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Abstract Background Since chronic kidney disease is highly insidious in the early stages, most diagnosed patients have already developed irreversible renal failure. There is a lack of effective implementation and standardization of health education management for patients with chronic kidney disease, and the impact of health education management on health information literacy is not yet known. Methods This randomized controlled clinical trial was conducted from March 2022 to March 2023. A total of 130 patients with chronic kidney disease stage 3–4 were selected from a tertiary hospital in Zhuhai via a convenience sampling method and were then randomly assigned to intervention and control groups. The Health Information Literacy Questionnaire for Chronic Kidney Disease was used to assess the health literacy of the patients at month 0 and month 12. In addition, the renal function-related indices of the patients were measured before and after the intervention. The study adhered to SPIRIT guidelines. Results There was no significant difference between the two groups in health information literacy, platelet count, estimated glomerular filtration rate, or albumin level. However, the intervention group showed a significant improvement in health behavioral status such as information acquisition, checkups, and physical activity. Subgroup analysis revealed that hemoglobin was significantly higher in non-employed patients than in the intervention group. There was a significant improvement in hemoglobin level after receiving health guidance in patients with intermediate education, and acquisition capacity and estimated glomerular filtration rate in the intervention group were lower than in the control group for patients with elementary education. Conclusion Receiving health coaching helped to improve self-management behaviors and hemoglobin levels of patients with stage 3–4 chronic kidney disease. Education level is an important factor influencing the effectiveness of health coaching techniques. Trial registration This study was prospectively registered in the China Clinical Trial Registry on November 10, 2021, with registration number: ChiCTR2100053103.

Abstract Background This study aimed to investigate the effect of laser peripheral iridotomy (LPI) on intraocular lens (IOL) power in patients with primary angle closure disease (PACD), and to construct mathematical models to assess changes in IOL power. Methods This study included 58 eyes of PACD patients. IOL Master700 was used to analyze and compare the changes of IOL power and ocular related parameters in each formula before and after LPI. The number of cases with IOL power changes greater than 0.5 diopters (D) in each group were counted and significant differences were analyzed using Fisher’s exact test. Pearson’s linear correlation analysis was used to ascertain the relationship between IOL power changes and ocular parameter changes to establish mathematical models. Results No significant difference was found in calculated IOL power changes before and after LPI in each group. There was significant difference in the number of cases with IOL change values greater than 0.5D between the primary angle closure glaucoma (PACG) and the other two groups for each formula. IOL power changes were mainly associated with △K and △AL. Mathematical models of IOL power changes after LPI were constructed based on linear regression analysis.(PAC group: △IOLHaigis=0.026–2.950×△AL-1.414×△K, △IOLHoffer Q=-3.578×△AL-1.412×△K, △IOLSRK/T=-3.152×△AL-1.114×△K, △IOLHolladay 1=-3.405×△AL-1.291×△K, △IOLHolladay 2=-3.467×△AL-1.483×△K, △IOLBUII=-3.185×△AL-1.301×△K; PACG group:△IOLHaigis=-1.632×△K, △IOLHoffer Q=-3.770×△AL-1.434×△K, △IOLSRK/T=-3.427×△AL-1.102×△K, △IOLHolladay 1=-3.625×△AL-1.278×△K, △IOLHolladay 2=-4.764×△AL-1.272×△K, △IOLBUII=-4.935×△AL-1.304×△K). Conclusions LPI will cause changes in some ocular parameters in patients with PACD, with great effects on IOL power calculations was observed in patients with PACG. Mathematical models based on multivariate analysis hold promise for predicting IOL power changes subsequent to LPI.

Abstract Dysregulation of macrophage polarization can prevent the invasion of trophoblast cells and further limit spiral artery remodeling in preeclampsia (PE). However, its mechanism is obscure. HTR8-/Svneo cells were cultured under normoxic or hypoxic conditions and extracellular vesicles (EVs) in the culture supernatants were extracted. Next, the cells were incubated with those EVs to investigate their effects on trophoblasts. A co-culture system consisting of HTR8-/Svneo cells and macrophages was used to reveal how the trophoblast-derived EVs affected the macrophage subtype. Finally, a PE mouse model and miR-141-3p knockout mice were used to verify the function of miR-141-3p in PE. Hypoxia induced abnormal increases in the levels of miR-141-3p in HTR8-/Svneo cells and EVs. EVs from hypoxia-treated HTR8-/Svneo cells could downregulate PTEN, a potential target of miR-141-3p, and inhibit trophoblast mitophagy and invasion. However, HTR8-/Svneo cells transfected with an miR-141-3p inhibitor could attenuate the influence of EVs. In an HTR8-/Svneo cell plus macrophage co-culture system, hypoxia-pretreated cells promoted the transformation of macrophages into the M1-phenotye, and HTR8-/Svneo invasion was inhibited by the macrophages. MiR-141 from EVs could target and downregulate dual specificity phosphatase 1 (DUSP1) expression in macrophages, induce formation of the M1 macrophage phenotype in THP-1 cells, downregulate DUSP1 expression, and upregulate TAB2/TAK1 signaling. These results were also demonstrated in normal pregnant mice and PE pregnant mice. A hypoxic environment could upregulate miR-141 expression in the EVs of HTR8-/Svneo cells, and THP-1-derived macrophages could uptake EVs releasing miR-141 to downregulate DUSP1 expression and induce the formation of M1 macrophages, which can lead to the development of PE.

Abstract The epidermal infiltration of neutrophils is a hallmark of psoriasis (PSO) and its activation leads to the release of neutrophil extracellular traps (NETs). However, the molecular mechanism of NETs-related genes (NETRGs) has not been extensively studied in PSO. To define NETs-related-biomarkers for PSO. The GSE13355 and GSE78097 datasets, and NETRGs gene set were included in this study. The datasets used in this study were all microarray data. The weighted gene co-expression network analysis (WGCNA) and machine learning algorithms were used to mine key genes. Later on, single-gene gene set enrichment analysis (GSEA) and immune infiltration analysis were implemented. Finally, the expression of key genes was verified using quantitative real-time fluorescence PCR (qRT-PCR). A total of 3 key genes (S100A9, CLEC7A, and CXCR4) were derived, and they all had excellent diagnostic performance. The single-gene GSEA enrichment results indicated that the key genes were mainly enriched in the chemokine signaling pathway and humoral immune response in the high-expression group, while focal adhesion was enriched in the low-expression group. The correlation analysis indicated that all key genes were strongly negatively correlated with resting mast cells and TGF-β family member receptor, while they were strongly positively correlated with activated CD4 memory T cells and antigen processing and presentation. Lastly, the experimental results showed that the expression trends of key genes were consistent with public database. In this study, we successfully screened three potential PSO diagnostic genes (S100A9, CLEC7A and CXCR4) that were closely related to NETs, and these findings not only provided new molecular marker candidates for the precise diagnosis of PSO patients, but also revealed possible future therapeutic targets. However, further in-depth research and validation were necessary.

Abstract The rise of object detection models has brought new breakthroughs to the development of clinical decision support systems. However, in the field of gastrointestinal polyp detection, there are still challenges such as uncertainty in polyp identification and inadequate coping with polyp scale variations. To address these challenges, this paper proposes a novel gastrointestinal polyp object detection model. The model can automatically identify polyp regions in gastrointestinal images and accurately label them. In terms of design, the model integrates multi-channel information to enhance the ability and robustness of channel feature expression, thus better coping with the complexity of polyp structures. At the same time, a hierarchical structure is constructed in the model to enhance the model’s adaptability to multi-scale targets, effectively addressing the problem of large-scale variations in polyps. Furthermore, a channel attention mechanism is designed in the model to improve the accuracy of target positioning and reduce uncertainty in diagnosis. By integrating these strategies, the proposed gastrointestinal polyp object detection model can achieve accurate polyp detection, providing clinicians with reliable and valuable references. Experimental results show that the model exhibits superior performance in gastrointestinal polyp detection, which helps improve the diagnostic level of digestive system diseases and provides useful references for related research fields.

