MR-based radiomics predictive modelling of EGFR mutation and HER2 overexpression in metastatic brain adenocarcinoma: a two-centre study.

OBJECTIVES: Magnetic resonance (MR)-based radiomics features of brain metastases are utilised to predict epidermal growth factor receptor (EGFR) mutation and human epidermal growth factor receptor 2 (HER2) overexpression in adenocarcinoma, with the aim to identify the most predictive MR sequence. METHODS: A retrospective inclusion of 268 individuals with brain metastases from adenocarcinoma across two institutions was conducted. Utilising T1-weighted imaging (T1 contrast-enhanced [T1-CE]) and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequences, 1,409 radiomics features were extracted. These sequences were randomly divided into training and test sets at a 7:3 ratio. The selection of relevant features was done using the least absolute shrinkage selection operator, and the training cohort's support vector classifier model was employed to generate the predictive model. The performance of the radiomics features was evaluated using a separate test set. RESULTS: For contrast-enhanced T1-CE cohorts, the radiomics features based on 19 selected characteristics exhibited excellent discrimination. No significant differences in age, sex, and time to metastasis were observed between the groups with EGFR mutations or HER2 + and those with wild-type EGFR or HER2 (p > 0.05). Radiomics feature analysis for T1-CE revealed an area under the curve (AUC) of 0.98, classification accuracy of 0.93, sensitivity of 0.92, and specificity of 0.93 in the training cohort. In the test set, the AUC was 0.82. The 19 radiomics features for the T2-FLAIR sequence showed AUCs of 0.86 in the training set and 0.70 in the test set. CONCLUSIONS: This study developed a T1-CE signature that could serve as a non-invasive adjunctive tool to determine the presence of EGFR mutations and HER2 + status in adenocarcinoma, aiding in the direction of treatment plans. CLINICAL RELEVANCE STATEMENT: We propose radiomics features based on T1-CE brain MR sequences that are both evidence-based and non-invasive. These can be employed to guide clinical treatment planning in patients with brain metastases from adenocarcinoma.

Polygalacturonase-inhibiting proteins as an exogenously applied natural solution for prevention of postharvest fungal infections.

Polygalacturonase inhibiting proteins (PGIPs) are plant proteins involved in the inhibition of polygalacturonases (PGs), cell-wall degrading enzymes often secreted by phytopathogenic fungi. Previously, we confirmed that PGIP2 from Phaseolus vulgaris (PvPGIP2) can inhibit the growth of Aspergillus niger and Botrytis cinerea on agar plate. In this study, we further validated the feasibility of using PGIP as an environmental and ecological friendly agent to prevent fungal infection post-harvest. We found that application of either purified PGIP (full length PvPGIP2 or truncated tPvPGIP2_5-8), or PGIP-secreting Saccharomyces cerevisiae strains can effectively inhibit fungal growth and necrotic lesions on tobacco leaf. We also examined the effective amount and thermostability of PGIP when applied on plants. A concentration of 0.75 mg/mL or higher can significantly reduce the area of B. cinerea lesions. The activity of full-length PvPGIPs is not affected after incubation at various temperatures ranging from -20 to 42 °C for 24 h, while truncated tPvPGIP2_5-8 lost some efficacy after incubation at 42 °C. Furthermore, we have also examined the efficacy of PGIP on tomato fruit. When the purified PvPGIP2 proteins were applied to tomato fruit inoculated with B. cinerea at a concentration of roughly 1.0 mg/mL, disease incidence and area of disease had reduced by more than half compared to the controls without PGIP treatment. This study explores the potential of PGIPs as exogenously applied, eco-friendly fungal control agents on fruit and vegetables post-harvest.

Subtype-Specific Association of Mitochondrial DNA Copy Number With Poststroke/TIA Outcomes in 10†241 Patients in China.

