Development and validation of a health literacy scale for family caregivers of older people with chronic illness.

BACKGROUND: Family caregivers (FCs) encounter a variety of health problems in older people with chronic illness, necessitating a certain level of health literacy to access, understand, appraise and apply health information and services. This study aimed to develop and validate a scale for measuring health literacy among FCs of older people with chronic illness. METHODS: Concept mapping was first employed to develop a conceptual model of health literacy of FCs. Scale domains were derived from the conceptual model, and item generation was performed using deductive and inductive methods. Quantitative methods, including merging scale dimensions and items, expert reviews, cognitive interviews, and item reduction analysis, were used to refine the scale. Confirmatory factor analysis was employed to validate the scale's structure. Concurrent validity, internal consistency, and test-retest reliability were also examined. RESULTS: A 20-dimension conceptual model was developed, and 60 items were generated for the scale. Expert review (content validity index > 0.85) and cognitive interview with FCs confirmed the relevance and clarity of the majority of the generated scale items. Confirmatory factor analysis with 451 FCs of older people with chronic illness supported a 5-factor structure (symptom management, daily personal care and household tasks, care coordination, communication and relationship with the care recipient, and self-care of caregivers) with 42 finalized scale items, including four levels of health literacy skills (accessing, understanding, appraising and applying health information). Concurrent validity with the European Health Literacy Questionnaire (HLS-EU-Q47) was satisfactory (r = 0.67, p < 0.01). The Cronbach's α coefficient of the scale was 0.96, with subscales ranging from 0.84 to 0.91. The two-week test-retest reliability was 0.77 (p < 0.01). CONCLUSION: This study developed a conceptual model explaining the concept and factors of health literacy among FCs of older people with chronic illness that could provide the groundwork for future studies in developing relevant evidence-based interventions. A new Health Literacy Scale-Family Caregiver (HLS-FC) with satisfactory psychometric properties was developed in this study, which can be utilized to identify caregivers with insufficient health literacy and facilitate timely interventions by healthcare professionals.

Integration of nonlinear two-photon excited fluorescence and photocatalysis boosts overall water splitting performance.

A nonlinear two-photon excited fluorescence photocatalytic system was constructed for the first time by integrating (ZnO)1-x(GaN)x photocatalyst and a fluorescence solution of phenanthridine derivatives. This work offers a strategy for increasing the photocatalytic solar spectral utilization rate and boosting the expectation for photocatalytic solar-to-hydrogen efficiencies.

Identification of a conserved G-quadruplex within the E165R of African swine fever virus (ASFV) as a potential antiviral target.

Identification of a conserved G-quadruplex in E165R of ASFVAfrican swine fever virus (ASFV) is a double-stranded DNA arbovirus with high transmissibility and mortality rates. It has caused immense economic losses to the global pig industry. Currently, no effective vaccines or medications are to combat ASFV infection. G-quadruplex (G4) structures have attracted increasing interest because of their regulatory role in vital biological processes. In this study, we identified a conserved G-rich sequence within the E165R gene of ASFV. Subsequently, using various methods, we verified that this sequence could fold into a parallel G4. In addition, the G4-stabilizers pyridostatin and 5,10,15,20-tetrakis-(N-methyl-4-pyridyl) porphin (TMPyP4) can bind and stabilize this G4 structure, thereby inhibiting E165R gene expression, and the inhibitory effect is associated with G4 formation. Moreover, the G4 ligand pyridostatin substantially impeded ASFV proliferation in Vero cells by reducing gene copy number and viral protein expression. These compelling findings suggest that G4 structures may represent a promising and novel antiviral target against ASFV.

IGF2BP3/NCBP1 complex inhibits renal tubular senescence through regulation of CDK6 mRNA stability.

