Core-Shell Gel Nanofiber Scaffolds Constructed by Microfluidic Spinning toward Wound Repair and Tissue Regeneration.

Growing demand for wound care resulting from the increasing chronic diseases and trauma brings intense pressure to global medical health service system. Artificial skin provides mechanical and microenvironmental support for wound, which is crucial in wound healing and tissue regeneration. However, challenges still remain in the clinical application of artificial skin since the lack of the synergy effect of necessary performance. In this study, a multi-functional artificial skin is fabricated through microfluidic spinning technology by using core-shell gel nanofiber scaffolds (NFSs). This strategy can precisely manipulate the microstructure of artificial skin under microscale. The as-prepared artificial skin demonstrates superior characteristics including surface wettability, breathability, high mechanical strength, strain sensitivity, biocompatibility and biodegradability. Notably, this artificial skin has the capability to deliver medications in a controlled and sustained manner, thereby accelerating the wound healing process. This innovative approach paves the way for the development of a new generation of artificial skin and introduces a novel concept for the structural design of the unique core-shell gel NFSs.

Advanced biomedical and electronic dual-function skin patch created through microfluidic-regulated 3D bioprinting.

Artificial skin involves multidisciplinary efforts, including materials science, biology, medicine, and tissue engineering. Recent studies have aimed at creating skins that are multifunctional, intelligent, and capable of regenerating tissue. In this work, we present a specialized 3D printing ink composed of polyurethane and bioactive glass (PU-BG) and prepare dual-function skin patch by microfluidic-regulated 3D bioprinting (MRBP) technique. The MRBP endows the skin patch with a highly controlled microstructure and superior strength. Besides, an asymmetric tri-layer is further constructed, which promotes cell attachment and growth through a dual transport mechanism based on hydrogen bonds and gradient structure from hydrophilic to superhydrophilic. More importantly, by combining the features of biomedical skin with electronic skin (e-skin), we achieved a biomedical and electronic dual-function skin patch. In vivo experiments have shown that this skin patch can enhance hemostasis, resist bacterial growth, stimulate the regeneration of blood vessels, and accelerate the healing process. Meanwhile, it also mimics the sensory functions of natural skin to realize signal detection, where the sensitivity reached up to 5.87 kPa-1, as well as cyclic stability (over 500 cycles), a wide detection range of 0-150 kPa, high pressure resolution of 0.1 % under the pressure of 100 kPa. This work offers a versatile and effective method for creating dual-function skin patches and provide new insights into wound healing and tissue repair, which have significant implications for clinical applications.

Macrophage polarization in the tumor microenvironment: Emerging roles and therapeutic potentials.

The tumor microenvironment (TME) is a combination of tumor cells and indigenous host stroma, which consists of tumor-infiltrating immune cells, endothelial cells, fibroblasts, pericytes, and non-cellular elements. Tumor-associated macrophages (TAMs) represent the major tumor-infiltrating immune cell type and are generally polarized into two functionally contradictory subtypes, namely classical activated M1 macrophages and alternatively activated M2 macrophages. Macrophage polarization refers to how macrophages are activated at a given time and space. The interplay between the TME and macrophage polarization can influence tumor initiation and progression, making TAM a potential target for cancer therapy. Here, we review the latest investigations on factors orchestrating macrophage polarization in the TME, how macrophage polarization affects tumor progression, and the perspectives in modulating macrophage polarization for cancer immunotherapy.

Combining transcriptome and metabolome analysis to understand the response of sorghum to Melanaphis sacchari.

