 months after treatment. Hematoxylin and eosin (HE) and Masson staining were performed to assess histologic changes as well as neocollagenesis. The dynamic changes of heat shock protein 47 (HSP47) and heat shock protein 72 (HSP72) were also detected by immunohistochemistry. RESULTS: Skin damage increased with pulse energy, duration, and pass. Longer durations or repeated treatments may cause particularly severe skin damage. During the wound healing process, the newborn collagen of the dermis is rearranged. The distribution of HSP47 and HSP72 was consistent with the extent of collagen remodeling. It peaked 1 month after treatment. CONCLUSION: MPRF can effectively cause epidermal ablation, dermal collagen hyperplasia, and remodeling. Increasing power should be the first choice when increasing treatment intensity. For longer durations or repeated treatments, caution should be taken to avoid excessive skin trauma.

11.
Nanoscale ; 16(13): 6669-6679, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38483277

RESUMO

Perovskite p-n homojunctions (PHJ) have been confirmed to play a crucial role in facilitating carrier separation/extraction in the perovskite absorption layer and provide an additional built-in potential, which benefits the inhibition of carrier recombination in perovskite solar cells (PSCs) and ultimately improves device performance. However, the diffusion and migration of ions between n-type and p-type perovskite films, particularly under operational and heating conditions, lead to the degradation of PHJ structures and limit the long-term stability of PSCs with PHJ structure (denoted as PHJ-PSCs). In this study, we propose an insert layer strategy by directly introducing an ultra-thin polyetheramine (PEA) layer between the n-type and p-type perovskite films to address those challenges arising from ion movements. Femtosecond transient absorption (fs-TAS) and photoluminescence (PL) measurements demonstrate that the PHJ (without and with the insert layer) enhances carrier separation/extraction compared to the single n-type perovskite film. Monitoring the evolution of bromine element distribution reveals that the insert layer can efficiently suppress ion diffusion between perovskite films, even under long-term illumination and heating conditions. Consequently, an efficiency of 23.53% with excellent long-term operational stability is achieved in the optimized PHJ-PSC with the insert layer.

12.
Microbiol Res ; 283: 127647, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38452551

RESUMO

The Type VI secretion system (T6SS) functions as a protein transport nanoweapon in several stages of bacterial life. Even though bacterial competition is the primary function of T6SS, different bacteria exhibit significant variations. Particularly in Extraintestinal pathogenic Escherichia coli (ExPEC), research into T6SS remains relatively limited. This study identified the uncharacterized gene evfG within the T6SS cluster of ExPEC RS218. Through our experiments, we showed that evfG is involved in T6SS expression in ExPEC RS218. We also found evfG can modulate T6SS activity by competitively binding to c-di-GMP, leading to a reduction in the inhibitory effect. Furthermore, we found that evfG can recruit sodA to alleviate oxidative stress. The research shown evfG controls an array of traits, both directly and indirectly, through transcriptome and additional tests. These traits include cell adhesion, invasion, motility, drug resistance, and pathogenicity of microorganisms. Overall, we contend that evfG serves as a multi-functional regulator for the T6SS and several crucial activities. This forms the basis for the advancement of T6SS function research, as well as new opportunities for vaccine and medication development.


Assuntos
Proteínas de Escherichia coli , Escherichia coli Extraintestinal Patogênica , Sistemas de Secreção Tipo VI , Sistemas de Secreção Tipo VI/genética , Sistemas de Secreção Tipo VI/metabolismo , Escherichia coli Extraintestinal Patogênica/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Virulência , Fatores de Virulência/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
13.
BMC Med Educ ; 24(1): 215, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429761