Renal aging and the subsequent rise in kidney-related diseases are attributed to senescence in renal tubular epithelial cells (RTECs). Our study revealed that the abnormal expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader of RNA N6-methyladenosine, is critically involved in cisplatin-induced renal tubular senescence. In cisplatin-induced senescence of RTECs, the promoter activity and transcription of IGF2BP3 is markedly suppressed. It was due to the down regulation of MYC proto-oncogene (MYC), which regulates IGF2BP3 transcription by binding to the putative site at 1852-1863 of the IGF2BP3 promoter. Overexpression of IGF2BP3 ameliorated cisplatin-induced renal tubular senescence in vitro. Mechanistic studies revealed that IGF2BP3 inhibits cellular senescence in RTECs by enhancing cyclin-dependent kinase 6 (CDK6) mRNA stability and increasing its expression. The inhibition effect of IGF2BP3 on tubular senescence is partially reversed by the knockdown of CDK6. Further, IGF2BP3 recruits nuclear cap binding protein subunit 1 (NCBP1) and inhibits CDK6 mRNA decay, by recognizing m6A modification. Specifically, IGF2BP3 recognizes m6A motif "GGACU" at nucleotides 110-114 in the 5' untranslated region (UTR) field of CDK6 mRNA. The involvement of IGF2BP3/CDK6 in alleviating tubular senescence was confirmed in a cisplatin-induced acute kidney injury (AKI)-to-chronic kidney disease (CKD) model. Clinical data also suggests an age-related decrease in IGF2BP3 and CDK6 levels in renal tissue or serum samples from patients. These findings suggest that IGF2BP3/CDK6 may be a promising target in cisplatin-induced tubular senescence and renal failure.

Efficacy and safety of acupuncture for postpartum hypogalactia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postpartum hypogalactia (PH) is prominent during lactation and may negatively impact the mother's or infant's health. Acupuncture is widely used to increase maternal breast milk production. However, the effects of acupuncture on PH remain unclear. Therefore, this review aimed to evaluate the efficacy and safety of acupuncture in individuals with PH. MATERIALS AND METHODS: Articles on potentially eligible randomized controlled trials (RCTs) on acupuncture for PH published from database inception to October 2023 were retrieved from the PubMed, Web of Science, Cochrane Library, EMBASE, EBSCO, Scopus, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, WanFang, and VIP databases. Two reviewers independently screened the records, extracted essential information, and evaluated the methodological quality of the RCTs using the revised Cochrane risk-of-bias (RoB) tool. The primary outcome was a change in serum prolactin (PRL) levels before and after treatment. Secondary outcomes included milk secretion volume (MSV), total effective rate (TER), mammary fullness degree (MFD), and exclusive breastfeeding rate (EBR). Meta-analyses were performed using RevMan v5.4. Finally, the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. RESULTS: This study included 19 RCTs involving 2,400 participants. The included studies were classified as having an unclear to high RoB. Our findings indicated that, overall, acupuncture showed a significant effect in increasing serum PRL levels (standardized mean differences [SMDs] = 1.09, 95% confidence interval [CI]: 0.50, 1.68), MSV (SMD = 1.69, 95% CI: 0.53, 2.86), TER (relative risk [RR] = 1.25, 95% CI: 1.10, 1.42), and EBR (RR = 2.01, 95% CI: 1.07, 3.78) compared to that in the control group; however, no difference in MFD (SMD = 1.17, 95% CI: -0.09, 2.42) was observed. In the subgroup analysis, acupuncture combined with Chinese herbs or conventional treatment was significantly more effective in increasing serum PRL levels, MSV, and TER than did Chinese herbs or conventional treatment alone. Moreover, acupuncture alone resulted in significantly higher serum PRL levels compared to Chinese herbs; however, this benefit was not observed for TER and MFD. The quality of evidence was critically low. CONCLUSION: Acupuncture may effectively increase milk secretion in women with PH. However, owing to the low quality of evidence, further rigorously designed studies are warranted to confirm our findings.

Cell-wall-anchored proteins affect invasive host colonization and biofilm formation in Staphylococcus aureus.

As a major human and animal pathogen, Staphylococcus aureus can attach to medical implants (abiotic surface) or host tissues (biotic surface), and further establish robust biofilms which enhances resistance and persistence to host immune system and antibiotics. Cell-wall-anchored proteins (CWAPs) covalently link to peptidoglycan, and largely facilitate the colonization of S. aureus on various surfaces (including adhesion and biofilm formation) and invasion into host cells (including adhesion, immune evasion, iron acquisition and biofilm formation). During biofilm formation, CWAPs function in adhesion, aggregation, collagen-like fiber network formation, and consortia formation. In this review, we firstly focus on the structural features of CWAPs, including their intracellular function and interactions with host cells, as well as the functions and ligand binding of CWAPs in different stages of S. aureus biofilm formation. Then, the roles of CWAPs in different biofilm processes with regards in development of therapeutic approaches are clarified, followed by the association between CWAPs genes and clonal lineages. By touching upon these aspects, we hope to provide comprehensive knowledge and clearer understanding on the CWAPs of S. aureus and their roles in biofilm formation, which may further aid in prevention and treatment infection and vaccine development.

