Walking Dead Macrophage-Based Positive Enhancement MRI for Ultrahighly Efficient Diagnosis of Nephritis.

Nephritis is an inflammatory condition of the glomerulus, and the clinical gold standard for its diagnosis is a kidney biopsy. However, obtaining biopsy results can take several days, which does not meet the requirement of rapid diagnosis, especially for rapidly progressive types. To achieve an effective and noninvasive diagnosis, we propose a nephritis-specific, positive magnetic resonance imaging (MRI) contrast agent based on Gd3+ anchored walking dead macrophage Gd-RAW. Gd-RAW exhibits high selectivity for inflammatory renal parenchyma and provides comparable results to histopathology methods. The Gd-RAW-based MRI contrast agent reduces the diagnostic time of nephritis from 14 days of biopsy to 1 h. Furthermore, in a unilateral nephritis model constructed by increasing the glycerol concentration, the T1WI of renal parenchyma exhibits an increased signal-to-noise ratio, which is crucial for evaluating nephritic severity. This work promotes rapid diagnosis of nephritis and potentially provides sufficient evidence for clinicians to offer timely treatment to patients. The methodology of paramagnetic ion-anchored macrophage corpse also opens up new prospects for designing more specific and biosafe MRI contrast agents.

Integrative single-cell transcriptomic analyses reveal the cellular ontological and functional heterogeneities of primary and metastatic liver tumors.

BACKGROUND: The global cellular landscape of the tumor microenvironment (TME) combining primary and metastatic liver tumors has not been comprehensively characterized. METHODS: Based on the scRNA-seq and spatial transcriptomic data of non-tumor liver tissues (NTs), primary liver tumors (PTs) and metastatic liver tumors (MTs), we performed the tissue preference, trajectory reconstruction, transcription factor activity inference, cell-cell interaction and cellular deconvolution analyses to construct a comprehensive cellular landscape of liver tumors. RESULTS: Our analyses depicted the heterogeneous cellular ecosystems in NTs, PTs and MTs. The activated memory B cells and effector T cells were shown to gradually shift to inhibitory B cells, regulatory or exhausted T cells in liver tumors, especially in MTs. Among them, we characterized a unique group of TCF7+ CD8+ memory T cells specifically enriched in MTs that could differentiate into exhausted T cells likely driven by the p38 MAPK signaling. With regard to myeloid cells, the liver-resident macrophages and inflammatory monocyte/macrophages were markedly replaced by tumor-associated macrophages (TAMs), with TREM2+ and UBE2C+ TAMs enriched in PTs, while SPP1+ and WDR45B+ TAMs in MTs. We further showed that the newly identified WDR45B+ TAMs exhibit an M2-like polarization and are associated with adverse prognosis in patients with liver metastases. Additionally, we addressed that endothelial cells display higher immune tolerance and angiogenesis capacity, and provided evidence for the source of the mesenchymal transformation of fibroblasts in tumors. Finally, the malignant hepatocytes and fibroblasts were prioritized as the pivotal cell populations in shaping the microenvironments of PTs and MTs, respectively. Notably, validation analyses by using spatial or bulk transcriptomic data in clinical cohorts concordantly emphasized the clinical significance of these findings. CONCLUSIONS: This study defines the ontological and functional heterogeneities in cellular ecosystems of primary and metastatic liver tumors, providing a foundation for future investigation of the underlying cellular mechanisms.

Aptamer-Modified Nb2C Multifunctional Nanomedicine for Targeted Photothermal/Chemotherapy Combined Therapy of Tumor.

The poor delivery efficiency of nanotherapeutic drugs and their potential off-target toxicity significantly limit their effectiveness and extensive application. An active targeting system with high efficiency and few side effects is a promising strategy for tumor therapy. Herein, a multifunctional nanomedicine Nb2C-PAA-DOX@Apt-M (NDA-M) was constructed for targeted photothermal/chemotherapy (PTT/CHT) combined tumor therapy. The specific targeting ability of aptamer could effectively enhance the absorption of nanomedicine by the MCF-7 cell. By employing Apt-M, the NDA-M nanosheets demonstrated targeted delivery to MCF-7 cells, resulting in enhanced intracellular drug concentration. Under 1060 nm laser irradiation, a rapid temperature increase of the NDA-M was observed within the tumor region to achieve PTT. Meanwhile, CHT was triggered when DOX release was induced by photothermal/acid stimulation. The experimental results demonstrated that aptamer-mediated targeting achieved enhanced PTT/CHT efficacy both in vitro and in vivo. Notably, NDA-M induced complete ablation of solid tumors without any adverse side effects in mice. This study demonstrated new and promising tactics for the development of nanomaterials for targeted tumor therapy.

