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Abstract With the development of industry and modern manufacturing, nondegradable low-density polyethylene (LDPE) has been widely used, posing a rising environmental hazard to natural ecosystems and public health. In this study, we isolated a series of LDPE-degrading fungi from landfill sites and carried out LDPE degradation experiments by combining highly efficient degrading fungi in pairs. The results showed that the mixed microorganisms composed of Alternaria sp. CPEF-1 and Trametes sp. PE2F-4 (H-3 group) had a greater degradation effect on heat-treated LDPE (T-LDPE). After 30 days of inoculation with combination strain H-3, the weight loss rate of the T-LDPE film was approximately 154% higher than that of the untreated LDPE (U-LDPE) film, and the weight loss rate reached 0.66 ± 0.06%. Environmental scanning electron microscopy (ESEM) and Fourier transform infrared spectroscopy (FTIR) were used to further investigate the biodegradation impacts of T-LDPE, including the changes on the surface and depolymerization of the LDPE films during the fungal degradation process. Our findings revealed that the combined fungal treatment is more effective at degrading T-LDPE than the single strain treatment, and it is expected that properly altering the composition of the microbial community can help lessen the detrimental impact of plastics on the environment.

Abstract Background The central component in impactful healthcare decisions is evidence. Understanding how nurse leaders use evidence in their own managerial decision making is still limited. This mixed methods systematic review aimed to examine how evidence is used to solve leadership problems and to describe the measured and perceived effects of evidence-based leadership on nurse leaders and their performance, organizational, and clinical outcomes. Methods We included articles using any type of research design. We referred nurses, nurse managers or other nursing staff working in a healthcare context when they attempt to influence the behavior of individuals or a group in an organization using an evidence-based approach. Seven databases were searched until 11 November 2021. JBI Critical Appraisal Checklist for Quasi-experimental studies, JBI Critical Appraisal Checklist for Case Series, Mixed Methods Appraisal Tool were used to evaluate the Risk of bias in quasi-experimental studies, case series, mixed methods studies, respectively. The JBI approach to mixed methods systematic reviews was followed, and a parallel-results convergent approach to synthesis and integration was adopted. Results Thirty-one publications were eligible for the analysis: case series (n = 27), mixed methods studies (n = 3) and quasi-experimental studies (n = 1). All studies were included regardless of methodological quality. Leadership problems were related to the implementation of knowledge into practice, the quality of nursing care and the resource availability. Organizational data was used in 27 studies to understand leadership problems, scientific evidence from literature was sought in 26 studies, and stakeholders’ views were explored in 24 studies. Perceived and measured effects of evidence-based leadership focused on nurses’ performance, organizational outcomes, and clinical outcomes. Economic data were not available. Conclusions This is the first systematic review to examine how evidence is used to solve leadership problems and to describe its measured and perceived effects from different sites. Although a variety of perceptions and effects were identified on nurses’ performance as well as on organizational and clinical outcomes, available knowledge concerning evidence-based leadership is currently insufficient. Therefore, more high-quality research and clinical trial designs are still needed. Trail registration The study was registered (PROSPERO CRD42021259624).

Abstract TNF receptor superfamily member 11a (TNFRSF11a, RANK) and its ligand TNF superfamily member 11 (TNFRSF11, RANKL) are overexpressed in many malignancies. However, the clinical importance of RANKL/RANK in colorectal cancer (CRC) is mainly unknown. We examined CRC samples and found that RANKL/RANK was elevated in CRC tissues compared with nearby normal tissues. A higher RANKL/RANK expression was associated with a worse survival rate. Furthermore, RANKL was mostly produced by regulatory T cells (Tregs), which were able to promote CRC advancement. Overexpression of RANK or addition of RANKL significantly increased the stemness and migration of CRC cells. Furthermore, RANKL/RANK signaling stimulated C-C motif chemokine ligand 20 (CCL20) production by CRC cells, leading to Treg recruitment and boosting tumor stemness and malignant progression. This recruitment process was accomplished by CCL20–CCR6 interaction, demonstrating a connection between CRC cells and immune cells. These findings suggest an important role of RANKL/RANK in CRC progression, offering a potential target for CRC prevention and therapy.

The Classifier Chains (CC) method is an effective method for multi-label classification, with its performance significantly contingent on the label order. However, most existing algorithms focus on determining the label order by considering label correlations as symmetric, ignoring that label correlations prevail asymmetric in real-world applications. To overcome the problem, we propose a novel Relative Entropy and PageRank-based Classifier Chains for multi-label classification (REPCC). Firstly, to completely capture label correlation, REPCC exploits relative entropy to estimate the asymmetric correlation between pairs of labels, filter out those pairs of labels with lower correlation, and construct a label correlation matrix. Secondly, by treating each label as a node, a directed graph is generated based on the filtered label correlation matrix. Finally, drawing an analogy between labels and web pages, the idea of PageRank, commonly used to measure the importance of web pages, is employed to rank labels in the directed graph and establish a classifier chain. Experimental results on ten public datasets from various domains show that REPCC outperforms state-of-the-art methods in CC.

Abstract Background This study aimed to investigate the neuroanatomical subtypes among early-onset schizophrenia (EOS) patients by exploring the association between structural alterations and molecular mechanisms using a combined analysis of morphometric similarity network (MSN) changes and specific transcriptional expression patterns. Methods We recruited 206 subjects aged 7 to 17 years, including 100 EOS patients and 106 healthy controls (HC). Heterogeneity through discriminant analysis (HYDRA) was used to identify the EOS subtypes within the MSN strength. The differences in morphometric similarity between each EOS subtype and HC were compared. Furthermore, we examined the link between morphometric changes and brain-wide gene expression in different EOS subtypes using partial least squares regression (PLS) weight mapping, evaluated genetic commonalities with psychiatric disorders, identified functional enrichments of PLS-weighted genes, and assessed cellular transcriptional signatures. Results Two distinct MSN-based EOS subtypes were identified, each exhibiting different abnormal MSN strength and cognitive functions compared to HC. The PLS1 score mapping demonstrated anterior–posterior gradients of gene expression in EOS1, whereas inverse distributions were observed in EOS2 cohorts. Genetic commonalities were identified in autistic disorder and adult schizophrenia with EOS1 and inflammatory bowel diseases with EOS2 cohorts. The EOS1 PLS1- genes (Z

Early-onset Schizophrenia (EOS) is a profoundly progressive psychiatric disorder characterized by both positive and negative symptoms, whose pathogenesis is influenced by genes, environment and brain structure development. In this study, the MIND (Morphometric Inverse Divergence) network was employed to explore the relationship between morphological similarity and specific transcriptional expression patterns in EOS patients. This study involved a cohort of 187 participants aged between 7 and 17 years, consisting of 97 EOS patients and 90 healthy controls (HC). Multiple morphological features were used to construct the MIND network for all participants. Furthermore, we explored the associations between MIND network and brain-wide gene expression in EOS patients through partial least squares (PLS) regression, shared genetic predispositions with other psychiatric disorders, functional enrichment of PLS weighted genes, as well as transcriptional signature assessment of cell types, cortical layers, and developmental stages. The MIND showed similarity differences in the orbitofrontal cortex, pericalcarine cortex, lingual gyrus, and multiple networks in EOS patients compared to HC. Moreover, our exploration revealed a significant overlap of PLS2 weighted genes linking to EOS-related MIND differences and the dysregulated genes reported in other psychiatric diseases. Interestingly, genes correlated with MIND changes (PLS2-) exhibited a significant enrichment not only in metabolism-related pathways, but also in specific astrocytes, cortical layers (specifically layer I and III), and posterior developmental stages (late infancy to young adulthood stages). However, PLS2+ genes were primarily enriched in synapses signaling-related pathways and early developmental stages (from early-mid fetal to neonatal early infancy) but not in special cell types or layers. These findings provide a novel perspective on the intricate relationship between macroscopic morphometric structural abnormalities and microscopic transcriptional patterns during the onset and progression of EOS.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. Effective treatments against COVID-19 remain urgently in need although vaccination significantly reduces the incidence, hospitalization, and mortality. At present, antiviral drugs including Nirmatrelvir/Ritonavir (Paxlovid™), Remdesivir, and Molnupiravir have been authorized to treat COVID-19 and become more globally available. On the other hand, traditional Chinese medicine (TCM) has been used for the treatment of epidemic diseases for a long history. Currently, various TCM formulae against COVID-19 such as Qingfei Paidu decoction, Xuanfei Baidu granule, Huashi Baidu granule, Jinhua Qinggan granule, Lianhua Qingwen capsule, and Xuebijing injection have been widely used in clinical practice in China, which may cause potential herb–drug interactions (HDIs) in patients under treatment with antiviral drugs and affect the efficacy and safety of medicines. However, information on potential HDIs between the above anti-COVID-19 drugs and TCM formulae is lacking, and thus this work seeks to summarize and highlight potential HDIs between antiviral drugs and TCM formulae against COVID-19, and especially pharmacokinetic HDIs mediated by metabolizing enzymes and/or transporters. These well-characterized HDIs could provide useful information on clinical concomitant medicine use to maximize clinical outcomes and minimize adverse and toxic effects.

