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Abstract Probe-based nucleic acid enrichment represents an effective route to enhance the detection capacity of next-generation sequencing (NGS) in a set of clinically diverse and relevant microbial species. In this study, we assessed the effect of the enrichment-based sequencing on identifying respiratory infections using tiling RNA probes targeting 76 respiratory pathogens and sequenced using both Illumina and Oxford Nanopore platforms. Forty respiratory swab samples pre-tested for a panel of respiratory pathogens by qPCR were used to benchmark the sequencing data. We observed a general improvement in sensitivity after enrichment. The overall detection rate increased from 73 to 85% after probe capture detected by Illumina. Moreover, enrichment with probe sets boosted the frequency of unique pathogen reads by 34.6 and 37.8-fold for Illumina DNA and cDNA sequencing, respectively. This also resulted in significant improvements on genome coverage especially in viruses. Despite these advantages, we found that library pooling may cause reads mis-assignment, probably due to crosstalk issues arise from post-capture PCR and from pooled sequencing, thus increasing the risk of bleed-through signal. Taken together, an overall improvement in the breadth and depth of pathogen coverage is achieved using enrichment-based sequencing method. For future applications, automated library processing and pooling-free sequencing could enhance the precision and timeliness of probe enrichment-based clinical metagenomics.

Abstract In recent years, the prevalence and fatality rates of atherosclerotic cardiovascular disease have not only shown a consistent rise that cannot be ignored, but have also become a pressing social health problem that requires urgent attention. While interventional surgery and drug therapy offer significant therapeutic results, they often come with common side effects. Geniposide, an active component extracted from the Chinese medicine Gardenia jasminoides Ellis, shows promise in the management of cardiac conditions. This review comprehensively outlines the underlying pharmacological mechanisms by which geniposide exerts its effects on atherosclerosis. Geniposide exhibits a range of beneficial effects including alleviating inflammation, inhibiting the development of macrophage foam cells, improving lipid metabolism, and preventing platelet aggregation and thrombosis. It also demonstrates mitochondrial preservation, anti-apoptotic effects, and modulation of autophagy. Moreover, geniposide shows potential in improving oxidative stress and endoplasmic reticulum stress by maintaining the body’s antioxidant and oxidative balance. Additionally, this review comprehensively details the biological properties of geniposide, including methods of extraction and purification, as well as its pharmacokinetics and toxicological characteristics. It further discusses the clinical applications of related biopharmaceuticals, emphasizing the potential of geniposide in the prevention and treatment of atherosclerotic cardiovascular diseases. Furthermore, it highlights the limitations of current research, aiming to provide insights for future studies. Graphical Abstract

Abstract Background Caregiver self-efficacy is crucial in improving patient outcomes and caregiver well-being, but there is a lack of suitable scales to assess this concept within the context of Chinese culture. This study aimed to cross-culturally translate the Caregiver Self-Efficacy in Contributing to Patient Self-Care (CSE-CSC) Scale and evaluate its psychometric properties using classical test theory and item response theory. Methods The CSE-CSC scale was adapted using Brislin’s translation model after obtaining authorization from the original author. A multicenter, cross-sectional study was conducted to assess the psychometric properties of this scale. Classical test theory was used to evaluate reliability (internal consistency, test-retest reliability), validity (content validity, structural validity, convergent validity), and floor and ceiling effects. Item response theory was employed to assess the fit of the rating scale model, reliability, item difficulties, and measurement invariance. Results The translation and cultural adaptation process was completed. Classical test theory demonstrated good internal consistency (Cronbach’s α = 0.935) and test-retest reliability (ICC from 0.784 to 0.829, p2, person/item reliability coefficients>0.8). The Wright map showed that item difficulty matched the respondents’ measured abilities. The analysis of differential item functioning (DIF) showed that all items were comparable in gender. Conclusions This study indicated that the CSE-CSC scale had good reliability, validity, difficulty degree, and measurement invariance. The CSE-CSC scale can be used to measure caregiver self-efficacy of Chinese patients with multiple chronic conditions.

Summary: Background: Loss of heterozygosity (LOH) diminishes genetic diversity within cancer genomes. A tumour arising in an individual heterozygous for a functional and a loss-of-function (LoF) allele of a gene occasionally retain only the LoF allele. This can result in deficiency of specific protein activities in cancer cells, creating unique differences between tumour cells and normal cells of the individual. Such differences may constitute vulnerabilities that can be exploited through allele-specific therapies. Methods: To discover frequently lost genes with prevalent LoF alleles, we mined the 1000 Genomes dataset for SNVs causing protein truncation through base substitution, indels or splice site disruptions, resulting in 60 LoF variants in 60 genes. From these, the variant rs3892097 in the liver enzyme CYP2D6 was selected because it is located within a genomic region that frequently undergoes LOH in several tumor types including hepatocellular cancers. To evaluate the relationship between CYP2D6 activity and the toxicities of anticancer agents, we screened 525 compounds currently in clinical use or undergoing clinical trials using cell model systems with or without CYP2D6 activity. Findings: We identified 12 compounds, AZD-3463, CYC-116, etoposide, everolimus, GDC-0349, lenvatinib, MK-8776, PHA-680632, talazoparib, tyrphostin 9, VX-702, and WZ-3146, using an engineered HEK293T cell model. Of these, talazoparib and MK-8776 demonstrated consistently heightened cytotoxic effects against cells with compromised CYP2D6 activity in engineered hepatocellular cancer cell models. Moreover, talazoparib displayed CYP2D6 genotype dependent effects on primary hepatocellular carcinoma organoids. Interpretation: Exploiting the loss of drug-metabolizing enzyme gene activity in tumor cells following loss of heterozygosity could present a promising therapeutic strategy for targeted cancer treatment. Funding: This work was funded by Barncancerfonden (T.S, PR2022-0099 and PR2020-0171, X.Z, TJ2021-0111), Cancerfonden (T.S, 211719Pj and D.G, 222449Pj), Vetenskapsrådet (T.S, 2020-02371 and D.G, 2020-04707), and the Erling Persson Foundation (T.S, 2020-0037 and T.S, 2023-0113).

Abstract Background Inflammatory bowel disease (IBD), a chronic inflammatory condition, is caused by several factors involving aberrant immune responses. Genetic factors are crucial in IBD occurrence. Mendelian randomization (MR) can offer a new perspective in understanding IBD’s genetic background. Methods Single nucleotide polymorphisms (SNPs) were considered instrumental variables (IVs). We analyzed the relationship between 731 immunophenotypes, 1,400 metabolite phenotypes, and IBD. The total effect was decomposed into indirect and direct effects, and the ratio of the indirect effect to the total effect was calculated. Results We identified the causal effects of HLA-DR-expressing CD14 + monocytes on IBD through MR analysis. The phenotype “HLA-DR expression on CD14 + monocytes” showed the strongest association among the selected 48 immune phenotypes. Chiro-inositol metabolites mediated the effect of CD14 + monocytes expressing HLA-DR on IBD. An increase in Chiro-inositol metabolites was associated with a reduced risk of IBD occurrence, accounting for 4.97%. Conclusion Our findings revealed a new pathway by which HLA-DR-expressing CD14 + monocytes indirectly reduced the risk of IBD occurrence by increasing the levels of Chiro-inositol metabolites. The results provided a new perspective on the immunoregulatory mechanisms underlying IBD, laying a theoretical foundation for developing new therapeutic targets in the future.

