Search

Background: Helicobacter pylori has been increasingly implicated in extra-gastric diseases. Current evidence regarding the association between serum thyroid-stimulating hormone (TSH), thyroxine (T4), and H. pylori infection remains inconclusive. Consequently, this study aimed to explore the correlation between TSH and T4 levels and H. pylori infection in a US-based population sample. Methods: Data from the US National Health and Nutrition Examination Survey (NHANES), comprising 971 participants aged 30–85 years from 1999 to 2000, were analyzed. Binary logistic regression was employed to analyze the correlation between H. pylori and TSH and T4 levels. The impact of TSH and T4 on H. pylori infection was further assessed using restricted cubic spline (RCS) analysis. In addition, subgroup analyses stratified by sex and age were conducted. Results: Subjects with H. pylori seropositivity demonstrated lower serum TSH levels and higher serum T4 levels compared to those with H. pylori seronegativity. A significant positive correlation was identified between H. pylori seropositivity and T4 levels with increasing quartiles of hormonal levels in both univariate regression models (Q4 vs. Q1: OR = 1.483; 95% CI, 1.033–2.129) and multivariate regression models (Q4 vs. Q1: OR = 1.004; 95% CI, 0.981–1.026). Conversely, a negative correlation was observed between H. pylori seropositivity and TSH levels with increasing quartiles of hormonal levels in univariate regression models (Q4 vs. Q1: OR = 0.579; 95% CI, 0.403–0.831) and in multivariate regression models (Q4 vs. Q1: OR = 0.580; 95% CI, 0.389–0.866). In stratified analyses, the adjusted association of serum T4 levels with H. pylori seropositivity was statistically significant among men (T4: Q4 vs. Q1: OR = 2.253; 95% CI, 1.311–3.873), age over 68 years in TSH levels (Q4 vs. Q1: OR = 0.434; 95% CI, 0.206–0.911), and age 41–54 years in T4 levels (Q4 vs. Q1: OR = 4.965; 95% CI, 2.071–11.903). RCS analysis revealed a non-linear relationship between TSH levels and H. pylori infection. Notably, when TSH < 0.98 IU/ml, the likelihood of H. pylori infection significantly increased. Conclusions: Lower TSH and higher T4 levels were associated with H. pylori infection, particularly among men and elderly individuals. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) presently poses a threat to approximately 24% of the global population. The consumption of healthy diets rich in an abundant assortment of vegetables has been scientifically validated to mitigate the progression of MAFLD. However, it remains uncertain whether all categories of vegetables confer benefits for MAFLD. The objective of this study is to investigate the impact of different types of vegetables on MAFLD, aiming to provide a scientific basis for developing more appropriate dietary recommendations for individuals at high risk of MAFLD. Methods: We investigated the associations between various types of vegetable consumption and the risk of MAFLD, utilizing data sourced from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 cycle. Employing multiple logistic regression and subgroup analyses, we estimated odds ratios (ORs) and 95% confidence intervals (CIs). Results: Our analysis encompassed a total of 3162 participants. Remarkably, heightened intake of dark green vegetables demonstrated an innovative association with reduced odds of MAFLD (OR = 0.54; 95% CI: 0.36–0.81; p-value = 0.01), while other kinds of vegetable shown no significant association with MAFLD in the full adjusted model (all p-vale > 0.05). In the subgroup analysis, a prominent inverse correlation between the consumption of dark green vegetables and MAFLD was discerned among female and non-Hispanic white people with higher educational attainment. Conclusions: Our study conclusively demonstrates that a heightened intake of dark green vegetables is linked to diminished odds of MAFLD. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the prevalence of smartphone addiction, physical activity levels, and depressive symptoms among secondary school students, and to analyze the combined impact of smartphone addiction and physical activity on depressive symptoms. Methods: A cluster sampling method was employed in two secondary schools in the Jing'an District of Shanghai, China. Univariate analysis was used to compare the prevalence of depressive symptoms across different demographic characteristics. Logistic regression was utilized to examine the associations between smartphone addiction, physical activity, and their combined effect on depressive symptoms. Results: A total of 1,316 respondents participated in the study, with reported prevalence rates of depressive symptoms (36.2%), smartphone addiction (19.2%), and insufficient physical activity (23.3%). Risk factors for depressive symptoms included being a non-only child (OR=1.421, 95% CI: 1.090-1.853, P=0.009), inadequate sleep duration (OR=2.722, 95% CI: 2.070-3.578, P<0.001) and smartphone addiction (OR=2.173, 95% CI: 1.621-2.913, P < 0.001). Adolescents with smartphone addiction were significantly more likely to report depressive symptoms compared to those without (OR=2.173, 95% CI: 1.621-2.913, P < 0.001). Joint analysis indicated that combined smartphone addiction and insufficient physical activity significantly increased the risk of depressive symptoms (OR=2.781, 95% CI: 1.627-4.753, P < 0.001). Conclusion: The study identified a high prevalence of severe smartphone addiction, insufficient physical activity, and elevated rates of depressive symptoms among secondary school students. Smartphone addiction and inadequate physical activity were associated with increased likelihood of depressive symptoms. Moreover, higher levels of physical activity appeared to mitigate the adverse impact of smartphone addiction on depressive symptoms. [ABSTRACT FROM AUTHOR]

Leaves have evolved shape diversity, ranging from simple leaves with a smooth margin to complicated shapes with toothed/serrated, lobed, and dissected leaves with leaflets. In the model plant Arabidopsis thaliana with simple leaves producing a serrated margin, boundary regulatory factor genes CUP SHAPED COTYLEDON 2 (CUC2) and CUC3 play important roles in promoting leaf initiation and maintenance of serration. Stem cell-related WUSCHEL-RELATED HOMEOBOX1 (WOX1) and PRESSED FLOWER (PRS)/ WOX3 are also essential for leaf margin morphogenesis, but the role of WOX1 and PRS as well as the relationships between CUCs and WOXs for tooth development are unclear. In this study, we found that WOX1, but not PRS, prevents overproduction of number of teeth and excessive tooth size by limiting CUC3 expression to a moderate level in a temporally regulated manner. We also revealed that BRASSINAZOLE RESISTANT 1 (BZR1), a known regulator of plant development including boundary regions, is involved in WOX1 negative regulation of tooth development by repressing CUC3 expression during the initiation/early stage of tooth development. WOX1 parallelly limits BZR1 and CUC3 expression from the late stage of the first two teeth, while it restricts CUC3 activity in a BZR1-dependent manner from the initiation/early stage of subsequently developed teeth. This study uncovers a new mechanism for WOX1 in fine-tuning the leaf margin geometry. [ABSTRACT FROM AUTHOR]