Objectives: To define the genotype-phenotype correlation of small supernumerary marker chromosomes (sSMCs) and conduct precise genetic counseling, we retrospectively searched and reviewed de novo sSMCs cases detected during prenatal diagnosis at The First Affiliated Hospital of Zhengzhou University. Materials and methods: Chromosome karyotypes of 20,314 cases of amniotic fluid from pregnant women were performed. For 16 samples with de novo sSMCs, 10 were subjected to single-nucleotide polymorphism (SNP) array or low-coverage massively parallel copy number variation sequencing (CNV-seq) analysis. Results: Among the 10 sSMCs cases, two sSMCs derived from chromosome 9, and three sSMCs derived from chromosomes 12, 18 and 22. The remaining 5 cases were not identified by SNP array or CNV-seq because they lacked euchromatin or had a low proportion of mosaicism. Four of them with a karyotype of 47,XN,+mar presented normal molecular cytogenetic results (seq[hg19] 46,XN), and the remaining patient with a karyotype of 46,XN,+mar presented with Turner syndrome (seq[hg19] 45,X). Five sSMCs samples were mosaics of all 16 cases. Conclusion: Considering the variable origins of sSMCs, further genetic testing of sSMCs should be performed by SNP array or CNV-seq. Detailed molecular characterization would allow precise genetic counseling for prenatal diagnosis.

BackgroundWhile the molecular underpinnings of vascular dysfunction in psychosis are under active investigation, their implications remain unclear due to inconsistent and sometimes sparse observations. We conducted a comprehensive meta-analysis to critically assess the alterations of vascular-related molecules in the cerebrospinal fluid (CSF) and blood of patients with psychotic disorders compared with healthy individuals.MethodsDatabases were searched from inception to February 23, 2023. Meta-analyses were performed using a random-effects model. Meta-regression and subgroup analyses were conducted to assess the effects of clinical correlates.ResultsWe identified 93 eligible studies with 30 biomarkers investigated in the CSF and/or blood. Among the biomarkers examined, psychotic disorders were associated with elevated CSF-to-serum albumin ratio (standardized mean difference [SMD], 0.69; 95% confidence interval [CI], 0.35–1.02); blood S100B (SMD, 0.88; 95% CI, 0.59–1.17), matrix metalloproteinase-9 (MMP-9; SMD, 0.66; 95% CI, 0.46–0.86), and zonulin (SMD, 1.17; 95% CI, 0.04–2.30). The blood levels of S100B, MMP-9, nerve growth factor (NGF), vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), and vascular adhesion molecule 1 (VCAM-1) were altered in patient subgroups differing in demographic and clinical characteristics. Blood S100B level was positively correlated with age and duration of illness. Substantial between-study heterogeneity was observed in most molecules.ConclusionThe alterations in certain vascular-related fluid markers in psychotic disorders suggest disturbances in normal vascular structures and functions. However, not all molecules examined displayed clear evidence of changes. While potential impacts of clinical factors, including the administered treatment, were identified, the exploration remained limited. Further studies are needed to investigate the diverse patterns of expression, and understand how these abnormalities reflect the pathophysiology of psychosis and the impact of clinical factors.

Introduction This study protocol describes two randomised feasibility trials that will evaluate the feasibility and preliminary effectiveness of an online training course to improve evidence-based leadership competences among nurse leaders working in hospitals in Finland and China.Methods and analysis Two randomised, parallel-group studies will be conducted separately: one in Finland (n=140) and one in China (n=160). Nurse leaders who fulfil the eligibility criteria will be randomly allocated (1:1) to participate in either the online evidence-based leadership training or conventional online training (reading material only). The primary outcomes will be acceptance of the online course (logging into the platform) and adherence in the online course (returned course tasks and drop-out rate of the participants). The secondary outcomes will be acceptance of the study regarding recruitment, feasibility of the eligibility criteria and outcome measures and potential effectiveness of the online course on leadership skills, evidence-based knowledge, attitudes, practice, self-efficacy, self-esteem and intention to leave. In addition, the feedback will be asked after the course.Ethics and dissemination Two separate trials have received ethical clearance from local ethics committees (12/2022 in Finland, E2021167 in China). Permission to conduct the study will be granted by hospital authorities. All participants will provide electronic informed consent before baseline data are collected. The trial results will be published locally, nationally and internationally in professional and peer-reviewed journals, and shared at national and international meetings and conferences.Trial registration numbers NCT05244512; NCT05244499.

This study synthesized and investigated the efficacy of a novel flame retardant, melamine formaldehyde microencapsulated piperazine pyrophosphate (MFPAPP), in improving the thermal and flame-retardant properties of thermoplastic polyurethane (TPU). When TPU was incorporated with 30wt% MFPAPP, the limiting oxygen index (LOI) value of the TPU/MFPAPP composite increased to 38.8%, achieving a V-0 rating. The thermogravimetric test (TG) results confirmed that MFPAPP significantly enhanced the thermal stability of the TPU/MFPAPP composite, as indicated by the increased char residue at 800°C, which was up to 22.4wt%. Compared with the pure TPU samples, the peak heat release rate (PHRR) and total heat release (THR) of TPU/MFPAPP30 decreased by 53% and 45%, respectively. TPU/MFPAPP10 maintained a V-0 rating after the water immersion test, whereas TPU/PAPP degraded to a V-2 rating. Scanning electron microscopy (SEM), Raman spectra, and X-ray photoelectron spectroscopy analyses revealed that MFPAPP promoted the formation of heat-resistant and dense expanded carbon layers. In summary, MFPAPP demonstrated remarkable flame retardancy and thermal stability, making it an ideal candidate for enhancing the fire safety of TPU materials.

BackgroundAlthough many efforts have been devoted to identify biomarkers to predict the responsiveness of immune checkpoint inhibitors, including expression of programmed death-ligand 1 (PD-L1) and major histocompatibility complex (MHC) I, microsatellite instability (MSI), mismatch repair (MMR) defect, tumor mutation burden (TMB), tertiary lymphoid structures (TLSs), and several transcriptional signatures, the sensitivity of these indicators remains to be further improved.Materials and methodsHere, we integrated T-cell spatial distribution and intratumor transcriptional signals in predicting the response to immune checkpoint therapy in MMR-deficient tumors including tumors of Lynch syndrome (LS).ResultsIn both cohorts, MMR-deficient tumors displayed personalized tumor immune signatures, including inflamed, immune excluded, and immune desert, which were not only individual-specific but also organ-specific. Furthermore, the immune desert tumor exhibited a more malignant phenotype characterized by low differentiation adenocarcinoma, larger tumor sizes, and higher metastasis rate. Moreover, the tumor immune signatures associated with distinct populations of infiltrating immune cells were comparable to TLSs and more sensitive than transcriptional signature gene expression profiles (GEPs) in immunotherapy prediction. Surprisingly, the tumor immune signatures might arise from the somatic mutations. Notably, patients with MMR deficiency had benefited from the typing of immune signatures and later immune checkpoint inhibition.ConclusionOur findings suggest that compared to PD-L1 expression, MMR, TMB, and GEPs, characterization of the tumor immune signatures in MMR-deficient tumors improves the efficiency of predicting the responsiveness of immune checkpoint inhibition.

