SadNet: a novel multimodal fusion network for protein-ligand binding affinity prediction.

Protein-ligand binding affinity prediction plays an important role in the field of drug discovery. Existing deep learning-based approaches have significantly improved the efficiency of protein-ligand binding affinity prediction through their excellent inductive bias capability. However, these methods only focus on fragmented three-dimensional data, which truncates the integrity of pocket data, leading to the neglect of potential long-range interactions. In this paper, we propose a dual-stream framework, with amino acid sequence assisting the atomic data fusion for graph neural network (termed SadNet), to fuse both 3D atomic data and sequence data for more accurate prediction results. In detail, SadNet consists of a pocket module and a sequence module. The sequence module expands the "receptive field" of the pocket module through a mid-term virtual node fusion. To better integrate sequence-level information from the sequence module and 3D structural information from the pocket module, we incorporate structural information for each amino acid within the sequence module. Besides, to better understand the intrinsic relationship between sequences and 3D atomic information, our SadNet utilizes information stacking from both the early stage and later stage. Experimental results on publicly available benchmark datasets demonstrate the superiority of the proposed dual-stream approach over the state-of-the-art alternatives. The code of this work is available online at https://github.com/wardhong/SadNet.

White matter hyperintensities mediate the association between frailty and cognitive impairment in moyamoya disease.

OBJECTIVES: The relationship between cognitive function and frailty in moyamoya disease (MMD) remains unclear, and the underlying mechanism is poorly understood. This study aims to investigate whether white matter hyperintensities (WMHs) mediate the association between frailty and cognitive impairment in MMD. METHODS: Patients with MMD were consecutively enrolled in our study from January 2021 to May 2023. Pre-admission frailty and cognition were assessed using the Clinical Frailty Scale (CFS) and cognitive tests, respectively. Regional deep WMH (DWMH) and periventricular WMH (PWMH) volumes were calculated using the Brain Anatomical Analysis using Diffeomorphic deformation toolbox based on SPM 12 software. Multivariate logistic regression analysis was conducted to evaluate the association between frailty and cognitive function in MMD. Mediation analysis was performed to assess whether WMHs explained the association between frailty and cognition. RESULTS: A total of 85 patients with MMD were enrolled in this study. On the basis of the CFS scores, 24 patients were classified as frail, 38 as pre-frail, and 23 as robust. Significant differences were observed in learning, memory, processing speed, executive functions, and semantic memory among the three groups (p < 0.001). Frailty was independently associated with memory and executive functions (p < 0.05); even after controlling for WMH. Mediation analysis indicated that the associations of frailty with memory and executive functions were partially mediated by WMH, DWMH, and PWMH (p < 0.05). CONCLUSION: Frailty is significantly correlated with a higher risk of cognitive impairment in MMD, even after adjusting for other covariates. WMHs partially mediate the association between frailty and cognitive impairment.

Discrepancy between arterial oxygen saturation and pulse oximetry measurement in a Chinese pediatric patient cohort.

Background: Increasing evidence suggest a racial bias in pulse oximetry measurement, but this was under investigated in Asian pediatric populations. Methods: Via the Pediatric Intensive Care database, this retrospective study included pediatric patient records of arterial oxygen saturation (SaO2) and oxygen saturation on pulse oximetry (SpO2) measured within 10 min. Discrepancy was examined, and potential predictors of occult hypoxemia (defined as SaO2 <88% with the paired SpO2 ≥92%) as well as its association with outcomes were explored by logistic regression. Results: A total of 390 patients were included with 454 pairs of SaO2-SpO2 readings. The study population consisted of Han Chinese (99.0%) and 43.6% were female. Occult hypoxemia was observed in 20.0% of the patients, with a mean SaO2 of 71.4 ± 15.8%. Potential predictors of occult hypoxemia included female, being first admitted to cardiac ICU, congenital heart disease, increased heart rate, while patients with prior surgery records were less likely to experience occult hypoxemia. Patients with occult hypoxemia had numerically higher in-ICU mortality (16.7% versus 10.9%) and in-hospital mortality (17.9% versus 10.9%), but the associations were not statistically significant. Conclusions: There was a substantial proportion of hypoxemia that was not detected by pulse oximetry in the Chinese pediatric patients, which might be predicted by several characteristics and seemed to associate with mortality.

