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In acidic proton exchange membrane water electrolysis (PEMWE), the anode oxygen evolution reaction (OER) catalysts rely heavily on the expensive and scarce iridium-based materials. Ruthenium dioxide (RuO 2 ) with lower price and higher OER activity, has been explored for the similar task, but has been restricted by the poor stability. Herein, we developed an anion modification strategy to improve the OER performance of RuO 2 in acidic media. The designed multicomponent catalyst based on sulfate anchored on RuO 2 /MoO 3 displays a low overpotential of 190 mV at 10 mA cm -2 and stably operates for 500 hours with a very low degradation rate of 20 μV h -1 in acidic electrolyte. When assembled in a PEMWE cell, this catalyst as an anode shows an excellent stability at 500 mA cm -2 for 150 h. Experimental and theoretical results revealed that MoO 3 could stabilize sulfate anion on RuO 2 surface to suppress its leaching during OER. Such MoO 3 -anchored sulfate not only reduces the formation energy of *OOH intermediate on RuO 2 , but also impedes both the surface Ru and lattice oxygen loss, thereby achieving the high OER activity and exceptional durability., (© 2024 Wiley-VCH GmbH.)

The dual inhibition of histone lysine-specific demethylase 1 (LSD1) and histone deacetylase (HDAC) has emerged as a promising strategy for cancer therapy. In this study, we report the discovery of novel 5-cyano-3-phenylindole-based LSD1/HDAC dual inhibitors, evaluated through both in vitro and in vivo assays. Among these inhibitors, compound 20c was identified as particularly potent, exhibiting high inhibitory activity against LSD1 (IC 50 = 39.0 nM) and HDAC1/2/3/6/8 (IC 50 = 1.4, 1.0, 1.3, 2.9, and 16.0 nM, respectively). Compound 20c effectively modulated the expression of biomarkers associated with LSD1 and HDAC inhibition and demonstrated superior antiproliferative activity compared to SAHA and 4SC-202 across multiple colorectal cancer cell lines. Following pharmacokinetic studies, 20c was further assessed in HCT-116 and HT-29 xenograft mouse models. It demonstrated significantly enhanced antitumor efficacy compared to SAHA, without causing observable toxicity. These findings highlight the potential of LSD1/HDAC dual inhibitors for the treatment of malignant cancers.

The high heterogeneity within and between breast cancer patients complicates treatment determination and prognosis assessment. Treatment decision-making is influenced by various factors, such as tumor subtype, histological grade, and genotype, necessitating personalized treatment strategies. Prognostic outcomes vary significantly depending on patient-specific conditions. As a critical branch of artificial intelligence, machine learning efficiently handles large datasets and automates decision-making processes. The introduction of machine learning offers new solutions for breast cancer treatment selection and prognosis assessment. In the field of cancer therapy, traditional methods for predicting treatment and survival outcomes often rely on single or few biomarkers, limiting their ability to capture the complexity of biological processes comprehensively. Machine learning analyzes patients' multi-omic data and the intricate patterns of variations during cancer initiation and progression to predict patients' survival and treatment outcomes. Consequently, it facilitates the selection of appropriate therapeutic interventions to implement early intervention and improve treatment efficacy for patients. Here, we first introduce common machine learning methods, and then elaborate on the application of machine learning in the field of survival prediction and prognosis from two aspects: evaluating survival and predicting treatment outcomes for breast cancer patients. The aim is to provide breast cancer patients with precise treatment strategies to improve therapeutic outcomes and quality of life.