Urban green spaces play a key role in constructing an ecological civilization in China. In this context, the realization and assessment of the social value of urban green spaces have received increasing attention. Taking the visitors of the Summer Palace in Beijing as the research object, this study used the public participation geographic information system (PPGIS) to collect research data, assess the social value of ecosystem services in the Summer Palace, and determine its spatial distribution. By examining the social value of urban green spaces, this study explored the relationship between the spatial distribution of ecosystem social value and environmental landscape features. The influence of different environmental values on the spatial distribution of the visitors’ perceived social value was also investigated to provide a decision-making basis for the planning and management of urban ecological spaces and the supply and protection of urban ecological products. This study found that cultural, historical, and aesthetic values were preferred by an increasing number of visitors. The hotspots of social value in the Summer Palace of Beijing have three cores and multiple centers. By analyzing the relationship between the three value types with higher preference and the environmental landscape features of the Summer Palace, this study found that the distribution of social values is closely related to the architectural complexes and waters. Anthropocentrists have smaller sample sizes and generally lower social value indices within the sample group, and ecocentrists have higher perceptions of overall social values.

Abstract Background The next generation sequencing (NGS) based non-invasive prenatal test (NIPT) has outplayed the traditional serum biochemical tests (SBT) in screen of fetal aneuploidies with a high sensitivity and specificity. However, it has not been widely used as a primary screen tool due to its high cost and the cheaper SBT is still the choice for primary screen even with well-known shortages in sensitivity and specificity. Here, we report a multiplex droplet digital PCR NIPT (dPCR-NIPT) assay that can detect trisomies 21, 18 and 13 (T21, T18 and T13) in a single tube reaction with a better sensitivity and specificity than the SBT and a much cheaper price than the NGS-NIPT. Methods In this study, the dPCR-NIPT assay’s non-clinical characteristics were evaluated to verify the cell free fetal DNA (cffDNA) fraction enrichment efficiencies, the target cell free DNA (cfDNA) concentration enrichment, the analytical sensitivity, and the sample quality control on the minimum concentration of cfDNA required for the assay. We validated the clinical performance for this assay by blindly testing 283 clinical maternal plasma samples, including 36 trisomic positive samples, from high risk pregnancies to access its sensitivity and specificity. The cost effectiveness of using the dPCR-NIPT assay as the primary screen tool was also analyzed and compared to that of the existing contingent strategy (CS) using the SBT as the primary screen tool and the strategy of NGS-NIPT as the first-tier screen tool in a simulating situation. Results For the non-clinical characteristics, the sample processing reagents could enrich the cffDNA fraction by around 2 folds, and the analytical sensitivity showed that the assay was able to detect trisomies at a cffDNA fraction as low as 5% and the extracted cfDNA concentration as low as 0.2 ng/μL. By testing the 283 clinical samples, the dPCR-NIPT assay demonstrated a detection sensitivity of 100% and a specificity of 95.12%. Compared to the existing CS and the NGS-NIPT as the first-tier screen strategy, dPCR-NIPT assay used as a primary screen tool followed by the NGS-NIPT rescreen is the most economical approach to screen pregnant women for fetal aneuploidies without sacrificing the positive detection rate. Conclusion This is the first report on a dPCR-NIPT assay, consisting of all the necessary reagents from sample processing to multiplex dPCR amplification, can detect T21, T18 and T13 in a single tube reaction. The study results reveal that this assay has a sensitivity and specificity superior to the SBT and a cost much lower than the NGS-NIPT. Thus, from both the test performance and the economic benefit points of views, using the dPCR-NIPT assay to replace the SBT as a primary screen tool followed by the NGS-NIPT rescreen would be a better approach than the existing CS for detection of fetal aneuploidies in maternal plasma.

Abstract Background Nursing students’ internship experiences may significantly impact their caring ability. However, there is a lack of comprehensive evaluation of undergraduate nursing students' caring ability pre-and post-internship in China. This study aimed to explore the differences in the caring ability of undergraduate nursing students before and after internship. Methods The sample comprised 305 undergraduate nursing students who had undergone internships during 2018–2020 in three hospitals in Changsha, China. Caring Ability Inventory was used to measure and compare nursing students' caring ability before and after internship. Descriptive statistics and paired t-test were employed to analyze data in SPSS software (version 22.0). Results A total of 300 students completed the survey (response rate = 98.37%). The overall score of caring ability and scores of cognitive and patience dimensions were higher after internship than before internship (P 0.05). Conclusions Caring ability of undergraduate nursing students in China was at a low level, their overall caring ability significantly improved after the internship, indicating a positive relationship between internship and caring ability. Nursing educators and clinical nurses should emphasize the importance of caring ability development in internship planning and encourage nursing students to engage more with patients.

Abstract Background An increasing number of interventions have focused on leadership development for healthcare managers, among which coaching is a common strategy. The purpose of the present systematic review is to synthesize evidence on the effect of coaching in developing leadership of healthcare managers. Methods and analysis A literature search will be conducted in six English databases (MEDLINE (Ovid), CINAHL, Embase, Cochrane library, Nursing & Allied Health Premium, and Scopus) and four Chinese databases (Wanfang, CNKI, SinoMed, and VIP) from inception to April 1st, 2022. The titles, abstracts, and full texts of the studies will be screened by two independent researchers to determine their eligibility. The RoB 2, ROBINS-I, CASP, and MMAT will be applied to assess the quality of randomized trials, non-randomized studies, qualitative studies, and mixed-method studies, respectively. We will then extract the study characteristics, participant characteristics, and study outcomes of the reviewed papers. The Aims, Ingredients, Mechanism, and Delivery framework will be used to extract the components of coaching strategies. For quantitative data, a meta-analysis will be performed if sufficient data are available; otherwise, we will conduct a narrative synthesis. Thematic synthesis methods will be used for qualitative data analysis. Discussion By conducting this systematic review, we expect to synthesize evidence regarding the components of coaching for leadership development among healthcare managers; the influence of coaching on leadership development among managers at the individual, unit-wide, or organizational level; and how managers view coaching as a leadership development strategy. Trial registration PROSPERO registration number: CRD42020194290 .

Abstract New-generation human body motion sensors for wearable electronics and intelligent medicine are required to comply with stringent requirements in terms of ultralight weight, flexibility, stability, biocompatibility, and extreme precision. However, conventional sensors are hard to fulfill all these criteria due to their rigid structure, high-density sensing materials used as the constituents, as well as hermetical and compact assembly strategy. Here, we report an ultralight sensing material based on radial anisotropic porous silver fiber (RAPSF), which has been manufactured by phase separation and temperature-controlled grain growth strategy on a modified blow-spinning system. The resistance of RAPSF could be dynamically adjusted depending on the deflected shape. Furthermore, an all-fiber motion sensor (AFMS) with an ultra-low density of 68.70 mg cm−3 and an overall weigh of 7.95 mg was fabricated via layer-by-layer assembly. The sensor exhibited outstanding flexibility, breathability, biocompatibility, and remarkable body motion recognition ability. Moreover, the AFMS was shown to have great potential as an artificial intelligence throat sensor for throat state identification at the accuracy above 85%, allowing one to spot the early onset of the viral throat illness.