BACKGROUND: Mitochondrial DNA copy number (mtDNA-CN) is associated with the severity and mortality in patients with stroke, but the associations in different stroke subtypes remain unexplored. METHODS: We conducted an observational prospective cohort analysis on patients with ischemic stroke or transient ischemic attack enrolled in the Third China National Stroke Registry. We applied logistic models to assess the association of mtDNA-CN with functional outcome (modified Rankin Scale score, 3-6 versus 0-2) and Cox proportional hazard models to assess the association with stroke recurrence (treating mortality as a competing risk) and mortality during a 12-month follow-up, adjusting for sex, age, physical activity, National Institutes of Health Stroke Scale at admission, history of stroke and peripheral artery disease, small artery occlusion, and interleukin-6. Subgroup analyses stratified by age and stroke subtypes were conducted. RESULTS: The Third China National Stroke Registry enrolled 15 166 patients, of which 10 241 with whole-genome sequencing data were retained (mean age, 62.2 [SD, 11.2] years; 68.8% men). The associations between mtDNA-CN and poststroke/transient ischemic attack outcomes were specific to patients aged ≤65 years, with lower mtDNA-CN significantly associated with stroke recurrence in 12 months (subdistribution hazard ratio, 1.15 per SD lower mtDNA-CN [95% CI, 1.04-1.27]; P=5.2×10-3) and higher all-cause mortality in 3 months (hazard ratio, 2.19 [95% CI, 1.41-3.39]; P=5.0×10-4). Across subtypes, the associations of mtDNA-CN with stroke recurrence were specific to stroke of undetermined cause (subdistribution hazard ratio, 1.28 [95% CI, 1.11-1.48]; P=6.6×10-4). In particular, lower mtDNA-CN was associated with poorer functional outcomes in stroke of undetermined cause patients diagnosed with embolic stroke of undetermined source (odds ratio, 1.53 [95% CI, 1.20-1.94]; P=5.4×10-4), which remained significant after excluding patients with recurrent stroke (odds ratio, 1.49 [95% CI, 1.14-1.94]; P=3.0×10-3). CONCLUSIONS: Lower mtDNA-CN is associated with higher stroke recurrence rate and all-cause mortality, as well as poorer functional outcome at follow-up, among stroke of undetermined cause, embolic stroke of undetermined source, and younger patients.

Tumor Microenvironment Remodeling-Mediated Sequential Drug Delivery Potentiates Treatment Efficacy.

Toll-like receptor 7/8 agonists, such as imidazoquinolines (IMDQs), are promising for the de novo priming of antitumor immunity. However, their systemic administration is severely limited due to the off-target toxicity. Here, this work describes a sequential drug delivery strategy. The formulation is composed of two sequential modules: a tumor microenvironment remodeling nanocarrier (poly(l-glutamic acid)-graft-methoxy poly(ethylene glycol)/combretastatin A4, termed CA4-NPs) and an immunotherapy nanocarrier (apcitide peptide-decorated poly(l-glutamic acid)-graft-IMDQ-N3 conjugate, termed apcitide-PLG-IMDQ-N3 ). CA4-NPs, as a vascular disrupting agent, are utilized to remodel the tumor microenvironment for enhancing tumor coagulation and hypoxia. Subsequently, the apcitide-PLG-IMDQ-N3 could identify and target tumor coagulation through the binding of surface apcitide peptide to the GPIIb-IIIa on activated platelets. Afterward, IMDQ is activated selectively through the conversion of "-N3 " to "-NH2 " in the presence of hypoxia. The biodistribution results confirm their high tumor uptake of activated IMDQ (22.66%ID/g). By augmenting the priming and immunologic memory of tumor-specific CD8+ T cells, 4T1 and CT26 tumors with a size of ≈500 mm3 are eradicated without recurrence in mouse models.

Super Resolution of Pulmonary Nodules Target Reconstruction Using a Two-Channel GAN Models.

