A novel flexible nerve guidance conduit promotes nerve regeneration while providing excellent mechanical properties.

JOURNAL/nrgr/04.03/01300535-202507000-00029/figure1/v/2024-09-09T124005Z/r/image-tiff Autografting is the gold standard for surgical repair of nerve defects > 5 mm in length; however, autografting is associated with potential complications at the nerve donor site. As an alternative, nerve guidance conduits may be used. The ideal conduit should be flexible, resistant to kinks and lumen collapse, and provide physical cues to guide nerve regeneration. We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them. Subsequently, we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen. The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers. The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability. Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model, suggesting that it has potential for clinical use in human nerve injuries.

The ubiquitin E3 ligase RZFP1 affects drought tolerance in poplar by mediating the degradation of the protein phosphatase PP2C-9.

Abscisic acid signaling has been implicated in plant responses to water deficit-induced osmotic stress. However, the underlying molecular mechanism remains unelucidated. This study identified the RING-type E3 ubiquitin ligase RING ZINC FINGER PROTEIN1 (PtrRZFP1) in poplar (Populus trichocarpa), a woody model plant. PtrRZFP1 encodes a ubiquitin E3 ligase that participates in protein ubiquitination. PtrRZFP1 mainly functions in the nucleus and endoplasmic reticulum and is activated by drought and abscisic acid. PtrRZFP1-overexpressing transgenic poplars (35S:PtrRZFP1) showed greater tolerance to drought, whereas PtrRZFP1-knockdown lines (KD-PtrRZFP1) showed greater sensitivity to drought. Under treatment with polyethylene glycol and abscisic acid, PtrRZFP1 promoted the production of NO and H2O2 in stomatal guard cells, ultimately enhancing stomatal closure and improving drought tolerance. Additionally, PtrRZFP1 physically interacted with the clade A Protein Phosphatase 2C protein PtrPP2C-9, a core regulator of abscisic acid signaling, and mediated its ubiquitination and eventual degradation through the ubiquitination-26S proteasome system, indicating that PtrRZFP1 positively regulates the abscisic acid signaling pathway. Furthermore, the PtrPP2C-9-overexpression line was insensitive to abscisic acid and more sensitive to drought than the wild-type plants, whereas the opposite phenotype was observed in 35S:PtrRZFP1 plants. In general, PtrRZFP1 negatively regulates the stability of PtrPP2C-9 to mediate poplar drought tolerance. The results of this study provide a theoretical framework for the targeted breeding of drought-tolerant traits in perennial woody plants.

Effects of direction specific exercise training on athletic performance: a systematic review and meta-analysis.

Background: The similarity between movement patterns and force-vector specificity of training exercises and the target movement will likely result in the greatest transfer of the practiced skills and physical abilities to the intended sports skill performance. Therefore, this review aimed to investigate whether specific adaptations in athletic performance would be observed following direction specific exercise training. Methodology: The literature search was performed in PubMed, Web of Science, and MEDLINE. Studies comparing acute (post-activation potentiation enhancement) and short-term (>2 weeks) effects of horizontally vs. vertically oriented resistance and plyometric training on athletic performance of recreationally active participants of either sex were included. The effect sizes were determined using a robust variance estimation random-effects model and were reported as Hedge's g. Results: Twenty-two studies were included. For acute studies (n = 4), a small non-significant effect favoring horizontal training (HT) for sprint performance improvements (g = -0.19, p = 0.17) was evident. For short-term studies (n = 18), the results showed non-significant, small to large differences between HT and vertical training (VT) in pooled vertical and horizontal jump improvements (g = 0.06, p = 0.67), vertical (g = 0.21, p = 0.17) and horizontal jump (g = -0.15, p = 0.40), pooled vertical and horizontal maximal strength (g = 0.27, p = 0.42), horizontal (g = -0.83, p = 0.16) and vertical maximal strength (g = 0.78, p = 0.28), pooled short and medium distance sprint (g = -0.23, p = 0.16), short (g = -0.33 [-0.85, 0.19], p = 0.19) and medium (g = -0.12 [-0.37, 0.13], p = 0.28) distance sprint, and COD speed and maneuverability (g = -0.45, p = 0.26). Conclusions: HT and VT were both equally effective in improving vertically and horizontally athletic performance, potentially refuting the theory of directional specificity of training on athletic performance outcomes.

