Ferroptosis in Obstetrical and Gynecological Diseases: A Mini Review.

Ferroptosis is an iron-dependent form of non-apoptotic cell programmed death, characterized by the disturbance of iron metabolism, accumulation of lipid peroxides and disruption of cellular antioxidant system. Ferroptosis induces oxidative cell death through decrease of antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in cells. In recent years, studies have confirmed that ferroptosis is closely related to numerous organ injuries, degenerative pathologies and even the tumorigenesis and therapeutic resistance of tumors. While the effect of ferroptosis in obstetrical and gynecological diseases remains unclear and the relevant researches are still limited. In this review, we summarize the current understanding of the molecular mechanisms and regulatory networks of ferroptosis, together with the potential physiological functions and pathological roles of ferroptosis in clinical obstetrical and gynecological diseases. Importantly, our review also aims to provide references for further understanding of its pathogenesis and explore potential therapeutic strategies for targeting ferroptosis in clinical obstetrical and gynecological diseases.

Structural Perspectives on Metal Dependent Roles of Ferric Uptake Regulator (Fur).

Iron is crucial for the metabolism and growth of most prokaryotic cells. The ferric uptake regulator (Fur) protein plays a central role in regulating iron homeostasis and metabolic processes in bacteria. It ensures the proper utilization of iron and the maintenance of cellular functions in response to environmental cues. Fur proteins are composed of an N-terminal DNA-binding domain (DBD) and a C-terminal dimerization domain (DD), typically existing as dimers in solution. Fur proteins have conserved metal-binding sites named S1, S2, and S3. Among them, site S2 serves as a regulatory site, and metal binding at S2 results in conformational changes. Additionally, as a transcriptional regulator, Fur specifically binds to a consensus DNA sequence called the Fur box. To elucidate the structural and functional properties of Fur proteins, various structures of metal- or DNA-bound Fur proteins or apo-Fur proteins have been determined. In this review, we focus on the structural properties of Fur proteins according to their ligand-bound state and the drug development strategies targeting Fur proteins. This information provides valuable insights for drug discovery.

CD47 and IFT57 Are Colinear Genes That Are Highly Coexpressed in Most Cancers and Exhibit Parallel Cancer-Specific Correlations with Survival.

An association between high CD47 expression and poor cancer survival has been attributed to its function on malignant cells to inhibit phagocytic clearance. However, CD47 mRNA expression in some cancers lacks correlation or correlates with improved survival. IFT57 encodes an essential primary cilium component and is colinear with CD47 across amniote genomes, suggesting coregulation of these genes. Analysis of The Cancer Genome Atlas datasets identified IFT57 as a top coexpressed gene with CD47 among 1156 human cancer cell lines and in most tumor types. The primary cilium also regulates cancer pathogenesis, and correlations between IFT57 mRNA and survival paralleled those for CD47 in thyroid and lung carcinomas, melanoma, and glioma. CD47 ranked first for coexpression with IFT57 mRNA in papillary thyroid carcinomas, and higher expression of both genes correlated with significantly improved overall survival. CD47 and IFT57 mRNAs were coordinately regulated in thyroid carcinoma cell lines. Transcriptome analysis following knockdown of CD47 or IFT57 in thyroid carcinoma cells identified the cytoskeletal regulator CRACD as a specific target of IFT57. CRACD mRNA expression inversely correlated with IFT57 mRNA and with survival in low-grade gliomas, lung adenocarcinomas, and papillary thyroid carcinomas, suggesting that IFT57 rather than CD47 regulates survival in these cancers.

An ADPLL-Based GFSK Modulator with Two-Point Modulation for IoT Applications.

