Genome-wide identification and evolution of the SAP gene family in sunflower (Helianthus annuus L.) and expression analysis under salt and drought stress.

Stress-associated proteins (SAPs) are known to play an important role in plant responses to abiotic stresses. This study systematically identified members of the sunflower SAP gene family using sunflower genome data. The genes of the sunflower SAP gene family were analyzed using bioinformatic methods, and gene expression was assessed through fluorescence quantification (qRT-PCR) under salt and drought stress. A comprehensive analysis was also performed on the number, structure, collinearity, and phylogeny of seven Compositae species and eight other plant SAP gene families. The sunflower genome was found to have 27 SAP genes, distributed across 14 chromosomes. The evolutionary analysis revealed that the SAP family genes could be divided into three subgroups. Notably, the annuus variety exhibited amplification of the SAP gene for Group 3. Among the Compositae species, C. morifolium demonstrated the highest number of collinearity gene pairs and the closest distance on the phylogenetic tree, suggesting relative conservation in the evolutionary process. An analysis of gene structure revealed that Group 1 exhibited the most complex gene structure, while the majority of HaSAP genes in Group 2 and Group 3 lacked introns. The promoter analysis revealed the presence of cis-acting elements related to ABA, indicating their involvement in stress responses. The expression analysis indicated the potential involvement of 10 genes (HaSAP1, HaSAP3, HaSAP8, HaSAP10, HaSAP15, HaSAP16, HaSAP21, HaSAP22, HaSAP23, and HaSAP26) in sunflower salt tolerance. The expression of these 10 genes were then examined under salt and drought stress using qRT-PCR, and the tissue-specific expression patterns of these 10 genes were also analyzed. HaSAP1, HaSAP21, and HaSAP23 exhibited consistent expression patterns under both salt and drought stress, indicating these genes play a role in both salt tolerance and drought resistance in sunflower. The findings of this study highlight the significant contribution of the SAP gene family to salt tolerance and drought resistance in sunflower.

Perioperative, functional and oncologic outcomes of percutaneous ablation versus minimally invasive partial nephrectomy for clinical T1 renal tumors: outcomes from a pooled analysis.

The objective of this study was to perform a comprehensive pooled analysis aimed at comparing the efficacy and safety of percutaneous ablation (PCA) versus minimally invasive partial nephrectomy (MIPN), including robotic and laparoscopic approaches, in patients diagnosed with cT1 renal tumors. We conducted a comprehensive search across four major electronic databases: PubMed, Embase, Web of Science, and the Cochrane Library, targeting studies published in English up to April 2024. The primary outcomes evaluated in this analysis included perioperative outcomes, functional outcomes, and oncological outcomes. A total of 2449 patients across 17 studies were included in the analysis. PCA demonstrated superior outcomes compared to MIPN in terms of shorter hospital stays (WMD: - 2.13 days; 95% Confidence Interval [CI]: - 3.29, - 0.97; p = 0.0003), reduced operative times (WMD: - 109.99 min; 95% CI: - 141.40, - 78.59; p < 0.00001), and lower overall complication rates (OR: 0.54; 95% CI: 0.40, 0.74; p = 0.0001). However, PCA was associated with a higher rate of local recurrence when compared to MIPN (OR: 3.81; 95% CI: 2.45, 5.92; p < 0.00001). Additionally, no significant differences were observed in major complications, estimated glomerular filtration rate decline, creatinine variation, overall survival, recurrence-free survival, and disease-free survival between the two treatment modalities. PCA presents a notable disadvantage regarding local recurrence rates in comparison to MIPN. However, PCA offers several advantages over MIPN, including shorter durations of hospital stay, reduced operative times, and lower complication rates, while achieving similar outcomes in other oncologic metrics.