Effectiveness of web-based intervention on reducing symptom burden, improving self-management capabilities and self-efficacy among prostate cancer survivors: a systematic review and meta-analysis protocol.

INTRODUCTION: Prostate cancer is the most common malignant disease within the male genitourinary system. Advances in cancer screening and treatment have significantly ameliorated the survival rates of patients with prostate cancer. Nonetheless, prostate cancer survivors report various degrees of cancer-related symptoms. These symptoms cause physiological and psychological suffering, leading to a deterioration of quality of life. Web-based interventions may facilitate the management of symptoms due to their flexibility, accessibility and convenience. However, the efficacy of web-based interventions in reducing symptom burden remains to be confirmed. Consequently, this systematic review and meta-analysis aims to comprehensively synthesise existing evidence, evaluate the effectiveness of web-based interventions in reducing symptom burden among patients and furnish a reference for clinical practice. METHODS AND ANALYSIS: This protocol strictly adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol guidelines. We will comprehensively search six databases (PubMed, Web of Science, Cochrane, Embase, CINAHL and PsycINFO) from their inception to March 2024 in order to identify clinical trials on the efficacy of web-based interventions for prostate cancer survivors. Two reviewers will independently conduct study selection, data extraction and quality assessment. The risk bias of included studies will be assessed using the Cochrane Risk of Bias Tool for randomised trials 2.0, and the strength of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline. Meta-analysis will be performed using STATA V.16.0, and the effect size will be calculated using the standardised mean difference and its 95% CI. Heterogeneity will be assessed using Cochran's Q statics and inconsistency will be measured using the I2 statistics. Potential sources of bias will be evaluated. ETHICS AND DISSEMINATION: Ethics approval is not required for this review as no human participants will be involved. The results will be disseminated via a peer-reviewed journal or an academic conference. PROSPERO REGISTRATION NUMBER: CRD42023457718.

Differential alteration in Lactiplantibacillus plantarum subsp. plantarum quorum-sensing systems and reduced Candida albicans yeast survival and virulence gene expression in dual-species interaction.

Candida albicans (C. albicans) and Lactiplantibacillus plantarum subsp. plantarum (L. plantarum) are frequently identified in various niches, but their dual-species interaction, especially with C. albicans in yeast form, remains unclear. This study aimed to investigate the dual-species interaction of L. plantarum and C. albicans, including proliferation, morphology, and transcriptomes examined by selective agar plate counting, microscopy, and polymicrobial RNA-seq, respectively. Maintaining a stable and unchanged growth rate, L. plantarum inhibited C. albicans yeast cell proliferation but not hyphal growth. Combining optical microscopy and atomic force microscopy, cell-to-cell direct contact and co-aggregation with L. plantarum cells surrounding C. albicans yeast cells were observed during dual-species interaction. Reduced C. albicans yeast cell proliferation in mixed culture was partially due to L. plantarum cell-free culture supernatant but not the acidic environment. Upon polymicrobial transcriptomics analysis, interesting changes were identified in both L. plantarum and C. albicans gene expression. First, two L. plantarum quorum-sensing systems showed contrary changes, with the activation of lamBDCA and repression of luxS. Second, the upregulation of stress response-related genes and downregulation of cell cycle, cell survival, and cell integrity-related pathways were identified in C. albicans, possibly connected to the stress posed by L. plantarum and the reduced yeast cell proliferation. Third, a large scale of pathogenesis and virulence factors were downregulated in C. albicans, indicating the potential interruption of pathogenic activities by L. plantarum. Fourth, partial metabolism and transport pathways were changed in L. plantarum and C. albicans. The information in this study might aid in understanding the behavior of L. plantarum and C. albicans in dual-species interaction.IMPORTANCEThe anti-Candida albicans activity of Lactiplantibacillus plantarum has been explored in the past decades. However, the importance of C. albicans yeast form and the effect of C. albicans on L. plantarum had also been omitted. In this study, the dual-species interaction of L. plantarum and C. albicans was investigated with a focus on the transcriptomes. Cell-to-cell direct contact and co-aggregation with L. plantarum cells surrounding C. albicans yeast cells were observed. Upon polymicrobial transcriptomics analysis, interesting changes were identified, including contrary changes in two L. plantarum quorum-sensing systems and reduced cell survival-related pathways and pathogenesis determinants in C. albicans.