Sourdough starters for making traditional steamed bread are rich in microbes. Studies have shown that, in addition to yeast and lactic acid bacteria (LAB), acetic acid bacteria (AAB) are other functional species in sourdough, but the influences of AAB on the properties of sourdough and steamed bread were rarely reported. This study aimed to assess the effects of a selected strain of acetic acid bacterium on the properties of sourdough and steamed bread. Sourdoughs and steamed breads were prepared from five different starter cultures, marked as CK (control check, with no starters), Y (only yeast), YL (yeast+LAB), YA (yeast+AAB) and YLA (yeast+LAB+AAB), and their properties were determined. The results of sourdough properties showed that the YLA sourdough had the highest total titratable acid of 14.6 mL and the lowest pH of 3.87 compared with the other groups after fermentation to 8 h; and the YLA sourdough had the greatest elasticity and viscosity. The results of quality properties of steamed bread revealed that the L* value (88.40 ± 0.09) of the YA steamed bread was significantly higher than those of the YLA and YL steamed breads; the YLA steamed bread had the highest specific volume and the highest sensory score of 89.6 ± 3.31 in comparison to those of the other groups; the hardness and chewiness of YLA and YA steamed breads were significantly lower than those of the other groups. Volatile compounds in the steamed breads were also determined by SPME–GC–MS. A total of 42 flavor substances were detected, including 3 kinds of alcohols, 8 kinds of aldehydes, 7 kinds of ketones, 2 kinds of acids, 15 kinds of esters, 1 furan, and 6 kinds of other types of compounds, mainly alkanes and esters, followed by alcohols and aldehydes. The YLA steamed bread was richer in esters, aldehydes, and acids than those from the other treatment groups. By contrast, alkanes and aldehydes were dominant in the Y and YL steamed breads. Therefore, the flavor and quality of the steamed bread made from the YLA sourdough could be improved obviously. These results could provide references for the application of AAB in dough fermentation and the improvement of new kinds of starters.

Abstract. Background:. The association between heart rate and 1-year clinical outcomes in heart failure (HF) patients with atrial fibrillation (AF), and whether this association depends on left ventricular ejection fraction (LVEF), are unclear. We investigated the relationship between discharge heart rate and 1-year clinical outcomes after discharge among hospitalized HF patients with AF, and further explored this association that differ by LVEF level. Methods:. In this analysis, we enrolled 1760 hospitalized HF patients with AF from the China Patient-centered Evaluative Assessment of Cardiac Events Prospective Heart Failure study from August 2016 to May 2018. Patients were categorized into three groups with low (

Studies on the degradation of plant cell wall polysaccharides by fungal extracellular enzymes have attracted recent attention from researchers. Xylan, abundant in hemicellulose, that play great role in connection between cellulose and lignin, has seen interest in its hydrolytic enzymatic complex. In this study, dozens of fungus species spanning genera were isolated from rotting leaves based on their ability to decompose xylan. Among these isolates, a strain with strong xylanase-producing ability was selected for further investigation by genome sequencing. Based on phylogenetic analysis of ITS (rDNA internal transcribed spacer) and LSU (Large subunit 28S rDNA) regions, the isolate was identified as Penicillium oxalicum. Morphological analysis also supported this finding. Xylanase activity of this isolated P. oxalicum 5-18 strain was recorded to be 30.83 U/mL using the 3,5-dinitro-salicylic acid (DNS) method. Further genome sequencing reveals that sequenced reads were assembled into a 30.78 Mb genome containing 10,074 predicted protein-encoding genes. In total, 439 carbohydrate-active enzymes (CAZymes) encoding genes were predicted, many of which were associated with cellulose, hemicellulose, pectin, chitin and starch degradation. Further analysis and comparison showed that the isolate P. oxalicum 5-18 contains a diverse set of CAZyme genes involved in degradation of plant cell wall components, particularly cellulose and hemicellulose. These findings provide us with valuable genetic information about the plant biomass-degrading enzyme system of P. oxalicum, facilitating a further exploration of the repertoire of industrially relevant lignocellulolytic enzymes of P. oxalicum 5-18.

Abstract Aims The study sought to investigate the association between admission systolic blood pressure (SBP) and 1‐year clinical outcomes in patients hospitalized for heart failure (HF) and in subgroups. Methods This study was based on the China Patient‐centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, which prospectively enrolled patients hospitalized for HF in 52 hospitals from 20 provinces in China between August 2016 and May 2018. Patients were divided into four groups according to the quartiles of SBP at admission. The multivariable Cox proportional hazards regression models were fitted to examine the association between admission SBP and all‐cause death and HF readmission within 1 year after the index hospitalization. Restricted cubic splines were used to explore the non‐linear association between SBP and the clinical outcomes. Results Among 4896 patients, those with lower admission SBP were younger, more likely to be male, have left ventricular ejection fraction

Abstract Background Endotracheal suctioning is one of the most frequently performed invasive procedures by intensive care nurses. Nurses should have adequate knowledge and skills to perform endotracheal suctioning based on the best evidence. Little is known about intensive care nurses’ knowledge and practice of evidence-based endotracheal suctioning in Chinese hospitals. The purpose of this study was to investigate intensive care nurses’ knowledge and practice of evidence-based recommendations regarding endotracheal suctioning. Specifically, the study aimed to examine (1) intensive care nurses’ awareness of and adherence to endotracheal suctioning guidelines and (2) factors influencing their level of awareness and adherence. Methods A cross-sectional survey of 310 staff nurses working in intensive care units was carried out at Changsha, China. Data on participants’ characteristics, awareness of, and adherence to the endotracheal suctioning guidelines were collected through online questionnaires. Following univariate descriptive statistics, the Mann–Whitney U test and Kruskal–Wallis H test were performed using Software Package Statistical Analysis Version 23.0. Results A total of 281 nurses completed and returned the survey (response rate = 90.6 %). One-half to three-quarters of the nurses knew 21 of the 26 evidence-based practices and believed their practices followed the guidelines. Over half of them were unaware of the difference between open and close suctions and the pros and cons of using hyperinflation. Almost 50 % of nurses believed some of their clinical practices did not follow the evidence-based recommendations, such as not routinely using normal saline and using 80–120 mmHg suction pressure during endotracheal suctioning. Nurses with endotracheal suctioning training demonstrated significantly higher awareness of endotracheal suctioning recommendations and higher adherence levels than untrained nurses. Conclusions The study findings revealed that Chinese intensive care nurses lacked awareness of several essential evidence-based endotracheal suctioning practices, and there were gaps between their current practice and the guideline recommendations. Further research should emphasize revealing barriers and facilitators of implementing evidence-based endotracheal suctioning practices as well as developing context-suitable interventions for guideline implementation.

Diabetes mellitus combined with ultraviolet (UV) radiation damage not only brings great mental stress to patients, but also seriously impairs their quality of life. A UV-irradiated diabetic rat trauma skin model was established by us to investigate the effects and possible mechanisms of ginsenoside and glycoprotein on skin trauma repair in UV-irradiated diabetic rats. In the study, ginsenosides and ginseng glycoproteins were extracted from different parts of ginseng roots. It found that it’s easier to prepare saponins in ginseng bark and proteins in ginseng core in large quantities. Since glycoprotein-like metabolites are relatively novel ginseng extracts, specifically characterized its structures. It was verified that the ginseng glycoproteins are not toxic to HaCaT cells and can significantly increase the survival of HaCaT cells after UV damage at the in vitro cellular level. Experiments in vivo were conducted to evaluate the therapeutic effects of ginsenoside and ginseng glycoprotein in a rat model of diabetes mellitus combined with UV irradiation injury. Histopathological changes on rat skin after treatment with ginsenoside and ginseng glycoprotein were evaluated by hematoxylin and eosin (H&E) staining and aldehyde fuchsine staining. The expression levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), matrix metalloproteinases (MMPs), hydroxyproline (HYP), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were measured. The results indicate that both ginsenoside and ginseng glycoprotein could improve skin damage and ulcers caused by diabetes combined with UV irradiation and could alleviate a range of skin damage caused by the combination of diabetes and UV irradiation, including peroxidation and collagen fiber loss. Ginsenoside and ginseng glycoproteins can be considered as natural product candidates for the development of new drugs to treat diabetes combined with UV irradiation-induced skin damage.

Tendinopathy has a high incidence in athletes and the aging population. It can cause pain and movement disorders, and is one of the most difficult problems in orthopedics. Animal models of tendinopathy provide potentially efficient and effective means to develop understanding of human tendinopathy and its underlying pathological mechanisms and treatments. The selection of preclinical models is essential to ensure the successful translation of effective and innovative treatments into clinical practice. Large animals can be used in both micro- and macro-level research owing to their similarity to humans in size, structure, and function. This article reviews the application of large animal models in tendinopathy regarding injuries to four tendons: rotator cuff, patellar ligament, Achilles tendon, and flexor tendon. The advantages and disadvantages of studying tendinopathy with large animal models are summarized. It is hoped that, with further development of animal models of tendinopathy, new strategies for the prevention and treatment of tendinopathy in humans will be developed.

