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Abstract Background To design a pulmonary ground-glass nodules (GGN) classification method based on computed tomography (CT) radiomics and machine learning for prediction of invasion in early-stage ground-glass opacity (GGO) pulmonary adenocarcinoma. Methods This retrospective study included pulmonary GGN patients who were histologically confirmed to have adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma cancer (IAC) from 2020 to 2023. CT images of all patients were automatically segmented and 107 radiomic features were obtained for each patient. Classification models were developed using random forest (RF) and cross-validation, including three one-versus-others models and one three-class model. For each model, features were ranked by normalized Gini importance, and a minimal subset was selected with a cumulative importance exceeding 0.9. These selected features were then used to train the final models. The models’ performance metrics, including area under the curve (AUC), accuracy, sensitivity, and specificity, were computed. AUC and accuracy were compared to determine the final optimal method. Results The study comprised 193 patients (mean age 54 ± 11 years, 65 men), including 65 AIS, 54 MIA, and 74 IAC, divided into one training cohort (N = 154) and one test cohort (N = 39). The final three-class RF model outperformed three individual one-versus-others models in distinguishing each class from the other two. For the multiclass classification model, the AUC, accuracy, sensitivity, and specificity were 0.87, 0.79, 0.62, and 0.88 for AIS; 0.90, 0.79, 0.54, and 0.89 for MIA; and 0.87, 0.69, 0.73, and 0.67 for IAC, respectively. Conclusions A radiomics-based multiclass RF model could effectively differentiate three types of pulmonary GGN, which enabled early diagnosis of GGO pulmonary adenocarcinoma.

Giant intracranial aneurysms (GIAs) pose a formidable challenge in cerebrovascular surgery. Despite remarkable advancements in microsurgical techniques, the associated morbidity and mortality rates remain alarmingly high, reaching up to 20%. The three-dimensional (3D) Slicer emerges as a valuable tool, offering sophisticated medical image visualization and analysis capabilities. This article reports on a captivating case where 3D-Slicer technology played a pivotal role in diagnosing GIA. The 3D-Slicer excels in assisting with surgical procedures like clipping and resection of both regular and giant thrombotic aneurysms. Its intuitive interface and advanced functionalities hold immense promise for revolutionizing the diagnosis and management of these challenging lesions.

Abstract Background The experiences and perceptions of geriatric specialist nurses are pivotal to understanding the complexities of managing delirium and to developing effective nursing interventions. This qualitative study aims to explore these experiences and perceptions to inform the enhancement of clinical geriatric nursing and care practices. Methods Utilizing a qualitative exploratory design, this research engaged a convenience sample of geriatric specialist nurses at a tertiary hospital in Shanghai, China through focus groups and semi-structured interviews. Data were rigorously analyzed using Colaizzi’s phenomenological method, which facilitated the identification of themes that emerged from the narratives of the geriatric specialist nurses. Results The thematic analysis yielded three major themes that encapsulate the nurses’ experiences and perceptions. Theme 1: Understanding of Delirium, highlighted the nurses’ awareness of the condition’s significance, yet it was often deprioritized due to the pressing demands of managing more acute and immediately life-threatening conditions. Theme 2: Barriers in Application, brought to light the multifaceted challenges faced by nurses, including language barriers, the frequency and consistency of delirium assessments, the social determinants of health, and the nurses’ own competencies in assessment. Theme 3: Evolution of Nursing Approaches, detailed the adaptive strategies employed by nurses, such as managing nursing adverse events, improving communication with patients’ families, and adopting a proactive stance towards long-term patient outcomes. Conclusions The findings suggest that while geriatric specialist nurses recognize the importance of delirium assessment, there are several barriers to effective application. The study underscores the imperative for the advancement of more refined delirium assessment and care protocols, tailored to address the unique requirements of geriatric nursing care.

Abstract The authors propose a novel object detection algorithm for identifying bird nests in medium voltage power line aerial images, which is crucial for ensuring the safe operation of the power grid. The algorithm utilises an improved Swin Transformer as the main feature extraction network of Fast R‐CNN, further enhanced with a channel attention and modified binary self‐attention mechanism to improve the feature representation ability. The proposed algorithm is evaluated on a newly constructed image dataset of medium voltage transmission lines containing bird nests, which are annotated and classified. Experimental results show that the proposed algorithm achieves satisfied accuracy and robustness in recognising bird nests compared to traditional algorithms.

Abstract Background This study aimed to explore the expression, molecular mechanism and its biological function of potassium two pore domain channel subfamily K member 1 (KCNK1) in bladder cancer (BC). Methods We integrated large numbers of external samples (n = 1486) to assess KCNK1 mRNA expression levels and collected in-house samples (n = 245) for immunohistochemistry (IHC) experiments to validate at the KCNK1 protein level. Single-cell RNA sequencing (scRNA-seq) analysis was performed to further assess KCNK1 expression and cellular communication. The transcriptional regulatory mechanisms of KCNK1 expression were explored by ChIP-seq, ATAC-seq and ChIA-PET data. Highly expressed co-expressed genes (HECEGs) of KCNK1 were used to explore potential signalling pathways. Furthermore, the immunoassay, clinical significance and molecular docking of KCNK1 were calculated. Results KCNK1 mRNA was significantly overexpressed in BC (SMD = 0.58, 95% CI [0.05; 1.11]), validated at the protein level (p

Abstract Rectal adenocarcinoma (READ) is a common malignant tumor of the digestive tract. Growing studies have confirmed Ras GTPase-activating proteins are involved in the progression of several tumors. This study aimed to explore the expression and function of Ras GTPase-activating proteins in READ. In this study, we analyzed RNA sequencing data from 165 patients with READ and 789 normal tissue samples, identifying 5603 differentially expressed genes (DEGs), including 2937 upregulated genes and 2666 downregulated genes. Moreover, we also identified two dysregulated genes, RASA4 and SYNGAP1, among six Ras GTPase-activating proteins. High NF1 expression was associated with longer overall survival, while high SYNGAP1 expression showed a trend towards extended overall survival. Further analysis revealed the mutation frequency and copy number variations of Ras GTPase-activating proteins in various cancer samples. Additionally, DNA methylation analysis demonstrated a negative correlation between DNA methylation of Ras GTPase-activating proteins and their expression. Moreover, among Ras GTPase-activating proteins, we focused on SYNGAP1, and experimental validation confirmed that the overexpression of SYNGAP1 in READ significantly suppressed READ cell proliferation and increased apoptosis via regulating the Wnt/β-Catenin signaling pathway. These findings underscored the potential significance of SYNGAP1 in READ and provide new insights for further research and treatment.

IntroductionVariants in the PARS2 gene have been previously associated with developmental and epileptic encephalopathy. PARS2 deficiency was characterized as a neurodevelopmental and neurodegenerative disorder with early-onset seizures and global developmental delay. Herein, we reported the first case with severe heart failure due to lethal mitochondrial cardiomyopathy with PARS2 compound heterozygous variants.Case presentationThis patient demonstrated fatigue, chest tightness, and shortness of breath. An acute major illness had been identified at the initial evaluation, which was characterized by severe diaphoresis, dizziness, and fatigue. Blood–urine tandem mass spectrometry found multiple disorders in acid metabolism, characterized as increased homovanillic acid (130.39 mmol/L) and 2-hydroxyisovaleric acid (1.70 mmol/L), which are associated with myocardial injuries. Therefore, an inherited metabolic disorder was suspected and whole-exome sequencing was performed, revealing a novel compound heterozygous variant of c.953C>T and c.283G>A on PARS2. Echocardiography confirmed the findings from the MRI, which presented an increased left ventricular diameter at the end of the diastolic stage. The molecular structure of SYPM was established as AF-Q7L3T8-F1, and the identified mutant sites were located in the proline-tRNA ligase domain. However, the patient died due to severe heart failure.ConclusionThis is the first case to reveal a novel compound heterozygous variant of PARS2-induced lethal cardiomyopathy with unreversed heart failure. Thus, this report enhances our understanding of mitochondrial tRNA function in maintaining heart function.