To establish ubiquitous and energy-efficient wireless sensor networks (WSNs), short-range Internet of Things (IoT) devices require Bluetooth low energy (BLE) technology, which functions at 2.4 GHz. This study presents a novel approach as follows: a fully integrated all-digital phase-locked loop (ADPLL)-based Gaussian frequency shift keying (GFSK) modulator incorporating two-point modulation (TPM). The modulator aims to enhance the efficiency of BLE communication in these networks. The design includes a time-to-digital converter (TDC) with the following three key features to improve linearity and time resolution: fast settling time, low dropout regulators (LDOs) that adapt to process, voltage, and temperature (PVT) variations, and interpolation assisted by an analog-to-digital converter (ADC). It features a digital controlled oscillator (DCO) with two key enhancements as follows: ΔΣ modulator dithering and hierarchical capacitive banks, which expand the frequency tuning range and improve linearity, and an integrated, fast-converging least-mean-square (LMS) algorithm for DCO gain calibration, which ensures compliance with BLE 5.0 stable modulation index (SMI) requirements. Implemented in a 28 nm CMOS process, occupying an active area of 0.33 mm2, the modulator demonstrates a wide frequency tuning range of from 2.21 to 2.58 GHz, in-band phase noise of -102.1 dBc/Hz, and FSK error of 1.42% while consuming 1.6 mW.

The MarR family regulator RmaH mediates acid tolerance of Lactococcus lactis through regulating peptidoglycan modification genes.

Lactococcus lactis, widely used in the food fermentation industry, has developed various ways to regulate acid adaptation in the process of evolution. The investigation into how peptidoglycan (PG) senses and responds to acid stress is an expanding field. Here, we addressed the regulation of murT-gatD genes which are responsible for the amidation of PG D-Glu. We found that lactic acid stress reduced murT-gatD expression, and overexpressing these genes notably decreased acid tolerance of L. lactis NZ9000, possibly due to a reduction in PG's negative charge, facilitating the influx of extracellular protons into the cell. Subsequently, using a combination of DNA pull-down assay and electrophoretic mobility shift assay (EMSA), we identified a novel MarR family regulator, RmaH, as an activator of murT-gatD transcription. Further MEME motif prediction, EMSA verification and fluorescent protein reporter assay showed that RmaH directly bound to the DNA motif 5'-KGVAWWTTTTGCT-3' located in the upstream region of murT-gatD. Beyond the mechanistic investigation of RmaH activation of murT-gatD, this study provides new insight into how peptidoglycan modification is regulated and responds to lactic acid stress.

Word of caution: early life-threatening complication linked to pulmonary flow restrictors.

A two-month-old female infant (3.4 kg, 50 cm) with Down syndrome and congenital heart disease underwent unsuccessful transcatheter ductal closure, followed by bilateral implantation of manually modified microvascular plugs (MVP-9Q) from Medtronic Inc., USA, used as pulmonary flow restrictors (PFRs). Post-procedure, she developed febrile respiratory distress, leading to ICU admission. Despite initial improvement, she was readmitted with respiratory syncytial virus infection, progressing to bilateral pneumonic consolidation. Subsequent complications included PA aneurysmal dilatation attributed to PFRs, necessitating urgent surgery to remove the PFRs and repair the PA injuries, followed by management including extracorporeal support and targeted antibiotics. The patient demonstrated recovery over 12 months.

Small molecule communication of Legionella: the ins and outs of autoinducer and nitric oxide signaling.

SUMMARYLegionella pneumophila is a Gram-negative environmental bacterium, which survives in planktonic form, colonizes biofilms, and infects protozoa. Upon inhalation of Legionella-contaminated aerosols, the opportunistic pathogen replicates within and destroys alveolar macrophages, thereby causing a severe pneumonia termed Legionnaires' disease. Gram-negative bacteria employ low molecular weight organic compounds as well as the inorganic gas nitric oxide (NO) for cell-cell communication. L. pneumophila produces, secretes, and detects the α-hydroxyketone compound Legionella autoinducer-1 (LAI-1, 3-hydroxypentadecane-4-one). LAI-1 is secreted by L. pneumophila in outer membrane vesicles and not only promotes communication among bacteria but also triggers responses from eukaryotic cells. L. pneumophila detects NO through three different receptors, and signaling through the volatile molecule translates into fluctuations of the intracellular second messenger cyclic-di-guanylate monophosphate. The LAI-1 and NO signaling pathways are linked via the pleiotropic transcription factor LvbR. In this review, we summarize current knowledge about inter-bacterial and inter-kingdom signaling through LAI-1 and NO by Legionella species.