Abstract Percutaneous coronary intervention (PCI) addresses myocardial ischaemia, but a significant subset of patients encounter major adverse cardiovascular events (MACE) post‐treatment. This meta‐analysis investigated the relationship between the post‐PCI triglyceride‐glucose (TyG) index and MACE. Comprehensive searches of the Embase, PubMed, Cochrane Library, and Web of Science databases were conducted up to 3 March 2023, using relevant keywords. The effect size was determined based on I2 statistic using random‐effects models. Cluster‐robust standard errors crafted the dose–response curve, and the GRADE Evaluation Scale was employed to rate the quality of evidence. The group with the highest TyG index had significantly higher post‐PCI MACE rates than the lowest index group, with hazard ratios (HRs) of 2.04 (95% CI 1.65–2.52; I2 = 77%). Each unit increase in TyG index corresponded to HRs of 1.82 for MACE (95% CI 1.34–2.46; I2 = 92%), 2.57 for non‐fatal MI (95% CI 1.49–4.41; I2 = 63%), and 2.06 for revascularization (95% CI 1.23–3.50; I2 = 90%). A linear relationship between TyG index and MACE risk was established (R2 = 0.6114). For all‐cause mortality, the HR was 1.93 (95% CI 1.35–2.75; I2 = 50%), indicating a higher mortality risk with elevated TyG index. The GRADE assessment yielded high certainty for non‐fatal MI but low certainty for all‐cause mortality, revascularization, and MACE. The TyG index may predict risks of post‐PCI MACE, all‐cause mortality, non‐fatal MI, and revascularization, with varied levels of certainty. A potential linear association between the TyG index and MACE post‐PCI was identified. Future research should validate these findings.

Wound dressings play a critical role in promoting healing by protecting wounds from external contaminants and providing an optimal environment for tissue regeneration. Traditional dressings, such as gauze and cotton, offer basic physical barriers but lack the ability to maintain a moist wound environment, which is essential for healing. Modern dressings, particularly those incorporating electrospun nanofibers, have emerged as advanced solutions that can sustain moisture, absorb exudate, and support cell growth and migration. This Review covers recent advances in electrospinning technologies and the design of composite materials that integrate natural and synthetic polymers, bioactive agents, and nanomaterials to enhance wound healing. In addition, it highlights key studies demonstrating the efficacy of these composites in various wound models. The primary objective of this Review is to inspire and guide future research endeavors, address existing limitations, and shed light on the promising research prospects in the field of wound healing and tissue regeneration.

ObjectiveTo evaluate the effectiveness of multimodal features based on gait analysis and eye tracking for elderly people screening with subjective cognitive decline in the community.MethodsIn the study, 412 cognitively normal older adults aged over 65 years were included. Among them, 230 individuals were diagnosed with non-subjective cognitive decline and 182 with subjective cognitive decline. All participants underwent assessments using three screening tools: the traditional SCD9 scale, gait analysis, and eye tracking. The gait analysis involved three tasks: the single task, the counting backwards dual task, and the naming animals dual task. Eye tracking included six paradigms: smooth pursuit, median fixation, lateral fixation, overlap saccade, gap saccade, and anti-saccade tasks. Using the XGBoost machine learning algorithm, several models were developed based on gait analysis and eye tracking to classify subjective cognitive decline.ResultsA total of 161 gait and eye-tracking features were measured. 22 parameters, including 9 gait and 13 eye-tracking features, showed significant differences between the two groups (p

IntroductionCisplatin is a widely used chemotherapeutic agent prescribed to treat solid tumors. However, its clinical application is limited because of cisplatin- induced nephrotoxicity. A known complication of cisplatin is acute kidney injury (AKI). Deletion polymorphisms of GSTM1 and GSTT1, members of the glutathione S-transferase family, are common in humans and are presumed to be associated with various kidney diseases. However, the specific roles and mechanisms of GSTM1 and GSTT1 in cisplatin induced AKI remain unclear.MethodsTo investigate the roles of GSTM1 and GSTT1 in cisplatin-induced AKI, we generated GSTM1 and GSTT1 knockout mice using CRISPR-Cas9 technology and assessed their kidney function under normal physiological conditions and cisplatin treatment. Using ELISA kits, we measured the levels of oxidative DNA and protein damage, along with MDA, SOD, GSH, and the GSH/GSSG ratio in wild-type and GSTM1/GSTT1 knockout mice following cisplatin treatment. Additionally, oxidative stress levels and the expression of ferroptosis-related proteins in kidney tissues were examined through Western blotting, qPCR, immunohistochemistry, and immunofluorescence techniques.ResultsHere, we found that GSTT1 and GSTM1 were downregulated in the renal tubular cells of AKI patients and cisplatin-treated mice. Compared with WT mice, Gstm1/Gstt1-DKO mice were phenotypically normal but developed more severe kidney dysfunction and exhibited increased ROS levels and severe ferroptosis after injecting cisplatin.DiscussionOur study revealed that GSTM1 and GSTT1 can protect renal tubular cells against cisplatin-induced nephrotoxicity and ferroptosis, and genetic screening for GSTM1 and GSTT1 polymorphisms can help determine a standard cisplatin dose for cancer patients undergoing chemotherapy.

BackgroundThe escalating global economic burden of ischemic stroke poses a significant public health challenge amid global aging trends. The broad therapeutic efficacy of new antidiabetic drugs may offer new options in the prevention and treatment of ischemic stroke. Consistent conclusions regarding the relationship between novel antidiabetic agents and the risk of ischemic stroke remain elusive, and the causal relationship deserves further investigation.Materials and methodsThree novel antidiabetic drug targets were selected, and cis-expression quantitative trait loci (cis-eQTL) were screened as instrumental variables. Genetic association data for ischemic stroke were obtained from the Genome-wide Association Study (GWAS) database. Mendelian randomization (MR) analysis, facilitated by R software, calculated MR estimates for each single nucleotide polymorphism (SNP), and meta-analysis was performed using five methods. To ensure robustness, sensitivity analyses, heterogeneity analyses, horizontal pleiotropy analyses, and co-localization analyses were conducted for significant MR associations.ResultsThree eQTLs for antidiabetic drug genes served as instrumental variables, utilizing a GWAS dataset comprising 34,217 cases and 406,111 controls for ischemic stroke. Genetic variants in glucagon-like peptide-1 receptor agonists (GLP-1 RA) targets exhibited a positive correlation with ischemic stroke risk (OR 1.06, 95% CI 1.04–1.08, P = 0.000), while genetic variation in dipeptidyl peptidase 4 inhibitors (DPP-4i) targets showed a negative association with ischemic stroke risk (OR 0.93, 95% CI 0.89–0.97, P = 0.003). Sensitivity analyses supported robust conclusions, revealing no heterogeneity or horizontal pleiotropy.ConclusionThis study found that GLP-1 RA and DPP-4i were associated with an increased risk of ischemic stroke by MR analysis. Although sensitivity analyses provide support for this result, it contradicts previous knowledge. Therefore, the results of this study still need to treated with caution. Updated and more in-depth GWAS data and high-quality real-world data are expected to validate the results.

In real forest fire scenarios, there are a large number of convex and concave terrains at the junction of flat land and slopes. In this paper, a typical charring material, kraft paper, is selected as the experimental sample, and the variation law of key characteristic parameters of flame spread over convex solid surface are investigated. The experimental results show that all the flame spread processes have obvious deceleration behaviors, and the influence mechanism of flame tangent angle on the flame spread deceleration of convex surfaces is revealed. The characteristic length of the pyrolysis zone shows a tendency of increasing and then decreasing with time. The variation curves of radiant heat flux present two peaks. Combining with the characteristic length, the reason for the occurrence of two peaks is explained. The exponential relationship between the instantaneous mass loss rate and the characteristic length of the pyrolysis zone is obtained. Based on the range of power exponents, the heat transfer controlling mechanism in the pyrolysis zone is classified into three categories for all the working conditions. Moreover, a piecewise power-law relationship between the dimensionless maximum flame height and the dimensionless heat release rate is established. The results of this study will fill the research gap of flame spread of solid materials with curved surfaces, and will be of great academic value for the improvement and development of theories on building and forest fire safety.