Research status and trends of physical activity on depression or anxiety: a bibliometric analysis.

Background: Anxiety and depression are prevalent mental disorders. As modern society continues to face mounting pressures, the incidence of anxiety and depression is on the rise. In recent years, there has been an increasing breadth of research exploring the relationship between anxiety, depression, and physical activity (PA). However, the current research progress and future development trends are unclear. The purpose of this study is to explore the research hotspots and development trends in this field, and to provide guidance for future studies and to provide some reference for clinicians. Methods: We searched the relevant literature of Web of Science Core Collection from the establishment of the database to August 15, 2023. CiteSpace, VOSviewer and Bibliometrix Packages based on the R language were used to analyze the number of publications, countries, institutions, journals, authors, references, and keywords. Results: A total of 1,591 studies were included in the analysis, and the research in the field of PA on anxiety or depression has consistently expanded. The USA (304 publications), Harvard University (93 publications), and the journal of affective disorders (97 publications) were the countries, institutions, and journals that published the highest number of articles, respectively. According to the keywords, students and pregnant women, adult neurogenesis, and Tai Chi were the groups of concern, physiological and pathological mechanisms, and the type of PA of interest, respectively. Conclusion: The study of PA on anxiety or depression is experiencing ongoing expansion. Clinicians can consider advising patients to take mind-body exercise to improve mood. In addition, future researchers can explore the mind-body exercise and its impact on anxiety or depression, PA and anxiety or depression in specific populations, and adult neurogenesis of various exercise in anxiety or depression.

Supplements for cognitive ability in patients with mild cognitive impairment or Alzheimer's disease: a protocol for systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: Considering the increasing incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI) worldwide, there is an urgent need to identify efficacious, safe and convenient treatments. Numerous investigations have been conducted on the use of supplements in this domain, with oral supplementation emerging as a viable therapeutic approach for AD or MCI. Nevertheless, given the multitude of available supplements, it becomes imperative to identify the optimal treatment regimen. METHODS AND ANALYSIS: Eight academic databases and three clinical trial registries will be searched from their inception to 1 June 2023. To identify randomised controlled trials investigating the effects of supplements on patients with AD or MCI, two independent reviewers (X-YZ and Y-QL) will extract relevant information from eligible articles, while the risk of bias in the included studies will be assessed using the Rob 2.0 tool developed by the Cochrane Collaboration. The primary outcome of interest is the overall cognitive function. Pair-wise meta-analysis will be conducted using RevMan V.5.3, while network meta-analysis will be carried out using Stata 17.0 and ADDIS 1.16.8. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The GRADE system will be employed to assess the quality of evidence. This study is scheduled to commence on 1 June 2023 and conclude on 1 October 2023. ETHICS AND DISSEMINATION: Ethics approval is not required for systematic review and network meta-analysis. The results will be submitted to a peer-reviewed journal or at a conference. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42023414700).

Clinical and Pathological Features of Pilomatrixoma in Children: A Retrospective Study.