Backgroud: In the previous era of functional genomics, it was widely believed that the expression levels of housekeeping genes (HKGs) remained relatively constant and were unaffected by variations in tissue type, cell development stage, cell cycle state, as well as internal and external cellular environments. With the improvement of gene microarray technology and quantitative polymerase chain reaction (qPCR) technology for expression analysis of high-throughput differential genes, changes in the expression levels of HKGs have been found in certain human cancers. The present study aimed to experimentally validate the expression of Surfeit 4 gene (SURF4), a member of HKGs, in esophageal squamous cell carcinoma (ESCC). Methods: The experimental techniques employed in this study encompassed real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) to assess the mRNA and protein expression of SURF4 in ESCC, and their clinicopathological significance was statistically analyzed. Results: All three tests showed significant differences between the three groups (Kruskal–Wallis test, P < 0.05). The results of the three methods indicated a significantly higher expression of SURF4 in the tumor group compared to both the adjacent paracancerous tissue group and the normal esophageal mucosal tissue group distant from the tumor. There was no significant difference between the latter two groups. Chi-square and Rank-sum test revealed the expression of SURF4 was significant statistical correlation with tumor cell differentiation, tumor progression and Ki-67 index, as well as the survival prognosis of patients (P < 0.05). Conclusions: The expression of SURF4 was up-regulated in ESCC and was associated with differentiation, proliferation, progression, and clinical prognosis of ESCC. This portended epigenetically that SURF4 may play a role in tumor progression in ESCC and could potentially serve as a novel therapeutic target. [ABSTRACT FROM AUTHOR]

In the light of the instability of trihalomethanes (THMs) in water, a fast and high accuracy method based on headspace gas chromatography-isotope dilution mass spectrometry (HS-GC-IDMS) technique was developed. The optimised method was validated using fortified water samples. Recoveries between 96.1% and 108.8% with an intermediate precision between 3.9% and 5.7% were achieved. The method was applied in the value assignment of THMs in water in an accuracy-based proficiency testing (PT) programme organised by the Health Sciences Authority (HSA) Singapore. The assigned values obtained for chloroform, bromodichloromethane, dibromochloromethane and bromoform were 73.6 ± 9.3 µg/L, 49.1 ± 5.2 µg/L, 47.7 ± 4.4 µg/L and 70.8 ± 6.8 µg/L, respectively. The PT programme was especially valuable and uncommon as it allowed local water testing laboratories to have access to traceable reference values for the benchmarking of their technical competencies. The procedure undertaken by the Laboratory to prepare a batch of PT sample comprising the unstable analytes, conduct homogeneity and stability testing, as well as value assignment, are presented. The between-samples relative standard deviations (RSDs) obtained in a feasibility batch of THMs concentrate in methanol were improved by four to six times compared to those from the first feasibility batch of THMs in water. Based on z-scores, evaluated using the assigned reference value determined by HS-GC-IDMS, 85% of the participating laboratories in the PT programme achieved satisfactory results. The provision of metrological assigned values heightened the testing laboratories' awareness on the importance of accuracy-based PT programmes for evaluation of true method biases, which is particularly valuable for analytes with regulated limits. [ABSTRACT FROM AUTHOR]

Background: The treatment of craniopharyngiomas (CPs) poses challenges due to their proximity to critical neural structures, the risk of serious complications, and the impairment of quality of life after treatment. However, long-term prognostic data are still scarce. Therefore, the purpose of this retrospective study is to evaluate the long-term outcomes of patients with CPs after treatment. Material and method: Our center retrospectively collected data on 83 children and adolescents who underwent craniopharyngioma surgery between 2001 and 2020. The medical records and radiological examination results of the patient were reviewed. Results: Outcomes were analysed for 80/83 patients who completed follow-up: 50 males (62.5%) and 30 females (37.5%), the median age at the time of diagnosis 8.4 (5.3–12.2) years. The median follow-up time was 136 (61–280) months. The 5-, 10- and 15-year overall survival (OS) rates were 100%, 98.3%, and 94.6%, respectively. Accordingly, the disease-specific survival (DSS) rates were 100%, 98.3% and 94.6%, respectively. Overall progression-free survival (PFS) rates after 5, 10 and 15 years of follow-up in the entire group were 85.4%, 72.2% and 70.1%, respectively. Multivariate analysis found that surgical resection grade was only associated with PFS outcomes [ HR = 0.031 (95% CI: 0.006, 0.163), P < 0.001], without improving OS or DSS. After undergoing recombinant human growth hormone (rhGH) replacement therapy, the total cholesterol (TC) level decreased by 0.90 mmol/L compared to baseline (P = 0.002), and the low-density lipoprotein cholesterol (LDL-C) level decreased by 0.73 mmol/L compared to baseline (P = 0.010). For liver function, compared with baseline data, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) showed a downward trend, but did not reach a statistically significant level (P > 0.05). Conclusion: Surgical treatment of CPs provides good long-time OS and DSS, even though combined with radiotherapy in only selected cases. Gross total resection (GTR) is individual positive prognostic factor. rhGH replacement could improve CPs lipid profile. [ABSTRACT FROM AUTHOR]

Soil hydraulic properties are mainly governed by the soil's heterogeneity, anisotropy, and discontinuous structural characteristics, primarily when connected soil macropores characterize the structures. Therefore, researchers must document reliable hydrological models to elucidate how the soil medium affects the movement of soil water. This study, utilizing a field-scale staining tracer test, distinguishes between matrix flow and preferential flow areas in the seepage field of Xi'an loess. The Xi'an loess's soil water characteristic curve (SWCC) was explored through field investigations and laboratory analyses. A dual-permeability model that couples matrix and macropore flow was developed using the Hydrus-2D model, enabling simulations of water migration under varying initial soil water content, rainfall intensity, and crack width. The results showed that (1) The SWCC of macropores in the preferential flow area exhibits a bimodal distribution, and the Fredlund & Xing model is applied for sectional fitting to obtain the corresponding soil water characteristic parameters. (2) Initial soil water content and rainfall intensity significantly influence water distribution, while crack width has a relatively minor effect. (3) The cumulative flux under the preferential flow is significantly higher than in the matrix area, and the wetting front depth increases with higher initial water content and rainfall intensity. This study reveals the key characteristics of preferential flow and moisture migration in the matrix zone and their influencing factors in loess. It constructs a two-domain infiltration model by integrating loess's diverse structural characteristics and pore morphology. This model provides a theoretical basis and technical support for simulating preferential flow and studying the moisture dynamics of loess profiles. [ABSTRACT FROM AUTHOR]