Shenfu injection ameliorates endotoxemia-associated endothelial dysfunction and organ injury via inhibiting PI3K/Akt-mediated glycolysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Microcirculatory dysfunction is one of the main characteristics of sepsis. Shenfu Injection (SFI) as a traditional Chinese medicine is widely applied in clinical severe conditions. Recent studies have shown that SFI has the ability to ameliorate sepsis-induced inflammation and to improve microcirculation perfusion. AIM OF THE STUDY: This study aims to investigate the underlying mechanism of SFI for ameliorating sepsis-associated endothelial dysfunction and organ injury. MATERIALS AND METHODS: Side-stream dark-field (SDF) imaging was used to monitor the sublingual microcirculation of septic patients treated with or without SFI. Septic mouse model was used to evaluate the effects of SFI in vivo. Metabolomics and transcriptomics were performed on endothelial cells to identify the underlying mechanism for SFI-related protective effect on endothelial cells. RESULTS: SFI effectively abolished the disturbance and loss of sublingual microcirculation in septic patients. Twenty septic shock patients with or without SFI administration were enrolled and the data showed that SFI significantly improved the levels of total vessel density (TVD), perfused vessel density (PVD), microvascular flow index (MFI), and the proportion of perfused vessels (PPV). The administration of SFI significantly decreased the elevated plasma levels of Angiopoietin-2 (Ang2) and Syndecan-1, which are biomarkers indicative of endothelial damage in sepsis patients. In the mouse septic model in vivo, SFI inhibited the upregulation of endothelial adhesion molecules and Ly6G + neutrophil infiltration while restored the expression of VE-Cadherin in the vasculature of the lung, kidney, and liver tissue. Additionally, SFI reduced the plasma levels of Ang2, Monocyte Chemoattractant Protein-1(MCP1), and Interleukin-6 (IL6), and alleviated liver and kidney injury in septic mice. Moreover, SFI significantly inhibited the inflammatory activation and increased permeability of endothelial cells induced by endotoxins in vitro. By performing metabolomics and transcriptomics, we identified the activation of PI3K/Akt-mediated glycolysis as the underlying mechanism for SFI-related protective effect on endothelial cells. CONCLUSIONS: Our findings revealed that SFI may improve microcirculation perfusion and endothelial function in sepsis via inhibiting PI3K/Akt-mediated glycolysis, providing theoretical evidence for the clinical application of SFI.

A biodegradable multifunctional pectin-montmorillonite fertilizer coating: Controlled-release, water-retention and soil-cementation.

Coated fertilizers have been widely used to improve fertility in barren land. However, improving soil structure and water-retention capacity is also essential for arid and semi-arid areas with sandy soils to promote crop growth. Most currently available coated fertilizers rarely meet these requirements, limiting their application scope. Therefore, this study "tailored" pectin-montmorillonite (PM) multifunctional coatings for arid areas, featuring intercalation reactions and nanoscale entanglement between pectin and montmorillonite via hydrogen bonding and electrostatic and van der Waals forces. Notably, PM coatings have demonstrated an effective "relay" model of action. First, the PM-50 coating could act as a "shield" to protect urea pills, increasing the mechanical strength (82.12 %). Second, this coating prolonged the release longevity of urea (<0.5 h to 15 days). Further, the remaining coating performed a water-retention function. Subsequently, the degraded coating improved the soil properties. Thus, this coating facilitated the growth of wheat seedlings in a simulated arid environment. Moreover, the cytotoxicity test, life cycle assessment, and soil biodegradation experiment showed that the PM coating exhibited minimal environmental impact. Overall, the "relay" model of PM coating overcomes the application limitations of traditional coated fertilizers and provides a sustainable strategy for developing coating materials in soil degradation areas.

Elucidation of the mechanism underlying the sequential catalysis of inulin by fructotransferase.

Glycoside hydrolase family 91 (GH91) inulin fructotransferase (IFTases) enables biotransformation of fructans into sugar substitutes for dietary intervention in metabolic syndrome. However, the catalytic mechanism underlying the sequential biodegradation of inulin remains unelusive during the biotranformation of fructans. Herein we present the crystal structures of IFTase from Arthrobacter aurescens SK 8.001 in apo form and in complexes with kestose, nystose, or fructosyl nystose, respectively. Two kinds of conserved noncatalytic binding regions are first identified for IFTase-inulin interactions. The conserved interactions of substrates were revealed in the catalytic center that only contained a catalytic residue E205. A switching scaffold was comprised of D194 and Q217 in the catalytic channel, which served as the catalytic transition stabilizer through side chain displacement in the cycling of substrate sliding in/out the catalytic pocket. Such features in GH91 contribute to the catalytic model for consecutive cutting of substrate chain as well as product release in IFTase, and thus might be extended to other exo-active enzymes with an enclosed bottom of catalytic pocket. The study expands the current general catalytic principle in enzyme-substrate complexes and shed light on the rational design of IFTase for fructan biotransformation.