BackgroundKawasaki disease (KD) is characterized as an acute febrile inflammatory disorder, which may potentially escalate into a more severe condition termed Kawasaki disease shock syndrome (KDSS). The objective of this research is to understand the clinical attributes of KDSS and to explore the predictive significance of coagulation profiles in the incidence of KDSS.MethodPatients with Kawasaki disease (KD) were prospectively enrolled and divided into the KDSS group (n = 29) and the non-KDSS group (n = 494). Multivariate logistic regression analysis was used to ascertain the relationship between coagulation profiles and KDSS. Furthermore, ROC curve analysis was conducted to evaluate the predictive value of the coagulation profile for the occurrence of KDSS.ResultAmong the KDSS patients, the median age was higher and cervical lymph node involvement was greater compared to the non-KDSS group. Additionally pericardial effusion, valve regurgitation, cardiac enlargement, coronary artery lesions (CALs), and Intravenous immunoglobulin (IVIG) resistance were significantly more frequent in the KDSS group than in non-KDSS group. Notably, Prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, and fibrin degradation products (FDP) were significantly elevated in the KDSS group compared to the non-KDSS group. Conversely, total thrombin time (TT), fibrinogen, and antithrombin III (ATIII) activity were significantly reduced. Multivariate logistic regression analysis revealed that PT, APTT, D-dimer, and ATIII were independent risk factors for predicting KDSS occurrence. ROC curve analysis established critical values for PT, D-dimer, FDP, and ATIII as 13.45 s, 2.03 mg/L, 7.45 μg/ml, and 77.5%, respectively. Sensitivity for predicting KDSS occurrence was 76%, 79%, 83%, and 76%, while specificity was 51%, 72%, 63%, and 80%, respectively. When we performed a combined ROC curve analysis of the four indicators, we found that its predictive sensitivity was much higher. Moreover, the Delong test results showed that the AUC of the combined analysis was significantly higher than that of the individual analyses.ConclusionCharacteristic features of KDSS include older age, a greater likelihood of experiencing pericardial effusion, valve regurgitation, cardiac enlargement, CALs, and IVIG resistance. KD patients with a hypercoagulable state during the acute phase are at a higher risk of developing KDSS.

Abstract Sweet taste receptors found in oral and extra oral tissues play important roles in the regulation of many physiological functions. Studies have shown that urine volume increases during the lifetime exposure to artificial sweeteners. However, the detailed molecular mechanism and the general effects of different artificial sweeteners exposure on urine volume remain unclear. In this study, we investigated the relationship between urinary excretion and the sweet taste receptor expression in mice after three artificial sweeteners exposure in a higher or lower concentration via animal behavioral studies, western blotting, and real-time quantitative PCR experiment in rodent model. Our results showed that high dose of acesulfame potassium and saccharin can significantly enhance the urine output and there was a positive correlation between K+ and urination volume. The acesulfame potassium administration assay of T1R3 knockout mice showed that artificial sweeteners may affect the urine output directly through the sweet taste signaling pathway. The expression of T1R3 encoding gene can be up-regulated specifically in bladder but not in kidney or other organs we tested. Through our study, the sweet taste receptors, distributing in many tissues as bladder, were indicated to function in the enhanced urine output. Different effects of long-term exposure to the three artificial sweeteners were shown and acesulfame potassium increased urine output even at a very low concentration.

Abstract Eosinophils are a group of granulocytes well known for their capacity to protect the host from parasites and regulate immune function. Diverse biological roles for eosinophils have been increasingly identified, but the developmental pattern and regulation of the eosinophil lineage remain largely unknown. Herein, we utilize the zebrafish model to analyze eosinophilic cell differentiation, distribution, and regulation. By identifying eslec as an eosinophil lineage-specific marker, we establish a Tg(eslec:eGFP) reporter line, which specifically labeled cells of the eosinophil lineage from early life through adulthood. Spatial-temporal analysis of eslec + cells demonstrates their organ distribution from larval stage to adulthood. By single-cell RNA-Seq analysis, we decipher the eosinophil lineage cells from lineage-committed progenitors to mature eosinophils. Through further genetic analysis, we demonstrate the role of Cebp1 in balancing neutrophil and eosinophil lineages, and a Cebp1-Cebpβ transcriptional axis that regulates the commitment and differentiation of the eosinophil lineage. Cross-species functional comparisons reveals that zebrafish Cebp1 is the functional orthologue of human C/EBPεP27 in suppressing eosinophilopoiesis. Our study characterizes eosinophil development in multiple dimensions including spatial-temporal patterns, expression profiles, and genetic regulators, providing for a better understanding of eosinophilopoiesis.

In this paper, an integrated device which realized the dual-mode integration of power amplifier (PA) and radio frequency (RF) switch based on GaN dual-gate (DG) structure is designed and fabricated. The integrated device provides two working modes and meets the performance requirements of PA and RF switch. In the transmit (Tx) mode, the integrated device is used as PA. At the frequency of 3.6 GHz, compared with the conventional GaN HEMT (high electron mobility transistor) as PA, due to the field modulation effect of the dual-gate structure, the current collapse is effectively suppressed, and the output power density $(P_{out})$ of the integrated device is increased from 6.90 W/mm to 7.85 W/mm, and the power added efficiency (PAE) is increased from 44.3% to 51.1%. In the receive (Rx) mode, the integrated device is used as RF switch. Compared with conventional RF switch, the isolation of integrated devices is significantly improved. At the frequency of 3.6GHz, the isolation is improved from 19.4 dB to 41.0 dB; At the frequency of 40 GHz, the isolation is improved from 3.0 dB to 29.7 dB. The integrated device provides a novel function integration scheme for RF frontends, with great potential for improving the integration and dimension of future communication systems.

Biotechnology has limited effectiveness in terms of removing mixed antibiotics at low temperatures, leading to ecological risks arising from the presence of antibiotics in environmental waters. In this study, the removal of tetracycline (TCs) and sulfonamide (SAs) from antibiotic wastewater was improved by the intermittent electrical stimulation of anaerobic-aerobic-coupled upflow bioelectrochemical reactors (AO-UBERs) at low temperatures. The removal effects of oxytetracycline and tetracycline were 48.6 ± 3.5 % and 71.5 ± 2.9 %, respectively. Under 0.9V, the removal rates of oxytetracycline, tetracycline, and trimethoprim were significantly increased in both the aerobic-cathodic and anaerobic anodic chambers, with a more obvious increase at low temperatures. Compared with the blank control group, the removal efficiency of oxytetracycline, trimethoprim and tetracycline in the electric group was increased by 11.8 ± 2.5 %, 27.8 ± 10.5 % and 11.2 ± 5.8 %. The anaerobic chamber contributed more to the removal of TCs and trimethoprim than the aerobic chamber. Furthermore, electrical stimulation selectively enriched electroactive bacteria (Methylophage and Pleuromonas), drug-resistant bacteria (Proteobacteria), and nitrifying bacteria associated with biodegradation. The abundance of antibiotic-resistance genes is related to the distribution of potential hosts and mobile genetic elements (sul1), and electrical stimulation induces the enrichment of both. This suggests that while potentially effective for treating TCs- and SAs-containing wastewater at low temperatures, AO-UBERs may lead to the accumulation of antibiotic-resistance genes.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune subepidermal blistering skin disease, manifested by erythematous plaques covered by circular blisters in a pattern of "string of pearls". Immune dysregulation and genetic factors are implicated in the onset of LABD. The pathogenesis includes abnormal deposition of IgA antibodies in the basement membrane zone and abnormal immune response. Although the pathological characteristics are atypical, direct immunofluorescence shows deposition of linear IgA antibody at the basement membrane zone. Advances in molecular biology and immunology offer new possibilities for enhancing precise diagnosis. Personalized treatment has become pivotal, while topical steroids and antihistamines are suitable for mild cases. Severe cases may require systemic immunosuppressants or even biologics. This review aims to summarize the latest research advances in LABD, including epidemiological features, pathogenesis, diagnostic and therapeutic strategies, and to provide an outlook on future research directions.

