Bidirectional correlation between gastroesophageal reflux disease and sleep problems: a systematic review and meta-analysis.

Objectives: Gastroesophageal reflux disease (GERD) and sleep problems are highly prevalent among the general population. Both them are associated with a variety of psychiatric disorders such as depression and anxiety, which is highlighting an underexplored connection between them. This meta-analysis aims to explore the association between sleep problems and GERD. Methods: We conducted a comprehensive search on PubMed, Cochrane Library, Embase, and Web of Science, using Medical Subject Headings (MeSH) and keywords, covering articles from the inception of the databases until August 2023. Stata statistical software, version 14.0, was utilized for all statistical analyses. A fixed-effects model was applied when p > 0.1 and I2 ≤ 50%, while a random-effects model was employed for high heterogeneity (p < 0.1 and I2 > 50%). Funnel plots and Egger's test were used to assess publication bias. Results: Involving 22 studies, our meta-analysis revealed that insomnia, sleep disturbance, or short sleep duration significantly increased the risk of GERD (OR = 2.02, 95% CI [1.64-2.49], p < 0.001; I2 = 66.4%; OR = 1.98, 95% CI [1.58-2.50], p < 0.001, I2 = 50.1%; OR = 2.66, 95% CI [2.02-3.15], p < 0.001; I2 = 62.5%, respectively). GERD was associated with an elevated risk of poor sleep quality (OR = 1.47, 95% CI [1.47-1.79], p < 0.001, I2 = 72.4%), sleep disturbance (OR = 1.47, 95% CI [1.24-1.74], p < 0.001, I2 = 71.6%), or short sleep duration (OR = 1.17, 95% CI [1.12-1.21], p < 0.001, I2 = 0). Conclusion: This meta-analysis establishes a bidirectional relationship between four distinct types of sleep problems and GERD. The findings offer insights for the development of innovative approaches in the treatment of both GERD and sleep problems.

Human Breast Milk Exosomal miRNAs are Influenced by Premature Delivery and Affect Neurodevelopment.

SCOPE: This study investigates the exosomal microRNA (miRNA) profiles of term and preterm breast milk, including the most abundant and differentially expressed (DE) miRNAs, and their impact on neurodevelopment in infants. METHODS AND RESULTS: Mature milk is collected from the mothers of term and preterm infants. Using high-throughput sequencing and subsequent data analysis, exosomal miRNA profiles of term and preterm human breast milk (HBM) are acquired and it is found that the let-7 and miR-148 families are the most abundant miRNAs. Additionally, 23 upregulated and 15 downregulated miRNAs are identified. MiR-3168 is the most upregulated miRNA in preterm HBM exosome, exhibiting targeting activity toward multiple genes involved in the SMAD and MAPK signaling pathways and playing a crucial role in early neurodevelopment. Additionally, the effects of miR-3168 on neurodevelopment is confirmed and it is determined that it is an essential factor in the differentiation of neural stem cells (NSCs). CONCLUSION: This study demonstrates that miRNA expression in breast milk exosomes can be influenced by preterm delivery, thereby potentially impacting neurodevelopment in preterm infants.

Management after cataract surgery for patients with diabetic retinopathy: a systematic review and meta-analysis.

PURPOSE: To evaluate the safety and effectiveness of various treatment modalities in patients with diabetic retinopathy (DR) who underwent cataract surgery. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted using the PubMed, Embase, Cochrane Library, and CNKI databases up to December 22, 2021. The safety and efficacy of treatment modalities were assessed using the risk ratio (RR) to compare the progression of DR and the mean difference to evaluate the best corrected visual acuity (BCVA) and macular thickness (MT). RESULTS: The meta-analysis of the RCTs revealed that anti-VEGF (anti-vascular endothelial growth factor) drugs significantly reduced the progression of DR [RR: 0.37 (95%CI 0.19, 0.70), P = 0.002] and improved BCVA [mean difference = - 0.06 (- 0.12, - 0.01), P = 0.03] in patients with pre-existing DR who underwent cataract surgery. Steroid drugs also showed a significant reduction in macular thickness [mean difference = - 55.63 (- 90.73, - 20.53), I2 = 56%, P = 0.002] in DR patients two weeks after cataract surgery compared to the control group. The safety profiles of different management options did not differ significantly. CONCLUSION: The present meta-analysis suggests that anti-VEGF drugs can effectively slow down the progression of diabetic retinopathy, improve BCVA, and reduce MT in DR patients who underwent cataract surgery. Steroid drugs also show promise in reducing MT. However, further studies with larger sample sizes are required to compare the efficacy and safety of different management options in a multi-center clinical setting.