IntroductionPrevious research has established associations between alterations in gut microbiota composition and various gynecologic tumors. However, establishing a causal relationship between gut microbiota and these tumors remains necessary. This study employs a two-sample Mendelian randomization (MR) approach to investigate causality, aiming to identify pathogenic bacterial communities potentially involved in gynecologic tumor development.MethodsData from the MiBioGen consortium’s Genome-Wide Association Study (GWAS) on gut microbiota were used as the exposure variable. Four common gynecologic neoplasms, including uterine fibroids (UF), endometrial cancer (EC), ovarian cancer (OC), and cervical cancer (CC), were selected as outcome variables. Single-nucleotide polymorphisms (SNPs) significantly associated with gut microbiota were chosen as instrumental variables (IVs). The inverse variance-weighted (IVW) method was used as the primary MR analysis to assess the causal relationship. External validation An was conducted using an independent. Sensitivity analyses were performed to ensure robustness. Reverse MR analysis was also conducted to assess potential reverse causation.ResultsCombining discovery and validation cohorts, we found that higher relative abundance of Lachnospiraceae is associated with lower UF risk (OR: 0.882, 95% CI: 0.793-0.982, P = 0.022). Conversely, higher OC incidence is associated with increased relative abundance of Lachnospiraceae (OR: 1.329, 95% CI: 1.019–1.732, P = 0.036). Sensitivity analyses confirmed these findings’ reliability. Reverse MR analysis showed no evidence of reverse causation between UF, OC, and Lachnospiraceae.DiscussionThis study establishes a causal relationship between Lachnospiraceae relative abundance and both UF and OC. These findings provide new insights into the potential role of gut microbiota in mechanisms underlying gynecological tumors development.

Abstract Nano drug delivery systems have been widely used in tumor therapy. Researchers have been devoted to exploring novel nano‐carriers to prolong circulation time biocompatibility and tumor targeting efficiency in vivo. Erythrocyte membranes as bionic nano‐drug delivery systems have attracted more attention recently. There are abundant red blood cells (RBCs) in circulation, which are natural carriers for nanomaterial delivery. There are mainly two strategies to use RBCs as nanomaterial carriers: RBC‐hitchhiking and bionic nanomaterial coated with erythrocyte membrane loading with drugs. Although nano‐carrier based on RBCs have yielded some progress, the mechanism of mutual effect between nanoparticles and RBCs is still unclear. Here, we review the effects of nanoparticles on RBCs (morphology and function, etc) and application of RBCs membrane as nano‐drug delivery carriers in tumor therapy.

Background: Most studies used animal serum-containing medium for bioengineered-root regeneration, but ethical and safety issues raised by animal serum are a potentially significant risk for clinical use. Thus, this study aimed to find a safer method for bioengineered-root regeneration. Methods: The biological properties of human dental pulp stem cells (hDPSCs) cultured in animal component-free (ACF) medium or serum-containing medium (5%, 10% serum-containing medium, SCM) were compared in vitro. hDPSCs were cultured in a three-dimensional (3D) environment with human-treated dentin matrix (hTDM). The capacity for odontogenesis was compared using quantitative real-time PCR (qPCR) and Western blot. Subsequently, the hDPSCs/hTDM complexes were transplanted into nude mice subcutaneously. Histological staining was then used to verify the regeneration effect in vivo. Results: ACF medium promoted the migration of hDPSCs, but slightly inhibited the proliferation of hDPSCs in the first three days of culture compared to SCM. However, it had no significant effect on cell aging and apoptosis. After 7 days of 3D culture in ACF medium with hTDM, qPCR showed that DMP1, DSPP, OCN, RUNX2, and β-tubulin III were highly expressed in hDPSCs. In addition, 3D cultured hDPSCs/hTDM complexes in ACF medium regenerated dentin, pulp, and periodontal ligament-like tissues similar to SCM groups in vivo. Conclusion: ACF medium was proved to be an alternative medium for bioengineered-root regeneration. The strategy of using ACF medium to regenerate bioengineered-root can improve clinical safety for tooth tissue engineering.

Abstract Lake Fuxian is one of the deepest tectonic plateau freshwater lakes in the southeastern Tibetan Plateau, China. However, questions such as how old the lake is, how deep the total sedimentary thickness sequences are, and what landscape of the lake basin settings and geological structures are unknown. Here, based on fifteen seismic reflection profiles, we applied seismic facies and seismic sequence stratigraphic analyses to interpret the lake sequences. The results of the seismic response reveal that the maximum thickness of the sedimentation is ca. 1238 m and lies toward the NNE region of the lake basin on the L10-2 survey line. Lake sediments can be categorized into five seismic sequences and six seismic horizons. The oldest clinoforms in the deepest sequence (Sq-5) show that the depositional center was shifted to ~ 19 km from the NNE region to the SSW modern location and was ~ 930 m lower than the current lake floor. Multiple and complex tectonic activities strongly impacted on the lake basin, and a series of normal faults created an overall crustal extensional regime, resulting in the formation of many horst and graben structures.

Abstract Geoscientists now identify coal layers using conventional well logs. Coal layer identification is the main technical difficulty in coalbed methane exploration and development. This research uses advanced quantile–quantile plot, self-organizing maps (SOM), k-means clustering, t-distributed stochastic neighbor embedding (t-SNE) and qualitative log curve assessment through three wells (X4, X5, X6) in complex geological formation to distinguish coal from tight sand and shale. Also, we identify the reservoir rock typing (RRT), gas-bearing and non-gas bearing potential zones. Results showed gamma-ray and resistivity logs are not reliable tools for coal identification. Further, coal layers highlighted high acoustic (AC) and neutron porosity (CNL), low density (DEN), low photoelectric, and low porosity values as compared to tight sand and shale. While, tight sand highlighted 5–10% porosity values. The SOM and clustering assessment provided the evidence of good-quality RRT for tight sand facies, whereas other clusters related to shale and coal showed poor-quality RRT. A t-SNE algorithm accurately distinguished coal and was used to make CNL and DEN plot that showed the presence of low-rank bituminous coal rank in study area. The presented strategy through conventional logs shall provide help to comprehend coal-tight sand lithofacies units for future mining.

Most of the previous research about unmanned surface vehicle (USV) control system just focuses on reaching the target but not considers berthing. Moreover, computation cost is rarely concerned. For automatic target arriving and berthing of USV in presence of multi-shape convex obstacles and disturbances, this paper designs a composite control system including trajectory optimization and trajectory tracking. In order to generate a smooth and optimal trajectory, two objectives including minimum running time and energy consumption are proposed, and their priority requirement is presented. Fuzzy satisfactory optimization is introduced to reformulate the objective functions, and the membership degree difference is used to model priority between two objectives. The obstacle avoidance constraint is developed based on the improved P-criterion. The comprehensive optimization model is established to obtain the maximum membership degree. Further, the priority optimization model is proposed to expand the feasible domain by relaxing the comprehensive optimization result. Two models are discretized by Gaussian pseudospectral method to find the optimal solution. To achieve good trajectory tracking under disturbances, two first-order active disturbance rejection control (ADRC) controllers are designed to follow the desired longitudinal velocity and course angular velocity. All the velocities of USV can converge. The simulation proves the effectiveness of the proposed co-designed system by comparing with other methods.