AbstractContext Crocin exhibits anti-depressant properties. However, its underlying mechanisms and its relationship with metabolomics remain unclear.Objective This study elucidates the mechanism of action and potential targets of crocin in treating chronic unexpected mild stress (CUMS)-induced depression in rats.Materials and methods Male Sprague-Dawley (SD) rats underwent 4 weeks of CUMS to establish the depression model. The normal control (distilled water), crocin (25 mg/kg), and fluoxetine (5.4 mg/kg) groups were orally administered for 4-weeks. Behavioural tests evaluated the effects of crocin, while liquid chromatography-mass spectrometry metabolomics identified differential metabolites and their associated metabolic pathways. Subsequently, network pharmacology was utilized to predict the targets of crocin.Results Crocin significantly increased body weight (from 319.16 ± 4.84 g to 325.67 ± 2.84 g), sucrose preference (from 0.46 ± 0.09 to 0.70 ± 0.09), vertical activity (from 2.83 ± 1.94 to 8 ± 2.36), horizontal activity (from 1 ± 0.63 to 4.5 ± 3.08) and decreased immobilization time (from 13.16 ± 2.69 to 3.97 ± 3.00). Metabolomics analysis identified 7 metabolites and 5 associated metabolic pathways. From the combined analysis of network pharmacology and metabolomics, three targets (PRMT1, CYP3A4, and GLB1) are the overlapping targets and the two most important metabolic pathways are tryptophan metabolism and glycerolipid metabolism.Discussion and conclusions This study provides insights into the antidepressant therapeutic effect of crocin and its underlying mechanisms. The findings contribute to a better understanding of the metabolic mechanism involved in the anti-depressant effect of crocin, establishing a strong foundation for future research in this area.

In recent decades, with the rapid development of the inorganic synthesis and the increasing discharge of pollutants in the process of industrialization, hollow-structured metal oxides (HSMOs) have taken on a striking role in the field of environmental catalysis. This is all due to their unique structural characteristics compared to solid nanoparticles, such as high loading capacity, superior pore permeability, high specific surface area, abundant inner void space, and low density. Although the HSMOs with different morphologies have been reviewed and prospected in the aspect of synthesis strategies and potential applications, there has been no systematic review focusing on the structures and compositions design of HSMOs in the field of environmental catalysis so far. Therefore, this review will mainly focus on the component dependence and controllable structure of HSMOs in the catalytic elimination of different environmental pollutants, including the automobile and stationary source emissions, volatile organic compounds, greenhouse gases, ozone-depleting substances, and other potential pollutants. Moreover, we comprehensively reviewed the applications of the catalysts with hollow structure that are mainly composed of metal oxides such as CeO2, MnOx, CuOx, Co3O4, ZrO2, ZnO, Al3O4, In2O3, NiO, and Fe3O4 in automobile and stationary source emission control, volatile organic compounds emission control, and the conversion of greenhouse gases and ozone-depleting substances. The structure–activity relationship is also briefly discussed. Finally, further challenges and development trends of HSMO catalysts in environmental catalysis are also prospected.

Abstract Background Pancreatic adenocarcinoma (PAAD) is one of the most fatal human cancers, but effective therapies remain to be established. Cancer stem cells (CSCs) are highly resistant to anti-cancer drugs and a deeper understanding of their microenvironmental niche has been considered important to provide understanding and solutions to cancer eradication. However, as the CSC niche is composed of a wide variety of biological and physicochemical factors, the development of multidisciplinary tools that recapitulate their complex features is indispensable. Synthetic polymers have been studied as attractive biomaterials due to their tunable biofunctionalities, while hydrogelation technique further renders upon them a diversity of physical properties, making them an attractive tool for analysis of the CSC niche. Methods To develop innovative materials that recapitulate the CSC niche in pancreatic cancers, we performed polymer microarray analysis to identify niche-mimicking scaffolds that preferentially supported the growth of CSCs. The niche-mimicking activity of the identified polymers was further optimized by polyethylene glycol (PEG)-based hydrogelation. To reveal the biological mechanisms behind the activity of the optimized hydrogels towards CSCs, proteins binding onto the hydrogel were analyzed by liquid chromatography with tandem mass spectrometry (LC–MS/MS), and the potential therapeutic targets were validated by looking at gene expression and patients’ outcome in the TCGA database. Results PA531, a heteropolymer composed of 2-methoxyethyl methacrylate (MEMA) and 2-(diethylamino)ethyl methacrylate (DEAEMA) (5.5:4.5) that specifically supports the growth and maintenance of CSCs was identified by polymer microarray screening using the human PAAD cell line KLM1. The polymer PA531 was converted into five hydrogels (PA531-HG1 to HG5) and developed to give an optimized scaffold with the highest CSC niche-mimicking activities. From this polymer that recapitulated CSC binding and control, the proteins fetuin-B and angiotensinogen were identified as candidate target molecules with clinical significance due to the correlation between gene expression levels and prognosis in PAAD patients and the proteins associated with the niche-mimicking polymer. Conclusion This study screened for biofunctional polymers suitable for recapitulation of the pancreatic CSC niche and one hydrogel with high niche-mimicking abilities was successfully fabricated. Two soluble factors with clinical significance were identified as potential candidates for biomarkers and therapeutic targets in pancreatic cancers. Such a biomaterial-based approach could be a new platform in drug discovery and therapy development against CSCs, via targeting of their niche.

Abstract Cerebral ischemia is a serious cerebrovascular disease with the characteristics of high morbidity, disability, and mortality. Currently, stem cell therapy has been extensively applied to a wide range of diseases, including neurological disorders, autoimmune deficits, and other diseases. Transplantation therapy with neural stem cells (NSCs) is a very promising treatment method, which not only has anti‐inflammatory, antiapoptotic, promoting angiogenesis, and neurogenesis effects, but also can improve some side effects related to thrombolytic therapy. NSCs treatment could exert protective effects in alleviating cerebral ischemia‐induced brain damage and neurological dysfunctions. However, the different injection routes and doses of NSCs determine diverse therapeutic efficacy. This review mainly summarizes the various injection methods and injection effects of NSCs in cerebral ischemia, as well as proposes the existing problems and prospects of NSCs transplantation.

Abstract Objective Sound touch elastography (STE) and sound touch quantification (STQ) are novel imaging methods to evaluate tissue stiffness. This study aims to investigate renal stiffness in patients with chronic kidney disease (CKD) by STE and STQ, using renal biopsy as ‘gold standard’. Methods Between 2019 January and 2022 June, 60 patients who underwent renal biopsy for proteinuria (cases) and 45 healthy volunteers (controls) at our hospital were included in this study. The maximum and mean elastic modulus (Emax, Emean) of region of interest in right kidney were measured by STE and STQ techniques. Biochemical profiles and renal biopsy findings were recorded. Results Both Emax and Emean measured by STE were significantly different between cases and controls. ROC analysis of STE measurements revealed using a cutoff of 13.53 kPa for Emax and 10.16 kPa for Emean, the area under the curve (AUC) to distinguish nephropathy from healthy was 0.718 and 0.744. Analysis of ROC for STQ measurements showed that using a cutoff value of 15.87 kPa for Emax and 9.95 kPa for Emean, the AUC for the nephropathy was 0.612 and 0.569. Emax and Emean values were significantly different among CKD patients with mild, moderate and severe pathological stage. The Emax value for STE was positively related to Scr, β2-MG (r = 0.257, 0.292, p