The role of goblet cells in Crohn' s disease.

The prevalence of Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD), is increasing worldwide. The pathogenesis of CD is hypothesized to be related to environmental, genetic, immunological, and bacterial factors. Current studies have indicated that intestinal epithelial cells, including columnar, Paneth, M, tuft, and goblet cells dysfunctions, are strongly associated with these pathogenic factors. In particular, goblet cells dysfunctions have been shown to be related to CD pathogenesis by direct or indirect ways, according to the emerging studies. The mucus barrier was established with the help of mucins secreted by goblet cells. Not only do the mucins mediate the mucus barrier permeability and bacterium selection, but also, they are closely linked with the endothelial reticulum stress during the synthesis process. Goblet cells also play a vital role in immune response. It was indicated that goblet cells take part in the antigen presentation and cytokines secretion process. Disrupted goblet cells related immune process were widely discovered in CD patients. Meanwhile, dysbiosis of commensal and pathogenic microbiota can induce myriad immune responses through mucus and goblet cell-associated antigen passage. Microbiome dysbiosis lead to inflammatory reaction against pathogenic bacteria and abnormal tolerogenic response. All these three pathways, including the loss of mucus barrier function, abnormal immune reaction, and microbiome dysbiosis, may have independent or cooperative effect on the CD pathogenesis. However, many of the specific mechanisms underlying these pathways remain unclear. Based on the current understandings of goblet cell's role in CD pathogenesis, substances including butyrate, PPARγagonist, Farnesoid X receptor agonist, nuclear factor-Kappa B, nitrate, cytokines mediators, dietary and nutrient therapies were all found to have potential therapeutic effects on CD by regulating the goblet cells mediated pathways. Several monoclonal antibodies already in use for the treatment of CD in the clinical settings were also found to have some goblet cells related therapeutic targets. In this review, we introduce the disease-related functions of goblet cells, their relationship with CD, their possible mechanisms, and current CD treatments targeting goblet cells.

Experimental observation of current-driven antiskyrmion sliding in stripe domains.

Magnetic skyrmions are promising as next-generation information units. Their antiparticle-the antiskyrmion-has also been discovered in chiral magnets. Here we experimentally demonstrate antiskyrmion sliding in response to a pulsed electric current at room temperature without the requirement of an external magnetic field. This is realized by embedding antiskyrmions in helical stripe domains, which naturally provide one-dimensional straight tracks along which antiskyrmion sliding can be easily launched with low current density and without transverse deflection from the antiskyrmion Hall effect. The higher mobility of the antiskyrmions in the background of helical stripes in contrast to the typical ferromagnetic state is a result of intrinsic material parameters and elastic energy of the stripe domain, thereby smearing out the random pinning potential, as supported by micromagnetic simulations. The demonstration and comprehensive understanding of antiskyrmion movement along naturally straight tracks offers a new perspective for (anti)skyrmion application in spintronics.

Long non-coding RNA GATA6-AS1 is mediated by N6-methyladenosine methylation and inhibits the proliferation and metastasis of gastric cancer.

BACKGROUND: Through experimental research on the biological function of GATA6-AS1, it was confirmed that GATA6-AS1 can inhibit the proliferation, invasion, and migration of gastric cancer cells, suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer. Further experiments confirmed that the overexpression of fat mass and obesity-associated protein (FTO) inhibited the expression of GATA6-AS1, thereby promoting the occurrence and development of gastric cancer. AIM: To investigate the effects of GATA6-AS1 on the proliferation, invasion and migration of gastric cancer cells and its mechanism of action. METHODS: We used bioinformatics methods to analyze the Cancer Genome Atlas (https://portal.gdc.cancer.gov/. The Cancer Genome Atlas) and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue. We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation, migration and invasion, and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer. Next, we used a database (http://starbase.sysu.edu.cn/starbase2/) to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1. Furthermore, RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme. These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer. RESULTS: Low expression levels of GATA6-AS1 were detected in gastric cancer. We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells. GATA6-AS1 had strong binding ability with the m6A demethylase FTO, which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1. Following transfection with siRNA to knock down the expression of FTO, the expression levels of GATA6-AS1 were up-regulated. Finally, the proliferation, migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression. CONCLUSION: During the occurrence and development of gastric cancer, the overexpression of FTO may inhibit the expression of GATA6-AS1, thus promoting the proliferation and metastasis of gastric cancer.