Ssc-miR-7139-3p suppresses foot-and-mouth disease virus replication by promoting degradation of 3Cpro through targeting apoptosis-negative regulatory gene Bcl-2.

Foot-and-mouth disease is a highly contagious and infectious disease affecting cloven-hoofed animals. Disease control is complicated by its highly contagious nature and antigenic diversity. Host microRNAs (miRNAs) are post-transcriptional regulators that either promote or repress viral replications in virus infection. In the present study, we found that ssc-miR-7139-3p (Sus scrofa miR-7139-3p) was significantly up-regulated in host cells during foot-and-mouth disease virus (FMDV) infection. Overexpression of miR-7139-3p attenuated FMDV replication, whereas inhibition promoted FMDV replication. In addition, the survival rate of FMDV infected suckling mice was increased through injection of miR-7139-3p agomiR. Further studies revealed that miR-7139-3p targets Bcl-2 to initiate the apoptotic pathway and caspase-3 cleaved 3Cpro behind the 174th aspartic acid (D174), which eventually promotes the degradation of 3Cpro. Overall, our findings demonstrate that miR-7139-3p suppresses FMDV replication by promoting degradation of 3Cpro through targeting the apoptosis-negative regulatory gene Bcl-2.

Investigating pigeon circovirus infection in a pigeon farm: molecular detection, phylogenetic analysis and complete genome analysis.

BACKGROUND: Pigeon circovirus infections in pigeons (Columba livia domestica) have been reported worldwide. Pigeons should be PiCV-free when utilized as qualified experimental animals. However, pigeons can be freely purchased as experimental animals without any clear guidelines to follow. Herein, we investigated the status quo of PiCV infections on a pigeon farm in Beijing, China, which provides pigeons for experimental use. RESULTS: PiCV infection was verified in at least three types of tissues in all forty pigeons tested. A total of 29 full-length genomes were obtained and deposited in GenBank. The whole genome sequence comparison among the 29 identified PiCV strains revealed nucleotide homologies of 85.8-100%, and these sequences exhibited nucleotide homologies of 82.7-98.9% as compared with those of the reference sequences. The cap gene displayed genetic diversity, with a wide range of amino acid homologies ranging from 64.5% to 100%. Phylogenetic analysis of the 29 full-genome sequences revealed that the PiCV strains in this study could be further divided into four clades: A (17.2%), B (10.4%), C (37.9%) and D (34.5%). Thirteen recombination events were also detected in 18 out of the 29 PiCV genomes obtained in this study. Phylogenetic research using the rep and cap genes verified the recombination events, which occurred between clades A/F, A/B, C/D, and B/D among the 18 PiCV strains studied. CONCLUSIONS: In conclusion, PiCV infection, which is highly genetically varied, is extremely widespread on pigeon farms in Beijing. These findings indicate that if pigeons are to be used as experimental animals, it is necessary to evaluate the impact of PiCV infection on the results.

Pathway of Room-Temperature Formation of CdSeS Magic-Size Clusters from Mixtures of CdSe and CdS Samples.

