Endoplasmic reticulum-targeted biomimetic nanoparticles induce apoptosis and ferroptosis by regulating endoplasmic reticulum function in colon cancer.

Colorectal cancer (CRC) is a major threat to human health, as it is one of the most common malignancies with a high incidence and mortality rate. The cancer cell membrane (CCM) has significant potential in targeted tumor drug delivery due to its membrane antigen-mediated homologous targeting ability. The endoplasmic reticulum (ER) in cancer cells plays a crucial role in apoptosis and ferroptosis. In this study, we developed an ER-targeted peptide-modified CCM-biomimetic nanoparticle-delivered lovastatin (LOV) nanomedicine delivery system (EMPP-LOV) for cancer treatment. Both in vitro and in vivo experiments demonstrated that EMPP could effectively target cancer cells and localize within the ER. EMPP-LOV modulated ER function to promote apoptosis and ferroptosis in tumor cells. Furthermore, synergistic antitumor efficacy was observed in both in vitro and in vivo models. EMPP-LOV induced apoptosis in CRC cells by over-activating endoplasmic reticulum stress and promoted ferroptosis by inhibiting the mevalonate pathway, leading to synergistic tumor growth inhibition with minimal toxicity to major organs. Overall, the EMPP-LOV delivery system, with its subcellular targeting capability within tumor cells, presents a promising therapeutic platform for CRC treatment.

A Fast, Efficient, and Tissue-Culture-Independent Genetic Transformation Method for Panax notoginseng and Lilium regale.

The Agrobacterium-based transgenic technique is commonly used for gene function validation and molecular breeding. However, it is not suitable for plants with a low regeneration capacity or a low transformation rate, such as Panax notoginseng (Burk) F.H. Chen and Lilium regale Wilson. In this study, a novel Agrobacterium transformation method based on injection in the meristems was developed using P. notoginseng and L. regale as experimental models. PCR analysis confirmed the successful integration of the reporter gene DsRed2 (Discosoma striata red fluorescence protein 2) into the genome of two experimental models. QRT-PCR and Western blot analysis demonstrated the transcriptional and translational expression of DsRed2. Additionally, laser confocal microscopy confirmed the significant accumulation of the red fluorescent protein in the leaves, stems, and roots of transformed P. notoginseng and L. regale. Most importantly, in the second year after injection, the specific bright orange fluorescence from DsRed2 expression was observed in the transgenic P. notoginseng and L. regale plants. This study establishes a fast, efficient, and tissue-culture-independent transgenic technique suitable for plants with a low regeneration capacity or a low transformation rate. This technique may improve the functional genomics of important medicinal and ornamental plants such as P. notoginseng and L. regale, as well as their molecular breeding.

Effects of rehabilitation interventions for old adults with long COVID: A systematic review and meta-analysis of randomised controlled trials.

