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Although advancements in genomic and epigenetic research have deepened our understanding of acute myeloid leukemia (AML), only one-third of patients can achieve durable remission. Growing evidence suggests that the immune microenvironment in bone marrow influences prognosis and survival in AML. There is a specific association between CD8+ T cells and the prognosis of AML patients. To develop a CD8+ T cell-related immune risk score for AML, we first evaluated the accuracy of CIBERSORTx in predicting the abundance of CD8+ T cells in bulk RNA-seq and found it significantly correlated with observed single-cell RNA sequencing data and the proportions of CD8+ T cells derived from flow cytometry. Next, we constructed the CTCG15, a 15-gene prognostic signature, using univariate and LASSO regression on the differentially expressed genes between CD8+ THigh and CD8+ TLow groups. The CTCG15 was further validated across six datasets in different platforms. The CTCG15 has been shown to be independent of established prognostic markers, and can distill transcriptomic consequences of several genetic abnormalities closely related to prognosis in AML patients. Finally, integrating this model into the 2022 European LeukemiaNet contributed to a higher predictive power for prognosis prediction. Collectively, our study demonstrates that CD8+ T cell-related signature could improve the comprehensive risk stratification and prognosis prediction in AML.

Background: Benign prostatic hyperplasia (BPH) is prevalent among the aging male population and often presents with distressing lower urinary tract symptoms. There is emerging evidence that commercial oral poly-herbal traditional Chinese medicine (TCM) formulation combined with Western medicine (WM) may offer enhanced therapeutic effects compared to WM alone in BPH treatment. Nevertheless, determining the optimal formulations for BPH remains controversial. We aimed to employ a network meta-analysis to compare and assess differences among commonly used and recommended poly-herbal TCM formulations outlined in the Chinese guidelines for BPH treatment, providing clinical medication recommendations and guidance.Methods: We extensively searched for RCTs of BPH patients that had oral poly-herbal TCM formulations and WM treatment, covering both English and Chinese databases up to 31 October 2023. The quality of the included studies was evaluated using the Cochrane risk-of-bias tool Version 2 (ROB2). A Bayesian network meta-analysis was performed to assess the effectiveness of various formulations, followed by sensitivity and subgroup analyses.Results: Our meta-analysis included 107 RCTs involving 11,037 patients across 16 oral poly-herbal TCM formulations. The quality of the selected studies was assessed as “Some concerns”. Most formulations combined with WM demonstrated superior therapeutic efficacy compared to WM alone. For clinical effective rate, Jingui Shenqi pill (JGSQ) + WM had the highest-ranking probability (87.38%). Concerning International Prostate Symptom Score (IPSS) and maximum flow rate of urine, Guizhi Fuling capsule (GZFL) + WM was most effective (91.10% and 98.55%). Regarding the quality of life score and postvoid residual urine, Pulean tablet (PLA) + WM ranked first (86.71% and 91.81%). In controlling prostate volume, Huange capsule (HE) + WM demonstrated the highest efficacy (95.65%). Additionally, among the interventions, Lingze (LZ) + WM capsule exhibited the lowest incidence of adverse drug reactions (2.32%).Conclusion: Combining oral poly-herbal TCM formulations with WM may provide greater therapeutic benefits in BPH treatment compared to WM alone. JGSQ, GZFL, PLA, and HE emerged as promising treatment options. However, further rigorous empirical studies are essential to substantiate these findings.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459651, CRD 42023459651.

Six new polyketides, which includes three new lactones (talarotones A–C) (1–3), one new polyketide (talarotide A) (4), two new polyenes (talaroyenes A, B) (5, 6), together with one new meroterpenoid (talaropenoid A) (7) and 13 known compounds (8–20) were isolated from the mangrove-derived fungus Talaromyces flavus TGGP35. The structure and configuration of the compounds 1–7 were elucidated from the data obtained from HR-ESI-MS, IR, 1D/2D NMR spectroscopy, Mo2 (OAc)4-induced electronic circular dichroism (ECD), CD spectroscopy, and modified Mosher's method. Compounds 5 and 20 displayed antioxidant activity with IC50 values of 0.40 and 1.36 mM, respectively. Compounds 3, 6, 11, 16, and 17 displayed cytotoxic activity against human cancer cells Hela, A549, and had IC50 values ranging from 28.89 to 62.23 μM. Compounds 7, 10–12, and 14–18 exhibited moderate or potent anti-insect activity against newly hatched larvae of Helicoverpa armigera Hubner, with IC50 values in the range 50–200 μg/mL. Compound 18 showed antibacterial activity against Ralstonia solanacearum with the MIC value of 50 μg/mL.

BackgroundHearing loss can exacerbate cognitive decline; therefore, exploring the mechanisms through which hearing loss affects cognitive function is crucial. The current study aimed to investigate the impact of hearing loss on cognitive function and the mediating role played by self-rated health and depressive anxiety symptoms.MethodsUsing stratified whole-group random sampling, the study employed a cross-sectional design and included 624 participants aged ≥65 years from three communities in Urumqi, China. Cognitive function was assessed using the Mini-Mental State Examination. Hearing function and self-rated health were determined by self-report. The 15-item Geriatric Depression Scale and the 7-item Generalized Anxiety Disorder Scale were used to assess depressive anxiety symptoms. Serial mediation analysis was performed using AMOS 26.0.ResultsHearing loss can not only negatively affect cognitive function in older adults directly (direct effect = −0.106; SE = 0.045; 95% confidence interval (CI): −0.201 to −0.016), but also indirectly affect the relationship between hearing loss and cognitive function through self-rated health and depressive anxiety symptoms. The results of the serial mediation analysis showed that the total indirect effect of self-rated health and depressive anxiety symptoms was −0.115 (95% CI: −0.168 to −0.070), and the total effect of the model was −0.221 (95% CI: −0.307 to −0.132), with the total indirect effect accounting for 52.04% of the total effect of the model.ConclusionOur study discovered that there is a partial mediation of the relationship between hearing loss and cognitive function by self-rated health and depressive anxiety symptoms. It is suggested that by enhancing self-rated health and ensuring good mental health, the decline in cognitive function among older adults with hearing loss can be delayed.

BackgroundMiddle-aged and older adults frequently experience hearing loss and a decline in cognitive function. Although an association between hearing difficulty and cognitive function has been demonstrated, its temporal sequence remains unclear. Therefore, we investigated whether there are bidirectional relationships between hearing difficulty and cognitive function and explored the mediating role of depressive symptoms in this relationship.MethodWe used the cross-lagged panel model and the random-intercept cross-lagged panel model to look for any possible two-way link between self-reported hearing difficulty and cognitive function. To investigate depressive symptoms’ role in this association, a mediation analysis was conducted. The sample was made up of 4,363 adults aged 45 and above from the China Health and Retirement Longitudinal Study (CHARLS; 2011–2018; 44.83% were women; mean age was 56.16 years). One question was used to determine whether someone had a hearing impairment. The tests of cognitive function included episodic memory and intelligence. The Center for Epidemiologic Studies Depression Scale, which consists of 10 items, was used to measure depressive symptoms.ResultsA bidirectional association between hearing and cognition was observed, with cognition predominating (Wald χ2 (1) = 7.241, p

Conventional polyvinyl alcohol (PVA) cementitious composites are susceptible to macroscopic cracking when subjected to reduced compressive strength, diminished toughness, tensile impact and other external loads. In order to address these issues, this study investigates the mechanism of the modifier's influence by modifying PVA fibers with a silane coupling agent (KH560) through experimental studies and molecular dynamics simulations for multiscale computational analyses. Macro test results showed that the mechanical properties of PVA fiber concrete were significantly improved after silane coupling agent modified PVA fiber. The microscopic test results showed that the SCA-modified polymer film acted as a bridging ligament in the interfacial transition zone, effectively prevented crack extension, and enhanced the interfacial adhesion between the organic components of the PVA fibers and the cement matrix. Nanoscale molecular dynamics simulations showed that the hydrated calcium silicate exhibited a stable skeletal structure, while the introduction of SCA expanded the hydrogen bonding interactions at the interface, thus enhancing its stability.

