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Turnip mosaic virus (TuMV) constitutes one of the primary diseases affecting Brassica rapa, severely impacting its production and resulting in crop failures in various regions worldwide. Recent research has demonstrated the significance of plant translation initiation factors, specifically the eIF4E and eIF4G family genes, as essential recessive disease resistance genes. In our study, we conducted evolutionary and gene expression studies, leading us to identify eIF(iso)4E.c as a potential TuMV-resistant gene. Leveraging CRISPR/Cas9 technology, we obtained mutant B. rapa plants with edited eIF(iso)4E.c gene. We confirmed eIF(iso)4E.c confers resistance against TuMV through phenotypic observations and virus content evaluations. Furthermore, we employed ribosome profiling assays on eif(iso)4e.c mutant seedlings to unravel the translation landscape in response to TuMV. Interestingly, we observed a moderate correlation between the fold changes in gene expression at the transcriptional and translational levels (R2 = 0.729). Comparative analysis of ribosome profiling and RNA-seq data revealed that plant–pathogen interaction, and MAPK signaling pathway–plant pathways were involved in eIF(iso)4E.c-mediated TuMV resistance. Further analysis revealed that sequence features, coding sequence length, and normalized minimal free energy, influenced the translation efficiency of genes. Our study highlights that the loss of eIF(iso)4E.c can result in a highly intricate translation mechanism, acting synergistically with transcription to confer resistance against TuMV.

Abstract Background Dendrobium officinale Kimura et Migo, a renowned traditional Chinese orchid herb esteemed for its significant horticultural and medicinal value, thrives in adverse habitats and contends with various abiotic or biotic stresses. Acid invertases (AINV) are widely considered enzymes involved in regulating sucrose metabolism and have been revealed to participate in plant responses to environmental stress. Although members of AINV gene family have been identified and characterized in multiple plant genomes, detailed information regarding this gene family and its expression patterns remains unknown in D. officinale, despite their significance in polysaccharide biosynthesis. Results This study systematically analyzed the D. officinale genome and identified four DoAINV genes, which were classified into two subfamilies based on subcellular prediction and phylogenetic analysis. Comparison of gene structures and conserved motifs in DoAINV genes indicated a high-level conservation during their evolution history. The conserved amino acids and domains of DoAINV proteins were identified as pivotal for their functional roles. Additionally, cis-elements associated with responses to abiotic and biotic stress were found to be the most prevalent motif in all DoAINV genes, indicating their responsiveness to stress. Furthermore, bioinformatics analysis of transcriptome data, validated by quantitative real-time reverse transcription PCR (qRT-PCR), revealed distinct organ-specific expression patterns of DoAINV genes across various tissues and in response to abiotic stress. Examination of soluble sugar content and interaction networks provided insights into stress release and sucrose metabolism. Conclusions DoAINV genes are implicated in various activities including growth and development, stress response, and polysaccharide biosynthesis. These findings provide valuable insights into the AINV gene amily of D. officinale and will aid in further elucidating the functions of DoAINV genes.

Background and objectivesThe advent of new clinical subtyping systems for Parkinson's disease (PD) has led to the classification of patients into distinct groups: mild motor predominant (PD-MMP), intermediate (PD-IM), and diffuse malignant (PD-DM). Our goal was to evaluate the efficacy of diffusion tensor imaging (DTI) in the early diagnosis, assessment of clinical progression, and prediction of prognosis of these PD subtypes. Additionally, we attempted to understand the pathological mechanisms behind white matter damage using single-photon emission computed tomography (SPECT) and cerebrospinal fluid (CSF) analyses.MethodsWe classified 135 de novo PD patients based on new clinical criteria and followed them up after 1 year, along with 45 healthy controls (HCs). We utilized tract-based spatial statistics to assess the microstructural changes of white matter at baseline and employed multiple linear regression to examine the associations between DTI metrics and clinical data at baseline and after follow-up.ResultsCompared to HCs, patients with the PD-DM subtype demonstrated reduced fractional anisotropy (FA), increased axial diffusivity (AD), and elevated radial diffusivity (RD) at baseline. The FA and RD values correlated with the severity of motor symptoms, with RD also linked to cognitive performance. Changes in FA over time were found to be in sync with changes in motor scores and global composite outcome measures. Furthermore, baseline AD values and their rate of change were related to alterations in semantic verbal fluency. We also discovered the relationship between FA values and the levels of α-synuclein and β-amyloid. Reduced dopamine transporter uptake in the left putamen correlated with RD values in superficial white matter, motor symptoms, and autonomic dysfunction at baseline as well as cognitive impairments after 1 year.ConclusionsThe PD-DM subtype is characterized by severe clinical symptoms and a faster progression when compared to the other subtypes. DTI, a well-established technique, facilitates the early identification of white matter damage, elucidates the pathophysiological mechanisms of disease progression, and predicts cognitively related outcomes. The results of SPECT and CSF analyses can be used to explain the specific pattern of white matter damage in patients with the PD-DM subtype.

Background Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors is limited in part by the distinctive biology of intrahepatic myeloid-derived suppressor cells (MDSC) and challenges with tumor-specific therapeutic delivery. We have shown that the regional delivery of type C TLR9 agonist via pressure-enabled drug delivery (PEDD) system improves delivery to the tumor, enhances depletion of MDSCs and overall, stimulates the immune system in combination with or without CPI. Currently, CPIs are delivered intravenously, although there is a growing interest in its subcutaneous (SQ) administration. We compared nelitolimod formerly known as SD-101 administered using PEDD in combination with systemic (Sys) or SQ CPI in murine liver metastases (LM).Methods The LM model was developed by injecting MC38-Luc cells via the spleen of 8–12 week old male C57/BL6 mice followed by splenectomy. After a week, fluorescently labeled nelitolimod (10 µg/mouse) was delivered via PEDD and co-administered anti-programmed cell death-1 (α-PD-1) either via Sys or SQ. Tumor burden was monitored by in vivo imaging system. Serum cytokine levels were analyzed by Luminex. Tissues were harvested on Day 3 (D3) or Day 10 (D10) post-PEDD to enrich CD45+ cells and were analyzed via NanoString targeted transcriptomics (D3) or flow cytometry (FC, D10) to interrogate immune cell populations (D10). For NanoString analysis, the innate immune panels were selected, and for FC, MDSCs (CD11b+Gr1+), B cells (B220+), dendritic cells (DC, CD11c+), T (CD3+) cells, and M1-like macrophages (F4/80+CD38+Egr2−) were quantified.Results Nelitolimod delivered via PEDD resulted in changes in innate and adaptive immune cells within LM, including depletion of liver MDSC and increased M1-like macrophages in the liver, which are supportive of antitumor immunity. While CPI monotherapy failed to control tumor progression, nelitolimod and CPI combination improved LM control, survival and antitumor immunity beyond the nelitolimod monotherapy effect, irrespective of CPI delivery route.Conclusion The SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment.

Purpose: To investigate the refractive and ocular biometric characteristics of children with mild hyperopia and distinguish between non-myopic and pseudomyopic eyes before cycloplegia. Methods: The eligible children underwent refractive error measurements using a NIDEK autorefractor before and after the administration of 0.5 % tropicamide. Ocular biometric parameters, including axial length (AL), anterior chamber depth (ACD), and lens thickness (LT), were measured using the IOLMaster 700 before cycloplegia. We performed comparative analyses between the non-myopic and pseudomyopic groups, categorized based on whether the spherical equivalent (SE) before cycloplegia exceeded −0.50 diopters (D). Univariable and multivariable regression analyses were performed to control for confounding factors. Results: The final analysis included 968 eyes. The participants with pseudomyopia were more likely to be boys (P = 0.029), younger (P = 0.004), less hyperopic (P

BackgroundA high-fat diet (HFD) contributes to various metabolic disorders and obesity, which are major contributors to cardiovascular disease. As an essential regulator for heart homeostasis, cardiac resident macrophages may go awry and contribute to cardiac pathophysiology upon HFD. Thus, to better understand how HFD induced cardiac dysfunction, this study intends to explore the transcriptional and functional changes in cardiac resident macrophages of HFD mice.MethodsC57BL/6J female mice that were 6 weeks old were fed with HFD or normal chow diet (NCD) for 16 weeks. After an evaluation of cardiac functions by echocardiography, mouse hearts were harvested and cardiac resident CCR2- macrophages were sorted, followed by Smart sequencing. Bioinformatics analysis including GO, KEGG, and GSEA analyses were employed to elucidate transcriptional and functional changes.ResultsHyperlipidemia and obesity were observed easily upon HFD. The mouse hearts also displayed more severe fibrosis and diastolic dysfunction in HFD mice. Smart sequencing and functional analysis revealed metabolic dysfunctions, especially lipid-related genes and pathways. Besides this, antigen-presentation-related gene such as Ctsf and inflammation, particularly for NF-κB signaling and complement cascades, underwent drastic changes in cardiac resident macrophages. GO cellular compartment analysis was also performed and showed specific organelle enrichment trends of the involved genes.ConclusionDysregulated metabolism intertwines with inflammation in cardiac resident macrophages upon HFD feeding in mice, and further research on crosstalk among organelles could shed more light on potential mechanisms.