The synthetic application of prenucleation-stage samples of colloidal semiconductor quantum dots (QDs) is in its infancy. It is shown that when two prenucleation-stage samples of binary CdSe and CdS are mixed, ternary CdSeS magic-size clusters (MSCs) grow at room temperature in dispersion. As the amount of the CdS sample increases, the optical absorption of the CdSeS MSCs blueshifts from ≈380 to ≈360 nm. It is proposed that the cluster in the CdSe sample reacts with the CdS monomer from the CdS sample. The monomer substitution reaction of CdSe by CdS can proceed continuously; thus, CdSeS MSCs with tunable compositions are obtained. The present study provides compelling evidence that clusters formed in the prenucleation stage of QDs. The clusters are precursor compounds (PCs) of MSCs, transforming at room temperature with the thermoneutrality principle of isodesmic reactions. The nucleation and growth of QDs follows a multi-step non-classical instead of one-step classical nucleation model.

Constructing and validating a risk model based on neutrophil-related genes for evaluating prognosis and guiding immunotherapy in colon cancer.

BACKGROUND: Colon cancer is one of the most common digestive tract malignancies. Although immunotherapy has brought new hope to colon cancer patients, there is still a large proportion of patients who do not benefit from immunotherapy. Studies have shown that neutrophils can interact with immune cells and immune factors to affect the prognosis of patients. METHODS: We first determined the infiltration level of neutrophils in tumors using the CIBERSORT algorithm and identified key genes in the final risk model by Spearman correlation analysis and subsequent Cox analysis. The risk score of each patient was obtained by multiplying the Cox regression coefficient and the gene expression level, and patients were divided into two groups based on the median of risk score. Differences in overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier survival analysis, and model accuracy was validated in independent dataset. Differences in immune infiltration and immunotherapy were evaluated by immunoassay. Finally, immunohistochemistry and western blotting were performed to verify the expression of the three genes in the colon normal and tumor tissues. RESULTS: We established and validated a risk scoring model based on neutrophil-related genes in two independent datasets, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, with SLC11A1 and SLC2A3 as risk factors and MMP3 as a protective factor. A new nomogram was constructed and validated by combining clinical characteristics and the risk score model to better predict patients OS and PFS. Immune analysis showed that patients in the high-risk group had immune cell infiltration level, immune checkpoint level and tumor mutational burden, and were more likely to benefit from immunotherapy. CONCLUSIONS: The low-risk group showed better OS and PFS than the high-risk group in the neutrophil-related gene-based risk model. Patients in the high-risk group presented higher immune infiltration levels and tumor mutational burden and thus may be more responsive to immunotherapy.

Thiotepa-busulfan-fludarabine-based conditioning as a promising approach prior to allogeneic hematopoietic stem cell transplantation in patients with blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy associated with a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a potential treatment strategy for BPDCN, standardized conditioning regimens remain lacking. In this manuscript, we present two cases of BPDCN that were treated with a thiotepa-busulfan-fludarabine (TBF)-based conditioning regimen prior to allo-HSCT. Both cases demonstrated complete remission post-transplantation, sustained donor chimerism, and remission maintenance, suggesting the potential efficacy of the TBF conditioning regimen for BPDCN transplantation. Given the small sample size in our study, we emphasize caution and advocate for larger studies to confirm the efficacy of TBF in the treatment of BPDCN.

Isthmin-1 alleviates cardiac ischemia/reperfusion injury through cGMP-PKG signaling pathway.