Preparation of µ-HMX/C-Based Composite Energy Composite Microspheres by Microdroplet Technology.

Taking µ-HMX particles as the main research subject, a set of microdroplet sphericalization coating technology platforms was designed and constructed to realize the preparation of composite microspheres by sphericalization coating of µ-HMX. The suspension stability of µ-HMX particles and the mechanism of droplet formation were investigated, and the application effect of nanocarbon materials was also analyzed. The results showed that the prepared sample microspheres all showed a better spherical morphology, as well as good dispersibility; the samples with micron-sized particles for spherical coating had a lower thermal decomposition temperature, a higher energy release efficiency, lower mechanical sensibility, and better combustion performance; the incorporation of CNFs changed the combustion mode of the system, which resulted in the microsphere system of µ-HMX having a good safety performance. The stability and feasibility of uniform spheronization when the dispersed phase is a low-concentration particle suspension system in the spheronization encapsulation process by microdroplet technology were verified.

Pd-Catalyzed Aerobic Synthesis of Allylic Sulfones from Allylic Alcohols and Sulfonyl Hydrazines in Water.

A mild and green synthesis of allylic sulfones from allylic alcohols and sulfonyl hydrazines was developed in water media. The simple and commercially available Pd(PPh3)4 is used as the best catalyst, and the reaction can proceed smoothly at 40 °C under air. This new method does not require the common nitrogen protection and organic media, and can be readily scaled up in gram scale, showing the good practicality value.

Reliability and Validity of the Chinese Version of the Revised Sociosexual Orientation Inventory.

The Revised Sociosexual Orientation Inventory (SOI-R) is a measurement tool for assessing an individual's willingness to engage in uncommitted sexual relations. Despite its widespread use in various contexts, no studies have validated the use of this instrument in China. Therefore, the current study aimed to assess the reliability and validity of an existing Chinese translation of the SOI-R. A total of 2,209 participants were recruited and randomly divided into two groups: exploratory factor analysis was conducted on one group and confirmatory factor analysis on the other, with 161 participants from the total sample recruited to assess the test-retest reliability. Criterion validity was measured by testing the correlations between sociosexuality and sexual desire, mate value, sexual attitudes, and personality traits. The results confirmed a three-factor structure (sociosexual behaviors, attitudes, and desire) for the SOI-R. Furthermore, the findings demonstrated good reliability (internal consistency and test-retest stability) and validity (criterion validity, convergent validity, and discriminant validity) of the SOI-R, supporting its suitability as an assessment tool for sociosexual orientation in China.

Zinc oxide nanoparticles exacerbate skin epithelial cell damage by upregulating pro-inflammatory cytokines and exosome secretion in M1 macrophages following UVB irradiation-induced skin injury.

BACKGROUND: Zinc oxide nanoparticles (ZnONPs) are common materials used in skin-related cosmetics and sunscreen products due to their whitening and strong UV light absorption properties. Although the protective effects of ZnONPs against UV light in intact skin have been well demonstrated, the effects of using ZnONPs on damaged or sunburned skin are still unclear. In this study, we aimed to reveal the detailed underlying mechanisms related to keratinocytes and macrophages exposed to UVB and ZnONPs. RESULTS: We demonstrated that ZnONPs exacerbated mouse skin damage after UVB exposure, followed by increased transepidermal water loss (TEWL) levels, cell death and epithelial thickness. In addition, ZnONPs could penetrate through the damaged epithelium, gain access to the dermis cells, and lead to severe inflammation by activation of M1 macrophage. Mechanistic studies indicated that co-exposure of keratinocytes to UVB and ZnONPs lysosomal impairment and autophagy dysfunction, which increased cell exosome release. However, these exosomes could be taken up by macrophages, which accelerated M1 macrophage polarization. Furthermore, ZnONPs also induced a lasting inflammatory response in M1 macrophages and affected epithelial cell repair by regulating the autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. CONCLUSIONS: Our findings propose a new concept for ZnONP-induced skin toxicity mechanisms and the safety issue of ZnONPs application on vulnerable skin. The process involved an interplay of lysosomal impairment, autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. The current finding is valuable for evaluating the effects of ZnONPs for cosmetics applications.