BACKGROUND: The sorghum aphid Melanaphis sacchari (Zehntner) (Homoptera: Aphididae) is an important insect in the late growth phase of sorghum (Sorghum bicolor L.). However, the mechanisms of sorghum response to aphid infestation are unclear. RESULTS: In this paper, the mechanisms of aphid resistance in different types of sorghum varieties were revealed by studying the epidermal cell structure and performing a transcriptome and metabolome association analysis of aphid-resistant and aphid-susceptible varieties. The epidermal cell results showed that the resistance of sorghum to aphids was positively correlated with epidermal cell regularity and negatively correlated with the intercellular space and leaf thickness. Transcriptome and metabolomic analyses showed that differentially expressed genes in the resistant variety HN16 and susceptible variety BTX623 were mainly enriched in the flavonoid biosynthesis pathway and differentially expressed metabolites were mainly related to isoflavonoid biosynthesis and flavonoid biosynthesis. The q-PCR results of key genes were consistent with the transcriptome expression results. Meanwhile, the metabolome test results showed that after aphidinfestation, naringenin and genistein were significantly upregulated in the aphid-resistant variety HN16 and aphid-susceptible variety BTX623 while luteolin was only significantly upregulated in BTX623. These results show that naringenin, genistein, and luteolin play important roles in plant resistance to aphid infestation. The results of exogenous spraying tests showed that a 1‰ concentration of naringenin and genistein is optimal for improving sorghum resistance to aphid feeding. CONCLUSIONS: In summary, the physical properties of the sorghum leaf structure related to aphid resistance were studied to provide a reference for the breeding of aphid-resistant varieties. The flavonoid biosynthesis pathway plays an important role in the response of sorghum aphids and represents an important basis for the biological control of these pests. The results of the spraying experiment provide insights for developing anti-aphid substances in the future.

Prediction of outcomes after chemoradiotherapy for cervical cancer by neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

BACKGROUND: Cervical cancer ranks as the second most fatal tumour globally among females. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been widely applied to the diagnosis of cancers. METHODS: The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy from January 2018 to December 2019 were retrospectively analysed. Receiver operating characteristic (ROC) curves were plotted to analyse the optimal cut-off values of NLR and PLR for predicting the therapeutic effects of concurrent chemoradiotherapy. The associations of PLR and other clinicopathological factors with 1-year survival rates were explored through univariate analysis and multivariate Cox regression analysis, respectively. RESULTS: NLR was significantly associated with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 2.89, area under the ROC curve (AUC) of 0.848 (95% confidence interval [CI]: 0.712-0.896), sensitivity of 0.892 (95% CI: 0.856-0.923) and specificity of 0.564 (95% CI: 0.512-0.592). PLR had a significant association with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 134.27, AUC of 0.766 (95% CI: 0.724-0.861), sensitivity of 0.874 (95% CI: 0.843-0.905) and specificity of 0.534 (95% CI: 0.512-0.556). Lymphatic metastasis ([95% CI: 1.435-5.461], [95% CI: 1.336-4.281], depth of invasion ([95% CI: 1.281-3.546], [95% CI: 1.183-3.359]) and tumour size ([95% CI: 1.129-3.451], [95% CI: 1.129-3.451]) were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR (95%CI: 1.256-4.039) and PLR (95%CI:1.281-3.546) were also independent factors affecting DFS. CONCLUSION: NLR and PLR in the peripheral blood before treatment may predict DFS of patients with stage IB2-IIB cervical cancer.

The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy were retrospectively analysed. Receiver operating characteristic curves showed that neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were significantly associated with the therapeutic effects of neoadjuvant therapy. Univariate and multivariate regression analysis revealed that lymphatic metastasis, depth of invasion and tumour size were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR and PLR in the peripheral blood before treatment may predict the DFS of patients with stage IB2-IIB cervical cancer.

Gandouling induces GSK3ß promoter methylation to improve cognitive impairment in Wilson's disease.