Objective: To explore the differences in ultra-processed food (UPF) consumption across different socioeconomic status (SES) levels. Methods: Data on UPF consumption (grams/day) were derived from the 2017–2018 National Health and Nutrition Examination Survey. The analysis controlled for age, marital status, race, and sex. A restricted cubic spline (RCS) model was applied to examine the nonlinear response curve. Results: UPF consumption increased with higher poverty income ratio (PIR), the ratio of household income to the established poverty line. Compared to the low PIR group, the medium group showed a non-significant increase (β = 34.23[95%CI: −28.81, 97.28], p = 0.287), while the high group exhibited a significant increase (β = 115.15[95%CI: 43.53, 186.76], p = 0.002). A linear positive correlation was observed in RCS analysis (p-nonlinear = 0.166, p-overall < 0.001). Conclusions: The study highlights that higher SES is associated with greater consumption of UPF in the US. The findings suggest that policy interventions should take SES into consideration. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) represents a rare and potentially fatal neurodegenerative disease. Diverse T-cell subsets could potentially exert diametrically opposite impacts upon ALS development. A two-sample Mendelian randomization (MR) analysis was performed to investigate the correlation between 244 T-cell subsets and ALS risk. Genetic instrumental variables were procured from a standard genome-wide association study (GWAS) that encompassed 244 T-cell subsets in 3757 individuals of European lineage. ALS-related data were collected from a GWAS comprising 20,806 ALS instances and 59,804 European control participants. Multiple sensitivity analyses were performed to verify the robustness of the significant results. Reverse MR analysis was used for delineating the effects of ALS on the characteristics of T-cells. After multiple comparison corrections, 24 out of the 244 subtypes demonstrated a potential association with ALS risk. Significantly, 75% of these associations encompassed the expression of the CD3 on diverse T-cell subtypes, revealing a highly consistent inverse relation to ALS risk. The proportion of T regulatory cells (Tregs) in CD4+ T cells and secreting Tregs in CD4+ T cells demonstrated negative associations with the risk of ALS. CCR7 expression on naive CD4+ T cells and CCR7 expression on naive CD8+ T cells showed positive associations with ALS risk. Certain T-cell subsets, particularly those identified by CD3 expression on terminally differentiated CD8+ T cells, proportions of Tregs, and CCR7 expression, indicated an association with ALS risk. These findings harmonize with and extend previous observational studies investigating the involvement of T lymphocyte subset-induced immunological processes in ALS. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed lymphocyte-to-monocyte ratio (LMR) changes to predict postoperative recurrence in Fusobacterium nucleatum-positive (Fn-positive) CRC patients. Patients and Methods: Clinical information and paraffin tissue specimens were collected from a retrospective cohort of 332 patients. The abundance of Fn in tumor tissue was measured using a quantitative polymerase chain reaction. We evaluated the prognostic value and diagnostic performance of the dynamic changes of LMR from pre-operative to post-treatment (pr-LMR-po) and the dynamic alterations of LMR from pre-operative to post-treatment to pre-end of follow-up (pr-LMR-f) in predicting recurrence in Fn-positive CRC. Results: In the total cohort and adjuvant therapy group cohort, pr-LMR-po independently predicted recurrence-free survival in Fn-positive CRC patients. In the adjuvant therapy group, pr-LMR-po (High-High vs Low-Low: HR: 3.896, 95% CI: 1.503– 10.095, p=0.005) was particularly significant. Meanwhile, pr-LMR-f can serve as a predictive biomarker for Fn-positive CRC recurrence, especially in the adjuvant therapy group cohort where the c-statistic for pr-LMR-f was 0.825 (95% CI: 0.804– 0.8251), with a sensitivity of 83.6% and a specificity of 79.3%. Compared to the overall adjuvant therapy group cohort, the prognostic performance of pr-LMR-f was superior in the Fn-positive CRC adjuvant therapy group cohort (AUC: 0.825 VS 0.711). Finally, we constructed a prediction model combining pr-LMR-f and CEA. After internal validation using the bootstrap resampling, the model had an AUC of 0.9295, a sensitivity of 94%, and a specificity of 72.7% in the Fn-positive CRC adjuvant therapy group cohort. Conclusion: This study found that pr-LMR-po predicts Fn-positive CRC prognosis, and pr-LMR-f may predict Fn-positive CRC recurrence. [ABSTRACT FROM AUTHOR]

Background and purpose: Elevated serum lipoprotein(a) (Lp[a]) levels have been linked to an increased incidence of stroke. This systematic review and meta‐analysis aimed to evaluate the impact of serum Lp(a) on the functional outcomes of patients with ischemic stroke (IS). Methods: We conducted a comprehensive search of the MEDLINE, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure databases to identify relevant cohort studies. A random effects model was utilized to synthesize the data, accounting for study heterogeneity. Results: The analysis included 11 cohort studies comprising 11,958 patients with IS. Pooled results indicated that high baseline Lp(a) levels were associated with an increased risk of poor functional outcomes during follow‐up (odds ratio [OR] = 2.13, 95% confidence interval = 1.67–2.71, p < 0.001, I2 = 62%). Subgroup analyses revealed that the relationship between high Lp(a) levels and the risk of poor functional outcomes was more pronounced at discharge (OR = 3.25), 3 months (OR = 2.02), and 6 months (OR = 2.11) poststroke, compared to 12 months (OR = 1.25, p for subgroup difference < 0.001). Furthermore, the association was attenuated yet remained significant in studies adjusting for low‐density lipoprotein cholesterol (LDL‐C) compared to those that did not adjust for LDL‐C (OR = 1.69 vs. 2.63, p for subgroup difference = 0.03). Conclusions: High serum Lp(a) levels at baseline are significantly associated with poor functional outcomes in patients with IS. [ABSTRACT FROM AUTHOR]