The Development of Composite Measures of Neighborhood Economic Factors for Use in Spinal Cord Injury Outcomes Studies: A Spinal Cord Injury Model Systems Database Study.

OBJECTIVE: To develop composite measures of neighborhood economic factors for use with the national Spinal Cord Injury Model Systems (SCIMS) database in cross-sectional and longitudinal investigations of the social determinants of health. DESIGN: Secondary data analysis of administrative data from the 2009, 2014, and 2019 American Community Survey (ACS) 5-year estimates and survey data collected for the SCIMS database. SETTING: Community INTERVENTIONS: Not applicable PARTICIPANTS: The validity of the neighborhood economic measures developed from the ACS data was tested with a sample of SCIMS participants who completed a follow-up interview between 2017-2021 (N=8,130). The predictive validity of the neighborhood measures was assessed with a subsample of cases with complete data on the outcome and covariate measures (N=6,457). MAIN OUTCOME MEASURES: A binary measure of self-rated health status (1=poor/fair health; 0=good/very good/excellent), RESULTS: A combination of panel review and data reduction techniques yielded two distinct measuring neighborhood socioeconomic status (SES) and neighborhood socioeconomic disadvantage that were validated using three waves of ACS data and the SCIMS data. The odds of reporting poor health were lower among people living in moderate and high SES neighborhoods and highest among people living in moderately and highly disadvantaged neighborhoods. The negative association between neighborhood SES and poor health was fully attenuated by differences in participants' individual demographic and economic characteristics whereas the positive association between neighborhood disadvantage and poor health persisted after adjusting for individual differences. CONCLUSIONS: The two composite measures of neighborhood economic factors developed by this study are robust in samples from different periods of time and valid for use with the SCIMS database. Future investigations conducting surveillance of the needs of the SCI population using this resource may consider using these measures to assess the impact of the social determinants of health in outcomes after SCI.

A Comparison of Demographics Across the Burn, Spinal Cord Injury, and Traumatic Brain Injury Model Systems.

OBJECTIVE: This study aims to analyze the demographic profiles of participants in the traumatic brain injury (TBI), burn injury (BI), and spinal cord injury (SCI) Model Systems Databases. DESIGN: Data from the Burn Model System (BMS) National Database, TBI Model Systems (TBIMS) National Database, and SCI Model System (SCIMS) Database was analyzed from 1994 to 2020. SETTING: Not applicable PARTICIPANTS: The study included 16 years and older participants with available data in selected variables, totaling 4,807 BI, 19,127 TBI, and 18,473 SCI participants. INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: Variables including age, race, ethnicity, sex, education level, primary payor source, family income level, employment status at one-year post-injury, etiology, and mortality at one-year post-injury were analyzed across the database. RESULTS: Median ages at injury for BMS (40.4), TBIMS (40), and SCIMS (38) Database participants were comparable. Males constituted about 75% of participants in BMS, TBIMS, and SCIMS datasets, with approximately 75% having a high school education or lower. The proportion of participants funded by Medicare during initial hospital care varied across the BMS (14%), TBIMS (15.6%), and SCIMS (10.2%). For family income (data available for BMS and SCIMS), roughly 30% of these participants reported a family income below $25,000. Etiology data indicated 49.0% of TBI and 40.7% of SCI cases resulted from vehicular incidents. CONCLUSIONS: An overlapping at-risk population for these injuries appears to be middle-aged males with lower education levels and family incomes, who have access to vehicles. This underscores the need for preventive initiatives tailored to this identified population to mitigate the risk of these injuries.

