Cuproptosis associated cytoskeletal destruction contributes to podocyte injury in chronic kidney disease.

The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored ATP synthesis. Among the transcriptome sequencing data, the difference of CXCL5 was the most significant. Both high copper and ADR exposure can cause up-regulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease.

The Identification of a Novel Nucleomodulin MbovP467 of Mycoplasmopsis bovis and Its Potential Contribution in Pathogenesis.

Mycoplasmopsis bovis is a causative agent of crucial diseases in both dairy and beef cattle leading to substantial economic losses. However, limited control measures for M. bovis-related diseases exist due to a lack of understanding about the virulence factors of this pathogen, a common challenge in mycoplasma research. Consequently, this study aimed to characterize a novel nucleomodulin as a virulence-related factor of M. bovis. Employing bioinformatic tools, we initially predicted MbovP467 to be a secreted protein with a nuclear localization signal based on SignalP scores and the cNLS (Nuclear Localization Signal) Mapper, respectively. Subsequently, the MbovP467 gene was synthesized and cloned into a pEGFP plasmid with EGFP labeling to obtain a recombinant plasmid (rpEGFP-MbovP467) and then was also cloned in pET-30a with a consideration for an Escherichia coli codon bias and expressed and purified for the production of polyclonal antibodies against the recombinant MbovP467 protein. Confocal microscopy and a Western blotting assay confirmed the nuclear location of MbovP467 in bovine macrophages (BoMacs). RNA-seq data revealed 220 up-regulated and 20 down-regulated genes in the rpEGFP-MbovP467-treated BoMac group compared to the control group (pEGFP). A GO- and KEGG-enrichment analysis identified associations with inflammatory responses, G protein-coupled receptor signaling pathways, nuclear receptor activity, sequence-specific DNA binding, the regulation of cell proliferation, IL-8, apoptotic processes, cell growth and death, the TNF signaling pathway, the NF-κB signaling pathway, pathways in cancer, and protein families of signaling and cellular processes among the differentially expressed up-regulated mRNAs. Further experiments, investigating cell viability and the inflammatory response, demonstrated that MbovP467 reduces BoMac cell viability and induces the mRNA expression of IL-1ß, IL-6, IL-8, TNF-α, and apoptosis in BoMac cells. Further, MbovP467 increased the promoter activity of TNF-α. In conclusion, this study identified a new nucleomodulin, MbovP467, for M. bovis, which might have an important role in M. bovis pathogenesis.

Association between Oral Health and Depressive Symptoms in Chinese Older Adults: The Mediating Role of Dietary Diversity.

Diet is a modifiable factor in healthy population aging. Additionally, oral health and diet are important factors affecting depressive symptoms. To assess the mediating role of dietary diversity (DD) in oral health and depressive symptoms in older adults, we selected 8442 participants aged ≥ 65 years from the 2018 Chinese Longitudinal Health Longevity Survey (CLHLS) for a cross-sectional study. Depressive symptoms were determined based on scores on the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10). Dietary diversity scores (DDS) were established based on the frequency of intake of food groups. Oral health was measured by denture use and toothbrushing frequency. Stepwise multiple linear regression and PROCESS macros were used for mediated effects analysis and testing. The sample had a positive detection rate of 44.1% for depressive symptoms, 40.8% for denture use, and 41.9% for once-a-day toothbrushing. Denture use (ρ = -0.077, p < 0.01) and toothbrushing frequency (ρ = -0.115, p < 0.01) were negative predictors of depressive symptoms in older adults. DD significantly mediated the association between denture use (indirect effect -0.047; 95%CI: -0.068-0.028; p < 0.001), toothbrushing frequency (indirect effect -0.041; 95%CI: -0.054-0.030; p < 0.001), and depressive symptoms. Denture use and toothbrushing frequency not only directly reduce the risk of depressive symptoms in older adults, but also indirectly affect depressive symptoms through DD.

The effect of sleep problems on core self-evaluations in undergraduate nursing students and the role of emotion regulation and resilience: A cross-sectional study.