Unveiling the molecular mechanisms of the type IX secretion system's response regulator: Structural and functional insights.

The type IX secretion system (T9SS) is a nanomachinery utilized by bacterial pathogens to facilitate infection. The system is regulated by a signaling cascade serving as its activation switch. A pivotal member in this cascade, the response regulator protein PorX, represents a promising drug target to prevent the secretion of virulence factors. Here, we provide a comprehensive characterization of PorX both in vitro and in vivo. First, our structural studies revealed PorX harbors a unique enzymatic effector domain, which, surprisingly, shares structural similarities with the alkaline phosphatase superfamily, involved in nucleotide and lipid signaling pathways. Importantly, such pathways have not been associated with the T9SS until now. Enzymatic characterization of PorX's effector domain revealed a zinc-dependent phosphodiesterase activity, with active site dimensions suitable to accommodate a large substrate. Unlike typical response regulators that dimerize via their receiver domain upon phosphorylation, we found that zinc can also induce conformational changes and promote PorX's dimerization via an unexpected interface. These findings suggest that PorX can serve as a cellular zinc sensor, broadening our understanding of its regulatory mechanisms. Despite the strict conservation of PorX in T9SS-utilizing bacteria, we demonstrate that PorX is essential for virulence factors secretion in Porphyromonas gingivalis and affects metabolic enzymes secretion in the nonpathogenic Flavobacterium johnsoniae, but not for the secretion of gliding adhesins. Overall, this study advances our structural and functional understanding of PorX, highlighting its potential as a druggable target for intervention strategies aimed at disrupting the T9SS and mitigating virulence in pathogenic species.

Peer review of the pesticide risk assessment of the active substance 1-methylcyclopropene.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State The Netherlands for the pesticide active substance 1-methylcyclopropene are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council for an amendment in approval conditions. The current approval of 1-methylcyclopropene includes the specific provision 'Only uses as plant growth regulator for post-harvest storage in sealable warehouse may be authorised'. The applicant AgroFresh Holding France SAS submitted, in accordance with Article 7 of Reg. (EC) 1107/2009, an application to remove this specific provision in order to allow member states to authorise the use of products containing 1-methylcyclopropene on outdoor crops pre-harvest. The conclusions were reached on the basis of the evaluation of the representative use(s) of 1-methylcyclopropene as a plant growth regulator via spray application on pome fruit. The reliable endpoints, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Molecular characterization of PSEUDO RESPONSE REGULATOR family in Rosaceae and function of PbPRR59a and PbPRR59b in flowering regulation.

BACKGROUND: PSEUDO RESPONSE REGULATOR (PRR) genes are essential components of circadian clock, playing vital roles in multiple processes including plant growth, flowering and stress response. Nonetheless, little is known about the evolution and function of PRR family in Rosaceae species. RESULTS: In this study, a total of 43 PRR genes in seven Rosaceae species were identified through comprehensive analysis. The evolutionary relationships were analyzed with phylogenetic tree, duplication events and synteny. PRR genes were classified into three groups (PRR1, PRR5/9, PRR3/7). The expansion of PRR family was mainly derived from dispersed and whole-genome duplication events. Purifying selection was the major force for PRR family evolution. Synteny analysis indicated the existence of multiple orthologous PRR gene pairs between pear and other Rosaceae species. Moreover, the conserved motifs of eight PbPRR proteins supported the phylogenetic relationship. PRR genes showed diverse expression pattern in various tissues of pear (Pyrus bretschneideri). Transcript analysis under 12-h light/ dark cycle and constant light conditions revealed that PRR genes exhibited distinct rhythmic oscillations in pear. PbPRR59a and PbPRR59b highly homologous to AtPRR5 and AtPRR9 were cloned for further functional verification. PbPRR59a and PbPRR59b proteins were localized in the nucleus. The ectopic overexpression of PbPRR59a and PbPRR59b significantly delayed flowering in Arabidopsis transgenic plants by repress the expression of AtGI, AtCO and AtFT under long-day conditions. CONCLUSIONS: These results provide information for exploring the evolution of PRR genes in plants, and contribute to the subsequent functional studies of PRR genes in pear and other Rosaceae species.