Invasive cardiac lipoma is a rare type of primary cardiac tumor that is composed of adipose tissue but infiltrating the adjacent structures. It is a benign tumor that can cause significant morbidity and mortality due to its size and location within the heart. We describe a giant invasive intracardiac lipoma across atrial wall extending to the ascending aorta and the superior vena cava. This review will provide an overview of invasive cardiac lipoma, including its clinical presentation, diagnosis, and management.

ObjectivePulmonary cement embolism is a rare but underestimated complication of vertebroplasty due to the relative lack of study and examination. This study aims to investigate the incidence of pulmonary cement embolism in patients with spinal metastasis who undergo PVP with RFA and to analyze the relative risk factors.MethodsA total of 47 patients were retrospectively included and classified into pulmonary cement embolism (PCE) group and non-pulmonary cement embolism (NPCE) group by comparing pre- and postoperative pulmonary CT scan images. The demographic and clinical information of the patients was obtained. Demographic data in the two groups were compared using the chi-square test for qualitative data and the unpaired t test for quantitative data. Multiple logistic regression analysis was used to identify risk factors related to pulmonary cement embolism.ResultsPulmonary cement embolism was detected in 11 patients (23.4%), and all patients were asymptomatic and followed up regularly. Risk analysis showed that multiple segments (≥3, p=0.022), thoracic vertebrae (p=0.0008), and unipedicular puncture approach (p=0.0059) were risk factors for pulmonary cement embolism. There was a high incidence of pulmonary cement embolism if bone cement leaked into the para vertebral venous plexus in the thoracic vertebra (p

Acute myeloid leukemia (AML) is a highly aggressive cancer with great heterogeneity and variability in prognosis. Though European Leukemia Net (ELN) 2017 risk classification has been widely used, nearly half of patients were stratified to “intermediate” risk and requires more accurate classification via excavating biological features. As new evidence showed that CD8+ T cell can kill cancer cells through ferroptosis pathway. We firstly use CIBERSORT algorithm to divide AMLs into CD8+ high and CD8+ low T cell groups, then 2789 differentially expressed genes (DEGs) between groups were identified, of which 46 ferroptosis-related genes associated with CD8+ T cell were sorted out. GO, KEGG analysis and PPI network were conducted based on these 46 DEGs. By jointly using LASSO algorithm and Cox univariate regression, we generated a 6-gene prognostic signature comprising VEGFA, KLHL24, ATG3, EIF2AK4, IDH1 and HSPB1. Low-risk group shows a longer overall survival. We then validated the prognostic value of this 6-gene signature using two independent external datasets and patient sample collection dataset. We also proved that incorporation of the 6-gene signature obviously enhanced the accuracy of ELN risk classification. Finally, gene mutation analysis, drug sensitive prediction, GSEA and GSVA analysis were conducted between high-risk and low-risk AML patients. Collectively, our findings suggested that the prognostic signature based on CD8+ T cell-related ferroptosis genes can optimize the risk stratification and prognostic prediction of AML patients.

Laser quenching is one of the most outstanding gear tooth surface quenching methods due to its high efficiency, environmental friendliness, and performance consistency. Since gear tooth surface laser quenching requires repeated scanning, changing the laser scanning velocity and power by program control can meet the needs of variable depth quenching. The effects of laser scanning velocity and output power on the quenching depth and surface Rockwell hardness after quenching were studied and experimentally analyzed. The result shows that by adjusting the parameters, the surface hardness of the specimen changes slightly with the actual received laser energy. However, the quenching depth can be consistent with the laser scanning velocity. The maximum surface Rockwell hardness that a laser quenched material can achieve depends on the material itself, not on the laser power or scanning velocity. Compared with accelerated laser quenching, decelerated laser quenching is more suitable for tooth surface machining due to the cumulative effect of energy within the quenching depth range of metal materials.

Three-dimensional cancer organoids derived from self-organizing cancer stems are ex vivo miniatures of tumors that faithfully recapitulate their structure, distinctive cancer features, and genetic signatures. As novel tools, current cancer organoids have been well established and rapidly applied in drug testing, genome editing, and transplantation, with the ultimate aim of entering clinical practice for guiding personalized therapy. However, given that the lack of a tumor microenvironment, including immune cells and fibrous cells, is a major limitation of this emerging methodology, co-culture models inspire high hope for further application of this technology in cancer research. Co-culture of cancer organoids and immune cells or fibroblasts is available to investigate the tumor microenvironment, molecular interactions, and chimeric antigen receptor-engineered lymphocytes in cancer treatment. In light of the recent progress in cancer organoid co-culture models, it is only possible to recognize the advantages and drawbacks of this novel model to exploit its full potential. In this review, we summarize the recent advances in the application of cancer organoids and co-culture models and how they could be improved in the future to benefit cancer research, especially precision medicine.

BackgroundThe objective of this study was to evaluate the quality of anticoagulation by the time in therapeutic range (TTR) for patients with 12-week INR follow-up interval.Materials and methodsFrom January 2018 to December 2020, a selective group of patients who underwent mechanical valve replacement and followed up at our anticoagulation clinic for adjustment of warfarin dose were enrolled. The incidences of complications of anticoagulation therapy were reported by linearized rates. TTR was calculated by the Rosendaal linear interpolation method.ResultsTwo hundred and seventy-four patients were eligible for this study. The mean age of these patients was 52.8 ± 12.7 years, and 65.7% (180 cases) of them were females. The mean duration of warfarin therapy was 16.7 ± 28.1 months. A total of 1309 INR values were collected, representing 66789 patient days. In this study, the mean TTR was 63.7% ± 18.6%, weekly doses of warfarin were 20.6 ± 6.0 mg/weekly, and the mean monitoring interval for the patient was 53.6 ± 27.1 days. There were 153 cases in good TTR group (TTR ≥ 60%) and 121 cases in poor TTR group (TTR < 60%). The calculated mean TTR in both groups was 42.6% ± 22.1% and 74.8% ± 10.4%, respectively. Compared with the TTR ≥ 60% group, the TTR < 60% group exhibited a more prevalence of female gender (p = 0.001), atrial fibrillation (p < 0.001), NYHA ≥ III (p < 0.001), and lower preoperative left ventricular ejection fraction (LVEF, p = 0.032). In multivariate analysis, female gender (p = 0.023) and atrial fibrillation (p = 0.011) were associated with TTR < 60%. The incidence of major bleeding and thromboembolic events was 2.7% and 1.1% patient-years, respectively. There was one death which resulted from cerebral hemorrhage. The incidence of death was 0.5% patient-years. The difference in anticoagulation-related complications between the TTR < 60% group and the TTR ≥ 60% group was not statistically significant.ConclusionFor patients with stable international normalized ratio monitoring results who are follow-up at anticoagulation clinics, a 12-week monitoring interval has an acceptable quality of anticoagulation. The female gender and atrial fibrillation were associated with TTR < 60%.