Abstract Background The Sinodielsia clade of the subfamily Apioideae (Apiacieae) was established in 2008, and it is composed of 37 species from 17 genera. Its circumscription is still poorly delimited and unstable, and interspecific relationships in the clade lack comprehensive analysis. Chloroplast (cp.) genomes provide valuable and informative data sources for evolutionary biology and have been widely used in studies on plant phylogeny. To infer the phylogenetic history of the Sinodielsia clade, we assembled complete cp. genomes of 39 species and then performed phylogenetic analysis based on these cp. genome sequence data combined with 66 published cp. genomes from 16 genera relative to the Sinodielsia clade. Results These 39 newly assembled genomes had a typical quadripartite structure with two inverted repeat regions (IRs: 17,599–31,486 bp) separated by a large single-copy region (LSC: 82,048–94,046 bp) and a small single-copy region (SSC: 16,343–17,917 bp). The phylogenetic analysis showed that 19 species were clustered into the Sinodielsia clade, and they were divided into two subclades. Six mutation hotspot regions were detected from the whole cp. genomes among the Sinodielsia clade, namely, rbcL–accD, ycf4–cemA, petA–psbJ, ycf1–ndhF, ndhF–rpl32 and ycf1, and it was found that ndhF–rpl32 and ycf1 were highly variable in the 105 sampled cp. genomes. Conclusion The Sinodielsia clade was subdivided into two subclades relevant to geographical distributions, except for cultivated and introduced species. Six mutation hotspot regions, especially ndhF–rpl32 and ycf1, could be used as potential DNA markers in the identification and phylogenetic analyses of the Sinodielsia clade and Apioideae. Our study provided new insights into the phylogeny of the Sinodielsia clade and valuable information on cp. genome evolution in Apioideae.

ABSTRACTThe re-emerging mpox (formerly monkeypox) virus (MPXV), a member of Orthopoxvirus genus together with variola virus (VARV) and vaccinia virus (VACV), has led to public health emergency of international concern since July 2022. Inspired by the unprecedent success of coronavirus disease 2019 (COVID-19) mRNA vaccines, the development of a safe and effective mRNA vaccine against MPXV is of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we rationally constructed and prepared a panel of multicomponent MPXV vaccine candidates encoding different combinations of viral antigens including M1R, E8L, A29L, A35R, and B6R. In vitro and in vivo characterization demonstrated that two immunizations of all mRNA vaccine candidates elicit a robust antibody response as well as antigen-specific Th1-biased cellular response in mice. Importantly, the penta- and tetra-component vaccine candidates AR-MPXV5 and AR-MPXV4a showed superior capability of inducing neutralizing antibodies as well as of protecting from VACV challenge in mice. Our study provides critical insights to understand the protection mechanism of MPXV infection and direct evidence supporting further clinical development of these multicomponent mRNA vaccine candidates.

Mosunetuzumab is a novel bispecific antibody targeting epitopes on CD3 on T cells and CD20 on B cells with the goal of inducing T-cell mediated elimination of malignant B cells. A recent pivotal phase I/II clinical trial (GO29781) demonstrated that mosunetuzumab induced an overall response rate of 80%, complete response rate of 60%, and a median progression-free survival of 17.9 months in patients with relapsed/refractory (r/r) follicular lymphoma (FL) following at least two prior lines of systemic therapy, including alkylator and anti-CD20 antibody-based therapy. Historical data from cohorts receiving therapy for r/r FL can provide some context for interpretation of single-arm trials. We compared the results from the mosunetuzumab trial to outcomes from a cohort of patients with r/r FL from the LEO Consortium for Real World Evidence (LEO CReWE). We applied clinical trial eligibility criteria to the LEO CReWE cohort and utilized matching-adjusted indirect comparison weighting to balance the clinical characteristics of the LEO CReWE cohort with those from the mosunetuzumab trial. Overall response rates (73%, 95% CI:65-80%) and complete response rates (53%, 95% CI:45-61%) observed in the weighted LEO CReWE cohort were lower than those reported on the mosunetuzumab trial (ORR=80%, 95% CI:70-88%; CR=60%, 95% CI:49-70% respectively). Progression-free survival at 12 months was similar in the weighted LEO CReWE (60%, 95% CI:51-69%) and the mosunetuzumab trial (PFS 58%, 95% CI:47-68%). Sensitivity analyses examining the impact of matching variables, selection of line of therapy, and application of eligibility criteria, provide context for best practices in this setting.

Abstract Biomimetic viral mineralization improves viral vaccine stability and immunogenicity using inorganic metals such as Ca, Al, or Fe. Mn is a metal found in high concentrations in mammalian tissues; however, under natural or laboratory conditions, Mn mineralization by medical viruses has yet to be established. Herein, a single IAV particle is successfully encapsulated with manganese phosphate (MnP) under specific conditions using the human influenza A virus (IAV). MnP‐mineralized IAVs (IAV@Mn) exhibited physiochemical and in vitro properties similar to Ca‐mineralized IAVs. In animal models, IAV@Mn shows limited replication in immune‐competent cells and a significant attenuation compared to naïve cells. Moreover, a single‐dose vaccination with IAV@Mn induced robust humoral and cellular immune responses and conferred significant protection against a wild‐type IAV challenge in mice. Thus, Mn mineralization in pathogenic viruses provides a rapid and universal strategy for generating an emergency vaccine in response to emerging viruses.

IntroductionIt is necessary to explore the evidence-based practice of perioperative management of elderly patients undergoing ambulatory surgery, to optimize the clinical workflow and improve the quality of nursing care.MethodsBased on the best evidence obtained from the previous study, the perioperative management model and examination index of elderly patients undergoing day surgery were established, and the evidence of best practice was obtained by using the evidence-based methodology. Then, we integrated evidence into clinical practice and improved the process. We made a comparative analysis of the effect before and after the implementation of the evidence.ResultsThis study summarized 26 pieces of evidence of perioperative management of elderly patients undergoing day surgery and transformed the evidence into 7 items and 11 items of examination index. After the application of the best evidence, knowledge, belief, and practice of perioperative management of nurses for elderly patients in the day operation ward reached 100%, and the rate of reaching the standard of most indicators increased after the application of evidence. The length of waiting for admission and waiting for operation and returning to the ward to discharge of elderly patients decreased significantly, and the difference was statistically significant (All p

ObjectiveTo analyze the clinical and ultrasonic characteristics of breast sclerosing adenosis (SA) and invasive ductal carcinoma (IDC), and construct a predictive nomogram for SA.Materials and methodsA total of 865 patients were recruited at the Second Hospital of Shandong University from January 2016 to November 2022. All patients underwent routine breast ultrasound examinations before surgery, and the diagnosis was confirmed by histopathological examination following the operation. Ultrasonic features were recorded using the Breast Imaging Data and Reporting System (BI-RADS). Of the 865 patients, 203 (252 nodules) were diagnosed as SA and 662 (731 nodules) as IDC. They were randomly divided into a training set and a validation set at a ratio of 6:4. Lastly, the difference in clinical characteristics and ultrasonic features were comparatively analyzed.ResultThere was a statistically significant difference in multiple clinical and ultrasonic features between SA and IDC (P

Abstract Background Coronary artery aneurysms (CAA) persistence prediction is critical in evaluating Kawasaki disease (KD). This study established a nomogram prediction system based on potential risk factors for assessing the risk of CAA persistence in a contemporary cohort of patients with KD. Methods This cohort comprised 105 patients with KD who had been diagnosed with CAA during the acute or subacute phase by echocardiography. The follow-up duration was at least 1 year. The clinical and laboratory parameters were compared between the CAA regression and persistence groups. Multivariable logistic regression analysis was used to identify the independent risk factors for CAA persistence, which were subsequently used to build the nomogram predictive model. Decision curve analysis was used to assess the net benefits of different nomogram scores. Results Of these patients with CAA, 27.6% of patients presented with persistent lesions. The incidences of CAA persistence were 14.1%, 81.3%, and 100.0% in patients with small, medium, and large aneurysms, respectively. The ratio of neutrophils to lymphocytes, γ-GT, and CAA size at diagnosis were considered as the independent risk factors for CAA persistence in patients with KD. The nomogram predictive models yielded a high capability in predicting CAA persistence, based on either univariable or multivariable analyses-identified parameters, compared with using CAA size as a single predictor. Conclusion The initial ratio of neutrophils to lymphocytes, γ-GT, and CAA size were the independent risk factors for CAA persistence in patients with KD. Nomogram scores could help elevate predictive efficacy in detecting CAA persistence.