Laser therapy decreases oral leukoplakia recurrence and boosts patient comfort: a network meta-analysis and systematic review.

BACKGROUND: Oral leukoplakia (OLK) is a prevalent precancerous lesion with limited non-pharmacological treatment options. Surgery and various lasers are the mainstay of treatment; however, their relative efficacy and optimal choice remain unclear. This first network meta-analysis compared the effects of different lasers and surgical excision on post-treatment recurrence and comfort in OLK patients. METHODS: We searched four databases for relevant randomized controlled trials (RCTs) up to April 2023. The primary outcome was post-treatment recurrence, and secondary outcomes included intraoperative hemorrhage and postoperative pain scores. The Cochrane Risk of Bias tool was used to assess the study quality. Meta-analysis and network meta-analysis were employed to determine efficacy and identify the optimal intervention. RESULTS: A total of 11 RCTs including 917 patients and 1138 lesions were included. Er,Cr:YSGG laser treatment showed significantly lower recurrence rates compared to CO2 laser (OR: 0.04; 95% CI: 0.01-0.18), CO2 laser with margin extension (OR: 0.06; 95% CI: 0.01-0.60), Er:YAG laser (OR: 0.10; 95% CI: 0.03-0.37), electrocautery (OR: 0.03; 95% CI: 0.00-0.18), and standard care (OR: 0.08; 95% CI: 0.02-0.33). Er,Cr:YSGG laser also ranked the best for reducing recurrence, followed by standard care and CO2 laser combined with photodynamic therapy (PDT). Er:YAG and Er:Cr:YSGG lasers minimized bleeding and pain, respectively. None of the interventions caused severe adverse effects. CONCLUSION: For non-homogeneous OLK, Er:YAG, Er:Cr:YSGG, and CO2 laser combined with PDT offer promising alternatives to surgical excision, potentially reducing recurrence and improving patient comfort. Further high-quality RCTs are necessary to confirm these findings and determine the optimal laser-PDT combination for OLK treatment.

Bibliometric analysis of research trends and hotspots on robot-assisted thyroid surgery.

BACKGROUND: Thyroid surgery involves the partial or complete removal of the thyroid gland and is a frequently performed surgical procedure. The adoption of robots, equipped with flexible and stable operating systems, has garnered acceptance among numerous surgeons for their capability to enable precise anatomical dissection in thyroid surgery. To gain a comprehensive insight into the present research landscape of robot-assisted thyroid surgery, this paper endeavored to conduct a thorough analysis of the field through bibliometric analysis. METHODS: Relevant literature pertaining to robot-assisted thyroid surgery was retrieved from the Web of Science Core Collection (WOSCC) database, spanning from the inception of WOSCC to October 17, 2022. Visual analyses of publication quantity, distribution across countries/regions, institutions/organizations, authorship, journals, references, and keywords were conducted using Microsoft Excel, the bibliometrix package in R, Citescape, and VOSviewer software. RESULTS: A total of 505 articles from 406 institutions in 36 countries/regions were included. South Korea emerged with highest number of publications. Notably, Professor CHUNG WY from Yonsei University in South Korea and the journal "Surg Endosc" stood out with the most publications. The current research landscape indicated significant interest in endoscopic thyroidectomy, surgical procedures, and the axillary approach. In addition, transoral robotic thyroidectomy (TROT), and learning curve (LC) were recognized as research frontiers, representing potential future hotspots in this field. CONCLUSION: This study marks the first bibliometric analysis of the literature on robot-assisted thyroid surgery. The results highlight endoscopic thyroidectomy, surgical procedures, and the axillary approach as current research hotspots, with TROT and LC identified as potential future research hotspots.