RESUMO

BACKGROUND: Expanding new nurse training and education is a priority for nursing educators as well as a critical initiative to stabilize the nursing workforce. Given that there is currently no standardized program for the training of new nurses in China, we investigated the effectiveness of the bridge-in, objective, pre-assessment, participatory learning, post-assessment, and summary model combined with case-based learning ((BOPPPS-CBL) for the standardized training of new nurses. METHODS: The mixed method approach with explanatory sequential (quantitative-qualitative) method was used. A questionnaire was used to compare the impact of the BOPPPS-CBL model and the Traditional Learning Model (TLM) on the core competencies of 185 new nurses for two years of standardized training. Quantitative data were analyzed using SPSS 22.0. Focus group interviews were used with four groups of new nurses and perceptions of BOPPPS-CBL training were recorded. Qualitative data were analyzed thematically. RESULTS: According to the quantitative data, more new nurses agreed that the BOPPPS-CBL model stimulated their learning and improved their core nursing competencies than the TLM. The BOPPPS-CBL group outperformed the TLM group on theoretical knowledge tests. Qualitative data revealed that 87.5% of new nurses agreed on the value of BOPPPS-CBL training, and three themes were extracted: (1) role promotion; (2) formation of new thinking to solve clinical problems; and (3) suggestions for improvement. CONCLUSION: BOPPPS-CBL training had a significant impact on improving new nurses' core competencies and promoting the transition of new nurses to clinical practice nurses in China. The study recommends BOPPPS-CBL training as an effective teaching model for the standardized training and education of new nurses.


Assuntos
Educação em Enfermagem , Internato e Residência , Humanos , Aprendizagem , China , Grupos Focais
14.
Heliyon ; 10(4): e26138, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38434073

RESUMO

Objective: The EKAN is a reliable and validated tool for objectively measuring the evidence-based practice (EBP) knowledge of nurses. Thus, we set out to translate and culturally modify the Evidence-Based Practice Knowledge Assessment in Nursing (EKAN), and then evaluate its validity and reliability among Chinese practicing nurses. Methods: This cross-sectional study consisted of two phases. The first phase involved translating the EKAN into Chinese (EKAN-Chinese), using a process of forward translation, back translation, review, cultural adjustment as well as a pilot study. The second phase aimed to assess the psychometric properties of the EKAN-Chinese and establish a baseline measure of EBP knowledge among 120 nurses from a large general hospital in Beijing, China. Data were collected from August to November 2022 and analyzed with Rasch software. This study was reported using the cross-sectional STROBE checklist. Results: The newly translated, EKAN-Chinese was pilot-tested after slight modification of four items without altering the intended meaning. The outfit unweighted mean square was 1.03 (SD = -0.13), the infit weighted mean square was 1.00 (-0.17), and the mean difficulty index ranged from -3.43 to 2.85 according to validity indices. The results of the reliability indices revealed low person reliability (0.49), high item reliability (0.96), moderate person separation index (0.99), and sufficient item separation index (4.71). The mean EKAN-Chinese sum score was 9.8 (max score = 20, SD = 2.9). Conclusion: The newly translated EKAN-Chinese showed sufficient psychometric evidence to support use in practicing Chinese nurses. The EKAN-Chinese can be used by nurse leaders in China as a potential screening tool to 1) objectively identify nurses who need educational training in evidence-based nursing practice, and 2) gauge the effectiveness of education and training programs to improve EBP knowledge and ultimately, evidence-based care.

15.
Explore (NY) ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38458955

RESUMO

OBJECTIVE: To investigate the effectiveness and safety of Jiejing Runmu decoction in relieving the clinical manifestations of dry eye disease (DED). DESIGN AND INTERVENTIONS: This single-arm prospective intervention study was conducted at the Peking University Third Hospital and People's Hospital of Yongqing. Of the 211 patients recruited, 200 completing the follow-up were included in the analysis. Patients received Jiejing Runmu decoction once a day for 4 weeks continuously, without any change in eye care habits. Individuals were evaluated at four time points: pretreatment (baseline), 2 weeks, 1 month, and 3 months (2 months after completion of treatment), using the Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), corneal fluorescein staining, Schirmer test I and meibomian gland assessments. Adverse effects were evaluated at each follow-up visit and systematic examinations were performed during the first and last visits. RESULTS: OSDI, TBUT, corneal fluorescein staining, Schirmer test I, meibomian gland expressibility, and quality of secretions improved at 2 weeks, 1 month and 3 months compared to baseline (P < 0.0001). No significant differences were found between the sexes. Patients above 45 years showed worse subjective symptoms and objective signs, and greater improvements in corneal fluorescein staining, meibomian gland expressibility, and quality of secretions were observed in this group. No obvious adverse effects were detected during any follow-up visit. CONCLUSION: Jiejing Runmu decoction significantly improved both the subjective symptoms and objective signs of DED, with favorable tolerance.