ETHNOPHARMACOLOGIC SIGNIFICANCE: Cognitive impairment is a serious clinical manifestation of Wilson's disease (WD) in the nervous system. Gandouling (GDL) is a hospital preparation of the First Affiliated Hospital of Anhui University of Chinese Medicine. Previous studies have found that GDL has an ameliorative effect on cognitive impairment in WD. AIM OF THE STUDY: We aimed to explore the molecular-level regulatory mechanisms underlying cognitive impairment in WD, and provide evidence supporting GDL as a promising candidate drug for the treatment of cognitive impairment in WD. We found that GSK3ß was significantly up-regulated in the brain tissue of C3He-Atp7Btx-J/J (tx-j) mice in the WD gene mutant model, and the monomer components of GDL could combine well with GSK3ß. Therefore, in this work, we used Behavioral tests, Hematoxylin and eosin (H&E), Nissl and Terminal deoxynucleotidyl transferase dUTP-biotin nick end labeling(TUNEL) staining, Ultrastructural morphological observation by Transmission electron microscopy (TEM), bisulfite sequencing (BSP), Quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, immunofluorescence, network pharmacology, molecular docking, and related methods to study the effects of GDL in tx-j mice and HT22 cell to clarify the effect of GDL on cognitive impairment in WD. RESULTS: In this study, MWM, NOR, H&E, Nissl TUNEL and TEM results showed that GDL could promote the repair of learning and memory function, improve the morphological damage to hippocampal neurons, and maintain mitochondria integrity. In the HT22 cell experiment, the CCK-8 method showed that GDL increased the viability of copper-overloaded cell models. The study found that GSK3ß may be a target of GDL for the treatment of WD cognitive impairment through network pharmacology. Western blot and qRT-PCR results confirmed that GDL significantly increased the expression of proteins and mRNA in DNMT1, Nrf2, and HO-1. BSP showed that GSK3ß promoter methylation was lower in the Model group than in the control group, and the promoter methylation of GSK3ß was further reduced after intraperitoneal injection with decitabine, and GDL could ameliorate this pathology. CONCLUSION: GDL demonstrates a protective role by inducing GSK3ß promoter methylatio, regulating the GSK3ß/Nrf2 signaling pathway in WD.

Abnormalities in subcortical function and their treatment response in Wilson's disease.

Extensive neuroimaging abnormalities in subcortical regions build the pathophysiological basis of Wilson's disease (WD). Yet, subcortical topographic organization fails to articulate, leaving a huge gap in understanding the neural mechanism of WD. Thus, how functional abnormalities of WD subcortical regions influence complex clinical symptoms and response to treatment remain unknown. Using resting-state functional MRI data from 232 participants (including 130 WD patients and 102 healthy controls), we applied a connectivity-based parcellation technique to develop a subcortical atlas for WD. The atlas was further used to investigate abnormalities in subcortical function (ASF) by exploring intrasubcortical functional connectivity (FC) and topographic organization of cortico-subcortical FC. We further used support vector machine (SVM) to integrate these functional abnormalities into the ASF score, which serves as a biomarker for characterizing individual subcortical dysfunction for WD. Finally, the baseline ASF score and one-year treatment data of the follow-up WD patients were used to assess treatment response. A group set of subcortical parcellations was evaluated, in which 26 bilateral regions well recapitulated the anatomical nuclei of the subcortical areas of WD. The results of cortico-subcortical FC and intrasubcortical FC reveal that dysfunction of the somatomotor networks-lenticular nucleus-thalamic pathways is involved in complex symptoms of WD. The ASF score was able to characterize disease progression and was significantly associated with treatment response of WD. Our findings provide a comprehensive elaboration of functional abnormalities of WD subcortical regions and reveal their association with clinical presentations, improving our understanding of the functional neural underpinnings in WD. Furthermore, abnormalities in subcortical function could serve as a potential biomarker for understanding the disease progression and evaluating treatment response of WD.

Disrupted Resting-State Functional Connectivity and Effective Connectivity of the Nucleus Accumbens in Chronic Low Back Pain: A Cross-Sectional Study.

Purpose: Chronic low back pain (cLBP) is a recurring and intractable disease that is often accompanied by emotional and cognitive disorders such as depression and anxiety. The nucleus accumbens (NAc) plays an important role in mediating emotional and cognitive processes and analgesia. This study investigated the resting-state functional connectivity (rsFC) and effective connectivity (EC) of NAc and its subregions in cLBP. Methods: Thirty-four cLBP patients and 34 age- and sex-matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based rsFC and Dynamic Causal Modelling (DCM) were used to examine the alteration of the rsFC and EC of the NAc. Results: Our results showed that the cLBP group had increased rsFC of the bilateral NAc-left superior frontal cortex (SFC), orbital frontal cortex (OFC), left angular gyrus, the left NAc-bilateral middle temporal gyrus, as well as decreased rsFC of left NAc-left supramarginal gyrus, right precentral gyrus, left cerebellum, brainstem (medulla oblongata), and right insula pathways compared with the HC; the results of the subregions were largely consistent with the whole NAc. In addition, the rsFC of the left NAc-left SFC was negatively correlated with Hamilton's Depression Scale (HAMD) scores (r = -0.402, p = 0.018), and the rsFC of left NAc-OFC was positively correlated with present pain intensity scores (r = 0.406, p = 0.017) in the cLBP group. DCM showed that the cLBP group showed significantly increased EC from the left cerebellum to the right NAc (p = 0.012) as compared with HC. Conclusion: Overall, our findings demonstrate aberrant rsFC and EC between NAc and regions that are associated with emotional regulation and cognitive processing in individuals with cLBP, underscoring the pivotal roles of emotion and cognition in cLBP.