ObjectiveMaintaining and delaying a decline in physical function in older adults is critical for healthy aging. This study aimed to explore trajectories, critical points of the trajectory changes, and predictors among older people in the Chinese community.DesignThis study was one with a longitudinal design performed in China.Setting and participantsThe target population was community-dwelling older adults aged over 65 years. A total of 2,503 older adults from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were included in this study.MethodsPhysical functioning was measured by instrumental activities of daily living (IADL). Population-based trajectory models were used to identify potential heterogeneity in longitudinal changes over 16 years and to investigate associations between baseline predictors and different trajectories for different cohort members using LASSO regression and logistic regression.ResultsFour trajectories of physical function were identified: slow decline (33.0%), poor function and moderate decline (8.1%), rapid decline (23.5%), and stable function (35.4%). Older age, male sex, worse self-reported health status, worse vision status, more chronic diseases, worse cognitive function, and a decreased frequency of leisure activity influenced changes in the trajectory of physical function. Having fewer teeth, stronger depressive symptoms, a lack of exercise, and reduced hearing may increase the rate of decline.Conclusion and implicationsFour trajectories of physical function were identified in the Chinese elderly population. Early prevention or intervention of the determinants of these trajectories can maintain or delay the rate of decline in physical function and improve healthy aging.

Retrieval of aerosol optical depth (AOD) and bidirectional reflectance over Case II waters is a challenging task because of the optical complexity of water and the significant influence of atmospheric scattering. We present a simultaneous retrieval algorithm, coupled with a bidirectional reflectance distribution function (BRDF) model centered on the water’s Inherent Optical Property (IOP), to retrieve AOD and bidirectional reflectance based on multi-angle measurements from the Multi-angle Imaging SpectroRadiometer (MISR) sensor. The algorithm was evaluated through retrievals performed in the proximity of four AERONET sites characterized by various water types. Consistency was observed between the results and in situ measurements. Accurate AODs can be retrieved, and atmospheric overcorrection can be avoided when obtaining remote sensing reflectance. Furthermore, the normalized remote sensing reflectance derived from our results showed a good correlation with the AERONET-OC products derived using the IOP-based correction approach. Our study provides theoretical support for future quantitative remote-sensing studies.

A recent study showed that patients with coronavirus disease 2019 (COVID-19) have gastrointestinal symptoms and intestinal flora dysbiosis. Yeast probiotics shape the gut microbiome and improve immune homeostasis. In this study, an oral candidate of yeast-derived spike protein receptor-binding domain (RBD) and fusion peptide displayed on the surface of the yeast cell wall was generated. The toxicity and immune efficacy of oral administration were further performed in Institute of Cancer Research (ICR) mice. No significant difference in body weights, viscera index, and other side effects were detected in the oral-treated group. The detectable RBD-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and more complex microbiota were detected from oral administration mice compared with those of the control group. Interestingly, the recombinant yeast was identified in female fetal of the high-dose group. These results revealed that the displaying yeast could fulfill the agent-driven immunoregulation and gut microbiome reconstitution. The findings will shed light on new dimensions against SARS-CoV-2 infection with the synergistic oral agents as promising non-invasive immunization and restoring gut flora.

Metaxylem vessels in maize brace roots are key tissue, and their number (MVN) affects plant water and inorganic salt transportation and lodging resistance. Dissecting the genetic basis of MVN in maize brace roots can help guide the genetic improvement of maize drought resistance and lodging resistance during late developmental stages. In this study, we used 508 inbred lines with tropical, subtropical, and temperate backgrounds to analyze the genetic architecture of MVN in maize brace roots. The phenotypic variation in MVN in brace roots was evaluated in three environments, which revealed broad natural variation and relative low levels of heritability (h2 = 0.42). Stiff-stalk lines with a temperate background tended to have higher MVNs than plants in other genetic backgrounds. MVN was significantly positively correlated with plant height, tassel maximum axis length, ear length, and kernel number per row, which indicates that MVN may affect plant morphological development and yield. In addition, MVN was extremely significantly negatively correlated with brace root radius, but significantly positively correlated with brace root angle (BRA), diameter, and number, thus suggesting that the morphological function of some brace root traits may be essentially determined by MVN. Association analysis of MVN in brace roots combined 1,253,814 single nucleotide polymorphisms (SNPs) using FarmCPU revealed a total of nine SNPs significantly associated with MVN at P < 7.96 × 10–7. Five candidate genes for MVN that may participate in secondary wall formation (GRMZM2G168365, GRMZM2G470499, and GRMZM2G028982) and regulate flowering time (GRMZM2G381691 and GRMZM2G449165). These results provide useful information for understanding the genetic basis of MVN in brace root development. Further functional studies of identified candidate genes should help elucidate the molecular pathways that regulate MVN in maize brace roots.

Brain-computer interface (BCI) based on steady-state visual evoked potential (SSVEP) has been widely studied due to the high information transfer rate (ITR), little user training, and wide subject applicability. However, there are also disadvantages such as visual discomfort and “BCI illiteracy.” To address these problems, this study proposes to use low-frequency stimulations (12 classes, 0.8–2.12 Hz with an interval of 0.12 Hz), which can simultaneously elicit visual evoked potential (VEP) and pupillary response (PR) to construct a hybrid BCI (h-BCI) system. Classification accuracy was calculated using supervised and unsupervised methods, respectively, and the hybrid accuracy was obtained using a decision fusion method to combine the information of VEP and PR. Online experimental results from 10 subjects showed that the averaged accuracy was 94.90 ± 2.34% (data length 1.5 s) for the supervised method and 91.88 ± 3.68% (data length 4 s) for the unsupervised method, which correspond to the ITR of 64.35 ± 3.07 bits/min (bpm) and 33.19 ± 2.38 bpm, respectively. Notably, the hybrid method achieved higher accuracy and ITR than that of VEP and PR for most subjects, especially for the short data length. Together with the subjects’ feedback on user experience, these results indicate that the proposed h-BCI with the low-frequency stimulation paradigm is more comfortable and favorable than the traditional SSVEP-BCI paradigm using the alpha frequency range.

Random flaps are widely used in tissue reconstruction, attributed to the lack of vascular axial limitation. Nevertheless, the distal end of the flap is prone to necrosis due to the lack of blood supply. Notoginseng triterpenes (NTs) are the active components extracted from Panax notoginseng, reducing oxygen consumption and improving the body’s tolerance to hypoxia. However, their role in random flap survival has not been elucidated. In this study, we used a mouse random skin flap model to verify that NT can promote cell proliferation and migration and that increasing blood perfusion can effectively improve the survival area of a skin flap. Our study also showed that the autophagy of random flaps after NT treatment was activated through the Beclin-1/VPS34/LC3 signaling pathway, and the therapeutic effect of NT significantly decreased after VPS34 IN inhibited autophagy. In conclusion, we have demonstrated that NT can significantly improve the survival rate of random flaps through the Beclin-1/VPS34/LC3 signaling pathway, suggesting that it might be a promising clinical treatment option.

BackgroundWe aimed to analyze the first progression sites of first-line tyrosine kinase inhibitor (TKI) treatment for EGFR-mutant lung adenocarcinoma patients with systemic metastasis to recognize the potential candidates who might benefit from radiotherapy and establish a radiomic-based model to predict the first progression sites.Materials and MethodsWe retrospectively collected the clinical information and pre-treatment chest CT images of patients in Shanghai Chest Hospital from 2013 to 2017. All patients were diagnosed with stage IV EGFR-mutant lung adenocarcinoma and received TKI as first-line treatment. The first progression sites and survival were analyzed. The pre-treatment chest non-contrast CT images were utilized to establish a radiomic-based model to predict the first progression sites.ResultsWe totally collected 233 patients with systemic metastasis, among whom, there were 84 (36.1%) and 149 (63.9%) patients developing first progression in original lesions (OP) and new lesions (NP), respectively. The PFS and OS of patients with OP were longer than those with NP (PFS 11 months vs. 8 months, p = 0.03, OS 50 months vs. 35 months, p = 0.046). For 67.9% of the patients with OF, disease progressed within five sites (oligoprogression). The radiomic-based model could predict the progression sites with an AUC value of 0.736, a specificity of 0.60, and a sensitivity of 0.750 in the independent validation set.ConclusionAmong patients with systemic metastasis, there were 36.1% of patients developing OP at first progression who had a better prognosis than those developing NP. Patients with OP may be potential candidates who might benefit from radiotherapy. Radiomics is a useful method to distinguish patients developing OP and could provide some indications for radiotherapy.