In response to the widespread issue of fake comments on e-commerce platforms, this study aims to analyze and propose a blockchain-based solution to incentivize authentic user feedback and reduce the prevalence of fraudulent reviews. Specifically, this paper constructs a tripartite evolutionary game model between sellers, buyers, and e-commerce platforms to study the real comment mechanism of blockchain. The strategy evolution under different incentive factors is simulated using replication dynamic equation analysis and Matlab software simulation. The study found that introducing smart contracts and "tokens" for incentives not only increased incentives for real comments but also reduced the negative experiences caused by "speculative" sellers, thereby influencing buyers to opt for authentic reviews. By structuring interactions through blockchain, the mechanism helped lower informational entropy thus reducing disorder and unpredictability in buyer and seller behavior and contributing to system stability. Further, by increasing penalties for dishonest behavior under the "credit on the chain" system, the platform lowered entropy in the system by promoting trust and reducing fraudulent activities. The real comment mechanism based on blockchain proposed in this paper can effectively enhance the order and transparency within the comment ecosystem. These findings contribute to theory and practice by providing strategic insights for e-commerce platforms to encourage genuine feedback, reduce informational entropy, and mitigate fake comments, ultimately fostering a more reliable online marketplace. [ABSTRACT FROM AUTHOR]

Aims Methicillin-resistant Staphylococcus aureus (MRSA) is an important zoonotic pathogen with multidrug-resistant phenotypes increasingly prevalent in both human and veterinary clinics. This study evaluated the potential of auranofin (AF) as an antibiotic adjuvant to enhance the anti-MRSA activity of florfenicol (FFC) and established a pharmacokinetic/pharmacodynamic (PK/PD) model to compare the efficacy of FFC alone or in combination with AF against MRSA. Methods and results We observed an increased susceptibility and significant synergistic effects of MRSA to FFC in the presence of AF. The combination treatment of FFC and AF significantly inhibited MRSA biofilm formation and decreased the metabolic activity of mature biofilms. Importantly, AF fully restored the efficacy of FFC in both Galleria mellonella larvae and murine models. PK/PD studies demonstrated that the AUC24h/MIC targets required to achieve the bacteriostatic and bactericidal effects were significantly lower with the combination therapy compared to florfenicol monotherapy. Conclusions These results reveal the potential of AF as a novel adjuvant to improve the efficacy of FFC in treating MRSA invasive infections and provide valuable PK/PD insights for designing effective combination therapies. [ABSTRACT FROM AUTHOR]

Lipoteichoic acid (LTA), an organic acid of Gram-positive bacteria, is closely related to mastitis in dairy cows. This study evaluates the effect of LTA-induced endoplasmic reticulum stress (ER stress) in vitro using MAC-T (mammary epithelial cells) and in dairy cows with mastitis. LTA stimulation significantly increases ER stress and apoptosis-related factors in MAC-T. Further analysis suggests that the increase in ER stress may be associated with interactions involving PTGS2 and GRP78. Protein structural studies indicate a strong interaction between PTGS2 and GRP78. Lipidomics results further demonstrate that LTA disrupts lipid balance in MAC-T cells, affecting lipid metabolism in the endoplasmic reticulum, including PC, PE, TAG, and DAG, thereby exacerbating inflammation and ER stress. In dairy cows with mastitis caused by Gram-positive bacterial infection, damaged epithelial cells, inflammatory cell infiltration, and apoptotic vesicles are observed in affected tissues. In contrast, tissues from healthy cows exhibit regular epithelial cells without inflammatory cells or apoptotic vesicles. Furthermore, a significant ER stress and apoptosis increase is observed in mastitis tissues. This study demonstrates the close association between LTA-induced cell damage and ER stress, contributing to understanding the mechanisms underlying LTA-induced damage and supporting strategies for mastitis prevention and control in dairy cows. [ABSTRACT FROM AUTHOR]

Ultra-processed foods dominate modern diets, often containing numerous additives to enhance flavor, texture, and shelf life. Concerns about the potential health risks of daily or excessive consumption have sparked online discussions. This study analyzed perceptions of food additives on Zhihu, a popular Chinese social platform. The findings revealed no significant difference in attitudes between experts and non-experts (p > 0.05), with experts relying on statistical data and non-experts drawing from personal experiences. An independent t-test indicated no significance in comment engagement (p > 0.05) among them. However, a chi-square test showed that experts were significantly more interactive, frequently replying directly to original posts and commenters (p < 0.05). This suggests that experts actively facilitate discussions, moving away from reliance on influencers and instead prioritizing high-quality, accessible scientific communication. The findings highlight the crucial role of interactive online platforms in bridging the gap between science and the public. [ABSTRACT FROM AUTHOR]

Background Type 2 diabetes mellitus (T2DM) intricately involves disrupted lipid metabolism. Exosomes emerge as carriers of biomarkers for early diagnosis and monitoring. This study aims to identify lipid metabolites in serum exosomes for T2DM diagnosis. Methods Serum samples were collected from newly diagnosed T2DM patients and age and body mass index−matched healthy controls. Exosomes were isolated using exosome isolation reagent, and untargeted/targeted liquid chromatography−tandem mass spectrometry (LC-MS/MS) was used to identify and validate altered lipid metabolites. Receiver operating characteristic curve analysis was used to evaluate the diagnostic value of candidate lipid metabolites. Results Serum exosomes were successfully isolated from both groups, with untargeted LC-MS/MS revealing distinct lipid metabolite alterations. Notably, phosphatidylethanolamine (PE) (22:2(13Z,16Z)/14:0) showed stable elevation in T2DM-serum exosomes. Targeted LC-MS/MS confirmed significant increase of PE (22:2(13Z,16Z)/14:0) in T2DM exosomes but not in serum. PE (22:2(13Z,16Z)/14:0) levels not only positively correlated with hemoglobin A1C levels and blood glucose levels, but also effectively distinguished T2DM patients from healthy individuals (area under the curve = 0.9141). Conclusion Our research sheds light on the importance of serum exosome lipid metabolites in diagnosing T2DM, providing valuable insights into the complex lipid metabolism of diabetes. [ABSTRACT FROM AUTHOR]