Objectives: The aim of this study was to estimate the global burden, trends and health inequality of childhood nutritional deficiencies (CND) from 1990 to 2019., Study Design: This was an epidemiological study., Methods: Data were extracted from the 2019 Global Burden of Disease study. Estimates and 95% uncertainty intervals (UIs) for the rates and numbers were used to evaluate the global burden of CND. Temporal trends in the burden of CND were examined using Joinpoint analysis and average annual percentage changes. To assess health inequality, the slope index was used., Results: In 2019, 52 million new cases of CND and 105,000 deaths related to CND were recorded. Additionally, 435 million prevalence cases and 26 million disability-adjusted life years (DALYs) were recorded in the same year. From 1990 to 2019, the incidence rate of CND generally increased globally, except for the years 2010-2017; conversely, the prevalence, death and DALY rates exhibited decreasing trends over the study period. Half of the analysed regions and countries/territories demonstrated decreasing trends in the incidence, prevalence, death and DALY rates associated with CND. The incidence and prevalence of CND remained high in low-middle sociodemographic index (SDI) and low-SDI regions; however, they exhibited decreasing trends over the 30-year study period. The slope indexes showed that there were no significant changes in SDI-related inequality over 30 years., Conclusions: Despite decreasing trends in the prevalence, death and DALY rates associated with CND over the three decades, the degree of inequality related to SDI in the burden of nutritional deficiencies has not shown a significant decline. In summary, CND remain a major public health burden in middle-SDI and low-SDI countries., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Impulsive decision-making has been linked to impulse control disorders and substance use disorders. However, the neural mechanisms underlying impulsive choice are not fully understood. While previous PET imaging and autoradiography studies have shown involvement of dopamine and D2/3 receptors in impulsive behavior, the roles of distinct D1, D2, and D3 receptors in impulsive decision-making remain unclear. In this study, we used a food reward delay-discounting task (DDT) to identify low- and high-impulsive rats, in which low-impulsive rats exhibited preference for large delayed reward over small immediate rewards, while high-impulsive rats showed the opposite preference. We then examined D1, D2, and D3 receptor gene expression using RNAscope in situ hybridization assays. We found that high-impulsive male rats exhibited lower levels of D2 and D3, and particularly D3, receptor expression in the nucleus accumbens (NAc), with no significant changes in the insular, prelimbic, and infralimbic cortices. Based on these findings, we further explored the role of the D3 receptor in impulsive decision-making. Systemic administration of a selective D3 receptor agonist (FOB02-04) significantly reduced impulsive choices in high-impulsive rats but had no effects in low-impulsive rats. Conversely, a selective D3 receptor antagonist (VK4-116) produced increased both impulsive and omission choices in both groups of rats. These findings suggest that impulsive decision-making is associated with a reduction in D3 receptor expression in the NAc. Selective D3 receptor agonists, but not antagonists, may hold therapeutic potentials for mitigating impulsivity in high-impulsive subjects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

High relapse rate during abstinence is a defining characteristic of drug addiction. We previously found that opioid seeking progressively increases after voluntary abstinence induced by adverse consequences of oxycodone seeking (crossing an electric barrier). Functional MRI revealed that this effect is associated with changes in functional connectivity within medial orbitofrontal cortex (mOFC)- and dorsomedial striatum (DMS)-related circuits. Here, we used a pharmacological manipulation and fMRI to determine the causal role of mOFC and DMS in oxycodone seeking after electric barrier-induced abstinence. We trained rats to self-administer oxycodone (6 h/day, 14 days). Next, we induced voluntary abstinence by exposing them to an electric barrier for 2 weeks. We inactivated the mOFC and DMS with muscimol+baclofen (GABA a and GABA b receptor agonists) and then tested them for relapse to oxycodone seeking on abstinence days 1 or 15 without the electric barrier or oxycodone. Inactivation of DMS (p < 0.001) but not mOFC decreased oxycodone seeking before or after electric barrier-induced abstinence. Functional MRI data revealed that DMS inactivation decreased cerebral blood volume levels in DMS and several distant cortical and subcortical regions (corrected p < 0.05). Furthermore, functional connectivity of DMS with several frontal, sensorimotor, and auditory regions significantly increased after DMS inactivation (corrected p < 0.05). Finally, an exploratory analysis of an existing functional MRI dataset showed that DMS inactivation restored voluntary abstinence-induced longitudinal changes in DMS functional connectivity with these brain regions (p < 0.05). Results indicate a role of DMS and related brain circuits in oxycodone seeking after voluntary abstinence, suggesting potential targets for intervention., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Aims: This study aimed to analyse the evolution of the public image of nursing in the context of the constantly developing nursing profession., Design: The Rodger's evolving concept analysis was applied., Methods: PubMed, CINAHL, Web of Science, Scopus, and ProQuest databases were searched for articles published between 1 January 2001, and 30 April 2022, using the search terms; "NURS * AND image". The selected literature was screened using Rodgers' evolutionary method to explore the attributes, antecedents and consequences of the concept., Results: The defining attributes were identified as nursing (nursing as the collective object), public (public as the collective subject) and information (the medium of interaction between the collective subject and the collective object). Nursing elements were classified into intrinsic elements (professional spirit, professional knowledge and professional skills) and extrinsic (appearance, language and behaviour) elements. Public elements were further subcategorized into public categories (internal organizational public and external organizational public) and public perceptions (cognition, emotion and behavioural intention). The information elements are mainly classified as information generation, dissemination, identification, processing and judgement. The antecedents and consequences of the public perception of nursing were also identified., Conclusions: The public image of nursing is dynamic and has evolved over time. Its dynamism and malleability imply that the traditional public image of nursing can be improved through targeted interventions in nursing practice, management and education., Implications for the Profession: Identifying the antecedents and consequences associated with the public image of nursing will help the healthcare organizations adopt effective strategies to alleviate the shortage of the nursing workforce and promote the development of the nursing profession. No Patient or Public Contribution., (© 2024 The Author(s). Nursing Open published by John Wiley & Sons Ltd.)