BACKGROUND: Nursing students are prone to sleep problems that affect their core self-evaluations. However, little attention has been paid to the specific roles of emotion regulation (including cognitive reappraisal and expressive suppression) and resilience in this process. OBJECTIVES: This study aimed to explore 1) the direct effect of sleep problems on core self-evaluations among nursing students; 2) the chain-mediating effect of cognitive reappraisal and resilience on the relationship between sleep problems and core self-evaluations; 3) the moderating effect of expressive suppression on the direct relationship between sleep problems and core self-evaluations; and 4) the moderating effect of expressive suppression on the indirect relationship between sleep problems affecting core self-evaluations through resilience. METHODS: A total of 345 nursing students completed a survey conducted between September and October 2022. Data was analyzed using descriptive analysis, Fisher exact test, Kruskal-Wallis H test, Spearman correlation analysis, and hierarchical regression analysis. Additionally, the SPSS PROCESS V4.0 plug-in was used to verify the moderated chain-mediating effect. RESULTS: Sleep problems directly affected core self-evaluations among nursing students. Cognitive reappraisal and resilience played a partial chain-mediating role in the relationship between sleep problems and core self-evaluations, with expressive suppression having a direct moderating effect. CONCLUSIONS: Opportunities exist for enhancing the core self-evaluations of nursing students by addressing their sleep problems, promoting cognitive reappraisal strategies, and increasing resilience. Additionally, encouraging expressive suppression can mitigate the negative impact of sleep problems on nursing students' core self-evaluations.

Self-aspiration sampling design for rapid analyses of volatile organic compounds based on atmospheric pressure chemical ionization/photoionization combined ionization source mass spectrometry.

Development of combined mass spectrometry ionization sources has enabled expansion of the application and scope of mass spectrometry. A novel hybrid ionization system combining vacuum ultraviolet (VUV) and atmospheric pressure chemical ionization (APCI) was constructed. Gaseous samples were self-aspirated into an ionization zone through a capillary by negative pressure, generated by high-speed airflow based on the Venturi effect. Compared with APCI mode alone, the signal-to-noise ratio (S/N) in APCI/VUV mode was increased by about 276-times. To increase the ionization efficiency further, correlated experimental conditions were optimized. Four types of volatile organic compounds (VOCs) were tested to evaluate the performance of the APCI/VUV ion source. Excellent linearity and limit of detection were achieved for compounds in mixed solutions. Quantitative analyses of four VOCs (toluene, cyclohexanone, styrene and ethylbenzene) using APCI/VUV-MS were done, and the relative standard deviations (RSDs) were 1.57%, 6.30%, 4.49% and 8.21%, respectively, indicating that the APCI/VUV ionization source had excellent reproducibility. Our results demonstrated that the developed method was promising for analyzing VOCs as well as being rapid, simple, and easy to operate.

A cross-sectional study: caregiver burden and related determinants of adult patients with ß-thalassemia major in mainland China.

BACKGROUND: The informal caregivers of adult patients with ß-thalassemia major (ß-TM) bear not only physical but also emotional and economic pressures of providing care. This study is the first to evaluate the caregiver burden by Zarit Burden Interview (ZBI) of adult patients with ß-TM in mainland China and to identify predictors of caregiver burden. METHODS: In this cross-sectional study, we conducted an online survey with snowball sampling covering seven provinces between September 1, 2021, and January 31, 2022, of patients aged ≥ 18 years with ß-TM and their informal caregivers. Caregiver burden was assessed using the ZBI. Data on patient demographics, disease and therapy characteristics, and informal caregivers' demographic characteristics were collected and analysed using independent t-tests, analysis of variance, Spearman's correlation and multiple linear regression. RESULTS: Of 75 included patients, more than half (50.7%) were male. The mean patient age was 24.69 ± 5.59 years. The mean age of the informal caregivers was 50.60 ± 9.16 years, with women (74.7%) being predominant. The ZBI score was 38.00 ± 17.02. Multiple linear regression analysis showed that patients with interrupted blood transfusion therapy and informal caregivers required to care of others were positively associated with caregiver burden (p < 0.05). Age of informal caregivers were borderline significant positively associated with caregiver burden (p < 0.1). Married informal caregivers were negatively associated with caregiver burden (p < 0.05). CONCLUSIONS: The informal caregivers of adult patients with ß-TM in mainland China experienced a moderate-to-severe level of caregiving burden. The caregiver burden was higher in patients with a history of interrupted blood transfusion therapy or in informal caregivers who were older or needed to care for others. Additionally, married informal caregivers experienced lower burdens compared to non-married informal caregivers. These findings provide a reference to identify informal caregivers with higher burdens among patients with ß-TM.

miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis.

Sepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 µg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1ß, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI.

Latent profiles of nursing students' professional identity and their relationship with stress and coping styles during clinical practicum.

AIM: This study aimed to identify the latent profiles of professional identity among nursing students and explore the factors associated with different profiles. BACKGROUND: Nursing students' professional identity is easily influenced by various factors. However, current studies mainly focused on the overall level of professional identity and its related factors, ignoring the population heterogeneity of nursing students' professional identity. DESIGN: A cross-sectional study. METHODS: A convenient sampling was used to collect data from 384 nursing students who were undergoing their clinical practicum in the affiliated hospitals of a medical university in China between January and April 2021. Data were collected using the demographic questionnaire, the nursing student internship stress scale, the simplified coping style questionnaire, and the professional identity scale for nursing students. A latent profile analysis was used to identify the latent profiles of professional identity. Kruskal-Wallis H test, analysis of variance and ordinal logistic regression were used to determine factors that were associated with different profiles of professional identity. RESULT: Nursing students' professional identity could be classified into four profiles: low professional identity, relatively low professional identity, relatively high professional identity and high professional identity. These four profiles showed unique relationships with choosing nursing voluntarily, willing to be a clinical nursing staff, stress in conflict between study and work, and positive coping styles. CONCLUSION: The majority of the nursing students were classified into profile 1 (low professional identity) and 2 ( relatively low professional identity). Nursing students' lower professional identity need to be further enhanced by improving social recognition of nurses to increase the willingness of high school graduates to choose nursing voluntarily, allocating nursing workforce rationally to increase the willingness of nursing student to be a clinical nursing staff, reducing nursing students' stress in conflict between study and work and encouraging them to adopt positive coping styles.

Chinese Materia Medica in Treating Depression: The Role of Intestinal Microenvironment.

Depression is a highly heterogeneous mental illness. Drug treatment is currently the main therapeutic strategy used in the clinic, but its efficacy is limited by the modulation of a single target, slow onset, and side effects. The gut-brain axis is of increasing interest because intestinal microenvironment disorders increase susceptibility to depression. In turn, depression affects intestinal microenvironment homeostasis by altering intestinal tissue structure, flora abundance and metabolism, hormone secretion, neurotransmitter transmission, and immune balance. Depression falls into the category of "stagnation syndrome" according to Traditional Chinese Medicine (TCM), which further specifies that "the heart governs the spirit and is exterior-interior with the small intestine". However, the exact mechanisms of the means by which the disordered intestinal microenvironment affects depression are still unclear. Here, we present an overview of how the Chinese materia medica (CMM) protects against depression by repairing intestinal microenvironment homeostasis. We review the past five years of research progress in classical antidepressant TCM formulae and single CMMs on regulating the intestinal microenvironment for the treatment of depression. We then analyze and clarify the multitarget functions of CMM in repairing intestinal homeostasis and aim to provide a new theoretical basis for CMM clinical application in the treatment of depression.

Socioeconomic status and quality of life among older adults with hypertension in rural Shandong, China: a mediating effect of social capital.