Spatial patterns of urban expansion and cropland loss during 2017-2022 in Guangdong, China.

Urban expansion often occurs at the expense of cropland loss, posing challenges to sustainable urban growth and food security. However, detailed investigations into urban expansion and cropland loss remain limited, particularly in regions with varying levels of urbanization. Here, we take Guangdong Province, China, as a case study to exemplify how urban expansion affects cropland using remotely sensed land use products. We adopted geospatial analysis, correlation indicators, and landscape metrics to uncover their spatial relationships at 10-m spatial resolutions. Results showed that urban areas increased by 6335 km2 while cropland decreased by 3780 km2 from 2017 to 2022. Notably, 41 % of newly expanded urban areas were from croplands, and 45 % of lost croplands were converted to urban areas. Western Guangdong experienced the largest extent of urban expansion and cropland loss, emerging as a hotspot region in recent years. Additionally, our analysis observed the increasing compactness of urban areas and the growing fragmentation of cropland landscapes over time. These findings shed light on the intricate dynamics between urban expansion and cropland loss in rapidly urbanizing regions, which provide valuable insights for sustainable urban development, agricultural practice, and land management in the future.

Gender and Mentorship in Military Medicine: A Survey Study.

INTRODUCTION: Mentorship is essential for professional development and advancement within the military. In civilian medicine, the intersection between gender and mentorship holds important implications for research opportunities, academic success, and career progression. However, the intersection of gender and mentorship has not yet been explored within the field of military medicine. The purpose of this study, therefore, was to investigate the role of gender in mentorship within the field of military medicine. MATERIALS AND METHODS: We investigated gender and mentorship within military medicine by developing and distributing a 16-item Likert survey to active-duty military physicians. We used the Chi-squared test of independence and the independent samples t-test to examine the role of gender in mentorship among the 16 questions. RESULTS: The male respondents reported more same-gender mentors than females (male [M]: 61.9% vs. female [F]: 33.0%), whereas the female respondents had significantly more mentors of the opposite gender than males (M: 12.4% vs. F: 47.3%). A higher proportion of males indicated no preference compared to females. Conversely, a significant preference for a same-sex mentor was expressed by female respondents compared to male respondents (M: 5.2% vs. F: 30.1%). In contrast, female respondents considered having a mentor more important than their male counterparts (t(206) = -2.26, P = .012, F: 3.86 vs. M: 3.57). Both male and female respondents had significantly more female mentees ($\chi _{\left( 1 \right)}^2$ = 12.92, P < .001, Cramer's V = 0.254). CONCLUSIONS: While the female participants in our study preferred female mentors, the male participants had more same-gender mentors than the female participants. In addition, more females reported that they did not have the time to be mentored. Our results, therefore, suggest that training males to be better mentors to females and providing accessible mentorship training to females may promote equitable career development within military medicine.

Association of healthy lifestyle score with control of hypertension among treated and untreated hypertensive patients: a large cross-sectional study.