BackgroundFor stage IV patients harboring EGFR mutations, there is a differential response to the first-line TKI treatment. We constructed three-dimensional convolutional neural networks (CNN) with deep transfer learning to stratify patients into subgroups with different response and progression risks.Materials and MethodsFrom 2013 to 2017, 339 patients with EGFR mutation receiving first-line TKI treatment were included. Progression-free survival (PFS) time and progression patterns were confirmed by routine follow-up and restaging examinations. Patients were divided into two subgroups according to the median PFS ( 9 months). We developed a PFS prediction model and a progression pattern classification model using transfer learning from a pre-trained EGFR mutation classification 3D CNN. Clinical features were fused with the 3D CNN to build the final hybrid prediction model. The performance was quantified using area under receiver operating characteristic curve (AUC), and model performance was compared by AUCs with Delong test.ResultsThe PFS prediction CNN showed an AUC of 0.744 (95% CI, 0.645–0.843) in the independent validation set and the hybrid model of CNNs and clinical features showed an AUC of 0.771 (95% CI, 0.676–0.866), which are significantly better than clinical features-based model (AUC, 0.624, P

BackgroundTo develop and validate a deep learning–based model on CT images for the malignancy and invasiveness prediction of pulmonary subsolid nodules (SSNs).Materials and MethodsThis study retrospectively collected patients with pulmonary SSNs treated by surgery in our hospital from 2012 to 2018. Postoperative pathology was used as the diagnostic reference standard. Three-dimensional convolutional neural network (3D CNN) models were constructed using preoperative CT images to predict the malignancy and invasiveness of SSNs. Then, an observer reader study conducted by two thoracic radiologists was used to compare with the CNN model. The diagnostic power of the models was evaluated with receiver operating characteristic curve (ROC) analysis.ResultsA total of 2,614 patients were finally included and randomly divided for training (60.9%), validation (19.1%), and testing (20%). For the benign and malignant classification, the best 3D CNN model achieved a satisfactory AUC of 0.913 (95% CI: 0.885–0.940), sensitivity of 86.1%, and specificity of 83.8% at the optimal decision point, which outperformed all observer readers’ performance (AUC: 0.846±0.031). For pre-invasive and invasive classification of malignant SSNs, the 3D CNN also achieved satisfactory AUC of 0.908 (95% CI: 0.877–0.939), sensitivity of 87.4%, and specificity of 80.8%.ConclusionThe deep-learning model showed its potential to accurately identify the malignancy and invasiveness of SSNs and thus can help surgeons make treatment decisions.

The prognosis of acute myeloid leukemia (AML) is closely related to immune response changes. Further exploration of the pathobiology of AML focusing on immune-related genes would contribute to the development of more advanced evaluation and treatment strategies. In this study, we established a novel immune-17 signature based on transcriptome data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases. We found that immune biology processes and transcriptional dysregulations are critical factors in the development of AML through enrichment analyses. We also formulated a prognostic model to predict the overall survival of AML patients by using LASSO (Least Absolute Shrinkage and Selection Operator) regression analysis. Furthermore, we incorporated the immune-17 signature to improve the prognostic accuracy of the ELN2017 risk stratification system. We concluded that the immune-17 signature represents a novel useful model for evaluating AML survival outcomes and may be implemented to optimize treatment selection in the next future.

As transcriptional co-activator of AP-1/Jun, estrogen receptors and NF-κB, nuclear protein RBM39 also involves precursor mRNA (pre-mRNA) splicing. Porcine reproductive and respiratory syndrome virus (PRRSV) causes sow reproductive disorders and piglet respiratory diseases, which resulted in serious economic losses worldwide. In this study, the up-regulated expression of RBM39 and down-regulated of inflammatory cytokines (IFN-β, TNFα, NF-κB, IL-1β, IL-6) were determined in PRRSV-infected 3D4/21 cells, and accompanied with the PRRSV proliferation. The roles of RBM39 altering phosphorylation of c-Jun to inhibit the AP-1 pathway to promote PRRSV proliferation were further verified. In addition, the nucleocytoplasmic translocation of RBM39 and c-Jun from the nucleus to cytoplasm was enhanced in PRRSV-infected cells. The three RRM domain of RBM39 are crucial to support the proliferation of PRRSV. Several PRRSV RNA (nsp4, nsp5, nsp7, nsp10-12, M and N) binding with RBM39 were determined, which may also contribute to the PRRSV proliferation. Our results revealed a complex mechanism of RBM39 by altering c-Jun phosphorylation and nucleocytoplasmic translocation, and regulating binding of RBM39 with viral RNA to prompt PRRSV proliferation. The results provide new viewpoints to understand the immune escape mechanism of PRRSV infection.

Protecting the death of nerve cells is an essential tactic for spinal cord injury (SCI) repair. Recent studies show that nerve growth factors can reduce the death of nerve cells and promote the healing of nerve injury. To investigate the conducive effect of fibroblast growth factor 21 (FGF21) on SCI repair. FGF21 proteins were systemically delivered into rat model of SCI via tail vein injection. We found that administration of FGF21 significantly promoted the functional recovery of SCI as assessed by BBB scale and inclined plane test, and attenuated cell death in the injured area by histopathological examination with Nissl staining. This was accompanied with increased expression of NeuN, GAP43 and NF200, and deceased expression of GFAP. Interestingly, FGF21 was found to attenuate the elevated expression level of the autophagy marker LC3-II (microtubules associated protein 1 light chain 3-II) induced by SCI in a dose-dependent manner. These data show that FGF21 promotes the functional recovery of SCI via restraining injury-induced cell autophagy, suggesting that systemic administration of FGF21 could have a therapeutic potential for SCI repair.

Mitochondria are potential targets for the treatment of cardio-cerebrovascular ischemia–reperfusion (I/R) injury. However, the role of the mitofusin 2 (Mfn2) protein in regulating mitochondrial fusion and cell survival has not been investigated. In the present study, an adenovirus-mediated Mfn2 overexpression assay was performed to understand the effects of Mfn2 on mitochondrial function and cell damage during cardio-cerebrovascular I/R injury. After exposure to I/R injury in vitro, the transcription and expression of Mfn2 were significantly downregulated, which correlated with decreased cell viability and increased apoptosis. By contrast, overexpression of Mfn2 significantly repressed I/R-mediated cell death through modulation of glucose metabolism and oxidative stress. Furthermore, Mfn2 overexpression improved mitochondrial fusion in cells, an effect that was followed by increased mitochondrial membrane potential, improved mitophagy, and inhibition of mitochondria-mediated apoptosis. Our data also demonstrated that Mfn2 overexpression was associated with activation of the AMPK/Sirt3 signaling pathway. Inhibition of the AMPK/Sirt3 pathway abolished the protective effects of Mfn2 on I/R-induced cell injury arising from mitochondrial damage. Our results indicate that Mfn2 protects against cardio-cerebrovascular I/R injury by augmenting mitochondrial fusion and activating the AMPK/Sirt3 signaling pathway.