PTBP1 promotes the progression of hepatocellular carcinoma by enhancing the oncogenic splicing switch of FGFR2.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer accounting for 90% of cases. It is a highly invasive and deadly cancer with a gradual onset. Polypyrimidine tract-binding protein 1 (PTBP1) is an important RNA-binding protein involved in RNA metabolism and has been linked to oncogenic splicing events. While the oncogenic role of PTBP1 in HCC cells has been established, the exact mechanism of action remains unclear. This study aimed to investigate the functional connection between PTBP1 and dysregulated splicing events in HCC. Through immunoprecipitation-mass spectrometry analyses, we discovered that the proteins bound to PTBP1 were significantly enriched in the complex responsible for the alternative splicing of FGFR2 (fibroblast growth factor receptor 2). Further RNA immunoprecipitation and quantitative PCR assays confirmed that PTBP1 down-regulated the FGFR2-IIIb isoform levels and up-regulated the FGFR2-IIIc isoform levels in HCC cells, leading to a switch from FGFR2-IIIb to FGFR2-IIIc isoforms. Subsequent functional evaluations using CCK-8, transwell, and plate clone formation assays in HCC cell lines HepG2 and Huh7 demonstrated that FGFR2-IIIb exhibited tumor-suppressive effects, while FGFR2-IIIc displayed tumor-promoting effects. In conclusion, this study provides insights into the PTBP1-mediated alternative splicing mechanism in HCC progression, offering a new theoretical basis for the prevention and treatment of this malignancy. Mechanistically, the isoform switch from FGFR2-IIIb to FGFR2-IIIc promoted epithelial-mesenchymal transformation (EMT) of HCC cells and activated the FGFR cascades ERK and AKT pathways.

Is it more effective for anhedonia and avolition? A systematic review and meta-analysis of non-invasive brain stimulation interventions for negative symptoms in schizophrenia.

BACKGROUND: Noninvasive brain stimulation (NIBS) techniques are a promising tool for treating the negative symptoms of schizophrenia. Growing evidence suggests that different dimensions of negative symptoms have partly distinct underlying pathophysiological mechanisms. Previous randomized controlled trials (RCTs) have shown inconsistent impacts of NIBS across dimensions. OBJECTIVE: This systematic review and meta-analysis evaluated the effects of NIBS on general negative symptoms, and on specific domains, including blunted affect, alogia, asociality, anhedonia, and avolition. DATA SOURCES: PubMed, Web of Science, Embase, Cochrane CENTRAL, PsycINFO, OpenGrey, and Clinicaltrials.gov from the first date available to October, 2023. RESULTS: Among 1049 studies, we identified eight high-quality RCTs. NIBS significantly affects general negative symptoms (SMD = -0.54, 95% CI [-0.88, -0.21]) and all five domains (SMD = -0.32 to -0.63). Among dimensions, better effects have been shown for improvement of avolition (SMD = -0.47, 95% CI [-0.81, -0.13]) and anhedonia (SMD = -0.63, 95% CI [-0.98, -0.28]). Subgroup analyses of studies that applied once daily stimulation or >10 sessions showed significantly reduced negative symptom severity. CONCLUSION: NIBS exerts distinct effects across multiple dimensions of negative symptom, with treatment effects related to stimulation frequency and total sessions. These results need to be confirmed in dedicated studies.

Indoor/Outdoor airborne microbiome characteristics in residential areas across four seasons and its indoor purification.

Bioaerosols are more likely to accumulate in the residential environment, and long-term inhalation may lead to a variety of diseases and allergies. Here, we studied the distribution, influencing factors and diffusion characteristics of indoor and outdoor microbiota pollution in six residential buildings in Guangzhou, southern China over a period of one year. The results showed that the particle sizes of bioaerosol were mainly in the range of inhalable particle size (<4.7 µm) with a small difference among four seasons (74.61 % ± 2.17 %). The microbial communities showed obvious seasonal differences with high abundance in summer, but no obvious geographical differences. Among them, the bacteria were more abundant than the fungi. The dominant microbes in indoor and outdoor environments were similar, with Anoxybacillu, Brevibacillus and Acinetobacter as the dominant bacteria, and Cladosporium, Penicillium and Alternaria as the dominant fungi. The airborne microbiomes were more sensitive to temperature and particulate matter (PM2.5, PM10) concentrations. Based on the Sloan neutral model, bacteria were more prone to random diffusion than fungi, and the airborne microbiome can be randomly distributed in indoor and outdoor environments and between the two environments in each season. Bioaerosol in indoor was mainly from outdoor. The health risk evaluation showed that the indoor inhalation risks were higher than those outdoor. The air purifier had a better removal efficiency on 1.1-4.7 µm microorganisms, and the removal efficiency on Gram-negative bacteria was better than that on Gram-positive bacteria. This study is of great significance for the risk assessment and control of residential indoor bioaerosol exposure.