RATIONALE AND OBJECTIVES: To develop a Dual generative-adversarial-network (GAN) Cascaded Network (DGCN) for generating super-resolution computed tomography (SRCT) images from normal-resolution CT (NRCT) images and evaluate the performance of DGCN in multi-center datasets. MATERIALS AND METHODS: This retrospective study included 278 patients with chest CT from two hospitals between January 2020 and June 2023, and each patient had all three NRCT (512×512 matrix CT images with a resolution of 0.70 mm, 0.70 mm,1.0 mm), high-resolution CT (HRCT, 1024×1024 matrix CT images with a resolution of 0.35 mm, 0.35 mm,1.0 mm), and ultra-high-resolution CT (UHRCT, 1024×1024 matrix CT images with a resolution of 0.17 mm, 0.17 mm, 0.5 mm) examinations. Initially, a deep chest CT super-resolution residual network (DCRN) was built to generate HRCT from NRCT. Subsequently, we employed the DCRN as a pre-trained model for the training of DGCN to further enhance resolution along all three axes, ultimately yielding SRCT. PSNR, SSIM, FID, subjective evaluation scores, and objective evaluation parameters related to pulmonary nodule segmentation in the testing set were recorded and analyzed. RESULTS: DCRN obtained a PSNR of 52.16, SSIM of 0.9941, FID of 137.713, and an average diameter difference of 0.0981 mm. DGCN obtained a PSNR of 46.50, SSIM of 0.9990, FID of 166.421, and an average diameter difference of 0.0981 mm on 39 testing cases. There were no significant differences between the SRCT and UHRCT images in subjective evaluation. CONCLUSION: Our model exhibited a significant enhancement in generating HRCT and SRCT images and outperformed established methods regarding image quality and clinical segmentation accuracy across both internal and external testing datasets.

Health characteristics and factors associated with transition shock in newly graduated registered nurses: a latent class analysis.

BACKGROUND: Transition shock occurs at a vulnerable time in newly graduated registered nurses' careers and has a clear impact on both newly graduated registered nurses' productivity and patient recovery outcomes. Identifying classification features of transition shock and targeting interventions to support newly graduated registered nurses is imperative. The study aimed to explore potential transition shock subgroups of newly graduated registered nurses and further explore the impact of population characteristics and two indices of health on transition shock. METHODS: A descriptive, cross-sectional design was conducted. An online questionnaire was sent via WeChat to newly graduated registered nurses who started work in 2021 at seven hospitals between August and November 2021, and 331 nurses filled out the questionnaire. Latent class analysis was used to identify the potential class of the transition shock of newly graduated registered nurses, and multinomial logistic regression analyses were used to determine the factors of potential classification. RESULTS: The study identified four classes of transition shock in newly graduated registered nurses, namely, "high transition shock", "physical fatigue-lack of knowledge", "development adaptation" and "low transition shock-worry" groups. Newly graduated registered nurses who urinated less than 4 times per day (OR = 0.051, 95% CI = 0.005-0.502) were likely to be in the "high transition shock" group. Newly graduated registered nurses who did not delay urination (OR = 4.267, 95% CI = 1.162-11.236) were more likely to belong to the "low transition shock-worry" group. Newly graduated registered nurses without sleep disturbance were more likely to be in the "physical fatigue - lack of knowledge" (OR = 3.109, 95% CI = 1.283-7.532), "development adaptation" (OR = 8.183, 95% CI = 2.447-27.066), and "low transition shock-worry" (OR = 8.749, 95% CI = 1.619-47.288) groups than in the 'high transition shock' group. CONCLUSIONS: This study highlights potential patterns of transition shock among newly graduated registered nurses. Two indices of health, namely, delayed urination and sleep disturbance, can predict the subgroups of newly graduated registered nurses with transition shock.

IRAK-M Plays A Role in the Pathology of Amyotrophic Lateral Sclerosis Through Suppressing the Activation of Microglia.

Microglial activation plays a crucial role in the disease progression in amyotrophic lateral sclerosis (ALS). Interleukin receptor-associated kinases-M (IRAK-M) is an important negative regulatory factor in the Toll-like receptor 4 (TLR4) pathway during microglia activation, and its mechanism in this process is still unclear. In the present study, we aimed to investigate the dynamic changes of IRAK-M and its protective effects for motor neurons in SOD1-G93A mouse model of ALS. qPCR (Real-time Quantitative PCR Detecting System) were used to examine the mRNA levels of IRAK-M in the spinal cord in both SOD1-G93A mice and their age-matched wild type (WT) littermates at 60, 100 and 140 days of age. We established an adeno-associated virus 9 (AAV9)-based platform by which IRAK-M was targeted mostly to microglial cells to investigate whether this approach could provide a protection in the SOD1-G93A mouse. Compared with age-matched WT mice, IRAK-M mRNA level was elevated at 100 and 140 days in the anterior horn region of spinal cords in the SOD1-G93A mouse. AAV9-IRAK-M treated SOD1-G93A mice showed reduction of IL-1ß mRNA levels and significant improvements in the numbers of spinal motor neurons in spinal cord. Mice also showed previously reduction of muscle atrophy. Our data revealed the dynamic changes of IRAK-M during ALS pathological progression and demonstrated that an AAV9-IRAK-M delivery was an effective and translatable therapeutic approach for ALS. These findings may help identify potential molecular targets for ALS therapy.