Abstract Integrated Sensing and Communications (ISAC) need to process data streams in high‐speed sensor data acquisition or high‐speed wireless communications. To process the data can require more computing and communication resources, resulting in higher power consumption. Halved‐Phase Only Multiple Input Multiple Output (HPO‐MIMO) communication technology can solve this problem by using low‐power nonlinear detection devices. In ISAC, Channel Estimation (CE) technology can provide key channel characteristics and state information for sensing and collaborative work of perception and communication tasks. However, HPO‐MIMO system cannot realize CE using traditional receiver schemes because of the missing amplitude. In order to solve this problem, two HPO‐MIMO CE schemes based on model‐driven deep learning are proposed in this paper. The proposed schemes include a Densely Residual Network (DRN) and a Inception‐Resnet (IR), which is suitable for the case of sufficient data and insufficient data, respectively. The simulation results show that the performance of DRN based scheme is better than that of IR based scheme when the data amount is sufficient, and the performance of IR based scheme is better when the dataset is small. In addition, the proposed CE schemes work well with a range of antenna sizes and distances.

Abstract Background The low efficiency of genetic transformation in Chinese cabbage (Brassica rapa L. ssp. pekinensis) is the key problem affecting functional verification. Particle bombardment is a widely used method along with the Agrobacterium-mediated method. As a physical means, it has almost no restrictions on the type of host and a wide range of receptor types, which largely avoids the restriction of explants. The bombardment parameters, which include the number of bombardments, the bombardment pressure, and the bombardment distance, may affect the microspores' genetic transformation efficiency. Results The transformation efficiency was improved using the particle bombardment method under the combination of bombardment shot times (3, 4, 5) × bombardment pressure (900, 1100, 1350 psi) × bombardment distance (3, 6, 9 cm). The average viability of microspores in the treatment group ranged from 74.76 to 88.55%, while the control group was 88.09%. When the number of shot times was 4, the number of embryos incubated in the treatment group ranged from 16 to 236 per dish, and the control group had 117 embryos per dish. When the bombardment parameters of the biolistic method were 4 shot times—1350 psi—3 cm, 4 times—1100 psi—3 cm, and 4 times—900 psi—3 cm, they had high transient expression efficiency, and the average number of transformed microspores was 21.67, 11.67, and 11.67 per dish (3.5 mL), respectively. When the bombardment parameters were 4 times, 900 psi, and 6 cm, the highest genetically transformed embryos were obtained, and the transformation efficiency reached 10.82%. Conclusion A new genetic transformation system with proper parameters for Chinese cabbage microspores was established using particle bombardment. This proper transformation system could provide a useful tool for the improvement of cultivar quality and the investigation of functional genes in Chinese cabbage.

Our research aims to investigate the impact mechanism of brand loyalty among gamers during the gaming process within the framework of brand loyalty theory and cognitive theory. We surveyed game players from Zhejiang Province, China. The research methods include a questionnaire survey and structural equation modelling. Results show that game experience, interaction, and impression are positively correlated with game trust, while game trust is positively correlated with game brand loyalty. Game trust, as a mediator variable, plays a complete mediation role. The clustering results of player gender and age as moderating effects are not significant. Based on the analysis results, we have suggested corresponding policy recommendations and reflections. Our research contributes to the analysation of impact mechanism of brand loyalty during the gaming process through the establishment of a structural equation model and provides suggestions and reflections on the development of the gaming industry.

Compound pollution with cadmium (Cd) and zinc (Zn) is common in nature. The effects of compounded Cd and Zn on the growth and development of Iris pseudacorus in the environment and the plant’s potential to remediate heavy metals in the environment remain unclear. In this study, the effects of single and combined Cd and Zn stress on I. pseudacorus growth and the enrichment of heavy metals in I. pseudacorus seedlings were investigated. The results showed that under Cd (160 μM) and Zn (800 μM) stress, plant growth was significantly inhibited and photosynthetic performance was affected. Cd+Zn200 (160 μM + 200 μM) reduced the levels of malondialdehyde, hydrogen peroxide, and non-protein thiols by 31.29%, 53.20%, and 13.29%, respectively, in the aboveground tissues compared with levels in the single Cd treatment. However, Cd+Zn800 (160 μM + 800 μM) had no effect. Cd and Zn800 inhibited the absorption of mineral elements, while Zn200 had little effect on plants. Compared with that for Cd treatment alone, Cd + Zn200 and Cd+Zn800 reduced the Cd content in aboveground tissues by 54.15% and 49.92%, respectively, but had no significant effect on Cd in the root system. Zn significantly reduced the Cd content in subcellular components and limited the content and proportion of Cd extracted using water and ethanol. These results suggest that a low supply of Zn reduces Cd accumulation in aboveground tissues by promoting antioxidant substances and heavy metal chelating agents, thus protecting the photosynthetic systems. The addition of Zn also reduced the mobility and bioavailability of Cd to alleviate its toxicity in I. pseudacorus.

It is crucial to estimate the theoretical carrying capacity of grasslands in Xinjiang to attain a harmonious balance between grassland and livestock, thereby fostering sustainable development in the livestock industry. However, there has been a lack of quantitative assessments that consider long-term, multi-scale grass-livestock balance and its impacts in the region. This study utilized remote sensing and empirical models to assess the theoretical livestock carrying capacity of grasslands. The multi-scale spatiotemporal variations of the theoretical carrying capacity in Xinjiang from 1982 to 2020 were analyzed using the Sen and Mann-Kendall tests, as well as the Hurst index. The study also examined the county-level grass-livestock balance and inter-annual trends. Additionally, the study employed the geographic detector method to explore the influencing factors. The results showed that: (1) The overall theoretical livestock carrying capacity showed an upward trend from 1982 to 2020; The spatial distribution gradually decreased from north to south and from east to west. In seasonal scale from large to small is: growing season > summer > spring > autumn > winter; at the monthly scale, the strongest livestock carrying capacity is in July. The different grassland types from largest to smallest are: meadow > alpine subalpine meadow > plain steppe > desert steppe > alpine subalpine steppe. In the future, the theoretical livestock carrying capacity of grassland will decrease. (2) From 1988 to 2020, the average grass-livestock balance index in Xinjiang was 2.61%, showing an overall increase. At the county level, the number of overloaded counties showed an overall increasing trend, rising from 46 in 1988 to 58 in 2020. (3) Both single and interaction factors of geographic detectors showed that annual precipitation, altitude and soil organic matter were the main drivers of spatiotemporal dynamics of grassland load in Xinjiang. The results of this study can provide scientific guidance and decision-making basis for achieving coordinated and sustainable development of grassland resources and animal husbandry in the region.