Abstract Background Understanding the factors that contribute to variability in breast cancer-related lymphedema (BCRL) is an important first step in developing targeted interventions to improve quality of life in breast cancer patients. Although previous research studies have has identified many risk factors for BCRL, dietary habits and catheterization type have rarely been studied until the present. Aim This study aims to explore the effects of nursing factors such as dietary habits and catheterization type on breast cancer-related lymphedema (BCRL). Methods This retrospective cohort study included 1,476 breast cancer patients who underwent surgery between January 1, 2012, and September 1, 2020. Lymphedema was assessed with a validated self-report questionnaire. All research data were obtained from medical records and a follow-up database. Multivariate Cox regression was conducted to explore the effects of dietary habits and catheterization type on BCRL. Results The results showed an increased risk for BCRL among breast cancer patients who followed a high-fat diet prehospitalization (HR = 2.47; 95% CI = 1.55–3.94; P

Abstract Introduction Lung and bronchus cancer is a leading cause of death in the United States. Compared with the national average, Michigan has an increased mortality rate and low early screening and treatment rates. This study aimed to explore the epidemiological trends and assess overall survival (OS) of patients diagnosed with lung cancer in Michigan from 1996 to 2017. Methods Data was acquired from the Michigan Cancer Surveillance Program (MCSP). Log‐rank test was used to test OS among the time periods, univariate and multivariate cox regression models were employed to determine factors that significantly affected OS. We hypothesized that the introduction of more inclusive lung cancer screening guidelines in 2013 would improve OS for patients diagnosed after its implementation and that individual characteristics and tumor characteristics would both affect OS. Results Notably, 153 742 individuals met inclusion criteria: 54.22% male and 45.78% female. Mean age at diagnosis was 69 years. No significant difference in OS was found among the three time periods (p = 0.99). Univariate analyses identified four individual characteristics associated with reduced OS: age at diagnosis, male sex, American Indian race, and living in rural or urban area. Reduced OS was associated with primary sites tumors at main bronchus, lung base, or within overlapping lobes, and SEER stage 7. Conclusions This study highlights several factors that influence OS. Consideration of these factors may be helpful as a community outreach tool to help increase early detection and reduce overall mortality.

Abstract Background The β-1,3-glucanase gene is widely involved in plant development and stress defense. However, an identification and expression analysis of the grape β-1,3-glucanase gene (VviBG) family had not been conducted prior to this study. Results Here, 42 VviBGs were identified in grapevine, all of which contain a GH-17 domain and a variable C-terminal domain. VviBGs were divided into three clades α, β and γ, and six subgroups A–F, with relatively conserved motifs/domains and intron/exon structures within each subgroup. The VviBG gene family contained four tandem repeat gene clusters. There were intra-species synteny relationships between two pairs of VviBGs and inter-species synteny relationships between 20 pairs of VviBGs and AtBGs. The VviBG promoter contained many cis-acting elements related to stress and hormone responses. Tissue-specific analysis showed that VviBGs exhibited distinct spatial and temporal expression patterns. Transcriptome analysis indicated that many VviBGs were induced by wounds, UV, downy mildew, cold, salt and drought, especially eight VviBGs in subgroup A of the γ clade. RT-qPCR analysis showed that these eight VviBGs were induced under abiotic stress (except for VviBG41 under cold stress), and most of them were induced at higher expression levels by PEG6000 and NaCl than under cold treatment. Conclusions The chromosome localization, synteny and phylogenetic analysis of the VviBG members were first conducted. The cis-acting elements, transcriptome data and RT-qPCR analysis showed that VviBG genes play a crucial role in grape growth and stress (hormone, biotic and abiotic) responses. Our study laid a foundation for understanding their functions in grape resistance to different stresses.

Abstract Background In hepatocellular carcinoma (HCC) treatment, first-line targeted therapy in combination with immune checkpoint inhibitors (ICIs) has improved patient prognosis, but the 5-year survival rate is far from satisfactory. Studies have shown that the extracellular matrix (ECM) is an essential part of the tumour microenvironment (TME) and participates in the progression of malignant tumours. ECM remodelling can enhance matrix stiffness in cirrhosis patients, induce an immunosuppressive microenvironment network, and affect the efficacy of targeted therapies and ICIs for treating HCC. However, the exact mechanism is still unclear. Methods We downloaded data from public databases, selected differentially expressed ECM proteins associated with matrix stiffness, constructed and validated a prognostic model of HCC using Lasso Cox regression, and investigated the roles and mechanism of one of the ECM proteins, dynein light chain LC8-type 1 (DYNLL1), in HCC proliferation, migration, and apoptosis via in vitro experiments. Results In this study, the risk score of the matrix stiffness-related ECM protein model effectively predicted the prognosis of HCC patients. The high- and low-risk subgroups of the model also showed differences in immune cells, immune functions, and drug sensitivity. DYNLL1 promoted HCC cell progression and migration and inhibited HCC cell apoptosis through the Wnt/β-catenin pathway in vitro. Conclusion The expression of matrix stiffness-related ECM proteins could be an independent predictor of HCC prognosis. DYNLL1, an oncogenic gene in HCC, has the potential to be a new target for HCC treatment.

Abstract Background and aims Despite concerns on the adverse health outcomes of sarcopenic obesity (SO), exploration regarding the applicability of different diagnostic criteria and the optimal screening methods is still lacking. This study aims to compare the prevalence and diagnostic agreement of SO under four diagnostic criteria in Chongming, Shanghai, China and assess the diagnostic value of nine screening methods for SO. Methods The study population included older people aged ≥ 65 years. The Asian Working Group for Sarcopenia-2019 (AWGS-2019) was used to diagnose sarcopenia. Obesity was defined using percentage of body fat (PBF), percent of body fat exceeding the 60th percentile (60% PBF), body mass index (BMI) and waist circumference (WC). The four diagnostic criteria for SO were AWGS + PBF, AWGS + 60% PBF, AWGS + BMI and AWGS + WC. Nine screening methods were the sarcopenia questionnaire [the questionnaire with five items to screen for sarcopenia (SARC-F), the addition of calf circumference to the SARC-F (SARC-CalF), and the addition of elderly age and BMI to the SARC-F (SARC-F + EBM)] combined with commonly used obesity indicators. Cohen’s kappa compared agreement between diagnostic criteria, whilst sensitivity, specificity, receiver operating characteristics (ROC) and area under the ROC curve (AUC) compared the diagnostic value of nine screening methods. Results A total of 1407 older people were enrolled. The prevalence of SO ranged from 0.3 to 9.9%. The highest agreement between AWGS + 60% PBF and AWGS + PBF. When the AWGS + PBF was used as the ‘gold standard’ (due to its high agreement and high prevalence), SARC-CalF + PBF had the highest AUC value, and SARC-F + BMI had the highest sensitivity. The recommended cut-off values for SARC-F + BMI are SARC-F ≥ 1 score and BMI ≥ 19.845 kg/m², and the recommended cut-off values for SARC-CalF + PBF are SARC-CalF ≥ 5 score and PBF ≥ 34.55%. Conclusion The prevalence of SO varied greatly amongst the four diagnostic criteria. AWGS + PBF is recommended for diagnosing SO in older people. SARC-F + BMI and SARC-CalF + PBF can be used as screening methods for SO.