Background: There is limited evidence on the effectiveness of the existing rehabilitation interventions for old adults with long coronavirus disease (COVID), which is of particular concern among old adults. Methods: We systematically searched studies published in PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases from their inception to 15 November 2023. Randomised controlled trials (RCTs) compared rehabilitation interventions with other controls in old adults (mean/median age of 60 or older) with long COVID were included. We performed a meta-analysis to compare the effects of the rehabilitation interventions with the common control group. Mean difference (MD) or standardised mean difference (SMD) with its 95% confidence intervals (CI) were used as summary statistics. Moreover, subgroup analyses based on the intervention programmes, the severity of acute infection, and the age of participants were carried out. Results: A total of 11 RCTs involving 832 participants (64.37 ± 7.94 years, 52.2% were men) were included in the analysis. Compared with the control groups, rehabilitation interventions significantly improved 6-minute walking test (6 MWT; MD = 15.77 metres (m), 95% CI = 5.40, 26.13, P < 0.01), 30-second sit-to-stand test (MD = 4.11 number of stands (n), 95% CI = 2.46, 5.76, P < 0.001), all aspects of quality of life, independence in activities of daily living (SMD = 0.31, 95% CI = 0.14, 0.48, P < 0.001), and relieved fatigue (SMD = -0.66, 95% CI = -1.13, -0.19, P < 0.01), depression (SMD = -0.89, 95% CI = -1.76, -0.02, P < 0.05) and anxiety (SMD = -0.81, 95% CI = -1.58, -0.05, P < 0.05). However, the improvement of hand grip strength and pulmonary function was not statistically significant (P > 0.05). Subgroup analyses showed that improvements in 6 MWT, fatigue, anxiety, and depression were more pronounced in old patients who received exercise training, while those who received respiratory rehabilitation had more pronounced improvements in pulmonary function and quality of life. Conclusions: Old adults with long COVID who underwent rehabilitation interventions experienced significant improvement in functional capacity, fatigue, quality of life, independence in activities of daily living, and mental health outcomes compared with usual/standard care. These findings suggest that screening, management, and rehabilitation interventions for long COVID in older adults should be strengthened to improve their complete health status and functional status, thereby reducing the long-term disease burden caused by long COVID and fostering healthy aging during the post-pandemic era.

Advancements and emerging trends in ophthalmic anti-VEGF therapy: a bibliometric analysis.

INTRODUCTION: Vascular Endothelial Growth Factor (VEGF) is associated with abnormal fundus neovascularization. Consequently, Anti-VEGF agents are vital for ophthalmic treatment. This paper reviews the application of anti-VEGF agents in ophthalmology over the past two decades with the aim of providing insights for further research. METHODS: A meticulous search strategy was employed in the Web of Science Core Collection literature from 2003 to 2023 to gather relevant literature, which was then analyzed using VOSviewer, CiteSpace, and the R package Bibliometrix. RESULTS: The study included 3,602 publications from 83 countries and 3,445 institutions. The United States and China have emerged as leading contributors in terms of the publication volume. Johns Hopkins University, the University of Sydney, and Genentech Inc were identified as frontrunners in this field. "Retina" had the highest publication volume, whereas "Ophthalmology" had the highest citation frequency. Among the 15,918 scholars, Bressler NM, Holz FG, Glassman AR, and Bandello F led in publication volume, while Brown DM was the most cited author. High-frequency keywords included "Endothelial Growth Factor," "Therapy," "Safety," and "Randomized Clinical Trial." CONCLUSION: Anti-VEGF drugs have shown notable success in treating neovascular eye diseases, especially wet age-related macular degeneration and diabetic macular edema, focusing on clinical efficacy, injection regimens, and safety. Future directions include developing new anti-VEGF drugs, drug delivery systems, non-invasive administration, multi-target drugs, leveraging big data and artificial intelligence, and addressing the current treatment limits. Continuous innovation and method improvement in this field promise more breakthroughs, providing effective, safe, and economical options for eye disease treatment.

Radiogenic heating sustains long-lived volcanism and magnetic dynamos in super-Earths.

Radiogenic heat production is fundamental to the energy budget of planets. Roughly half of the heat that Earth loses through its surface today comes from the three long-lived, heat-producing elements (potassium, thorium, and uranium). These three elements have long been believed to be highly lithophile and thus concentrate in the mantle of rocky planets. However, our study shows that they all become siderophile under the pressure and temperature conditions relevant to the core formation of large rocky planets dubbed super-Earths. Mantle convection in super-Earths is then primarily driven by heating from the core rather than by a mix of internal heating and cooling from above as in Earth. Partitioning these sources of radiogenic heat into the core remarkably increases the core-mantle boundary (CMB) temperature and the total heat flow across the CMB in super-Earths. Consequently, super-Earths are likely to host long-lived volcanism and strong magnetic dynamos.

Efficacy and safety of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) in the treatment of paediatric drug-resistant epilepsy: A retrospective analysis.