AIMS: Ischemia/reperfusion (I/R) injury is an important complication of reperfusion therapy for acute myocardial infarction, extremely compromising the cardiac benefits of revascularization, however, specific and efficient treatment for cardiac I/R injury is still lacking. Isthmin-1 (ISM1) is a novel adipokine, and plays indispensable roles in regulating glycolipid metabolism and cell survival. The present study aims to investigate the potential role and molecular mechanism of ISM1 in cardiac I/R injury using gain- and loss-of-function approaches. METHODS AND RESULTS: Cardiac-specific ISM1 overexpression and silence were achieved using an adeno-associated virus serotype 9 system, and then these mice were subjected to I/R surgery, followed by biochemical test, echocardiography and histopathologic examinations, etc. Meanwhile, neonatal rat cardiomyocytes (NRCMs) with ISM1 silence or overexpression also received simulated I/R (sI/R) injury to further verify its role in vitro. The potential downstream pathways and molecular targets of ISM1 were screened by RNA-sequencing. We also treated injured mice and NRCMs with recombinant ISM1 (rISM1) to explore whether supplementation with ISM1 was sufficient to protect against I/R injury. Furthermore, acute myocardial infarction patients with percutaneous coronary intervention (PCI) and paired healthy controls were included to reveal the clinical relevance of circulating ISM1. Cardiac-specific ISM1 silencing aggravated while ISM1 overexpression alleviated I/R-induced acute cardiac injury and cardiac remodeling and dysfunction. Mechanistically, ISM1 targeted αvß5 integrin to facilitate the nuclear accumulation of nuclear transcription factor Y subunit alpha, transcriptionally increased soluble guanylyl cyclase beta subunit expression, and eventually enhanced cGMP generation. Besides, we confirmed that treatment with rISM1 before or after reperfusion could confer cardioprotective effects in mice. Clinically, lower ISM1 levels post-PCI was associated with worse outcome in patients. CONCLUSION: ISM1 can protect against cardiac I/R injury through cGMP-PKG signaling pathway, and it is a promising therapeutic and predictive target of cardiac I/R injury.

Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway.

Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)-NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing.

Lipophilic Group-Modified Manganese(II)-Based Contrast Agents for Vascular and Hepatobiliary Magnetic Resonance Imaging.

Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure-activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N',N'-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides.

Phosphoproteomic analysis of APP/PS1 mice of Alzheimer's disease by DIA based mass spectrometry analysis with PRM verification.

Traditional Chinese medicine has been utilized in China for approximately thousands of years in clinical settings to prevent Alzheimer's disease (AD) and enhance memory, despite the lack of a systematic exploration of its biological underpinnings. Exciting research has corroborated the beneficial effects of tetrahydroxy stilbene glycoside (TSG), an extract derived from Polygonum multiflorum, in delaying learning and memory impairment in a model that mimics AD. Therefore, the primary objective of this study is to investigate the major function of TSG upon protein regulation in AD. Herein, a novel approach, encompassing data independent acquisition (DIA), DIA phosphorylated proteomics, and parallel reaction monitoring (PRM), was utilized to integrate quantitative proteomic data collected from APP/PS1 mouse model exhibiting toxic intracellular aggregation of Aß. Initially, we deliberated upon both single and multi-dimensional data pertaining to AD model mice. Furthermore, we authenticated disparities in protein phosphorylation quantity and expression, phosphorylation function, and ultimately phosphorylation kinase analysis. In order to validate the results, we utilized PRM ion monitoring technology to identify potential protein or peptide biomarkers. In the mixed samples, targeted detection of 50 target proteins revealed that 26 to 33 target proteins were stably detected by PRM. In summary, our findings provide new candidates for AD biomarker, which have been identified and validated through protein researches conducted on mouse brains. This offers a wealth of potential resources for extensive biomarker validation in neurodegenerative diseases. SIGNIFICANCE: DIA phosphorylated proteomics technique was used to detect and analyze phosphorylated proteins in brain tissues of mice with AD. Data were analyzed by various bioinformatics tools to explore the phosphorylation events and characterize them related to TSG. The results of DIA were further verified by PRM. Besides, we mapped the major metabolite classes emerging from the analyses to key biological pathways implicated in AD to understand the potential roles of the molecules and the interactions in triggering symptom onset and progression of AD. Meanwhile, we clarified that in the context of AD onset and TSG intervention, the changes in proteins, protein phosphorylation, phosphorylation kinases, and the internal connections.

Tunneling nanotubes: The transport highway for astrocyte-neuron communication in the central nervous system.