Abstract Background Th22 subset is a particular type of CD4+ T helper cells subset. Our study aimed to explore the expression level of circulating Th22, Th17, Th1, and Th2 cells and the possible mechanism of these cells in breast cancer (BC) with different pathological features. Methods Our study enrolled 43 newly diagnosed BC patients and 30 healthy controls. Frequencies of peripheral Th22, Th17, Th1, and Th2 cells were tested by flow cytometry. Concentrations of IL‐22 cytokine in plasma were examined by enzyme‐linked immunosorbent assay (ELISA). Real‐time PCR was done to test aromatic hydrocarbon receptor (AHR) and RAR‐associated orphan receptor C (RORC) gene expression. Results Frequencies of Th22, Th17, Th2 subsets, and the plasma IL‐22 level was obviously higher in the BC patients. A positive correlation between Th22 frequency and IL‐22 concentration in plasma was detected in BC patients. Furthermore, the percentage of Th22, Th2 subsets in peripheral blood of HER2 positive BC was higher than that in HER2 negative BC patients. A negative correlation between Th1 subset and Ki‐67% as well as a positive correlation between Th2 subset and Ki‐67% was found in BC patients. The proportion of Th1 cells in BC patients was significantly lower than that of the control group. Expression of AHR and RORC transcription factors were also observed to be upregulated in the BC patients. Furthermore, Th22 cells were positively correlated with BC tumor stage and clinical outcomes. The BC patients with a higher percentage of Th22, Th17, Th1 cells or a lower percentage of Th1 cells showed a decreased trend of survival rate. Conclusion Th22, Th17, Th1, and Th2 subsets may play an essential role in BC patients. Th22, Th17, Th1, and Th2 cells may have potential significance to be used as clinical markers in BC patients with different molecular classification. Th22 cells may have potential value in BC patients’ outcomes prediction, providing clinical value.

Abstract Background Coronavirus disease 2019 (COVID-19) is a rapidly developing and sometimes lethal pulmonary disease. Accurately predicting COVID-19 mortality will facilitate optimal patient treatment and medical resource deployment, but the clinical practice still needs to address it. Both complete blood counts and cytokine levels were observed to be modified by COVID-19 infection. This study aimed to use inexpensive and easily accessible complete blood counts to build an accurate COVID-19 mortality prediction model. The cytokine fluctuations reflect the inflammatory storm induced by COVID-19, but their levels are not as commonly accessible as complete blood counts. Therefore, this study explored the possibility of predicting cytokine levels based on complete blood counts. Methods We used complete blood counts to predict cytokine levels. The predictive model includes an autoencoder, principal component analysis, and linear regression models. We used classifiers such as support vector machine and feature selection models such as adaptive boost to predict the mortality of COVID-19 patients. Results Complete blood counts and original cytokine levels reached the COVID-19 mortality classification area under the curve (AUC) values of 0.9678 and 0.9111, respectively, and the cytokine levels predicted by the feature set alone reached the classification AUC value of 0.9844. The predicted cytokine levels were more significantly associated with COVID-19 mortality than the original values. Conclusions Integrating the predicted cytokine levels and complete blood counts improved a COVID-19 mortality prediction model using complete blood counts only. Both the cytokine level prediction models and the COVID-19 mortality prediction models are publicly available at http://www.healthinformaticslab.org/supp/resources.php .

Tissue engineering scaffolds have been dedicated to regenerating damaged tissue by serving as host biomaterials for cell adhesion, growth, differentiation, and proliferation to develop new tissue. In this work, the design and fabrication of a biodegradable bilayer scaffold consisting of a ternary PLLA/PCL/CAB blend film layer and a PLGA/curcumin (CC) electrospun fiber layer were studied and discussed in terms of surface morphology, tensile mechanical properties, and molecular interactions. Three different compositions of PLLA/PCL/CAB—60/15/25 (TBF1), 75/10/15 (TBF2), and 85/5/10 (TBF3)—were fabricated using the solvent casting method. The electrospun fibers of PLGA/CC were fabricated using chloroform (CF) and dimethylformamide (DMF) co-solvents in 50:50 and 60:40 volume ratios. Spherical patterns of varying sizes were observed on the surfaces of all blend films—TBF1 (17–21 µm) > TBF2 (5–9 µm) > TBF3 (1–5 µm)—caused by heterogeneous surfaces inducing bubble nucleation. The TBF1, TBF2, and TBF3 films showed tensile elongation at break values of approximately 170%, 94%, and 43%, respectively. The PLGA/CC electrospun fibers fabricated using 50:50 CF:DMF had diameters ranging from 100 to 400 nm, which were larger than those of the PLGA fibers (50–200 nm). In contrast, the PLGA/CC electrospun fibers fabricated using 60:40 CF:DMF had diameters mostly ranging from 200 to 700 nm, which were larger than those of PLGA fibers (200–500 nm). Molecular interactions via hydrogen bonding were observed between PLGA and CC. The surface morphology of the bilayer scaffold demonstrated adhesion between these two solid surfaces resembling “thread stitches” promoted by hydrophobic interactions, hydrogen bonding, and surface roughness.

Objective: The objective of this study was to explore the influence of the polymorphism of the protocadherin 9 (PCDH9) gene and the narcissistic personality trait (NPT) on the risk of major depressive disorder (MDD) in Chinese first-year university students.Methods: A 2-year cohort study was conducted among Chinese first-year university students who were enrolled in 2018 from two universities in Shandong Province, China. The snapshot technique was used to detect the genotypes of PCDH9 (rs9540720). The Chinese version of the Composite International Diagnostic Interview was used for the MDD assessment. The NPTs were measured by 11 items based on DSM-IV. Patient Health Questionnaire-9 and the Beck Anxiety Inventory were used to assess depressive and anxiety symptoms, respectively. Logistic regression modeling was carried out to examine the relationship between rs9540720, NPTs, and the incidence of MDD.Results: A total of 5,327 students participated in the baseline and follow-up studies and provided their blood samples. PCDH9 (rs9540720) (ORGG+GA = 2.33, 95% CI: 1.35–4.02) and NPTs (OR5–9 = 2.26, 95% CI: 1.40–3.64) increased the risk of MDD onset. There was no multiplicative interaction between NPTs and Rs9540720 (OR = 1.51, 95% CI: 0.30–7.63). Furthermore, there was no additive interaction between them (RERI = 2.40, 95% CI: –0.82–5.62; AP = 0.47, 95% CI: –0.04–0.97; and S = 2.37, 95% CI: 0.54–10.33).Conclusion:PCDH9 (rs9540720) and more NPTs are the risk factors for the incidence of MDD in Chinese first-year university students.

Our research objective is to establish a fuzzy evaluation mechanism for rural village officials in China using the theory of triangular multiplication preference relationships. Our survey targets villagers in rural areas of China where village autonomy is implemented. The research methods include a questionnaire survey, Delphi, and fuzzy evaluation methods. After research analysis and comparison of results, it is shown that for the evaluation index system of village officials constructed using the Delphi method, practical evaluation of village officials can be achieved through fuzzy comprehensive evaluation based on triangular multiplication preference relationships. Using the Delphi technique, this article first created a village official assessment index system. It then performed validity tests based on the Kaiser-Meyer-Olkin (KMO) and Bartlett index system, as well as reliability testing using the Cronbach coefficient. Then, the preference relationship of triangular multiplication and the root product square method were used to determine the weight of the questionnaire indicators, and consistency was judged. Then, based on the membership function, the fuzzy boundaries of various indicators are displayed to construct a fuzzy evaluation matrix. Finally, the evaluation matrix is subjected to the Zadeh operation to obtain a fuzzy, comprehensive evaluation result of the work performance of village officials. Our main contribution is establishing an evaluation index system for village officials through the Delphi method and achieving a practical evaluation of village officials using triangular multiplication preference relationships and fuzzy evaluation theory.

Abstract This is the protocol for an evidence and gap map. The objectives are as follows: To map available randomized control trials, economic evaluations, and systematic reviews that assess the effectiveness and cost‐effectiveness of non‐pharmacological interventions for older people with a diagnosis of depression and identify any existing gaps in the evidence that can inform future research.

BackgroundTumor abnormal protein (TAP), the sugar chain protein released by tumor cells during metabolism, allows the development of a technique that exploits aggregated tumor-associated abnormal sugar chain signals in diagnosing malignancies. Clinically, we have found that TAP detection can well predict some malignancies, but several physicians have not paid attention, and related studies have been minimal.MethodsWe evaluated TAP’s ability to distinguish between malignancies and benign diseases by receiver operating characteristic (ROC) curve analysis and studied the possibility of monitoring malignancy progression by evaluating TAP levels in follow-up. We used Kaplan-Meier survival curves and Cox proportional hazard regression models to investigate the relationship between TAP and prognosis.ResultsTAP levels were higher in whole solid malignancies and every type of solid malignancy than in benign patients. ROC curve analysis showed that TAP levels aid in distinguishing between malignancies and benign diseases. TAP levels decreased in patients with complete remission (CR) after treatment and increased in patients with relapse from CR. Patients with metastases had higher TAP levels than non-CR patients without metastases. There was no difference in overall survival among patients with different TAP levels, and multivariate analysis suggested that TAP was not an independent risk factor for solid malignancies.ConclusionTAP is an effective screening biomarker for many solid malignancies that can be used to monitor the progression of malignancies but not to prognosticate.