Agrobacterium tumefaciens is the causal agent of crown gall disease in nature; in the laboratory the bacterium is widely used for plant genetic modification. The bacterium delivers a single-stranded transferred DNA (T-DNA) and a group of crucial virulence proteins into host cells. A putative T-complex is formed inside host cells that is composed of T-DNA and virulence proteins VirD2 and VirE2, which protect the foreign DNA from degradation and guide its way into the host nucleus. However, little is known about how the T-complex is assembled inside host cells. We combined the split-GFP and split-sfCherry labeling systems to study the interaction of Agrobacterium-delivered VirE2 and VirE3 in host cells. Our results indicated that VirE2 co-localized with VirE3 on the cytoplasmic side of the host cellular membrane upon the delivery. We identified and characterized two tandem domains at the VirE3 C-terminus that interacted with VirE2 in vitro. Deletion of these two domains abolished the VirE2 accumulation on the host plasma membrane and affected the transformation. Furthermore, the two VirE2-interacting domains of VirE3 exhibited different affinities with VirE2. Collectively, this study demonstrates that the anchorage protein VirE3 uses the two tandem VirE2-interacting domains to facilitate VirE2 protection for T-DNA at the cytoplasmic side of the host cell entrance.

Osteoarthritis (OA) is a chronic degenerative disease wherein the articular cartilage exhibits inflammation and degradation. Scutellarin (SCU) is a flavonoid glycoside with a range of pharmacological activities, as shown in previous studies demonstrating its anti-inflammatory activity. How SCU impacts the progression of OA, however, has not been explored to date. Herein, we assessed the impact of SCU on murine chondrocytes in an OA model system. In in vitro assays, we measured chondrocyte expression of key OA-associated factors such as matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) via qRT-PCR and Western blotting, the expression of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were detected by qRT-PCR. Our results showed that the downregulation of MMP-13, ADAMTS-5, COX-2, and iNOS expression by SCU and the overproduction of IL-6, TNF-α, and PGE2 induced by IL-1β were all inhibited by SCU in a concentration-dependent manner. Moreover, SCU was able to reverse aggrecan and collagen II degradation and nuclear factor-κB (NF-κB) and nuclear factor erythroid-derived 2-like 2 (Nrf2) signaling pathway activation both in vivo and in vitro. We further used a destabilization of the medial meniscus (DMM) murine model of OA to explore the therapeutic benefits of SCU in vivo. Together, our findings suggest SCU to be a potentially valuable therapeutic agent useful for treating OA.

Inhibition of histone deacetylases (HDACs) has been an important emerging therapy for the treatment of multiple cancers. However, the application of HDAC inhibitors is restricted by the limited potency against solid tumors. In order to discover novel HDAC inhibitors with potent antitumor activities, nitrogen mustard group was introduced to the structure of CI994. The derived molecule N-(2-aminophenyl)-4-(bis(2-chloroethyl)amino)benzamide (NA) exhibited enzyme inhibitory pattern of class I selectivity with IC50 values of 95.2, 260.7, and 255.7 nM against HDAC1, HDAC2, and HDAC3, respectively. In the antiproliferative assay, NA exhibited 10.3-fold (2.66 μM) and 11.3-fold (1.73 μM) higher potency than did suberoylanilide hydroxamic acid (SAHA) (27.3 and 19.5 μM) in inhibition of A2780 and HepG2 cell growth, respectively. Further HepG2 cell-based cell cycle and apoptosis studies revealed that induction of the G2/M phase arrest and cell apoptosis contributes to the antitumor effects of NA. It is suggested that NA could be utilized as a lead compound in the development of bifunctional HDAC inhibitors for the treatment of solid tumors.

The Asian citrus psyllid (Diaphorina citri) is a major pest of citrus trees as it transmits Candidatus Liberibacter asiaticus (CLas). The composition of a host’s microbiota can affect the evolution and ecological distribution of the host. This study monitored the compositional shifts in the citrus psyllid microbiota through all the life stages (egg, nymph 1–5 stages, and adult) by next-generation sequencing (NGS) and quantitative real-time PCR. There were clear differences in both α- and β-diversity of microbiota through the psyllid life stages. Microbiota diversity was markedly higher in the nymph 2–5 stages than in the adult, egg, and nymph 1 stages. Proteobacteria were dominant in all the life stages of D. citri, representing >97.5% of the total bacterial community, and Candidatus Profftella armature was the dominant genus in all the life stages. Data from the qPCR analysis showed an exponential increase in the populations of three D. citri endosymbionts: Candidatus Profftella armature, Candidatus Carsonella ruddii, and Wolbachia. The gut bacterium Pantoea was present in all the life stages, but it was markedly higher in the nymph 2–5 stages. The microbiota composition substantially differed among the egg–nymph 1, nymphs 2–5, and adult stages. Therefore, we successfully characterized the microbiota dynamics and thus identified a microbiota shift during the life cycle of D. citri by 16S rRNA gene sequencing and quantitative PCR. Moreover, 16S rRNA gene sequencing suggested that D. citri acquired the ability to bear CLas in the nymph 1 stage. This study enhances our understanding of microbial establishment in the developing D. citri and provides a reference resource for the identification of potential biocontrol approaches against this pest.

Antibiotic residues that enter the soil through swine manure could disturb the number, community structure and functions of microbiota which could also degrade antibiotics in soil. Five different concentrations of doxycycline (DOX) incorporated into swine manure were added to soil to explore the effects of DOX on microbiota in soil and degradation itself. The results showed that the soil microbiome evolved an adaptation to the soil containing DOX by generating resistance genes. Moreover, some of the organisms within the soil microbiome played crucial roles in the degradation of DOX. The average degradation half-life of DOX in non-sterile groups was 13.85 ± 0.45 days, which was significantly shorter than the 29.26 ± 0.98 days in the group with sterilized soil (P < 0.01), indicating that the soil microbiome promoted DOX degradation. DOX addition affected the number of tetracycline resistance genes, depending on the type of gene and the DOX concentration. Among these genes, tetA, tetM, tetW, and tetX had significantly higher copy numbers when the concentration of DOX was higher. In contrast, a lower concentration of DOX had an inhibitory effect on tetG. At the same time, the microbial compositions were affected by the initial concentration of DOX and the different experimental periods. The soil chemical indicators also affected the microbial diversity changes, mainly because some microorganisms could survive in adversity and become dominant bacterial groups, such as the genera Vagococcus and Enterococcus (which were associated with electrical conductivity) and Caldicoprobacter spp. (which were positively correlated with pH). Our study mainly revealed soil microbiota and DOX degradation answered differently under variable concentrations of DOX mixed with swine manure in soil.

Bovine herpesvirus 1 (BoHV-1) is a highly contagious viral pathogen which causes infectious bovine rhinotracheitis in cattle worldwide. Currently, there is no antiviral prophylactic treatment available capable of mitigating the disease impact and facilitating recovery from latent infection. In this study, we have engineered a novel recombinant anti-BoHV-1 immunotoxin construct termed “BoScFv-PE38” that consists of a single-chain monoclonal antibody fragment (scFv) fused with an active domain of Pseudomonas exotoxin A as a toxic effector (PE38). The recombinant BoScFv-PE38 immunotoxin expressed in a prokaryotic expression system has specific binding affinity for BoHV-1 glycoprotein D (gD) with a dissociation constant (Kd) of 12.81 nM and for BoHV-1 virus particles with a Kd value of 97.63 nM. We demonstrate that the recombinant BoScFv-PE38 is internalized into MDBK cell compartments that inhibit BoHV-1 replication with a half-maximal inhibitory concentration (IC50) of 4.95 ± 0.33 nM and a selective index (SI) of 456 ± 31. Furthermore, the BoScFv-PE38 exerted a cytotoxic effect through the induction of ATP and ammonia, leading to apoptosis of BoHV-1-infected cells and the inhibition of BoHV-1 replication in MDBK cells. Collectively, we show that BoScFv-PE38 can potentially be employed as a therapeutic agent for the treatment of BoHV-1 infection.