Rhododendron molle is a deciduous rhododendron, a high-altitude plant prized for its medicinal and ornamental properties. A major challenge when introducing this plant to lower altitudes is understanding its response to high-temperature stress. Using transcriptome analysis, this study examined leaves under varying temperatures, identifying 344,593 transcripts, 124,901 Unigenes, and 12,089 differentially expressed genes (DEGs) at 36 °C high-temperature stress (ST). At 42 °C high-temperature stress (SY), 12,032 DEGs were found, indicating a significant impact of temperature on gene expression. A Gene Ontology analysis (GO) revealed that these DEGs are mostly involved in stress response, catalytic activity, binding, transporter activity, and immune processes. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted enrichment in pathways such as plant-pathogen interaction and spliceosomes, suggesting their key roles in the temperature stress response. Key genes such as Brassinosteroid-Insensitive 1-Associated Receptor Kinase (BAK1) and Pathogenesis-Related Gene Transcription Activation Factor (PTI6) were upregulated under ST stress, whereas heat shock proteins (HSP83A) and HSP90-1 were downregulated under SY. These findings offer insights into the molecular response of Rhododendron molle to high temperature, aiding further research in this area and potentially improving the plant’s cultivation and application.

Logistics service quality (LSQ) plays a vital role in providing excellent customer experience, particularly in e-commerce. Using mobile devices for food and fresh product orders is very common, but delivering these products is very challenging. In this study, we aim to evaluate the factors influencing logistics service quality (LSQ) in the context of fresh product e-commerce. The relevant literature was reviewed and a preliminary survey among field experts was conducted to establish the proposed LSQ scale. A qualitative study was carried out on fresh product e-commerce customers. A survey involving 222 participants was analyzed, and an LSQ evaluation scale was formed and evaluated scientifically and empirically. Research results showed that reliability, convenience, freshness, and personnel contact quality are the four key dimensions of the LSQ scale in the e-commerce platform for fresh and perishable items. The results of the study can help the managers of e-commerce companies to understand the LSQ criteria that determine customer satisfaction and consequently make the appropriate LSQ improvements.

Physical inactivity poses a significant public health challenge. Numerous studies have argued that urban parks can promote physical activity (PA). However, evidence of physical activity observed over long periods of time in parks is still very lacking. Our serial cross-sectional study within urban parks in Shanghai investigated seasonal and daily variations in PA. Employing a geographically and temporally weighted regression (GTWR) model, we established spatiotemporal relationships between urban park characteristics and PA levels. We found that (1) Highest PA levels occur in winter, while the lowest levels are observed in summer, with a V-shaped daily pattern. (2) Robust and significant associations between specific park characteristics and PA levels, while other characteristics exhibited varying associations in different temporal and spatial contexts. These insights offer valuable guidance for urban planners and park designers aiming to create more active and sustainable urban environments.

Objective: To investigate the correlations of hip muscle composition with age and body mass index (BMI) in middle-aged and elderly patients with hip fracture. Methods: In total of 175 patients aged 51~95 years with low-energy hip fracture who underwent hip computed tomography scans were divided into ＜80 and ≥80 year-old groups. Quantitative computed tomography (QCT) was performed to obtain the cross-sectional muscle area (CSMA), total adipose area (TAA), intra-muscular adipose area (IMAA), subcutaneous adipose area (SAA) and muscle fat infiltration (MFI) of the hip. An independent t-test was used to compare the differences between gender and groups, and correlation analysis was used to determine the relationships between hip muscle fat area and age and BMI. Results: The hip TAA, SAA and MFI of men were significantly lower than those of women (t=−2.356, −2.550, −3.090), and CSMA was significantly higher than that of women. The CSMA in the ＜80 year-old age group was higher than that of the ≥80 year-old age group, and the MFI was lower than that found in the ≥80 years age old group. After adjusting for BMI, the age of men and women positively correlated with IMAA and MFI (r=0.445 and 0.612 for men, r=0.202 and 0.390 for women), and negatively correlated with CSMA (r=−0.673 for men, r=−0.428 for women). After adjusting for age, the BMI of men positively correlated with TAA, IMAA, SAA, and CSMA (r=0.430, 0.491, 0.389, 0.623), whereas the BMI of women positively correlated with TAA, IMAA, SAA, CSMA, and MFI (r=0.510, 0.389, 0.478, 0.295, 0.296). Conclusion: In middle-aged and elderly patients with hip fragility fractures, men had more muscle and less total fat than those in women, but similar intermuscular fat to that of women. Hip muscle mass decreased and intermuscular fat increased with age. Generally, higher BMI, correlated with more muscle and fat. However, MFI in men was not associated with BMI.

Nanobody (Nb) is derived from the variable domain of heavy-chain antibody (HCAb), naturally displaying notable properties like nano-scale size, exceptional stability, high specificity, low immunogenicity, and cryptic epitope accessibility. These features contribute to its great therapeutic potential as a valuable research tool across diverse diseases, especially autoimmune diseases (AIDs). Caplacizumab (Cablivi®) is the first nanobody drug approved for treating acquired thrombotic thrombocytopenic purpura (aTTP). This review summarizes the biomolecular structure, usage of Nb as a foundation of recombinant constructs, and biochemical properties of nanobodies. As attractive therapeutic candidates, many clinical trials of Nbs have been conducted, elucidating potential therapeutic strategies for AIDs. Therefore, the preclinical development and application of Nbs in AIDs are emphasized throughout this review.

Abstract Background There were limited data investigating platelet indices in predicting peritoneal dialysis (PD) outcomes on comorbidities. The aim of this study was to evaluate the association between platelet indices and new-onset comorbidity and all-cause mortality in PD patients. Methods A single-center, retrospective observational cohort study was conducted in incident PD patients from 28 December 2011 to 24 January 2018, and followed up until 31 December 2022. Time to the first new-onset cardiovascular disease (CVD) and time to the first new-onset infection event after PD were identified as the primary outcomes. All-cause mortality was identified as the secondary endpoint. The correlation between platelet indices and comorbidities and all-cause mortality were assessed by Cox model. Data of liver disease status was not collected and analyzed. Survival curves were performed by Kaplan-Meier method with log-rank tests. Results A total of 250 incident PD patients with a median follow-up of 6.79 (inter-quarter range 4.05, 8.89) years was included. A total of 81 and 139 patients experienced the first new-onset CVD and infection event respectively during the follow-up period. High mean platelet volume (MPV) was independently associated with high risk of time to the first new-onset CVD (HR 1.895, 95% CI 1.174–3.058, p = 0.009) and all-cause mortality (HR 1.710, 95% CI 1.155–2.531, p = 0.007). Patients with low mean platelet volume to platelet count ratio (MPV/PC) were prone to occur the new-onset infection events (log rank 5.693, p = 0.017). Low MPV/PC (HR 0.652, 95% CI 0.459–0.924, p = 0.016) was significantly associated with the time to the first new-onset infection event on PD. Conclusions Platelet indices were associated with the new-onset CVD, infectious comorbidities and all-cause mortality on PD. Low MPV/PC was associated with time to the first new-onset infection event in PD patients. Moreover, high MPV was associated with new-onset CVD and all-cause mortality in the incident PD patients.