Background: Hypertension stands as the leading single contributor to the worldwide burden of mortality and disability. Limited evidence exists regarding the association between the combined healthy lifestyle score (HLS) and hypertension control in both treated and untreated hypertensive individuals. Therefore, we aimed to investigate the association between HLS and hypertension control among adults with treated and untreated hypertension. Methods: This cross-sectional study, including 311,994 hypertension patients, was conducted in Guangzhou using data from the National Basic Public Health Services Projects in China. The HLS was defined based on five low-risk lifestyle factors: healthy dietary habits, active physical activity, normal body mass index, never smoking, and no alcohol consumption. Controlled blood pressure was defined as systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg. A multivariable logistic regression model was used to assess the association between HLS and hypertension control after adjusting for various confounders. Results: The HLS demonstrated an inverse association with hypertension control among hypertensive patients. In comparison to the low HLS group (scored 0-2), the adjusted odds ratios (95% confidence intervals) for hypertension were 0.76 (0.74, 0.78), 0.59 (0.57, 0.60), and 0.48 (0.46, 0.49) for the HLS groups scoring 3, 4, and 5, respectively (Ptrend < 0.001). Notably, an interaction was observed between HLS and antihypertensive medication in relation to hypertension control (Pinteraction < 0.001). When comparing the highest HLS (scored 5) with the lowest HLS (scored 0-2), adjusted odds ratios (95% confidence intervals) were 0.50 (0.48, 0.52, Ptrend < 0.001) among individuals who self-reported using antihypertensive medication and 0.41 (0.38, 0.44, Ptrend < 0.001) among those not using such medication. Hypertensive patients adhering to a healthy lifestyle without medication exhibited better blood pressure management than those using medication while following a healthy lifestyle. Conclusion: HLS was associated with a reduced risk of uncontrolled blood pressure.

Physician educators' perceptions of experiences contributing to teaching.

INTRODUCTION: Physician educators are essential in training the next generation of physicians. However, physician educators' perspectives about what experiences they find beneficial to their teaching and the prevalence of these experiences remain unknown. Guided by social cognitive career theory (SCCT) and communities of practice (CoP), we explored what experiences physician educators perceive as beneficial in preparing them to teach. METHODS: In 2019, the Uniformed Services University School of Medicine in the United States surveyed its physician alumni to understand their education experiences during medical school, their current career path and what has contributed to their teaching role. Content analysis was applied to extract themes across the text response. Chi-square analysis was applied to examine if perceived contributing factors vary based on physician educators' gender, specialty and academic ranks. RESULTS: The five most prevalent contributing factors participants (n = 781) identified are (1) experiences gained during residency and fellowship (29.8%), (2) teaching as faculty member (28.9%) and (3) class experiences and peer interaction during medical school (26%). We organised three themes that reflected major avenues of how physician educators acquire teaching skills: reflection about quality teaching, journey as learners and learning by doing. Gender and clinical specialty were differentially associated with contributing factors such as faculty development and meta-reflection. CONCLUSION: The results are in line with theories of SCCT and CoP, in which we identified self-directed learning and regulation in shaping physician educators' teaching. The findings also revealed gaps and potential contexts for more formalised teaching practices to develop physician educators.

Association of adiposity indicators with cardiometabolic multimorbidity risk in hypertensive patients: a large cross-sectional study.

Background: Cardiometabolic multimorbidity (CMM) has emerged as a prominent public health concern. Hypertensive patients are prone to develop comorbidities. Moreover, the accumulation of visceral adipose tissue is the main cause for the development of cardiometabolic diseases. The cardiometabolic index (CMI), lipid accumulation product (LAP), visceral adiposity index (VAI), and Chinese visceral adiposity index (CVAI) not only assess adipose tissue mass but also reflect adipose tissue dysfunction. So far, no study has been reported to evaluate the association of CMI, LAP, VAI, and CVAI with CMM risk in hypertensive patients. Therefore, this study aimed to assess the association between these adiposity indicators and the risk of CMM among Chinese hypertensive patients. Methods: In this cross-sectional study, a total of 229,287 hypertensive patients aged 35 years and older were included from the National Basic Public Health Service Project. All participants underwent a face-to-face questionnaire survey, physical examination, and the collection of fasting venous blood samples. Multivariable logistic regression models were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic curve was utilized to evaluate the identification ability for CMM. Results: After adjusting for confounders, each 1-standard deviation increase in CMI, LAP, VAI, and CVAI was associated with a 14%, 8%, 12%, and 54% increased risk of CMM, respectively. When comparing the highest quartile of these indicators with the lowest quartile, individuals in the highest quartile of CMM, LAP, VAI, and CVAI had a 1.39-fold (95% CI 1.30, 1.48), 1.28-fold (95% CI 1.19, 1.37), 1.37-fold (95% CI 1.29, 1.46), and 2.56-fold (95% CI 2.34, 2.79) increased risk of CMM after adjusting for potential confounders. Notably, a nonlinear association was observed for CMI, LAP, and VAI with the risk of CMM (all P nonlinearity < 0.001). CVAI exhibited the highest area under the receiver operating characteristic curve (AUC) among all the included adiposity indices in this analysis. Conclusion: This study indicated the significant positive association of CMI, LAP, VAI, and CVAI with the risk of CMM in hypertensive patients. Among these indicators, CVAI demonstrated the most robust performance in predicting CMM risk and may serve as a valuable tool for identifying CMM risk in Chinese hypertensive patients.

