RESUMO
The minimization of the commutator of the Fock and density matrices as the error matrix in the direct inversion of the iterative subspace (CDIIS) developed by Pulay is a powerful self-consistent field (SCF) acceleration technique for the construction of optimum Fock matrix, if initiated with a fair initial guess. In this work, we present an alternative minimized error matrix to the commutator in the CDIIS, namely the residual or the gradient of the energy-functional for a Slater determinant subject to the orthonormality constraints among orbitals, representing the search for a newly improved Fock matrix in the direction of the residual in the direct inversion of the iterative subspace (RDIIS). Implemented in the computational chemistry package GAMESS, the RDIIS is compared with the standard CDIIS and the second order SCF orbital optimization (SOSCF) for tested molecules started with a crude guess. As a result, the RDIIS stably and efficiently performs the SCF convergence acceleration. Furthermore, the RDIIS is considerably independent on the subspace size with the concentrated linear coefficients accounting proportionally for the Fock matrices close to the current iteration.
RESUMO
The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.
Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Xantenos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Xantenos/síntese química , Xantenos/farmacologia , Xantenos/química , Testes de Sensibilidade Microbiana , Estereoisomerismo , Compostos Policíclicos/síntese química , Compostos Policíclicos/farmacologia , Compostos Policíclicos/química , Descoberta de Drogas , Estrutura MolecularRESUMO
Volatile organic compounds (VOCs) originating from diverse sources with complex compositions pose threats to both environmental safety and human health. Photocatalytic treatment of VOCs has garnered attention due to its high efficacy at room temperature. However, the intricate photochemical reaction generates ozone (O3), causing secondary pollution. Herein, our work developed a novel "synergistic effect" system for photocatalytic co-treatment of VOCs and O3 secondary pollution. Under the optimized reactor conditions simulated with computational fluid dynamics (CFD), MgO-loaded g-C3N4 composites (MgO/g-C3N4) were synthesized as efficient catalysts for the photocatalytic synergistic treatment process. Density functional theory (DFT) calculations, characterization, and electron paramagnetic resonance (EPR) tests revealed that the addition of MgO reduced the band gap of g-C3N4, and increased O3 molecule adsorption in the composites, efficiently harnessing the synergistic effect of O3 to generate a significant quantity of reactive oxygen radicals, thereby facilitating the removal of VOCs and O3. This study provides new insights for simultaneous elimination of VOCs and O3 secondary pollution by a photocatalytic process.
RESUMO
Li-rich antiperovskite (LiRAP) hydroxyhalides are emerging as attractive solid electrolyte (SEs) for all-solid-state Li metal batteries (ASSLMBs) due to their low melting point, low cost, and ease of scaling-up. The incorporation of rotational polyanions can reduce the activation energy and thus improve the Li ion conductivity of SEs. Herein, we propose a ternary rotational polyanion coupling strategy to fasten the Li ion conduction in tetrafluoroborate (BF4 -) ion doped LiRAP Li2OHCl. Assisted by first-principles calculation, powder X-ray diffraction, solid-state magnetic resonance and electrochemical impedance spectra, it is confirmed that Li ion transport in BF4 - ion doped Li2OHCl is strongly associated with the rotational coupling among OH-, BF4 - and Li2-O-H octahedrons, which enhances the Li ion conductivity for more than 1.8â times with the activation energy lowering 0.03â eV. This work provides a new perspective to design high-performance superionic conductors with multi-polyanions.
RESUMO
Objective: In the present study, we investigated the impact of left atrial appendage closure (LAAC) following catheter ablation (CA) on the left atrial structure and functioning of patients with paroxysmal atrial fibrillation (AF). Methods: Patients with paroxysmal AF were enrolled in this single-center prospective cohort study between April 2015 and July 2021; 353 patients received CA alone, while 93 patients received CA in combination with Watchman LAAC. We used age, gender, CHA2DS2-VASc, and HAS-BLED scores as well as other demographic variables to perform propensity score matching. Patients with paroxysmal AF were randomly assigned to the CA combined with Watchman LAAC group (combined treatment group) and the simple CA group, with 89 patients in each group. The left atrial structure, reserve, ventricular diastole, and pump functions and their changes in patients were assessed using routine Doppler echocardiography and 2D speckle tracking echocardiography over the course of a 1-year follow-up. Results: At 1-week follow-up, the reserve, ventricular diastole, and pump functions of the left atrium (LA) increased in both groups; these functions were gradually restored at the 1- to 3-month follow-up; they were close to or returned to their pre-operative levels at the 3-month follow-up; and no significant differences were found compared with the pre-operative levels at the 12-month follow-up. In the first 3 months, the reserve (Ƹ, SRs) and pump functions (SRa) in the combined treatment group decreased significantly when compared with the simple CA group, and the differences were statistically significant. Conclusion: Patients with paroxysmal AF may experience a short term, partial effect of LAAC on LA reserve and pump functions, which are gradually restored and the effect disappears by 12 months.