BackgroundChronic kidney disease (CKD) has a significant negative impact on bone health. Bone marrow is an essential component of bone, mainly composed of trabecular bone and fat. The IDEAL-IQ sequence of MRI allows indirect quantification of trabecular bone mass by R2* and direct quantification of bone marrow fat content by FF map, respectively.ObjectiveOur objective was to explore the association of CKD severity with bone marrow using IDEAL-IQ and whether mineral and bone metabolism markers alter this association.MethodWe recruited 68 CKD patients in this cross-sectional research (15 with CKD stages 3-4, 26 with stage 5, and 27 with stage 5d). All patients underwent lumbar spine IDEAL-IQ, BMD, and several bone metabolism markers (iPTH, 25-(OH)-VitD, calcium and phosphorus). Multiple linear regression analysis was used to examine the association of CKD severity with MRI measurements (R2* and FF).ResultsMore severe CKD was associated with a higher R2* value [CKD 5d versus 3-4: 30.077 s-1 (95% CI: 12.937, 47.217), P for trend < 0.001], and this association was attenuated when iPTH was introduced [CKD 5d versus 3-4: 19.660 s-1 (95% CI: 0.205, 39.114), P for trend = 0.042]. Furthermore, iPTH had an association with R2* value [iPTH (pg/mL): 0.033 s-1 (95% CI: 0.001, 0.064), P = 0.041]. Besides, FF was mainly affected by age and BMI, but not CKD.ConclusionsThe bone marrow R2* value measured by IDEAL-IQ sequence is associated with CKD severity and iPTH. The R2* of IDEAL-IQ has the potential to reflect lumbar bone changes in patients with CKD.

Currently, more than 60% of the approved anti-cancer drugs come from or are related to natural products. Natural products and exosomal non-coding RNAs (ncRNAs) exert anti-cancer effects through various regulatory mechanisms, which are of great research significance. Exosomes are a form of intercellular communication and contain ncRNAs that can act as intercellular signaling molecules involved in the metabolism of tumor cells. This review exemplifies some examples of natural products whose active ingredients can play a role in cancer prevention and treatment by regulating exosomal ncRNAs, with the aim of illustrating the mechanism of action of exosomal ncRNAs in cancer prevention and treatment. Meanwhile, the application of exosomes as natural drug delivery systems and predictive disease biomarkers in cancer prevention and treatment is introduced, providing research ideas for the development of novel anti-tumor drugs.

Low density polyethylene (LDPE) has been widely used commercially for decades; however, as a non-degradable material, its continuous accumulation has contributed to serious environmental issues. A fungal strain, Cladosporium sp. CPEF-6 exhibiting a significant growth advantage on MSM-LDPE (minimal salt medium), was isolated and selected for biodegradation analysis. LDPE biodegradation was analyzed by weight loss percent, change in pH during fungal growth, environmental scanning electron microscopy (ESEM), and Fourier transformed infrared spectroscopy (FTIR). Inoculation with the strain Cladosporium sp. CPEF-6 resulted in a 0.30 ± 0.06% decrease in the weight of untreated LDPE (U-LDPE). After heat treatment (T-LDPE), the weight loss of LDPE increased significantly and reached 0.43 ± 0.01% after 30 days of culture. The pH of the medium was measured during LDPE degradation to assess the environmental changes caused by enzymes and organic acids secreted by the fungus. The fungal degradation of LDPE sheets was characterized by ESEM analysis of topographical alterations, such as cracks, pits, voids, and roughness. FTIR analysis of U-LDPE and T-LDPE revealed the appearance of novel functional groups associated with hydrocarbon biodegradation as well as changes in the polymer carbon chain, confirming the depolymerization of LDPE. This is the first report demonstrating the capacity of Cladosporium sp. to degrade LDPE, with the expectation that this finding can be used to ameliorate the negative impact of plastics on the environment.

Abstract Aims Current evidence about the effect of angiotensin receptor blocker (ARB) on the outcome of heart failure with mid‐range ejection fraction (HFmrEF) is lacking. We aim to assess the association between use of ARB and 1 year all‐cause mortality after hospitalization for HFmrEF. Methods and results We analysed the data of patients with ejection fraction of 40–49% in China Patient‐centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study; 4907 patients hospitalized for heart failure from 52 Chinese hospitals were enrolled from August 2016 to May 2018. Use of ARB was determined by prescriptions at discharge. Patients who died during hospitalization or were using angiotensin‐converting enzyme inhibitors at discharge were excluded. The association between the use of ARB and outcome was assessed using stabilized inverse probability of treatment weighting‐adjusted Kaplan–Meier and Cox regression analyses. A total of 701 patients with HFmrEF were included for analysis. The mean age was 66.4 ± 12.8 years, and 267 (38.1%) were female. Of them, 244 were treated (34.8%) with ARB. During the 1 year follow‐up period, patients treated with ARB had lower all‐cause mortality compared with untreated patients (11.5% vs. 21.9%, P = 0.0005). Inverse probability of treatment weighting‐adjusted Cox regression analysis showed that use of ARB was associated with significantly reduced all‐cause mortality (adjusted hazard ratio 0.44, 95% confidence interval 0.28–0.69, P = 0.0004). Conclusions Among patients hospitalized for HFmrEF, the use of ARB was associated with lower 1 year mortality after discharge.

Abstract Although adipose‐derived mesenchymal stem cells (ADMSCs) isolated from patients’ fat are considered as the most important autologous stem cells for tissue repair, significant difficulties in the neural differentiation of ADMSCs still impede stem cell therapy for neurodegenerative diseases. Herein, a wireless‐electrical stimulation method is proposed to direct the neural differentiation of ADMSCs based on the electromagnetic effect using a graphene film as a conductive scaffold. By placing a rotating magnet on the top of a culture system without any inducer, the ADMSCs cultured on graphene differentiate into functional neurons within 15 days. As a conductive biodegradable nanomaterial, graphene film acts as a wireless electrical signal generator driven by the electromagnetic induction, and millivolt‐level voltage generated in situ provokes ADMSCs to differentiate into neurons, proved by morphological variation, extremely high levels of neuron‐specific genes, and proteins. Most importantly, Ca2+ intracellular influx is observed in these ADMSC‐derived neurons once exposure to neurotransmitters, indicating that these cells are functional neurons. This research enhances stem cell therapy for neurodegenerative diseases using autologous ADMSCs and overcomes the lack of neural stem cells. This nanostructure‐mediated physical‐signal simulation method is inexpensive, safe, and localized, and has a significant impact on neural regeneration.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the cause of the COVID-19 pandemic, is initiated by its binding to the ACE2 receptor and other co-receptors on mucosal epithelial cells. Variable outcomes of the infection and disease severity can be influenced by pre-existing risk factors. Human immunodeficiency virus (HIV), the cause of AIDS, targets the gut mucosal immune system and impairs epithelial barriers and mucosal immunity. We sought to determine the impact and mechanisms of pre-existing HIV infection increasing mucosal vulnerability to SARS-CoV-2 infection and disease. We investigated changes in the expression of ACE2 and other SARS-CoV-2 receptors and related pathways in virally inflamed gut by using the SIV infected rhesus macaque model of HIV/AIDS. Immunohistochemical analysis showed sustained/enhanced ACE2 expression in the gut epithelium of SIV infected animals compared to uninfected controls. Gut mucosal transcriptomic analysis demonstrated enhanced expression of host factors that support SARS-CoV-2 entry, replication, and infection. Metabolomic analysis of gut luminal contents revealed the impact of SIV infection as demonstrated by impaired mitochondrial function and decreased immune response, which render the host more vulnerable to other pathogens. In summary, SIV infection resulted in sustained or increased ACE2 expression in an inflamed and immune-impaired gut mucosal microenvironment. Collectively, these mucosal changes increase the susceptibility to SARS-CoV-2 infection and disease severity and result in ineffective viral clearance. Our study highlights the use of the SIV model of AIDS to fill the knowledge gap of the enteric mechanisms of co-infections as risk factors for poor disease outcomes, generation of new viral variants and immune escape in COVID-19.