Abstract Background Anaplastic thyroid carcinoma (ATC) was a rare and extremely malignant endocrine cancer with the distinct hallmark of high proportion of cancer stem cell-like characteristics. Therapies aiming to cancer stem-like cells (CSCs) were emerging as a new direction in cancer treatment, but targeting ATC CSCs remained challenging, mainly due to incomplete insights of the regulatory mechanism of CSCs. Here, we unveiled a novel role of ISG15 in the modulation of ATC CSCs. Methods The expression of ubiquitin-like proteins were detected by bioinformatics and immunohistochemistry. The correlation between ISG15 expression and tumor stem cells and malignant progression of ATC was analyzed by single-cell RNA sequence from the Gene Expression Omnibus. Flow cytometry combined with immunofluorescence were used to verify the enrichment of ISG15 and ISGyaltion in cancer stem cells. The effect and mechanism of ISG15 and KPNA2 on cancer stem cell-like characteristics of ATC cells were determined by molecular biology experiments. Mass spectrometry combined with immunoprecipitation to screen the substrates of ISG15 and validate its ISGylation modification. Nude mice and zebrafish xenograft models were utilized to demonstrate that ISG15 regulates stem cell characteristics and promotes malignant progression of ATC. Results We found that among several ubiquitin proteins, only ISG15 was aberrantly expressed in ATC and enriched in CSCs. Single-cell sequencing analysis revealed that abnormal expression of ISG15 were intensely associated with stemness and malignant cells in ATC. Inhibition of ISG15 expression dramatically attenuated clone and sphere formation of ATC cells, and facilitated its sensitivity to doxorubicin. Notably, overexpression of ISGylation, but not the non-ISGylation mutant, effectively reinforced cancer stem cell-like characteristics. Mechanistically, ISG15 mediated the ISGylation of KPNA2 and impeded its ubiquitination to promote stability, further maintaining cancer stem cell-like characteristics. Finally, depletion of ISG15 inhibited ATC growth and metastasis in xenografted mouse and zebrafish models. Conclusion Our studies not only provided new insights into potential intervention strategies targeting ATC CSCs, but also uncovered the novel biological functions and mechanisms of ISG15 and ISGylation for maintaining ATC cancer stem cell-like characteristics. Graphical Abstract

Abstract Stressful life events (SLEs) closely correlates with depressive symptoms. Although vulnerability-stress model suggests SLEs interacted with dysfunctional attitudes (DA) to predict depression, the mediation role of DA is poorly understood. Therefore, this study intended to investigate the mediating role of DA and the moderating role of sex between SLEs and self-reported depression. A cross-sectional survey was conducted with a sample of 7769 Chinese college students. Participants were assessed in terms of self-reported SLEs, DA and depression variables. Results showed that there were significant sex differences in both SLE and DA. DA mediated the association between SLE and self-reported depression. The moderated mediation model analysis showed that the interaction of SLEs and sex significantly predicted DA in mediator variable model and self-reported depression in dependent variable model. Results indicated that DA partially mediated the association between SLEs and self-reported depression, and sex moderates the association between SLEs and both DA and self-reported depression, which females have bigger changes of DA and depressive symptoms across low and high levels of SLEs than males.

In today’s fast-paced and ever-changing environment, the need for algorithms with enhanced global optimization capability has become increasingly crucial due to the emergence of a wide range of optimization problems. To tackle this issue, we present a new algorithm called Random Particle Swarm Optimization (RPSO) based on cosine similarity. RPSO is evaluated using both the IEEE Congress on Evolutionary Computation (CEC) 2022 test dataset and Convolutional Neural Network (CNN) classification experiments. The RPSO algorithm builds upon the traditional PSO algorithm by incorporating several key enhancements. Firstly, the parameter selection is adapted and a mechanism called Random Contrastive Interaction (RCI) is introduced. This mechanism fosters information exchange among particles, thereby improving the ability of the algorithm to explore the search space more effectively. Secondly, quadratic interpolation (QI) is incorporated to boost the local search efficiency of the algorithm. RPSO utilizes cosine similarity for the selection of both QI and RCI, dynamically updating population information to steer the algorithm towards optimal solutions. In the evaluation using the CEC 2022 test dataset, RPSO is compared with recent variations of Particle Swarm Optimization (PSO) and top algorithms in the CEC community. The results highlight the strong competitiveness and advantages of RPSO, validating its effectiveness in tackling global optimization tasks. Additionally, in the classification experiments with optimizing CNNs for medical images, RPSO demonstrated stability and accuracy comparable to other algorithms and variants. This further confirms the value and utility of RPSO in improving the performance of CNN classification tasks.

Yanbian cattle have a unique meat flavor, and high-grade meat is in short supply. Therefore, in this study, we aimed to improve the added value of Yanbian cattle low-fat meat and provide a theoretical reference for the subsequent development of an excellent starter. Rump meat from Yanbian cattle was dry-aged and then screened for protease-producing fungi. Three protease-producing fungi (Yarrowia hollandica (D4 and D11), Penicillium oxalicum (D5), and Meesziomyces ophidis (D20)) were isolated from 40 d dry-aged beef samples, and their ability to hydrolyze proteins was determined using bovine sarcoplasmic protein extract. SDS-PAGE showed that the ability of Penicillium oxalicum (D5) to degrade proteins was stronger than the other two fungi. In addition, the volatile component content of sarcoplasmic proteins in the D5 group was the highest (45.47%) and comprised the most species (26 types). Metabolic pathway analysis of the fermentation broth showed that phenylalanine, tyrosine, and tryptophan biosynthesis was the most closely related metabolic pathway in sarcoplasmic protein fermentation by Penicillium oxalicum (D5). Dry-aged beef-isolated Penicillium oxalicum serves as a potential starter culture for the fermentation of meat products.

Abstract Background Type 2 diabetes mellitus (T2DM) and diabetic complications threaten human health seriously. Healthy lifestyles can lower the risk of cardiovascular disease (CVD) and long‐term complications. However, the relationship between alcohol consumption and CVD mortality is still controversial, and there is a lack of evidence from large‐scale longitudinal studies in the Chinese population. Based on the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study), this paper explores the association between alcohol consumption and all‐cause mortality, stroke, and coronary heart disease (CHD) in patients with abnormal glucose metabolism during a 10‐year follow‐up period to provide evidence for lifestyle counselling for these patients. Methods First, baseline data were collected from the REACTION study cohort in Changchun, Jilin Province, China, in 2011–2012. A questionnaire survey was performed among patients with abnormal glucose metabolism aged over 40 years. The frequency of their alcohol intake, the type of alcohol, and the amount of alcohol consumed daily were surveyed. Physical and biochemical examinations were also performed. Then, through the Primary Public Health Service System of Jilin Province, we collected outcomes during the 10‐year follow‐up up to October 1, 2021, including all‐cause mortality, stroke, and CHD. Next, we conducted logistic regression to analyze the relationship between baseline alcohol consumption and 10‐year outcomes, and risk ratio (RR) and 95% CI were calculated by adjusting for different clinical indicators. A p value

Abstract Non-protein target drugs, especially RNA-based gene therapies for treating hereditary diseases, have been recognized worldwide. As cancer is an insurmountable challenge, no miracle drug is currently available. With the advancements in the field of biopharmaceuticals, research on cancer therapy has gradually focused on non-protein target-targeted drugs, especially RNA therapeutics, including oligonucleotide drugs and mRNA vaccines. This review mainly summarizes the clinical research progress in RNA therapeutics and highlights that appropriate target selection and optimized delivery vehicles are key factors in increasing the effectiveness of cancer treatment in vivo.