Background: Improving the quality of life (QoL) of older adults is becoming an important global issue. However, very few studies have been focused on the relationship between socioeconomic status (SES) and QoL in older adults with hypertension. The purpose of this study is to investigate (a) the status of QoL and (b) the mediating effect of social capital in the relationship between SES and QoL, among rural older adults with hypertension in China. Methods: Using multistage stratified random sampling, a face-to-face questionnaire survey was conducted among rural older adults with hypertension in Shandong province of China from June to July 2021. Three typical measures representing SES were used, namely, annual household income, educational level, and employment status. Individual social capital and QoL were assessed by the Resource Generator-China Scale (RG-China) and a 34-item simplified Patient Report Outcome (PRO)-specific scale for older adults with hypertension, respectively. A total of 950 rural older adults with hypertension were included in the analysis. The mediation model based on bootstrap analyses was employed to explore the relationship between SES and QoL and the mediating role of social capital in the SES-QoL nexus. Results: The sampled rural older adults with hypertension had an upper-middle level of QoL, and the average score was 132.57 ± 19.40. SES was positively correlated with both QoL and individual social capital; individual social capital was significantly positively correlated with QoL. Controlling for sociodemographic variables, SES was still significantly associated with individual social capital (ß = 0.140, P < 0.001), and the higher the individual social capital, the better QoL (ß = 0.153, P < 0.001). Individual social capital played a partially mediating role in the association between SES and QoL (indirect effect = 0.021, 95% CI: 0.010-0.038), which accounted for 9.38% of the total effect. Conclusion: This study provides evidence that the effect of SES on QoL was partially mediated by individual social capital among rural older adults with hypertension in China. The government should pay more attention to the rural older hypertensive population with lower SES and strive to reduce the negative impact of poor SES on their QoL, based on effective strategies including improving their individual social capital.

Job burnout on subjective wellbeing among clinicians in China: the mediating role of mental health.

Background: Although job burnout and mental health difficulties are prevalent negative influences on clinicians' subjective wellbeing (SWB), there are few investigations into their relationships. This research investigates the mediating role of mental illness in the association between clinicians' SWB and job burnout in China. Methods: This study used the data collected from a cross-sectional survey conducted in China. Using convenience sampling, we conducted a face-to-face questionnaire survey among clinicians in a tertiary hospital in Shandong Province from August to September 2019. The 22-item Maslach Burnout Inventory-Human Service Survey (Chinese version) and the Personal Wellbeing Index-Adult assessed job burnout and SWB. The Chinese short version of Depression, Anxiety and Stress Scale (DASS-C21) assessed mental health. We also collected data on participants' sociodemographic characteristics and job-related factors. Structural equation modeling (SEM) was applied to examine the associations between variables. Results: Among the 422 participants, 80.8% of the participants reported at least one symptom of job burnout, whereas 5.7% reported all three symptoms of burnout. The prevalence rates of depression, anxiety, and stress were 40.3, 41.7, and 24.9%, respectively. Only 12.8% of the participants had high level of SWB. In mediation analysis, job burnout is positively associated with mental illness (ß = 0.809, P < 0.001), mental illness had a significant negative association with SWB (ß = -0.236, P = 0.013), and a negative association between job burnout and SWB was significant (ß = -0.377, P = 0.002). Mental illness played a partially mediated role in the association between job burnout and SWB (indirect effect = -0.191, 95% CI: -0.361∼-0.017), and the mediating effect of mental illness can explain the 33.6% of the total effect of job burnout on SWB. Conclusion: This study provides evidence that the effect of job burnout on SWB is partially mediated by mental illness among clinicians in China. Medical administration departments and hospital administrators should pay close attention to the job burnout and mental health of clinicians, so as to effectively improve the SWB of clinicians.

Longitudinal association of chronic diseases with depressive symptoms in middle-aged and older adults in China: Mediation by functional limitations, social interaction, and life satisfaction.