RESUMO
Armcx1 is a member of the ARMadillo repeat-Containing protein on the X chromosome (ARMCX) family, which is recognized to have evolutionary conserved roles in regulating mitochondrial transport and dynamics. Previous research has shown that Armcx1 is expressed at higher levels in mice after axotomy and in adult retinal ganglion cells after crush injury, and this protein increases neuronal survival and axonal regeneration. However, its role in traumatic brain injury (TBI) is unclear. Therefore, the aim of this study was to assess the expression of Armcx1 after TBI and to explore possible related mechanisms by which Armcx1 is involved in TBI. We used C57BL/6 male mice to model TBI and evaluated the role of Armcx1 in TBI by transfecting mice with Armcx1 small interfering RNA (siRNA) to inhibit Armcx1 expression 24 h before TBI modeling. Western blotting, immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, Nissl staining, transmission electron microscopy, adenosine triphosphate (ATP) level measurement, neuronal apoptosis analysis, neurological function scoring and the Morris water maze were performed. The results demonstrated that Armcx1 protein expression was elevated after TBI and that the Armcx1 protein was localized in neurons and astroglial cells in cortical tissue surrounding the injury site. In addition, inhibition of Armcx1 expression further led to impaired mitochondrial transport, abnormal morphology, reduced ATP levels, aggravation of neuronal apoptosis and neurological dysfunction, and decrease Miro1 expression. In conclusion, our findings indicate that Armcx1 may exert neuroprotective effects by ameliorating neurological injury after TBI through a mitochondrial transport pathway involving Miro1.
Assuntos
Proteínas do Domínio Armadillo , Lesões Encefálicas Traumáticas , Camundongos Endogâmicos C57BL , Mitocôndrias , Proteínas rho de Ligação ao GTP , Animais , Masculino , Camundongos , Trifosfato de Adenosina/metabolismo , Apoptose/fisiologia , Proteínas do Domínio Armadillo/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Modelos Animais de Doenças , Aprendizagem em Labirinto/fisiologia , Mitocôndrias/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
AIMS: Neuronal cell death is a primary factor that determines the outcome after traumatic brain injury (TBI). We previously revealed the importance of receptor for activated C kinase (RACK1), a multifunctional scaffold protein, in maintaining neuronal survival after TBI, but the specific mechanism remains unclear. The aim of this study was to explore the mechanism underlying RACK1-mediated neuroprotection in TBI. METHODS: TBI model was established using controlled cortical impact injury in Sprague-Dawley rats. Genetic intervention and pharmacological inhibition of RACK1 and PERK-autophagy signaling were administrated by intracerebroventricular injection. Western blotting, coimmunoprecipitation, transmission electron microscopy, real-time PCR, immunofluorescence, TUNEL staining, Nissl staining, neurobehavioral tests, and contusion volume assessment were performed. RESULTS: Endogenous RACK1 was upregulated and correlated with autophagy induction after TBI. RACK1 knockdown markedly inhibited TBI-induced autophagy, whereas RACK1 overexpression exerted the opposite effects. Moreover, RACK1 overexpression ameliorated neuronal apoptosis, neurological deficits, and cortical tissue loss after TBI, and these effects were abrogated by the autophagy inhibitor 3-methyladenine or siRNAs targeting Beclin1 and Atg5. Mechanistically, RACK1 interacted with PERK and activated PERK signaling. Pharmacological and genetic inhibition of the PERK pathway abolished RACK1-induced autophagy after TBI. CONCLUSION: Our findings indicate that RACK1 protected against TBI-induced neuronal damage partly through autophagy induction by regulating the PERK signaling pathway.