BackgroundHigh systolic blood pressure (SBP) is an important risk factor for the progression of heart failure (HF); however, the association between SBP and prognosis among patients with established HF was uncertain. This study aimed to investigate the association between SBP and long-term clinical outcomes in patients hospitalized for HF.MethodsThis study prospectively enrolled adult patients hospitalized for HF in 52 hospitals from 20 provinces in China. SBPs were measured in a stable condition judged by clinicians during hospitalization before discharge according to the standard research protocol. The primary outcomes included 1-year all-cause death and HF readmission. The multivariable Cox proportional hazards regression models were fitted to examine the association between SBP and clinical outcomes. Restricted cubic splines were used to examine the non-linear associations.ResultsThe 4,564 patients had a mean age of 65.3 ± 13.5 years and 37.9% were female. The average SBP was 123.2 ± 19.0 mmHg. One-year all-cause death and HF readmission were 16.9 and 32.7%, respectively. After adjustment, patients with SBP < 110 mmHg had a higher risk of all-cause death compared with those with SBP of 130–139 mmHg (HR 1.71; 95% CI: 1.32–2.20). Patients with SBP < 110 mmHg (HR 1.36; 95% CI: 1.14–1.64) and SBP ≥ 150 mmHg (HR 1.26; 95% CI: 1.01–1.58) had a higher risk of HF readmission, and the association between SBP and HF readmission followed a J-curve relationship with the nadir SBP around 130 mmHg. These associations were consistent regardless of age, sex, left ventricular ejection fraction, hypertension, coronary heart disease, and medications for HF.ConclusionIn patients hospitalized for HF, lower SBP in a stable phase during hospitalization portends an increased risk of 1-year death, and a J-curve association has been observed between SBP and 1-year HF readmission. These associations were consistent among clinically important subgroups.

BackgroundLipid-lowering therapy (LLT) is one of the key strategies for reducing the atherosclerotic cardiovascular disease (ASCVD) burden. However, little is known about the percentage of people in need of different LLT regimens to achieve optimal targets of low-density lipoprotein cholesterol (LDL-C), and the corresponding cost and benefit.MethodsWe conducted a simulation study based on the data from the nationwide China PEACE MPP population cohort (2015–2020), from which we included 2,904,914 participants aged 35–75 years from all the 31 provinces in mainland China. Participants were grouped based on their 10-year ASCVD risks, then entered into a Monte Carlo model which was used to perform LLT intensification simulation scenarios to achieve corresponding LDL-C goals in each risk stratification.ResultsAfter standardizing age and sex, the proportions of participants included at low, moderate, high, and very-high risk were 70.8%, 15.6%, 11.5%, and 2.1%, respectively. People who failed to achieve the corresponding LDL-C goals −8.1% at low risk, 19.6% at moderate risk, 53.2% at high risk, and 93.6% at very-high risk (either not achieving the goal or not receiving LLT)—would be in need of the LLT intensification simulation. After the use of atorvastatin 20 mg was simulated, over 99% of the population at low or moderate risk could achieve the LDL-C goals; while 11.3% at high and 24.5% at very-high risk would still require additional non-statin therapy. After the additional use of ezetimibe, there were still 4.8% at high risk and 11.3% at very-high risk in need of evolocumab; and 99% of these two groups could achieve the LDL-C goals after the use of evolocumab. Such LLT intensification with statin, ezetimibe, and evolocumab would annually cost $2.4 billion, $4.2 billion, and $24.5 billion, respectively, and prevent 264,170, 18,390, and 17,045 cardiovascular events, respectively.ConclusionsModerate-intensity statin therapy is pivotal for the attainment of optimal LDL-C goals in China, and around 10–25% of high- or very-high-risk patients would require additional non-statin agents. There is an opportunity to reduce the rising ASCVD burden in China by optimizing LLT.

Lectin, Mannose Binding 2 (LMAN2) encodes a type I transmembrane lectin that shuttles between the plasma membrane, the Golgi apparatus, and the endoplasmic reticulum. However, its expression, prognosis, and function in invasive breast carcinoma remain unknown. Nine databases were consulted to evaluate LMAN2 expression and prognosis in breast cancer. The possible function of LMAN2 in breast cancer was investigated in the Human Cell Landscape (HCL) database, Gene Regulatory Network database (GRNdb), and CancerSEA database. Moreover, N6-methyladenosine (m6A) modifications were analyzed using the RMBase v2.0 and M6A2Target databases. Seven databases were then used to analyze the potential action mechanisms of LMAN2. Our findings suggest that LMAN2, which is expressed at a high level in breast cancer, is linked to an unfavorable prognosis. Therefore, LMAN2 has the potential to be utilized as a treatment target in breast cancer. Furthermore, the single-cell analysis illustrated that LMAN2 expression had a positive link to breast cancer stemness, proliferation, metastasis, and differentiation. Moreover, m6A modifications were found in the LMAN2 gene. Consequently, modifications to m6A methylation may influence LMAN2 expression, which is associated with the homologous recombination (HR) in its DNA damage repair pathway .

Abstract Background X-linked agammaglobulinaemia (XLA) is a rare immunodeficiency disease for which recurrent severe infection is the major clinical symptom. BTK is the main causative gene, with X chromosome recessive inheritance. However, the mutations reported to date do not fully explain the disorder. Methods We detected the percentage of CD19+ B cells and serum immunoglobulin (IgG, IgA, and IgM) levels by flow cytometry and rate scatter immunoturbidimetry, and investigated the BTK mutation profile in 22 XLA patients using Sanger sequencing and real-time PCR . Results We evaluated the clinical symptoms of 22 XLA patients and investigated genetic mutations present, identifying six novel mutations in the BTK gene: 2 missense mutations (c.23G > T and c.112 T > C), 2 frameshift mutations (c.522_523insC and c.1060delA), 1 large deletion (deletion of exon 2 to 5), and 1 splice-site mutation (c.1631 + 2 T > C). Prenatal diagnoses were performed in six families (F10, F11, F15, F18, F20 and F21), with the following results: the male fetus in Family 10 (F10) did not carry the c.922_923delGA mutation; the male fetus in Family 15 (F15) did not carry the c.1631 + 1G > T splicing mutation; the female fetus in Family 20 (F20) did not carry the c.1931 T > C mutation; the female fetus in Family 21 (F21) did not carry the large deletion mutation. Hence, these four fetuses are not likely to develop XLA. Male fetuses with c.1060delA and c.1684C > T mutations were identified in Family 11 and Family 18, respectively. The pregnant woman in F18 chose to terminate the pregnancy, whereas the pregnant woman in F11 chose to continue the pregnancy. Conclusion We confirmed the diagnosis of 22 XLA patients from 22 unrelated families and detected six new pathogenic mutations. Prenatal diagnosis was performed in six families. Early genetic diagnosis and routine lifelong immunoglobulin replacement therapy can prevent and treat infections in XLA children, saving their lives.

Abstract Objective To recognize risk factors and build up and validate a simple risk model predicting 8‐year cancer events after nonalcoholic fatty liver disease (NAFLD). Methods This was a retrospective cohort study. Patients with NAFLD (n = 5561) were randomly divided into groups: training (n = 1254), test (n = 627), evaluation (n = 627), and validation (n = 3053). Risk factors were recognized by statistical method named as a Cox model with Markov chain Monte Carlo (MCMC) simulation. This prediction score was established based on the training group and was further validated based on the testing and evaluation group from January 1, 2007 to December 31, 2009 and another 3053 independent cases from January 1, 2010 to February 13, 2014. Results The main outcomes were NAFLD‐related cancer events, including those of the liver, breast, esophagus, stomach, pancreas, prostate and colon, within 8 years after hospitalization for NAFLD diagnosis. Seven risk factors (age (every 5 years),LDL, smoking, BMI, diabetes, OSAS, and aspartate aminotransferase (every 5 units)) were identified as independent indicators of cancer events. This risk model contained a predictive range of 0.4%‐37.7%, 0.3%‐39.6%, and 0.4%‐39.3% in the training, test, evaluation group, respectively, with a range 0.4%‐30.4% for validation groups. In the training group, 12.6%, 76.9%, and 10.5% of patients, which corresponded to the low ‐, moderate ‐, and high‐risk groups, had probabilities of,

The build-up of iron in the body can have serious consequences; current treatment therapies suffer from adverse side effects and toxicity. Here, the authors developed renal clearable nanochelators with improved pharmacodynamics and demonstrated their efficacy and safety in iron overload animal models.