Summary: Schwann cells play critical roles in peripheral neuropathies; however, the regulatory mechanisms of their homeostasis remain largely unknown. Here, we show that nucleoporin Seh1, a component of nuclear pore complex, is important for Schwann cell homeostasis. Expression of Seh1 decreases as mice age. Loss of Seh1 leads to activated immune responses and cell necroptosis. Mice with depletion of Seh1 in Schwann cell lineage develop progressive reduction of Schwann cells in sciatic nerves, predominantly non-myelinating Schwann cells, followed by neural fiber degeneration and malfunction of the sensory and motor system. Mechanistically, Seh1 safeguards genome stability by mediating the interaction between SETDB1 and KAP1. The disrupted interaction after ablation of Seh1 derepresses endogenous retroviruses, which triggers ZBP1-dependent necroptosis in Schwann cells. Collectively, our results demonstrate that Seh1 is required for Schwann cell homeostasis by maintaining genome integrity and suggest that decrease of nucleoporins may participate in the pathogenesis of periphery neuropathies.

Abstract As the world continues to experience the COVID-19 pandemic, seasonal influenza remain a cause of severe morbidity and mortality globally. Worse yet, coinfection with SARS-CoV-2 and influenza A virus (IAV) leads to more severe clinical outcomes. The development of a combined vaccine against both COVID-19 and influenza is thus of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we developed and characterized a novel mRNA vaccine encoding the HA antigen of influenza A (H1N1) virus, termed ARIAV. Then, ARIAV was combined with our COVID-19 mRNA vaccine ARCoV, which encodes the receptor-binding domain (RBD) of the SARS-CoV-2 S protein, to formulate the final combined vaccine, AR-CoV/IAV. Further characterization demonstrated that immunization with two doses of AR-CoV/IAV elicited robust protective antibodies as well as antigen-specific cellular immune responses against SARS-CoV-2 and IAV. More importantly, AR-CoV/IAV immunization protected mice from coinfection with IAV and the SARS-CoV-2 Alpha and Delta variants. Our results highlight the potential of the LNP-mRNA vaccine platform in preventing COVID-19 and influenza, as well as other respiratory diseases.

Sepsis-induced acute kidney injury (SI-AKI), a common critically ill, represents one of the leading causes of global death. Emerging evidence reveals autophagy as a pivotal modulator of SI-AKI. Autophagy affects the cellular processes of renal lesions, including cell death, inflammation, and immune responses. Herein, we conducted a systematic and comprehensive review on the topic of the proposed roles of autophagy in SI-AKI. Forty-one relevant studies were finally included and further summarized and analyzed. This review revealed that a majority of included studies (24/41, 58.5%) showed an elevation of the autophagy level during SI-AKI, while 22% and 19.5% of the included studies reported an inhibition and an elevation at the early stage but a declination of renal autophagy in SI-AKI, respectively. Multiple intracellular signaling molecules and pathways targeting autophagy (e.g. mTOR, non-coding RNA, Sirtuins family, mitophagy, AMPK, ROS, NF-Kb, and Parkin) involved in the process of SI-AKI, exerting multiple biological effects on the kidney. Multiple treatment modalities (e.g. small molecule inhibitors, temsirolimus, rapamycin, polydatin, ascorbate, recombinant human erythropoietin, stem cells, Procyanidin B2, and dexmedetomidine) have been found to improve renal function, which may be attributed to the elevation of the autophagy level in SI-AKI. Though the exact roles of autophagy in SI-AKI have not been well elucidated, it may be implicated in preventing SI-AKI through various molecular pathways. Targeting the autophagy-associated proteins and pathways may hint towards a new prospective in the treatment of critically ill patients with SI-AKI, but more preclinical studies are still warranted to validate this hypothesis.

Passivation is commonly used to suppress current collapse in AlGaN/GaN HEMTs. However, the conventional PECV-fabricated SiNx passivation layer is incompatible with the latest process, like the “passivation-prior-to-ohmic” method. Research attention has therefore turned to high-temperature passivation schemes. In this paper, we systematically investigated the differences between the SiNx/GaN interface of two high-temperature passivation schemes, MOCVD-SiNx and LPCVD-SiNx, and investigated their effects on the ohmic contact mechanism. By characterizing the device interface using TEM, we reveal that during the process of MOCVD-SiNx, etching damage and Si diffuses into the semiconductor to form a leakage path and reduce the breakdown voltage of the AlGaN/GaN HEMTs. Moreover, N enrichment at the edge of the ohmic region of the LPCVD-SiNx device indicates that the device is more favorable for TiN formation, thus reducing the ohmic contact resistance, which is beneficial to improving the PAE of the device. Through the CW load-pull test with drain voltage VDS = 20V, LPCVD-SiNx devices obtain a high PAE of 66.35%, which is about 6% higher than MOCVD-SiNx devices. This excellent result indicates that the prospect of LPCVD-SiNx passivation devices used in 5G small terminals will be attractive.

Abstract Background Intestinal ischemia/reperfusion (I/R) injury has high morbidity and mortality rates. Gut microbiota is a potential key factor affecting intestinal I/R injury. Populations exhibit different sensitivities to intestinal I/R injury; however, whether this interpopulation difference is related to variation in gut microbiota is unclear. Here, to elucidate the interaction between the gut microbiome and intestinal I/R injury, we performed 16S DNA sequencing on the preoperative feces of C57BL/6 mice and fecal microbiota transplantation (FMT) experiments in germ-free mice. The transwell co-culture system of small intestinal organoids extracted from control mice and macrophages extracted from control mice or Toll-like receptor 2 (TLR2)-deficient mice or interleukin-10 (IL-10)-deficient mice were established separately to explore the potential mechanism of reducing intestinal I/R injury. Results Intestinal I/R-sensitive (Sen) and intestinal I/R-resistant (Res) mice were first defined according to different survival outcomes of mice suffering from intestinal I/R. Fecal microbiota composition and diversity prior to intestinal ischemia differed between Sen and Res mice. The relative abundance of Lactobacillus murinus (L. murinus) at the species level was drastically higher in Res than that in Sen mice. Clinically, the abundance of L. murinus in preoperative feces of patients undergoing cardiopulmonary bypass surgery was closely related to the degree of intestinal I/R injury after surgery. Treatment with L. murinus significantly prevented intestinal I/R-induced intestinal injury and improved mouse survival, which depended on macrophages involvement. Further, in vitro experiments indicated that promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury. Conclusion The gut microbiome is involved in the postoperative outcome of intestinal I/R. Lactobacillus murinus alleviates mice intestinal I/R injury through macrophages, and promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury. This study revealed a novel mechanism of intestinal I/R injury and a new therapeutic strategy for clinical practice. Video Abstract.

In this paper, the impact of ohmic structure on channel-to-channel (C2C) coupling effect in InAlN/GaN double channel (DC) HEMTs is systematically analyzed and studied. For the un-recessed ohmic structure, the electrons in the upper channel can easily inject into the bottom channel due to the ultra-thin InAlN back barrier layer. Therefore, the maximum drain current and transconductance peak of the bottom channel significantly increase. For recessed ohmic structure, the reduced vertical electric field strength of the upper channel can effectively weaken the coupling effect between the two GaN channels. Benefiting from the suppressed vertical transport of electrons in the upper channel, higher drain current and transconductance of the upper channel are obtained in the recessed ohmic structure. In addition, the transmission electron microscope (TEM) microstructural analysis of the DC HEMTs with recessed ohmic structure was also performed. This work shows that the recessed ohmic structure can modulate the electron transport mode in the InAlN/GaN DC HEMTs. The coupling effect of the two channels will play a major role in influencing the characteristics of current gain cutoff frequency ( $\,f_{\mathrm{ T}}$ ) / maximum power gain cutoff frequency ( $\,f_{\mathrm{ max}}$ ) versus $V_{\mathrm{ GS}}$ and have a significant effect on large-signal characteristics, which is quite attractive for the fabrication of power microwave GaN-based HEMTs with wide gate swing.