Rationale and Objectives: To explore and validate the clinical value of ultrasound (US) viscosity imaging in differentiating breast lesions by combining with BI-RADS, and then comparing the diagnostic performances with BI-RADS alone., Materials and Methods: This multicenter, prospective study enrolled participants with breast lesions from June 2021 to November 2022. A development cohort (DC) and validation cohort (VC) were established. Using histological results as reference standard, the viscosity-related parameter with the highest area under the receiver operating curve (AUC) was selected as the optimal one. Then the original BI-RADS would upgrade or not based on the value of this parameter. Finally, the results were validated in the VC and total cohorts. In the DC, VC and total cohorts, all breast lesions were divided into the large lesion, small lesion and overall groups respectively., Results: A total of 639 participants (mean age, 46 years ± 14) with 639 breast lesions (372 benign and 267 malignant lesions) were finally enrolled in this study including 392 participants in the DC and 247 in the VC. In the DC, the optimal viscosity-related parameter in differentiating breast lesions was calculated to be A'-S2-Vmax, with the AUC of 0.88 (95% CI: 0.84, 0.91). Using > 9.97 Pa.s as the cutoff value, the BI-RADS was then modified. The AUC of modified BI-RADS significantly increased from 0.85 (95% CI: 0.81, 0.88) to 0.91 (95% CI: 0.87, 0.93), 0.85 (95% CI: 0.80, 0.89) to 0.90 (95% CI: 0.85, 0.93) and 0.85 (95% CI: 0.82, 0.87) to 0.90 (95% CI: 0.88, 0.92) in the DC, VC and total cohorts respectively (P < .05 for all)., Conclusion: The quantitative viscous parameters evaluated by US viscosity imaging contribute to breast cancer diagnosis when combined with BI-RADS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Crabapple is a valuable tree species in gardens due to its captivating array of flower and leaf colors, rendering it a favored choice in landscaping. The economic and ornamental values of Malus crabapple are closely associated with the biosynthesis of anthocyanin, a pigment responsible for its vibrant hues. The intricate regulation of anthocyanin biosynthesis involves the concerted activity of various genes. However, the specific mechanism governing this process in crabapple warrants in-depth exploration. In this study, we explored the inhibitory role of MsMYB62-like in anthocyanin biosynthesis. We identified MsDFR and MsANS as two downstream target genes of MsMYB62-like. These genes encode enzymes integral to the anthocyanin biosynthetic pathway. The findings demonstrate that MsMYB62-like directly binds to the promoters of MsDFR and MsANS , resulting in the downregulation of their expression levels. Additionally, our observations indicate that the plant hormone cytokinins exert a suppressive effect on the expression levels of MsMYB62-like , while concurrently upregulating MsDFR and MsANS . This study reveals that the MsMYB62-like- MsDFR / MsANS module plays an important role in governing anthocyanin levels in Malus crabapple. Notably, the regulatory interplay is modulated by the plant hormone cytokinins.