Molecular basis of SAP05-mediated ubiquitin-independent proteasomal degradation of transcription factors.

SAP05, a secreted effector by the obligate parasitic bacteria phytoplasma, bridges host SPL and GATA transcription factors (TFs) to the 26 S proteasome subunit RPN10 for ubiquitination-independent degradation. Here, we report the crystal structures of SAP05 in complex with SPL5, GATA18 and RPN10, which provide detailed insights into the protein-protein interactions involving SAP05. SAP05 employs two opposing lobes with an acidic path and a hydrophobic path to contact TFs and RPN10, respectively. Our crystal structures, in conjunction with mutagenesis and degradation assays, reveal that SAP05 targets plant GATAs but not animal GATAs dependent on their direct salt-bridged electrostatic interactions. Additionally, SAP05 hijacks plant RPN10 but not animal RPN10 due to structural steric hindrance and the key hydrophobic interactions. This study provides valuable molecular-level information into the modulation of host proteins to prevent insect-borne diseases.

Adenosinergic metabolism pathway: an emerging target for improving outcomes of solid organ transplantation.

Extracellular nucleotides are widely recognized as crucial modulators of immune responses in peripheral tissues. Adenosine triphosphate (ATP) and adenosine are key components of extracellular nucleotides, the balance of which contributes to immune homeostasis. Under tissue injury, ATP exerts its pro-inflammatory function, while the adenosinergic pathway rapidly degrades ATP to immunosuppressive adenosine, thus inhibiting excessive and uncontrolled inflammatory responses. Previous reviews have explored the immunoregulatory role of extracellular adenosine in various pathological conditions, especially inflammation and malignancy. However, current knowledge regarding adenosine and adenosinergic metabolism in the context of solid organ transplantation remains fragmented. In this review, we summarize the latest information on adenosine metabolism and the mechanisms by which it suppresses the effector function of immune cells, as well as highlight the protective role of adenosine in all stages of solid organ transplantation, including reducing ischemia reperfusion injury during organ procurement, alleviating rejection, and promoting graft regeneration after transplantation. Finally, we discuss the potential for future clinical translation of adenosinergic pathway in solid organ transplantation.

Metal-Oxide Heterojunction: From Material Process to Neuromorphic Applications.

As technologies like the Internet, artificial intelligence, and big data evolve at a rapid pace, computer architecture is transitioning from compute-intensive to memory-intensive. However, traditional von Neumann architectures encounter bottlenecks in addressing modern computational challenges. The emulation of the behaviors of a synapse at the device level by ionic/electronic devices has shown promising potential in future neural-inspired and compact artificial intelligence systems. To address these issues, this review thoroughly investigates the recent progress in metal-oxide heterostructures for neuromorphic applications. These heterostructures not only offer low power consumption and high stability but also possess optimized electrical characteristics via interface engineering. The paper first outlines various synthesis methods for metal oxides and then summarizes the neuromorphic devices using these materials and their heterostructures. More importantly, we review the emerging multifunctional applications, including neuromorphic vision, touch, and pain systems. Finally, we summarize the future prospects of neuromorphic devices with metal-oxide heterostructures and list the current challenges while offering potential solutions. This review provides insights into the design and construction of metal-oxide devices and their applications for neuromorphic systems.