Large strain gradient is crucial for flexoelectricity. Here, the authors reveal the generality and tunability of large strain gradients at grain boundaries in oxides, explaining the possible effects on the electrical activities of ceramics.

Abstract Sepsis-induced cardiac dysfunction can lead to death in sepsis. In this case, we targeted to explore in detail the relative mechanism of microRNA (miR)-124-3p in sepsis-induced myocardial injury via the specific protein 1/histone deacetylase 4/hypoxia-inducing factor 1α (SP1/HDAC4/HIF-1α) axis. Septic rats were modeled by cecal ligation puncture while in vitro septic cardiomyocyte H9C2 were induced by lipopolysaccharide (LPS). miR-124-3p/SP1/HDAC4/HIF-1α expression levels in myocardial tissues of septic rats and LPS-treated H9C2 cells were measured. miR-124-3p overexpression and SP1 silencing assays were implemented on LPS-treated H9C2 cells to explore theirs actions in inflammation, oxidative stress and cell apoptosis. The interactions of miR-124-3p, SP1, and HDAC4 were testified. miR-124-3p was lowly expressed while SP1, HDAC4, and HIF-1α were highly expressed in sepsis. Upregulation of miR-124-3p ameliorated inflammation, oxidative stress, and apoptosis of LPS-treated H9C2 cells. Silencing SP1 improved LPS-induced damage to cardiomyocytes. miR-124-3p targeted SP1 and HDAC4 interacted with SP1. SP1 overexpression antagonized miR-124-3p upregulation-induced improvements in LPS-induced cardiomyocyte damage. This study illustrates that miR-124-3p improves myocardial injury in septic rats through targeted regulation of SP1 to mediate HDAC4/HIF-1α.

In this study, AlGaN/GaN nanochannel high-electron-mobility transistors (HEMTs) with tri-gate (TGN-devices) and dual-gate (DGN-devices) structures were fabricated and investigated. It was found that the peak value of the transconductance (Gm), current gain cut-off frequency (fT) and power gain cut-off frequency (fmax) of the TGN-devices were larger than that of the DGN-devices because of the enhanced gate control from the top gate. Although the TGN-devices and DGN-devices demonstrated flattened transconductance, fT and fmax profiles, the first and second transconductance derivatives of the DGN-devices were lower than those of the TGN-devices, implying an improvement in linearity. With the nanochannel width decreased, the peak value of the transconductance and the first and second transconductance derivatives increased, implying the predominant influence of sidewall gate capacitance on the transconductance and linearity. The comparison of gate capacitance for the TGN-devices and DGN-devices revealed that the gate capacitance of the tri-gate structure was not simply a linear superposition of the top planar gate capacitance and sidewall gate capacitance of the dual-gate structure, which could be attributed to the difference in the depletion region shape for tri-gate and dual-gate structures.

Abstract Hematopoietic stem cells (HSCs) possess the potential for self-renew and the capacity, throughout life, to differentiate into all blood cell lineages. Yet, the mechanistic basis for HSC development remains largely unknown. In this study, we characterized a zebrafish smu471 mutant with hematopoietic stem/progenitor cell (HSPC) defects and found that sart3 was the causative gene. RNA expression profiling of the sart3 smu471 mutant revealed spliceosome and p53 signaling pathway to be the most significantly enriched pathways in the sart3 smu471 mutant. Knock down of p53 rescued HSPC development in the sart3 smu471 mutant. Interestingly, the p53 inhibitor, mdm4, had undergone an alternative splicing event in the mutant. Restoration of mdm4 partially rescued HSPC deficiency. Thus, our data suggest that HSPC proliferation and maintenance require sart3 to ensure the correct splicing and expression of mdm4, so that the p53 pathway is properly inhibited to prevent definitive hematopoiesis failure. This study expands our knowledge of the regulatory mechanisms that impact HSPC development and sheds light on the mechanistic basis and potential therapeutic use of sart3 in spliceosome-mdm4-p53 related disorders.

Enteral nutrition (EN) is a diet-remission therapy for inflammatory bowel disease (IBD) that plays a more important role in children than adults. EN includes exclusive enteral nutrition (EEN), partial enteral nutrition (PEN), and maintenance enteral nutrition (MEN). However, EEN remains an unstandardized treatment for pediatric IBD. The types and methods of EN differ around the world. The current study reviewed the EN literature on children with IBD. A total of 12 survey studies were identified that analyzed the current state of EN use, including clinical opinions, implementation methods, treatment course, EEN formula, IBD classification, progress, dietary reintroduction, and patient feedback. The findings revealed that EEN has a strong effect on mild to moderate Crohn’s disease (CD). The usage rates of this treatment in different sites were ileum/colon (Paris classification L3) > ileum (L1) > upper digestive tract (L4) > colon (L2) > perianal disease (P) > ulcerative colitis (UC) > extraintestinal lesions. The polymeric formula was the most used EN formulation. New EN diets include a CD exclusion diet (CDED), a specific carbohydrate diet (SCD), and a CD treatment-with-eating (CD-TREAT) diet. Children with IBD responded similarly to EEN administered orally or using a feeding tube. Most guidelines recommended 6–8 weeks of EEN treatment to induce remission. Many clinicians preferred to combine drug medications during EEN and recommended that MEN accounts for at least 25–35% of daily caloric intake. EN remains an unstandardized therapy that requires teamwork across disciplines.

Purpose2019 Coronavirus disease (COVID-19) is endangering health of populations worldwide. Latest research has proved that Lianhua Qingwen granules (LHQW) can reduce tissue damage caused by inflammatory reactions and relieve patients’ clinical symptoms. However, the mechanism of LHQW treats COVID-19 is currently lacking. Therefore, we employed computer simulations to investigate the mechanism of LHQW treats COVID-19 by modulating inflammatory response.MethodsWe employed bioinformatics to screen active ingredients in LHQW and intersection gene targets. PPI, GO and KEGG was used to analyze relationship of intersection gene targets. Molecular dynamics simulations validated the binding stability of active ingredients and target proteins. Binding free energy, radius of gyration and the solvent accessible surface area were analyzed by supercomputer platform.ResultsCOVID-19 had 4628 gene targets, LHQW had 1409 gene targets, intersection gene targets were 415. Bioinformatics analysis showed that intersection targets were closely related to inflammation and immunomodulatory. Molecular docking suggested that active ingredients (including: licopyranocoumarin, Glycyrol and 3-3-Oxopropanoic acid) in LHQW played a role in treating COVID-19 by acting on CSF2, CXCL8, CCR5, NLRP3, IFNG and TNF. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets.ConclusionThe mechanism of active ingredients in LHQW treats COVID-19 was investigated by computer simulations. We found that active ingredients in LHQW not only reduce cell damage and tissue destruction by inhibiting the inflammatory response through CSF2, CXCL8, CCR5 and IFNG, but also regulate cell survival and growth through NLRP3 and TNF thereby reducing apoptosis.