A review for the impacts of circadian disturbance on urological cancers.

Circadian rhythm is an internal timing system and harmonizes a variety of cellular, behavioral, and physiological processes to daily environment. Circadian disturbance caused by altered life style or disrupted sleep patterns inevitably contributes to various disorders. As the rapidly increased cancer occurrences and subsequent tremendous financial burdens, more researches focus on reducing the morbidity rather than treating it. Recently, many epidemiologic studies demonstrated that circadian disturbance was tightly related to the occurrence and development of cancers. For urinary system, numerous clinical researches observed the incidence and progress of prostate cancer were influenced by nightshift work, sleep duration, chronotypes, light exposure, and meal timing, this was also proved by many genetic and fundamental findings. Although the epidemiological studies regarding the relationship between circadian disturbance and kidney/bladder cancers were relative limited, some basic researches still claimed circadian disruption was closely correlated to these two cancers. The role of circadian chemotherapy on cancers of prostate, kidney, and bladder were also explored, however, it has not been regularly recommended considering the limited evidence and poor standard protocols. Finally, the researches for the impacts of circadian disturbance on cancers of adrenal gland, penis, testis were not found at present. In general, a better understanding the relationship between circadian disturbance and urological cancers might help to provide more scientific work schedules and rational lifestyles which finally saving health resource by reducing urological tumorigenesis, however, the underlying mechanisms are complex which need further exploration.

Metabolic coupling between glutamate and N-acetylaspartate in the human brain.

A metabolic coupling between glutamate and N-acetylaspartate measured by in vivo magnetic resonance spectroscopy has been recently reported in the literature with inconsistent findings. In this study, confounders originating from Pearson's spurious correlation of ratios and spectral correlation due to overlapping magnetic resonance spectroscopy signals of glutamate and N-acetylaspartate were practically eliminated to facilitate the determination of any metabolic link between glutamate and N-acetylaspartate in the human brain using in vivo magnetic resonance spectroscopy. In both occipital and medial prefrontal cortices of healthy individuals, correlations between glutamate and N-acetylaspartate were found to be insignificant. Our results do not lend support to a recent hypothesis that N-acetylaspartate serves as a significant reservoir for the rapid replenishment of glutamate during signaling or stress.

Age-related changes in meningeal lymphatic function are closely associated with vascular endothelial growth factor-C expression.

Meningeal lymphatic vessels (MLVs) have crucial roles in removing metabolic waste and toxic proteins from the brain and transporting them to the periphery. Aged mice show impaired meningeal lymphatic function. Nevertheless, as the disease progresses, and significant pathological changes manifest in the brain, treating the condition becomes increasingly challenging. Therefore, investigating the alterations in the structure and function of MLVs in the early stages of aging is critical for preventing age-related central nervous system degenerative diseases. We detected the structure and function of MLVs in young, middle-aged, and aged mice. Middle-aged mice, compared with young and aged mice, showed enhanced meningeal lymphatic function along with MLV expansion and performed better in the Y maze test. Moreover, age-related changes in meningeal lymphatic function were closely associated with vascular endothelial growth factor-C (VEGF-C) expression in the brain cortex. Our data suggested that the cerebral cortex may serve as a target for VEGF-C supplementation to ameliorate meningeal lymphatic dysfunction, thus providing a new strategy for preventing age-related central nervous system diseases.

Lithium isotopic constraints on the evolution of continental clay mineral factory and marine oxygenation in the earliest Paleozoic Era.