Purpose: In malignant tumours, elastography and serum tumour markers have shown high diagnostic efficacy. Therefore, we aimed to quantitatively analyse the results of endobronchial elastography combined with serum tumour markers of lung cancer to accurately distinguish benign and malignant mediastinal and hilar lymph nodes.Methods: Data of patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal lymph node enlargement in our hospital between January 2018 and August 2022 were retrospectively collected. The characteristics of quantitative elastography and serum tumour markers were evaluated.Results: We enrolled 197 patients (273 lymph nodes). In the differential diagnosis of benign and malignant mediastinal and hilar lymph nodes, the stiffness area ratio (SAR), strain ratio (SR), and strain rate in lymph nodes were significant, among which SAR had the highest diagnostic value (cut-off value, 0.409). The combination of the four tumour markers had a high diagnostic value (AUC, 0.886). Three types of quantitative elastography indices combined with serum tumour markers for lung cancer showed a higher diagnostic value (AUC, 0.930; sensitivity, 83.5%; specificity, 89.3%; positive predictive value, 88.1%; negative predictive value, 85%) (p < 0.05). In the differential diagnosis of pathological types of lung cancer, different quantitative elastography indicators and serum tumour markers for lung cancer have different diagnostic significance for the differential diagnosis of lung cancer pathological types.Conclusion: The quantitative analysis of endobronchial ultrasound elastography combined with tumour markers can improve the diagnosis rate of benign and malignant mediastinal and hilar lymph nodes, help guide the puncture of false negative lymph nodes, and reduce the misdiagnosis rate.

The flywheel energy storage system (FESS) has been attracting the attention of national and international academicians gradually with its benefits such as high energy power density, high conversion productivity, and inexpensive pollution. For the mutual limitation problem of reaction speed and overshoot of the conventional PI controller, it is hard to satisfy the demand of high efficiency control. In this study, the Active Disturbance Rejection Controller (ADRC) is adopted to substitute the classical PI controller in the flywheel energy storage control system. The control system of an external loop of speed and an internal loop of current is adopted at the motor side. The standard ADRC is adopted by increasing the new nonlinear control function. The control system adopted the control strategy of the DC bus voltage external loop and the current internal loop on the grid side, as well as the second-order Linear Active Disturbance Rejection Controller (LADRC), to enhance the control ability of the DC bus voltage. In the charge/discharge control of the FESS, both the velocity external loop and current internal loop control strategies are utilized to simplify the system structure. The performance shows that the improved control system could effectively enhance the charging and discharging speed of the FESS and effectively suppress the DC bus voltage rise caused by flywheel state switching so that the system has better robustness.

PurposeThe aim of this study was to investigate the risk factors for acute exacerbation (AE) of interstitial lung disease caused by chemotherapy for lung cancer.MethodsWe searched PubMed, Embase, and The Cochrane Library databases from the establishment of each database to April 2023. Eligible studies were included, and the data on risk factors related to AE caused by chemotherapy in interstitial lung disease were extracted.ResultsA total of 878 articles were retrieved and 21 met the inclusion criteria. The studies included 1,275 patients with lung cancer combined with interstitial lung disease. The results of the meta-analysis showed four significant risk factors for AE of interstitial lung disease, namely age < 70 years (odds ratio [OR]: 1.98, 95% confidence interval [CI]: 1.05–3.72), forced vital capacity (FVC) (MD=-9.33, 95% CI: -13.7–4.97), usually interstitial pneumonia (UIP) pattern on computed tomography (CT) (OR: 2.11, 95% CI: 1.43–3.11), and serum surfactant protein D (SP-D) (SMD: 0.35, 95% CI: 0.03–0.67).ConclusionWhen patients with lung cancer complicated with interstitial lung disease are aged < 70 years, have a UIP pattern on CT, have lower FVC values, and have higher serum levels of SP-D, chemotherapy should be carried out with care.

Introduction The COVID-19 pandemic posed a detrimental impact on the conduct of non-COVID-19 related clinical trials, raising concerns about the completeness of these studies and waste of resources. While several measures and strategies have been suggested to address these issues, a thorough and timely summarisation is still lacking. Therefore, our aim is to conduct a scoping review to summarise the negative effects of COVID-19 on non-COVID-19 clinical trials, outline the effective measures for mitigating these impacts, and provide insights for future pandemics.Methods and analysis This scoping review will be conducted in line with the Joanna Briggs Institute’s scoping review methodological framework, and the results will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Relevant articles will be searched in PubMed, Embase and the Cochrane Library from 1 December 2019 to 1 July 2023. We will also screen the reference lists of the included studies manually to identify more potentially relevant articles. Articles focusing on the adverse impacts of COVID-19 on non-COVID-19 clinical trials and effective measures for mitigating them will be included. Two investigators will perform study selection and data extraction independently. A narrative summary as well as a descriptive analysis of the basic characteristics and key results of the included studies will be performed.Ethics and dissemination Ethical approval is not required, as this scoping review will be completed based only on published literature. The findings of this scoping review will be disseminated through a peer-reviewed publication and/or conference presentations.

Sparrow search algorithm (SSA) suffers from a tendency to fall into local optima, as well as a preference for zero locations. Therefore, to improve this drawback, we propose a non-uniform mutation sparrow search algorithm (NMSSA). In the initialization stage of the population, we introduce a tent chaos map and a generalized opposition-based learning strategy to improve the diversity of the population; We introduce adaptive weight to dynamically adjust the search range of the discoverer to improve the search efficiency of the algorithm; To prevent the algorithm from deviating from the target in the early stage, we adopt a non-uniform mutation strategy to improve the flexibility of the follower search to improve the convergence accuracy of the algorithm. Finally, we use the somersault strategy to reduce the probability of the algorithm falling into local optimum. In the test experiments with 10 benchmark functions and CEC2017 functions, we compare the experimental results of NMSSA with those of other algorithms, and the experimental results verify the effectiveness of NMSSA. In addition, we also applied NMSSA to engineering problems optimization and K-means image segmentation, and the experimental results show that NMSSA has good performance in practical applications.

Spatiotemporal variations in Central Asian vegetation phenology provide insights into arid ecosystem behavior and its response to environmental cues. Nevertheless, comprehensive research on the integrated impact of meteorological factors (temperature, precipitation, soil moisture, saturation vapor pressure deficit), topography (slope, aspect, elevation), and greenhouse gases (carbon dioxide, methane, nitrous oxide) on the phenology of Central Asian vegetation remains insufficient. Utilizing methods such as partial correlation and structural equation modeling, this study delves into the direct and indirect influences of climate, topography, and greenhouse gases on the phenology of vegetation. The results reveal that the start of the season decreased by 0.239 days annually, the length of the season increased by 0.044 days annually, and the end of the season decreased by 0.125 days annually from 1982 to 2021 in the arid regions of Central Asia. Compared with topography and greenhouse gases, meteorological factors are the dominant environmental factors affecting interannual phenological changes. Temperature and vapor pressure deficits (VPD) have become the principal meteorological elements influencing interannual dynamic changes in vegetation phenology. Elevation and slope primarily regulate phenological variation by influencing the VPD and soil moisture, whereas aspect mainly affects the spatiotemporal patterns of vegetation phenology by influencing precipitation and temperature. The findings of this study contribute to a deeper understanding of how various environmental factors collectively influence the phenology of vegetation, thereby fostering a more profound exploration of the intricate response relationships of terrestrial ecosystems to environmental changes.