Assuntos
Lesões Encefálicas Traumáticas , Transdução de Sinais , Ratos , Animais , Ratos Sprague-Dawley , Lesões Encefálicas Traumáticas/metabolismo , Neuroproteção , Apoptose , Autofagia , Receptores de Quinase C AtivadaRESUMO
Purpose: The objective of this study was to investigate the epidemiological characteristics, distribution of isolates, prevailing patterns, and antibiotic susceptibility of bacterial keratitis (BK) in a Tertiary Referral Hospital located in Southwest China. Methods: A retrospective analysis was conducted on 660 cases of bacterial keratitis occurring between January 2015 and December 2022. The demographic data, predisposing factors, microbial findings, and antibiotic sensitivity profiles were examined. Results: Corneal trauma emerged as the most prevalent predisposing factor, accounting for 37.1% of cases. Among these cases, bacterial culture results were positive in 318 cases, 68 species of bacteria were identified. The most common Gram-Positive bacteria isolated overall was the staphylococcus epidermis and the most common Gram-Negative bacteria isolated was Pseudomonas aeruginosa. Methicillin-Resistant Staphylococci accounted for 18.1% of all Gram-Positive bacteria. The detection rate of P. aeruginosa showed an increasing trend over time (Rs=0.738, P=0.037). There was a significant decrease in the percentage of Gram-Negative microorganisms over time (Rs=0.743, P=0.035). The sensitivity of Gram-Positive bacteria to linezolid, vancomycin, tigecycline, quinupristin/dalfopristin, and rifampicin was over 98%. The sensitivity rates of Gram-Negative bacteria to amikacin, meropenem, piperacillin/tazobactam, cefoperazone sodium/sulbactam, ceftazidime, and cefepime were all above 85%. In patients with a history of vegetative trauma, the possibility of BK should be taken into account in addition to the focus on fungal keratitis. Conclusion: The microbial composition primarily consists of Gram-Positive cocci and Gram-Negative bacilli. Among the Gram-Positive bacteria, S. epidermidis and Streptococcus pneumoniae are the most frequently encountered, while P. aeruginosa is the predominant Gram-Negative bacteria. To combat Gram-Positive bacteria, vancomycin, linezolid, and rifampicin are considered excellent antimicrobial agents. When targeting Gram-Negative pathogens, third-generation cephalosporins exhibit superior sensitivity compared to first and second-generation counterparts. As an initial empirical treatment for severe cases of bacterial keratitis and those unresponsive to fourth-generation fluoroquinolones in community settings, the combination therapy of vancomycin and tobramycin is a justifiable approach. Bacterial keratitis can be better managed by understanding the local etiology and antibacterial drug susceptibility patterns.
Assuntos
Infecções Oculares Bacterianas , Ceratite , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Linezolida/uso terapêutico , Vancomicina , Rifampina , Estudos Retrospectivos , Centros de Atenção Terciária , Farmacorresistência Bacteriana , Cefoperazona/uso terapêutico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/epidemiologia , Sulbactam/uso terapêutico , Bactérias Gram-Positivas , Staphylococcus , Bactérias Gram-Negativas , Ceratite/tratamento farmacológico , Ceratite/epidemiologia , Ceratite/microbiologia , Testes de Sensibilidade MicrobianaRESUMO
In order to study the pollution characteristics of volatile organic compounds ï¼VOCsï¼ï¼ continuous monitoring of VOCs in two pollution processes was conducted in June and December 2021 in Zhengzhou. Combined with meteorological conditionsï¼ the pollution characteristicsï¼ source contributionsï¼ and reactivity of VOCs in winter and summer were compared and analyzed. The results showed that the volume fraction of atmospheric VOCs in two episodes were ï¼27.92±12.68ï¼×10-9 and ï¼24.30±5.93ï¼×10-9ï¼ respectively. The volume fraction of atmospheric VOCs in the haze pollution process in winter was larger than that in the ozone pollution process in summer. The analysis results of winter sources were as followsï¼ industrial source ï¼27.0%ï¼ï¼ motor vehicle source ï¼22.5%ï¼ï¼ combustion source ï¼20.1%ï¼ï¼ solvent use source ï¼16.3%ï¼ï¼ and oil and gas volatilization source ï¼14.1%ï¼. The analysis results of summer sources were as followsï¼ motor vehicle source ï¼24.8%ï¼ï¼ industrial source ï¼24.1%ï¼ï¼ solvent source ï¼17.4%ï¼ï¼ oil and gas volatilization source ï¼14.2%ï¼ï¼ combustion source ï¼11.2%ï¼ï¼ and plant source ï¼8.4%ï¼. The results of the smog production model showed that the proportion of days in the synergistic control zone of VOCs during the two pollution processes in summer ï¼66.7%ï¼ was smaller than that in winter ï¼100.0%ï¼. The secondary reaction activity results showed that the average ·OH loss rate ï¼L·OHï¼ values in winter and summer were 4.12 s-1 and 4.75 s-1ï¼ respectively. The average ozone formation potential ï¼OFPï¼ values in summer were 108.36 µg·m-3. The olefins were dominant in the top ten species due to L·OH and OFP contributions in summer. The total SOAFP values in winter in Zhengzhou were 54.38 µg·m-3. Among the top ten species contributing to SOAFP in winterï¼ nine were aromatic hydrocarbons.