Canalizing kernel for cell fate determination.

The tendency for cell fate to be robust to most perturbations, yet sensitive to certain perturbations raises intriguing questions about the existence of a key path within the underlying molecular network that critically determines distinct cell fates. Reprogramming and trans-differentiation clearly show examples of cell fate change by regulating only a few or even a single molecular switch. However, it is still unknown how to identify such a switch, called a master regulator, and how cell fate is determined by its regulation. Here, we present CAESAR, a computational framework that can systematically identify master regulators and unravel the resulting canalizing kernel, a key substructure of interconnected feedbacks that is critical for cell fate determination. We demonstrate that CAESAR can successfully predict reprogramming factors for de-differentiation into mouse embryonic stem cells and trans-differentiation of hematopoietic stem cells, while unveiling the underlying essential mechanism through the canalizing kernel. CAESAR provides a system-level understanding of how complex molecular networks determine cell fates.

Functional characterization of two survival factor 1 genes in Mucor lusitanicus.

Survival factor 1 (Svf1) protein has been described in some ascomycetous fungi where it was found to be contributing to several essential physiological processes, such as response to osmotic, oxidative and cold stresses, sphingolipid biosynthesis, morphogenesis, sporulation, antifungal resistance, and pathogenicity. It was also suggested that it can be a novel central regulator affecting the expression of various genes. In the present study, function of this protein and the encoding genes is described for the first time in a fungus (i.e., in Mucor lusitanicus) belonging to the order Mucorales. M. lusitanicus has two putative svf1 genes named svf1a and svf1b. Expression of both genes was proven. Although the expression of svf1a was affected by several environmental stresses and knocking out the gene affected adaptation to low temperatures and the sporulation ability, the main survival factor functions, such as participation in the maintenance of the viability, the response to oxidative and cold stresses, and the sphingolipid biosynthesis, could be associated with Svf1b, suggesting a central regulatory role to this protein. Interestingly, knockout of both genes affected the pathogenicity of the fungus in a Drosophila model. IMPORTANCE: Mucor lusitanicus is a widely used model organism to study various biological processes in the basal fungal group Mucorales. Several members of this group can be agents of mucormycosis, an opportunistic fungal infection, which is associated with high mortality, rapid progression, and wide resistance to the commonly used antifungal agents. Svf1 proteins have so far only been identified in fungi, where they have been involved in pathogenicity and resistance to antifungal agents in many cases. Only a limited number of factors affecting the stress response, antifungal resistance, and virulence of Mucorales fungi have been revealed. Elucidating the function of a fungus-specific protein that may regulate these processes may bring us closer to understanding the pathogenesis of these fungi.

Glucagon-like-peptide-1 agonist therapy in adults with cystic fibrosis.