Characterization of the complete mitogenome of Tiarella polyphylla, commonly known as Asian foamflower: insights into the multi-chromosomes structure and DNA transfers.

BACKGROUND: Tiarella polyphylla D. Don has been traditionally used to cure asthma and skin eruptions. However, the sequence and the structure of the mitogenome of T. polyphylla remained elusive, limiting the genomic and evolution analysis based on the mitogenome. RESULTS: Using a combination of Illumina and Nanopore sequencing reads, we de novo assembled the complete mitogenome of T. polyphylla. In addition to unveiling the major configuration of the T. polyphylla mitogenome was three circular chromosomes with lengths of 430,435 bp, 126,943 bp, and 55,269 bp, we revealed five (R01-R05) and one (R06) repetitive sequence could mediate the intra- and inter-chromosomal recombination, respectively. Furthermore, we identified 208 short and 25 long tandem segments, seven cp-derived mtDNAs, 106 segments of mtDNAs transferred to the nuclear genome, and 653 predicted RNA editing sites. Based on the sequence of the mitogenomes, we obtained the resolved phylogeny of the seven Saxifragales species. CONCLUSIONS: These results presented the mitogenome features and expanded its potential applications in phylogenetics, species identification, and cytoplasmic male sterility (CMS) in the future.

Correlation between Interleukin-10 Effects on Th1/Th2 Immune Balance and Pregnancy Induced Hypertension.

OBJECTIVE: Pregnancy induced hypertension (PIH) is a common disease in obstetrics. CD4+ T cells can be divided into Th1 and Th2 sub-populations. Imbalance between Th1 and Th2 directly affects body immune status and participates in PIH occurrence and progression. Whether IL-10 affects Th1/Th2 immune balance as a negative regulator of immune response in PIH remains unknown. The aim of the present study was to investigate the role of IL-10 in PIH. METHODS: A total of 52 PIH patients were recruited and divided into mild-moderate and severe PIH groups in parallel with 25 normal pregnant women as a control group. Real-time PCR was used to test mRNA levels of Th1 cytokines IL-2, tumor necrosis factor-α (TNF-α), and Th2 cytokines IL-4, IL-6, and IL-10. Enzyme linked immunosorbent assay (ELISA) tested serum levels of cytokines to analyze their correlation with disease progression. RESULTS: Our results showed PIH patients had significantly elevated IL-2 and TNF-α levels and decreased IL-4, IL-6, or IL-10 expressions compared with the control group (p<0.05). With disease progression, IL-4, IL-6, and IL-10 expressions were further decreased while IL-2 and TNF-α were increased (p<0.05). Moreover, IL-10 was negatively correlated with Th1 cytokines IL-2 and TNF-α while being positively correlated with Th2 cytokines IL-4 and IL-6. In addition, IL-10 was negatively correlated with PIH severity (p<0.05). CONCLUSION: IL-10 can affect Th1/Th2 immune balance and is associated with PIH severity, suggesting IL-10 might be a risk factor for PIH occurrence and progression.

Qualitative exploration of the lived experiences of loneliness in later life to inform technology development.

PURPOSE: Loneliness is a negative emotional state which is common in later life. The accumulative effects of loneliness have a significant impact on the physical and mental health of older adults. We aim to qualitatively explore the experiences of loneliness in later life and identify relevant behaviours and indicators which will inform novel methods of loneliness detection and intervention. METHODS: We conducted 60 semi-structured interviews with people aged 65 and over between September 2022 and August 2023. Data were analysed using a reflective thematic approach with early theme development on NVIVO software. RESULTS: Three themes were identified from the experiences of loneliness in older adults. 1) Unique responses to loneliness, including crying, increased eating or drinking and sleep difficulties, 2) Age-related losses, such as networks, roles, and abilities to engage in activities reducing over time and 3) Individual differences in overcoming loneliness, where strategies such as keeping busy and adopting a positive mindset were impacted by motivation and mood of older adults. CONCLUSION: Distinct signs and relevant factors to loneliness in later life have been identified which can be detected by future sensing technologies. Findings of this in-depth qualitative study highlight that loneliness is a subjective experience requiring a holistic and person-centred approach to detection and intervention.