INTRODUCTION: Pilomatrixoma is a benign skin neoplasm that is common in children and is often misdiagnosed. This study aimed to summarize the clinical and pathological features of pilomatrixoma in children. METHODS: Data on demographic information, clinical and pathological features, diagnosis, and treatment of 171 patients with pilomatrixoma from Shenzhen Baoan Women's and Children's Hospital were collected and analyzed retrospectively. RESULTS: The mean age of the patients was 5.7 (standard deviation [SD] = 3.9) years old, and there were 2 age peaks (≤1 year old, 5-11 years old) and 2 age valleys (2-4 years old, ≥12 years old). The mean disease course was 9.3 (SD = 14.1) months, 69.0%, 86.5%, and 95.3% of the patients' disease course in 6 months, 12 months, and 24 months, respectively. The mean tumor volume was 0.6 (SD = 1.0) cm3, and 81.3% of the patients' tumor volume ≤1.0 cm3. Tumors were distributed sequentially in the head and neck (77.2%), upper limbs (12.9%), trunk (7.6%), and lower limbs (2.3%). The correct rates of clinical and ultrasonic diagnosis were 50.9% and 38.6%, respectively. The two most common pathological features of pilomatrixoma were shadow cells (99.4%) and basaloid cells (94.7%). There were no significant differences in age, disease course, or tumor volume between the male and female patients (p > 0.05). The age and tumor volume of the patients in different body parts were significantly different (P1 = 3.10E-05 and P2 = 5.60E-05, respectively). The correlation between the disease course and tumor volume was positively significant (p ≤ 0.05). There was a significant correlation between the disease course and tumor volume in patients with tumors at upper limbs (p = 0.03). CONCLUSION: The age of children with pilomatrixoma presented 2 peaks and 2 valleys. Most patients had disease courses in 24 months and with tumor volumes ≤1.0 cm3. The correct rates of clinical and ultrasonic diagnosis were relatively low. The head and neck were the most common distribution sites of pilomatrixoma, and shadow cells and basaloid cells were the most common pathological features. The tumor volume was positively correlated with disease course in patients with pilomatrixoma.

SUTrans-NET: a hybrid transformer approach to skin lesion segmentation.

Melanoma is a malignant skin tumor that threatens human life and health. Early detection is essential for effective treatment. However, the low contrast between melanoma lesions and normal skin and the irregularity in size and shape make skin lesions difficult to detect with the naked eye in the early stages, making the task of skin lesion segmentation challenging. Traditional encoder-decoder built with U-shaped networks using convolutional neural network (CNN) networks have limitations in establishing long-term dependencies and global contextual connections, while the Transformer architecture is limited in its application to small medical datasets. To address these issues, we propose a new skin lesion segmentation network, SUTrans-NET, which combines CNN and Transformer in a parallel fashion to form a dual encoder, where both CNN and Transformer branches perform dynamic interactive fusion of image information in each layer. At the same time, we introduce our designed multi-grouping module SpatialGroupAttention (SGA) to complement the spatial and texture information of the Transformer branch, and utilize the Focus idea of YOLOV5 to construct the Patch Embedding module in the Transformer to prevent the loss of pixel accuracy. In addition, we design a decoder with full-scale information fusion capability to fully fuse shallow and deep features at different stages of the encoder. The effectiveness of our method is demonstrated on the ISIC 2016, ISIC 2017, ISIC 2018 and PH2 datasets and its advantages over existing methods are verified.

Novel biomarkers of inflammation-associated immunity in cervical cancer.

Background: Cervical cancer (CC) is a highly malignant gynecological cancer with a direct causal link to inflammation, primarily resulting from persistent high-risk human papillomavirus (HPV) infection. Given the challenges in early detection and mid to late-stage treatment, our research aims to identify inflammation-associated immune biomarkers in CC. Methods: Using a bioinformatics approach combined with experimental validation, we integrated two CC datasets (GSE39001 and GSE63514) in the Gene Expression Omnibus (GEO) to eliminate batch effects. Immune-related inflammation differentially expressed genes (DGEs) were obtained by R language identification. Results: This analysis identified 37 inflammation-related DEGs. Subsequently, we discussed the different levels of immune infiltration between CC cases and controls. Weighted gene co-expression network analysis (WGCNA) identified seven immune infiltration-related modules in CC. We identified 15 immune DEGs associated with inflammation at the intersection of these findings. In addition, we constructed a protein interaction network using the String database and screened five hub genes using "CytoHubba": CXC chemokine ligand 8 (CXCL8), CXC chemokine ligand 10 (CXCL10), CX3C chemokine receptor 1 (CX3CR1), Fc gamma receptors 3B (FCGR3B), and SELL. The expression of these five genes in CC was determined by PCR experiments. In addition, we assessed their diagnostic value and further analyzed the association of immune cells with them. Conclusions: Five inflammation- and immune-related genes were identified, aiming to provide new directions for early diagnosis and mid to late-stage treatment of CC from multiple perspectives.