Tunneling nanotubes (TNTs) have emerged as pivotal structures for intercellular communication, enabling the transfer of cellular components across distant cells. Their involvement in neurological disorders has attracted considerable scientific interest. This review delineates the functions of TNTs within the central nervous system, examining their role in the transmission of bioenergetic substrates, and signaling molecules, and their multifaceted impact on both physiological and pathological processes, with an emphasis on neurodegenerative diseases. The review highlights the selectivity and specificity of TNTs as dedicated pathways for intercellular cargo delivery, particularly under stress conditions that provoke increased TNT formation. The potential of TNTs as therapeutic targets is explored in depth. We pay particular attention to the interactions between astrocytes and neurons mediated by TNTs, which are fundamental to brain architecture and function. Dysfunctions in these interactions are implicated in the spread of protein aggregates and mitochondrial anomalies, contributing to the pathogenesis of neurodegenerative diseases. The review culminates with a synthesis of the current understanding of TNT biology and identifies research gaps, advocating for intensified exploration into TNTs as a promising therapeutic frontier.

Effect of Infusion Set Replacement Intervals on Central Line-Associated Bloodstream Infection in the Intensive Care Unit: Study Protocol of the INSPIRATION Study.

INTRODUCTION: The replacement intervals for infusion sets may differ among healthcare institutions, which may have an impact on the occurrence of central line-associated bloodstream infections (CLABSI). Nevertheless, there exists a limited amount of high-quality evidence available to assist clinicians in determining the most suitable replacement intervals for infusion sets. Therefore, the objective of this trial is to compare the efficacy of 24-h and 96-h replacement intervals for infusion sets on CLABSI among critically ill adults who have central venous access devices. METHODS: This is a multicenter, parallel-group randomized controlled trial that will investigate the effect of infusion set replacement intervals on CLABSI in adult patients admitted to intensive care units (ICUs). The study will enroll 1240 participants who meet the inclusion criteria, which includes being 18 years or older, expected to stay in the ICU for longer than 96 h, and in need of central venous access. Participants will be randomly assigned to either a control group receiving a 96-h replacement interval or a treatment group receiving a 24-h replacement interval. PLANNED OUTCOME: The primary outcome of this trial is the rate of CLABSI within 28 days after randomization. CONCLUSION: This is the first randomized controlled trial to investigate the effects of infusion set replacement at 24-h and 96-h intervals on CLABSI in ICU patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05359601.

High-throughput antigen microarray identifies longitudinal prognostic autoantibody for chemoimmunotherapy in advanced non-small cell lung cancer.

Chemoimmunotherapy has evolved as a standard treatment for advanced non-small cell lung cancer (aNSCLC). However, inevitable drug resistance has limited its efficacy, highlighting the urgent need for biomarkers of chemoimmunotherapy. A three-phase strategy to discover, verify, and validate longitudinal predictive autoantibodies (AAbs) for aNSCLC before and after chemoimmunotherapy was employed. A total of 528 plasma samples from 267 aNSCLC patients before and after anti-PD1 immunotherapy were collected, plus 30 independent formalin-fixed paraffin-embedded samples. Candidate AAbs were firstly selected using a HuProtTM high-density microarray containing 21,000 proteins in the discovery phase, followed by validation using an aNSCLC-focused microarray. Longitudinal predictive AAbs were chosen for enzyme-linked immunosorbent assay (ELISA) based on responders versus non-responders comparison and progression-free survival (PFS) survival analysis. Prognostic markers were also validated using immunohistochemistry and publicly available immunotherapy datasets. We identified and validated a panel of two AAbs (MAX and DHX29) as pre-treatment biomarkers and another panel of two AAbs (MAX and TAPBP) as on-treatment predictive markers in aNSCLC patients undergoing chemoimmunotherapy. All three AAbs exhibited a positive correlation with early responses and PFS (p < 0.05). The kinetics of MAX AAb showed an increasing trend in responders (p < 0.05) and a tendency to initially increase and then decrease in non-responders (p < 0.05). Importantly, MAX protein and mRNA levels effectively discriminated PFS (p < 0.05) in aNSCLC patients treated with immunotherapy. Our results present a longitudinal analysis of changes in prognostic AAbs in aNSCLC patients undergoing chemoimmunotherapy.