16.
Virol Sin ; 39(2): 301-308, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38452856

RESUMO

Hand, foot, and mouth disease (HFMD) is a common pediatric illness mainly caused by enteroviruses, which are important human pathogens. Currently, there are no available antiviral agents for the therapy of enterovirus infection. In this study, an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed. Using this screening system, we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors. Fangchinoline (FAN), a bis-benzylisoquinoline alkaloid, exhibits potential inhibitory effects against various enteroviruses that cause HFMD, such as EV-A71, CV-A10, CV-B3 and CV-A16. Further investigations revealed that FAN targets the early stage of the enterovirus life cycle. Through the selection of FAN-resistant EV-A71 viruses, we demonstrated that the VP1 protein could be a potential target of FAN, as two mutations in VP1 (E145G and V258I) resulted in viral resistance to FAN. Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.


Assuntos
Antivirais , Benzilisoquinolinas , Farmacorresistência Viral , Antivirais/farmacologia , Humanos , Benzilisoquinolinas/farmacologia , Farmacorresistência Viral/genética , Replicação Viral/efeitos dos fármacos , Enterovirus Humano A/efeitos dos fármacos , Enterovirus Humano A/genética , Avaliação Pré-Clínica de Medicamentos , Genes Reporter , Ensaios de Triagem em Larga Escala , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/antagonistas & inibidores , Enterovirus/efeitos dos fármacos , Enterovirus/genética , Linhagem Celular , Proteínas de Fluorescência Verde/genética
17.
Front Microbiol ; 15: 1224855, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333584

RESUMO

Introduction: Ligninolytic bacteria can secrete extracellular enzymes to depolymerize lignin into small-molecular aromatics that are subsequently metabolized and funneled into the TCA cycle. Carbohydrates, which are the preferred carbon sources of bacteria, influence the metabolism of lignin-derived aromatics through bacteria. Methods: In this study, untargeted metabolomics and transcriptomics analyses were performed to investigate the effect of carbohydrates on lignin degradation mediated by Bacillus amyloliquefaciens MN-13, a strain with lignin-degrading activity that was isolated in our previous work. Results: The results demonstrated that the cell growth of the MN-13 strain and lignin removal were promoted when carbohydrates such as glucose and sodium carboxymethyl cellulose were added to an alkaline lignin-minimal salt medium (AL-MSM) culture. Metabolomics analysis showed that lignin depolymerization took place outside the cells, and the addition of glucose regulated the uptake and metabolism of lignin-derived monomers and activated the downstream metabolism process in cells. In the transcriptomics analysis, 299 DEGs were screened after 24 h of inoculation in AL-MSM with free glucose and 2 g/L glucose, respectively, accounting for 8.3% of the total amount of annotated genes. These DEGs were primarily assigned to 30 subcategories, including flagellar assembly, the PTS system, RNA degradation, glycolysis/gluconeogenesis, the TCA cycle, pyruvate metabolism, and tryptophan metabolism. These subcategories were closely associated with the cell structure, generation of cellular energy, and precursors for biosynthetic pathways, based on a - log 10 (P adjust) value in the KEGG pathway analysis. Conclusion: In summary, the addition of glucose increased lignin degradation mediated by the MN-13 strain through regulating glycolysis, TCA cycle, and central carbon metabolism.