Purpose2019 Coronavirus disease (COVID-19) has caused millions of confirmed cases and deaths worldwide. TMPRSS2-mediated hydrolysis and maturation of spike protein is essential for SARS-CoV-2 infection in vivo. The latest research found that a TMPRSS2 inhibitor called N-0385 could effectively prevent the infection of the SARS-CoV-2 and its variants. However, it is not clear about the mechanism of N-0385 treatment COVID-19. Therefore, this study used computer simulations to investigate the mechanism of N-0385 treatment COVID-19 by impeding SARS-CoV-2 infection.MethodsThe GeneCards database was used to search disease gene targets, core targets were analyzed by PPI, GO and KEGG. Molecular docking and molecular dynamics were used to validate and analyze the binding stability of small molecule N-0385 to target proteins. The supercomputer platform was used to simulate and analyze the number of hydrogen bonds, binding free energy, stability of protein targets at the residue level, radius of gyration and solvent accessible surface area.ResultsThere were 4,600 COVID-19 gene targets from GeneCards database. PPI, GO and KEGG analysis indicated that signaling pathways of immune response and inflammation played crucial roles in COVID-19. Molecular docking showed that N-0385 could block SARS-CoV-2 infection and treat COVID-19 by acting on ACE2, TMPRSS2 and NLRP3. Molecular dynamics was used to demonstrate that the small molecule N-0385 could form very stable bindings with TMPRSS2 and TLR7.ConclusionThe mechanism of N-0385 treatment COVID-19 was investigated by molecular docking and molecular dynamics simulation. We speculated that N-0385 may not only inhibit SARS-CoV-2 invasion directly by acting on TMPRSS2, ACE2 and DPP4, but also inhibit the immune recognition process and inflammatory response by regulating TLR7, NLRP3 and IL-10 to prevent SARS-CoV-2 invasion. Therefore, these results suggested that N-0385 may act through multiple targets to reduce SARS-CoV-2 infection and damage caused by inflammatory responses.

BackgroundIn extant literature, the concept of social isolation has been explored primarily in the context of older adults. However, people with cancer may also experience social isolation, and there is a need for increased clarity regarding this phenomenon in this population.ObjectiveTo conceptualize social isolation in adult cancer care.MethodsPubMed, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure, Wanfang Data, and the Chinese Biomedical Literature Database were systematically searched using the key terms “cancer,” “social isolation,” “social alienation,” and “social exclusion” for studies (from the earliest date available to June 2022). The main disciplines involved were psychology, nursing, medicine, and public health. Rodgers’ evolutionary concept analysis was employed to clarify the antecedents, attributes, and consequences of social isolation in adults with cancer.ResultsA total of 60 eligible articles were reviewed entirely and the main findings were categorized into antecedents, attributes, and consequences. The antecedents of social isolation were classified into six categories: cancer-related physiological changes, cognitive beliefs, psychological wellbeing, unsatisfactory social supports or relationships, restrictions associated with receiving treatments, and social-level barriers. Attributes were characterized according to behavior or social avoidance and negative affective experiences, while consequences were attributed to low therapeutic compliance, poor health conditions and mental health problems, and low quality of life. White’s heuristic model is a potential theoretical context applicable to social isolation in adults with cancer.ConclusionThis concept analysis provides a basis for developing multidimensional assessment tools and measures to alleviate social isolation in adults with cancer, a complex and varied phenomenon. However, while this review contributes to the current knowledge on social isolation in people with cancer, studies should further investigate the relationships among attributes associated with social isolation.

Abstract Background To illustrate the mechanism of miRNA and mRNA in coronary artery diseasen (CAD), differentially expressed microRNAs (DEmiRNAs) and genes (DEGs) were analyzed. Methods The mRNA transcription profiles of GSE20680 (including 87 blood samples of CAD and 52 blood samples of control), GSE20681 (including 99 blood samples of CAD and 99 blood samples of control) and GSE12288 (including 110 blood samples of CAD and 112 blood samples of control) and the miRNA transcription profiles of GSE59421 (including 33 blood samples of CAD and 37 blood samples of control), GSE49823 (including 12 blood samples of CAD and 12 blood samples of control) and GSE28858 (including 13 blood samples of CAD and 13 blood samples of control) were downloaded from Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/ ). Then, the homogenous expressed mRNAs and miRNAs across the three mRNA transcription profiles and three miRNA transcription profiles were screened using the Fishers exact test in MetaDE. ES package. The weighted gene co-expression network analysis (WGCNA) was used to analyze gene modules. Additionally, the integrated miRNAs–targets regulatory network using the DEmiRNA and their targets was constructed using Cytoscape. Results A total of 1201 homogenously statistically significant DEGs were identified including 879 up-regulated and 322 down-regulated DEGs, while a total of 47 homogenously statistically significant DEmiRNAs including 37 up-regulated and 10 down-regulated DEmiRNAs in CAD compared with the controls across the three mRNA transcription profiles and the three miRNA transcription profiles. A total of 5067 genes were clustered into 9 modules in the training dataset, among which, 8 modules were validated. In the miRNAs-targets network, there existed 267 interaction relationships among 5 miRNAs (hsa-miR-361-5p, hsa-miR-139-5p, hsa-miR-146b-5p, hsa-miR-502-5p and hsa-miR-501-5p) and 213 targets. CAV1 could be the target of hsa-miR-361-5 while HSF2 was the target of both hsa-miR-361-5p and hsa-miR-146b-5p. CAV1 was significantly enriched in the GO term of regulation of cell proliferation. Conclusion hsa-miR-361-5p, has-miR-146b-5p, CAV1 and HSF2 could play an important role in CAD.

Abstract Background Intravenous immunoglobulin (IVIG) resistance prediction is one of the primary clinical issues and study hotspots in KD. This study aimed to prospectively investigate the value of albumin-bilirubin grade (ALBI) in predicting IVIG resistance in KD and to assess whether ALBI has more predictive value or accuracy than either ALB or TBil alone in predicting IVIG resistance. Methods A total of 823 patients with KD were prospectively enrolled. The clinical and laboratory data were compared between the IVIG-response group (n = 708) and the IVIG-resistance group (n = 115). Multivariate logistic regression analysis was performed to identify the independent risk factors for IVIG resistance. Receiver operating characteristic (ROC) curves analysis was applied to assess the validity of ALBI, ALB, and TBil in predicting IVIG resistance. Results ALBI was significantly higher in patients with IVIG resistance and was identified as an independent risk factor for IVIG resistance in KD. The parameter of ALBI ≥ − 2.57 (AUC: 0.705, 95 %CI: 0.672–0.736), ALB ≤ 33.0 g/L (AUC: 0.659, 95 %CI: 0.626–0.692), and TBil ≥ 16.0µmol/L (AUC: 0.626, 95 %CI: 0.592–0.659), produced a sensitivity, specificity, PPV, and NPV of 0.617, 0.657, 0.226 and 0.914; 0.374, 0.850, 0.289 and 0.893; 0.269, 0.941, 0.425 and 0.888, respectively. Conclusions A higher ALBI was an independent risk factor for IVIG resistance in KD. It yielded better predictive ability than ALB and TBil alone for initial IVIG resistance.

A controllable magnetoelectric phase based on symmetry engineering is challenge in natural bulk crystals. Here, via engineering of interfacial Dzyaloshinskii-Moriya interaction, the authors design a magnetoelectric phase transition in oxide superlattices of correlated electron systems.

Common autoimmune bullous diseases (AIBDs) include pemphigus and bullous pemphigoid (BP), which are primarily caused by IgG autoantibodies against the structural proteins of desmosomes at the cell–cell junction and hemidesmosomes at the epidermal–dermal junction. Few studies have assessed nail changes in patients with pemphigus or BP. In the present study, we collected the clinical data of 191 patients with AIBDs (108 patients with pemphigus and 83 patients with BP) and 200 control subjects. Nail changes were observed in 77.0% (147/191), 77.8% (84/108), and 75.9% (63/83) of patients with AIBDs, pemphigus, and BP, respectively, and 14.5% (29/200) of control subjects. Beau's lines and paronychia were the most common nail involvement, observed in 22.5% (43/191) and 22.5% (43/191) of patients with AIBDs, 25.0% (27/108) and 25.9% (28/108) of patients with pemphigus, 19.3% (16/83) and 18.1% (15/83) of patients with BP, respectively. The autoimmune bullous skin disorder intensity score (ABSIS) and the onset time of patients with pemphigus or BP with nail changes were different. Onychomycosis accounted for 21.5% (41/191) of all patients with AIBDs. The ABSIS was correlated with nail involvement in patients with BP (r = 0.46, p < 0.001), and weakly correlated with nail involvement in patients with AIBDs (r = 0.37, p < 0.001), pemphigus (r = 0.29, p = 0.009), and pemphigus vulgaris (PV; r = 0.35, p = 0.008). No correlation was observed between nail involvement and disease antibody titers. In conclusion, nail changes are frequently observed in patients with pemphigus and BP. The type and onset time of nail changes may indicate the severity of pemphigus and BP, which warrants the attention of dermatologists.