INTRODUCTION: This investigation evaluates the effectiveness and safety of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) as a treatment modality for drug-resistant epilepsy. MATERIAL AND METHODS: A retrospective review of clinical data from 40 paediatric patients with drug-resistant epilepsy, who underwent SEEG-guided RF-TC at our Epilepsy Center between 2020 and 2022, was conducted. This review included the patients' medical history, imaging and electroencephalography results, surgical procedures, and follow-up outcomes. RESULTS: The duration of SEEG monitoring, accompanied by concurrent electrical stimulation tests, varied from 3 days to 4 weeks. Following RF-TC surgery, 4 patients demonstrated temporary neurological impairments, including central facial and tongue weakness, reduced limb strength, and challenges in fine motor hand movements. All these symptoms were related to lesions in the central region, but showed improvement within 2 weeks to 3 months post-surgery. There were no reported instances of status epilepticus, intracranial haemorrhage, or infections. During a follow-up period of 6 months to 2.5 years, seizure control was achieved in 25 patients (62.5%) at 6 months post-surgery, and a > 50% decrease in seizure frequency was observed in 10 patients. In 5 patients where seizure control was not achieved, the management of epilepsy seemed to be independent of factors such as age at surgery, duration of preoperative disease, seizure type, or negative MRI findings ( p > 0.05). Patients with controlled epilepsy exhibited cognitive improvement, with some demonstrating no EEG abnormalities upon follow-up and a decrease in antiepileptic medication. CONCLUSIONS: SEEG-guided RF-TC appears to be a potentially effective and safe therapeutic approach for paediatric patients with drug-resistant epilepsy.

Crystal structure combined with metabolomics and biochemical studies indicates that FAM3A participates in fatty acid beta-oxidation upon binding of acyl-L-carnitine.

As the first member of the family with sequence similarity 3 (FAM3), FAM3A promotes synthesis of ATP in mitochondria of hepatic cells and cells from other organs. Dysregulations of FAM3A are involved in the development of diabetes and nonalcoholic fatty liver disease (NAFLD). So far, the molecule mechanism under the physiological and pathological functions of FAM3A is largely unexplored. Here, we determined the crystal structure of FAM3A at high resolution of 1.38Å, complexed with an unknown-source compound which was characterized through metabolomics and confirmed as methacholine by thermal shift assay and surface plasmon resonance (SPR). Exploration for natural ligands of FAM3A was conducted through the same molecular interaction assays. The observed binding of acyl-L-carnitine molecules indicated FAM3A participating in fatty acid beta-oxidation. Knockdown and rescue assays coupled with fatty acid oxidation determination confirmed the role of FAM3A in beta-oxidation. This investigation reveals the molecular mechanism for the biological function of FAM3A and would provide basis for identifying drug target for treatment of diabetes and NAFLD.

Valence band-tunable NiFe electrocatalyst triggered by the dynamic Mo exudation and re-deposition for superior high current density oxygen evolution reaction.

Developing energy- and time-efficient strategies to derive high-performance non-precious electrocatalysts for anodic oxygen evolution reaction (OER), especially stably working at industrial-demanding current density, is still a big challenge. In this work, a concise molten salt erosion scenario was devised to rapidly modulate the smooth surface of the commercial NiMo foam substrate into the rough, electronically coupled, and hierarchically porous Ni/Fe/Mo(oxy)hydroxide catalyst layer assembled by the nanosphere array. This self-supported catalyst is super-hydrophilic for the alkaline electrolyte and distinguished by a balanced Mo leaching/surface-readsorption process to tune the metal d band center and electronic perturbation. The altered electronic environment with the favored OER intermediate adsorption behavior attains the outstanding OER activity in terms of a very small overpotential of 230.21 mV at 10 mA cm-2 and an ultra-long stability for 1179.45 h to sustain the initial commercial-level current density of ca. 1000 mA cm-2. This superb performance transcends most of the edge-cutting transition metal peers reported recently and can satisfy the standards of industrial applications. This industrial-compatible synthesis technology holds profound implications for hydrogen production via water splitting and other electrochemical applications.