Background: Several previous studies have shown that the development of depression is often accompanied by chronic diseases; although closely related, the mechanism between them is not clear. Here we investigate the potential role of functional limitations, social interaction, and life satisfaction in the relationship between chronic diseases and depressive symptoms in middle-aged and older adults in China. Methods: We selected 2407 respondents aged ≥45 from the China Health and Retirement Longitudinal Study conducted in 2013, 2015, and 2018. We established panel data to estimate the longitudinal impact of chronic diseases on depressive symptoms and the mediating role of functional limitations, social interaction, and life satisfaction. Results: Chronic diseases were associated with more depressive symptoms. All of the mediating pathways examined passed functional limitations, and approximately 43.4% of the association between chronic diseases and depressive symptoms was explained by these three mediating variables. Conclusions: The impact of chronic diseases on depressive symptoms was primarily mediated by functional limitations, and the mediating role of social interaction and life satisfaction was also confirmed. Therefore, attention should be paid to reducing the level of functional limitation in middle-aged and older adults with chronic diseases and improving life satisfaction by increasing social opportunities to alleviate depressive symptoms in middle-aged and older adults.

Emotion regulation in undergraduate nursing students: A latent profile analysis.

BACKGROUND: Current research on emotion regulation of undergraduate nursing students mainly focused on the overall level of emotion regulation and its relationship with other variables, ignoring the individual heterogeneity of emotion regulation of undergraduate nursing students. AIM: By latent profile analysis (LPA), this study aimed to identify different emotion regulation profiles among undergraduate nursing students and to explore demographic and personal factors associated with different emotion regulation profiles. METHOD: This was a cross-sectional study. A total of 578 nursing students were investigated by the demographic questionnaire, the emotion regulation scale, the Connor-Davidson resilience scale-10 item and the core self-evaluations scale. LPA was used to analyze the latent profiles of emotion regulation among undergraduate nursing students. And multiple logistic regression was used to explore the predictors of different profiles. RESULT: Three potential profiles were identified: profile 1-- low suppression and moderate reappraisal group, profile 2-- moderate suppression and high reappraisal group, profile 3-- high suppression and high reappraisal group. Resilience, family monthly income and perception of nursing profession were predictors of different profiles. CONCLUSION: Most nursing students were classified into profile 2 and their emotion regulation was relatively good. However, students in profile 1 were with moderate cognitive reappraisal and students in profile 3 were with high expressive suppression, and their emotion regulation need to be further improved by increasing their cognitive reappraisal and decreasing their expressive suppression. Strategies tails to improve resilience, increase scholarships and change the perception of nursing profession may be effective ways to improve emotion regulation of undergraduate nursing students in different profiles.

Molecular mechanisms of caramel-like odorant-olfactory receptor interactions based on a computational chemistry approach.

Molecular mechanisms of caramel-like odorant-olfactory receptor interactions were investigated based on molecular docking and molecular dynamics simulations. The transmembrane regions TM-3, TM-5 and TM-6 of receptors were main contributors of amino acid residues in the docking. Molecular docking results showed that hydrogen bonding and pi-pi stacking were the key forces for the stabilization of caramel-like odorants. The binding energies were positively correlated with the molecular weight of caramel-like odorants. Residues Asn155 (84%, OR2W1), Asn206 (86%, OR8D1), Ser155 (77%, OR8D1), Asp179 (87%, OR5M3), Val182 (84%, OR2J2) and Tyr260 (94%, OR2J2) with high frequencies played an important role in the complexes formation. Odorants 4-hydroxy-5-methylfuran-3(2H)-one (16#) and methylglyoxal (128#) were screened by molecular field-based similarity analysis, which tended to bind to the receptors OR1G1 and OR52H1 respectively, resulting a caramel-like aroma perception. The obtained results are useful for better understanding the perception of caramel-like odorants and their high-throughput screening.

Psychometric properties of the post-stroke depression scale in the sequelae stage.

Aim: To evaluate the psychometric properties of the Post-Stroke Depression Scale in the Sequelae Stage (PSDS-SS). Background: The incidence of the sequelae stage Post-Stroke Depression (PSD) is high, and the best screening tools are still lacking. Under this circumstances, our research team developed the PSDS-SS by Delphi method, but its psychometric properties need to be further verified. Method: This was a cross-sectional study. Seven hundred and sixteen stroke patients in the sequelae stage were enrolled by purpose sampling from May 2022 to September 2022. The exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to verify the factor structure of the scale. The reliability of the scale was tested by Cronbach's α coefficient, test-retest reliability and composite reliability. The validity of the scale was tested by criterion-related validity, convergent and discriminant validity. Result: Eight items were deleted through item analysis. The EFA ended up with a 5-factor scale including 24 items after removing one item with low factor loading. Finally, a 21-item model was established by confirmatory factor analysis, and all the fit indexes were acceptable. The reliability and validity of the total scale and each factor are acceptable. Conclusion: The PSDS-SS has a stable factor structure, and demonstrated good reliability and validity. And it would be an effective tool to assess PSD in the sequelae stage.