Multi-grained contrastive representation learning for label-efficient lesion segmentation and onset time classification of acute ischemic stroke.

Ischemic lesion segmentation and the time since stroke (TSS) onset classification from paired multi-modal MRI imaging of unwitnessed acute ischemic stroke (AIS) patients is crucial, which supports tissue plasminogen activator (tPA) thrombolysis decision-making. Deep learning methods demonstrate superiority in TSS classification. However, they often overfit task-irrelevant features due to insufficient paired labeled data, resulting in poor generalization. We observed that unpaired data are readily available and inherently carry task-relevant cues, but are less often considered and explored. Based on this, in this paper, we propose to fully excavate the potential of unpaired unlabeled data and use them to facilitate the downstream AIS analysis task. We first analyze the utility of features at the varied grain and propose a multi-grained contrastive learning (MGCL) framework to learn task-related prior representations from both coarse-grained and fine-grained levels. The former can learn global prior representations to enhance the location ability for the ischemic lesions and perceive the healthy surroundings, while the latter can learn local prior representations to enhance the perception ability for semantic relation between the ischemic lesion and other health regions. To better transfer and utilize the learned task-related representation, we designed a novel multi-task framework to simultaneously achieve ischemic lesion segmentation and TSS classification with limited labeled data. In addition, a multi-modal region-related feature fusion module is proposed to enable the feature correlation and synergy between multi-modal deep image features for more accurate TSS decision-making. Extensive experiments on the large-scale multi-center MRI dataset demonstrate the superiority of the proposed framework. Therefore, it is promising that it helps better stroke evaluation and treatment decision-making.

CXCR4-Targeted 68 Ga-Pentixafor PET/CT Imaging in Inflammatory Bowel Disease.

PURPOSE: To investigate the role of CXCR4-targeted 68 Ga-pentixafor PET/CT imaging in inflammatory bowel disease (IBD). METHODS: Five IBD patients and 12 control subjects performing 68 Ga-pentixafor PET/CT examinations were included. 68 Ga-pentixafor PET/CT imaging and endoscopic findings were recorded and compared. The semiquantitative parameters of 68 Ga-pentixafor uptake by the lesion segments in IBD patients and the normal intestines in the control were investigated. RESULTS: Among these 5 IBD patients, endoscopy successfully examined a total of 26 intestinal segments, with 13 segments showing endoscopic lesions. 68 Ga-pentixafor PET/CT was positive in all endoscopy-proven lesions (13/13). Additionally, 68 Ga-pentixafor PET/CT revealed the lesions in small intestines and colons that cannot be reached by endoscopy due to severe stenosis, and mesenteric lymphadenitis accompanied IBD. The SUV max of the lesion segments in IBD patients was significantly higher than that of the normal intestines in the control group (median, 3.15 [range, 1.61-6.26] vs 1.67 [1.18-2.29], P < 0.001). Moreover, the SUV max ratios of the lesion segments/liver or blood pool were higher when compared with the control (2.20 [1.13-3.26] vs 0.85 [0.54-1.20]; 1.66 [0.94-2.95] vs 0.67 [0.52-1.04]; P ≤ 0.001). CONCLUSIONS: 68 Ga-pentixafor PET/CT can be a potentially valuable tool to assess the active intestinal lesions of IBD with high sensitivity. Moreover, this noninvasive approach does not require fasting or bowel preparation, offering good tolerance and safety.

Efficacy and Side Effects of Mixed-Strategy Electroconvulsive Therapy: A Proof-of-Concept Randomized Clinical Trial on Late Life Depression.

OBJECTIVE: Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient's resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects. METHODS: This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies. RESULTS: In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004). CONCLUSION: msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.

Drivers and collaborative governance of public health emergency response in the context of digital city.