Abstract Objective This study aimed to assess the efficacy and safety of bilateral superselective adrenal arterial embolization (SAAE) in patients with bilateral idiopathic hyperaldosteronism (IHA), a subtype of PA. Methods Ninety-eight patients with bilateral IHA underwent bilateral SAAE between August 2022 and August 2023. Sixty-eight patients were followed up for up to 12 months. The study outcomes were evaluated using the criteria provided by the Primary Aldosteronism Surgical Outcome (PASO) guidelines. Results The mean reductions in systolic and diastolic blood pressure were 27.4 ± 21.3 mmHg and 23.1 ± 17.4 mmHg, respectively (p

Abstract The mortality of ovarian cancer (OC) has long been the highest among gynecological malignancies. Although OC is considered to be an immunogenic tumor, the effect of immunotherapy is not satisfactory. The immunosuppressive microenvironment is one reason for this, and the absence of recognized effective antigens for vaccines is another. Chemotherapy, as one of the most commonly used treatment for OC, can produce chemotherapy-associated antigens (CAAs) during treatment and show the effect of in situ vaccine. Herein, we designed an antigen capture nano-vaccine NP-TP1@M-M with tumor targeting peptide TMTP1 and dendritic cell (DC) receptor mannose assembled on the surface and adjuvant monophosphoryl lipid A (MPLA) encapsulated in the core of poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA itself possessed the ability of antigen capture. TMTP1 was a tumor-homing peptide screened by our research team, which held extensive and excellent tumor targeting ability. After these modifications, NP-TP1@M-M could capture and enrich more tumor-specific antigens after chemotherapy, stimulate DC maturation, activate the adaptive immunity and combined with immune checkpoint blockade to maximize the release of the body’s immune potential, providing an eutherapeutic strategy for the treatment of OC.

Abstract Purpose This study aims to investigate the association of serum TSH with BMD in Chinese adults with normal thyroid function. Methods These participants were divided into tertiles based on serum TSH levels. Linear regression model and multinomial logistic regression models were used to analyze the associations of continuous BMD and categorical BMD with serum TSH, respectively. Results In women younger than 60 years, BMD decreased with the increase of TSH at normal level, while in women older than 60 years, BMD increased with the increase of TSH at normal level; besides, the BMD of women younger than 60 years old was significantly higher than that of women over 60 years old (156.05 ± 39.34 mg/cm3 vs. 86.95 ± 29.51 mg/cm3, P

Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine (TCM) for over 13 centuries. However, the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear welfare. Here, we present a new approach for creating artificial bear bile (ABB) as a high-quality and sustainable alternative to natural bear bile. This study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary collaborations across various fields, including resources, chemistry, biology, medicine, pharmacology, and TCM. A comprehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established, allowing for the systematic screening of therapeutic constituents. Through the utilization of chemical synthesis and enzyme engineering technologies, our research has achieved the environmentally friendly, large-scale production of bear bile therapeutic compounds, as well as the optimization and recomposition of ABB formulations. The resulting ABB not only closely resembles natural bear bile in its composition but also offers advantages such as consistent product quality, availability of raw materials, and independence from threatened or wild resources. Comprehensive preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from commercially available drained bear bile (DBB). Furthermore, preclinical toxicological assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used DBB. This innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs, thereby strengthening the integrity and sustainability of TCM.

Abstract Objective To examine the influences and mechanisms of MicroRNA-19a-3p (miR-19a-3p) on endothelial dysfunction in atherosclerosis. Methods An analysis of miR-19a expression was carried out using the Gene Expression Omnibus (GEO) database. The effect of miR-19a-3p on endothelial function in HUVECs was evaluated by miR-19a-3p overexpression under TNF-α treatment. Luciferase assays were performed to explore the potential target genes. Overexpression of junctional protein associated with coronary artery disease (JCAD) was used to examine the effects of miR-19a-3p on cell adhesion, and proliferation. Results MiR-19a-3p expression in endothelial cells decreased after exposure to TNF-α and/or oscillatory flow, consistent with the expression change of miR-19a-3p found in atherosclerotic plaques. Additionally, endothelial cell dysfunction and inflammation were significantly diminished by miR-19a-3p overexpression but markedly exacerbated by miR-19a-3p inhibition. MiR-19a-3p transfection significantly decreased the expression of JCAD by binding to the 3’-UTR of JCAD mRNA. Furthermore, the protective effect of miR-19a-3p against endothelial cell dysfunction and inflammation was achieved by regulating JCAD and was closely linked to the Hippo/YAP signaling pathway. Conclusion MiR-19a-3p expression is a crucial molecular switch in the onset of atherosclerosis and miR-19a-3p overexpression is a possible pharmacological therapeutic strategy for reversing the development of atherosclerosis.

Abstract Bacillus cereus is a bacterium capable of causing late-onset neonatal sepsis. By analyzing 11 cases, this study investigates the diagnosis, treatment, and prognosis of Bacillus cereus infections, aiming to provide insights into clinical diagnosis and therapy. The study scrutinized 11 instances of late-onset neonatal sepsis, including two fatalities attributable to Bacillus cereus, one accompanied by cerebral hemorrhage. An examination and analysis of these cases’ symptoms, signs, laboratory tests, and treatment processes, along with a review of related literature from 2010 to 2020, revealed a high mortality rate of 41.38% in non-gastrointestinal infections caused by Bacillus cereus. Our findings underscore the critical importance of rapid diagnosis and effective antimicrobial therapy in reducing mortality rates. Once the source of infection is identified, implementing effective infection control measures is essential.

Abstract Background Olanzapine (OLZ) reverses chronic stress-induced anxiety. Chronic stress promotes cancer development via abnormal neuro-endocrine activation. However, how intervention of brain-body interaction reverses chronic stress-induced tumorigenesis remains elusive. Methods Kras LSL−G12D/WT lung cancer model and LLC1 syngeneic tumor model were used to study the effect of OLZ on cancer stemness and anxiety-like behaviors. Cancer stemness was evaluated by qPCR, western-blotting, immunohistology staining and flow-cytometry analysis of stemness markers, and cancer stem-like function was assessed by serial dilution tumorigenesis in mice and extreme limiting dilution analysis in primary tumor cells. Anxiety-like behaviors in mice were detected by elevated plus maze and open field test. Depression-like behaviors in mice were detected by tail suspension test. Anxiety and depression states in human were assessed by Hospital Anxiety and Depression Scale (HADS). Chemo-sensitivity of lung cancer was assessed by in vivo syngeneic tumor model and in vitro CCK-8 assay in lung cancer cell lines. Results In this study, we found that OLZ reversed chronic stress-enhanced lung tumorigenesis in both Kras LSL−G12D/WT lung cancer model and LLC1 syngeneic tumor model. OLZ relieved anxiety and depression-like behaviors by suppressing neuro-activity in the mPFC and reducing norepinephrine (NE) releasing under chronic stress. NE activated ADRB2-cAMP-PKA-CREB pathway to promote CLOCK transcription, leading to cancer stem-like traits. As such, CLOCK-deficiency or OLZ reverses NE/chronic stress-induced gemcitabine (GEM) resistance in lung cancer. Of note, tumoral CLOCK expression is positively associated with stress status, serum NE level and poor prognosis in lung cancer patients. Conclusion We identify a new mechanism by which OLZ ameliorates chronic stress-enhanced tumorigenesis and chemoresistance. OLZ suppresses mPFC-NE-CLOCK axis to reverse chronic stress-induced anxiety-like behaviors and lung cancer stemness. Decreased NE-releasing prevents activation of ADRB2-cAMP-PKA-CREB pathway to inhibit CLOCK transcription, thus reversing lung cancer stem-like traits and chemoresistance under chronic stress.

Landscape architecture education in the 21st century witnessed a transition from merely art and engineering to a future that integrates knowledge in science, psychology, environmental studies, ecology, and more. Using planting and environmental design practice as an example, the education focus needs to shift from purely demonstrating aesthetics to a comprehensive framework that integrates aesthetics, ecological services, and social and spatial functionality. This paper explored the gaps in planting and environmental design between pedagogy and practice. The result indicates that college-level education in planting and environmental design is majorly focused on plant identification, ornamental properties, and construction drawing communications, whereas the practical field indicates an expectation of more horticultural and ecological knowledge in design practice from college-level education. To bridge the gap, the article identified the proper trajectories through qualitative research including a questionnaire survey, semi-structured interview, content analysis and cross analysis to explore a sustainable development education framework of planting and environmental design based on the barriers of knowledge dissemination between academia and practice.