Three-Four Photon Transition Mn(II) Complex Monitoring Lysosome-Related ATP in Real Time via Fluorescence Lifetime Imaging.

Currently, in situ monitoring of the adenosine triphosphate (ATP) level in lysosomes is critical to understand their involvement in various biological processes, but it remains difficult due to the interferences of limited targeting and low resolution of fluorescent probes. Herein, we report a classic Mn(II) probe (FX2-MnCl2) with near-infrared (NIR) nonlinear (NLO) properties, accompanied by three-four photon transition and fivefold fluorescence enhancement in the presence of ATP. FX2-MnCl2 combines with ATP through dual recognition sites of diethoxy and manganese ions to reflect slightly fluorescence lifetime change. Through the synergy of multiphoton fluorescence imaging (MP-FI) and multiphoton fluorescence lifetime imaging microscopy (MP-FLIM), it is further demonstrated that FX2-MnCl2 displays lysosome-specific targeting behavior, which can monitor lysosome-related ATP migration under NIR laser light. This work provides a novel multiphoton transformation fluorescence complex, which might be a potential candidate as a simple and straightforward biomarker of lysosome ATP in vitro for clinical diagnosis.

The effect of acupuncture on oxidative stress in animal models of vascular dementia: a systematic review and meta-analysis.

BACKGROUND: Growing evidence showed that acupuncture may improve cognitive function by reducing oxidative stress, key to the pathogenesis in vascular dementia (VaD), but this is yet to be systematically analysed. This study aimed to summarize and evaluate the effect of acupuncture on oxidative stress in animal models of VaD. METHOD: Eight databases including PubMed, Embase, Web of Science, Cochrane library, CNKI, Wan Fang, CBM, and VIP were searched since their establishment until April 2023, for studies that reported the effect of acupuncture on oxidative stress in VaD animal models. Relevant literature was screened, and information was extracted by two reviewers. The primary outcomes were the levels of oxidative stress indicators. The methodological quality was assessed via the SYRCLE Risk of Bias Tool. Statistical analyses were performed using the RevMan and Stata software. RESULTS: In total, 22 studies with 747 animals were included. The methodology of most studies had flaws or uncertainties. The meta-analysis indicated that, overall, acupuncture significantly reduced the expression of pro-oxidants including reactive oxygen species (standardized mean differences [SMDs] = -4.29, 95% confidence interval [CI]: -6.26, -2.31), malondialdehyde (SMD = -2.27, 95% CI: -3.07, -1.47), nitric oxide (SMD = -0.85, 95% CI: -1.50, -0.20), and nitric oxide synthase (SMD = -1.01, 95% CI: -1.69, -0.34) and enhanced the levels of anti-oxidants including super oxide dismutase (SMD = 2.80, 95% CI: 1.98, 3.61), glutathione peroxidase (SMD = 1.32, 95% CI: -0.11, 2.76), and catalase (SMD = 1.31, 95% CI: 0.05, 2.58) in VaD animal models. In subgroup analyses, acupuncture showed significant effects on most variables. Only partial modelling methods and treatment duration could interpret the heterogeneity of some outcomes. CONCLUSION: Acupuncture may inhibit oxidative stress to improve cognitive deficits in animal models of VaD. Nevertheless, the methodological quality is unsatisfactory. More high-quality research with a rigorous design and further experimental researches and clinical trials are needed to confirm these findings. SYSTEMATIC REVIEW REGISTRATION: This study was registered in PROSPERO (CRD42023411720).

Anomalous right coronary artery originating from the left anterior descending artery with stenosis: a highlighted imaging observation.

This imaging observation underscores a rare single coronary artery anomaly, wherein the right coronary artery originates from the left anterior descending artery (LAD). The stenosis in the proximal LAD adds complexity, emphasizing the need for multidisciplinary evaluation and decision-making.

Drug repurposing screens identify Tubercidin as a potent antiviral agent against porcine nidovirus infections.