Glucagon-like-peptide-1 (GLP-1) agonists are commonly used to improve glycemic control and promote weight loss in individuals with type 2 diabetes mellitus (T2DM) and/or obesity. However, there is a paucity of evidence regarding GLP-1 agonist use in people with cystic fibrosis (pwCF). We present 11 people with CF (males: 3, females: 7; age range 24-47; BMI range 25.7-43.7) treated with GLP-1 agonists (semaglutide: 9,tirzepatide: 2) for variable duration (1-50 months). All experienced weight loss on GLP- 1 agonist therapy (median change in weight = -7.2 kg; change in BMI [kg/m2] = -0.9 to -8.1). Eight pwCF showed improvement in percent predicted forced expiratory volume in 1 second (ppFEV1) [change = -5 to + 18] and nine pwCF showed improvement in percent predicted forced vital capacity (ppFVC) [change= +1 to + 26]. Of the 7 pwCF with CFRD, all reduced their insulin quantity (mean, 31.5 % decrease in total daily insulin dose), and glucose time in range improved for most (mean, +11 % increase from baseline). Four pwCF stopped using GLP-1 agonists: 2 due to severe nausea/vomiting, 1 due to lack of perceived benefit, and 1 due to change in insurance coverage. This report is the largest published series to date of pwCF treated with GLP-1 agonist therapy. With the addition of GLP-1 agonists, all individuals experienced weight loss and a reduction in daily insulin dose, and most had improvement in pulmonary function. Future multi-center studies are needed to corroborate the efficacy and safety of these agents in the CF population.

Functional and radiological sinonasal outcomes of CFTR modulators for sinus disease in cystic fibrosis: A meta-analysis.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in cystic fibrosis (CF) by stabilizing the CFTR protein on respiratory epithelial surfaces. To determine the efficacy of CFTR modulators on sinonasal outcomes in patients with CF, we performed a meta-analysis of clinical trials to date that include functional and radiographic evidence of sinus disease. METHODS: English full-text articles were searched in PubMed, Embase, and Scopus databases. Two reviewers screened articles and a third reviewer resolved disagreements. Articles were included if they reported functional or radiological sinonasal outcomes in patients with CF before and after CFTR modulator therapies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the risk of bias in non-randomized studies of interventions tool was used for quality assessment. The generic inverse variance method with random effects model was used for meta-analysis. Standardized mean difference (SMD) and mean difference (MD) were used as effect measurements. RESULTS: Seven prospective and two retrospective studies representing 248 patients were included in this analysis. There was a significant improvement in sinonasal outcome test-22 scores on elexacaftor‒tezacaftor‒ivacaftor (MD = 12.80, [95% confidence interval, CI: 10.46‒15.13], p < 0.001, n = 222), with no heterogeneity detected (I2 = 0%, p = 0.820). There was also a significant improvement in Lund‒Mackay scores (SMD = 1.25, [95% CI: 0.58‒1.91], p < 0.001, n = 88), with heterogeneity detected (I2 = 67%, p = 0.030). CONCLUSIONS: CFTR modulators improve functional and radiologic sinonasal outcomes. Given the utility of CFTR modulators, the treatment paradigm for CF-related chronic rhinosinusitis promises to evolve.

A 640 nA IQ Output-Capacitor-Less Low Dropout (LDO) Regulator with Sub-Threshold Slew-Rate Enhancement for Narrow Band Internet of Things (NB-IoT) Applications.

An ultra-low quiescent current output-capacitor-less low dropout (OCL-LDO) regulator for power-sensitive applications is proposed in this paper. To improve the gain of the OCL-LDO feedback loop, the error amplifier employs a combination of a cross-coupled input stage for boosting the equivalent input transconductance and a negative resistance technique to improve the gain. Meanwhile, in order to address the issue of transient response of the ultra-low quiescent current OCL-LDO, a sub-threshold slew-rate enhancement circuit is proposed in this paper, which consists of a transient signal input stage and a slew-rate current increase branch. The proposed OCL-LDO is fabricated in a 0.18 µm CMOS process with an effective area of 0.049 mm2. According to the measurement results, the proposed OCL-LDO has a maximum load current of 100 mA and a minimum quiescent current of 640 nA at an input voltage of 1.2 V and an output voltage of 1 V. The overshoot and undershoot voltages are 197 mV and 201 mV, respectively, and the PSR of the OCL-LDO is -72.4 dB at 1 kHz when the load current is 100 µA. In addition, the OCL-LDO has a load regulation of 7.6 µV/mA and a line regulation of 0.87 mV/V.

Engineered sensor actuator modulator as aqueous humor outflow actuator for gene therapy of primary open-angle glaucoma.