Abstract Objective To investigate risk factors associated with long-term mortality in patients with stage II and III tuberculous meningitis (TBM). Methods This retrospective analysis examined patients who were first diagnosed with stage II and III TBM at West China Hospital of Sichuan University between January 1, 2018 and October 1, 2019. Patients were followed via telephone and categorized into survival and mortality groups based on 4-year outcomes. Multivariate logistic regression identified independent risk factors for long-term mortality in stage II and III TBM. Results In total, 178 patients were included, comprising 108 (60.7%) males and 36 (20.2%) non-survivors. Mean age was 36 ± 17 years. Compared to survivors, non-survivors demonstrated significantly higher age, heart rate, diastolic blood pressure, blood glucose, rates of headache, neurological deficits, cognitive dysfunction, impaired consciousness, hydrocephalus, and basal meningeal inflammation. This group also exhibited significantly lower Glasgow Coma Scale (GCS) scores, blood potassium, albumin, and cerebrospinal fluid chloride. Multivariate analysis revealed age (OR 1.042; 95% CI 1.015–1.070; P = 0.002), GCS score (OR 0.693; 95% CI 0.589–0.814; P

Abstract Background Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and early detection is critical to improve the clinical outcome of this disease. In this study, the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 (an investigational medicinal product) positron emission tomography (PET) imaging in UM xenografts and UM patients were evaluated. The cell uptake, cell binding ability and in vitro stability of [18F]AlF-NOTA-PRGD2 were evaluated in 92-1 UM cell line. MicroPET imaging and biodistribution study of [18F]AlF-NOTA-PRGD2 were conducted in 92-1 UM xenografts. Then, UM patients were further recruited for evaluating the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 PET imaging (approval no. NCT02441972 in clinicaltrials.gov). In addition, comparison of [18F]AlF-NOTA-PRGD2 and 18F-labelled fluorodeoxyglucose ([18F]FDG) PET imaging in UM xenografts and UM patients were conducted. Results The in vitro data showed that [18F]AlF-NOTA-PRGD2 had a high cell uptake, cell binding ability and in vitro stability in 92-1 UM cell line. The in vivo data indicated that 92-1 UM tumors were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer in the subcutaneous and ocular primary UM xenografts model at 60 min post-injection. And the tumor uptake of the tracer was 2.55 ± 0.44%ID/g and 1.73 ± 0.15%ID/g at these two tissue locations respectively, at 7 days after animal model construction. The clinical data showed that tumors in UM patients were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer at 60 min post-injection. In addition, [18F]AlF-NOTA-PRGD2 tracer showed higher sensitivity and specificity for PET imaging in UM xenografts and UM patients compared to [18F]FDG tracer. Conclusion [18F]AlF-NOTA-PRGD2 PET imaging may be a more preferred approach in the diagnosis of primary UM compared to [18F]FDG PET imaging. Additionally, due to the high tumor-to-background ratio, [18F]AlF-NOTA-PRGD2 PET imaging seems also to be applicable for the diagnosis of UM patients with liver metastasis. Trial registration: ClinicalTrials.gov: NCT02441972, Registered 1 January 2012, https://clinicaltrials.gov/study/NCT02441972 .

The occurrence mechanism of coal and gas outburst disasters is still unclear. According to the rheological hypothesis, gas-bearing coal and rock may enter the “strength limit neighborhood” under long-term load, and it is more likely to be destroyed by external impact disturbance. The “strength limit neighborhood” of gas-bearing coal rock under different loading conditions is studied to find the influence law of entering this state, and the corresponding micro-discrimination criteria are established,” using the self-developed triaxial test system of rock rheological disturbance effect and the seepage experimental device of coal rock rheological disturbance effect, the rheological disturbance experiment of gas-bearing coal rock under different confining pressures, different gas pressures and axial pressures was carried out. The coal rock before and after rheological disturbance was analyzed and compared by means of nuclear magnetic resonance, and the T2 spectrum curve, porosity and pore size distribution under different loading conditions were obtained. The test results show that: ① In the rheological process of coal rock under different loading conditions, there is a critical value for the sensitivity of external disturbance. When the applied force is less than this critical value, after the impact disturbance, the porosity of coal rock decreases and the specimen is compressed closely. When the force is greater than this critical value, after the impact disturbance, the large pore size of coal rock increases obviously, the T2 spectrum curve shifts to the right, and the peak height increases, It shows that the stress threshold is the key to determine whether the coal rock enters the “strength limit neighborhood”. ② Confining pressure and gas pressure have opposite mechanical properties to coal rock. It is shown in the compressive capacity, damage degree, long-term strength and “strength limit neighborhood”. Among them, the greater the confining pressure, the earlier the coal rock enters the “strength limit neighborhood;” The greater the gas pressure, The greater the gas pressure, the earlier the coal rock enters the neighborhood. ③ the pore size distribution and T2 spectrum curve of coal rock can directly reflect the internal and external micro-variation characteristics of rock’s “strength limit neighborhood.” ④The constitutive equation of axial pressure, confining pressure and gas pressure determined by the porosity of coal rock can be used to judge the timing of coal rock entering the “strength limit neighborhood” under different loading conditions. As a criterion for entering the “strength limit neighborhood,” the greater the confining pressure, the greater the stress threshold when entering the “strength limit neighborhood,” the greater the gas pressure, and the smaller the stress threshold when entering the “strength limit neighborhood.”

Abstract Background Ginsenoside Rg3 is a component of ginseng that protects against myocardial ischemia/reperfusion (MI/R) injury. Ferroptosis is a new form of cell death characterized by oxidative damage to phospholipids. The purpose of this study was to examine the role and of ginsenoside Rg3 in MI/R and the mechanism. Methods A mouse model of left anterior descending (LAD) ligation-induced myocardial ischemia/reperfusion (MI/R) injury and oxygen-glucose deprivation/reperfusion (OGD/R) were used as in vitro and in vivo models, respectively. Echocardiographic analysis, 2,3,5-triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (H&E) staining were used to assess the cardioprotective effects of ginsenoside Rg3. Western blotting, biochemical analysis, small interfering RNA analysis and molecular docking were performed to examine the underlying mechanism. Results Ginsenoside Rg3 improved cardiac function and infarct size in mice with MI/R injury. Moreover, ginsenoside Rg3 increased the expression of the ferroptosis-related protein GPX4 and inhibited iron deposition in mice with MI/R injury. Ginsenoside Rg3 also activated the Nrf2 signaling pathway. Ginsenoside Rg3 attenuated myocardial ischemia/reperfusion-induced ferroptosis via the Nrf2 signaling pathway. Notably, ginsenoside Rg3 regulated the keap1/Nrf2 signaling pathway to attenuate OGD/R-induced ferroptosis in H9C2 cells. Taken together, ginsenoside Rg3 attenuated myocardial ischemia/reperfusion-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway. Conclusions Our findings demonstrated that ginsenoside Rg3 ameliorate MI/R-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway.