Stereoconvergent and Chemoenzymatic Synthesis of Tumor-Associated Glycolipid Disialosyl Globopentaosylceramide for Probing the Binding Affinity of Siglec-7.

Disialosyl globopentaosylceramide (DSGb5) is a tumor-associated complex glycosphingolipid. However, the accessibility of structurally well-defined DSGb5 for precise biological functional studies remains challenging. Herein, we describe the first total synthesis of DSGb5 glycolipid by an efficient chemoenzymatic approach. A Gb5 pentasaccharide-sphingosine was chemically synthesized by a convergent and stereocontrolled [2 + 3] method using an oxazoline disaccharide donor to exclusively form ß-anomeric linkage. After investigating the substrate specificity of different sialyltransferases, regio- and stereoselective installment of two sialic acids was achieved by two sequential enzyme-catalyzed reactions using α2,3-sialyltransferase Cst-I and α2,6-sialyltransferase ST6GalNAc5. A unique aspect of the approach is that methyl-ß-cyclodextrin-assisted enzymatic α2,6-sialylation of glycolipid substrate enables installment of the challenging internal α2,6-linked sialoside to synthesize DSGb5 glycosphingolipid. Surface plasmon resonance studies indicate that DSGb5 glycolipid exhibits better binding affinity for Siglec-7 than the oligosaccharide moiety of DSGb5. The binding results suggest that the ceramide moiety of DSGb5 facilitates its binding by presenting multivalent interactions of glycan epitope for the recognition of Siglec-7.

Expression profiles of host miRNAs and circRNAs and ceRNA network during Toxoplasma gondii lytic cycle.

Toxoplasma gondii is an opportunistic protozoan parasite that is highly prevalent in the human population and can lead to adverse health consequences in immunocompromised patients and pregnant women. Noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), play important regulatory roles in the pathogenesis of many infections. However, the differentially expressed (DE) miRNAs and circRNAs implicated in the host cell response during the lytic cycle of T. gondii are unknown. In this study, we profiled the expression of miRNAs and circRNAs in human foreskin fibroblasts (HFFs) at different time points after T. gondii infection using RNA sequencing (RNA-seq). We identified a total of 7, 7, 27, 45, 70, 148, 203, and 217 DEmiRNAs and 276, 355, 782, 1863, 1738, 6336, 1229, and 1680 DEcircRNAs at 1.5, 3, 6, 9, 12, 24, 36, and 48 h post infection (hpi), respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the DE transcripts were enriched in immune response, apoptosis, signal transduction, and metabolism-related pathways. These findings provide new insight into the involvement of miRNAs and circRNAs in the host response to T. gondii infection.

Longitudinal plasma proteomic profiling of EML4-ALK positive lung cancer receiving ALK-TKIs therapy.