The evolution of oxygen cycles on Earth's surface has been regulated by the balance between molecular oxygen production and consumption. The Neoproterozoic-Paleozoic transition likely marks the second rise in atmospheric and oceanic oxygen levels, widely attributed to enhanced burial of organic carbon. However, it remains disputed how marine organic carbon production and burial respond to global environmental changes and whether these feedbacks trigger global oxygenation during this interval. Here, we report a large lithium isotopic and elemental dataset from marine mudstones spanning the upper Neoproterozoic to middle Cambrian [~660 million years ago (Ma) to 500 Ma]. These data indicate a dramatic increase in continental clay formation after ~525 Ma, likely linked to secular changes in global climate and compositions of the continental crust. Using a global biogeochemical model, we suggest that intensified continental weathering and clay delivery to the oceans could have notably increased the burial efficiency of organic carbon and facilitated greater oxygen accumulation in the earliest Paleozoic oceans.

An artificial biocatalytic cascade for efficient synthesis of norepinephrine by combination of engineered L-threonine transaldolase with multi-enzyme expression fine-tuning.

Norepinephrine, a kind of ß-adrenergic receptor agonist, is commonly used for treating shocks and hypotension caused by a variety of symptoms. The development of a straightforward, efficient and environmentally friendly biocatalytic route for manufacturing norepinephrine remains a challenge. Here, we designed and realized an artificial biocatalytic cascade to access norepinephrine starting from 3, 4-dihydroxybenzaldehyde and L-threonine mediated by a tailored-made L-threonine transaldolase PsLTTA-Mu1 and a newly screened tyrosine decarboxylase ErTDC. To overcome the imbalance of multi-enzymes in a single cell, engineering of PsLTTA for improved activity and fine-tuning expression mode of multi-enzymes in single E.coli cells were combined, leading to a robust whole cell biocatalyst ES07 that could produce 100 mM norepinephrine with 99% conversion, delivering a highest time-space yield (3.38 g/L/h) ever reported. To summarized, the current study proposed an effective biocatalytic approach for the synthesis of norepinephrine from low-cost substrates, paving the way for industrial applications of enzymatic norepinephrine production.

Poly-(lactic acid) composite films comprising carvacrol and cellulose nanocrystal-zinc oxide with synergistic antibacterial effects.

Herein, carvacrol (CRV) and modified cellulose nanocrystal-zinc oxide (CNC-ZnO) were incorporated into a poly (lactic acid) (PLA) matrix to prepare a PLA-based composite film using a simple solution casting method to achieve antimicrobial effects for application in antimicrobial food packaging. Compared with films obtained from neat PLA, the PLA@CRV20%@CNC-ZnO3% composite film shows better performance in terms of mechanical properties, ultraviolet (UV) blocking, and antimicrobial effects. The PLA composites containing CRV and 3 wt% CNC-ZnO blends exhibit improved tensile strength (21.8 MPa) and elongation at break (403.1 %) as well as excellent UV resistance. In particular, CRV and the CNC-ZnO hybrid endow the obtained PLA composite films with a synergistic antibacterial effect, resulting in good antibacterial properties for microbes, such as Escherichia coli, Staphylococcus aureus and Aspergillus niger. The diameters of the inhibition zone of the PLA@CRV20%@CNC-ZnO3% composite films against E. coli, S. aureus, and A. niger were 4.9, 5.0, and 3.4 cm, respectively. Appling the PLA@CRV20%@CNC-ZnO3% composite film as an antibacterial food packaging material, the storage period for strawberries was considerably extended. This study provides a theoretical basis for developing new organic/inorganic composite antimicrobial film materials from PLA.

Associations between neutrophil-to-lymphocyte/platelet-to-lymphocyte and recovery in sudden sensorineural hearing loss.

Aims: This study investigated the nonlinear associations between neutrophil-to-lymphocyte (NLR)/platelet-to-lymphocyte (PLR) and recovery rates in sudden sensorineural hearing loss (SSNHL). Methods: Total of 244 SSNHL patients were included. The primary outcome was recovery rate. Results: A nonlinear association was detected between NLR and recovery rate using the LOWESS method, with a knot of 3. Patients with NLR ≥3 had a higher recovery rate than NLR <3. Using the linear-spline function, NLR was significantly associated with high recovery rate when NLR was <3. However, when NLR was ≥3, this association became nonsignificant. The trend test showed a similar result. PLR was not associated with recovery rate. Conclusion: The association between NLR and recovery rate is nonlinear, with a knot of around three. PLR is not associated with recovery rate.