Abstract Off-line leachate collection from agricultural landscapes cannot guarantee precise evaluation of agricultural non-point source (ANPS) due to geospatial variations, time, and transportation from the field to the laboratory. Implementing an in-situ nitrogen and phosphorous monitoring system with a robust photochemical flow analysis is imperative for precision agriculture, enabling real-time intervention to minimize non-point source pollution and overcome the limitations posed by conventional analysis in laboratory. A reliable, robust and in-situ approach was proposed to monitor nitrogen and phosphorous for determining ANPS pollution. In this study, a home-made porous ceramic probe and the frequency domain reflectometer (FDR) based water content sensors were strategically placed at different soil depths to facilitate the collection of leachates. These solutions were subsequently analyzed by in-situ photochemical flow analysis monitoring system built across the field to estimate the concentrations of phosphorus and nitrogen. After applying both natural and artificial irrigation to the agricultural landscape, at least 10 mL of soil leachates was consistently collected using the porous ceramic probe within 20 min, regardless of the depth of the soil layers when the volumetric soil water contents are greater than 19%. The experimental results showed that under different weather conditions and irrigation conditions, the soil water content of 50 cm and 90 cm below the soil surface was 19.58% and 26.08%, respectively. The average concentrations of NH4 +-N, NO3 −-N, PO4 3− are 0.584 mg/L, 15.7 mg/L, 0.844 mg/L, and 0.562 mg/L, 16.828 mg/L and 0.878 mg/L at depths of 50 cm and 90 cm below the soil surface, respectively. Moreover, the comparison with conventional laboratory spectroscopic analysis confirmed R2 values of 0.9951, 0.9943, 0.9947 average concentration ranges of NH4 +-N, NO3 −-N, and PO4 3−, showcasing the accuracy and reliability of robust photochemical flow analysis in-situ monitoring system. The suggested monitoring system can be helpful in the assessment of soil nutrition for precision agriculture.

Abstract Background The aim of the study was to investigate the muscle differences in children with osteogenesis imperfecta (OI) using opportunistic low-dose chest CT and to compare different methods for the segmentation of muscle in children. Methods This single center retrospective study enrolled children with OI and controls undergoing opportunistic low-dose chest CT obtained during the COVID pandemic. From the CT images, muscle size (cross-sectional area) and density (mean Hounsfield Units [HU]) of the trunk muscles were measured at the mid-T4 and the mid-T10 level using two methods, the fixed thresholds and the Gaussian mixture model. The Bland-Altman method was also used to compute the strength of agreement between two methods. Comparison of muscle results between OI and controls were analyzed with Student t tests. Results 20 children with OI (mean age, 9.1 ± 3.3 years, 15 males) and 40 age- and sex-matched controls were enrolled. Mean differences between two methods were good. Children with OI had lower T4 and T10 muscle density than controls measured by the fixed thresholds (41.2 HU vs. 48.0 HU, p

Abstract Retained placenta is a common health issue, and appropriate prevention strategies are effective in postpartum health management. This study aimed to evaluate whether early intervention using GYS can prevent retained placenta and puerperal metritis, as well as enhance reproductive outcomes in cows. Each bovine in the GYS group (n = 591) received a single prophylactic dose of GYS (0.5 g/kg body weight) orally within 2 h after parturition, while those in the control group (n = 598) received no intervention. GYS treatment was associated with a decreased incidence of retained placenta (4.6% vs. 12.0%, P

Abstract Background Despite the numerous advantages of mastering biostatistics, medical students generally perceive biostatistics as a difficult and challenging subject and even experience anxiety during the courses. Evidence for the correlation between students’ academic achievements and their attitudes, indicating that attitudes at the beginning of the biostatistics course may affect cognitive competence at the end of the course and subsequently influence student academic performance. However, there are current disagreements regarding the measurement and evaluation of attitudes related to statistics. Thus, there is a need for standard instruments to assess them. This study was conducted to develop a Chinese version of the Survey of Attitudes Toward Statistics (SATS-36) in order to acquire a valid instrument to measure medical students’ attitudes toward biostatistics under Chinese medical educational background. Methods The Chinese version SATS-36 was developed through translation and back-translation of the original scale, with subsequent revisions based on expert advice to ensure the most appropriate item content. The local adaption was performed with a cohort of 1709 Chinese-speaking medical undergraduate and graduate students enrolled in biostatistics courses. And then, the reliability, validity and discrimination of the questionnaires were evaluated through correlation coefficient calculation, factor analysis, parallel analysis and other methods. Results The Chinese version SATS-36 consisted of 36 items and loaded a five-factor structure by factor analysis, which offered an alternative similar but not equal to that original six-factor structure. The cumulative variance contribution rate was 62.20%, the Cronbach’s α coefficient was 0.908, the Guttman split-half reliability coefficient was 0.905 and the test–retest reliability coefficient was 0.752. Discriminant analysis revealed small to large significant differences in the five attitude subscales. Conclusions The Chinese version SATS-36 with good validity and reliability in this study can be used to evaluate the learning framework of Chinese medical students.

Optical coherence tomography (OCT) imaging technology has significant advantages in in situ and noninvasive monitoring of biological tissues. However, it still faces the following challenges: including data processing speed, image quality, and improvements in three-dimensional (3D) visualization effects. OCT technology, especially functional imaging techniques like optical coherence tomography angiography (OCTA), requires a long acquisition time and a large data size. Despite the substantial increase in the acquisition speed of swept source optical coherence tomography (SS-OCT), it still poses significant challenges for data processing. Additionally, during in situ acquisition, image artifacts resulting from interface reflections or strong reflections from biological tissues and culturing containers present obstacles to data visualization and further analysis. Firstly, a customized frequency domain filter with anti-banding suppression parameters was designed to suppress artifact noises. Then, this study proposed a graphics processing unit (GPU)-based real-time data processing pipeline for SS-OCT, achieving a measured line-process rate of 800[Formula: see text]kHz for 3D fast and high-quality data visualization. Furthermore, a GPU-based real-time data processing for CC-OCTA was integrated to acquire dynamic information. Moreover, a vascular-like network chip was prepared using extrusion-based 3D printing and sacrificial materials, with sacrificial material being printed at the desired vascular network locations and then removed to form the vascular-like network. OCTA imaging technology was used to monitor the progression of sacrificial material removal and vascular-like network formation. Therefore, GPU-based OCT enables real-time processing and visualization with artifact suppression, making it particularly suitable for in situ noninvasive longitudinal monitoring of 3D bioprinting tissue and vascular-like networks in microfluidic chips.

BackgroundThe relationship between serum uric acid (SUA) levels and prostate cancer (PCa) remains controversial. This cross-sectional study investigated the association between SUA levels and PCa incidence.MethodsA total of 9,776 participants aged ≥40 from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2020 were included, 503 of whom had PCa. Weighted univariate logistic regression, multivariate logistic regression, and smooth-fitting curve analyses were used to analyze the association between SUA and PCa incidence. Concurrently, the fitted smoothing curves were used to explore the potential non-linear relationships. If non-linearity was observed, a recursive algorithm further calculated the inflection point.ResultsThree models were used to analyze the correlation between SUA levels and PCa incidence. All regression models demonstrated a negative correlation between SUA levels and PCa incidence (model 1: OR = 0.88, 95% CI=0.80–0.97; model 2: OR = 0.87, 95% CI=0.80–0.96; model 3: OR = 0.87, 95% CI=0.78–0.96). According to the trend test, with increasing SUA, the risk of PCa showed a downward trend (three models P for trend = 0.037, 0.015, 0.016). According to the subgroup analysis, a significant negative correlation between SUA and PCa was detected in individuals aged >60 years, non-Hispanic whites, those of other races, and those with hypertension. Moreover, the association between SUA and PCa followed a U-shaped curve among participants without hypertension, and the inflection point of SUA was 5.1 mg/dl.ConclusionsThis cross-sectional study revealed a negative relationship between SUA levels and the risk of PCa, particularly in specific demographic groups. These findings offer a fresh perspective on the role of SUA in PCa patients, potentially paving the way for new approaches for the prevention and treatment of PCa. However, further studies are necessary to validate these findings.