Untargeted Metabolomics Using UHPLC-HRMS Reveals Metabolic Changes of Fresh-Cut Potato during Browning Process.

Surface browning plays a major role in the quality loss of fresh-cut potatoes. Untargeted metabolomics were used to understand the metabolic changes of fresh-cut potato during the browning process. Their metabolites were profiled by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS). Data processing and metabolite annotation were completed by Compound Discoverer 3.3 software. Statistical analysis was applied to screen the key metabolites correlating with browning process. Fifteen key metabolites responsible for the browning process were putatively identified. Moreover, after analysis of the metabolic causes of glutamic acid, linolenic acid, glutathione, adenine, 12-OPDA and AMP, we found that the browning process of fresh-cut potatoes was related to the structural dissociation of the membrane, oxidation and reduction reaction and energy shortage. This work provides a reference for further investigation into the mechanism of browning in fresh-cut products.

Equity in the Allocation of General Practitioner Resources in Mainland China from 2012 to 2019.

BACKGROUND: General practitioners (GPs) play a vital role in primary health care services and promoting the health equity of residents, but there is a paucity of evidence on equity in the allocation of GP resources in mainland China. This study explores equity in the allocation of GP resources from 2012 to 2019 in mainland China. METHODS: We used GP data from 31 provinces, autonomous regions, and municipalities in mainland China. Lorenz curves, Gini coefficients, Theil indices, and agglomeration degree were used to analyze the data. RESULTS: The total number of GPs in China was 365,082 in 2019, which corresponded to 2.61 GPs per 10,000 residents and accounted for 9.44% of the total number of practicing doctors in 2019. From 2012 to 2019, the Gini coefficient of GP allocation based on population decreased from 0.3123 to 0.1872. However, the Gini coefficient based on geographical area was maintained at 0.7108-0.7424. The Theil index of GP allocation based on population decreased from 0.0742 to 0.0270, but GP allocation based on geographical area was maintained at 0.5765-0.6898. The intra-regional contribution rates were higher than the inter-regional rates. The agglomeration degree based on geographical area and population decreased in the eastern region but increased in the central and western regions. CONCLUSIONS: The number of Chinese GPs has increased rapidly in recent years, but the distribution of GPs across China is uneven. In the western and middle regions, there is a relative shortage. Equity in the allocation of GP resources based on population was far greater than that based on geographical area. In the future, the tough issue of inequitable GP resource allocation should be resolved by comprehensive measures from a multidisciplinary perspective.

HOXA3 functions as the on-off switch to regulate the development of hESC-derived third pharyngeal pouch endoderm through EPHB2-mediated Wnt pathway.

Objectives: Normal commitment of the endoderm of the third pharyngeal pouch (3PP) is essential for the development and differentiation of the thymus. The aim of this study was to investigate the role of transcription factor HOXA3 in the development and differentiation of 3PP endoderm (3PPE) from human embryonic stem cells (hESCs). Methods: The 3PPE was differentiated from hESC-derived definitive endoderm (DE) by mimicking developmental queues with Activin A, WNT3A, retinoic acid and BMP4. The function of 3PPE was assessed by further differentiating into functional thymic epithelial cells (TECs). The effect of HOXA3 inhibition on cells of 3PPE was subsequently investigated. Results: A highly efficient approach for differentiating 3PPE cells was developed and these cells expressed 3PPE related genes HOXA3, SIX1, PAX9 as well as EpCAM. 3PPE cells had a strong potential to develop into TECs which expressed both cortical TEC markers K8 and CD205, and medullary TEC markers K5 and AIRE, and also promoted the development and maturation of T cells. More importantly, transcription factor HOXA3 not only regulated the differentiation of 3PPE, but also had a crucial role for the proliferation and migration of 3PPE cells. Our further investigation revealed that HOXA3 controlled the commitment and function of 3PPE through the regulation of Wnt signaling pathway by activating EPHB2. Conclusion: Our results demonstrated that HOXA3 functioned as the on-off switch to regulate the development of hESC-derived 3PPE through EPHB2-mediated Wnt pathway, and our findings will provide new insights into studying the development of 3PP and thymic organ in vitro and in vivo.