Purpose: The rapid worldwide spread of Corona Virus Disease 2019 (COVID-19) has become not only a global challenge, but also a lack of effective clinical treatments. Studies have shown that licorice can significantly improve clinical symptoms such as fever, dry cough and shortness of breath in COVID-19 patients with no significant adverse effects. However, there is still a lack of in-depth analysis of the specific active ingredients of licorice in the treatment of COVID-19 and its mechanism of action. Therefore, we used molecular docking and molecular dynamics to explore the mechanism of action of licorice in the treatment of COVID-19.Methods: We used bioinformatics to screen active pharmaceutical ingredients and potential targets, the disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulations were carried out to verify that active ingredients were stably combined with protein targets. The supercomputer platform was used to measure and analyze stability of protein targets at the residue level, solvent accessible surface area, number of hydrogen bonds, radius of gyration and binding free energy.Results: Licorice had 255 gene targets, COVID-19 had 4,628 gene targets, the intersection gene targets were 101. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) analysis showed that licorice played an important role mainly through the signaling pathways of inflammatory factors and oxidative stress. Molecular docking showed that Glycyrol, Phaseol and Glyasperin F in licorice may playe a role in treating COVID-19 by acting on STAT3, IL2RA, MMP1, and CXCL8. Molecular dynamics were used to demonstrate and analyze the binding stability of active ingredients to protein targets.Conclusion: This study found that Phaseol in licorice may reduce inflammatory cell activation and inflammatory response by inhibiting the activation of CXCL8 and IL2RA; Glycyrol may regulate cell proliferation and survival by acting on STAT3. Glyasperin F may regulate cell growth by inhibiting the activation of MMP1, thus reducing tissue damage and cell death caused by excessive inflammatory response and promoting the growth of new tissues. Therefore, licorice is proposed as an effective candidate for the treatment of COVID-19 through STAT3, IL2RA, MMP1, and CXCL8.

PurposeThe Corona Virus Disease 2019 (COVID-19) pandemic has become a challenge of world. The latest research has proved that Xuanfei Baidu granule (XFBD) significantly improved patient’s clinical symptoms, the compound drug improves immunity by increasing the number of white blood cells and lymphocytes, and exerts anti-inflammatory effects. However, the analysis of the effective monomer components of XFBD and its mechanism of action in the treatment of COVID-19 is currently lacking. Therefore, this study used computer simulation to study the effective monomer components of XFBD and its therapeutic mechanism.MethodsWe screened out the key active ingredients in XFBD through TCMSP database. Besides GeneCards database was used to search disease gene targets and screen intersection gene targets. The intersection gene targets were analyzed by GO and KEGG. The disease-core gene target-drug network was analyzed and molecular docking was used for verification. Molecular dynamics simulation verification was carried out to combine the active ingredient and the target with a stable combination. The supercomputer platform was used to measure and analyze the number of hydrogen bonds, the binding free energy, the stability of protein target at the residue level, the solvent accessible surface area, and the radius of gyration.ResultsXFBD had 1308 gene targets, COVID-19 had 4600 gene targets, the intersection gene targets were 548. GO and KEGG analysis showed that XFBD played a vital role by the signaling pathways of immune response and inflammation. Molecular docking showed that I-SPD, Pachypodol and Vestitol in XFBD played a role in treating COVID-19 by acting on NLRP3, CSF2, and relieve the clinical symptoms of SARS-CoV-2 infection. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets, CSF2/I-SPD combination has the strongest binding energy.ConclusionFor the first time, it was found that the important active chemical components in XFBD, such as I-SPD, Pachypodol and Vestitol, reduce inflammatory response and apoptosis by inhibiting the activation of NLRP3, and reduce the production of inflammatory factors and chemotaxis of inflammatory cells by inhibiting the activation of CSF2. Therefore, XFBD can effectively alleviate the clinical symptoms of COVID-19 through NLRP3 and CSF2.

Physically effective neutral detergent fiber (peNDF) is a concept that accounts for the particle length of NDF in diets, sustaining the normal chewing behavior and rumen fermentation of ruminants. Specifically, peNDF>1.18 is the commonest one that is calculated from NDF and the percentage of feed dry matter left on the 1.18, 8.00, and 19.00 mm sieves. This study aimed to investigate the effects of different levels of peNDF>1.18 on the rumen microbiome and its correlation with nutrient digestibility and rumen fermentation in goats. A total of 30 Lezhi black goats were randomized and blocked to five dietary treatments (n = 6). All the diets were identical in composition but varied in hay lengths, leading to the different peNDF>1.18 content of the diets: 32.97, 29.93, 28.14, 26.48, and 24.75%. The results revealed that the nutrient digestibility increased when dietary peNDF>1.18 levels decreased from 32.97% to 28.14%, with the highest digestibility at 28.14% peNDF>1.18 treatment, after which nutrient digestibility decreased with the decreasing of dietary peNDF levels. Ruminal NH3-N concentrations in the 29.93% and 28.14% groups were higher than that in the 24.75% group (p < 0.05). Ruminal microbial protein concentration was the highest in the 32.97% group (p < 0.05). Daily CH4 production in the 32.97% and 24.75% peNDF>1.18 treatments was lower than that in the 26.48% group (p < 0.05) and no differences were observed among other groups. The relative abundance of rumen fungi at the phylum and genus levels and archaea at the species were affected by dietary peNDF>1.18 content. In conclusion, decreasing dietary peNDF>1.18 levels within a certain range can improve nutrient digestibility and change the rumen microbial community structure of goats. Dietary peNDF>1.18 level should be 28.14% (roughage length around 1 cm) among the five levels for 4 months Lezhi black goats with the purpose of optimal nutrient digestibility.

Purpose: Dapansutrile is an orally active β-sulfonyl nitrile compound that selectively inhibits the NLRP3 inflammasome. Clinical studies have shown that dapansutrile is active in vivo and limits the severity of endotoxin-induced inflammation and joint arthritis. However, there is currently a lack of more in-depth research on the effect of dapansutrile on protein targets such as NLRP3 in gouty arthritis. Therefore, we used molecular docking and molecular dynamics to explore the mechanism of dapansutrile on NLRP3 and other related protein targets.Methods: We use bioinformatics to screen active pharmaceutical ingredients and potential disease targets. The disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulations were utilized to verify and analyze the binding stability of small molecule drugs to target proteins. The supercomputer platform was used to measure and analyze the binding free energy, the number of hydrogen bonds, the stability of the protein target at the residue level, the radius of gyration and the solvent accessible surface area.Results: The protein interaction network screened out the core protein targets (such as: NLRP3, TNF, IL1B) of gouty arthritis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that gouty arthritis mainly played a vital role by the signaling pathways of inflammation and immune response. Molecular docking showed that dapansutrile play a role in treating gouty arthritis by acting on the related protein targets such as NLRP3, IL1B, IL6, etc. Molecular dynamics was used to prove and analyze the binding stability of active ingredients and protein targets, the simulation results found that dapansutrile forms a very stable complex with IL1B.Conclusion: We used bioinformatics analysis and computer simulation system to comprehensively explore the mechanism of dapansutrile acting on NLRP3 and other protein targets in gouty arthritis. This study found that dapansutrile may not only directly inhibit NLRP3 to reduce the inflammatory response and pyroptosis, but also hinder the chemotaxis and activation of inflammatory cells by regulating IL1B, IL6, IL17A, IL18, MMP3, CXCL8, and TNF. Therefore, dapansutrile treats gouty arthritis by attenuating inflammatory response, inflammatory cell chemotaxis and extracellular matrix degradation by acting on multiple targets.