Concealed faults can be important for understanding the regional structural geology and the subsurface fluid distribution. However, such faults are usually difficult to identify and characterize because of their small size and complex mechanism. To address this issue, we present an integrated approach of three-dimensional seismic data mapping and physical modeling experiments to examine the geometrical and kinematic characteristics of concealed faults and their relationship with the main faults in the Huawa area, east China. Three series of experiments were designed to characterize the differences in the scale of concealed faults and main faults, which also allowed us to examine how the concealed faults grow with the main faults in the area. Through this integrated study, we have demonstrated that: 1) NE-SW-striking concealed faults are below the resolution of the available seismic datasets and not easily recognized in seismic sections and that most of them grew later than the E-W-striking main faults, with some of them having grown at the same time; 2) pre-existing faults, rather than asymmetry of the basin structure, affect the faults that develop during subsequent episodes of extension; 3) E-W-striking pre-existing faults under a NW-SE stress direction of extension are most likely the formation mechanism of concealed faults. This study is of reference value in the interpretation of concealed faults in other regions.

Chronic kidney disease (CKD) has a significant negative impact on bone health. However, the mechanisms of cortical bone deterioration and cortical porosity enlargement caused by CKD have not been fully described. We therefore examined the association of CKD stages with cortical porosity index (PI), and explored potential mediators of this association. Double-echo ultrashort echo-time magnetic resonance imaging (UTE MRI) provides the possibility of quantifying cortical porosity in vivo. A total of 95 patients with CKD stages 2-5 underwent 3D double-echo UTE-Cones MRI (3.0T) of the midshaft tibia to obtain the PI. PI was defined as the ratio of the image signal intensity of a sufficiently long echo time (TE) to the shortest achievable TE. Parathyroid hormone (PTH), β-CrossLaps (β-CTX), total procollagen type I amino-terminal propeptide (T-P1NP), osteocalcin (OC), 25-hydroxyvitamin D (25OHD), and lumbar bone mineral density (BMD) were measured within one week of the MRI. Partial correlation analysis was performed to address associations between PI, eGFR and potential mediators (PTH, β-CTX, T-P1NP, OC, 25OHD, BMD, and T-score). Multiple linear regression models were used to assess the association between CKD stages and PI value. Then, a separate exploratory mediation analysis was carried out to explore the impact of CKD stages and mediators on the PI value. The increasing CKD stages were associated with a higher PI value (Ptrend < 0.001). The association of CKD stages and PI mediated 34.4% and 30.8% of the total effect by increased PTH and β-CTX, respectively. Our study provides a new idea to monitor bone health in patients with CKD, and reveals the internal mechanism of bone deterioration caused by CKD to some extent.

ObjectiveThis study aimed to establish optimal surgical strategies via reviewing the clinical outcomes of various surgical approaches for the pertroclival meningiomas (PCMs).MethodsThis retrospective study enrolled 107 patients with PCMs at the authors’ institution from year 2010 to 2020. Patient demographics, the clinical characteristics, various operative approaches, major morbidity, post-operative cranial nerve deficits and tumor progression or recurrence were analyzed.ResultsThe subtemporal transtentorial approach (STA), the Kawase approach (KA), the retrosigmoid approach (RSA) and the anterior sigmoid approach (ASA), namely the posterior petrosal approach (PPA) were adopted for 17 cases, 22 cases, 31 cases and 34 cases respectively. Total or subtotal resection was achieved in 96 cases (89.7%). The incidence of new-onset and aggravated cranial nerve dysfunction were 13.1% (14/107) and 10.4% (15/144), respectively. Furthermore, 14 cases suffered from intracranial infection, 9 cases had cerebrospinal fluid leakage, and 3 cases sustained intracranial hematoma (1 case underwent second operation). The mean preoperative and postoperative Karnofsky Performance Status (KPS) score was 80 (range 60-100) and 78.6 (range 0-100), but this was not statistically significant (P>0.05). After a mean follow-up of 5.1 years (range 0.3- 10.6 years), tumor progression or recurrence was confirmed in 23 cases. Two cases died from postoperative complications.ConclusionsFor the treatment of PCMs, it is still a challenge to achieve total resection. With elaborate surgical plans and advanced microsurgical skills, most patients with PCMs can be rendered tumor resection with satisfactory extent and functional preservation, despite transient neurological deterioration during early postoperative periods.

CircRNAs (circRNAs) are commonly dysregulated in a variety of human diseases and are involved in the development and progression of cancer. However, the role of circRNAs in hepatic fibrosis (HF) is still unclear. Our previous high throughput screen revealed changes in many circRNAs in mice with carbon tetrachloride (CCl4)-induced HF. For example, circCREBBP was significantly down-regulated in primary hepatic stellate cells (HSCs) and liver tissue of HF mice induced by CCl4 compared to those in the vehicle group. Overexpression of circCREBBP with AAV8-circCREBBP in vivo prevented CCl4-induced HF worsening by reducing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) contents, liver hydroxyproline levels, collagen deposition, and levels of pro-fibrosis genes and pro-inflammatory cytokines. Furthermore, in vitro function loss and function gain analysis showed that circCREBBP inhibited HSCs activation and proliferation. Mechanically, circCREBBP acts as a sponge for hsa-miR-1291 and subsequently promotes LEFTY2 expression. In conclusion, our current results reveal a novel mechanism by which circCREBBP alleviates liver fibrosis by targeting the hsa-miR-1291/LEFTY2 axis, and also suggest that circCREBBP may be a potential biomarker for heart failure.

Due to the unique physical characteristics of intervertebral disc degeneration (IVDD) and the pathological microenvironment that it creates, including inflammation and oxidative stress, effective self-repair is impossible. During the process of intervertebral disc degeneration, there is an increase in the infiltration of M1 macrophages and the secretion of proinflammatory cytokines. Here, we designed a novel injectable composite hydrogel scaffold: an oligo [poly (ethylene glycol) fumarate]/sodium methacrylate (OPF/SMA) hydrogel scaffold loaded with dual-drug/sustained-release PLGA microspheres containing IL-4 (IL-4-PLGA) and kartogenin (KGN-PLGA). This scaffold exhibited good mechanical properties and low immunogenicity while also promoting the sustained release of drugs. By virtue of the PLGA microspheres loaded with IL-4 (IL-4-PLGA), the composite hydrogel scaffold induced macrophages to transition from the M1 phenotype into the M2 phenotype during the early induced phase and simultaneously exhibited a continuous anti-inflammatory effect through the PLGA microspheres loaded with kartogenin (KGN-PLGA). Furthermore, we investigated the mechanisms underlying the immunomodulatory and anti-inflammatory effects of the composite hydrogel scaffold. We found that the scaffold promoted cell proliferation and improved cell viability in vitro. While ensuring mechanical strength, this composite hydrogel scaffold regulated the local inflammatory microenvironment and continuously repaired tissue in the nucleus pulposus via the sequential release of drugs in vivo. When degenerative intervertebral discs in a rat model were injected with the scaffold, there was an increase in the proportion of M2 macrophages in the inflammatory environment and higher expression levels of type II collagen and aggrecan; this was accompanied by reduced levels of MMP13 expression, thus exhibiting long-term anti-inflammatory effects. Our research provides a new strategy for promoting intervertebral disc tissue regeneration and a range of other inflammatory diseases.