RESUMO
Organic acids in atmospheric particulate matter are widely involved in various physical and chemical reactions in the atmosphere and contribute greatly to the formation of secondary organic aerosols and haze pollutions. Thereforeï¼ the concentration distribution characteristicsï¼ sourcesï¼ and secondary formation of organic acids in particulate matter are of great significance for further investigation of organic aerosols and their secondary transformation. Fine particulate matter ï¼PM2.5ï¼ samples were collected in Zhengzhouï¼ and three types of organic acidsï¼ including dicarboxylic acidsï¼ fatty acidsï¼ and resin acidsï¼ were analyzed to explore their species distributionï¼ seasonal variationsï¼ source contributionï¼ and secondary generation. Malonic acid ï¼di-C3ï¼ and succinate acid ï¼di-C4ï¼ were the most abundant in the identified dicarboxylic acidsï¼ which showed obvious seasonal variations in the order of summer > autumn > winter > spring. Fatty acids had the highest concentration in winter and the lowest concentration in springï¼ showing obvious bimodal advantagesï¼ with the most abundant compounds being palmitic acid and stearic acid ï¼C18ï¼. Principal component analysis and multiple linear regression ï¼MLRï¼ were used to analyze the source of organic acids in PM2.5 in Zhengzhouï¼ the results showed that 35% of the organic acids came from combustion and traffic sourcesï¼ 24% from cooking sourcesï¼ 23% from secondary formationï¼ and 17% from natural sources. The ratios of the selected marker species ï¼i.e.ï¼ di-C3 / di-C4ï¼ F/Mï¼ and C18ï¼1 / C18ï¼ were used as tracers for the secondary formation of the organic aerosol and its aging process. The results showed that the photochemical reaction was intense in summerï¼ and the proportion of organic aerosol aging or secondary production was highï¼ whereas the photochemical reaction was weak in winterï¼ and the aging degree of organic aerosol was low. Correlation analysis and MLR were used in combination to quantify the relative contribution of gas-phase oxidation and liquid-phase oxidation to dicarboxylic acid formationï¼ and the results showed that gas-phase oxidation played a dominant role in the sampling period ï¼accounting for 58%ï¼ï¼ especially in summer ï¼61%ï¼.
RESUMO
Earlier onset of rigor mortis is a critical physiological progress occurring in the development of pale soft and exudative (PSE) meat. However, how rigor cross-bridges denature under different physiological conditions and their impacts on water-holding capacity remains unclear. To address this scientific question, we firstly established a method to quantify the extent of rigor cross-bridge denaturation using skinned fibres prepared from porcine longissimus thoracis et lumborum muscle. Effects of pH and temperature on the kinetics of rigor cross-bridge denaturation, actomyosin denaturation and shrinkage of muscle fibre were studied. We then manipulated the number of rigor cross-bridges before the denaturation condition was initiated (pH 5.5, 38 °C). Results suggested that the loss of water-holding capacity in PSE meat is determined by the number of denatured rigor cross-bridges. Physiochemical analysis on myofibrils demonstrated that increase in protein oxidation, surface hydrophobicity and loss of electrostatic repulsive force between myofibrils may be involved in the mechanism.