Abstract Background The instrumental activities of daily living (IADL) among the elderly have been found to be heterogeneous, with different trajectories. However, the transition of the IADL over time remains unclear. We aimed to explore the transition probabilities and the predictors of IADL among the elderly. Methods Longitudinal data from the 2014 (T1) and 2018 (T2) waves of the Chinese Longitudinal Healthy Longevity Survey were extracted. A sample of 2,944 participants aged 65 years or older, with complete responses to the IADL scale, was included. Latent profile analysis (LPA) and latent transition analysis (LTA) were employed to identify latent profiles of IADL and investigate the transition probabilities between profiles from T1 to T2. The predictors of latent profiles and transition probabilities were examined using multinomial regression analysis. Results The results of LPA at both T1 and T2 supported a 4-profile model solution. They were labeled as the “Normal function profile,” “Mildly impaired profile,” “Moderately impaired profile,” and “Highly impaired profile”. The Normal function profile and Highly impaired profile were characterized by maintaining stability rather than transitioning over time, with transition probabilities of 0.71 and 0.68, respectively, for maintaining stability. The Mildly impaired profile and Moderately impaired profile were characterized by a stronger tendency towards transition rather than stability, with transition probabilities of 0.29 and 0.45, respectively, of transitioning to the Highly impaired profile. The transition probabilities from the three impaired function profiles to the Normal function profile ranged from 0.05 to 0.19. Age, gender, place of residence, and social participation were significant predictors of profile attribution at T1 and transition probabilities over time. Conclusions This study employed the LTA to examine the transition probability of IADL among the Chinese elderly. By recognizing the different profiles of IADL and understanding the factors associated with transitions among the elderly, interventions can be tailored to improve their functional independence and successful reintegration into families and society.

Abstract The population with dementia is expected to rise to 152 million in 2050 due to the aging population worldwide. Therefore, it is significant to identify and intervene in the early stage of dementia. The Rey-Osterreth complex figure (ROCF) test is a visuospatial test scale. Its scoring methods are numerous, time-consuming, and inconsistent, which is unsuitable for wide application as required by the high number of people at risk. Therefore, there is an urgent need for a rapid, objective, and sensitive digital scoring method to detect cognitive dysfunction in the early stage accurately. This study aims to clarify the organizational strategy of aMCI patients to draw complex figures through a multi-dimensional digital evaluation system. At the same time, a rapid, objective, and sensitive digital scoring method is established to replace traditional scoring. The data of 64 subjects (38 aMCI patients and 26 NC individuals) were analyzed in this study. All subjects completed the tablet's Geriatric Complex Figure (GCF) test, including copying, 3-min recall, and 20-min delayed recall, and also underwent a standardized neuropsychological test battery and classic ROCF test. Digital GCF (dGCF) variables and conventional GCF (cGCF) scores were input into the forward stepwise logistic regression model to construct classification models. Finally, ROC curves were made to visualize the difference in the diagnostic value of dGCF variables vs. cGCF scores in categorizing the diagnostic groups. In 20-min delayed recall, aMCI patients' time in air and pause time were longer than NC individuals. Patients with aMCI had more short strokes and poorer ability of detail integration (all p

Gamma-aminobutyric acid (GABA) signals in various non-neuronal cells including hepatocytes and some immune cells. Studies, including ours, show that type A GABA receptors (GABAARs)-mediated signaling occurs in macrophages regulating tissue-specific functions. Our recent study reveals that activation of GABAARs in liver macrophages promotes their M2-like polarization and increases HBV replication in mice. This short article briefly summarizes the GABA signaling system in macrophages and discusses potential mechanisms by which GABA signaling promotes HBV replication.

Accurate prediction of the structurally diverse complementarity determining region heavy chain 3 (CDR-H3) loop structure remains a primary and long-standing challenge for antibody modeling. Here, we present the H3-OPT toolkit for predicting the 3D structures of monoclonal antibodies and nanobodies. H3-OPT combines the strengths of AlphaFold2 with a pre-trained protein language model and provides a 2.24 Å average RMSDCα between predicted and experimentally determined CDR-H3 loops, thus outperforming other current computational methods in our non-redundant high-quality dataset. The model was validated by experimentally solving three structures of anti-VEGF nanobodies predicted by H3-OPT. We examined the potential applications of H3-OPT through analyzing antibody surface properties and antibody–antigen interactions. This structural prediction tool can be used to optimize antibody–antigen binding and engineer therapeutic antibodies with biophysical properties for specialized drug administration route.

To further enhance the application of nobiletin (an important active ingredient in Citrus fruits), we used ultrasonic homogenization-assisted antisolvent precipitation to create ultrafine particles of nobiletin (UPN). DMSO was used as the solvent, and deionized water was used as the antisolvent. When ultrasonication (670 W) and homogenization (16000 r/min) were synergistic, the solution concentration was 57 mg/mL, and the minimum particle size of UPN was 521.02 nm. The UPN samples outperformed the RN samples in terms of the inhibition of porcine pancreatic lipase, which was inhibited (by 500 mg/mL) by 68.41 % in the raw sample, 90.34 % in the ultrafine sample, and 83.59 % in the positive control, according to the data. Fourier transform infrared spectroscopy analysis revealed no chemical changes in the samples before or after preparation. However, the crystallinity of the processed ultrafine nobiletin particles decreased. Thus, this work offers significant relevance for applications in the realm of food chemistry and indirectly illustrates the expanded application potential of nobiletin.

Background: Human-treated dentin matrix (hTDM) has recently been studied as a natural extracellular matrix-based biomaterial for dentin pulp regeneration. However, porcine-treated dentin matrix (pTDM) is a potential alternative scaffold due to limited availability. However, there is a dearth of information regarding the protein composition and underlying molecular mechanisms of pTDM.Methods: hTDM and pTDM were fabricated using human and porcine teeth, respectively, and their morphological characteristics were examined using scanning electron microscopy. Stem cells derived from human exfoliated deciduous teeth (SHEDs) were isolated and characterized using flow cytometry and multilineage differentiation assays. SHEDs were cultured in three-dimensional environments with hTDM, pTDM, or biphasic hydroxyapatite/tricalcium phosphate. The expression of odontogenesis markers in SHEDs were assessed using real-time polymerase chain reaction and immunochemical staining. Subsequently, SHEDs/TDM and SHEDs/HA/TCP complexes were transplanted subcutaneously into nude mice. The protein composition of pTDM was analyzed using proteomics and compared to previously published data on hTDM.Results: pTDM and hTDM elicited comparable upregulation of odontogenesis-related genes and proteins in SHEDs. Furthermore, both demonstrated the capacity to stimulate root-related tissue regeneration in vivo. Proteomic analysis revealed the presence of 278 protein groups in pTDM, with collagens being the most abundant. Additionally, pTDM and hTDM shared 58 identical proteins, which may contribute to their similar abilities to induce odontogenesis. Conclusions: Both hTDM and pTDM exhibit comparable capabilities in inducing odontogenesis, potentially owing to their distinctive bioactive molecular networks.

Abstract The participation of external scientific research teams is an important support for the success of open innovation of scientific and technological-based small and medium enterprise (SMEs). The incentive mechanism should not only focus on traditional influencing factors but also on the scientific research innovation team’s internal characteristics and external environment. Considering the fairness preference of scientific research innovation teams, this paper constructs an open innovation reputation incentive model for scientific and technological-based SMEs and discusses the impact of relevant factors on the reputation and effort level of scientific research innovation teams under the situation of complete information and incomplete information. The results show that: (1) under the condition of complete information, the fairness preference of scientific research innovation teams is positively related to reputation incentive other than the effort level; (2) under the condition of incomplete information, the fairness preference of scientific research innovation teams has no significant impact on the reputation incentive but is negatively related to the effort level; (3) whether considering the fairness preference or not, the effort level and innovation capability of the scientific research innovation teams are positively correlated with the reputation incentive, while the effort cost, risk aversion coefficient, income distribution coefficient, and variance of external environment variable are negatively correlated with the reputation incentive; (4) the innovation ability of scientific research innovation teams is positively related to the effort level, while the effort cost, risk aversion coefficient, and variance of external environment variable are negatively related to the effort level.