Promotion Effect of Catalpol on Angiogenesis and Potential Mechanisms: A Research Based on Network Pharmacology.

Catalpol, a natural iridoid glycoside, has potential therapeutic benefits, including anti-inflammatory and neuroprotective effects. Investigating catalpol's role in angiogenesis is critical for understanding its potential therapeutic applications, particularly in diseases where modulating angiogenesis is beneficial. This study investigates catalpol's influence on angiogenesis and its mechanisms, combining network pharmacology and in vitro experiments. The target genes corresponding to the catalpol were analyzed by SwissTargetPrediction. Then angiogenesis-related targets were acquired from databases like GeneCards. Subsequently, the Database for Annotation, Visualization and Integrated Discovery was employed for Gene Ontology and pathway analysis, while Cytoscape visualized protein interactions. The effect of catalpol on viability and angiogenesis of HUVECs was further examined using Cell Counting Kit-8 and angiogenesis assays. RT-qPCR and western blot were applied to check the expression of angiogenesis-related proteins. Totally, 312 target genes of catalpol and 823 angiogenesis-related targets were obtained with 56 common targets leading to PPI network analysis, highlighting hub genes (AKT1, EGFR, STAT3, MAPK3, and CASP3). These hub genes were mainly enriched in lipid and atherosclerosis pathway and EGFR-related pathway. The in vitro experimental results showed that catalpol achieved a concentration-dependent increase in HUVECs viability. Catalpol also promoted the migration and angiogenesis of HUVECs and up-regulated the expression of EGFR. EGFR knockdown inhibited the effect of catalpol on HUVECs. Catalpol promotes angiogenesis in HUVECs by upregulating EGFR and angiogenesis-related proteins, indicating its potential therapeutic application in vascular-related diseases.

Miniature Modular Reconfigurable Underwater Robot Based on Synthetic Jet.

Modular reconfigurable robots exhibit prominent advantages in the reconnaissance and exploration tasks within unstructured environments for their characteristics of high adaptability and high robustness. However, due to the limitations in locomotion mechanism and integration requirements, the modular design of miniature robots in the aquatic environment encounters significant challenges. Here, a modular strategy based on the synthetic jet principle is proposed, and a modular reconfigurable robot system is developed. Specialized bottom and side jet actuators are designed with vibration motors as excitation sources, and a motion module is developed incorporating the jet actuators to realize three-dimensional agile motion. Its linear, rotational, and ascending motion speeds reach 70.7 mm s-1, 3.3 rad s-1, and 28.7 mm s-1, respectively. The module integrates the power supply, communication, and control system with a small size of 48 mm × 38 mm × 38 mm, which ensures a wireless controllable motion. Then, various configurations of the multi-module robot system are established with corresponding motion schemes, and the experiments with replaceable intermediate modules are further conducted to verify the transportation and image-capturing functions. This work demonstrates the effectiveness of synthetic jet propulsion for aquatic modular reconfigurable robot systems, and it exhibits profound potential in future underwater applications.

Current Status, Hotspots, and Prospects of Artificial Intelligence in Ophthalmology: A Bibliometric Analysis (2003-2023).

PURPOSE: Artificial intelligence (AI) has gained significant attention in ophthalmology. This paper reviews, classifies, and summarizes the research literature in this field and aims to provide readers with a detailed understanding of the current status and future directions, laying a solid foundation for further research and decision-making. METHODS: Literature was retrieved from the Web of Science database. Bibliometric analysis was performed using VOSviewer, CiteSpace, and the R package Bibliometrix. RESULTS: The study included 3,377 publications from 4,035 institutions in 98 countries. China and the United States had the most publications. Sun Yat-sen University is a leading institution. Translational Vision Science & Technology"published the most articles, while "Ophthalmology" had the most co-citations. Among 13,145 researchers, Ting DSW had the most publications and citations. Keywords included "Deep learning," "Diabetic retinopathy," "Machine learning," and others. CONCLUSION: The study highlights the promising prospects of AI in ophthalmology. Automated eye disease screening, particularly its core technology of retinal image segmentation and recognition, has become a research hotspot. AI is also expanding to complex areas like surgical assistance, predictive models. Multimodal AI, Generative Adversarial Networks, and ChatGPT have driven further technological innovation. However, implementing AI in ophthalmology also faces many challenges, including technical, regulatory, and ethical issues, and others. As these challenges are overcome, we anticipate more innovative applications, paving the way for more effective and safer eye disease treatments.