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Transforming growth factor (TGF)-ß is a group of cytokines with anti-inflammatory effects in the TGF family, which participates in the development of stress and depression-related mechanisms, and plays roles in the regulation of inflammatory response in depression and the recovery of various cytokine imbalances. The core symptoms of depression is associated with TGF-ß level, and the psychological symptoms of depression are related to TGF-ß gene polymorphism. Various antidepressants may up-regulate TGF-ß level through the complex interaction between neurotransmitters and inflammatory factors, inhibiting inflammatory response and regulating cytokine imbalance to improve depressive symptoms. Studies have shown that recombinant TGF-ß1 protein has beneficial effects in mouse depression models, indicating TGF-ß1 might be a potential therapeutic target for depression and nasal sprays having the advantage of being fast acting delivery method. This article reviews the research progress on dynamic changes of TGF-ß level before and after depression treatment and the application of TGF-ß level as an indicator for the improvement of depressive symptoms. We provide ideas for the development of new antidepressants and for the evaluation of the treatment efficacy in depression.

A latent class analysis of resilience and its association with patient-reported symptoms in patients with esophageal cancer after esophagectomy.

Purpose: To identify the latent classes of resilience in patients with esophageal cancer after esophagectomy and develop a deeper understanding of the association between these classes and patient-reported symptoms. Background: China accounts for more than half of the global burden of esophageal cancer, and patients with esophageal cancer experience numerous symptoms that affect their quality of life and prognosis. Given that resilience is a key element that alleviates the progression of symptoms, it may represent a potential means of to enhancing cancer patients' physical and psychological well-being. Methods: The study was implemented in the thoracic surgery departments of three tertiary hospitals in eastern China. The participants were patients who were still hospitalized after esophagectomy. Data were gathered by self-report questionnaires, and a latent class analysis was utilized to identify different categories of resilience among the patients. Results: A total of 226 patients were recruited. The three classes of resilience identified included high strength and striving (53.5%), medium resilience but weak self-recovery (35.9%), and minimal tenacity and external support (10.6%). Patients with low income (OR = 12.540, p = 0.004) were more likely to be in the minimal tenacity and external support class. Patients without comorbidities (OR = 2.413, p = 0.013) and aged 66-70 years (OR = 4.272, p < 0.001) were more likely to be in the high strength and striving class. The patient-reported symptoms and symptom-related interference of patients after esophagectomy varied considerably among the three categories of resilience. Conclusion: Accurate interventions should be devised and executed according to the features of each type of resilience in patients after esophagectomy to maximize intervention efficacy. These findings highlight the important role of precision nursing.

The mediating role of cognitive emotion regulation in the relationship between self-concealment and quality of life among breast cancer chemotherapy patients.

PURPOSE: This study aimed to explore whether self-concealment (SC) affects the quality of life (QOL), and whether cognitive emotion regulation (CER) mediates the relationship between SC and QOL among breast cancer chemotherapy patients. METHODS: This cross-sectional study was conducted among 228 breast cancer chemotherapy patients from November 2021 to March 2022 in Anhui Province, China. Data were collected using the Self-Concealment Scale, Cognitive Emotion Regulation Questionnaire, and Short Form 36 Questionnaire. Descriptive statistics, independent-sample t test, one-way analysis of variance, and structural equation modeling were used to explore associations among SC, CER, and QOL. RESULTS: QOL levels differed significantly by participant age, monthly per capita household income and home location. SC was negatively correlated with QOL. SSC was negatively correlated with adaptive-CER strategies and positively correlated with maladaptive-CER strategies. Adaptive-CER strategies were positively correlated with QOL. Maladaptive-CER strategies were negatively correlated with QOL. CER fully mediated the association between SC and QOL in breast cancer chemotherapy patients. CONCLUSION: Nursing staff should help breast cancer chemotherapy patients reduce the use of maladaptive-CER strategies in the care of patients in the future. Helping patients reduce SC is more conductive to improving the QOL of breast cancer chemotherapy patients.

Impacts of census differential privacy for small-area disease mapping to monitor health inequities.

The U.S. Census Bureau will implement a modernized privacy-preserving disclosure avoidance system (DAS), which includes application of differential privacy, on publicly released 2020 census data. There are concerns that the DAS may bias small-area and demographically stratified population counts, which play a critical role in public health research, serving as denominators in estimation of disease/mortality rates. Using three DAS demonstration products, we quantify errors attributable to reliance on DAS-protected denominators in standard small-area disease mapping models for characterizing health inequities. We conduct simulation studies and real data analyses of inequities in premature mortality at the census tract level in Massachusetts and Georgia. Results show that overall patterns of inequity by racialized group and economic deprivation level are not compromised by the DAS. While early versions of DAS induce errors in mortality rate estimation that are larger for Black than non-Hispanic white populations in Massachusetts, this issue is ameliorated in newer DAS versions.