Periodontitis exacerbates pulmonary hypertension by promoting IFNγ+ T cell infiltration in mice.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease. In the current study, we showed that experimental periodontitis, which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis, exacerbated hypoxia-induced pulmonary hypertension in mice. Mechanistically, periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs, contributing to pulmonary infiltration of interferon gamma positive (IFNγ+) T cells and aggravating the progression of pulmonary hypertension. In addition, we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis, and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies. Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

The novel HLA-DPB1*1550:01 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPB1*1550:01 differs from HLA-DPB1*02:02:01:01 by one nucleotide in exon 2.

Development and testing of a post competency scale for traditional Chinese medicine physicians undergoing standardized training.

Objective: To develop and test a post competency scale for traditional Chinese medicine (TCM) physicians undergoing standardized training to provide an applicable tool for scientific evaluation. Methods: Based on literature analysis, behavioral event interviews, and expert consultations, measurement questions were formulated and the initial scale was designed. A questionnaire survey was conducted from July 2022 to May 2023 among TCM physicians undergoing standardized training in China. The rationality of the scale was confirmed through item purification, factor analysis, and tests of reliability and validity. Results: The post competency scale consisted of three dimensions (TCM fundamentals and research abilities, TCM thinking and skill abilities, and personal traits and communication abilities) with 21 items. Exploratory factor analysis identified three common factors, accounting for a cumulative variance contribution rate of 62.165%. Confirmatory factor analysis demonstrated that the fit indices of the three-factor model fell within a relatively ideal level. The Cronbach's alpha coefficient of the scale was 0.885. Through convergent validity analysis, the standardized loading coefficients of the 21 items were >0.5, and the average extracted variance (AVE) of the three factors was also >0.5. Moreover, the square roots of the AVE values for each dimension exceeded the correlation coefficients between it and the other dimensions. Conclusions: The findings suggest that the post competency scale of TCM physicians undergoing standardized training can provide a reliable scientific basis for training and assessment within China.

Development and Initial Validation of the Shame Frequency Questionnaire in Medical Students.

PURPOSE: This study presents the steps taken to develop and collect initial validity evidence for the Shame Frequency Questionnaire in Medical Students. METHOD: The instrument was based on a 7-step survey design; validity evidence was collected from content, response process, internal structure, and relationship to other variables. A literature review and qualitative interviews led to the design of the initial 16-item scale. Expert review and cognitive interviewing led to minor modifications in the original structure. Initial pilot testing was conducted in August 2019 in Uniformed Services University (USU) medical students; reliability assessment and exploratory factor analysis were performed. The revised 12-item scale was tested in January 2022 in Duke University School of Medicine medical students; reliability assessment, exploratory factor analysis, and correlation analysis with depression, burnout, anxiety, emotional thriving, and emotional well-being were performed. RESULTS: A total of 336 of 678 USU students (50%) and 106 of 522 Duke students (20%) completed the survey. Initial exploratory factor analysis of the USU data revealed 1 factor (shame), and 4 items were dropped from the scale according to predefined rules. Subsequent exploratory factor analysis of the Duke data revealed 1 factor; no further items were removed according to predefined rules. Internal consistent reliability was 0.95, and all interitem correlations were less than 0.85 for USU and Duke samples. As predicted, mean shame scale scores were positively correlated with anxiety ( r = 0.54, P < .001), burnout ( r = 0.50, P < .001), and depression ( r = 0.47, P < .001) and negatively correlated with emotional thriving ( r = -0.46, P < .001) and emotional recovery ( r = -0.46, P < .001). CONCLUSIONS: The Shame Frequency Questionnaire in Medical Students is a psychometrically sound instrument with strong internal reliability and multisource validity evidence, supporting its use in studying shame in medical students.