Introduction: With the frequent occurrence of public health events, the government inevitably makes many mistakes in emergency management. In modern emergency management, it is particularly important to promote the diversification of emergency management subjects and improve the government's emergency management ability. Methods: In order to make up for the deficiency of government's participation in public health emergency management, this paper analyzes the driving factors and driving effects of enterprises' participation in public health emergency response under the background of digital city. A fully explained structural model is used to analyze the relationship between the different drivers. In addition, the spatial and temporal distribution characteristics of public health events were analyzed through spatial auto-correlation. On this basis, the government cooperative governance strategy is discussed. Results and discussion: The results show that in the context of digital cities, there are 14 driving factors for enterprises to participate in public health emergency response. The most important factors are the company's own development needs, relative technical advantages and so on. The driving efficiency is mainly concentrated in three aspects: psychology, resources and structure. Public health events have periodicity in time distribution and regional differences in spatial distribution. The significance of this study is to help the government improve the emergency management ability from different angles.

Comprehensive analysis of single-cell transcriptomics and genetic factors reveals the mechanisms and preventive strategies for the progression from pulmonary fibrosis to lung cancer.

BACKGROUND: Pulmonary fibrosis (PF) leads to excessive deposition of fibrous connective tissue in the lungs, increasing the risk of lung cancer due to the enhanced activity of fibroblasts (FBs). Fibroblast-mediated collagen fiber deposition creates a tumor-like microenvironment, laying the foundation for tumorigenesis. Clinically, numerous cases of lung cancer induced by pulmonary fibrosis have been observed. In recent years, the study of nucleotide point mutations, which provide more detailed insights than gene expression, has made significant advancements, offering new perspectives for clinical research. METHODS: We initially employed Mendelian randomization to ascertain that the initial stage of lung cancer induced by PF belongs to small cell lung cancer (SCLC). Subsequently, pulmonary neuroendocrine cells (PNECs) were identified by using pseudo-time series analysis as cell clusters with carcinogenic potential. We categorized FBs into four groups according to their cellular metabolism, and then analyzed the cellular communication between FBs and PNECs, as well as changes in intracellular pathways of PNECs. Additionally, we examined the characteristic genome of FBs which is significantly associated with PF and investigated the impact of FBs on immune cells in the PF microenvironment. Finally, we explored strategies for preventing the progression from PF to lung cancer. RESULTS: The genetic features of cells with carcinogenic potential in PF tissues were revealed, characterized by upregulation of Achaete-Scute Family BHLH Transcription Factor 1 (ASCL1), Homeobox B2 (HOXB2), Teashirt Zinc Finger Homeobox 2 (TSHZ2), Insulinoma-associated 1 (INSM1), and reduced activity of RE1 Silencing Transcription Factor (REST). FBs characterized by high glycolysis and low tricarboxylic acid (TCA) cycling played a key role in the progression of PF. The microenvironment of PF resembles the tumor microenvironment, providing a conducive immunosuppressive environment for the occurrence of cancer cells. In dendritic cells, rs9265808 is a susceptibility locus for progression from pulmonary fibrosis to lung cancer, mutations at this locus increase the expression of Complement Factor B (CFB), and excessive activation of the complement pathway is a crucial factor leading to lung cancer development in patients with pulmonary fibrosis. Ensuring adequate nutritional supply and physical function is one of the effective measures to prevent progression from pulmonary fibrosis to lung cancer. CONCLUSION: CFB promotes lung cancer occurrence by inducing the accumulation and polarization of a large number of monocytes/macrophages in the lungs, driving disease progression by reducing the physical fitness of patients with pulmonary fibrosis.

Single Center Experience in Surgical Treatment of Extracranial Supra-Aortic Aneurysms.

Objective To evaluate the effect of surgical treatment on extracranial supra-aortic aneurysms and summarize the experience.Methods The clinical data of 10 patients undergoing surgical treatment of extracranial supra-aortic aneurysms from May 2019 to November 2023 in the Department of Vascular Surgery of Beijing Tiantan Hospital affiliated to Capital Medical University were collected.The 10 patients included 5 patients with internal carotid artery aneurysm,2 patients with subclavian artery aneurysm,2 patients with vertebral artery aneurysm,and 1 patient with internal carotid artery aneurysm combined with ipsilateral subclavian artery aneurysm.The surgical indications,surgical regimens,clinical efficacy,and complications were retrospectively analyzed. Results All the 10 patients underwent surgery successfully,with the surgery duration range of 60-420 min and the median surgery duration of 180.0 (121.5,307.5) min.Intraoperative bleeding volume varied within 30-400 mL,with a median of 90 (50,125) mL.The time of carotid artery blocking and vertebral artery blocking varied within the ranges of 10-20 min and 20-30 min,with the medians of 15.0 (11.5,16.3) min and 25.0 (15.0,22.5) min,respectively.No cardiac accident,cerebral infarction,or cerebral hemorrhage occurred during the perioperative period.The 10 patients were followed up for 3-58 months,with the median follow-up time of 8.5 (5.3,17.0) months.One patient with subclavian artery aneurysm developed artificial vessel occlusion 20 months after surgery.One patient with internal carotid artery aneurysm developed distal carotid artery stenosis 6 months after surgery. Conclusion Surgical treatment should be actively adopted for extracranial supra-aortic aneurysms,and individualized surgical regimens should be designed according to patient conditions.