Bacterial diversity in a continuum from supraglacial habitats to a proglacial lake on the Tibetan Plateau.

Mountain glaciers are frequently assessed for their hydrological connectivity from glaciers to proglacial lakes. Ecological process on glacier surfaces and downstream ecosystems have often been investigated separately, but few studies have focused on the connectivity between the different glacial habitats. Therefore, it remains a limited understanding of bacterial community assembly across different habitats along the glacier hydrological continuum. In this study, we sampled along a glacial catchment from supraglacial snow, cryoconite holes, supraglacial runoff, ice-marginal moraine and proglacial lake on the Tibetan Plateau. The bacterial communities in these habitats were analyzed using high-throughput DNA sequencing of the 16S rRNA gene to determine the bacterial composition and assembly. Our results showed that each habitat hosted unique bacterial communities, with higher bacterial α-diversity in transitional habitats (e.g. runoff and ice-marginal moraine). Null model analysis indicated that deterministic processes predominantly shaped bacterial assembly in snow, cryoconite holes and lake, while stochastic process dominantly governed bacterial community in transitional habitats. Collectively, our findings suggest that local environment play a critical role in filtering bacterial community composition within glacier habitats. This study enhances our understanding of microbial assembly process in glacier environments and provides valuable insights into the factors governing bacterial community compositions across different habitats along the glacial hydrological continuum.

Enhanced sensitivity of extracellular antibiotic resistance genes (ARGs) to environmental concentrations of antibiotic.

As emerging contaminants, antibiotics are frequently present in various environments, particularly rivers, albeit often at sublethal concentrations (ng/L∼µg/L). Assessing the risk associated with these low levels, which are far below the lethal threshold for most organisms, remains challenging. In this study, using microcosms containing planktonic bacteria and biofilm, we examined how antibiotic resistance genes (ARGs) in different physical states, including intracellular ARGs (iARGs) and extracellular ARGs (eARGs) responded to these low-level antibiotics. Our findings reveal a positive correlation between sub-lethal antibiotic exposure (ranging from 0.1 to 10 µg/L) and increased prevalence (measured as ARG copies/16s rDNA) of both iARGs and eARGs in planktonic bacteria. Notably, eARGs demonstrated greater sensitivity to antibiotic exposure compared to iARGs, with a lower threshold (0.1 µg/L for eARGs versus 1 µg/L for iARGs) for abundance increase. Moreover, ARGs in biofilms demonstrates higher sensitivity to antibiotic exposure compared to planktonic bacteria. To elucidate the underlying mechanisms, we established an integrated population dynamics-pharmacokinetics-pharmacodynamics (PD-PP) model. This model indicates that the enhanced sensitivity of eARGs is primarily driven by an increased potential for plasmid release from cells under low antibiotic concentrations. Furthermore, the accumulation of antibiotic in biofilms induces a greater sensitivity of ARG compared to the planktonic bacteria. This study provides a fresh perspective on the development of antibiotic resistance and offers an innovative approach for assessing the risk of sublethal antibiotic in the environment.

Ferroptosis in thyroid cancer: Potential mechanisms, effective therapeutic targets and predictive biomarker.

Thyroid cancer is a prevalent endocrine malignancy whose global incidence has risen over the past several decades. Ferroptosis, a regulated form of cell death distinguished by the excessive buildup of iron-dependent lipid peroxidates, stands out from other programmed cell death pathways in terms of morphological and molecular characteristics. Increasing evidence suggests a close association between thyroid cancer and ferroptosis, that is, inducing ferroptosis effectively suppresses the proliferation of thyroid cancer cells and impede tumor advancement. Therefore, ferroptosis represents a promising therapeutic target for the clinical management of thyroid cancer in clinical settings. Alterations in ferroptosis-related genes hold potential for prognostic prediction in thyroid cancer. This review summarizes current studies on the role of ferroptosis in thyroid cancer, elucidating its mechanisms, therapeutic targets, and predictive biomarkers. The findings underscore the significance of ferroptosis in thyroid cancer and offer valuable insights into the development of innovative treatment strategies and accurate predictors for the thyroid cancer.

Cucurbitacin B suppresses hepatocellular carcinoma progression through inducing DNA damage-dependent cell cycle arrest.