Abstract Backgrounds Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia. Maintaining a balance between the proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs) is crucial for preventing the erosion of bone and cartilage and, ultimately, mitigating the progression of RA. We found that the lncRNA LEF1-AS1 was expressed at low levels in the RASFs and inhibited their abnormal proliferation by targeting PIK3R2 protein and regulating the PI3K/AKT signal pathway through its interaction with miR-30-5p. In this study, we fabricated a nano-drug delivery system for LEF1-AS1 using Zn-Adenine nanoparticles (NPs) as a novel therapeutic strategy against RA. Methods The expression levels of LEF1-AS1, miR-30-5p, PIK3R2, p-PI3K, and p-AKT were detected in the primary RASFs and a human fibroblast-like synovial cell line (HFLS). Zn-Adenine nanoparticles (NPs) were functionalized with anti-CD305 antibody to construct (Zn-Adenine)@Ab. These NPs were then loaded with LEF1-AS1 to form (Zn-Adenine)@Ab@lncRNA LEF1-AS1. Finally, the (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs were locally injected into a rat model with collagen-induced arthritis (CIA). The arthritic injuries in each group were evaluated by HE staining and other methods. Results LEF1-AS1 was expressed at low levels in the primary RASFs. High expression levels of LEF1-AS1 were detected in the HFLS cells, which corresponded to a significant downregulation of miR-30-5p. In addition, the expression level of PIK3R2 was significantly increased, and that of p-PI3K and p-AKT were significantly downregulated in these cells. The (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly inhibited the proliferation of RASFs and decreased the production of inflammatory cytokines (IL-1β, IL-6, TNF-α). Intra-articular injection (IAI) of (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly alleviated cartilage destruction and joint injury in the CIA-modeled rats. Conclusions LEF1-AS1 interacts with miR-30-5p to inhibit the abnormal proliferation of RASFs by regulating the PI3K/AKT signal pathway. The (Zn-Adenine)@Ab NPs achieved targeted delivery of the loaded LEF1-AS1 into the RASFs, which improved the cellular internalization rate and therapeutic effects. Thus, LEF1-AS1 is a potential target for the treatment of RA.

Abstract Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death in the world. In most cases, drug resistance and tumor recurrence are ultimately inevitable. One obstacle is the presence of chemotherapy-insensitive quiescent cancer cells (QCCs). Identification of unique features of QCCs may facilitate the development of new targeted therapeutic strategies to eliminate tumor cells and thereby delay tumor recurrence. Here, using single-cell RNA sequencing, we classified proliferating and quiescent cancer cell populations in the human colorectal cancer spheroid model and identified ATF3 as a novel signature of QCCs that could support cells living in a metabolically restricted microenvironment. RNA velocity further showed a shift from the QCC group to the PCC group indicating the regenerative capacity of the QCCs. Our further results of epigenetic analysis, STING analysis, and evaluation of TCGA COAD datasets build a conclusion that ATF3 can interact with DDIT4 and TRIB3 at the transcriptional level. In addition, decreasing the expression level of ATF3 could enhance the efficacy of 5-FU on CRC MCTS models. In conclusion, ATF3 was identified as a novel marker of QCCs, and combining conventional drugs targeting PCCs with an option to target QCCs by reducing ATF3 expression levels may be a promising strategy for more efficient removal of tumor cells.

To address the challenges posed by the complex shapes of hollow parts, this study examined the ultrasonic-assisted granular medium hydroforming (UGMF) process for tubular components. The dynamics of the deformation behavior and deformation control during 6063-T5 aluminum alloy tube free forming by UGMF were studied via simulations and experiments. Based on the ABAQUS software platform, a coupled method based on finite element (FE) simulation analysis and discrete element (DE) analysis for the UGMF free forming process was used. The results showed that ultrasonic vibration (UV) could reduce the forming force required for expansion and promote the flow of material at the end to the forming area as well as inhibit the decrease in the wall thickness. The accuracy of the FE-DE coupled simulation model and a parabolic geometric model was verified by testing. The results found that UV enhances material flow, decreases the forming force needed, and minimizes damage to the granular surface.

The demand for accurate and efficient immunoassays calls for the development of precise, high-throughput analysis methods. This paper introduces a novel approach utilizing a weak measurement interface sensor for immunoassays, offering a solution for high throughput analysis. Weak measurement is a precise quantum measurement method that amplifies the weak value of a system in the weak interaction through appropriate pre- and post-selection states. To facilitate the simultaneous analysis of multiple samples, we have developed a chip with six flow channels capable of conducting six immunoassays concurrently. We can perform real-time immunoassay to determine the binding characteristics of spike protein and antibody through real-time analysis of the flow channel images and calculating the relative intensity. The proposed method boasts a simple structure, eliminating the need for intricate nano processes. The spike protein concentration and relative intensity curve were fitted using the Log-Log fitting regression equation, and R2 was 0.91. Utilizing a pre-transformation approach to account for slight variations in detection sensitivity across different flow channels, the present method achieves an impressive limit of detection(LOD) of 0.85 ng/mL for the SARS-CoV-2 the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, with a system standard deviation of 5.61. Furthermore, this method has been successfully verified for monitoring molecular-specific binding processes and differentiating binding capacities.

Quantitative assessment and trade-off/synergy analysis of land use multifunctions can effectively identify regional conflicts and dominant functions, providing decision support for promoting sustainable socio-economic and land use development. However, current research in this field still faces challenges due to coarse scale of studies and limited availability of accurate data. Taking Harbin City as a research case, this research employed an improved mutation level method, Pearson correlation analysis, and a multi-scale geographically weighted regression model to comprehensively investigate the profiling of land use multifunctions and their trade-off /synergy relationships. The comparative advantage theory was adopted to identify dominant functional zones using the NRCA index at a grid scale, in order to achieve a territorial spatial functional zoning delineation. The results showed that there were intricate trade-off/synergy relationships among production–living–ecology functions. Moreover, the types and intensity of trade-off/synergy evolved continuously with socio-economic development and regional resource endowment disparities. Due to its exceptional resource endowment, the agricultural dominated, urban dominated, and ecological dominated functional areas accounted for a significant proportion of 29%, 7%, and 26%, respectively. However, owing to the intricate trade-offs/synergies inherent in land use multifunctions, only a mere 2% (agricultural), 1% (urban), and 1% (ecological) of the area were identified as Optimization Guidance Zones. Conversely, Remediation Improvement Zones constituted the largest share at 63% of the total area, with agricultural, urban, and ecological Remediation Improvement Zones accounting for approximately 33%, 12%, and 18%, respectively. Based on the results of the type and intensity of trade-off/synergy among production–living–ecological functions, as well as the dominant zones and the integrated territorial spatial functional zoning delineation, this article provided targeted recommendations for the sustainable development of the region. These recommendations took into account both resource endowment and socio-economic development characteristics specific to the study area. The study aims to contribute to related research gaps, while providing valuable insights for other regional studies.