IntroductionHyperarousal has been a significant pathophysiological theory related to insomnia disorder (ID), characterized by excessive cortical activation and abnormal electroencephalogram (EEG) power during daytime or sleep. However, there is currently insufficient attention to the EEG power during rapid eye movement (REM) sleep and different stages of non-rapid eye movement (NREM) sleep. Additionally, whether the abnormal sleep EEG power in ID patients can be restored by repetitive transcranial magnetic stimulation (rTMS) remains unclear.Methods> Data of 26 ID patients and 26 healthy controls (HCs) were included in the current observational study. The comparisons of relative power between patients and HCs at baseline in each band of each sleep stage and the changes in patients before and after rTMS treatment were performed. The correlations between relative power and behavioral measures of the patients were also investigated.ResultsAbnormalities in sleep EEG relative power in the delta, beta and gamma bands of the patients were observed in NREM2, NREM3 and REM sleep. Correlations were identified between relative power and behavioral measures in ID group, primarily encompassing sleep efficiency, sleep onset latency and depression scores. Post-treatment improvements in relative power of the delta and beta band were observed in NREM2 sleep.DiscussionThe relative power of sleep EEG exhibited a significant correlation with sleep measures in ID patients, and demonstrated notable differences from HCs across the delta, beta, and gamma frequency bands. Furthermore, our findings suggest that rTMS treatment may partially ameliorate relative power abnormalities in patients with ID.

ObjectiveThe appropriate use of statins plays a vital role in reducing the risk of atherosclerotic cardiovascular disease (ASCVD). However, due to changes in diet and lifestyle, there has been a significant increase in the number of individuals with high cholesterol levels. Therefore, it is crucial to ensure the rational use of statins. Adverse reactions associated with statins, including liver enzyme abnormalities and statin-associated muscle symptoms (SAMS), have impacted their widespread utilization. In this study, we aimed to develop a predictive model for statin efficacy and safety based on real-world clinical data using machine learning techniques.MethodsWe employed various data preprocessing techniques, such as improved random forest imputation and Borderline SMOTE oversampling, to handle the dataset. Boruta method was utilized for feature selection, and the dataset was divided into training and testing sets in a 7:3 ratio. Five algorithms, including logistic regression, naive Bayes, decision tree, random forest, and gradient boosting decision tree, were used to construct the predictive models. Ten-fold cross-validation and bootstrapping sampling were performed for internal and external validation. Additionally, SHAP (SHapley Additive exPlanations) was employed for feature interpretability. Ultimately, an accessible web-based platform for predicting statin efficacy and safety was established based on the optimal predictive model.ResultsThe random forest algorithm exhibited the best performance among the five algorithms. The predictive models for LDL-C target attainment (AUC = 0.883, Accuracy = 0.868, Precision = 0.858, Recall = 0.863, F1 = 0.860, AUPRC = 0.906, MCC = 0.761), liver enzyme abnormalities (AUC = 0.964, Accuracy = 0.964, Precision = 0.967, Recall = 0.963, F1 = 0.965, AUPRC = 0.978, MCC = 0.938), and muscle pain/Creatine kinase (CK) abnormalities (AUC = 0.981, Accuracy = 0.980, Precision = 0.987, Recall = 0.975, F1 = 0.981, AUPRC = 0.987, MCC = 0.965) demonstrated favorable performance. The most important features of LDL-C target attainment prediction model was cerebral infarction, TG, PLT and HDL. The most important features of liver enzyme abnormalities model was CRP, CK and number of oral medications. Similarly, AST, ALT, PLT and number of oral medications were found to be important features for muscle pain/CK abnormalities. Based on the best-performing predictive model, a user-friendly web application was designed and implemented.ConclusionThis study presented a machine learning-based predictive model for statin efficacy and safety. The platform developed can assist in guiding statin therapy decisions and optimizing treatment strategies. Further research and application of the model are warranted to improve the utilization of statin therapy.

Tobacco cembranoids, known for their anti-insect and antifungal properties, were shown to be mainly present on the surface of leaves and flowers, being biosynthesized by their trichomes. It remains unclear whether they could be biosynthesized in other organs without trichomes. Cembratrien-ol synthases (CBTSs) catalyze the conversion of GGPP to CBT-ols and thus play an important role in cembranoid biosynthesis. This study identified the CBTS family genes in tobacco and examined their spatiotemporal expression patterns. The CBTS genes showed diverse expression patterns in tobacco organs, with the majority highly expressed in leaves and a few highly expressed in flowers. The expression of CBTS genes were also correlated with the development of tobacco plants, and most of them showed the highest expression level at the budding stage. Furthermore, their expression is mediated by the JA (jasmonate) signaling in all tobacco organs. Several CBTS genes were found to be highly expressed in tobacco roots that have no trichomes, which prompted us to determine the cembranoid production in roots and other organs. GC-MS and UPLC assays revealed that cembranoids were produced in all tobacco organs, which was supported by the bioactivity assay results that almost all these CBTS enzymes could catalyze CBT-ol biosyntheis in yeast, and that the content ratio of CBT-ols and CBT-diols in tobacco roots was different to that in leaves. This work sheds insights into the expression profiles of tobacco CBTS genes and provides a feasibility to engineer tobacco roots for industrial production of cembranoids.

Osteoimmunology is a concept involving molecular and cellular crosstalk between the skeletal and immune systems. Toll-like receptors (TLRs) are widely expressed both on mesenchymal stromal cells (MSCs), the hematopoietic cells, and immune cells in the osteogenic microenvironment for bone development or repair. TLRs can sense both exogenous pathogen-associated molecular patterns (PAMPs) derived from microorganisms, and damage-associated molecular patterns (DAMPs) derived from normal cells subjected to injury, inflammation, or cell apoptosis under physiological or pathological conditions. Emerging studies reported that TLR signaling plays an important role in bone remodeling by directly impacting MSC osteogenic differentiation or osteoimmunology. However, how to regulate TLR signaling is critical and remains to be elucidated to promote the osteogenic differentiation of MSCs and new bone formation for bone tissue repair. This review outlines distinct TLR variants on MSCs from various tissues, detailing the impact of TLR pathway activation or inhibition on MSC osteogenic differentiation. It also elucidates TLR pathways’ interplay with osteoclasts, immune cells, and extracellular vesicles (EVs) derived from MSCs. Furthermore, we explore biomaterial-based activation to guide MSCs’ osteogenic differentiation. Therefore, understanding TLRs’ role in this context has significant implications for advancing bone regeneration and repair strategies.