Copper (Cu) is a common heavy metal and a hazardous environmental pollutant. Emerging epidemiological evidence suggests that Cu exposure is associated with female infertility, especially ovarian dysfunction. However, the mechanisms underlying ovarian toxicity remain poorly understood. Granulosa cells play crucial roles in follicle development and are the main target cells of environmental pollutants for ovarian toxicity. In this study, we investigated the effects of Cu exposure on human granulosa (KGN) cells by using cell biology and metabolomics methods, and explored the molecular mechanisms of Cu-induced cytotoxicity. We found that Cu reduced cell viability in a dose- and time-dependent manner. Then, metabolomic analyses led to the identification of 279, 368 and 466 differentially expressed metabolites (DEMs) in KGN cells exposed to 10, 60 and 240 μM Cu, respectively. Pathway enrichment analysis revealed that high Cu led to disturbances of glutathione metabolism, nucleotide metabolism, glycerophospholipid and ether lipid metabolism. Using cell biological assays, we found that exposure to high Cu significantly decreased the GSH/GSSG ratio and altered the activities of the antioxidant enzymes SOD and CAT. Exposure to high Cu significantly increased the level of mitochondrial ROS. These findings further supported the results revealed by metabolomic analysis and provided clues for elucidating the mechanism by which Cu interferes with the development of ovarian follicles.

Hepatitis B virus (HBV) infection is a common cause of liver disease worldwide. The current antiviral treatment using nucleotide analogues (NAs) can only suppress de novo HBV replication but cannot eliminate chronic HBV infection due to the persistence of covalently closed circular (ccc) DNA that sustains viral replication. The CRISPR/Cas9 system is a novel genome-editing tool that enables precise gene disruption and inactivation. With high efficiency and simplicity, the CRISPR/Cas9 system has been utilized in multiple studies to disrupt the HBV genome specifically, eliciting varying anti-HBV effects both in vitro and in vivo. Additionally, multi-locus gene targeting has shown enhanced antiviral activity, paving the way for combination therapy to disrupt and inactivate HBV cccDNA as well as integrated HBV DNA. Despite its promising antiviral effects, this technology faces several challenges that need to be overcome before its clinical application, i.e., off-target effects and in vivo drug delivery. As such, there is a need for improvement in CRISPR/Cas9 efficiency, specificity, versatility, and delivery. Here, we critically review the recent literature describing the tools employed in designing guide RNAs (gRNAs) targeting HBV genomes, the vehicles used for expressing and delivering CRISPR/Cas9 components, the models used for evaluating CRISPR-mediated HBV gene disruption, the methods used for assessing antiviral and off-target effects induced by CRISPR/Cas9-mediated HBV gene disruption, and the prospects of future directions and challenges in leveraging this HBV gene-editing approach, to advance the HBV treatment toward a clinical cure.

Accumulation of acylcarnitines is a characteristic feature of various metabolic disorders affecting fatty acid metabolism. Despite extensive research, no specific molecules have been identified to induce ferroptosis through the regulation of acylcarnitine metabolism. In this study, acylcarnitine accumulation was identified based on cell metabolomics study after the treatment with Stemona alkaloid derivative (SA-11), which was proved to induce ferroptosis in our previous research. Furthermore, the CPT-1 level was proved to significantly increase, while the CPT-2 level indicated no significant difference, which resulted in the accumulation of acylcarnitine. Besides, the ferroptosis-inducing ability of SA-11 was significantly enhanced by the addition of exogenous acylcarnitine, presumably due to the production of additional ROS. This hypothesis was corroborated by the observation of increased ROS levels in HCT-116 cells treated with SA-11 compared to the control group. These findings suggest that targeting acylcarnitine metabolism, particularly through CPT-1, may offer a novel therapeutic strategy for cancer treatment by enhancing ferroptosis induction.

The lack of accurate and reliable in vitro brain models hinders the development of brain science and research on brain diseases. Owing to the complex structure of the brain tissue and its highly nonlinear characteristics, the construction of brain-like in vitro tissue models remains one of the most challenging research fields in the construction of living tissues. This study proposes a multi-scale design of a brain-like model with a biomimetic cortical structure, which includes the macroscopic structural features of six layers of different cellular components, as well as micrometer-scale continuous fiber structures running through all layers vertically. To achieve integrated biomanufacturing of such a complex multi-scale brain-like model, a multi-material composite printing/culturing integrated bioprinting platform was developed in-house by integrating cell-laden hydrogel ink direct writing printing and electrohydrodynamic fiber 3D printing technologies. Through integrated bioprinting, multi-scale models with different cellular components and fiber structural parameters were prepared to study the effects of macroscopic and microscopic structural features on the directionality of neural cells, as well as the interaction between glial cells and neurons within the tissue model in a three-dimensional manner. The results revealed that the manufactured in vitro biomimetic cortical model achieved morphological connections between the layers of neurons, reflecting the structure and cellular morphology of the natural cortex. Micrometer-scale (10 μm) cross-layer fibers effectively guided and controlled the extension length and direction of the neurites of surrounding neural cells but had no significant effect on the migration of neurons. In contrast, glial cells significantly promoted the migration of surrounding PC12 cells towards the glial layer but did not contribute to the extension of neurites. This study provides a basis for the design and manufacture of accurate brain-like models for the functionalization of neuronal tissues.

Mendelian Randomization (MR) is a widely embraced approach to assess causality in epidemiological studies. Two-stage least squares (2SLS) method is a predominant technique in MR analysis. However, it can lead to biased estimates when instrumental variables (IVs) are weak. Moreover, the issue of the winner's curse could emerge when utilizing the same dataset for both IV selection and causal effect estimation, leading to biased estimates of causal effects and high false positives. Focusing on one-sample MR analysis, this paper introduces a novel method termed Mendelian Randomization with adaptive Sample-sPLitting with cross-fitting InstrumenTs (MR-SPLIT), designed to address bias issues due to IV selection and weak IVs, under the 2SLS IV regression framework. We show that the MR-SPLIT estimator is more efficient than its counterpart cross-fitting MR (CFMR) estimator. Additionally, we introduce a multiple sample-splitting technique to enhance the robustness of the method. We conduct extensive simulation studies to compare the performance of our method with its counterparts. The results underscored its superiority in bias reduction, effective type I error control, and increased power. We further demonstrate its utility through the application of a real-world dataset. Our study underscores the importance of addressing bias issues due to IV selection and weak IVs in one-sample MR analyses and provides a robust solution to the challenge.

The health condition monitoring of harmonic drives plays an important role in ensuring the rotational motion accuracy of robot or manipulator joints. Capitalizing on the periodic and repetitive nature of manipulator tasks, a novel on-line data-driven evaluation method is developed in this paper, which employs a One-Dimensional Convolutional Neural Network (1D-CNN) and Hidden Markov Model (HMM) to classify static transmission errors of harmonic drives based on the current and torque data of their driving motors. The 1D-CNN encodes multiple dimensional data including numerical features, Wavelet Packet Energy Entropy (WPEE) values, and marginal spectrums of the current and torque data. Then, based on these features, the HMMs under different transmission error levels are trained. In order to demonstrate this method, a test rig is developed, in which the load moves in a reciprocating motion as an inverted pendulum. The load is driven by the servo motor and the harmonic drive. The experimental results show that the proposed evaluation method can identify six distinct levels of static transmission errors in harmonic drives with an accuracy greater than 91% in this study. The presented research holds potential for the development of a Prognostics and Health Management (PHM) system for robots.