Phenotypic and genotypic characteristics of children with PCDH19 clustering epilepsy in China.

PURPOSE: PCDH19 gene variants, termed PCDH19 clustering epilepsy, represent a distinct etiology of epilepsy. This study aimed to elucidate the clinical manifestations and explore the genotypes and phenotypes of children affected by PCDH19 clustering epilepsy. METHODS: This retrospective study included medical history, magnetic resonance imaging, video-electroencephalography, and genetic analysis of patients diagnosed with PCDH19 Clustering Epilepsy at the Neurology Department of Beijing Children's Hospital from 2015 to 2023. Chi-square tests and logistic regression analyses were conducted to study the factors associated with developmental delay in patients. RESULTS: The age at seizure onset ranged from 5 to 61 months among all 30 patients (median 14 months; IQR 9.25-22.5 months). Among the 30 patients, 29 were female and 1 was male. Clusters of seizures and fever-triggered seizures were observed, with the most prevalent seizure types being focal to bilateral tonic-clonic seizures (FBTCS). Seizures were successfully controlled in 15 patients. Unfortunately, one patient experienced a sudden unexpected death in epilepsy (SUDEP). Additionally, 14 patients had hereditary mutations, 14 had de novo mutations, 1 had both hereditary and de novo mutations, and 1 male patient had a mosaic component mutation of 0.64 due to a somatic mutation. Developmental delays were identified in 17 patients (56.7 %), and 6 patients (20 %) were diagnosed with autism spectrum disorder (ASD). Among the 17 patients, 9 experienced developmental delays before the onset of epilepsy, while 8 were initially normal but later developed developmental delays during disease progression. Statistical analysis revealed that the presence of drug-resistant epilepsy was an independent risk factor for the occurrence of developmental delays (P = 0.020, OR = 9.758, 95 % CI (1.440-66.111)). CONCLUSION: In this study, 13 new potential rare pathogenic variations in PCDH19 clustering epilepsy were identified. The clinical features observed in patients are consistent with known phenotypic features, and we found that patients with drug-resistant epilepsy are more likely to have developmental delays. The severity of the phenotype in patients with PCDH19 variants ranged from drug-responsive seizures to refractory epilepsy.

Association of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and gallstones among US adults aged ≤ 50 years: a cross-sectional study from NHANES 2017-2020.

BACKGROUND: The chronic digestive condition gallstones is quite common around the world, the development of which is closely related to oxidative stress, inflammatory response and abnormalities of lipid metabolism. In the last few years, as a novel biomarker of lipid metabolism, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has garnered significant interest. However, its relationship with gallstones has not been studied yet. METHODS: 3,772 people, all under 50, were included in this study, and their full data came from the National Health and Nutrition Examination Survey (NHANES) database for the years 2017-2020. Information on gallstones was obtained through self-reported questionnaires. Smoothed curve fitting multifactorial logistic regression was utilized to evaluate the connection of NHHR with gallstone formation incidence. Subsequently, subgroup analysis and interaction tests were applied. Finally, to create a prediction model, logistic regression and feature screening by last absolute shrinkage and selection operator (LASSO) were used. The resulting model was displayed using a nomogram. RESULTS: In multivariate logistic regression that accounted for all factors, there was a 77% increase in the likelihood of gallstones for every unit rise in lnNHHR (OR 1.77 [CI 1.11-2.83]). Following NHHR stratification, the Q4 NHHR level was substantially more linked to the risk of gallstones than the Q1 level (OR 1.86 [CI 1.04-3.32]). This correlation was stronger in women, people under 35, smokers, abstainers from alcohol, non-Hispanic White people, those with excessively high cholesterol, people with COPD, and people without diabetes. After feature screening, a predictive model and visualized nomogram for gallstones were constructed with an AUC of 0.785 (CI 0.745-0.819), which was assessed by DCA to be clinically important. CONCLUSION: In the group of people ≤ 50 years of age, elevated NHHR levels were substantially linked to a higher incidence of gallstones. This correlation was stronger in several specific groups such as females, under 35 years of age, smokers, and so on. Predictive models constructed using the NHHR have potential clinical value in assessing gallstone formation.