Frozen shoulder (FS) is a common shoulder condition accompanied by shoulder pain and a loss of shoulder range of motion (ROM). The typical clinical assessment tools such as questionnaires and ROM measurement are susceptible to subjectivity and individual bias. To provide an objective evaluation for clinical assessment, this study proposes an inertial measurement unit (IMU)-based identification system to automatically identify shoulder tasks whether performed by healthy subjects or FS patients. Two groups of features (time-domain statistical features and kinematic features), seven machine learning (ML) techniques, and two deep learning (DL) models are applied in the proposed identification system. For the experiments, 24 FS patients and 20 healthy subjects were recruited to perform five daily shoulder tasks with two IMUs attached to the arm and the wrist. The results demonstrate that the proposed system using deep learning presented the best identification performance using all features. The convolutional neural network achieved the best identification accuracy of 88.26%, and the multilayer perceptron obtained the best F1 score of 89.23%. Further analysis revealed that the identification performance based on wrist features had a higher accuracy compared to that based on arm features. The system's performance using time-domain statistical features has better discriminability in terms of identifying FS compared to using kinematic features. We demonstrate that the implementation of the IMU-based identification system using ML is feasible for FS assessment in clinical practice. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) is consistently challenging to conquer with numerous complications and fatalities. Despite the effectiveness of antiviral therapies in suppressing hepatitis B virus (HBV) replication, there is an urgent need for novel and more effective treatment modalities. Current strategies predominantly emphasize immune activation but still face challenges in sufficiently eliciting T cell responses. Taking into account the targeted delivery of nanoparticles to the liver and spleen via intravenous injection, we have proposed a dual-pronged therapeutic strategy based on antigen-presenting cells (APCs)-derived exosomes. Specifically, exosomes targeted to the spleen can activate specific immune responses, while those targeted to the liver can modulate or reverse the liver's immunosuppressive microenvironment. After immunization, exosome formulations exhibit the remarkable ability to effectively activate APCs, thereby triggering the proliferation of CD8+T cells. Simultaneously, they also play an immunoregulatory role by converting M2 macrophages into M1 macrophages. This two-pronged therapeutic strategy precisely addresses the issues of T cell dysfunction and immune suppression, both characteristic features of CHB patients. When combined with Aluminum (Alum)-adjuvanted vaccine, these exosome formulations not only demonstrate a high level of cellular immune response but also secrete specific antibodies comparable to those induced by Alum adjuvant. This combined approach effectively enhances both cellular and humoral immunity, offering a promising avenue for the development of therapeutic hepatitis B vaccines based on exosome formulations. [ABSTRACT FROM AUTHOR]

Background: The treatment-free interval is a significant predictor of worse prognosis and poor response rates of the second-line treatment in patients with carboplatin and paclitaxel (PT)-pretreated, advanced, or recurrent endometrial cancer (EC). Whether lenvatinib plus pembrolizumab still confers a survival benefit compared with doxorubicin in patients with platinum-free intervals of <6 months remains unclear. Methods: This multi-institutional retrospective analysis was performed using de-identified electronic health records from the TriNetX Research Network. Patients with advanced or recurrent ECs who received lenvatinib plus pembrolizumab or doxorubicin within six months of first-line PT were identified. A 1:1 propensity score matching (PSM) was conducted to control for potential confounding variables. Overall survival (OS) and adverse event profile were the primary and secondary outcomes. Results: Between January 2018 and February 2024, 130 patients with PT-treated, advanced, or recurrent ECs who received lenvatinib plus pembrolizumab and 122 patients who received doxorubicin at a platinum-free interval of <6 months were identified across 31 healthcare organizations. In the balanced cohort following PSM with 117 patients in each group, treatment with lenvatinib plus pembrolizumab was associated with improved OS compared with treatment with doxorubicin (12.8 vs. 8.2 months, p = 0.012, hazard ratio: 0.65, 95% confidence interval: 0.46–0.91). Regarding adverse event analysis, a higher incidence of hypothyroidism and proteinuria was observed with lenvatinib plus pembrolizumab, and more hematological toxicities were observed with doxorubicin. Conclusions: in patients with treatment-free intervals of <6 months, lenvatinib plus pembrolizumab still confers improved survival compared with doxorubicin in PT-treated, advanced, or recurrent ECs. [ABSTRACT FROM AUTHOR]

We develop a dynamic incomplete-markets model of entrepreneurial firms and demonstrate the implications of preferences for liquidity to entrepreneur's interdependent consumption, portfolio allocation, hedging and financing decisions. The numerical results provide several important implications. Preferences for liquidity reduce hedging demand using risky assets. Besides, the existence of preferences for liquidity decreases the implied equity value and encourages the entrepreneur to issue more debt. Especially, the preferences for liquidity can overturn the risk-shifting incentives of a risk-averse entrepreneur. [ABSTRACT FROM AUTHOR]

Histidine kinases (HKs) are important sensor proteins in fungi and play an essential role in environmental adaptation. However, the mechanisms by which fungi sense and respond to fungivores attack via HKs are not fully understood. In this study, we utilized Neurospora crassa to investigate the involvement of HKs in responding to fungivores attack. We found that the 11 HKs in N. crassa not only affected the growth and development, but also led to fluctuations in antioxidant production. Ten mutants in the genes encoding HKs (except ∆phy1) showed increased production of reactive oxygen species (ROS), especially upon Sinella curviseta attack. The ROS burst triggered changes in conidia and perithecial beaks formation, as well as accumulation of β-glucan, ergothioneine, ergosterol, and carotenoids. β-glucan was increased in ∆hk9, ∆os1, ∆hcp1, ∆nik2, ∆sln1, ∆phy1 and ∆phy2 mutants compared to the wild-type strain. In parallel, ergothioneine accumulation was improved in ∆phy1 and ∆hk16 mutants and further increased upon attack, except in ∆os1 and ∆hk16 mutants. Additionally, fungivores attack stimulated ergosterol and dehydroergosterol production in ∆hk9 and ∆os1 mutants. Furthermore, deletion of these genes altered carotenoid accumulation, with wild-type strain, ∆hk9, ∆os1, ∆hcp1, ∆sln1, ∆phy2, and ∆dcc1mutants showing an increase in carotenoids upon attack. Taken together, HKs are involved in regulating the production of conidia and antioxidants. Thus, HKs may act as sensors of fungivores attack and effectively improve the adaptive capacity of fungi to environmental stimuli. [ABSTRACT FROM AUTHOR]