Background: There are few studies on death education models for nursing students in China. It is of great significance to construct a model of nursing students' death education combined with clinical practice. This study aims to evaluate the effect of death education on nursing students based on the Peace of Mind Tea House., Methods: The randomized controlled trial commenced from February 7 to March 18, 2021,featuring a two-month intercession at a hospital situated in Xiamen, China. The research subjects were chosen using a convenient sampling approach with nursing students from the hospital's internship program. Ninety-two participants were enrolled, with 46 in each group. Thirteen participants were lost to follow-up, corresponding to 14% of the total study population. The samples were then allocated randomly into either the intervention group or the control group. In addition to their hospital internship, the intervention group participated in six death education courses that focused on cognitive, emotional, and motor skills as well as the "Peace of Mind Tea House" program. Control participants will undergo regular internships. Before and two weeks after the course, both groups were evaluated for death anxiety, attitude towards death, and the meaning of life to assess the intervention's effectiveness., Results: In the fear of death item of the Death Attitude Scale and the meaning of life section, the post-test score minus the pre-test score of the intervention group were 2.50 ± 3.90 (p = 0.011), and 8.90 ± 11.07 (p = 0.035), respectively. During the communication and sharing session of the reassurance card activity, 41 participants (95.3%) found the activity meaningful., Conclusion: Our data analysis demonstrates that nursing students have accepted and acknowledged the Peace of Mind Tea House-based education on death, which positively impacted their attitudes towards deathand the meaning of life. The content of death education should be integrated with traditional culture, and a new model of death education should be constructed with the Heart to Heart cards as its core. This research presents proof of the efficacy of implementing appropriate death education for nursing students, and provides a successful intervention plan to alleviate their future death anxiety and develop a positive outlook on death., Trial Registration: This study was approved by the Ethical Committee of Xiamen University School of Medicine (No. XDYX202304K21)(Date:18/01/2021). Written consent to participate was obtained from all the students., (© 2024. The Author(s).)

Fruit peel color is a major factor that influences fruit quality and customers' demand. However, the molecular mechanisms underlying the green fruit peel color trait of Cucurbita pepo L. remain unknown. Two parental lines, RP16 and RP38, were used to study the fruit peel color trait in C. pepo . The parental line RP16 shows white peel color, whereas RP38 exhibits green peel color. 384 F 2 populations were used to identify the inheritance pattern associated with green fruit and white fruit peel in Cucurbita pepo L. 293 F 2 individuals were white, and 91 F 2 individuals were green, resulting in a ratio of 3:1. Hence, white peel is dominant over the green fruit peel trait, and a single recessive green peel gene ( Cpgp ) controls the green fruit peel. The fruit chlorophyll (Chll) content decreases as fruit matures in the RP16 line. In contrast, Chll increases during the fruit growing periods on fruit peels of the RP38 line. The BSA-sequence analysis revealed the Cpgp locus on Chr5, within a 2.3 Mb region. Subsequent fine-mapping analysis, using 699 F 2 plants, narrowed down this region to 23.90 kb on the same chromosome. Within this region, two annotated genes, namely Cp4.1LG05g02070 and Cp4.1LG05g02060 , are present. These genes are predicted to encode a two-component Arabidopsis Pseudo-Response Regulator 2-like protein (APRR2), which may be involved in green pigmentation processes in plants. Consequently, sequence alignment and gene expression analyses at various fruit development stages supported that Cp4.1LG05g02070 may be the primary candidate gene responsible for regulating the green fruit peel color trait in Cucurbita pepo L. This study may provide a basis for further study on the basic mechanisms that control the fruit peel colors in Cucurbita spp ., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01492-7., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Synthetic magnetic resonance imaging (SyMRI) is a fast, standardized, and robust novel quantitative technique that has the potential to circumvent the subjectivity of interpretation in prostate multiparametric magnetic resonance imaging (mpMRI) and the limitations of existing MRI quantification techniques. Our study aimed to evaluate the potential utility of SyMRI in the diagnosis and aggressiveness assessment of prostate cancer (PCA)., Methods: We retrospectively analyzed 309 patients with suspected PCA who had undergone mpMRI and SyMRI, and pathologic results were obtained by biopsy or PCA radical prostatectomy (RP). Pathological types were classified as PCA, benign prostatic hyperplasia (BPH), or peripheral zone (PZ) inflammation. According to the Gleason Score (GS), PCA was divided into groups of intermediate-to-high risk (GS ≥4+3) and low-risk (GS ≤3+4). Patients with biopsy-confirmed low-risk PCA were further divided into upgraded and nonupgraded groups based on the GS changes of the RP results. The values of the apparent diffusion coefficient (ADC), T1, T2 and proton density (PD) of these lesions were measured on ADC and SyMRI parameter maps by two physicians; these values were compared between PCA and BPH or inflammation, between the intermediate-to-high-risk and low-risk PCA groups, and between the upgraded and nonupgraded PCA groups. The risk factors affecting GS grades were identified via univariate analysis. The effects of confounding factors were excluded through multivariate logistic regression analysis, and independent predictive factors were calculated. Subsequently, the ADC+Sy(T2+PD) combined models for predicting PCA risk grade or GS upgrade were constructed through data processing analysis. The diagnostic performance of each parameter and the ADC+Sy(T2+PD) model was analyzed. The calibration curve was calculated by the bootstrapping internal validation method (200 bootstrap resamples)., Results: The T1, T2, and PD values of PCA were significantly lower than those of BPH or inflammation (P≤0.001) in both the PZ or transitional zone. Among the 178 patients with PCA, intermediate-to-high-risk PCA group had significantly higher T1, T2, and PD values but lower ADC values compared with the low-risk group (P<0.05), and the diagnostic efficacy of each single parameter was similar (P>0.05). The ADC+Sy(T2+PD) model showed the best performance, with an area under the curve (AUC) 0.110 [AUC =0.818; 95% confidence interval (CI): 0.754-0.872] higher than that of ADC alone (AUC =0.708; 95% CI: 0.635-0.774) (P=0.003). Among the 68 patients initially classified as PCA in the low-risk group by biopsy, PCA in the postoperative upgraded GS group had significantly higher T1, T2, and PD values but lower ADC values than did those in the nonupgraded group (P<0.01). In addition, the ADC+Sy(T2+PD) model better predicted the upgrade of GS, with a significant increase in AUC of 0.204 (AUC =0.947; 95% CI: 0.864-0.987) compared with ADC alone (AUC =0.743; 95% CI: 0.622-0.841) (P<0.001)., Conclusions: Quantitative parameters (T1, T2, and PD) derived from SyMRI can help differentiate PCA from non-PCA. Combining SyMRI parameters with ADC significantly improved the ability to differentiate between intermediate-to-high risk PCA from low-risk PCA and could predict the upgrade of low-risk PCA as confirmed by biopsy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-291/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objective: To explore the clinical efficacy of double beam double tunnel enhanced reconstruction technique in the treatment of knee anterior cruciate ligament(ACL) training injuries., Methods: Twenty-nine cases of ACL injury of knee joint from January 2021 to December 2021 were retrospectively analyzed. All the cases were underwent ligament reconstruction surgery. Cases were grouped by surgical technique:there were 14 patients in conventional reconstruction group, including 13 males and 1 female, aged from 22 to 31 years old with an average of (27.07±7.28) years old, autogenous hamstring tendon was used for ligament reconstruction. There were 15 patients in the enhanced reconstruction group, including 13 males and 2 females, aged from 25 to 34 years old with an average of (29.06±4.23) years old, double tunnel ligament reconstruction, the autogenous hamstring muscle was used as the anteromedial bundle, and the posterolateral bundle was replaced by a high-strength line. The difference between knee tibial anterior distance, Lysholm score, International Knee Literature Committee (IKDC) subjective score, Tegner motor level score and visual analog scale (VAS) at 6th and 12th months after the surgery, limb symmetry index (LSI) were recorded at the last follow-up and surgery-related adverse effects during follow-up., Results: All patients were followed up, ranged from 13 to 15 months with an average of (13.7±0.8) months. There were no serious adverse reactions related to surgery during the period. There was no statistical difference between the preoperative general data and the observation index of the two groups ( P >0.05). The difference in tibial anterior distance at 6 and 12 months in the enhanced reconstruction group (1.45±0.62) mm and (1.74±0.78) mm which were lower those that in the conventional reconstruction group (2.42±0.60) mm and (2.51±0.63) mm( P <0.05). There was no significant difference in postoperative Lysholm score, Tegner motor level score, IKDC score, VAS, and limb symmetry index at the last follow-up( P >0.05)., Conclusion: The enhanced reconstruction technique can more effectively maintain the stability of the knee joint and has no significant effect on the postoperative knee joint function compared with the traditional ligament reconstruction technique. The short-term curative effect is satisfactory, and it is suitable for the group with high sports demand.