Abstract Background Gene expression signatures can be used as prognostic biomarkers in various types of cancers. We aim to develop a gene signature for predicting the response to radiotherapy in glioma patients. Methods Radio-sensitive and radio-resistant glioma cell lines (M059J and M059K) were subjected to microarray analysis to screen for differentially expressed mRNAs. Additionally, we obtained 169 glioblastomas (GBM) samples and 5 normal samples from The Cancer Genome Atlas (TCGA) database, as well as 80 GBM samples and 4 normal samples from the GSE7696 set. The “DESeq2” R package was employed to identify differentially expressed genes (DEGs) between the normal brain samples and GBM samples. Combining the prognostic-related molecules identified from the TCGA, we developed a radiosensitivity-related prognostic risk signature (RRPRS) in the training set, which includes 152 patients with glioblastoma. Subsequently, we validated the reliability of the RRPRS in a validation set containing 616 patients with glioma from the TCGA database, as well as an internal validation set consisting of 31 glioblastoma patients from the Nanfang Hospital, Southern Medical University. Results Based on the microarray and LASSO COX regression analysis, we developed a nine-gene radiosensitivity-related prognostic risk signature. Patients with glioma were divided into high- or low-risk groups based on the median risk score. The Kaplan–Meier survival analysis showed that the progression-free survival (PFS) of the high-risk group was significantly shorter. The signature accurately predicted PFS as assessed by time-dependent receiver operating characteristic curve (ROC) analyses. Stratified analysis demonstrated that the signature is specific to predict the outcome of patients who were treated using radiotherapy. Univariate and multivariate Cox regression analysis revealed that the predictor was an independent predictor for the prognosis of patients with glioma. The prognostic nomograms accompanied by calibration curves displayed the 1-, 2-, and 3-year PFS and OS in patients with glioma. Conclusion Our study established a new nine-gene radiosensitivity-related prognostic risk signature that can predict the prognosis of patients with glioma who received radiotherapy. The nomogram showed great potential to predict the prognosis of patients with glioma treated using radiotherapy.

Background and objective The relationship between nutritional status and prognosis of cancer patients has emerged as a hotspot for research. The aim of this study is to explore the application value of the geriatric nutritional risk index (GNRI) in assessing the prognosis of elderly patients with non-small cell lung cancer (NSCLC), and establish a Nomogram to predict the prognosis of elderly patients with NSCLC. Methods The data of patients with NSCLC aged ≥65 years who were initially treated in the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019 were retrospectively analyzed. To determine the optimal cut-off value for GNRI, receiver operating characteristic (ROC) curve was constructed, and the patients were divided into high and low GNRI groups. Kaplan-Meier curve and Log-rank test were used to compare overall survival (OS) of the two groups. Univariate and multivariate Cox regression was used to analyze the risk factors for poor prognosis in elderly patients with NSCLC. Nomogram predicting survival in elderly patients with NSCLC was constructed and validated by using R software. Results Statistically significant differences in age, gender, body mass index (BMI), histological type, albumin, treatment methods, neutrophil to lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII) and cytokeratin 19 fragment (CYFRA21-1) were observed between the high and low GNRI groups (P3.3 ng/mL was an independent risk factor for the development of OS in patients with NSCLC, and GNRI>97.09 was a protective factor [hazard ratio (HR)=0.52, 95% confidence interval (CI): 0.34-0.79, P

In order to evaluate the potential application of pigskin collagen peptides (PCP) in fresh pork stuffing products, the effects of PCP content (0.5%, 1%, 2%, 4% and 6%) on the quality characteristics, water distribution and microstructure of fresh pork stuffing were investigated in this study. For comparison, the pork stuffing without PCP and the pork stuffing with a compound modifier (2% soybean protein and 0.15% carrageenan) were used as blank and control, respectively. The results showed that when the PCP content was more than 2%, the cooking loss rate of the sample was significantly reduced (P

Summary: Background: Living with heart failure can severely affect the physical and mental health of patients with heart failure and their caregivers. Available dyadic self-care interventions for heart failure are scarce, especially in China. We aimed to develop and test the family FOCUS programme. Methods: This single-blind, randomised, controlled study was conducted at four hospitals in Tianjin, China. Patients with heart failure (aged at least 18 years) and their caregiver (dyads) were randomly assigned to either the intervention (n = 71) or control (n = 71) group in a 1:1 ratio. The primary outcomes of this study were patient self-care, with three specific dimensions (self-care maintenance, symptom perception, and self-care management), and caregiver contribution to self-care, mirroring these three dimensions. The outcomes were assessed at baseline (T0) and 4 (T1), 12 (T2), and 24 (T3) weeks post-discharge, respectively. This work is registered on ChiCTR, ChiCTR2100053168. Findings: Between May 20, 2022, and September 30, 2022, 142 dyads with heart failure were enrolled. The intervention group exhibited dropout rates of 6%, 8.5%, and 18.3% at 4, 12, and 24 weeks after discharge, while the control group showed 9.9%, 12.3%, and 25.4%. Compared with the control group, patients in the intervention group reported improved self-care maintenance (β: 8.5, 95% CI: 0.7, 16.4) and management (β: 7.2, 95% CI: 0.1, 14.3) at T1, as well as improved symptom perception at both T1 (β: 9.7, 95% CI: 1.5, 17.9) and T2 (β: 9.6, 95% CI: 0.6, 18.6). Furthermore, caregiver contributions to self-care maintenance, self-care management, and symptom perception (excluding T3) exhibited significant improvements at all timepoints. Interpretation: Although the significant improvements in patients' self-care were not long-lasting, this study suggested that the family FOCUS programme consistently enhanced caregivers' contributions to self-care. Future work could explore the effect of the family FOCUS programme on families with multiple chronic conditions. Funding: The National Natural Science Foundation of China.

To apply the natural ingredients of plants in the field of food preservation, the essential oil of Cinnamomum camphor peel was isolated by salt-out pretreatment and microwave-assisted hydrodistillation. Using the single-factor mixed response surface approach, the extraction yield was optimized. A total of 14.98 mL/kg DW (dry weight: DW) was the greatest essential oil yield recorded. By using GC–MS analysis, a total of 29 compounds were found in the essential oil, with methyl eugenol (12.66 %) and safrole (10.36 %) being the two predominant compounds. However, the essential oil had a clear inhibitory effect on Pseudocercospora psidii at a concentration of 10 mg/mL. In conclusion, Cinnamomum camphora pericarp essential oil is anticipated to be a green natural pesticide that significantly inhibits pathogenic bacteria in crops.

With more and more vehicles becoming autonomous, intelligent, and connected, paying attention to the future usage of car human-machine interface (HMI) with these vehicles should also get more relevant. While car HMI has been addressed in several scientific studies, little attention is being paid to designing and implementing interactive glazing into everyday (autonomous) driving contexts. Through reflecting on what was found before in theory and practice, we describe an engineering psychology practice and the design of six novel future user scenarios, which envision the application of a specific set of augmented reality (AR) support user interactions. We also present evaluations conducted with the scenarios and experiential prototypes and found that these AR scenarios support our target user groups in experiencing a new type of interactions. The overall evaluation was positive, with some valuable assessment results and suggestions. We envision that this paper will interest applied psychology educators who aspire to teach how to operationalize AR in a human-centered design (HCD) process to students with little preexisting expertise or little scientific knowledge about engineering psychology.