With the rapid development of communication technology and the diversification and rapid growth of network application demands, the requirements for the anti-destruction capability of information networks have also increased. Therefore, an efficient and accurate metric of the survivability of satellite networks has become a hotspot of current research. Firstly, in this paper, we propose a transfer matrix-based spatial information network invulnerability evaluation algorithm. The algorithm draws the idea of a node deletion method to determine the initial importance of nodes and then establishes a formula for the importance transfer probability of the nodes. In addition, an evaluation algorithm of spatial information network invulnerability is obtained using the network structure entropy theory. Simulations show that our new evaluation algorithm based on the transfer matrix is more accurate compared to degree centricity, natural connectivity and other methods in evaluating the importance of the nodes. The proposed index can effectively reflect the change in the network topology and evaluate the network survivability.

Phosphorus is one of the main nutrients necessary for plant growth and development. Phosphorus-dissolving microorganisms may convert insoluble phosphorus in soil into available phosphorus that plants can easily absorb and utilize. In this study, four phosphorus-solubilizing fungi (L3, L4, L5, and L12) were isolated from the rhizosphere soil of a poplar plantation in Dongtai, Jiangsu Province, China. Phylogenetic analysis based on the internal transcribed spacer (ITS) and large subunit (LSU) of the ribosomal DNA sequences showed that the ITS and 28S sequences of isolates were the most similar to those of Mortierella. Morphological observation showed that most colonies grew in concentric circles and produced spores under different culture conditions. These results and further microscopic observations showed that these isolated fungi belonged to the genus Mortierella. Pikovskaya (PKO) medium, in which tricalcium phosphate was the sole phosphorus source, was used to screen strain L4 with the best phosphorus-solubilizing effect for further study. When the carbon source was glucose, the nitrogen source was ammonium chloride, the pH was 5, and the available phosphorus content was the highest. By exploring the possible mechanism of phosphorus release by phosphorus-solubilizing fungi, it was found that strain L4 produces several organic acids, such as oxalic acid, lactic acid, acetic acid, succinic acid, tartaric acid, malic acid, and citric acid. At 24 h, the alkaline phosphatase and acid phosphatase activities reached 154.72 mol/(L·h) and 120.99 mol/(L·h), respectively.

Plant diseases lead to a significant decline in the output and quality of Chinese herbal medicines. Actinomycetes play a vital role in the rhizosphere ecosystem. This is especially true for Streptomyces, which have become a valuable biological control resource because of their advantages in producing various secondary metabolites with novel structures and remarkable biological activities. The purpose of this study was to isolate an effective antagonistic actinomycete against the pathogen of corm rot in saffron. An antagonistic actinomycete, CM253, was screened from the rhizosphere soil samples of Crocus sativus, by plate co-culture with four pathogenic fungi (Fusarium oxysporum, Fusarium solani, Penicillium citreosulfuratum, and Penicillium citrinum). CM253 inhibited the growth and development of F. oxysporum hyphae by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, by analyzing the degrading enzyme, the growth-promoting performance, and the whole genome of strain CM253, it was identified as Streptomyces yangpuensis, which produces NH3, protease, glucanase, cellulase, IAA, and ACC deaminase. In addition, 24 secondary metabolite synthesis gene clusters were predicted in antiSMASH. We identified genes encoding 2,3-butanediol; methionine; isoprene (metH, mmuM, ispEFH, gcpE, idi, and ilvABCDEH); biofilm formation; and colonization (upp, rfbBC, efp, aftA, pssA, pilD, fliA, and dhaM). Above all, S. yangpuensis CM253 showed the potential for future development as a biocontrol agent.

Ganoderma tsugae is an endemic medicinal mushroom in Northeast China, providing important source of pharmaceutical product. Comparing with other Ganoderma species, wild G. tsugae can utilize coniferous wood. However, functional genes related to medicinal component synthesis and the genetic mechanism of conifer substrate utilization is still obscure. Here, we assembled a high-quality G. tsugae genome with 18 contigs and 98.5% BUSCO genes and performed the comparative genomics with other Ganoderma species. G. tsugae diverged from their common ancestor of G. lingzhi and G. sinense about 21 million years ago. Genes in G. tsugae-specific and G. tsugae-expanded gene families, such as salh, phea, cyp53a1, and cyp102a, and positively selected genes, such as glpk and amie, were functionally enriched in plant-pathogen interaction, benzoate degradation, and fanconi anemia pathway. Those functional genes might contribute to conifer substrate utilization of G. tsugae. Meanwhile, gene families in the terpene synthesis were identified and genome-wide SNP variants were detected in population. Finally, the study provided valuable genomic resources and offered useful hints for the functional gene mapping and investigation of key gene contributing to conifer cultivation substrate utilization and medicinal component biosynthesis.

Inflammasomes are large multimolecular complexes best recognized because of their ability to control activation of caspase-1, which in turn regulates the maturation of interleukin-18 (IL-18) and interleukin-1 β (IL-1β). IL-1β was originally identified as a pro-inflammatory cytokine, capable of inducing local and systemic inflammation as well as a fever response reaction in response to infection or injury. Excessive production of IL-1β is related to inflammatory and autoimmune diseases. Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are characterized by excessive inflammatory response. For SARS, there is no correlation between viral load and worsening symptoms. However, there is no specific medicine which is available to treat the disease. As an important part of medical practice, TCM showed an obvious therapeutic effect in SARS-CoV-infected patients. In this article, we summarize the current applications of TCM in the treatment of COVID-19 patients. Herein, we also offer an insight into the underlying mechanisms of the therapeutic effects of TCM, as well as introduce new naturally occurring compounds with anti-coronavirus activity, in order to provide a new and potential drug development strategy for the treatment of COVID-19.

In this paper, we suggest a new methodology which combines Neural Networks (NN) into Data Assimilation (DA). Focusing on the structural model uncertainty, we propose a framework for integration NN with the physical models by DA algorithms, to improve both the assimilation process and the forecasting results. The NNs are iteratively trained as observational data is updated. The main DA models used here are the Kalman filter and the variational approaches. The effectiveness of the proposed algorithm is validated by examples and by a sensitivity study.

Abstract Background Availability of nursing home care has declined and national efforts have been initiated to improve the quality of nursing home care in the U.S. Yet, data are limited on whether there are geographic variations in declines of availability and quality of nursing home care, and whether variations persist over time. We sought to assess geographic variation in availability and quality of nursing home care. Methods Retrospective study using Medicaid/Medicare-certified nursing home data from the Centers for Medicare & Medicaid Services, 1996–2016. Outcomes were 1) availability of all nursing home care (1996–2016), measured by the number of Medicaid/Medicare-certified beds for a given county per 100,000 population aged ≥65 years, regardless of nursing home star rating; 2) availability of 5-star nursing home care, measured by the number of Medicaid/Medicare-certified beds provided by 5-star nursing homes; and 3) utilization of nursing home beds, defined as the rate of occupied Medicaid/Medicare-certified beds among the total Medicaid/Medicare-certified beds. Results From 1999 to 2016, availability of all nursing home care declined from 4882 (standard deviation: 931) to 3480 (912) beds, per 100,000 population aged ≥65 years. Persistent geographic variation in availability of nursing home care was observed; the correlation coefficient of county-specific availabilities from 1996 to 2016 was 0.78 (95% CI 0.77–0.79). From 2011 to 2016, availability of 5-star nursing home beds increased from 658 (303) to 895 (661) per 100,000 population aged ≥65 years. The correlation coefficient for county-specific availabilities from 2011 to 2016 was 0.54 (95% CI 0.51–0.56). Availability and quality of nursing home care were not highly correlated. In 2016, the correlation coefficient for county-specific availabilities between all nursing home and 5-star nursing home beds was 0.33 (95% CI 0.30–0.36). From 1996 to 2016, the utilization of certified beds declined from 78.5 to 72.2%. This decline was consistent across all census divisions, but most pronounced in the Mountain division and less in the South-Atlantic division. Conclusion We observed persistent geographic variations in availability and quality of nursing home care. Availability of all nursing home care declined but availability of 5-star nursing home care increased. Availability and quality of nursing home care were not highly correlated.