Objective: To explore the effects of live music to decrease psychological distress in adolescent and young adult (AYA) patients undergoing hematopoietic stem cell transplantation (HSCT)., Method: A quasi-experimental study was conducted. Sixty patients undergoing HSCT were divided into two groups, receiving either 4 week of live music ( n  = 31) or standard care ( n  = 29). Psychological distress, anxiety, the severity of symptom clusters and symptom interference were measured., Results: When compared with the immediately and 1 month after intervention, patients in LM intervention group had significantly lower psychological distress and anxiety level than wait-list group. AYA undergoing HSCT reported significantly milder general symptom cluster and neurological symptom cluster at T3 than at baseline., Conclusions: Live music intervention showed a positive effect on relieving psychological distress and anxiety in AYA patients undergoing HSCT. However, further researches are warranted to explore the effects of live music intervention on symptom cluster.

Introduction: Nutritional literacy (NL) has a critical influence on food choices. The objective of the present study was to examine the association of NL with nutrition label use., Methods: A cross-sectional study was conducted in Bengbu, China. In total, 955 adults were interviewed using a questionnaire designed for the present study to collect information on demographics, lifestyle, nutrition label use, and NL. Binary logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for nutrition label use and its predictive variables., Results: In total, 40.4% of the participants reported looking at nutrition label when purchasing prepackaged foods. NL was significantly positively associated with nutrition label use and specifically with checking nutrition facts table, purported nutrition benefits and purported health benefits. In terms of specific facets of NL, nutrition knowledge, applying skills, and critical skills were associated with nutrition label use. After stratification by monthly income and education, the association between NL and nutrition label use was discovered only in individuals with low monthly income. Additionally, nutrition knowledge was associated with nutrition label use only in adults with high education level, whereas applying skills were associated with nutrition label use only in those with low education level., Conclusion: The use of nutrition label remains low among Chinese community residents, especially the purported nutritional benefits and purported health benefits. NL is positively associated with nutrition label use, especially with respect to functional and critical NL, with differences based on socioeconomic status. The findings highlight the need for NL interventions targeting individuals with different levels of education and income to encourage use of nutrition label in China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Cui, Du, Liu, Duan, Qi, Liu and Zhang.)

Decoy receptor 3 (DcR3), a novel soluble protein belonging to the tumor necrosis factor receptor (TNFR) family, has been previously associated with tumorigenesis in various cancers. However, in our study, we unexpectedly found that DcR3 may promote patient survival time in colorectal cancer (CRC). Through an analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we discovered that high levels of DcR3 are associated with improved overall survival (OS) and disease-free survival (DFS) in CRC patients. Further investigation revealed that DcR3 is correlated with favorable clinical features in Metastasis 0 (M0) and stage I/II CRC patients, suggesting it may act as a suppressive factor in CRC. Gene Set Enrichment Analysis (GSEA) demonstrated that the high DcR3 group is enriched in the IL-17 signaling pathway and other immune-related pathways, and Single Sample Gene Set Enrichment Analysis (ssGSEA) revealed a higher abundance of Tumor Infiltrating Lymphocytes (TIL) in the DcR3 high group. To better understand the function of DcR3, we constructed a DcR3-associated riskscore (DARS) model using machine learning, comprising three genes (DPP7, KDM3A, and TMEM86B). The DARS model indicated that high riskscore patients have an unfavorable prognosis, and it is associated with advanced stages (III/IV), T3/4 tumors, and N1/2 lymph node involvement. Additionally, high riskscore group exhibited more frequent gene mutations, such as TTN, MUC16, and SYNE1, with SYNE1 mutation being related to poor prognosis. Intriguingly, DcR3 showed higher expression in the low riskscore group. These results suggest that DcR3 could serve as a potential prognostic biomarker in CRC and may play a crucial role in favorably modulating the immune response in this malignancy., (© 2024. The Author(s).)