Carboxymethyl chitosan-based hydrogel-Janus nanofiber scaffolds with unidirectional storage-drainage of biofluid for accelerating full-thickness wound healing.

Self-pumping wound scaffolds designed for directional biofluid transport are extensively investigated. They efficiently extract excessive biofluids from wounds, while maintaining an optimally humid wound environment, thus facilitating rapid wound healing. However, the existing designed scaffolds are insufficiently focused on stimulating the hydrophobic layer at the wound site, thereby exacerbating inflammation and impeding the wound healing process. Herein, we engineered and fabricated a hydrophilic-hydrophobic-hydrophilic sandwich-structured hydrogel-Janus nanofiber scaffold (NFS) employing a Layer-by-Layer (LbL) method. This scaffold comprises a hydrophilic carboxymethyl chitosan/silver (CMCS-Ag) hydrogel component in conjunction with a poly(caprolactone)/poly(caprolactone)-poly(citric acid)-co-ε-polylysine (PCL/PCL-PCE) Janus NFS. It is noteworthy that the hydrogel-Janus nanofiber scaffold not only demonstrates outstanding water absorption (202.2 %) and unidirectional biofluid transport capability but also possesses high breathability (308.663 m3/m2 h kPa), appropriate pore size (6.7-7.5 µm), excellent tensile performance (270 ± 10 %), and superior mechanical strength (26.36 ± 1.77 MPa). Moreover, in vitro experimentation has convincingly demonstrated the impeccable biocompatibility of hydrogel-Janus NFS. The inherent dual-antibacterial properties in CMCS-Ag and PCE significantly augment fibroblast proliferation and migration. In vivo studies further underscore its capability to expedite wound healing by absorption and expulsion of wound exudates, thereby fostering collagen deposition and vascularization. As such, this work potentially provides fresh insights into the design and fabrication of multifunctional biomimetic scaffolds, holding immense potential in the medical field for efficient wound healing.

Amino acid-based supramolecular chiral hydrogels promote osteogenesis of human dental pulp stem cells via the MAPK pathway.

Critical-size defects (CSDs) of the craniofacial bones cause aesthetic and functional complications that seriously impact the quality of life. The transplantation of human dental pulp stem cells (hDPSCs) is a promising strategy for bone tissue engineering. Chirality is commonly observed in natural biomolecules, yet its effect on stem cell differentiation is seldom studied, and little is known about the underlying mechanism. In this study, supramolecular chiral hydrogels were constructed using L/d-phenylalanine (L/D-Phe) derivatives. The results of alkaline phosphatase expression analysis, alizarin red S assay, as well as quantitative real-time polymerase chain reaction and western blot analyses suggest that right-handed D-Phe hydrogel fibers significantly promoted osteogenic differentiation of hDPSCs. A rat model of calvarial defects was created to investigate the regulation of chiral nanofibers on the osteogenic differentiation of hDPSCs in vivo. The results of the animal experiment demonstrated that the D-Phe group exhibited greater and faster bone formation on hDPSCs. The results of RNA sequencing, vinculin immunofluorescence staining, a calcium fluorescence probe assay, and western blot analysis indicated that L-Phe significantly promoted adhesion of hDPSCs, while D-Phe nanofibers enhanced osteogenic differentiation of hDPSCs by facilitating calcium entry into cells and activate the MAPK pathway. These results of chirality-dependent osteogenic differentiation offer a novel therapeutic strategy for the treatment of CSDs by optimising the differentiation of hDPSCs into chiral nanofibers.