BACKGROUND: The mortality rate of liver cancer ranks third in the world, and hepatocellular carcinoma (HCC) is a malignant tumor of the digestive tract. Cucurbitacin B (CuB), a natural compound extracted from Cucurbitaceae spp., is the main active component of Chinese patent medicine the Cucurbitacin Tablet, which has been widely used in the treatment of various malignant tumors in clinics, especially HCC. PURPOSE: This study explored the role and mechanism of CuB in the suppression of liver cancer progression. METHODS: Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect the inhibitory function of CuB in Huh7, Hep3B, and Hepa1/6 hepatoma cells. Calcein-AM/propidium iodide (PI) staining and lactate dehydrogenase (LDH) measurement assays were performed to determine cell death. Mitochondrial membrane potential (Δψm) was measured, and flow cytometry was performed to evaluate cell apoptosis and cell cycle. Several techniques, such as proteomics, Western blotting (WB), and ribonucleic acid (RNA) interference, were utilized to explore the potential mechanism. The animal experiment was performed to verify the results of in vitro experiments. RESULTS: CuB significantly inhibited the growth of Huh7, Hep3B, and Hepa1/6 cells and triggered the cell cycle arrest in G2/M phage without leading to cell death, especially apoptosis. Knockdown of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a target of CuB, did not reverse CuB elicited cell cycle arrest. CuB enhanced phosphorylated ataxia telangiectasia mutated (p-ATM) and phosphorylated H2A histone family member X (γ-H2AX) levels. Moreover, CuB increased p53 and p21 levels and decreased cyclin-dependent kinase 1 (CDK1) expression, accompanied by improving phosphorylated checkpoint kinase 1 (p-CHK1) level and suppressing cell division cycle 25C (CDC25C) protein level. Interestingly, these phenomena were partly abolished by a deoxyribonucleic acid (DNA) protector methylproamine (MPA). Animal studies showed that CuB also significantly suppressed tumor growth in BALB/c mice bearing Hepa1/6 cells. In tumor tissues, CuB reduced the expression levels of proliferating cell nuclear antigen (PCNA) and γ-H2AX but did not change the terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) level. CONCLUSION: This study demonstrated for the first time that CuB could effectively impede HCC progression by inducing DNA damage-dependent cell cycle arrest without directly triggering cell death, such as necrosis and apoptosis. The effect was achieved through ataxia telangiectasia mutated (ATM)-dependent p53-p21-CDK1 and checkpoint kinase 1 (CHK1)-CDC25C signaling pathways. These findings indicate that CuB may be used as an anti-HCC drug, when the current findings are confirmed by independent studies and after many more clinical phase 1, 2, 3, and 4 testings have been done.

Visualization and correlation of drug release of risperidone/clozapine microspheres in vitro and in vivo based on FRET mechanism.

This study addresses the challenging task of quantitatively investigating drug release from PLGA microspheres after in vivo administration. The objective is to employ Förster resonance energy transfer (FRET) to visualize drug-encapsulated microspheres in both in vitro and in vivo settings. The primary goal is to establish a quantitative correlation between FRET fluorescence changes and microsphere drug release. The study selects drugs with diverse structures and lipid solubility to explore release mechanisms, using PLGA as the matrix material. Clozapine and risperidone serve as model drugs. FRET molecules, Cy5 and Cy5.5, along with Cy7 derivatives, create FRET donor-acceptor pairs. In vitro results show that FRET fluorescence changes align closely with microsphere drug release, particularly for the Cy5.5-Cy7 pair. In vivo experiments involve subcutaneous administration of microspheres to rats, tracking FRET fluorescence changes while collecting blood samples. Pharmacokinetic studies on clozapine and risperidone reveal in vivo absorption fractions using the Loo-Riegelman method. Correlating FRET and in vivo absorption data establishes an in vitro-in vivo relationship (IVIVR). The study demonstrates that FRET-based fluorescence changes quantitatively link to microsphere drug release, offering an innovative method for visualizing and monitoring release in both in vitro and in vivo settings, potentially advancing clinical applications of such formulations.

Predicting human epidermal growth factor receptor 2 status of patients with gastric cancer by computed tomography and clinical features.