Wireless Optogenetic Targeting Nociceptors Helps Host Cells Win the Competitive Colonization in Implant-Associated Infections.

The role of nociceptive nerves in modulating immune responses to harmful stimuli via pain or itch induction remains controversial. Compared to conventional surgery, various implant surgeries are more prone to infections even with low bacterial loads. In this study, an optogenetic technique is introduced for selectively activating peripheral nociceptive nerves using a fully implantable, wirelessly rechargeable optogenetic device. By targeting nociceptors in the limbs of awake, freely moving mice, it is found that activation induces anticipatory immunity in the innervated territory and enhances the adhesion of various host cells to the implant surface. This effect mediates acute immune cell-mediated killing of Staphylococcus aureus on implants and enables the host to win "implant surface competition" against Staphylococcus aureus. This finding provides new strategies for preventing and treating implant-associated infections.

Synergistic enhancement of fluorescein-K3[Fe(CN)6] CL by MoO3-x NPs for sensitive and noninvasive detection of uric acid in saliva.

MoO3-x NPs was rapidly synthesized at room temperature by an easy stirring method. It was interesting to find that MoO3-x NPs induce OH- to generate active free radicals (ROS), which is a highly promising property in chemiluminescence (CL). Benefiting from the abundant oxygen vacancy, MoO3-x NPs adsorbs H2O2 and turn it into ·OH. The oxidase activity of fluorescein under visible light had already been reported, which catalyzes dissolved oxygen to become O2-· and continue to convert to H2O2. By creating the synergy effect with fluorescein, MoO3-x NPs strengthen the CL intensity of K3[Fe(CN)6]-fluorescein system significantly. Utilizing the quench effect of uric acid for the CL intensity, we developed a rapid, simple, and highly sensitive CL platform for uric acid detection. The linear range was 5-80 µM and the detection limit (LOD) for uric acid was 3.11 µM (S/N = 3). This work expanded the application of MoO3-x NPs in the CL field and developed a simple and highly sensitive CL sensing system to detect UA in human saliva.

Honokiol Mitigates Metabolic-Associated Fatty Liver Disease by Regulating Nrf2 and RIPK3 Signaling Pathways.

BACKGROUND/AIMS:  Metabolic-associated fatty liver disease (MAFLD) is a common cause of chronic liver disease worldwide. However, there is currently no recognized effective drugs for treating it. MATERIALS AND METHODS:  In this study, we investigated the efficacy of Honokiol (HNK) in vitro for mitigating MAFLD. Then, 0.4 mM palmitic acid (PA) and LO2 cells were used to establish the MAFLD model. The protective effect of HNK on MAFLD was confirmed by Oil Red O staining and cell counting kit (CCK-8) assay in LO2 cell line. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were carried out to analyze the regulatory role of HNK on Nrf2 and RIPK3 signaling pathways. The effect of HNK and its downstream signaling pathways on oxidative stress were verified by the detection of reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD). The concentration of IL-1ß, IL-6L, and TNF-α was assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS:  The middle concentration of HNK (50 µmol/L) was selected as the best option for inhibiting lipidosis and oxidative stress in MAFLD models. Honokiol mitigates MAFLD via activation of nuclear factor E2-related factor 2 (Nrf2) signaling pathways in vitro. Honokiol suppressed MAFLD via activating the Nrf2 signaling pathway to play an antioxidant and anti-inflammatory role. Also, HNK regulates Nrf2 and RIPK3 signaling pathways to mitigate MAFLD. CONCLUSION:  Our results showed that HNK may suppress the oxidative stress and inflammation in MAFLD via activation of Nrf2 signaling pathway.