In order to further develop the commercial use of Melaleuca bracteata (F. Muell), this report studied the extraction of essential oil from Melaleuca bracteata (F. Muell) leaves using ultrasonic pretreatment, cellulase-inorganic salt soaked and combined with microwave-assisted hydrodistillation. To optimize the primary contributing parameters, the Box–Behnken design (BBD) was applied. The optimum yield of essential oil was 9.61 mL/kg DW at a microwave power of 510.77 W, lithium chloride dose of 63.56 μmol, and microwave irradiation period of 46.97 min. The essential oil included a total of 41 compounds, and methyl eugenol (76.53%) and methyl cinnamate (12.62%) were the main compounds. The inhibitory impact was notable when the essential oil concentration was 1.6 mg/mL. Therefore, it has the potential to replace chemical pesticides. When the concentration of the essential oil solution was 1.6 mg/mL, the three pathogenic species of fungus (Pseudocercospora psidii, Colletotrichum eriobotryae, and Colletotrichum siamense) were greatly affected; at this dose, the fungus was unable to develop and its growth diameter was 0 mm. Additionally, the fungus’s inhibition rate reached 100%.

To explore the impacts of multiple environmental stressors on animal communities in aquatic ecosystems, we selected protozoa—a highly sensitive group of organisms—to assess the effect of environmental change. To conduct this simulation we conducted a three-factor, outdoor, mesocosm experiment from March to November 2021. Changes in the community structure and functional group composition of protozoan communities under the separate and combined effects of these three environmental stressors were investigated by warming and the addition of nitrogen, phosphorus, and pesticides. The results were as follows: (1) Both eutrophication and pesticides had a considerable promotional effect on the abundance and biomass of protozoa; the effect of warming was not considerable. When warming was combined with eutrophication and pesticides, there was a synergistic effect and antagonistic effect, respectively. (2) Eutrophication promoted α diversity of protozoa and affected their species richness and dominant species composition; the combination of warming and pesticides remarkably reduced the α diversity of protozoa. (3) Warming, eutrophication, and pesticides were important factors affecting the functional groups of protozoa. Interaction among different environmental factors could complicate changes in the aquatic ecological environment and its protozoan communities. Indeed, in the context of climate change, it might be more difficult to predict future trends in the protozoan community. Therefore, our results provide a scientific basis for the protection and restoration of shallow lake ecosystems; they also offer valuable insights in predicting changes in shallow lakes.

IntroductionExercise addiction (EA) is a dysfunctional behavior characterized by exaggerated training which has adverse effects on physiology and psychology. To examine the reliability and validity of the Chinese version of the Exercise Dependence Scale-Revised (EDS-R) and the social and psychological aspects related to EA, a large sample behavioral study was conducted.MethodsCollege students were selected as the target group. All of them were asked to finish the scales about exercise, including the Chinese version of EDS-R and the Motives for Physical Activity Measure-Revised scales. A confirmatory factor analysis, Mann-Whitney U test, and hierarchical regression test were performed to test the reliability and validity of the Chinese version of EDS-R and find the explanatory variables of EA.ResultsA total of 837 (556 female) students with a mean age of 20.38 years were recruited in the present study. The Chinese version of EDS-R showed good reliability and validity (McDonald’s ω = 0.973, CR = 0.99, AVE = 0.80) in Chinese college students. EA was positively correlated with exercise frequency and ability motivation across the study sample. Besides, the Mann-Whitney U test revealed that the exercise motivation difference is the primary cause of the gender gap in EA.ConclusionThe Chinese version of EDS-R is a relatively robust and accurate instrument to assess the risk of EA. Additionally, exercise frequency and motivation may be the potential risk factors for EA. The screening of risk factors is of great significance for the early detection and prevention of EA.

The study of pressure stimulated current (PSC) changes of rocks is significant to monitor dynamic disasters in mines and rock masses. The existing studies focus on change laws and mechanism of currents generated under the loading of rocks. An electrical and mechanics test system was established in this paper to explore the impacts of loading rates on PSCs. The results indicated that PSC curves of different rocks had different change laws under low/high loading rates. When the loading rate was relatively low, PSC curves firstly changed gently and then increased exponentially. Under high loading rates, PSC curves experienced the rapid increase stage, gentle increase stage and sudden change stage. The compressive strength could greatly affect the peak PSC in case of rock failure. The loading rate was a key factor in average PSC. Under low loading rates, the variations of PSCs conformed to the damage charge model of fracture mechanics, while they did not at the fracture moment. Under high loading rates, the PSCs at low stress didn’t fit the model due to the stress impact effects. The experimental results could provide theoretical basis for the influence of loading rates on PSCs.

Due to a large number of mutations in the spike protein and immune escape, the Omicron variant (B.1.1.529) has become a predominant variant of concern (VOC) strain. To prevent the disease, we developed a candidate inactivated vaccine (Omicron COVID-19 Vaccine (Vero Cell), Inactivated). To evaluate the safety of the vaccine, we tested the repeat-dose toxicity in Sprague-Dawley (SD) rats. The doses were administered randomly to three groups: physiological saline solution (control), aluminum adjuvant in PBS solution adjuvant (adjuvant group), and low-dose and high-dose omicron vaccines (vaccine group) for 6 weeks. The SD rats were allowed to recover for 4 weeks after withdrawal. We evaluated the physiological condition of the rats, including their ophthalmological condition, body weight, food intake, body temperature, blood biochemistry, urine, neutralizing antibody, inflammation at the injection site, and organs weight. In summary, no dose-dependent adverse toxicological changes were observed, and a recovery trend was obvious, which proved the preclinical safety of the candidate omicron vaccine and provided evidence for clinical trials in humans.

Abstract Aims Previous prediction studies for 30 day readmission in patients with heart failure were built mainly based on electronic medical records and rarely involved patient‐reported outcomes. This study aims to develop and validate a nomogram including patient‐reported outcomes to predict the possibility of 30 day all‐cause readmission in older patients with heart failure and to explore the value of patient‐reported outcomes in prediction model. Methods and results This was a prospective cohort study. The nomogram was developed and internally validated by Logistic regression analysis based on 381 patients in training group from March to December 2019. The nomogram was externally validated based on 170 patients from July to October 2020. Receiver operating characteristic curves, calibration plots and decision‐curve analysis were used to evaluate the performance of the nomogram. A total of 381 patients' complete data were analysed in the training group and 170 patients were enrolled in the external validation group. In the training group, 14.4% (n = 55) patients were readmitted to hospitals within 30 days of discharge and 15.9% (n = 27) patients were readmitted in the external validation group. The nomogram included six factors: history of surgery, changing the type of medicine by oneself, information acquisition ability, subjective support, depression level, quality of life, all of which were significantly associated with 30 day readmission in older patients with heart failure. The areas under the receiver operating characteristic curves of nomogram were 0.949 (95% CI: 0.925, 0.973, sensitivity: 0.873, specificity: 0.883) and 0.804 (95% CI: 0.691, 0.917, sensitivity: 0.778, specificity: 0.832) respectively in the training and external validation groups, which indicated that the nomogram had better discrimination ability. The calibration plots demonstrated favourable coordination between predictive probability of 30 day readmission and observed probability. Decision‐curve analysis showed that the net benefit of the nomogram was better between threshold probabilities of 0–85%. Conclusions A novel and easy‐to‐use nomogram is constructed and demonstrated which emphasizes the important role of patient‐reported outcomes in predicting studies. The performance of the nomogram drops in the external validation cohort and the nomogram must be validated in a wide prospective cohort of HF patients before its clinical relevance can be demonstrated. All these findings in this study can assist professionals in identifying the needs of HF patients so as to reduce 30 day readmission.