Characterization of Traditional Chinese Sesame Oil by Using Headspace Solid-Phase Microextraction/Gas Chromatography-Mass Spectrometry, Electronic Nose, Sensory Evaluation, and RapidOxy.

Xiao Mo Xiang You (XMXY) is a traditional Chinese sesame oil variety that is obtained through a hot water flotation process. This unique process gives the oil a unique aroma, health benefits, and excellent product stability. Although XMXY is always the most expensive among all the sesame oil varieties, it is usually used as a flavoring in many traditional Chinese daily food products and is increasingly popular. In order to reveal the characteristics of the oil, the volatile components, sensory evaluation, and oxidation stability of five XMXY samples were, respectively, analyzed by using headspace solid-phase microextraction/gas chromatography−mass spectrometry, an electronic nose, sensory evaluation, and RapidOxy. Comparisons and multidimensional statistical analysis were also carried out to distinguish XMXY from roasted sesame oil (RSO) and cold-pressed sesame oil (CSO) samples. In total, 69 volatiles were identified from XMXY, RSO, and CSO samples. Some compounds possessed high odor activity value (OAV > 1) in XMXY, including heterocyclic compounds, phenols, and sulfur-containing compounds. Additionally, they were also the main volatile components that distinguish XMXY from RSO and CSO. Roasted and nutty aromas were the dominant aroma attributes of XMXY. XMXY had better flavor intensity and oxidation stability than the other two sesame oil samples. These results are very valuable for the quality control and product identification of traditional Chinese sesame oil.

The Regulatory Role of H19/miR-181a/ATG5 Signaling in Perinatal Nicotine Exposure-Induced Development of Neonatal Brain Hypoxic-Ischemic Sensitive Phenotype.

Nicotine exposure either from maternal cigarette smoking or e-cigarette vaping is one of the most common risk factors for neurodevelopmental disease in offspring. Previous studies revealed that perinatal nicotine exposure programs a sensitive phenotype to neonatal hypoxic-ischemic encephalopathy (HIE) in postnatal life, yet the underlying mechanisms remain undetermined. The goal of the present study was to determine the regulatory role of H19/miR-181a/ATG5 signaling in perinatal nicotine exposure-induced development of neonatal brain hypoxic-ischemic sensitive phenotype. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps. All experiments were conducted in offspring pups at postnatal day 9 (P9). Perinatal nicotine exposure significantly enhanced expression of miR-181a but attenuated autophagy-related protein 5 (ATG5) mRNA and protein levels in neonatal brains. Of interest, miR-181a mimicking administration in the absence of nicotine exposure also produced dose-dependent increased hypoxia/ischemia (H/I)-induced brain injury associated with a decreased ATG5 expression, closely resembling perinatal nicotine exposure-mediated effects. Locked nucleic acid (LNA)-miR-181a antisense reversed perinatal nicotine-mediated increase in H/I-induced brain injury and normalized aberrant ATG5 expression. In addition, nicotine exposure attenuated a long non-coding RNA (lncRNA) H19 expression level. Knockdown of H19 via siRNA increased the miR-181a level and enhanced H/I-induced neonatal brain injury. In conclusion, the present findings provide a novel mechanism that aberrant alteration of the H19/miR-181a/AGT5 axis plays a vital role in perinatal nicotine exposure-mediated ischemia-sensitive phenotype in offspring and suggests promising molecular targets for intervention and rescuing nicotine-induced adverse programming effects in offspring.