Hepatic and extrahepatic metabolic modulation in hbv-related decompensated cirrhosis and acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (RatioHep/Port, RatioPeri/Hep, and RatioPort/Peri) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher RatioPeri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher RatioPort/Peri of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.

The inertial-based gait normalcy index of dual task cost during turning quantifies gait automaticity improvement in early-stage Parkinson's rehabilitation.

BACKGROUND: The loss of gait automaticity is a key cause of motor deficits in Parkinson's disease (PD) patients, even at the early stage of the disease. Action observation training (AOT) shows promise in enhancing gait automaticity. However, effective assessment methods are lacking. We aimed to propose a novel gait normalcy index based on dual task cost (NIDTC) and evaluate its validity and responsiveness for early-stage PD rehabilitation. METHODS: Thirty early-stage PD patients were recruited and randomly assigned to the AOT or active control (CON) group. The proposed NIDTC during straight walking and turning tasks and clinical scale scores were measured before and after 12 weeks of rehabilitation. The correlations between the NIDTCs and clinical scores were analyzed with Pearson correlation coefficient analysis to evaluate the construct validity. The rehabilitative changes were assessed using repeated-measures ANOVA, while the responsiveness of NIDTC was further compared by t tests. RESULTS: The turning-based NIDTC was significantly correlated with multiple clinical scales. Significant group-time interactions were observed for the turning-based NIDTC (F = 4.669, p = 0.042), BBS (F = 6.050, p = 0.022) and PDQ-39 (F = 7.772, p = 0.011) tests. The turning-based NIDTC reflected different rehabilitation effects between the AOT and CON groups, with the largest effect size (p = 0.020, Cohen's d = 0.933). CONCLUSION: The turning-based NIDTC exhibited the highest responsiveness for identifying gait automaticity improvement by providing a comprehensive representation of motor ability during dual tasks. It has great potential as a valid measure for early-stage PD diagnosis and rehabilitation assessment. Trial registration Chinese Clinical Trial Registry: ChiCTR2300067657.

MEOX1 triggers myofibroblast apoptosis resistance, contributing to pulmonary fibrosis in mice.

The apoptosis resistance of myofibroblasts is a hallmark in the irreversible progression of pulmonary fibrosis (PF). While the underlying molecular mechanism remains elusive. In this study, we unveiled a previously unrecognized mechanism underlying myofibroblast apoptosis resistance during PF. Our investigation revealed heightened expression of mesenchyme homeobox 1 (MEOX1) in the lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin-induced PF mice. Silencing MEOX1 significantly attenuated PF progression in mice. In vitro, we found a notable increase in MEOX1 expression in transforming growth factor-ß1 (TGF-ß1)-induced myofibroblasts. Silencing MEOX1 enhanced apoptosis of myofibroblasts. Mechanistically, we identified G-protein signaling pathway regulatory factor 4 (RGS4) as a critical downstream target of MEOX1, as predicted by bioinformatics analysis. MEOX1 enhanced apoptosis resistance by upregulating RGS4 expression in myofibroblasts. In conclusion, our study highlights MEOX1 as a promising therapeutic target for protecting against PF by modulating myofibroblast apoptosis resistance.

Neutrophil extracellular traps trigger alveolar epithelial cell necroptosis through the cGAS-STING pathway during acute lung injury in mice.