ObjectivesInitial precipitating injury (IPI) such as febrile convulsion and intracranial infection will increase the susceptibility to epilepsy. It is still unknown if the functional deficits differ between mesial temporal lobe epilepsy with IPI (mTLE-IPI) and without IPI (mTLE-NO).MethodsWe recruited 25 mTLE-IPI patients, 35 mTLE-NO patients and 33 healthy controls (HC). Static regional homogeneity (sReHo) and dynamic regional homogeneity (dReHo) were then adopted to estimate the alterations of local neuronal activity. One-way analysis of variance was used to analyze the differences between the three groups in sReHo and dReHo. Then the results were utilized as masks for further between-group comparisons. Besides, correlation analyses were carried out to detect the potential relationships between abnormal regional homogeneity indicators and clinical characteristics.ResultsWhen compared with HC, the bilateral thalamus and the visual cortex in mTLE-IPI patients showed an increase in both sReHo and variability of dReHo. Besides, mTLE-IPI patients exhibited decreased sReHo in the right cerebellum crus1/crus2, inferior parietal lobule and temporal neocortex. mTLE-NO patients showed decreased sReHo and variability of dReHo in the bilateral temporal neocortex compared with HC. Increased sReHo and variability of dReHo were found in the bilateral visual cortex when mTLE-IPI patients was compared with mTLE-NO patients, as well as increased variability of dReHo in the left thalamus and decreased sReHo in the right dorsolateral prefrontal cortex. Additionally, we discovered a negative correlation between the national hospital seizure severity scale testing score and sReHo in the right cerebellum crus1 in mTLE-IPI patients.ConclusionAccording to the aforementioned findings, both mTLE-IPI and mTLE-NO patients had significant anomalies in local neuronal activity, although the functional deficits were much severer in mTLE-IPI patients. The use of sReHo and dReHo may provide a novel insight into the impact of the presence of IPI on the development of mTLE.

BackgroundPANoptosis is an inflammatory type of programmed cell death regulated by PANopotosome. Mounting evidence has shown that PANoptosis could be involved in cancer pathogenesis and the tumor immune microenvironment. Nevertheless, there have been no studies on the mechanism of PANoptosis on pancreatic cancer (PC) pathogenesis.MethodsWe downloaded the data on transcriptomic and clinical features of PC patients from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. Additionally, the data on copy number variation (CNV), methylation and somatic mutations of genes in 33 types of cancers were obtained from TCGA. Next, we identified the PANoptosis-related molecular subtype using the consensus clustering analysis, and constructed and validated the PANoptosis-related prognostic model using LASSO and Cox regression analyses. Moreover, RT-qPCR was performed to determine the expression of genes involved in the model.ResultsWe obtained 66 PANoptosis-related genes (PANRGs) from published studies. Of these, 24 PC-specific prognosis-related genes were identified. Pan-cancer analysis revealed complex genetic changes, including CNV, methylation, and mutation in PANRGs were identified in various cancers. By consensus clustering analysis, PC patients were classified into two PANoptosis-related patterns: PANcluster A and B. In PANcluster A, the patient prognosis was significantly worse compared to PANcluster B. The CIBERSORT algorithm showed a significant increase in the infiltration of CD8+ T cells, monocytes, and naïve B cells, in patients in PANcluster B. Additionally, the infiltration of macrophages, activated mast cells, and dendritic cells were higher in patients in PANcluster A. Patients in PANcluster A were more sensitive to erlotinib, selumetinib and trametinib, whereas patients in PANcluster B were highly sensitive to irinotecan, oxaliplatin and sorafenib. Moreover, we constructed and validated the PANoptosis-related prognostic model to predict the patient’s survival. Finally, the GEPIA and Human Protein Atlas databases were analyzed, and RT-qPCR was performed. Compared to normal tissues, a significant increase in CXCL10 and ITGB6 (associated with the model) expression was observed in PC tissues.ConclusionWe first identified the PANoptosis-related molecular subtypes and established a PANoptosis-related prognostic model for predicting the survival of patients with PC. These results would aid in exploring the mechanisms of PANoptosis in PC pathogenesis.

Densified wood possesses outstanding mechanical properties and serves as a desired construction material for modern timber buildings. However, the limited research on its flame behavior hinders its broader applications. The authors of this paper experimentally and analytically investigated the influence of wood species and density on horizontal flame spread behavior. Densified oak and densified fir were tested. The flame spread rate decreased with wood density in both densified wood types. Their values were close at the same density. The mass loss rate (m˙) of the densified wood decreased with the increase in wood density. The densified oak had higher m˙ due to its lower lignin content. Dimensionless correlations between the m˙ and density were obtained which agree with the experiments. The flame heights (Lf) of the densified wood also decreased with the increase in wood density. The densified oak had higher Lf due to its higher m˙. As the densified wood density increased, the radiation (and conduction) was reduced (and enhanced), but the convection remained constant. The densified oak had lower convection, lower conduction, and higher radiation than the densified fir at the same density. Gas-phase heat transfer was dominant in the flame spread of the densified wood, but conduction was also significant as its contribution can be as high as 70% of gaseous heat transfer.

Background: It is unclear whether serum calcium on admission is associated with clinical outcomes in dilated cardiomyopathy (DCM). In this study, we conducted a retrospective study spanning a decade to investigate the prognostic value of baseline calcium in elderly patients with DCM. Methods: A total of 1,089 consecutive elderly patients (age ≥60 years) diagnosed with DCM were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to investigate the association of serum calcium with their clinical outcomes. Results: In this study, the average age of the subjects was 68.36 ± 6.31 years. Receiver operating characteristic (ROC) curve analysis showed that serum calcium level had a great sensitivity and specificity for predicting in-hospital death, with an AUC of 0.732. Kaplan–Meier survival analysis showed that patients with a serum calcium >8.62 mg/dL had a better prognosis than those with a serum calcium ≤8.62 mg/dL (log-rank χ2 40.84, p < 0.001). After adjusting for several common risk factors, a serum calcium ≤8.62 mg/dL was related to a higher risk of long-term mortality (HR: 1.449; 95% CI: 1.115~1.882; p = 0.005). Conclusions: Serum calcium level could be served as a simple and affordable tool to evaluate patients’ prognosis in DCM.

Abstract Distant metastasis is the primary cause of breast cancer-associated death. The existing information, such as the precise molecular mechanisms and effective therapeutic strategies targeting metastasis, is insufficient to combat breast cancer. This study demonstrates that the protein tyrosine phosphatase PTPN18 is downregulated in metastatic breast cancer tissues and is associated with better metastasis-free survival. Ectopic expression of PTPN18 inhibits breast cancer cell metastasis. PTPN18 is translocated from the cytoplasm to the nucleus by MVP and importin β2 in breast cancer. Then, nuclear PTPN18 dephosphorylates ETS1 and promotes its degradation. Moreover, nuclear PTPN18 but not cytoplasmic PTPN18 suppresses transforming growth factor-β signaling and epithelial-to-mesenchymal transition by targeting ETS1. Our data highlight PTPN18 as a suppressor of breast cancer metastasis and provide an effective antimetastatic therapeutic strategy.

Abstract The hybrid visible light communication (VLC)/radio frequency (RF) communications are investigated with the aid of reconfigurable intelligent surfaces (RISs) in dynamic wireless networks, where the RIS access selection processes of VLC/RF users are updated depending on the channel quality dynamically. Specifically, a dynamic optimization problem due to the mobility of users and time‐varying selection strategy is formulated. Under the constraints of the average minimum rate for VLC/RF users and the maximum transmit power constraints for VLC/RF access points (APs), the target is to minimize the average long‐term power consumption, by jointly considering the active beamforming at APs and the passive beamforming at RISs. Based on the Lyapunov optimization framework and the drift‐plus‐penalty (DPP) algorithm, the original optimization problem is transformed into corresponding short‐term problems at each frame. Furthermore, the closed form solutions with active‐passive beamforming are derived using the fractional programming method based on the Lagrangian dual theory. Finally, numerical results demonstrate the convergence and effectiveness of the proposed optimization algorithm.