Diabetic muscle atrophy is an inflammation-related complication of type-2 diabetes mellitus (T2DM). Even though regular exercise prevents further deterioration of atrophic status, there is no effective mediator available for treatment and the underlying cellular mechanisms are less explored. In this study, we investigated the therapeutic potential of MCC950, a specific, small-molecule inhibitor of NLRP3, to treat pyroptosis and diabetic muscle atrophy in mice. Furthermore, we used MCC950 to intervene in the protective effects of aerobic exercise against muscle atrophy in diabetic mice. Blood and gastrocnemius muscle (GAS) samples were collected after 12 weeks of intervention and the atrophic state was assessed. We initially corroborated a diabetic muscle atrophy phenotype in db/db mice (D) by comparison with control m/m mice (W) by examining parameters such as fasting blood glucose (D vs. W: 24.47 ± 0.45 mmol L−1 vs. 4.26 ± 0.6 mmol L−1, p < 0.05), grip strength (D vs. W: 166.87 ± 15.19 g vs. 191.76 ± 14.13 g, p < 0.05), exercise time (D vs. W: 1082.38 ± 104.67 s vs. 1716 ± 168.55 s, p < 0.05) and exercise speed to exhaustion (D vs. W: 24.25 ± 2.12 m min−1 vs. 34.75 ± 2.66 m min−1, p < 0.05), GAS wet weight (D vs. W: 0.07 ± 0.01 g vs. 0.13 ± 0.01 g, p < 0.05), the ratio of GAS wet weight to body weight (D vs. W: 0.18 ± 0.01% vs. 0.54 ± 0.02%, p < 0.05), and muscle fiber cross-sectional area (FCSA) (D vs. W: 1875 ± 368.19 µm2 vs. 2747.83 ± 406.44 µm2, p < 0.05). We found that both MCC950 (10 mg kg−1) treatment and exercise improved the atrophic parameters that had deteriorated in the db/db mice, inhibited serum inflammatory markers and significantly attenuated pyroptosis in atrophic GAS. In addition, a combined MCC950 treatment with exercise (DEI) exhibited a further improvement in glucose uptake capacity and muscle performance. This combined treatment also improved the FCSA of GAS muscle indicated by Laminin immunofluorescence compared to the group with the inhibitor treatment alone (DI) (DEI vs. DI: 2597 ± 310.97 vs. 1974.67 ± 326.15 µm2, p < 0.05) or exercise only (DE) (DEI vs. DE: 2597 ± 310.97 vs. 2006.33 ± 263.468 µm2, p < 0.05). Intriguingly, the combination of MCC950 treatment and exercise significantly reduced NLRP3-mediated inflammatory factors such as cleaved-Caspase-1, GSDMD-N and prevented apoptosis and pyroptosis in atrophic GAS. These findings for the first time demonstrate that targeting NLRP3-mediated pyroptosis with MCC950 improves diabetic muscle homeostasis and muscle function. We also report that inhibiting pyroptosis by MCC950 can enhance the beneficial effects of aerobic exercise on diabetic muscle atrophy. Since T2DM and muscle atrophy are age-related diseases, the young mice used in the current study do not seem to fully reflect the characteristics of diabetic muscle atrophy. Considering the fragile nature of db/db mice and for the complete implementation of the exercise intervention, we used relatively young db/db mice and the atrophic state in the mice was thoroughly confirmed. Taken together, the current study comprehensively investigated the therapeutic effect of NLRP3-mediated pyroptosis inhibited by MCC950 on diabetic muscle mass, strength and exercise performance, as well as the synergistic effects of MCC950 and exercise intervention, therefore providing a novel strategy for the treatment of the disease.

In this paper we present a detailed single-pulse and polarization study of PSR J0614+2229 based on the archived data observed on 2019 August 15 (MJD 58710) and 2019 September 12 (MJD 58738) using the ultra−wide-bandwidth low-frequency receiver on the Parkes radio telescope. The single-pulse sequences show that this pulsar switches between two emission states, in which the emission of state A occurs earlier than that of state B in pulse longitude. We found that the variation in relative brightness between the two states varies temporally and both states follow a simple power law very well. Based on the phase-aligned multifrequency profiles, we found that there is a significant difference in the distributions of spectral index across the emission regions of the two states. Furthermore, we obtained the emission height evolution for the two emission states and found that, at a fixed frequency, the emission height of state A is higher than that of state B. What is even more interesting is that the emission heights of both states A and B do not change with frequency. Our results suggest that the mode switching of this pulsar is possibly caused by changes in the emission heights that alter the distributions of spectral index across the emission regions of states A and B, resulting in frequency-dependent behaviors, i.e., intensity and pulse width.

We report the nulling and subpulse-drifting properties of PSR J1649+2533 with observations of the Five-hundred-meter Aperture Spherical Radio Telescope (FAST). The FAST observations reveal that the nulling fraction of this pulsar is about 20.9% ± 0.8% at 1250 MHz. The statistical study of the durations of the nulling and burst states shows that the burst states can persist for extended pulse periods, exceeding 100 periods in some cases, while the shortest lasts only a few pulse periods. The null states have a much shorter duration, with a maximum duration of less than 30 pulse periods. A comparative study between the pulse profiles of the first active pulse (FAP) and the last active pulse (LAP) shows that the pulse profiles of LAPs are stronger and wider than those of FAPs. An analysis of the two-dimensional fluctuation spectrum for the single-pulse stack indicates that the pulsar exhibits clear amplitude modulation and subpulse drifting. The periods are a P _3 = 2.5 ± 0.1 spin period and P _2 = 17.°0 ± 0.°5 at 1250 MHz, respectively. In addition, the multiband investigation shows that P _2 seems to increase with the increase of the observing frequency, i.e., P _2 ∝ ν ^0.8±0.1 . This seems to be caused by the increasing pulse-profile width with the frequency. The high-sensitivity FAST observations will enable a detailed understanding of the emission of this pulsar and provide important clues for theoretical studies of the radiation mechanism.

The mode of urban renewal in China has changed from incremental expansion to a value-added stage, and the development of cities has increasingly focused on the human experience and quality improvement. However, Cultural Street Vending and the unique street spaces in the historic districts that bear important connotations to the city have shown a trend of rapid decline and even disappearance. Therefore, how to identify the characteristics and connotations of such street vending spaces, grasp the relationship between perception of locality and built environment elements in different states and formulate targeted protection and renewal strategies is presently an urgent problem to be solved. Many studies have now discussed in detail the identification of elements, street perception and preservation strategies for historic districts. However, the Cultural Street Vending space, which carries special urban memory connotations, has been neglected, especially the characterisation of this type of space in different time dimensions. This paper takes the Cultural Street Vending space as a research object and focuses on the perceptual differences between its market day and non-market day, aiming at grasping the perceptual characteristics and constituent elements of this type of street space in different time states, as well as the patterns of changes they undergo. This paper took the Baxian Temple, a typical Cultural Street Vending space in a historic district of Xi’an, as the research object and took 30 architecture students as the evaluators to score 33 pairs of adjectives and recall the elements of nine streets. This paper compared and analysed the differences in the structure of people’s psychological perception of the street in the state of market day and non-market day by SD method. It was found that the activities of the vendors obviously promoted people’s positive emotions, and three commonality factors including impression, vitality and morphosis were extracted through the factor analysis. Moreover, through the element recall method to understand the change in element perception on the market day, we found that the range of people’s perception was smaller on the market day and summarised the element map of the space and the element components of high, medium and low characteristics. The correlation analysis between psychological quantities and environmental elements revealed that people’s positive psychology has a positive correlation with vendors, goods and street components and a negative correlation with greening, colour and texture. This study can provide an important research basis for the development of conservation and renewal strategies for this type of Cultural Street Vending space.

Soybean peptides (SPs) have bioactivities of enzyme inhibition that are beneficial to human health, but their mechanism is not clear. This study aimed to identify peptide fragments in SPs that simultaneously inhibit α-amylase and α-glucosidase and to explore their enzyme inhibition mechanism. Firstly, the inhibitory activity of SPs against the enzymes was determined. And two octapeptides, LDQTPRVF and SRNPIYSN, were identified for the first time by using HPLC-QTOF-MS/MS and virtual screening. Molecular simulation results showed that hydrogen bonds and π–π bonds were the key factors, and the N-terminal (Leu and Ser) and C-terminal (Phe) of peptide were important inhibiting sites. Both octapeptides were synthesized, and their IC50 values were 3.08 and 5.58 mmol/L for α-amylase, and 2.52 and 4.57 mmol/L for α-glucosidase, respectively. This study provided evidence for SPs as a potential inhibitor of α-amylase and α-glucosidase in special dietary foods.