IntroductionAtrial fibrillation (AF) is a challenging cardiovascular disease worldwide. Wearable electrocardiograph devices (WEDs) have great potential to improve the detection rate of AF in primary care. However, the factors that influence general practitioners’ (GPs) perception and acceptance of WEDs are not well understood. To identify factors that influence the intention of GPs to utilize WEDs in a clinical setting to screen patients for AF.MethodThe research hypotheses and questionnaire items were designed and developed based on the unified theory of acceptance and technology (UTAUT) framework. We used stratified sampling and obtained the data through an online survey. Structural equation modeling was used to analyze the collected data.Results: A total of 1,004 valid questionnaires from GPs across Sichuan province in China were collected. Three factors increased GPs’ intention to utilize WEDs to screen patients for AF, including performance expectancy (β = 0.121, p = 0.004), social influence (β = 0.356, p

BackgroundFew studies have explored the mechanisms linking adverse childhood experiences (ACEs) to depression in medical students. This study aimed to investigate the relationship between ACEs and depression through the serial mediation effect of family functioning and insomnia.MethodsA cross-sectional survey was conducted with 368 medical students from university in Chengdu in 2021. The participants were asked to complete four self-report questionnaires, including ACEs scale, the family APGAR index, the ISI and PHQ-9. Singe and serial mediation analyses were conducted using structural equation modeling by Mplus 8.3.ResultsACEs had a significant direct effect on depression (β = 0.438, p

Citric acid is the primary organic acid that affects the taste of strawberry fruit. Glycolysis supplies key substrates for the tricarboxylic acid cycle (TCA cycle). However, little is known about the regulatory mechanisms of glycolytic genes on citric acid metabolism in strawberry fruits. In this study, the citric acid content of strawberry fruit displayed a trend of rising and decreasing from the initial red stage to the full red stage and then dark red stage. Thus, a difference in citric acid metabolic regulation was suspected during strawberry fruit development. In addition, overexpression of either cytoplasm glyceraldehyde-3-phosphate dehydrogenase (FxaC_14g13400, namely FaGAPC2) or pyruvate kinase (FxaC_15g00080, namely FaPKc2.2) inhibited strawberry fruit ripening and the accumulation of citric acid, leading to a range of maturity stages from partial red to full red stage. The combined transcriptome and metabolome analysis revealed that overexpression of FaGAPC2 and FaPKc2.2 significantly suppressed the expression of phosphoenolpyruvate carboxykinase (FxaC_1g21491, namely FaPEPCK) but enhanced the content of glutamine and aspartic acid. Meanwhile, the activities of PEPCK and glutamate decarboxylase (GAD) were inhibited, but the activities of glutamine synthase (GS) were increased in FaGAPC2/FaPKc2.2-overexpressed fruit. Further, functional verification demonstrated that overexpression of FaPEPCK can promote strawberry fruit ripening, resulting in a range of maturity stage from full red to dark red stage, while the citric acid synthase (CS) activities and citric acid content were significantly decreased. Overall, this study revealed that FaGAPC2/FaPKc2.2 and FaPEPCK perform an important role in reducing citric acid content in strawberry fruit, and FaGAPC2/FaPKc2.2 mainly by promoting the GS degradation pathway and FaPEPCK mainly by inhibiting the CS synthesis pathway.

The plant U-box (PUB) proteins are a type of E3 ubiquitin ligases well known for their functions in response to various stresses. They are also related to fruit development and ripening. However, PUB members possess such roles that remain unclear in strawberry. In this study, 155 PUB genes were identified in octoploid strawberry and classified into four groups. Their promoters possessed a variety of cis-acting elements, most of which are associated with abiotic stresses, followed by phytohormones response and development. Protein-protein interaction analysis suggested that FaU-box members could interact with each other as well as other proteins involved in hormone signaling and stress resistance. Transcriptome-based and RT-qPCR expression analysis revealed the potential involvement of FaU-box genes in resistance to stresses and fruit ripening. Of these, FaU-box98 and FaU-box136 were positively while FaU-box52 was negatively related to strawberry ripening. FaU-box98 comprehensively participated in resistance of ABA, cold, and salt, while FaU-box83 and FaU-box136 were broadly associated with drought and salt stresses. FaU-box18 and FaU-box52 were ABA-specific; FaU-box3 was specific to salt stress. In addition, the functional analysis of a randomly selected FaU-box (FaU-box127) showed that the transient overexpression of FaU-box127 promoted the ripening of strawberry fruit, along with significant changes in the expression levels of some ripening-related genes and the content of organic acid and soluble sugar. Overall, these findings provided comprehensive information about the FaU-box gene family and identified the potential FaU-box members participating in stress resistance and strawberry fruit ripening regulation.

BackgroundSelf-management is important for the blood sugar control of middle-aged and elderly Type 2 diabetes mellitus (T2DM) patients, of which diet, exercise, and drug compliance are the most common components. The Information-Motivation-Behavioral Skills Model (IMB) has been widely used in health behavior management and intervention.ObjectiveThe purpose of this study is to develop and validate the Diabetic Self-Management Scale (DSMS) based on the IMB model.MethodsSelf-report survey data was collected from middle-aged and elderly T2DM patients in Zhongmu City, Henan Province, China in November 2021 using convenience sampling. The original DSMS was developed through a literature review and summary of previous similar scales using an inductive approach. Item modification was finished by a panel of specialists. Exploratory factor analysis and confirmatory factor analysis were used to evaluate the reliability, convergent validity, discriminant validity, and criterion validity of DSMS.ResultsFour hundred and sixty nine T2DM patients completed the questionnaire survey. The final DSMS consists of 22 items with three dimensions, including information (five items), motivation (eight items), and behavior skills (nine items). The results of simple factor analysis showed that the KMO value was 0.839, Bartlett spherical test 2 = 3254.872, P < 0.001. The results of confirmatory factor analysis showed that 2/df = 2.261, RMSEA = 0.073, CFI = 0.937, TLI = 0.930, and SRMR = 0.096. The standardized factor loadings of 22 DSMS items were all above 0.6, and the CR values of 3 dimensions were all higher than 0.9. In addition, DSMS also showed good discriminant and criterion validity.ConclusionThe 22-item DSMS has good reliability and validity, and can be used to make diabetic self-management assessment regarding diet, physical activity, and medication among middle-aged and elderly Chinese T2DM patients. DSMS is of moderate length and easy to understand. It can be promoted in China in the future to understand the self-management status of middle-aged and elderly T2DM patients in China.

Background and purposeAcute aortic dissection (AAD) is a life-threatening cardiovascular emergency. Both neutrophil granzyme and interleukin (IL)-33/ST2 systems have proven to be effective diagnostic markers for AAD. This study aimed to investigate the relationship between plasma IL-33, soluble suppression of tumorigenesis-2 (sST2), myeloperoxidase (MPO), and matrix metalloproteinase (MMP)-9 levels at admission and all-cause mortality in patients with AAD.MethodsA total of 155 patients with AAD were enrolled from the Prospective Evaluation of Acute Chest Pain (PEACP) study. Plasma concentrations of IL-33, sST2, and MMP-9 were measured using an enzyme-linked immunosorbent assay, and MPO was detected using a chemiluminescence immunoassay. Aortic anatomical parameters were measured using CT radiography. The primary endpoint was all-cause mortality rate.ResultsThe median age of the patients was 55 years, and 96 (61.9%) were diagnosed with type A-AAD. After adjusting for confounding factors, the highest tertiles of IL-33, sST2, MPO, and MMP-9 had hazard risks of 0.870 (95% CI: 0.412–1.836, P = 0.714), 3.769 (95% CI: 1.504–9.446, P = 0.005), 4.689 (95% CI: 1.985–11.076, P < 0.001), and 4.748 (95% CI: 1.763–12.784, P = 0.002), respectively, compared to the lowest tertile. Pearson’s correlation analysis revealed a significant correlation between these markers (P < 0.001). Moreover, sST2, MPO, and MMP-9 levels had a significant positive correlation with aortic diameter and pseudolumen area (P < 0.001).ConclusionThe biomarkers sST2, MPO, and MMP-9 were independently associated with mortality in patients with AAD. The significant correlation between these biomarkers suggests a pathogenic role for the IL-33/ST2/neutrophil granzyme system in patients with AAD.