Extensive loss of alveolar epithelial cells (AECs) undergoing necroptosis is a crucial mechanism of acute lung injury (ALI), but its triggering mechanism needs to be thoroughly investigated. Neutrophil extracellular traps (NETs) play a significant role in ALI. However, the effect of NETs on AECs' death has not been clarified. Our study found that intratracheal instillation of NETs disrupted lung tissue structure, suggesting that NETs could induce ALI in mice. Moreover, we observed that NETs could trigger necroptosis of AECs in vivo and in vitro. The phosphorylation levels of RIPK3 and MLKL were increased in MLE12 cells after NETs treatment (P < 0.05). Mechanistically, NETs taken up by AECs through endocytosis activated the cGAS-STING pathway and triggered AECs necroptosis. The expression of cGAS, STING, TBK1 and IRF3 were increased in MLE12 cells treated with NETs (P < 0.05). Furthermore, the cGAS inhibitor RU.521 inhibited NETs-triggered AECs necroptosis and alleviated the pulmonary damage induced by NETs in mice. In conclusion, our study demonstrates that NETs taken up by AECs via endocytosis can activate the cGAS-STING pathway and trigger AECs necroptosis to promote ALI in mice. Our findings indicate that targeting the NETs/cGAS-STING/necroptosis pathway in AECs is an effective strategy for treating ALI.

Krüppel-like transcription factor 14 alleviates alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress in pulmonaryfibrosis.

Pulmonary fibrosis (PF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia, occurring primarily in older adults with poor prognosis. Alveolar epithelial cell (AEC) senescence is the critical pathological mechanism of PF. However, the molecular mechanisms regulating AEC senescence in PF are incompletely understood. Herein, we provided evidence to support the function of Krüppel-like factor 14 (KLF14), a novel Krüppel-like transcription factor, in the regulation of AEC senescence during PF. We confirmed that the expression of KLF14 was up-regulated in PF patients and mice treated with bleomycin (BLM). KLF14 knockdown resulted in more pronounced structural disruption of the lung tissue and swelling of the alveolar septum, which led to significantly increased mortality in BLM-induced PF mice. Mechanistically, RNA-seq analysis indicated that KLF14 decreased the senescence of AECs by inhibiting endoplasmic reticulum (ER) stress. Furthermore, the pharmacological activation of KLF14 conferred protection against PF in mice. In conclusion, our findings reveal a protective role for KLF14 in preventing AECs from senescence and shed light on the development of KLF14-targeted therapeutics for PF.

Identification of hypoxic macrophages in glioblastoma: Unveiling therapeutic insights from tumour microenvironment analysis.

Tumor-associatedmacrophages (TAMs) exhibit remarkable heterogeneity in glioblastoma. Spatially resolved single-cell transcriptomic studies identified a monocyte-derived TAM subset localized in the peri-necrotic niche, driven by hypoxic cues to acquire ahypoxia response signature. These hypoxia-TAMs destabilize endothelial adherens junctions through adrenomedullin paracrine signaling, promoting the formation of hyperpermeable neovasculature that impedes drug delivery. Blocking adrenomedullin produced by hypoxia-TAMs restores vascular integrity, increases drug deliveryinto tumors, and provides combinatorial therapeutic benefits. Here we discuss the heterogeneity of TAMs regarding functional states and locations in glioblastomas, and propose future directions for studying the temporospatial dynamics of multifaceted TAM. HIGHLIGHTS: Single-cell omics reveal a functionally and spatially distinct hypoxia-TAM subset in glioblastoma. Adrenomedullin secreted by hypoxia-TAM destabilizes tumor vasculature and its blockade enhances vessel integrity and drug delivery.

MOG-antibody-associated transverse myelitis with the H-sign and unusual MRI enhancement: a case report and literature review.

Transverse myelitis is the second most common symptoms in myelin oligodendrocyte antibody-associated diseases (MOGAD), causing obvious clinical manifestation. T2-hyperintense lesions mainly restricted to the gray matter in the spinal cord on axial magnetic resonance imaging, produce the H-sign, which is thought to be the typical finding of MOGAD. Contrast enhancement can be observed in some cases of myelin oligodendrocyte antibody-associated transverse myelitis (MOG-TM). However, reports on the enhancement pattern associated with the H-sign are rarely seen. In this report, we describe a case of pediatric MOG-TM in which the H-sign was observed without enhancement, while the surrounding white matter exhibited enhancement. This pattern contradicts the previously observed gray matter involvement. Then we reviewed the literatures of myelin oligodendrocyte antibody-positive myelitis to focus on the neuroimaging features and discuss the implications of our finding.

Heteroatom Immobilization Engineering toward High-Performance Metal Anodes.