CT-based pancreatic radiomics predicts secondary loss of response to infliximab in biologically naïve patients with Crohn's disease.

OBJECTIVES: Predicting secondary loss of response (SLR) to infliximab (IFX) is paramount for tailoring personalized management regimens. Concurrent pancreatic manifestations in patients with Crohn's disease (CD) may correlate with SLR to anti-tumor necrosis factor treatment. This work aimed to evaluate the potential of pancreatic radiomics to predict SLR to IFX in biologic-naive individuals with CD. METHODS: Three models were developed by logistic regression analyses to identify high-risk subgroup prone to SLR. The area under the curve (AUC), calibration curve, decision curve analysis (DCA), and integrated discrimination improvement (IDI) were applied for the verification of model performance. A quantitative nomogram was proposed based on the optimal prediction model, and its reliability was substantiated by 10-fold cross-validation. RESULTS: In total, 184 CD patients were enrolled in the period January 2016 to February 2022. The clinical model incorporated age of onset, disease duration, disease location, and disease behavior, whereas the radiomics model consisted of five texture features. These clinical parameters and the radiomics score calculated by selected texture features were applied to build the combined model. Compared to other two models, combined model achieved favorable, significantly improved discrimination power (AUCcombined vs clinical 0.851 vs 0.694, p = 0.02; AUCcombined vs radiomics 0.851 vs 0.740, p = 0.04) and superior clinical usefulness, which was further converted into reliable nomogram with an accuracy of 0.860 and AUC of 0.872. CONCLUSIONS: The first proposed pancreatic-related nomogram represents a credible, noninvasive predictive instrument to assist clinicians in accurately identifying SLR and non-SLR in CD patients. CRITICAL RELEVANCE STATEMENT: This study first built a visual nomogram incorporating pancreatic texture features and clinical factors, which could facilitate clinicians to make personalized treatment decisions and optimize cost-effectiveness ratio for patients with CD. KEY POINTS: • The first proposed pancreatic-related model predicts secondary loss of response for infliximab in Crohn's disease. • The model achieved satisfactory predictive accuracy, calibration ability, and clinical value. • The model-based nomogram has the potential to identify long-term failure in advance and tailor personalized management regimens.

Comparative Analysis of Six Complete Plastomes of Tripterospermum spp.

The Tripterospermum, comprising 34 species, is a genus of Gentianaceae. Members of Tripterospermum are mostly perennial, entwined herbs with high medicinal value and rich in iridoids, xanthones, flavonoids, and triterpenes. However, our inadequate understanding of the differences in the plastid genome sequences of Tripterospermum species has severely hindered the study of their evolution and phylogeny. Therefore, we first analyzed the 86 Gentianae plastid genomes to explore the phylogenetic relationships within the Gentianae subfamily where Tripterospermum is located. Then, we analyzed six plastid genomes of Tripterospermum, including two newly sequenced plastid genomes and four previously published plastid genomes, to explore the plastid genomes' evolution and phylogenetic relationships in the genus Tripterospermum. The Tripterospermum plastomes have a quadripartite structure and are between 150,929 and 151,350 bp in size. The plastomes of Tripterospermum encoding 134 genes were detected, including 86 protein-coding genes (CDS), 37 transfer RNA (tRNA) genes, eight ribosomal RNA (rRNA) genes, and three pseudogenes (infA, rps19, and ycf1). The result of the comparison shows that the Tripterospermum plastomes are very conserved, with the total plastome GC content ranging from 37.70% to 37.79%. In repeat sequence analysis, the number of single nucleotide repeats (A/T) varies among the six Tripterospermum species, and the identified main long repeat types are forward and palindromic repeats. The degree of conservation is higher at the SC/IR boundary. The regions with the highest divergence in the CDS and the intergenic region (IGS) are psaI and rrn4.5-rrn5, respectively. The average pi of the CDS and the IGS are only 0.071% and 0.232%, respectively, indicating that the Tripterospermum plastomes are highly conserved. Phylogenetic analysis indicated that Gentianinae is divided into two clades, with Tripterospermum as a sister to Sinogeniana. Phylogenetic trees based on CDS and CDS + IGS combined matrices have strong support in Tripterospermum. These findings contribute to the elucidation of the plastid genome evolution of Tripterospermum and provide a foundation for further exploration and resource utilization within this genus.