Assuntos
Fibras Musculares Esqueléticas , Músculo Esquelético , Suínos , Animais , Miofibrilas , Carne/análise , ÁguaRESUMO
Nitrate (NO3-), sulfate (SO42-), and ammonium (NH4+) are important components of PM2.5, and studying their characteristics and influencing factors is essential for the continuous improvement of air quality. A series of online instruments were used to analyze the chemical components of PM2.5 in Zhengzhou in the summer of 2020. The results showed that the average ρ(PM2.5) was (28 ±13) µg·m-3, showing a daily variation characteristic of high at night and low during the day. The main concentrations of NO3-, SO42-, and NH4+ were (7.8 ±6.7), (7.2 ±3.7), and (5.5 ±3.1) µg·m-3, accounting for 22%, 21%, and 16% in PM2.5, respectively. The proportions of NO3- (27%) and SO42- (23%) in PM2.5, respectively, increased with the increase in PM2.5 and O3 concentration. In addition, the proportions of NO3- and NH4+ increased under low wind speed, high humidity, low temperature, and rainfall conditions. Moreover, the proportion of NO3- showed a daily variation characteristic of high at night and low during the day, whereas the opposite was true for SO42-. The gas-particle partitioning process of NH4NO3 was the main factor affecting the concentrations of NO3- and NH4+ in PM2.5. Low temperature, high humidity, and high aerosol water content concentrations favored the partitioning of HNO3 and NH3 to the particulate phase. High pH also favored the partitioning of gas-phase HNO3 to NO3-; however, it was not conducive to the partition of NH3 to NH4+. These trends partially explained the increase in the concentration and proportion of NO3- in PM2.5 under different scenarios.
RESUMO
BACKGROUND: This study aimed to evaluate the dynamic impact of the micropapillary (MIP) component on local recurrence (LR), distant metastasis (DM), and multiple recurrence (MR) of pathological stage IA3 lung adenocarcinoma. METHODS: Between July 2012 and July 2020, a total of 351 patients at two medical institutions were enrolled in this study. Cumulative incidence of curves, dynamic risk curves, and time-dependent multivariate analysis was performed to evaluate the effect of the MIP component on patients. RESULTS: The 5-year cumulative incidence of total recurrence with or without an MIP component was 34.2% and 12.3%, respectively (p = 0.001). In three recurrence patterns, our findings revealed that the 5-year cumulative incidence of LR (p = 0.048) and DM (p = 0.005) was higher in the 'MIP-present' group than in the 'MIP-absent' group. In the dynamic recurrence curve, the risk of the three recurrence patterns was different and varied over time between the two groups, especially in DM. Moreover, the dynamic cumulative event curve showed that after 1, 2, and 3 years of survival, the cumulative incidence of DM in the group with MIP continued to be higher than that in the group without MIP (all p < 0.05). Time-dependent Cox regression analysis indicated that the MIP component continued to be an independent risk factor for the cumulative incidence of DM in patients with 3-year survival. CONCLUSIONS: Of the three recurrence patterns, the MIP component mainly aggravated the risk of DM in patients with pathological stage IA3 lung adenocarcinoma, which persisted for 3 years.
Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Adenocarcinoma de Pulmão/patologia , PrognósticoRESUMO
The underlying mechanism of fluorosis has not been fully elucidated. The purpose of this study was to explore the mechanism of fluorosis induced by sodium fluoride (NaF) using proteomics. Six offspring rats exposed to fluoride without dental fluorosis were defined as group A, 8 offspring rats without fluoride exposure were defined as control group B, and 6 offspring rats exposed to fluoride with dental fluorosis were defined as group C. Total proteins from the peripheral blood were extracted and then separated using liquid chromatography-tandem mass spectrometry. The identified criteria for differentially expressed proteins were fold change > 1.2 or < 0.83 and P < 0.05. Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the oeCloud tool. The 177 upregulated and 22 downregulated proteins were identified in the A + C vs. B group. KEGG pathway enrichment analysis revealed that transforming growth factor-ß (TGF-ß) signaling pathway significantly enriched. PPI network constructed using Cytoscape confirmed RhoA may play a crucial role. The KEGG results of genes associated with fluoride and genes associated with both fluoride and inflammation in the GeneCards database also showed that TGF-ß signaling pathway was significantly enriched. The immunofluorescence in HPA database showed that the main expression sites of RhoA are plasma membrane and cytosol, while the main expression site of Fbn1 is the Golgi apparatus. In conclusion, long-term NaF intake may cause inflammatory response in the peripheral blood of rats by upregulating TGF-ß signaling pathway, in which RhoA may play a key role.
Assuntos
Intoxicação por Flúor , Fluorose Dentária , Ratos , Animais , Fluoretos/toxicidade , Proteômica/métodos , Fluoreto de Sódio/toxicidade , Biomarcadores , Transdução de Sinais , Fator de Crescimento Transformador beta/genéticaRESUMO
The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.