Vibration-Induced-Flow Mechanism and Its Application in Water Surface Robot.

Vibration is a common strategy for aquatic organisms to achieve their life activities, especially at the air-water interface. For the locomotion of small creatures, the organs with plate features are often used on water surfaces, which inspires relevant studies about using thin plates for robot propulsions. However, the influence of the general deformations of thin plates on the generated flow fields has not been considered. Here, a comprehensive investigation is conducted about the flow fields that arose by vibrations of thin plates and the potential as locomotion strategies are explored. It is discovered that as thin plates are subjected to vibration excitations on the water surface, the produced flow fields are mainly determined by the vibration shapes, and the influence rules of plate deformations on the flow fields are identified. The main factors producing asymmetric flow fields are analyzed to realize the morphology control of the flow fields. Then, to determine effective locomotion strategies on the water surface, the flow fields stimulated by integrated vibration exciters are explored, and 2 water surface robots are developed consequentially, which exhibit superior motion performance. This work reveals the basic rules of the vibration-induced-flow mechanism by thin plates and establishes new locomotion strategies for aquatic robots.

Knockdown of SMYD3 by RNA Interference Regulates the Expression of Autophagy-Related Proteins and Inhibits Bone Formation in Fluoride-Exposed Osteoblasts.

This study aimed to explore the role of histone methyltransferase SET and MYND domain containing 3 (SMYD3) in bone metabolism of osteoblasts exposed to fluoride. The levels of urine fluoride, BALP, and OC and the mRNA expression of SMYD3 were determined in patients with skeletal fluorosis and non-fluoride-exposed people on informed consent. The expression of SMYD3 protein, OC contents, and BALP activities were detected in human osteoblast-like MG63 cells and rat primary osteoblasts treated with sodium fluoride (NaF) for 48 h. The autophagosomes were observed by transmission electron microscopy. Then, we knocked down SMYD3 to confirm whether it was involved in the regulation of bone formation and related to autophagy and Wnt/ß-catenin pathway. We observed that OC and BALP levels in patients with skeletal fluorosis significantly increased, while the mRNA expression of SMYD3 significantly decreased in the skeletal fluorosis groups. In vitro, the OC contents, BALP activities, and expression of SMYD3 significantly increased, and many autophagosomes were observed in NaF treated osteoblasts. The downregulation of SMYD3 significantly inhibited OC contents, BALP activities, and expression of autophagy-related proteins, but with no significant changes in the Wnt/ß-catenin pathway. Our results demonstrated that fluoride exposure with coal-burning pollution caused orthopedic injuries and abnormalities in the levels of OC and BALP and hindered normal bone metabolism. Silencing the SMYD3 gene could significantly reduce OC and BALP levels via inhibiting the increase in autophagy induced by fluoride.

LARP7 Contributes to Glucose-Induced Cardiac Dysfunction, Apoptosis and Fibrosis by Inhibiting the Degradation of STING.