Background: The molecular mechanisms and signaling pathways involved in tooth morphogenesis have been the research focus in the fields of tooth and bone development. However, the cell population in molars at the late bell stage and the mechanisms of hard tissue formation and mineralization remain limited knowledge. Results: Here, we used the rat mandibular first and second molars as models to perform single-cell RNA sequencing (scRNA-seq) analysis to investigate cell identity and driver genes related to dental mesenchymal cell differentiation during the late bell hard tissue formation stage. We identified seven main cell types and investigated the heterogeneity of mesenchymal cells. Subsequently, we identified novel cell marker genes, including Pclo in dental follicle cells, Wnt10a in pre-odontoblasts, Fst and Igfbp2 in periodontal ligament cells, and validated the expression of Igfbp3 in the apical pulp. The dynamic model revealed three differentiation trajectories within mesenchymal cells, originating from two types of dental follicle cells and apical pulp cells. Apical pulp cell differentiation is associated with the genes Ptn and Satb2, while dental follicle cell differentiation is associated with the genes Tnc, Vim, Slc26a7, and Fgfr1. Cluster-specific regulons were analyzed by pySCENIC. In addition, the odontogenic function of driver gene TNC was verified in the odontoblastic differentiation of human dental pulp stem cells. The expression of osteoclast differentiation factors was found to be increased in macrophages of the mandibular first molar. Conclusions: Our results revealed the cell heterogeneity of molars in the late bell stage and identified driver genes associated with dental mesenchymal cell differentiation. These findings provide potential targets for diagnosing dental hard tissue diseases and tooth regeneration. [ABSTRACT FROM AUTHOR]

Tailings dust can negatively affect the surrounding environment and communities because the tailings are vulnerable to wind erosion. In this study, the effects of halides (sodium chloride [NaCl], calcium chloride [CaCl2], and magnesium chloride hexahydrate [MgCl2·6H2O]), and polymer materials (polyacrylamide [PAM], polyvinyl alcohol [PVA], and calcium lignosulfonate [LS]) were investigated for the stabilization of tailings for dust control. Erect milkvetch (Astragalus adsurgens), ryegrass (Lolium perenne L.), and Bermuda grass (Cynodon dactylon) were planted in the tailings and sprayed with chemical dust suppressants. The growth status of the plants and their effects on the mechanical properties of tailings were also studied. The results show that the weight loss of tailings was stabilized by halides and polymers, and decreased with increasing concentration and spraying amount of the solutions. The penetration resistance of tailings stabilized by halides and polymers increased with increasing concentration and spraying amount of the solutions. Among the halides and polymers tested, the use of CaCl2 and PAM resulted in the best control of tailings dust, respectively. CaCl2 solution reduces the adaptability of plants and therefore makes it difficult for grass seeds to germinate normally. PAM solutions are beneficial for the development of herbaceous plants. Among the three herbaceous species, ryegrass exhibited the best degree of development and was more suitable for growth in the tailings. The ryegrass plants planted in the tailings sprayed with PAM grew the best, and the root-soil complex that formed increased the shear strength of the tailings. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of sodium picosulfate/magnesium citrate (SPMC) and 3 L split-dose polyethylene glycol (PEG) with or without dimethicone on bowel preparation before colonoscopy. Methods: In this multicenter, prospective, randomized, controlled study conducted from April 2021 to December 2021, consecutive adult patients scheduled for colonoscopy were prospectively randomized into four groups: SPMC, SPMC plus dimethicone, 3 L PEG, and 3 L PEG plus dimethicone. Primary endpoint was colon cleansing based on Boston Bowel Preparation Scale (BBPS). Secondary endpoints were bubble score, time to cecal intubation, adenoma detection rate (ADR), patient safety and compliance, and adverse events. Results: We enrolled 223 and 291 patients in SPMC and 3 L PEG group, respectively. The proportion with acceptable bowel cleansing, total BBPS score and cecal intubation time were similar in all four subgroups (p > 0.05). Patient-reported acceptability and tolerability was significantly greater in SPMC than 3 L PEG group (p < 0.001); adverse events were significantly lower in SPMC than latter group (p < 0.001). ADR in both groups was greater than 30%. Conclusion: SPMC had significantly higher acceptability and tolerability than 3 L PEG, however, was similar in terms of bowel-cleansing effect and cecal intubation time and hence can be used before colonoscopy preparation. [ABSTRACT FROM AUTHOR]

Thyroid eye disease (TED) is a complex autoimmune disorder that impairs various orbital structures, leading to cosmetic damage and vision loss. Magnetic resonance imaging (MRI) is a fundamental diagnostic tool utilized in clinical settings of TED, for its accurate demonstration of orbital lesions and indication of disease conditions. The application of quantitative MRI has brought a new prospect to the management and research of TED, offering more detailed information on morphological and functional changes in the orbit. Therefore, many researchers concentrated on the implementation of different quantitative MRI techniques on TED for the exploration of clinical practices. Despite the abundance of studies utilizing quantitative MRI in TED, there remain considerable barriers and disputes on the best exploitation of this tool. This could possibly be attributed to the complexity of TED and the fast development of MRI techniques. It is necessary that clinical and radiological aspects of quantitative MRI in TED be better integrated into comprehensive insights. Hence, this review traces back 30 years of publications regarding quantitative MRI utilized in TED and elucidates this promising application in the facets of imaging techniques and clinical practices. We believe that a deeper understanding of the application of quantitative MRI in TED will enhance the efficacy of the multidisciplinary management of TED. Level of Evidence: 2 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to provide an updated analysis of suicide characteristics in China from 2002 to 2021, with the aim of informing the development of evidence‐based suicide prevention strategies. Methods: The Ministry of Health‐Vital Registration System (MOH‐VR) provided the data on suicide mortality, which enabled us to examine the average annual percentage change (AAPC) in suicide rates using a Poisson regression model. Results: Notably, there has been a significant decline in suicide rates observed in both urban and rural areas. In the early years of the study period, higher suicide rates were observed among females compared to males; however, a shift occurred after 2005, with male suicide rates surpassing those of females. Except for 2005, rural areas consistently exhibited higher suicide rates than urban areas. Furthermore, suicide rates exhibited an increasing trend with age, irrespective of gender or region. Conclusion: These findings highlight a decreasing trend in suicide rates in China over the past two decades, although gender and regional disparities persist. Going forward, sustained efforts in suicide prevention, with a specific focus on mental health, are warranted. [ABSTRACT FROM AUTHOR]