RESUMO
Sepsis is known to cause damage to the intestinal mucosa, leading to bacterial translocation, and exacerbation of both local and remote organ impairments. In the present study, fecal samples were collected from both septic and healthy individuals. Analysis through 16s rRNA sequencing of the fecal microbiota revealed that sepsis disrupts the balance of the gut microbial community. Recent research has highlighted the association of lipid metabolism with disease. By analyzing the fecal metabolome, four lipid metabolites that showed significant differences between the two groups were identified: PE (O-16:0/0:0), PE (17:0/0:0), PE (0:0/14:0), and PE (12:0/20:5 (5Z, 8Z, 11Z, 14Z, 17Z)). Notably, the serum levels of PE (0:0/14:0) were higher in the healthy group. Subsequent in vitro and in vivo experiments demonstrated the protective effects of this compound against sepsis-induced intestinal barrier damage. Label-free proteomic analysis showed significant differences in the expression levels of the aryl hydrocarbon receptor (AHR), a protein implicated in sepsis pathogenesis, between the LPS-Caco-2 and LPS-Caco-2 + PE (0:0/14:0) groups. Further analysis, with the help of Discovery Studio 3.5 software and co-immunoprecipitation assays, confirmed the direct interaction between AHR and PE (0:0/14:0). In the cecal ligation and puncture (CLP) model, treatment with PE (0:0 /14:0) was found to up-regulate the expression of tight junction proteins through the AHR/Cytochrome P450, family 1, subfamily A, and polypeptide 1 (CYP1A1) pathway. This highlights the potential therapeutic use of PE (0:0/14:0) in addressing sepsis-induced intestinal barrier damage.
Assuntos
Microbioma Gastrointestinal , Sepse , Humanos , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/farmacologia , Células CACO-2 , Microbioma Gastrointestinal/fisiologia , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Hidrocarboneto Arílico/uso terapêutico , RNA Ribossômico 16S , Lipopolissacarídeos/farmacologia , Proteômica , Sepse/metabolismo , Mucosa Intestinal/metabolismoRESUMO
OBJECTIVES: To establish the menstrual blood identification model based on Naïve Bayes and multivariate logistic regression methods by using specific mRNA markers in menstrual blood detection technology combined with statistical methods, and to quantitatively distinguish menstrual blood from other body fluids. METHODS: Body fluids including 86 menstrual blood, 48 peripheral blood, 48 vaginal secretions, 24 semen and 24 saliva samples were collected. RNA of the samples was extracted and cDNA was obtained by reverse transcription. Five menstrual blood-specific markers including members of the matrix metalloproteinase (MMP) family MMP3, MMP7, MMP11, progestogens associated endometrial protein (PAEP) and stanniocalcin-1 (STC1) were amplified and analyzed by electrophoresis. The results were analyzed by Naïve Bayes and multivariate logistic regression. RESULTS: The accuracy of the classification model constructed was 88.37% by Naïve Bayes and 91.86% by multivariate logistic regression. In non-menstrual blood samples, the distinguishing accuracy of peripheral blood, saliva and semen was generally higher than 90%, while the distinguishing accuracy of vaginal secretions was lower, which were 16.67% and 33.33%, respectively. CONCLUSIONS: The mRNA detection technology combined with statistical methods can be used to establish a classification and discrimination model for menstrual blood, which can distignuish the menstrual blood and other body fluids, and quantitative description of analysis results, which has a certain application value in body fluid stain identification.
Assuntos
Líquidos Corporais , Menstruação , Feminino , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Teorema de Bayes , Modelos Logísticos , Saliva , Sêmen , Genética Forense/métodosRESUMO
The intestinal epithelial barrier plays an important role during human immunodeficiency virus (HIV) disease progression. However, the extent to which the intestinal epithelial barrier is damaged in immunological non-responders (INRs) and immunological responders (IRs) is largely unknown. In this study, we investigated and compared the levels of intestinal gland damage and related molecules, including the tight junction protein claudin-1, apoptosis marker caspase-3, HIV DNA, CD4+ T cell count, and inflammation marker tumor necrosis factor-α (TNF-α) among the IRs (n = 10), INRs (n = 8), and healthy controls (HCs, n = 7). Intestinal damage was not completely restored in both INRs and IRs and was more serious in INRs than that in IRs. Moreover, intestinal damage was positively correlated with HIV DNA levels and negatively correlated with CD4+ T cell counts. These results provide insight into understanding the characteristics of intestinal epithelial barrier damage between IRs and INRs.