Background: There have been no studies on predicting human epidermal growth factor receptor 2 (HER2) status in patients with resectable gastric cancer (GC) in the neoadjuvant and perioperative settings. We aimed to investigate the use of preoperative contrast-enhanced computed tomography (CECT) imaging features combined with clinical characteristics for predicting HER2 expression in GC. Methods: We retrospectively enrolled 301 patients with GC who underwent curative resection and preoperative CECT. HER2 status was confirmed by postoperative immunohistochemical analysis with or without fluorescence in situ hybridization. A prediction model was developed using CECT imaging features and clinical characteristics that were independently associated with HER2 status using multivariate logistic regression analysis. Receiver operating characteristic curves were constructed and the performance of the prediction model was evaluated. The bootstrap method was used for internal validation. Results: Three CECT imaging features and one serum tumor marker were independently associated with HER2 status in GC: enhancement ratio in the arterial phase (odds ratio [OR] = 4.535; 95% confidence interval [CI], 2.220-9.264), intratumoral necrosis (OR = 2.64; 95% CI, 1.180-5.258), tumor margin (OR = 3.773; 95% CI, 1.968-7.235), and cancer antigen 125 (CA125) level (OR = 5.551; 95% CI, 1.361-22.651). A prediction model derived from these variables showed an area under the receiver operating characteristic curve of 0.802 (95% CI, 0.740-0.864) for predicting HER2 status in GC. The established model was stable, and the parameters were accurately estimated. Conclusions: Enhancement ratio in the arterial phase, intratumoral necrosis, tumor margin, and CA125 levels were independently associated with HER2 status in GC. The prediction model derived from these factors may be used preoperatively to estimate HER2 status in GC and guide clinical treatment.

Career adaptability and career coping styles among Chinese medicine specialty students during the COVID-19: The mediating role of career decision-making self-efficacy.

Over the past decade, the attrition rate of Chinese medical graduates has remained high, and the COVID-19 pandemic has exacerbated this situation. Medicine specialty students are the main force of the future healthcare industry. The career choices and career confidence of those entering the healthcare industry will have a huge influence on the quality of future healthcare provision. Considering the possible emergence of public health emergencies such as COVID-19 in the future, helping students develop good career adaptability will contribute to their future career development. However, the relationship between career adaptability, career coping styles and career decision-making self-efficacy remains unclear during the COVID-19. This study aims to examine the interconnections amongst career coping styles, career adaptability and career decision-making self-efficacy among Chinese medicine specialty students and the mediating role of career decision-making self-efficacy. Questionnaire survey was conducted on 747 medicine specialty students from China. The results showed that positive coping style has a significant positive correlation with career decision-making self-efficacy, career adaptability, and their sub-dimensions. There was a partial mediating effect of career decision self-efficacy between the predictor variable positive coping style and the outcome variable career adaptability. By promoting the level of positive coping style or career decision-making self-efficacy among medicine specialty students, the career adaptability can be directly or indirectly enhanced. This survey will help to guide future medical education decisions during a similar pandemic to prevent further loss of healthcare professionals in the medical service.

Physiologically based pharmacokinetic modeling to predict maternal pharmacokinetics and fetal carbamazepine exposure during pregnancy.

Carbamazepine is an antiepileptic drug commonly used in pregnant women, during which the physiological changes may affect its efficacy. The aim of this study was to establish a physiologically based pharmacokinetic (PBPK) model of carbamazepine and its active metabolite carbamazepine-10,11-epoxide, and simulate maternal and fetal pharmacokinetic changes of carbamazepine and carbamazepine-10,11-epoxide in different trimesters and propose dose adjustment. We established pregnancy PBPK models for carbamazepine and carbamazepine-10,11-epoxide in PK-Sim® and Mobi® and validated the models with observed data from clinical reports. The placental transfer parameters obtained using different methods were also imported into the model and compared with the observed data to establish and validate fetal pharmacokinetic curves. The simulated results showed that mean steady-state trough plasma concentration of carbamazepine decreased by 27, 43.1, and 52 % during the first, second, and third trimesters, respectively. Therefore, to achieve an optimum therapeutic concentration, administering at least 1.4, 1.8, and 2.1 times the baseline dose of carbamazepine in the first, second, and third trimesters, respectively can be used as a dose reference. In conclusion, this study established and validated a pregnancy PBPK model of carbamazepine and carbamazepine-10,11-epoxide to assess exposure in pregnant women and fetuses, which provided a reference for the dosage adjustment of carbamazepine during pregnancy.