MADS-box genes play a vital role in the vegetative and reproductive growth of plants. In this study, a MiAGL1 gene was cloned and identified from mango (Mangifera indica L.). The DNA sequence of AGAMOUS-LIKE1 (MiAGL1) was 8741 bp in length, including a 723 bp open reading frame and encoding 241 amino acids. MiAGL1 belongs to the MADS-box family. This gene was expressed not only in vegetative tissues but also in floral organs, and the highest expression level was found in flowers. MiAGL1 was expressed in leaves at different floral developmental stages, but the peak appeared at the floral organ differentiation stage. MiAGL1 was present in the cell membrane and nucleus. Ectopic expression of MiAGL1 in Arabidopsis resulted in significant early flowering under long-day conditions. Overexpression of MiAGL1 resulted in abnormal flowering and silique morphology, such as a decrease or absence of petals, smaller petals, and shorter, bent or distorted capsules. The endogenous Arabidopsis thaliana flowering-related genes FT, AP1, and SEP were significantly upregulated, and AtSVP was downregulated in the transgenic lines. Therefore, our data showed that the MiAGL1 gene may play a crucial role in flowering time regulation and floral organ identity. [ABSTRACT FROM AUTHOR]

The Food-First Strategy advocates seeking a nutritional solution for the prevention and treatment of disease before resorting to supplements or therapeutic agents. Advances in knowledge of nutrition at the cellular level are providing information on how micronutrients are incorporated into cells and how they exert their actions. Micronutrients, in the form of naturally occurring nanoparticles, are more bioavailable and also act as antioxidants to tackle inflammation and promote cellular regeneration and repair. They are the new "superheroes of nutrition" and an understanding of their metabolic impact can explain and support associated health claims. [ABSTRACT FROM AUTHOR]

Controllable and long‐term release remains a great challenge in current drug delivery systems. Benefiting from their efficient drug loading and painless administration, microneedles (MNs) have emerged as a promising platform for transdermal drug delivery, while they often fail to achieve long‐term tissue adhesion and controllable extended drug release. Here, 3D printing of an innovative MN patch is presented with succulent‐inspired responsive microstructures and light‐controllable long‐term release capability. The MN exhibits a reversible shrink‐swell volume change behavior in response to surrounding humidity, which enables sufficient mechanical strength for skin penetration under the shrinkage conditions and efficient long‐term adhesion when swollen in skin tissues. Moreover, the MN patch introduces a controllable long‐term drug release system, achieved through the integration of thiolated heparin (Hep‐SH) for sustained growth factor release and graphene oxide (GO) nanosheets for controlled drug release via near infrared (NIR) laser irradiation. The MN patches with growth factor loading have good biocompatibility and can promote the proliferation, migration, and proangiogenesis of endothelial cells is further demonstrated. Thus, it is believed that such flexible MN patches can be promising candidates for controllable long‐term transdermal drug delivery as well as other related tissue engineering applications. [ABSTRACT FROM AUTHOR]

Exosomes are small extracellular vesicles secreted by almost all cell types, and carry diverse cargo including RNA, and other substances. Recent studies have focused exosomal microRNAs (miRNAs) on various human diseases, including type 2 diabetes mellitus (T2DM) and metabolic syndrome (METS) which accompany the occurrence of insulin resistance. The regulation of insulin signaling has connected with some miRNA expression which play a significant regulatory character in insulin targeted cells or organs, such as fat, muscle, and liver. The miRNAs carried by exosomes, through the circulation in the body fluids, mediate all kinds of physiological and pathological process involved in the human body. Studies have found that exosome derived miRNAs are abnormally expressed and cross-talked with insulin targeted cells or organs to affect insulin pathways. Further investigations of the mechanisms of exosomal miRNAs in T2DM will be valuable for the diagnostic biomarkers and therapeutic targets of T2DM. This review will summarize the molecular mechanism of action of the miRNAs carried by exosomes which are secreted from insulin signaling related cells, and elucidate the pathogenesis of insulin resistance to provide a new strategy for the potential diagnostic biomarkers and therapeutic targets for the type 2 diabetes. [ABSTRACT FROM AUTHOR]

The engineering general contracting mode is an advanced engineering transaction mode, and design optimization is one of the important driving forces for vigorously promoting the general contracting mode. The application proportion of the general contracting mode in infrastructure projects is not high, the number of successful projects is not large, and the implementation effect is not ideal. One of the main reasons is that the design optimization theory and practice of international standard general contracting projects cannot adapt to the general contracting projects in the Chinese context, making local general contracting projects face huge challenges such as low enthusiasm for design optimization from all parties and unsatisfactory design optimization effects. Therefore, under the premise of bounded rationality, when the owner adopts control methods of different intensities, an evolutionary game study on the selection of design optimization strategies between the design and construction parties is carried out, and stability control strategies are proposed through case experiments and simulations. The research results indicate the following: firstly, the design optimization of general contracting projects in the Chinese context is feasible, but it depends on the distribution ratio of benefits obtained from the design optimization. Compared with general civil construction general contracting projects, the design optimization allocation ratio of industrial construction general contracting projects is more significant; secondly, the mixed control method of strong control and weak control is the optimal choice for the owner of the general contracting project; and thirdly, there are multiple evolutionary stable points, and mechanism design or incentive measures should be used to guide owners to choose weak control strategies, while design and construction parties should choose their design optimization strategies. The research results provide a reference for owners to determine the proportion and scheme of design optimization allocation, and for construction parties to determine design optimization strategies. [ABSTRACT FROM AUTHOR]

Purpose: We examined the associations of soy product intake with all-cause, cardiovascular disease (CVD), and cancer mortality and mediations through CVD risk factors based on the Guangzhou Biobank Cohort Study (GBCS), and conducted updated meta-analyses. Methods: A total of 29,825 participants aged 50 + years were included. Causes of death were identified through record linkage. Soy product intake was assessed by food frequency questionnaire. Cox proportional hazards regression was used to analyze the associations between soy product intake and mortality, yielding hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses with CVD risk factors as mediators, and updated meta-analyses were conducted. Results: During 454,689 person-years of follow-up, 6899 deaths occurred, including 2694 CVD and 2236 cancer. Participants who consumed soy product of 1–6 portions/week, versus no consumption, had significantly lower risks of all-cause and CVD mortality (adjusted HR (95% CI) 0.91 (0.86, 0.97) and 0.87 (0.79, 0.96), respectively). In participants who consumed soy product of ≥ 7 portions/week, the association of higher intake with lower CVD mortality was modestly mediated by total cholesterol (4.2%, 95% CI 1.0–16.6%). Updated meta-analyses showed that the highest level of soy product intake, versus the lowest, was associated with lower risks of all-cause and CVD mortality (pooled HR (95% CI) 0.92 (0.88, 0.96) and 0.92 (0.87, 0.98), respectively). Conclusion: Moderate and high soy product intake were associated with lower risks of all-cause and CVD mortality. Our findings provide support for current dietary guidelines recommending moderate soy product intake, and contribute additional evidence regarding the potential protective effects of high soy product intake. [ABSTRACT FROM AUTHOR]