Introduction Heart failure (HF) with preserved ejection fraction (HFpEF) has become the main type of HF worldwide. Although large randomised controlled studies have demonstrated the beneficial effects of sodium–glucose cotransporter 2 inhibitors among patients with HFpEF, the mechanisms remain unclear. Basic research suggests that empagliflozin inhibits myocardial fibrosis. Myocardial extracellular volume (ECV) can be calculated using cardiac MRI (CMRI), which can reflect the degree of diffuse myocardial fibrosis. Studies show that empagliflozin can reduce ECV and left ventricular mass (LVM) assessed by CMRI in patients with diabetes with coronary heart disease and patients without diabetes with HF with reduced ejection fraction. However, whether empagliflozin reduces ECV and LVM among patients with HFpEF is unclear. This study intends to use CMRI to evaluate ECV and LVM, combined with echocardiography and an assessment of related biomarkers, to determine whether empagliflozin can improve myocardial fibrosis and left ventricular remodelling in patients with HFpEF.Methods and analysis This report describes the study design of a prospective, multicentre, randomised, double-blind, placebo-controlled and parallel-group clinical study. A total of 180 participants with HFpEF aged 40–80 years old who meet the inclusion and exclusion criteria will be randomly divided into an empagliflozin treatment group or a placebo control group. The empagliflozin treatment group will receive 10 mg of empagliflozin per day for 6 months in addition to guideline-directed medical treatment, while the control group will receive placebo oral administration with guideline-directed medical therapy for 6 months. The primary outcomes are ECV and LVM changes measured by CMRI after 6 months of treatment.Ethics and dissemination The study design is approved by the ethical committee of Beijing Hospital (2022BJYYEC-070-02). The trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn). The trial results will be published in peer-reviewed journals and conferences.Trial registration number Chinese Clinical Trial Registry (ChiCTR2200060862).

Background: Little is known about changes in astigmatism during atropine treatment. We aimed to explore the effects of atropine 0.01% eye drops on both spherical and cylindrical refractive errors in myopic children. Methods: Children aged 6–14 years with myopia ≥ −6.00 D and −2.00 D in at least one eye were enrolled. Subjects were randomised either to receive atropine 0.01% once nightly with single-vision lenses or simply to wear single-vision lenses and were followed up at 3-month intervals. Cycloplegic refraction and axial length were measured. The magnitude and direction of total astigmatism (TA), corneal astigmatism (CA), and residual astigmatism (RA) were evaluated. Results: Overall, 119 eyes (69 eyes in the atropine group and 50 eyes in the control group) were included in the final analyses after 9 months. Atropine-treated eyes showed significantly less progression of myopia than did control eyes (spherical equivalent: −0.35 ± 0.33 vs. −0.56 ± 0.49 D, p = 0.001; axial length: 0.20 ± 0.19 vs. 0.33 ± 0.19 mm, p

Cadmium (Cd) pollution is a global problem affecting soil ecology and plant growth. Abscisic acid (ABA) acts as a growth and stress hormone, regulates cell wall synthesis, and plays an important role in plant responses to stress. There are few studies on the mechanisms behind abscisic acid alleviation of cadmium stress in Cosmos bipinnatus, especially in regards to regulation of the root cell wall. This study examined the effects of different concentrations of abscisic acid at different concentrations of cadmium stress. Through adding 5 μmol/L and 30 μmol/L cadmium, followed by spraying 10 μmol/L and 40 μmol/L ABA in a hydroponic experiment, it was found that under two concentrations of cadmium stress, low concentration of ABA improved root cell wall polysaccharide, Cd, and uronic acid content. Especially in pectin, after the application of low concentration ABA, the cadmium concentration was significantly increased by 1.5 times and 1.2 times compared with the Cd concentration under Cd5 and Cd30 treatment alone, respectively. Fourier-Transform Infrared spectroscopy (FTIR) demonstrated that cell wall functional groups such as -OH and -COOH were increased with exposure to ABA. Additionally, the exogenous ABA also increased expression of three kinds of antioxidant enzymes and plant antioxidants. The results of this study suggest that ABA could reduce Cd stress by increasing Cd accumulation, promoting Cd adsorption on the root cell wall, and activating protective mechanisms. This result could help promote application of C. bipinnatus for phytostabilization of cadmium-contaminated soil.

ABSTRACTHuman milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6’-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6’-SL in the maternal rat milk of St6gal1 knockouts (St6gal1−/−) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6′-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6′-SL synthesis in mammary glands after SA+Pro intervention through the gut – breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.

Abstract The semiconductive shield layer is between the conductive core and the insulation layer of high voltage direct current transmission cables and plays an important role in suppressing the accumulation of space charge in the insulation layer. Since the prevalent positive temperature coefficient effect (PTC) of the semiconducting layer leads to cable ageing and failure, this paper proposes the use of lithium cobaltate to modify the semiconducting shield to suppress its PTC effect and improve its ability to inhibit space charge injection. The ionic conductor LiCoO2 was prepared by the sol–gel method. LiCoO2 particles with particle sizes ranging from tens to hundreds of nanometres were obtained by ball milling. The prepared LiCoO2 was used as a filler to modify the carbon black (CB)/ethylene vinyl acetate copolymer (EVA)/low density polyethylene (LDPE) composites. After melt blending and moulding cross‐linking, LiCoO2/CB/EVA/LDPE semiconductive shielding specimens were successfully fabricated. Resistivity, Thermally Stimulated Depolarisation Currents (TSDC), and pulsed electro‐acoustic measurements were conducted for the prepared specimens. The PTC effect, which is common in polymer composites, was successfully suppressed, and the PTC strength was reduced by 17%. The resistivity of the semiconductive shielding layer was significantly reduced. The ability of the semiconducting shield to inhibit space charge injection from the conductive core to the insulation layer was significantly improved. When LiCoO2 content is 0.5 wt%, the semiconductive shielding layer has the best performance, and the space charge in the insulation layer was reduced by 70% compared to the undoped semiconducting shield.

Abstract Although diaphragmatic dysfunction is an important indicator of severity of illness and poor prognosis in ICU patients, there is no convenient and practical method to monitor diaphragmatic function. This study was designed to analyze diaphragmatic dynamic dysfunction by bedside ultrasound in septic patients and provide quantitative evidence to assess diaphragm function systematically. This prospective observational study was conducted from October 2019 to January 2021 in the Department of Respiratory and Critical Care Medicine. 74 patients suffered from sepsis were recruited and divided into two groups, sepsis group 1 (2 ≤ SOFA ≤ 5, n = 41) and sepsis group 2 (SOFA > 5, n = 33). 107 healthy volunteers were randomly recruited as the control group. In all participants, the diaphragmatic thickness and excursion were measured directly and the dynamic parameters including thickening fraction (TF), EQB/EDB, Contractile velocity, and area under diaphragmatic movement curve (AUDMC) were calculated by bedside ultrasound during quiet breathing (QB) and deep breathing (DB). Each parameter among three groups was analyzed separately by covariance analysis, which was adjusted by age, sex, body mass index, MAP, hypertension, and diabetes. First, contractile dysfunction occurred before diaphragmatic atrophy both in sepsis group 1 and sepsis group 2. Second, compared with the control group, the dynamic parameters showed significant decrease in sepsis group 1 and more obvious change in sepsis group 2, including TF, EQB/EDB. Third, the maximum contractile velocity decreased in sepsis group 1, reflecting the damage of intrinsic contraction efficiency accurately. Finally, per breathing AUDMC in two septic groups were lower than those in control group. However, per minute AUDMC was compensated by increasing respiratory rate in sepsis group 1, whereas it failed to be compensated which indicated gradual failure of diaphragm in sepsis group 2. Diaphragmatic ultrasound can be used to quantitatively evaluate the severity of sepsis patients whose contractile dysfunction occurred before diaphragmatic atrophy. As dynamic parameters, TF and EQB/EDB are early indicator associated with diaphragmatic injury. Furthermore, maximum contractile velocity can reflect intrinsic contraction efficiency accurately. AUDMC can evaluate diaphragmatic breathing effort and endurance to overcome resistance loads effectively.

Natural starch mainly consists of two forms of α-D-glucan, i.e. amylose and amylopectin. The ratio of these two components is not only related to gelatinization, retrogradation, gelation and other physicochemical properties and food functions of starch, but also determines the economic value of starch. This means, the quantification technologies of amylose/amylopectin ratio determination can be widely used in grain crop breeding, high-value utilization of starch and the quality assurance and innovation of food. In this paper, the diverse demands of the quantification of amylose/amylopectin ratio in the field of food science research and production are reviewed. The principles, pros and cons, and applications of various classic and novel quantitative technology of amylose/amylopectin ratio are reviewed and compared. The innovative application of the quantitative technology of amylose/amylopectin ratio in future food-related fields is also prospected.