Glaucoma, a blinding eye disease with optic neuropathy, is usually associated with elevated intraocular pressure (IOP). The currently available pharmacological and surgical treatments for glaucoma have significant limitations and side effects, which include systemic reactions to medications, patient non-compliance, eye infections, surgical device failure, and damage to the eye. Here, we present Sensor-Actuator-Modulator (SAM), an engineered double mutant version of the bacterial stretch-activated mechanosensitive channel of large conductance (MscL) that directly senses tension in the membrane lipid bilayer of cells and in response, transiently opens its large nonspecific pore to release cytoplasmic fluid. The heterologously expressed mechanosensitive SAM channel acts as a tension-activated pressure release valve in trabeculocytes. In the trabecular meshwork (TM), SAM is activated by membrane stretch caused by elevated IOP. We have identified several SAM variants that are activated at physiologically relevant pressures. Using this barogenetic technology, we have demonstrated that SAM is functional in cultured TM cells, and successfully transduced in vivo in TM cells by use of AAV2/8. Further, it is effective in enhancing aqueous humor outflow facility leading to lowering the IOP in a mouse model of ocular hypertension.

Autoregulation of intraocular pressure via expression of a mechanosensitive channel of large conductance in trabecular meshwork serves as a mutation-agnostic gene therapy for glaucoma.

Enhancing growth and phytoremediation efficiency of Pennisetum purpureum cv. Mahasarakham in weathered PAH-contaminated soil through thidiazuron application.

Polycyclic aromatic hydrocarbons (PAHs) are phytotoxic, which can limit their phytoremediation. When the ability of plants to phytoremediation PAHs is compromised, the application of plant growth regulators can enhance the growth of the plants. This study aimed to determine the best plant growth regulator (1-naphthalene acetic acid, 6-benzyladenine, or thidiazuron) to enhance the phytoremediation ability of sweet grass (Pennisetum purpureum cv. Mahasarakham) when grown in weather PAH-contaminated soil. In a greenhouse study, 0.01 mg/l thidiazuron resulted in the highest growth of sweet grass when compared to the other tested plant growth regulators (dry shoot weight 24.11 ± 1.28 g and dry root weight 0.70 ± 0.02 g). Sweet grass was grown in soil contaminated with PAH, which demonstrated the toxicity to sweet grass by reducing the total chlorophyll (1.01 µg/g fresh weight) and carotenoid (0.28 µg/g fresh weight) contents with proline increased (6.63 µg/g fresh weight). Meanwhile, total chlorophyll, carotenoid, and proline content in leaves of sweet grass grown in non-contaminated soil were 1.68, 0.44, and 5.23 µg/g fresh weight, respectively. When sweet grass was used to phytoremediate PAHs, there were reductions in acenaphthylene (4.69 ± 0.50%), acenaphthene (10.69 ± 1.47%), and phenanthrene (3.61 ± 0.07%), which compared to levels of over 30% in non-planted soil. For the three PAHs, the bioconcentration factors were 1.6 to 2.4, but the translocation factors were below 1, showing limited movement to the aerial parts of the plant, thereby suggesting that the main mechanism is rhizoremediation. Sweet grass is an excellent candidate for PAH remediation, especially when thidiazuron is applied to relieve plant stress.

Thidiazuron at 0.01 mg/l was the best plant growth regulator to stimulate the growth of sweet grass when compared to 1-naphthalene acetic acid and 6-benzyladenine. Sweetgrass enhanced the removal of acenaphthylene, acenaphthene, and phenanthrene from contaminated soil. A possible mechanism for polycyclic aromatic hydrocarbon (PAH) remediation was rhizoremediation, as the accumulation of PAH in sweet grass biomass was limited, and the translocation factor from the root to the shoot was lower than 1. Thidiazuron may indirectly enhance the PAH phytoremediation by sweet grass via increased plant tolerance to PAH toxicity.

BmfR, a novel GntR family regulator, regulates biofilm formation in marine-derived, Bacillus methylotrophicus B-9987.