The STROMICS genome study: deep whole-genome sequencing and analysis of 10K Chinese patients with ischemic stroke reveal complex genetic and phenotypic interplay.

Ischemic stroke is a leading cause of global mortality and long-term disability. However, there is a paucity of whole-genome sequencing studies on ischemic stroke, resulting in limited knowledge of the interplay between genomic and phenotypic variations among affected patients. Here, we outline the STROMICS design and present the first whole-genome analysis on ischemic stroke by deeply sequencing and analyzing 10,241 stroke patients from China. We identified 135.59 million variants, > 42% of which were novel. Notable disparities in allele frequency were observed between Chinese and other populations for 89 variants associated with stroke risk and 10 variants linked to response to stroke medications. We investigated the population structure of the participants, generating a map of genetic selection consisting of 31 adaptive signals. The adaption of the MTHFR rs1801133-G allele, which links to genetically evaluated VB9 (folate acid) in southern Chinese patients, suggests a gene-specific folate supplement strategy. Through genome-wide association analysis of 18 stroke-related traits, we discovered 10 novel genetic-phenotypic associations and extensive cross-trait pleiotropy at 6 lipid-trait loci of therapeutic relevance. Additionally, we found that the set of loss-of-function and cysteine-altering variants present in the causal gene NOTCH3 for the autosomal dominant stroke disorder CADASIL displayed a broad neuro-imaging spectrum. These findings deepen our understanding of the relationship between the population and individual genetic layout and clinical phenotype among stroke patients, and provide a foundation for future efforts to utilize human genetic knowledge to investigate mechanisms underlying ischemic stroke outcomes, discover novel therapeutic targets, and advance precision medicine.

Identification of a Prunus MAX1 homolog as a unique strigol synthase.

Strigol is the first identified and one of the most important strigolactones (SLs), but the biosynthetic pathway remains elusive. We functionally identified a strigol synthase (cytochrome P450 711A enzyme) in the Prunus genus through rapid gene screening in a set of SL-producing microbial consortia, and confirmed its unique catalytic activity (catalyzing multistep oxidation) through substrate feeding experiments and mutant analysis. We also reconstructed the biosynthetic pathway of strigol in Nicotiana benthamiana and reported the total biosynthesis of strigol in the Escherichia coli-yeast consortium, from the simple sugar xylose, which paves the way for large-scale production of strigol. As proof of concept, strigol and orobanchol were detected in Prunus persica root extrudes. This demonstrated a successful prediction of metabolites produced in plants through gene function identification, highlighting the importance of deciphering the sequence-function correlation of plant biosynthetic enzymes to more accurately predicate plant metabolites without metabolic analysis. This finding revealed the evolutionary and functional diversity of CYP711A (MAX1) in SL biosynthesis, which can synthesize different stereo-configurations of SLs (strigol- or orobanchol-type). This work again emphasizes the importance of microbial bioproduction platform as an efficient and handy tool to functionally identify plant metabolism.

Effect of different doses of almorexant on learning and memory in 8-month-old APP/PS1 (AD) mice.