In order to study the effects of heat treatment and antioxidant addition on the digestive characteristics of meat oil of Antarctic krill, an in vitro gastrointestinal digestion model was established to measue the changes of peroxide value, acid value, malondialdehyde content, astaxanthin content and fatty acid composition of the oil in untreated blank group, 85 ℃ heat treatment group and 85 ℃ heat treatment with tert-butylhydroquinone (TBHQ) group after digestion. The results showed as follows: After gastrointestinal digestion, the peroxide value, acid value and malondialdehyde content of oil in blank group significantly increased (P

H2RDC (heuristic handover based on RCC-DTSK-C), a heuristic algorithm based on a highly interpretable deep Takagi–Sugeno–Kang fuzzy classifier, is proposed for suppressing the mobile heterogeneous networks problem of frequent handover and handover ping-pong in the multibase-station scenario. This classifier uses a stack structure between subsystems to form a deep classifier before generating a base station (BS) priority sequence during the handover process, and adaptive handover hysteresis is calculated. Simulation results show that H2RDC allows user equipment to switch to the best antenna at the optimal time. In high-BS density load and mobility scenarios, the proposed algorithm’s handover success rate is similar to those of classic algorithms such as best connection (BC), self tuning handover algorithm (STHA), and heuristic for handover based on AHP-TOPSIS-FUZZY (H2ATF). Moreover, the handover rate is 83% lower under H2RDC than under BC, whereas the handover ping-pong rate is 76% lower.

The human gastrointestinal mucosa is colonized by thousands of microorganisms, which participate in a variety of physiological functions. Intestinal dysbiosis is closely associated with the pathogenesis of several human diseases. Innate lymphoid cells (ILCs), which include NK cells, ILC1s, ILC2s, ILC3s and LTi cells, are a type of innate immune cells. They are enriched in the mucosal tissues of the body, and have recently received extensive attention. The gut microbiota and its metabolites play important roles in various intestinal mucosal diseases, such as inflammatory bowel disease (IBD), allergic disease, and cancer. Therefore, studies on ILCs and their interaction with the gut microbiota have great clinical significance owing to their potential for identifying pharmacotherapy targets for multiple related diseases. This review expounds on the progress in research on ILCs differentiation and development, the biological functions of the intestinal microbiota, and its interaction with ILCs in disease conditions in order to provide novel ideas for disease treatment in the future.

Sulfur poisoning could result in fast deterioration of Pd-based membranes by the formation of metal sulfides and reduction of hydrogen purity. The introduction of an MoO2/TS-1 layer could provide an effective protection of the Pd layer. Therefore, in this paper a synthetic method is presented for preparation of sulfur-resistant MoO2/TS-1 zeolite modified PdCu alloy composite membranes and their application in hydrogen separation under H2S containing steam. According to the stability test results, the MoO2/TS-1 zeolite armored layer obviously prolonged the stability of Pd based membrane. After 50 h stability test with 100 ppm H2S, there were no obvious structural changes and metal sulfide formation detected in the PdCu bulk from SEM images and XRD patterns, indicating that MoO2/TS-1 armor structure was good enough for protecting the PdCu alloy bulk.

Cold seep foraminifera have attracted considerable attention as they provide valuable insights into the study of cold seeps. This study provides a comprehensive overview of the manifestations of foraminifera in cold seep environments and methane seepage activities. Certain taxa of benthic foraminifera, such as Uvigerina, Bolivina, Bulimina, Chilostomella, Globobulimina, Nonionella, Melonis, Epistominella, Cibicidoides, and Globocassidulina, are known to inhabit geochemical conditions induced by methane-rich environments and may feed on associated methanotrophic microbial communities. Secondary mineralization on foraminifera shells is a widespread manifestation in seep sediments, and alters the microstructure, elementary composition, and isotopic signatures of foraminifera. On one hand, the precipitation of secondary authigenic Mg-rich, Mn-rich, Sr-rich, and Ba-rich calcite coatings have been observed on microfossils. On the other hand, micron-sized crystal pyrite and gypsum aggregates can also grow on the foraminifera walls. The negative δ13C and positive δ18O anomalies in both planktonic and benthic foraminifera from seep-associated sediments can serve as proxies for tracing past seepage activities, either in their live form or being adulterated by methane-derived authigenic carbonate after deposition. Seeping activities are recognized with a significant impact on benthic foraminifera, and the presence of cold seep-related species and significant isotopic anomalies in shells can be used to reconstruct past methane seepage events. Intensive methane seepage tends to suppress benthic foraminifera populations, while moderate intensity seepage may lead to a thriving benthic foraminiferal community, with hypoxia-enduring taxa such as Uvigerina, Melonis, and Bulimina being predominant. In contrast, oxygen-loving epibenthic taxa such as Cibicidoides often occur in areas of low methane flux. Compared to planktonic foraminifera, the single species of benthic foraminifera can provide a more comprehensive record of seepage evolution. Live benthic specimens are preferred for in-situ seep studies, while the superimposition of secondary minerals on the original shells should not be ignored when observing dead individuals. The significance of the evolution of methane seepage, changes in environmental parameters of the living habitat, and species sensitivity in cold seeps are emphasized in explaining the variation in foraminiferal assemblages and fluctuations in stable isotopes.

Xinjiang grasslands play a crucial role in regulating the regional carbon cycle and maintaining ecosystem stability, and grassland net primary productivity (NPP) is highly vulnerable to drought. Drought events are frequent in Xinjiang due to the impact of global warming. However, there is a lack of more systematic research results on how Xinjiang grassland NPP responds to drought and how its heterogeneity is characterized. In this study, the CASA (Carnegie Ames Stanford Application) model was used to simulate the 1982–2020 grassland NPP in Xinjiang, and the standardized Precipitation Evapotranspiration Index (SPEI) was calculated using meteorological station data to characterize drought. The spatial and temporal variability of NPP and drought in Xinjiang grasslands from 1982 to 2020 were analyzed by the Sen trend method and the Mann-Kendall test, and the response characteristics of NPP to drought in Xinjiang grasslands were investigated by the correlation analysis method. The results showed that (1) the overall trend of NPP in Xinjiang grassland was increasing, and its value was growing season > summer > spring > autumn. Mild drought occurred most frequently in the growing season and autumn, and moderate drought occurred most frequently in spring. (2) A total of 64.63% of grassland NPP had a mainly concurrent effect on drought, and these grasslands were primarily located in the northern region of Xinjiang. The concurrent effect of drought on NPP was strongest in plain grassland and weakest in alpine subalpine grassland. (3) The lagged effect is mainly in the southern grasslands, the NPP of alpine subalpine meadows, meadows, and alpine subalpine grasslands showed mainly a 1-month time lag effect to drought, and desert grassland NPP showed mainly a 3-month time lag effect to drought. This research can contribute to a reliable theoretical basis for regional sustainable development.

In the process of climate warming, drought has increased the vulnerability of ecosystems. Due to the extreme sensitivity of grasslands to drought, grassland drought stress vulnerability assessment has become a current issue to be addressed. First, correlation analysis was used to determine the characteristics of the normalized precipitation evapotranspiration index (SPEI) response of the grassland normalized difference vegetation index (NDVI) to multiscale drought stress (SPEI-1 ~ SPEI-24) in the study area. Then, the response of grassland vegetation to drought stress at different growth periods was modeled using conjugate function analysis. Conditional probabilities were used to explore the probability of NDVI decline to the lower percentile in grasslands under different levels of drought stress (moderate, severe and extreme drought) and to further analyze the differences in drought vulnerability across climate zones and grassland types. Finally, the main influencing factors of drought stress in grassland at different periods were identified. The results of the study showed that the spatial pattern of drought response time of grassland in Xinjiang had obvious seasonality, with an increasing trend from January to March and November to December in the nongrowing season and a decreasing trend from June to October in the growing season. August was the most vulnerable period for grassland drought stress, with the highest probability of grassland loss. When the grasslands experience a certain degree of loss, they develop strategies to mitigate the effects of drought stress, thereby decreasing the probability of falling into the lower percentile. Among them, the highest probability of drought vulnerability was found in semiarid grasslands, as well as in plains grasslands and alpine subalpine grasslands. In addition, the primary drivers of April and August were temperature, whereas for September, the most significant influencing factor was evapotranspiration. The results of the study will not only deepen our understanding of the dynamics of drought stress in grasslands under climate change but also provide a scientific basis for the management of grassland ecosystems in response to drought and the allocation of water in the future.

In the original publication [...]