Heteroatom immobilization engineering (HAIE) is becoming a forefront approach in materials science and engineering, focusing on the precise control and manipulation of atomic-level interactions within heterogeneous systems. HAIE has emerged as an efficient strategy to fabricate single-atom sites for enhancing the performance of metal-based batteries. Despite the significant progress achieved through HAIE in metal anodes for metal-based batteries, several critical challenges such as metal dendrites, side reactions, and sluggish reaction kinetics are still present. In this review, we delve into the fundamental principles underlying heteroatom immobilization engineering in metal anodes, aiming to elucidate its role in enhancing the electrochemical performance in batteries. We systematically investigate how HAIE facilitates uniform nucleation of metal in anodes, how HAIE inhibits side reactions at the metal anode-electrolyte interface, and the role of HAIE in promoting the desolvation of metal ions and accelerating reaction kinetics within metal-based batteries. Finally, we discuss various strategies for implementing HAIE in electrode materials, such as high-temperature pyrolysis, vacancy reduction, and molten-salt etching and anchoring. These strategies include selecting appropriate heteroatoms, optimizing immobilization methods, and constructing material architectures. They can be utilized to further refine the performance to enhance the capabilities of HAIE and facilitate its widespread application in next-generation metal-based battery technologies.

O-GlcNAcylation mediates Wnt-stimulated bone formation by rewiring aerobic glycolysis.

Wnt signaling is an important target for anabolic therapies in osteoporosis. A sclerostin-neutralizing antibody (Scl-Ab), that blocks the Wnt signaling inhibitor (sclerostin), has been shown to promote bone mass in animal models and clinical studies. However, the cellular mechanisms by which Wnt signaling promotes osteogenesis remain to be further investigated. O-GlcNAcylation, a dynamic post-translational modification of proteins, controls multiple critical biological processes including transcription, translation, and cell fate determination. Here, we report that Wnt3a either induces O-GlcNAcylation rapidly via the Ca2+-PKA-Gfat1 axis, or increases it in a Wnt-ß-catenin-dependent manner following prolonged stimulation. Importantly, we find O-GlcNAcylation indispensable for osteoblastogenesis both in vivo and in vitro. Genetic ablation of O-GlcNAcylation in the osteoblast-lineage diminishes bone formation and delays bone fracture healing in response to Wnt stimulation in vivo. Mechanistically, Wnt3a induces O-GlcNAcylation at Serine 174 of PDK1 to stabilize the protein, resulting in increased glycolysis and osteogenesis. These findings highlight O-GlcNAcylation as an important mechanism regulating Wnt-induced glucose metabolism and bone anabolism.

Fracture risk prediction in diabetes patients based on Lasso feature selection and Machine Learning.

Fracture risk among individuals with diabetes poses significant clinical challenges due to the multifaceted relationship between diabetes and bone health. Diabetes not only affects bone density but also alters bone quality and structure, thereby increases the susceptibility to fractures. Given the rising prevalence of diabetes worldwide and its associated complications, accurate prediction of fracture risk in diabetic individuals has emerged as a pressing clinical need. This study aims to investigate the factors influencing fracture risk among diabetic patients. We propose a framework that combines Lasso feature selection with eight classification algorithms. Initially, Lasso regression is employed to select 24 significant features. Subsequently, we utilize grid search and 5-fold cross-validation to train and tune the selected classification algorithms, including KNN, Naive Bayes, Decision Tree, Random Forest, AdaBoost, XGBoost, Multi-layer Perceptron (MLP), and Support Vector Machine (SVM). Among models trained using these important features, Random Forest exhibits the highest performance with a predictive accuracy of 93.87%. Comparative analysis across all features, important features, and remaining features demonstrate the crucial role of features selected by Lasso regression in predicting fracture risk among diabetic patients. Besides, by using a feature importance ranking algorithm, we find several features that hold significant reference values for predicting early bone fracture risk in diabetic individuals.

Recent Advances in Piezoelectric Coupled with Photocatalytic Reaction System: Synergistic Mechanism, Enhancement Factors, and Application.