Analysis of immunoinfiltration and EndoMT based on TGF-ß signaling pathway-related genes in acute myocardial infarction.

Acute myocardial infarction (AMI), a critical manifestation of coronary heart disease, presents a complex and not entirely understood etiology. This study investigates the potential role of immune infiltration and endothelial-mesenchymal transition (EndoMT) in AMI pathogenesis. We conducted an analysis of the GSE24519 and MSigDB datasets to identify differentially expressed genes associated with the TGF-ß signaling pathway (DE-TSRGs) and carried out a functional enrichment analysis. Additionally, we evaluated immune infiltration in AMI and its possible link to myocardial fibrosis. Key genes were identified using machine learning and LASSO logistic regression. The expression of MEOX1 in the ventricular muscles and endothelial cells of Sprague-Dawley rats was assessed through RT-qPCR, immunohistochemical and immunofluorescence assays, and the effect of MEOX1 overexpression on EndoMT was investigated. Our study identified five DE-TSRGs, among which MEOX1, SMURF1, and SPTBN1 exhibited the most significant associations with AMI. Notably, we detected substantial immune infiltration in AMI specimens, with a marked increase in neutrophils and macrophages. MEOX1 demonstrated consistent expression patterns in rat ventricular muscle tissue and endothelial cells, and its overexpression induced EndoMT. Our findings suggest that the TGF-ß signaling pathway may contribute to AMI progression by activating the immune response. MEOX1, linked to the TGF-ß signaling pathway, appears to facilitate myocardial fibrosis via EndoMT following AMI. These novel insights into the mechanisms of AMI pathogenesis could offer promising therapeutic targets for intervention.

Assessing care dependence status and associated influencing factors among middle-aged hemiplegic stroke patients during the post-acute rehabilitation phase: A correlational study.

AIMS: To comprehensively examine the prevailing condition of care dependence among middle-aged individuals who have experienced hemiplegia subsequent to a stroke and were currently undergoing post-acute rehabilitation. Additionally, the study sought to analyse the determinants that impacted this phenomenon. DESIGN: A single-centre, cross-sectional study design. METHODS: During the period from January 2020 to October 2022, a cohort of 196 hemiplegic stroke patients, aged between 40 and 65, and within 6 months of their stroke onset, was selected from the cerebrovascular outpatient clinic at a tertiary hospital in Hangzhou. The demographic and disease-related data, care dependence level, mental state, nutrition and depression status were collected. Furthermore, all collected data were analysed by descriptive and correlative statistical methods. RESULTS: The care dependence level was 51.04 ± 9.42, with an incidence of care dependence of 78.1%. Multivariate regression analysis showed that age, history of falls, physical dysfunction, chronic comorbidities, depression, nutritional status and cognitive dysfunction were influencing factors for care dependence in the participants after a stroke. CONCLUSION: The incidence of care dependence among hemiplegic patients aged from 40 to 65 years old in the early stage after a stroke was high. Nursing staff should focus on these patients with a history of falling, physical dysfunction, comorbidity, depression status, nutritional status and cognitive dysfunction in clinical practice. RELEVANCE TO CLINICAL PRACTICE: The incidence of care dependence in middle-aged hemiplegic patients following a stroke is significantly increased. Some risk factors should be assessed, monitored, and controlled by nursing staff as early as possible in order to reduce the dependence levels in post-acute rehabilitation period and improve the quality of life of hemiplegia patients. REPORTING METHOD: Our study complies with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Checklist: cross-sectional studies (see Table S1). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.