COMPARATIVE WHOLE METAGENOME ANALYSIS IN LESIONAL AND NON-LESIONAL SCALP AREAS OF PSORIASIS CAPITIS PATIENTS AND HEALTHY INDIVIDUALS.

Psoriasis is an immune-mediated inflammatory disorder, where the majority of the patients suffer from psoriasis capitis or scalp psoriasis. Current therapeutics remain ineffective to treat scalp lesions. Here, we present a whole-metagenome characterisation of the scalp microbiome in psoriasis capitis. We investigated how changes in the homeostatic cutaneous microbiome correlate with the condition and identified metagenomic biomarkers (taxonomic, functional, virulence factors, antimicrobial resistance genes) that could partly explain its emergence. Within this study, 83 top and back scalp samples from healthy individuals and 64 lesional and non-lesional scalp samples from untreated psoriasis capitis subjects were analysed. Using qPCR targeting the 16S and 18S rRNA genes, we found a significant decrease in microbial load within scalp regions affected by psoriasis compared to their non-lesional counterparts. Metagenomic analysis revealed that psoriatic lesions displayed significant lower Cutibacterium species (incl. C. modestum, C. namnetense, C. granulosum, C. porci), along with an elevation in Staphylococcus aureus. A heightened relative presence of efflux pump protein-encoding genes was detected, suggesting potential antimicrobial resistance mechanisms. These mechanisms are known to specifically target human antimicrobial peptides (incl. cathelicidin LL-37) which are frequently encountered within psoriasis lesions. These shifts in microbial community dynamics may contribute to psoriasis disease pathogenesis.

Oleanane-type triterpenoids from Sabia limoniacea and their anti-inflammatory activities.

Eighteen new oleanane-type triterpenoids were isolated from the stems of Sabia limoniacea, including sabialimon A (1), a triterpenoid with an unprecedented 6/6/6/7/7 pentacyclic skeleton and seventeen undescribed triterpenoids, sabialimons B-R (2 - 18), along with six previously described analogs (19 - 24). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), experimental electronic circular dichroism measurements and X-ray crystallographic studies. Compound 1 is the first triterpenoid that possesses a rare ring system (6/6/6/7/7) with an oxygen-bearing bridge between C-17 and C-18 and a hemiketal form at C-17, which is generated a larger ring by the degradation of C-28 and D/E-ring expansion. Biological evaluation revealed that sabialimon I (9), sabialimon K (11), sabialimon P (16) and 11,13(18)-oleanadien-28-hydroxymethyl 3-one (20) exhibited significantly inhibitory activities against nitric oxide (NO) release with IC50 values of 29.65, 23.41, 18.12 and 26.64 µM, respectively, as compared with the positive control (dexamethasone, IC50 value: 40.35 µM). Furthermore, sabialimon P markedly decreased the secretion of TNF-α, iNOS, IL-6 and NF-κB and inhibited the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner.

Induction of hepatic fibrosis in mice with schistosomiasis by extracellular microRNA-30 derived from Schistosoma japonicum eggs.