The field of photocatalysis has demonstrated numerous advantages in the domains of environmental protection, energy, and materials science. However, conventional modification methods fail to simultaneously enhance carrier separation efficiency, redox capacity, and visible light absorption solely through light activation due to the intrinsic band structure limitations of photocatalysts. In addition to modification methods, the introduction of an external field, such as a piezoelectric field, can effectively address deficiencies in each step of the photocatalytic process and enhance the overall performance. The assistance of a piezoelectric field overcomes the limitations inherent in traditional photocatalytic systems. Hence, this review provides a comprehensive overview of recent advancements in piezoelectric-assisted photocatalysis and thoroughly investigates the interaction between the alternating piezoelectric field and photocatalytic processes. Various ideas for synergistic enhancement of the piezoelectric and photocatalytic properties are also explored. This multifield catalytic system shows remarkable performance in stability, pollutant degradation, and energy conversion, distinguishing it from single catalytic systems. Finally, an in-depth analysis is conducted to address the challenges and prospects associated with piezoelectric photocatalysis technology.

RNA reading protein YTHDF2 mediates Benzo(k)fluoranthene induced male reproductive injury by regulating the stability of BCL2.

Benzo (k) fluoranthene (BkF) has adverse effects on male reproduction, but its specific mechanism of action is still unclear. This study focused on the role of RNA reading protein YTHDF2 and its mechanism in BkF induced male reproductive injury. Mouse GC-2 spermatocytes were exposed to 0, 40, 80, 160 µM BkF. It was found that BkF significantly increased the apoptosis of GC-2 cell and decreased its survival rate. BCL2 in spermatocytes decreased significantly, while the expression of P53 and BAX exhibited a notable increase. Interestingly, the expression of RNA reading protein YTHDF2 progressively rose in tandem with the escalating BkF exposure dosage. Overexpression of YTHDF2 significantly reduced the viability of cells and increased the apoptosis rate. Meanwhile, there was a substantial increase in the expression of P53 and BAX, BCL2 was significantly down-regulated. On the contrary, interfering with YTHDF2 increased cell proliferation and reduced cell apoptosis. Furthermore, YTHDF2 overexpression exacerbated the decrease in cell viability under BkF exposure, while YTHDF2 knockdown was the opposite. The results from the RIP assay demonstrated a significant enhancement in the interaction of YTHDF2 protein with BCL2 mRNA following the overexpression of YTHDF2. In addition, animal experiments showed that there was an increase in apoptosis and a decrease in proliferation of testicular cells in mice in the high-dose (30 mg/kg) BkF group by TUNEL staining and Ki67 staining. Immunohistochemical analysis showed that BCL2 levels were significantly lower in the high-dose group than in the control group, while YTHDF2, P53 and BAX were dramatically increased. In summary, our study suggests that YTHDF2 has been implicated in BkF-induced male reproductive injury by promoting the degradation of BCL2.

Structure-Based Discovery of Symmetric Disulfides from Garlic Extract as Pseudomonas aeruginosa Quorum Sensing Inhibitors.

Microorganisms are the most common cause of food spoilage. Pseudomonas aeruginosa is a common foodborne pathogen that causes food spoilage and poses a serious threat to food safety. As a crucial target in antitoxicity strategies, the quorum sensing (QS) system shows promising potential for further development. The garlic extract diallyl disulfide exhibits inhibitory activity against the QS system of P. aeruginosa, with disulfide bonds serving as the active component. However, the biological activity of other symmetric disulfides has not been investigated in this capacity. The study synthesized 39 disulfide bond-containing analogs and evaluated their activity as quorum sensing inhibitors (QSIs). The results showed that p-hydroxyphenyl substitution can replace the allyl groups while maintaining strong biological activity. The virulence factors production was reduced by compound 2i, with the strongest inhibitory effect being observed on elastase production. Synergistic inhibition was observed in the presence of antibiotics like ciprofloxacin and tobramycin. 2i successfully inhibited P. aeruginosa infection in the Galleria mellonella larvae model. Primary mechanism studies using transcriptome, surface plasmon resonance and molecular docking suggested that 2i inhibits the QS system by targeting the LasR protein. Thus, compound 2i could be used in developing QSIs for the control of P. aeruginosa infections.