OBJECTIVE: To explore the effects of different doses of almorexant (an dual orexin receptor antagonist) on learning and memory in Alzheimer's disease (AD) mice. METHODS: Forty-four APP/PS1 (model of Alzheimer's disease; AD) mice were randomly divided into 4 groups: the control group (CON) and those that received 10 mg/kg almorexant (low dose; LOW), 30 mg/kg almorexant (medium dose; MED) and 60 mg/kg almorexant (high dose; HIGH). During the 28-day intervention period, mice received an intraperitoneal injection at the beginning of the light period (6:00 am). The effects of different doses of almorexant on learning and memory and 24-hour sleep-wake behaviour were assessed by immunohistochemical staining. The above continuous variables are expressed as the mean ± standard deviation (SD), and then univariate regression analysis and generalized estimating equations were performed to compare the groups; these results are expressed as the mean difference (MD) and 95% confidence interval (CI). The statistical software used STATA 17.0 MP. RESULTS: Forty-one mice completed the experiment (3 died: 2 mice in the HIGH group and 1 mouse in the CON group). Compared with the CON group, the LOW group (MD=6803 s, 95% CI: 4470 to 9137 s), MED group (MD=14,473 s, 95% CI: 12,140-16,806 s) and the HIGH group (MD=24,505 s, 95% CI: 22,052-26,959 s) had significantly longer sleep durations. The Y maze results showed that LOW group (MD=0.14,95%CI: 0.078-0.20) and MED group (MD=0.14,95%CI = 0.074-0.20) mice compared to the CON group, and the low-medium dose of Almorexant did not damage the short-term learning and memory performance of APP / PS1 (AD) mice.Compared with the CON, LOW, and MED groups, the HIGH group exhibited a significant decrease in the Aß plaque-positive area in the cortex (MD= -0.030, 95% CI: -0.035 to -0.025; MD=-0.049, 95% CI: -0.054 to -0.044; and MD=-0.07, 95% CI: -0.076 to -0.066, respectively). CONCLUSION: The moderate dose of almorexant (30 mg/kg) prolonged the sleep duration of APP/PS1 (AD) mice to a greater extent than the low dose (10 mg/kg) without altering learning and memory. The MED mice showed a good sleep response and a small residual effect on the next day. High-dose (60 mg / kg) almorexant impaired behavioral learning and memory performance in mice.Compared to the CON group and the LOW group, the MED group exhibited improved working memory. Thus, treatment with almorexant may reduce ß-amyloid deposition in AD, slowing neurodegeneration. Additional studies are needed to determine the mechanism of action.

Patient-derived models facilitate precision medicine in liver cancer by remodeling cell-matrix interaction.

Liver cancer is an aggressive tumor originating in the liver with a dismal prognosis. Current evidence suggests that liver cancer is the fifth most prevalent cancer worldwide and the second most deadly type of malignancy. Tumor heterogeneity accounts for the differences in drug responses among patients, emphasizing the importance of precision medicine. Patient-derived models of cancer are widely used preclinical models to study precision medicine since they preserve tumor heterogeneity ex vivo in the study of many cancers. Patient-derived models preserving cell-cell and cell-matrix interactions better recapitulate in vivo conditions, including patient-derived xenografts (PDXs), induced pluripotent stem cells (iPSCs), precision-cut liver slices (PCLSs), patient-derived organoids (PDOs), and patient-derived tumor spheroids (PDTSs). In this review, we provide a comprehensive overview of the different modalities used to establish preclinical models for precision medicine in liver cancer.

Experience in developing innovative practical ability for Master of Nursing Specialist degree program in China: A qualitative descriptive study of postgraduates.

BACKGROUND: Nursing talent training should be adjusted in accordance with policies and regulations, the priority areas of health care, the development of nursing disciplines, and changes in nurses' roles. Experience from nursing education stakeholders indicates that postgraduate education faces numerous challenges. Thus, it is necessary to discuss postgraduates' experience in cultivating innovative practical ability. OBJECTIVES: To analyze the experiences of nursing specialist postgraduates in cultivating innovative practical ability to provide a reference for further improvement of the Master of Nursing Specialist program. DESIGN: A qualitative study. SETTING: A university and its three affiliated tertiary hospitals in H city, China. PARTICIPANTS AND METHODS: Individual, semi-structured interviews were conducted face-to-face with 12 postgraduates currently in clinical practice and six postgraduate nurses within two years of graduation between April and June 2022. All interviews were audio-recorded and transcribed verbatim, and the data were analyzed using the Colaizzi method. RESULTS: Three key themes emerged: (1) the cognition of innovative practical ability; (2) the experience of cultivating innovative practical ability at school; and (3) the experience of cultivating innovative practical ability in the hospital. CONCLUSIONS: With a full understanding of the training experience of postgraduates' innovative practical ability, policymakers and training units can clarify the shortcomings of the training model, make targeted improvements, and work together to build a more scientific and complete MNS training model. Our findings have the potential to inform faculty structure, catalyze curriculum reform, optimize clinical practice to facilitate the development of Master of Nursing Specialist programs, improve the quality of care, and promote patient recovery.