This study aims to explore tooth growth variation by regions and ethnicity in China, and to validate the modified Tibetan so as to assist in proposing a better approach. A total of 1320 orthopantomograms of Han children aged 4–14.99 were retrospectively collected from eastern and western regions of China. The Demirjian method and modified Tibetan method were applied. Results showed that dental maturity scores (DMS) in eastern children were significantly greater than western children. Age was overestimated by both methods in eastern children. MAE was 0.88 and 1.3 years by Demirjian method, 1.01 and 1.21 years by modified Tibetan method in eastern girls and boys respectively. In western children, age was significantly underestimated in girls and slightly overestimated by Demirjian method; by modified method, age was generally overestimated. MAE was 0.79 and 0.84 years by Demirjian method, 0.51 and 0.69 years by modified Tibetan method in girls and boys respectively. The current study reveals that tooth growth was significantly advanced in Eastern Han children compared with Western Han children. Ethnic variation between Eastern Han and Tibetan Chinese was substantial. Neither method was sufficiently accurate in Eastern Han children. The modified Tibetan method was reliable in Western Han children. [ABSTRACT FROM AUTHOR]

The conservation biology field underscores the importance of understanding genetic diversity and gene flow within plant populations and the factors that influence them. This study employs Simple Sequence Repeat (SSR) molecular markers to investigate the genetic diversity of the endangered plant species Saussurea involucrata, offering a theoretical foundation for its conservation efforts. Utilizing sequencing results to screen SSR loci, we designed and scrutinized 18 polymorphic microsatellite primers across 112 samples from 11 populations in the Bayinbuluke region. Our findings reveal high genetic diversity (I = 0.837, He = 0.470) and substantial gene flow (Nm = 1.390) among S. involucrata populations (China, Xinjiang), potentially attributed to efficient pollen and seed dispersal mechanisms. Principal Coordinate Analysis (PCoA) indicates a lack of distinct genetic structuring within the Bayinbuluke populations. The cluster analysis using STRUCTURE reflected the genetic structure of S. involucrata to a certain extent compared with PCoA. The results showed that all samples were divided into four groups. To safeguard this species, we advocate for the in situ conservation of all S. involucrata populations in the area. The SSR markers developed in this study provide a valuable resource for future genetic research on S. involucrata. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is an ongoing "one health" challenge of global concern. The acyl-ACP synthetase (termed AasS) of the zoonotic pathogen Vibrio harveyi recycles exogenous fatty acid (eFA), bypassing the requirement of type II fatty acid synthesis (FAS II), a druggable pathway. A growing body of bacterial AasS-type isoenzymes compromises the clinical efficacy of FAS II-directed antimicrobials, like cerulenin. Very recently, an acyl adenylate mimic, C10-AMS, was proposed as a lead compound against AasS activity. However, the underlying mechanism remains poorly understood. Here we present two high-resolution cryo-EM structures of AasS liganded with C10-AMS inhibitor (2.33 Å) and C10-AMP intermediate (2.19 Å) in addition to its apo form (2.53 Å). Apart from our measurements for C10-AMS' Ki value of around 0.6 μM, structural and functional analyses explained how this inhibitor interacts with AasS enzyme. Unlike an open state of AasS, ready for C10-AMP formation, a closed conformation is trapped by the C10-AMS inhibitor. Tight binding of C10-AMS blocks fatty acyl substrate entry, and therefore inhibits AasS action. Additionally, this intermediate analog C10-AMS appears to be a mixed-type AasS inhibitor. In summary, our results provide proof of principle that inhibiting salvage of eFA by AasS reverses the FAS II bypass. This facilitates the development of next-generation of anti-bacterial therapeutics, esp. the dual therapy consisting of C10-AMS scaffold derivatives combined with certain FAS II inhibitors. Author summary: An AasS-aided eFA recycling compromises the clinical efficacy of FAS II-directed antimicrobials. The C10-AMS compound is an effective inhibitor for AasS with the Ki value of ~0.6 μM. Efficient binding of AasS by C10-AMS blocks the entry of fatty acyl substrates of various length. The C10-AMS inhibitor mimics an acyl-AMP adenylate to trap AasS in a closed conformation rather than an open state. Collectively, inhibiting a bacterial eFA scavenger AasS enables the re-sensitization of FAS II-targeted antimicrobials. This provides proof of concept that a combination of C10-AMS scaffold derivatives with appropriate FAS II inhibitors constitutes a next-generation anti-virulence biotherapy. [ABSTRACT FROM AUTHOR]

Bone age assessment (BAA) is crucial in various fields, including legal proceedings, athletic competitions, and clinical medicine. However, the use of X-ray methods for age estimation without medical indication is subject to ethical debate, especially in forensic and athletic fields. The application of magnetic resonance imaging (MRI) with non-ionizing radiation can overcome this limitation in BAA. This study aimed to compare the application value of several MRI modalities of proximal humeral in BAA. A total of 468 patients with shoulder MRIs were retrospectively collected from a Chinese Han population aged 12–30 years (259 males and 209 females) for training and testing, including T1 weighted MRI (T1WI), T2 weighted MRI (T2WI), and Proton density weighted MRI (PDWI). Optimal regression models were established for age estimation, yielding mean absolute error (MAE) values below 2.0 years. The MAE values of T1WI were the lowest, with 1.700 years in males and 1.798 years in females. The area under the curve (AUC) and accuracy values of different MRI modalities of 16-year and 18-year thresholds were all around 0.9. For the 18-year threshold, T1WI outperformed T2WI and PDWI. In conclusion, the three MRI modalities of the proximal humerus can serve as reliable indicators for age assessment, while the T1WI performed better in age assessment and classification. [ABSTRACT FROM AUTHOR]

Aims This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant Pasteurella multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis. Methods and Results Danofloxacin at seven dosing regimens and 5 days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h area under the concentration–time curve (AUC) to minimum inhibitory concentration (MIC) ratios (AUC24h/MIC) of danofloxacin associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/mutant prevention concentration (MPC)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of three times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS , and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants. Conclusions The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg−1) may have a risk of treatment failure due to inducible fluoroquinolone resistance. [ABSTRACT FROM AUTHOR]