Analog circuit is an crucial component of electronic equipment, and the ability to diagnose its fault state quickly and accurately is essential for ensuring the safety and reliability of these electronic equipment. This paper addresses the problems of low diagnostic accuracy and the difficulties associated with model parameter selection in traditional fault diagnosis methods, particularly when dealing with nonlinear and non-stationary fault signals. A fault diagnosis method for analog circuits is proposed, which utilizes Ensemble Empirical Mode Decomposition (EEMD) for features extraction, the Maximum Information Coefficient algorithm (MIC) for features selection, and Particle Swarm Optimization (PSO) for optimizing Support Vector Machine (SVM) classification. Firstly, EEMD is used to adaptively decompose the fault signals in the circuit to extract multi-scale fault features. Secondly, the extracted features are quantitatively evaluated using the Pearson correlation coefficient and energy value analysis, leading to the construction of a fault feature vector is constructed. On this basis, the MIC feature selection algorithm is applied to further optimize the feature vector. Finally, an efficient fault classification model is developed by optimizing the hyperparameters of the SVM model using PSO. The simulation results show that the proposed method effectively overcome the problems of model complexity and low classification accuracy caused by improper selection of wavelet basis function. The accuracy of fault diagnosis and the efficiency of model training are significantly superior to those of traditional methods.

PurposeTo analyze the application of ‘instrument and equipment surface cleaning and disinfection’ in hospitals based on standardization and the management of cleaning and disinfection information systems.MethodsEmployees and all cleaning and disinfected instruments and equipment from 56 inpatient departments in our hospital were selected as the subjects of observation. The period before the intervention (January 2023) was designated as the control group, while the period after the intervention (July 2023) was designated as the study group. In the control group, the instruments and equipment under routine management were disinfected. The research team applied the Failure Mode and Effects Analysis (FMEA) method to clean and disinfect the surfaces of instruments and equipment on the basis of standardization and cleaning and disinfection information system management. Employees’ theoretical knowledge points and operational skill scores before and after the intervention were compared and evaluated. The changes in the risk priority coefficient (RPN) values of high-risk factors were analyzed. Fifty-six clinical medical staff from 56 inpatient departments in the hospital were selected to evaluate the clinical satisfaction of the cleaning and disinfection management of instruments and equipment before and after the intervention, and the clinical satisfaction of the two groups was compared.ResultsThe scores of theoretical knowledge and operational skills of the staff in the research group were significantly higher than those in the control group. The passing rates of theoretical knowledge and operational skills in the control group and the research group were 44.64 and 94.64% respectively, and 55.36 and 96.43%, respectively. The qualified rate of theoretical knowledge and operational skills of staff in the study group was significantly higher than that in the control group (p

Background and purpose: The composite score for insulin resistance (IR), known as the Metabolic Score of Insulin Resistance (METS-IR), serves as an assessment tool for IR and has been previously linked to symptomatic intracranial hemorrhage and poor functional outcomes in patients with acute ischemic stroke (AIS). Despite these associations, the impact of METS-IR on early neurological deterioration (END) in patients with minor AIS who underwent intravenous administration of recombinant tissue-type plasminogen activator (IV-rtPA) remains inadequately established. This investigation explored the link between METS-IR and END in patients with minor AIS receiving IV-rtPA treatment. Methods: In this study, a cohort comprising 425 consecutive patients with National Institutes of Health Stroke Scale Score (NIHSS)≤5 who underwent IV-rtPA treatment was included. The METS-IR was computed using the formula ln METS-IR=ln (2 × FBG + TG) × BMI/ln (HDL). END was defined as a NIHSS ≥2 within 24 h post IV-rtPA administration, while poor functional outcome was defined as a modified Rankin Scale (mRS) of 2–6. Multivariate logistical regression was performed to investigate the association between METS-IR and both poor functional outcomes and END. Results: Among the 425 enrolled patients, 64 (15.1 %) patients experienced END, while 80 (18.8 %) had poor functional outcomes three months post-discharge. Upon adjusting for confounding factors, a higher METS-IR emerged as an independent predictor for both END and poor functional outcomes. Similarly, noteworthy findings were observed when METS-IR was defined as a categorical group. The restricted cubic spline (RCS) analysis indicated a linear relationship between METS-IR and END (P = 0.593 for non-linearity, P = 0.034 for overall). The incorporation of METS-IR into the conventional model resulted in a significant enhancement of predictive accuracy for both END and poor functional outcomes. Conclusion: METS-IR emerges as an independent predictor for END and poor functional outcome at three months post-discharge in patients with minor AIS subjected to IV-rtPA. Considering its simplicity and clinical accessibility as an indicator of IR, METS-IR may hold guiding significance in clinical practice.

After normal pollination and fertilization of pseudoparthenocarpic seedless grapes, their embryos often stop developing due to certain developmental factors, resulting in embryo abortion. Hybrid breeding using seedless grapes as the maternal parent requires embryo rescue breeding technology. This technology plays a crucial role in seedless grape breeding. Although previous studies have extensively explored this technology, knowledge regarding its impact on embryo abortion and the effectiveness of rescue techniques remains limited. This study aimed to investigate the correlation between embryo rescue and hormonal changes in seedless grapes. Four Eurasian seedless grape cultivars, “Thompson Seedless,” “Flame Seedless,” “Heshi Seedless,” and “Ruby Seedless,” were selected for examination. We investigated endogenous hormone levels, including indole-3-acetic acid (IAA), gibberellic acid (GA3), and abscisic acid (ABA), in both berries and in vitro ovules during the most suitable embryo rescue time for these cultivars. Based on the observed fluctuations in endogenous hormone levels and previous research findings, appropriate doses of exogenous hormones, such as IAA, GA3, and ABA, were applied during seedless grape embryo rescue. The results indicated significant differences in endogenous hormone levels between berries with varying ovule counts of the same cultivar and ovules cultured in vitro, suggesting a hormonal influence on ovule abortion and embryo development in seedless grapes. Further research has identified effective ratios of exogenous hormones: 30 mg·L–1 IAA + 30 mg·L–1 ABA for berry ovule development, 1.0 mg·L–1 IAA + 2.0 mg·L–1 6-benzylaminopurine (6-BA) + 1.0 mg·L–1 GA3 + 1.0 mg·L-1 ABA for in vitro ovule development, and 1.0 mg·L–1 IAA + 2.0 mg·L–1 6-BA + 1.0 mg·L–1 GA3 for embryo germination and seedling formation. In summary, hormonal changes significantly influence ovule and embryo development and are closely related to seedless grape embryo rescue breeding. This study deepened our understanding of the correlation between seedless grape embryo rescue and hormonal changes. It also resulted in the successful production of a batch of embryo rescue seedlings, further improving embryo rescue breeding technology and providing new germplasm materials for developing new seedless grape cultivars.

BackgroundBiological age (BA) offers an effective assessment of true aging state. The progression of Osteoarthritis (OA) is closely associated with an increase in chronological age, the correlation between BA and OA has not been fully elucidated.MethodsThis study analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2005–2018. Thirteen commonly used clinical traits were employed to calculate two measures of BA: the Klemera-Doubal method age (KDM-Age) and phenotypic age (Pheno-Age). The residuals of the regression of these ages based on chronological age were calculated as KDM-Age or Pheno-Age acceleration, respectively. OA was determined through self-reported prior diagnoses. The prevalence of OA across different quartiles of BA was compared using weighted chi-square tests and linear trend tests. The association between BA and OA was assessed using weighted multivariate logistic regression models.ResultsA total of 30,547 participants aged ≥20 years were included in this study, 3,922 (14%) were diagnosed with OA. Participants with OA exhibited higher chronological age, KDM-Age, Pheno-Age, KDM-Age advance, and Pheno-Age advance compared to those without OA (p