BACKGROUND: Diabetic cardiomyopathy (DCM) is an important cause of heart failure in diabetic patients. The aim of this study was to investigate the pathogenesis of DCM and to identify potential therapeutic targets. METHODS: A mouse model of type 1 DCM was constructed by continuous intraperitoneal injection of streptozotocin (STZ). Systolic and diastolic functions were measured by ultrasound. The expression of La-related protein 7 (LARP7), the stimulator of interferon genes (STING) pathway and light chain 3 (LC3) in myocardial tissue was detected by Western blot and immunofluorescence analyses. Neonatal mouse ventricular cardiomyocytes (NMVCMs) were isolated and cultured. An in vitro type 1 diabetes mellitus (T1DM) model was established by treatment with high glucose. Knockdown/overexpression of LARP7 and STING was achieved by adenovirus transduction, C-176 (a potent covalent inhibitor of STING), and plasmid transfection. The expression, activation, and localization of STING and LARP7 in cardiomyocytes was evaluated, as well as the interaction between the two. The effect of this interaction on the STING-dependent autophagy‒lysosomal pathway was also explored. In addition, the fibrosis and apoptosis of cardiomyocytes were evaluated. RESULTS: High glucose was found to increase the expression and activation of STING and LARP7 in mouse myocardial tissue. This was accompanied by myocardial fibrosis, impaired autophagy degradation function and impaired cardiac function. These findings were further confirmed by in vitro experiments. High glucose caused LARP7 to translocate from the nucleus to the cytoplasm, where it interacted with accumulated STING to inhibit its degradation. Inhibition of STING or LARP7 expression significantly improved myocardial injury induced by high glucose. CONCLUSIONS: Targeted inhibition of LARP7 or STING expression may be a potential therapeutic strategy for the treatment of DCM.

Exploring the underlying molecular mechanisms of acute myocardial infarction after SARS-CoV-2 infection.

An increase in acute myocardial infarction (AMI)-related deaths has been reported during the COVID-19 pandemic. Despite evidence suggesting the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and AMI, the underlying mechanisms remain unclear. Here, we integrated mRNA and microRNA expression profiles related to SARS-CoV-2 infection and AMI from public databases. We then performed transcriptomic analysis using bioinformatics and systems biology approaches to explore the potential molecular mechanisms of SARS-CoV-2 infection affects AMI. First, twenty-one common differentially expressed genes (DEGs) were identified from SARS-CoV-2 infection and AMI patients in endothelial cells datasets and then we performed functional analysis to predict the roles of these DEGs. The functional analysis emphasized that the endothelial cell response to cytokine stimulus due to excessive inflammation was essential in these two diseases. Importantly, the tumor necrosis factor and interleukin-17 signaling pathways appeared to be integral factors in this mechanism. Interestingly, most of these common genes were also upregulated in transcriptomic datasets of SARS-CoV-2-infected cardiomyocytes, suggesting that these genes may be shared in cardiac- and vascular-related injuries. We subsequently built a protein-protein interaction network and extracted hub genes and essential modules from this network. At the transcriptional and post-transcriptional levels, regulatory networks with common DEGs were also constructed, and some key regulator signatures were further identified and validated. In summary, our research revealed that a highly activated inflammatory response in patients with COVID-19 might be a crucial factor for susceptibility to AMI and we identified some candidate genes and regulators that could be used as biomarkers or potential therapeutic targets.

Aneuploidy underlies brefeldin A-induced antifungal drug resistance in Cryptococcus neoformans.