The emergence of new coronaviruses poses a significant threat to animal husbandry and human health. Porcine epidemic diarrhea virus (PEDV) is considered a re-emerging porcine enteric coronavirus, which causes fatal watery diarrhea in piglets. Currently, there are no effective drugs to combat PEDV. Drug repurposing screens have emerged as an attractive strategy to accelerate antiviral drug discovery and development. Here, we screened 206 natural products for antiviral activity using live PEDV infection in Vero cells and identified ten candidate antiviral agents. Among them, Tubercidin, a nucleoside analog derived from Streptomyces tubercidicus, showed promising antiviral activity against PEDV infection. Furthermore, we demonstrated that Tubercidin exhibited significant antiviral activity against both classical and variant PEDV. Time of addition assay showed that Tubercidin displayed a significant inhibitory effect on viral post-entry events but not during other periods. Molecular docking analysis indicated that Tubercidin had better docking efficiency and formed hydrophobic interactions with the active pocket of RNA-dependent RNA polymerase (RdRp) of PEDV and other nidoviruses. Additionally, Tubercidin can effectively suppress other porcine nidoviruses, such as SADS-CoV and PRRSV, demonstrating its broad-spectrum antiviral properties. In summary, our findings provide valuable evidence for the antiviral activity of Tubercidin and offer insights into the development of new strategies for the prevention and treatment of coronavirus infections.

Blocking the interaction between circTNRC18 and LIN28A promotes trophoblast epithelial-mesenchymal transformation and alleviates preeclampsia.

Defects in migration and invasion caused by dysregulation of trophoblastic epithelial-mesenchymal transformation (EMT) play a vital role in preeclampsia (PE). We have previously shown that circTNRC18 inhibits the migration and EMT of trophoblasts; however, its role in PE remains unknown. Herein, we demonstrate that circTNRC18 interacts with an RNA-binding protein, lin-28 homolog A (LIN28A), and this interaction is enhanced in PE placental tissue. LIN28A overexpression suppresses circTNRC18-mediated inhibition of trophoblast migration, invasion, and EMT, whereas LIN28A knockdown promotes them. The intracellular distribution of LIN28A is regulated by circTNRC18, where it promotes the expression of insulin-like growth factor II by stabilizing its mRNA. circTNRC18 also promotes complex formation between GATA-binding factor 1 (GATA1) and sine oculis homeobox 1 (SIX1) by inhibiting LIN28A-GATA1 interaction. GATA1-SIX1 promotes transcription of grainyhead-like protein 2 homolog and circTNRC18-mediated regulation of cell migration and invasion. Moreover, blocking circTNRC18-LIN28A interaction with antisense nucleotides alleviates PE in a mouse model of reduced uterine perfusion pressure. Thus, targeting the circTNRC18-LIN28A regulatory axis may be a novel PE treatment method.

A classical herbal formula alleviates high-fat diet induced nonalcoholic steatohepatitis (NASH) via targeting mitophagy to rehabilitate dysfunctional mitochondria, validated by UPLC-HRMS identification combined with in vivo experiment.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) has caused a significant burden on public health care systems, the economy and society. However, there has still been no officially approved pharmacotherapy for NASH. It has been suggested that oxidative stress and mitochondrial dysfunction play vital roles in NASH pathological progression. Shugan Xiaozhi (SG) formula, as a kind of classical herbal formula, was shown to attenuate NASH. PURPOSE: This study aimed to explore the potential mechanisms of SG formula treating NASH. STUDY DESIGN AND METHODS: Ultra-high-performance liquid chromatography-high resolution mass spectrometry combined with bioinformatics analysis was applied to explore the therapeutic targets and main components of SG formula. Moreover, in vivo NASH model was utilized to confirmed the therapeutic effects of SG formula. Molecular docking analysis and further validation experiments were conducted to verify the results of bioinformatics analysis. RESULTS: The in vivo experiments confirmed SG formula significantly attenuated hepatic pathological progression and relieved oxidative stress in high-fat diet (HFD) induced - NASH model. Ultra-high-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) combined with bioinformatics analysis expounded the components of SG formula and revealed the mitochondrial regulation mechanism of SG formula treating NASH. Further in vivo experiments validated that SG formula could alleviate oxidative stress by rehabilitating the structure and function of mitochondria, which was strongly related to regulating mitophagy. CONCLUSION: In summary, this study demonstrated that SG formula, which could attenuate NASH by regulating mitochondria and might be a potential pharmacotherapy for NASH.