Biofilms are common living states for microorganisms, allowing them to adapt to environmental changes. Numerous Bacillus strains can form complex biofilms that play crucial roles in biocontrol processes. However, our current understanding of the molecular mechanisms of biofilm formation in Bacillus is mainly based on studies of Bacillus subtilis. Knowledge regarding the biofilm formation of other Bacillus species remains limited. In this study, we identified a novel transcriptional regulator, BmfR, belonging to the GntR family, that regulates biofilm formation in marine-derived Bacillus methylotrophicus B-9987. We demonstrated that BmfR induces biofilm formation by activating the extracellular polysaccharide structural genes epsA-O and negatively regulating the matrix gene repressor, SinR; of note it positively affects the expression of the master regulator of sporulation, Spo0A. Furthermore, database mining for BmfR homologs has revealed their widespread distribution among many bacterial species, mainly Firmicutes and Proteobacteria. This study advances our understanding of the biofilm regulatory network of Bacillus strains, and provides a new target for exploiting and manipulating biofilm formation.

[Role of reactive oxygen species/silent information regulator 1 in hyperoxia-induced bronchial epithelial cell injury]. / 活性氧簇/æ²‰é»˜ä¿¡æ¯è°ƒèŠ‚å› å­1在高氧致支气管上皮细胞损伤中的作用.

OBJECTIVES: To investigate the effect of reactive oxygen species (ROS)/silent information regulator 1 (SIRT1) on hyperoxia-induced mitochondrial injury in BEAS-2B cells. METHODS: The experiment was divided into three parts. In the first part, cells were divided into H0, H6, H12, H24, and H48 groups. In the second part, cells were divided into control group, H48 group, H48 hyperoxia+SIRT1 inhibitor group (H48+EX 527 group), and H48 hyperoxia+SIRT1 agonist group (H48+SRT1720 group). In the third part, cells were divided into control group, 48-hour hyperoxia+N-acetylcysteine group (H48+NAC group), and H48 group. The ROS kit was used to measure the level of ROS. Western blot and immunofluorescent staining were used to measure the expression levels of SIRT1 and mitochondria-related proteins. Transmission electron microscopy was used to observe the morphology of mitochondria. RESULTS: Compared with the H0 group, the H6, H12, H24, and H48 groups had a significantly increased fluorescence intensity of ROS (P<0.05), the H48 group had significant reductions in the expression levels of SIRT1 protein and mitochondria-related proteins (P<0.05), and the H24 and H48 groups had a significant reduction in the fluorescence intensity of mitochondria-related proteins (P<0.05). Compared with the H48 group, the H48+SRT1720 group had significant increases in the expression levels of mitochondria-related proteins and the mitochondrial aspect ratio (P<0.05), and the H48+EX 527 group had a significant reduction in the mitochondrial area (P<0.05). Compared with the H48 group, the H48+NAC group had a significantly decreased fluorescence intensity of ROS (P<0.05) and significantly increased levels of SIRT1 protein, mitochondria-related proteins, mitochondrial area, and mitochondrial aspect ratio (P<0.05). CONCLUSIONS: The ROS/SIRT1 axis is involved in hyperoxia-induced mitochondrial injury in BEAS-2B cells.

The novel MFS efflux pump SxtP, regulated by the LysR-type transcriptional activator SxtR, is involved in the susceptibility to sulfamethoxazole/trimethoprim (SXT) and the pathogenesis of Acinetobacter baumannii.

Acinetobacter baumannii is a notorious opportunistic pathogen responsible for healthcare-associated infections worldwide. Efflux pumps play crucial roles in mediating antimicrobial resistance, motility, and virulence. In this study, we present the identification and characterization of the new A. baumannii efflux pump SxtP belonging to the MFS superfamily (major facilitator superfamily), along with its associated activator LysR-type transcriptional regulator (LTTR) SxtR, demonstrating their roles in sulfamethoxazole/trimethoprim (also known as co-trimoxazole or SXT) resistance, surface-associated motility and virulence.