Cartilage endplate (CEP) plays important roles in the onset and progression of intervertebral disc degeneration (IVDD). Icariin (ICA) is the major active ingredient of Herba Epimedii and has various biological activities such as anti-inflammatory and antioxidant, which is used to treat many degenerative diseases. However, the effects and mechanism of ICA on endplate chondrocytes are still unclear. Herein, we studied the effects of ICA on CEP degeneration and elucidated the underlying mechanisms. Endplate chondrocytes were isolated, and TNF-α and TBHP were applied to mimic an IVDD pathological environment. Also, an IVDD mice model was established by transection of bilateral facet joints to investigate the protective effect of ICA in vivo. We found that ICA treatment inhibited the chondrocytes apoptosis and the decrease of extracellular matrix production in a dose-dependent manner. Our in vivo experiments demonstrated that ICA could ameliorate IVDD development and CEP calcification. We also found that the ICA-activated Nrf-2/HO-1 pathway thus promoted the Parkin-mediated mitophagy process and inhibited chondrocytes ferroptosis, thus alleviated redox imbalance and mitochondrial dysfunction and eventually improved cell survival. Knockdown of Nrf-2 using siRNA reversed the protective effect of ICA on endplate chondrocytes apoptosis and degeneration. In conclusion, our study demonstrated that ICA could protect against CEP degeneration and calcification under IVDD pathological conditions, the associated mechanism may be related to Nrf-2/HO-1-mediated mitophagy activation and ferroptosis inhibition. Our results suggest that ICA may be a potential effective medicine for IVDD prevention and treatment.

ObjectiveTo explore the risk factors of ectopic pregnancy after in vitro fertilization.MethodsThis retrospective cohort study was conducted at the Reproductive Medical Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to April 2020. Univariate and multivariate analysis were used to analyze the related factors affecting the occurrence of ectopic pregnancy (EP) and to construct a nomographic prediction model for the incidence of ectopic pregnancy.ResultsA total of 12,766 cycles of 10109 patients were included, comprising 214 cases of EP and 12,552 cases of intrauterine pregnancy (IUP). Multivariate logistic regression analysis showed that the tubal factor was associated with a 2-fold increased risk for EP (aOR = 2.72, 95% CI: 1.69-4.39, P < 0.0001). A stratified analysis showed that women with an endometrial thickness (EMT) between 7.6 to 12.1mm (aOR = 0.57, 95%CI: 0.36-0.90, P = 0.0153) and >12.1mm (aOR = 0.42, 95%CI: 0.24-0.74, P = 0.0026) had a significant reduction of the risk of EP compared to women with an EMT of

Pyroptosis is primarily considered a pro-inflammatory class of caspase-1- and gasdermin D (GSDMD)-dependent programmed cell death. Inflammasome activation promotes the maturation and release of interleukin (IL)-1β and IL-18, cleavage of GSDMD, and development of pyroptosis. Recent studies have reported that NLRP3 inflammasome activation-mediated pyroptosis aggravates the formation and development of diabetes cardiomyopathy (DCM). These studies provide theoretical mechanisms for exploring a novel approach to treat DCM-associated cardiac dysfunction. Accordingly, this review aims to summarize studies that investigated possible DCM therapies targeting pyroptosis and elucidate the molecular mechanisms underlying NLRP3 inflammasome-mediated pyroptosis, and its potential association with the pathogenesis of DCM. This review may serve as a basis for the development of potential pharmacological agents as novel and effective treatments for managing and treating DCM.

BackgroundClinical cardiovascular disease (CVD) and cognition impairment are common and often coexist in aging populations, and CVD is associated with greater cognition impairment risk; however, the association between cognition impairment and CVD risk is inconsistent. It is unknown if pathways that contribute to CVD are caused by impaired cognition. We hypothesized that cognition impairment would be associated with greater subclinical CVD including subclinical myocardial damage [assessed by high-sensitivity cardiac troponin T (hs-cTnT)] and cardiac strain or dysfunction [assessed by N-terminal pro-B-type natriuretic peptide (NT-proBNP)].MethodsThis analysis included Atherosclerosis Risk in Communities Study (ARIC) participants who underwent global cognition z-score tests between 1991 and 1993. Cardiac biomarkers were measured from stored plasma samples collected between 1996 and 1999. Logistic regression models were used to determine the association of cognitive function with subclinical CVD risk.ResultsThere were 558/9216 (6.1%) and 447/9097 (5.0%) participants with incident elevated hs-CTnT (≥14 ng/L) and NT-proBNP (≥300 pg/mL) levels, respectively. Comparing the lowest and highest quartiles of global cognition z-scores, a higher incidence of elevated hs-CTnT [odds ratio (OR) = 1.511, 95% confidence interval (CI): 1.093–2.088, P = 0.013] and NT-proBNP (OR = 1.929, 95% CI: 1.350–2.755, P < 0.001) were observed, respectively. In structural equation modeling, the indirect effect of global cognition z-score on major adverse cardiac events was 42.1% (P < 0.05).ConclusionImpairments in baseline cognitive function were associated with subclinical myocardial damage or wall strain. Although future studies are warranted to investigate the pathophysiological mechanisms behind these associations, our study suggests common pathways between cognitive and cardiac dysfunction.

The enriched phenolic content attributes to the promising health benefit of strawberry fruits. On behalf of screening and seeking the breeding material with high phytochemical composition, a mutant (MT) of strawberry ‘Benihoppe’ (WT) with high total flavonoid content (TFC), especially anthocyanins and proanthocyanidins (PAs), was identified in this study. To investigate the possible reason for these disparities during strawberry fruit development, an integrated transcriptomic and metabolomic analysis was conducted using these two specific materials. As a result, a total of 113 flavonoid compounds were detected, a specific anthocyanin, namely, petunidin 3-O-rutinoside was detected for the first time in strawberry. By comparing with the WT fruits, a significant reduction of petunidin 3-O-rutinoside while around 24 times higher of cyanidin 3-O-rutinoside in MT fruits were observed. However, the cyanidin 3-glucoside content did not show obvious changes between MT and WT fruits, the pelargonidin and its derivatives were up-regulated only in partial red (PR) stage, but not in large green (LG) and fully red (FR) stages. Notably, the PAs such as procyanidin B2, procyanidin A1, catechin, gallocatechin gallate, epigallacatechin, and theaflavin were markedly up-regulated in MT. These results revealed a differential flavonoid biosynthesis between the two detected strawberry genotypes. A joint analysis with transcriptome data explained the up-regulation of cyanidin-based anthocyanins and PAs were caused by the down-regulation of F3′5′H, and up-regulation of F3'H and LAR expression, which might be regulated by the upregulation of potential TFs such as C3H, MADS, and AP2/ERF TFs. Metabolite correlation analysis suggested that it was PAs but not anthocyanins strongly correlated with the total phenolic content (TPC), indicated that PAs might contribute more to TPC than anthocyanins in our detected strawberry samples. This study not only potentially provided a new mutant for further breeding program to obtain high flavonoid content strawberry but also gave insights into strawberry flavonoid metabolic regulatory network, laid the foundation for identifying new flavonoid regulators in strawberry.

With the rapidly aging population, frailty, characterized by an increased risk of adverse outcomes, has become a major public health problem globally. Several frailty guidelines or consensuses recommend screening for frailty, especially in primary care settings. However, most of the frailty assessment tools are based on questionnaires or physical examinations, adding to the clinical workload, which is the major obstacle to converting frailty research into clinical practice. Medical data naturally generated by routine clinical work containing frailty indicators are stored in electronic health records (EHRs) (also called electronic health record (EHR) data), which provide resources and possibilities for frailty assessment. We reviewed several frailty assessment tools based on primary care EHRs and summarized the features and novel usage of these tools, as well as challenges and trends. Further research is needed to develop and validate frailty assessment tools based on EHRs in primary care in other parts of the world.