Background: Schistosomiasis is a zoonotic parasitic disorder induced by the infestation of schistosomes, a genus of trematodes. MicroRNAs (miRNAs) in egg-derived exosomes are crucial for modulating the host's immune responses and orchestrating the pathophysiological mechanisms. Although the exosomes secreted by S. japonicum contain abundant miRNAs, the specific roles of these miRNAs in the pathogenesis of schistosomiasis-induced hepatic fibrosis are yet to be comprehensively elucidated. The egg exosomes of S. japonicum secrete miRNA-30, a novel miRNA. Methods: In vitro, the effect of miRNA-30 was evaluated by transfecting HSCs with miRNA mimics. The target gene biosignature for miRNA-30 was predicted using the miRDB software. The effect of miRNA-30 in hepatic fibrosis was evaluated by either elevating its expression in healthy mice or by inhibiting its activity in infected mice by administration of recombinant adeno-associated virus serotype eight vectors expressing miRNA-30 or miRNA sponges. Results: This novel miRNA can activate hepatic stellate cells (HSCs), the prinary effector cells of hepatic fibrosis, in vitro, i.e., it significantly increases the fibrogenic factors Col1(α1), Col3(α1), and α-SMA at both mRNA and protein levels. In addition, miRNA-30 may activate HSCs by targeting the host RORA gene. In addition, in vivo experiments were conducted by administering a recombinant adeno-associated viral vector to modulate the expression levels of miRNA-30. The overexpression of miRNA-30 in healthy mice significantly elevated the expression of Col1(α1), Col3(α1), and α-SMA at both the transcriptomic and proteomic scales. This overexpression was coupled with a pronounced augmentation in the hepatic hydroxyproline content. Conversely, the in vivo silencing of miRNA-30 in infected mice induced a considerable reduction in the size of hepatic granulomas and areas of collagen deposition. Hence, in vivo, modulation of miRNA-30 expression may play a pivotal role in ameliorating the severity of hepatic fibrosis in mice afflicted with S. japonica. Conclusions: The study results suggest that miRNA-30 may augment schistosomiasis-induced hepatic fibrosis through a probable interaction with the host RORA. Our study may improve the current theoretical framework regarding cross-species regulation by miRNAs of hepatic fibrosis in schistosomiasis.

One-year outcomes of rate versus rhythm control of atrial fibrillation in the Kerala-AF Registry.

Background: There is ongoing debate around rate versus rhythm control strategies for managing atrial fibrillation (AF), however, much of the data comes from Western cohorts. Kerala-AF represents the largest prospective AF cohort study from the Indian subcontinent. Objectives: To compare 12-month outcomes between rate and rhythm control strategies. Methods: Patients aged ≥18 years with non-transient AF were recruited from 53 hospitals across Kerala. Patients were stratified by rate or rhythm control. The primary outcome was a composite of all-cause mortality, arterial thromboembolism, acute coronary syndrome or hospitalization due to heart failure or arrhythmia at 12 months. Secondary outcomes included bleeding events and individual components of the primary. Predictors of the composite outcome were analysed by logistic regression. Results: A total of 2901 patients (mean age 64.6 years, 51% female) were included (2464 rate control, 437 rhythm control). Rates of the primary composite outcome did not differ between groups (29.7% vs 30.0%; p = .955), nor did any component of the primary. Bleeding outcomes were also similar (1.6% vs 1.9%; p = .848). Independent predictors of the primary composite outcome were older age (aOR 1.01; p = .013), BMI <18 (aOR 1.51; p = .025), permanent AF (aOR 0.78; p = .010), HFpEF (aOR 1.40; p = .023), HFrEF (aOR 1.39; p = .004), chronic kidney disease (aOR 1.36; p < .001), and prior thromboembolism (aOR 1.31; p = .014). Conclusion: In the Kerala-AF registry, 12-month outcomes did not differ between rate and rhythm control cohorts.

Detection of rare microorganisms in bone and joint infections by metagenomic next-generation sequencing.

Aims: This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment. Methods: A retrospective analysis was conducted on 235 patients with BJIs who were treated at our hospital between January 2015 and December 2021. Patients were divided into the no-mNGS group (microbial culture only) and the mNGS group (mNGS testing and microbial culture) based on whether mNGS testing was used or not. Results: A total of 147 patients were included in the no-mNGS group and 88 in the mNGS group. The mNGS group had a higher detection rate of rare pathogens than the no-mNGS group (21.6% vs 10.2%, p = 0.016). However, the mNGS group had lower rates of antibiotic-related complications, shorter hospital stays, and higher infection control rates compared with the no-mNGS group (p = 0.017, p = 0.003, and p = 0.028, respectively), while there was no significant difference in the duration of antibiotic use (p = 0.957). In culture-negative cases, the mNGS group had lower rates of antibiotic-related complications, shorter hospital stays, and a higher infection control rate than the no-mNGS group (p = 0.036, p = 0.033, p = 0.022, respectively), while there was no significant difference in the duration of antibiotic use (p = 0.748). Conclusion: mNGS improves detection of rare pathogens in BJIs. mNGS testing reduces antibiotic-related complications, shortens hospital stay and antibiotic use duration, and improves treatment success rate, benefits which are particularly evident in culture-negative cases.