Cryptococcus neoformans is at the top of the list of "most wanted" human pathogens. Only three classes of antifungal drugs are available for the treatment of cryptococcosis. Studies on antifungal resistance mechanisms are limited to the investigation of how a particular antifungal drug induces resistance to a particular drug, and the impact of stresses other than antifungals on the development of antifungal resistance and even cross-resistance is largely unexplored. The endoplasmic reticulum (ER) is a ubiquitous subcellular organelle of eukaryotic cells. Brefeldin A (BFA) is a widely used chemical inducer of ER stress. Here, we found that both weak and strong selection by BFA caused aneuploidy formation in C. neoformans, mainly disomy of chromosome 1, chromosome 3, and chromosome 7. Disomy of chromosome 1 conferred cross-resistance to two classes of antifungal drugs: fluconazole and 5-flucytosine, as well as hypersensitivity to amphotericin B. However, drug resistance was unstable, due to the intrinsic instability of aneuploidy. We found overexpression of AFR1 on Chr1 and GEA2 on Chr3 phenocopied BFA resistance conferred by chromosome disomy. Overexpression of AFR1 also caused resistance to fluconazole and hypersensitivity to amphotericin B. Furthermore, a strain with a deletion of AFR1 failed to form chromosome 1 disomy upon BFA treatment. Transcriptome analysis indicated that chromosome 1 disomy simultaneously upregulated AFR1, ERG11, and other efflux and ERG genes. Thus, we posit that BFA has the potential to drive the rapid development of drug resistance and even cross-resistance in C. neoformans, with genome plasticity as the accomplice.

Encapsulation of thermochromic tetradecyl myristate/methyl red composite via full poplar-based cellulose/lignin/SiO2 framework for preparation of thermochromic wood with thermal response and storage.

Thermochromic wood (TW), a smart material that can respond to temperature changes and store thermal energy, holds broad potential for application in the construction industry. This study fabricated thermochromic poplar (TP) by encapsulating a thermochromic phase change material (TPCM), consisting of tetradecyl myristate and methyl red, within a full poplar-based cellulose/lignin/SiO2 framework. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses indicate that the poplar matrix and the incorporated SiO2 formed an integrated cellulose/lignin/SiO2 framework, which encapsulated the TPCM within the poplar ducts. The TP exhibits a color change from light purple to dark purple within the temperature range of 30-48 °C, with a pronounced shift at approximately 42 °C, correlating with the sensation of scalding. Thus, TP-based products can alert users to the risk of scalding through a noticeable color change. The full poplar-based framework mitigates the impact of ultraviolet (UV) radiation on the TP and prevents the loss of TPCM during thermal processing. The mechanical properties of TP are enhanced to a strength grade comparable to that of Manchurian ash wood, making it suitable for load-bearing components in wooden structures. Additionally, the average temperature of TP is around 10 °C higher than that of untreated poplar within 25 min after the same thermal treatment. Consequently, TP can serve as a building material with capabilities for temperature response, thermal energy storage, and structural load-bearing.

Nomogram to predict radicular grooves in maxillary lateral incisors in preoperative orthodontic population.

OBJECTIVES: This study aimed to develop and validate a predictive nomogram for diagnosing radicular grooves (RG) in maxillary lateral incisors (MLIs), integrating demographic information, anatomical measurements, and Cone Beam Computed Tomography (CBCT) data to diagnose the RG in MLIs based on the clinical observation before resorting to the CBCT scan. MATERIALS AND METHODS: A retrospective cohort of orthodontic patients from the School and Hospital of Stomatology, Wuhan University, was analyzed, including demographic characteristics, photographic anatomical assessments, and CBCT diagnoses. The cohort was divided into development and validation groups. Univariate and multivariate logistic regression analyses identified significant predictors of RG, which informed the development of a nomogram. This nomogram's performance was validated using receiver operating characteristic analysis. RESULTS: The study included 381 patients (64.3% female) and evaluated 760 MLIs, with RG present in 26.25% of MLIs. The nomogram incorporated four significant anatomical predictors of RG presence, demonstrating substantial predictive efficacy with an area under the curve of 0.75 in the development cohort and 0.71 in the validation cohort. CONCLUSIONS: A nomogram for the diagnosis of RG in MLIs was successfully developed. This tool offers a practical checklist of anatomical predictors to improve the diagnostic process in clinical practice. CLINICAL RELEVANCE: The developed nomogram provides a novel, evidence-based tool to enhance the detection and treatment planning of MLIs with RG in diagnostic and therapeutic strategies.