BACKGROUND: Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) has demonstrated remarkable therapeutic effects in ALK-positive non-small cell lung cancer (NSCLC) patients. Identifying prognostic biomarkers can enhance the clinical efficacy of relapsed or refractory patients. METHODS: We profiled 737 plasma proteins from 159 pre-treatment and on-treatment plasma samples of 63 ALK-positive NSCLC patients using data-independent acquisition-mass spectrometry (DIA-MS). The consensus clustering algorithm was used to identify subtypes with distinct biological features. A plasma-based prognostic model was constructed using the LASSO-Cox method. We performed the Mfuzz analysis to classify the patterns of longitudinal changes in plasma proteins during treatment. 52 baseline plasma samples from another independent ALK-TKI treatment cohort were collected to validate the potential prognostic markers using ELISA. RESULTS: We identified three subtypes of ALK-positive NSCLC with distinct biological features and clinical efficacy. Patients in subgroup 1 exhibited activated humoral immunity and inflammatory responses, increased expression of positive acute-phase response proteins, and the worst prognosis. Then we constructed and verified a prognostic model that predicts the efficacy of ALK-TKI therapy using the expression levels of five plasma proteins (SERPINA4, ATRN, APOA4, TF, and MYOC) at baseline. Next, we explored the longitudinal changes in plasma protein expression during treatment and identified four distinct change patterns (Clusters 1-4). The longitudinal changes of acute-phase proteins during treatment can reflect the treatment status and tumor progression of patients. Finally, we validated the prognostic efficacy of baseline plasma CRP, SAA1, AHSG, SERPINA4, and TF in another independent NSCLC cohort undergoing ALK-TKI treatment. CONCLUSIONS: This study contributes to the search for prognostic and drug-resistance biomarkers in plasma samples for ALK-TKI therapy and provides new insights into the mechanism of drug resistance and the selection of follow-up treatment.

Isthmin-1 Improves Aging-Related Cardiac Dysfunction in Mice through Enhancing Glycolysis and SIRT1 Deacetylase Activity.

Aging-related cardiac dysfunction poses a major risk factor of mortality for elderly populations, however, efficient treatment for aging-related cardiac dysfunction is far from being known. Isthmin-1 (ISM1) is a novel adipokine that promotes glucose uptake and acts indispensable roles in restraining inflammatory and fibrosis. The present study aims to investigate the potential role and molecular mechanism of ISM1 in aging-related cardiac dysfunction. Aged and matched young mice were overexpressed or silenced with ISM1 to investigate the role of ISM1 in aging-related cardiac dysfunction. Moreover, H9C2 cells were stimulated with D-galactose (D-gal) to examine the role of ISM1 in vitro. Herein, we found that cardiac-specific overexpression of ISM1 significantly mitigated insulin resistance by promoting glucose uptake in aging mice. ISM1 overexpression alleviated while ISM1 silencing deteriorated cellular senescence, cardiac inflammation, and dysfunction in natural and accelerated cardiac aging. Mechanistically, ISM1 promoted glycolysis and activated Sirtuin-1 (SIRT1) through increasing glucose uptake. ISM1 increased glucose uptake via translocating GLUT4 to the surface, thereby enhancing glycolytic flux and hexosamine biosynthetic pathway (HBP) flux, ultimately leading to increased SIRT1 activity through O-GlcNAc modification. ISM1 may serve as a novel potential therapeutic target for preventing aging-related cardiac disease in elderly populations. ISM1 prevents aging-related cardiac dysfunction by promoting glycolysis and enhancing SIRT1 deacetylase activity, making it a promising therapeutic target for aging-related cardiac disease.

High-substituted hydroxypropyl cellulose prepared by homogeneous method and its clouding and self-assembly behaviors.

Hydroxypropyl cellulose (HPC) is a sustainable cellulose derivative valued for its excellent biocompatibility and solubility and is widely used in various fields. Recent scientific research on high-substituted HPC mainly focused on its efficient preparation and phase transition behavior. Herein, a novel strategy of high-substituted HPC synthesis was demonstrated by employing DMSO/TBAF·3H2O as a cellulose solvent, exhibiting more efficiency than traditional approaches. High-substituted HPC prepared has remarkable thermal stability, exceptional hydrophilicity, and satisfactory solubility. Phase transition behavior of HPC with varying molar degrees of substitution (MS) was delved and a notable negative correlation between MS and cloud point temperature (TCP), was revealed, particularly evident at an MS of 12.3, where the TCP drops to 33 °C. Moreover, a unique self-assembly behavior featuring structural color and responsiveness to force in a solvent-free environment emerged when the MS exceeded 10.4. These insights comprehensively strengthen the understanding and knowledge of high-substituted HPC, simultaneously paving the way for further HPC investigation and exploitation.