18.
Food Chem ; 444: 138639, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38330609

RESUMO

With the rapid development of society, food safety to public health has been a topic that cannot be ignored. In recent years, lanthanide-based materials are studied to be potential candidates in the detection of food samples. Cerium (Ce)-based materials (such as Ce ions, CeO2, Ce-metal organic framework (Ce-MOF), etc.) have also attracted more attention in food detection by virtue of colorimetric, fluorescence, sensing, and other methods. This is because the mixed valence of Ce (Ce3+ and Ce4+), the formation of oxygen vacancies, and their optical and electrochemical properties. In this review, Ce-based materials will be introduced and discussed in the field of food detection, including biogenesis, construction, catalytic mechanisms, combination, and applications. In addition, the current challenges and future development trend of these Ce-based materials in food safety detection are also proposed and discussed. Therefore, it is meaningful to explore the Ce-based materials for detection of biomarkers in food samples.


Assuntos
Cério , Elementos da Série dos Lantanídeos , Estruturas Metalorgânicas , Cério/química , Estruturas Metalorgânicas/química , Oxigênio/química , Colorimetria
19.
Chem Commun (Camb) ; 60(18): 2472-2488, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38314874

RESUMO

Slow charging speed has been a serious constraint to the promotion of electric vehicles (EVs), and therefore the development of advanced lithium-ion batteries (LIBs) with fast-charging capability has become an urgent task. Thanks to its low price and excellent overall electrochemical performance, graphite has dominated the anode market for the past 30 years. However, it is difficult to meet the development needs of fast-charging batteries using graphite anodes due to their fast capacity degradation and safety hazards under high-current charging processes. This feature article describes the failure mechanism of graphite anodes under fast charging, and then summarizes the basic principles, current research progress, advanced strategies and challenges of fast-charging anodes represented by graphite, lithium titanate (Li4Ti5O12) and niobium-based oxides. Moreover, we look forward to the development prospects of fast-charging anodes and provide some guidance for future research in the field of fast-charging batteries.

20.
Int J Antimicrob Agents ; 63(4): 107104, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38325720

RESUMO

OBJECTIVES: Antimicrobial resistance has raised concerns regarding untreatable infections and poses a growing threat to public health. Rational design of new AMPs is an ideal solution to this threat. METHODS: In this study, we designed, modified, and synthesised an excellent AMP, L-10, based on the original sequence of the Cyprinus carpio chemokine. All experimental data were presented as the mean ± standard deviation (SD), and the two-tailed unpaired T-test method was used to analyze all data. RESULTS: L-10 exhibited excellent antibacterial activity with negligible toxicity and improved the efficacy of a broad class of antibiotics against MDR Gram-negative pathogens, including tetracycline, meropenem, levofloxacin, and rifampin. Mechanistic studies have suggested that L-10 targets the bacterial membrane components, LPS and PG, to disrupt bacterial membrane integrity, thereby exerting antibacterial effects and enhancing the efficacy of antibiotics. Moreover, in animal infection models, L-10 significantly increased the survival rate of infected animals and effectively reduced the tissue bacterial load and inflammatory factor levels. In addition to its direct antibacterial activity, L-10 dramatically reduced pulmonary pathological alterations in a mouse model of endotoxemia and suppressed LPS-induced proinflammatory cytokines in vitro and in vivo. Lastly, L-10 was successfully expressed in Pichia pastoris and maintained antimicrobial activity against MDR Gram-negative pathogens in vivo and in vitro. CONCLUSION: Collectively, these results reveal the potential of L-10 as an ideal candidate against MDR bacterial infections and provide new insights into the design, development, and clinical application of AMPs.


Assuntos
Carpas , Infecções por Escherichia coli , Camundongos , Animais , Lipopolissacarídeos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Quimiocinas , Infecções por Escherichia coli/tratamento farmacológico , Testes de Sensibilidade Microbiana
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