Agricultural by-products of sesame are promising bioresources in food processing. This study extracted lignin from the by-products of sesame oil production, namely, the capsules and straw of black and white sesame. Using acid, alkali, and ethanol methods, 12 distinct lignins were obtained to prepare biochar, aiming to investigate both the structural characteristics of lignin-based biochar (LBB) and its ability to remove benzo[a]pyrene (BaP) from sesame oil. The results showed that white sesame straw was the most suitable raw material for preparing biochar. In terms of the preparation method, acid-extracted lignin biochar was more effective in removing BaP than alkaline or ethanol methods. Notably, WS-1LB (white sesame straw acid-extracted lignin biochar) exhibited the highest BaP adsorption efficiency (91.44 %) and the maximum specific surface area (1065.8187 m 2 /g), characterized by porous structures. The pseudo 2 nd and Freundlich models were found to be the best fit for the adsorption kinetics and isotherms of BaP on LBB, respectively, suggesting that a multilayer adsorption process was dominant. The high adsorption of LBB mainly resulted from pore filling. This study provides an economical and highly efficient biochar adsorbent for the removal of BaP in oil., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Apple rust is a serious fungal disease affecting Malus plants worldwide. Infection with the rust pathogen Gymnosporangium yamadae induces the accumulation of anthocyanins in Malus to resist rust disease. However, the mechanism of anthocyanin biosynthesis regulation in Malus against apple rust is still unclear. Here, we show that MpERF105 and MpNAC72 are key regulators of anthocyanin biosynthesis via the ethylene-dependent pathway in M. 'Profusion' leaves under rust disease stress. Exogenous ethephon treatment promoted high expression of MpERF105 and MpNAC72 and anthocyanin accumulation in G. yamadae-infected M. 'Profusion' leaves. Overexpression of MpERF105 increased the total anthocyanin content of Malus plant material and acted by positively regulating its target gene, MpMYB10b. MpNAC72 physically interacted with MpERF105 in vitro and in planta, and the two form a protein complex. Coexpression of the two leads to higher transcript levels of MpMYB10b and higher anthocyanin accumulation. In addition, overexpression of MpERF105 or MpNAC72 enhanced the resistance of M. 'Profusion' leaves to apple rust. In conclusion, our results elucidate the mechanism by which MpERF105 and MpNAC72 are induced by ethylene in G. yamadae-infected M. 'Profusion' leaves and promote anthocyanin accumulation by mediating the positive regulation of MpMYB10b expression., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Objectives: To explore the association between drinking water sources and cognitive functioning among older adults residing in rural China., Methods: Data were extracted from the 2008-2018 Chinese Longitudinal Healthy Longevity Survey. Drinking water sources were categorized according to whether purification measures were employed. The Chinese version of the Mini-Mental State Examination was used for cognitive functioning assessment, and the score of <24 was considered as having cognitive dysfunction. Cox regression analyses were conducted to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the effects of various drinking water sources, changes in such sources, and its interaction with exercise on cognition dysfunction., Results: We included 2304 respondents aged 79.67 ± 10.02 years; of them, 1084 (44.49%) were men. Our adjusted model revealed that respondents consistently drinking tap water were 21% less likely to experience cognitive dysfunction compared with those drinking untreated water (HR = 0.79, 95% CI: 0.70-0.90). Respondents transitioning from natural to tap water showed were 33% less likely to experience cognitive dysfunction (HR = 0.67, 95% CI: 0.58-0.78). Moreover, the HR (95% CI) for the interaction between drinking tap water and exercising was 0.86 (0.75-1.00) when compared with that between drinking untreated water and not exercising. All results adjusted for age, occupation, exercise, and body mass index., Conclusions: Prolonged tap water consumption and switching from untreated water to tap water were associated with a decreased risk of cognitive dysfunction in older individuals. Additionally, exercising and drinking tap water was synergistically associated with the low incidence of cognitive dysfunction. These findings demonstrate the importance of prioritizing drinking water health in rural areas, indicating that purified tap water can enhance cognitive function among older adults., (© 2024 John Wiley & Sons Ltd.)

The Golgi apparatus plays a crucial role in mediating the modification, transport, and sorting of intracellular proteins and lipids. The morphological changes occurring in the Golgi apparatus are exceptionally important for maintaining its function. When exposed to external pressure or environmental stimulation, the Golgi apparatus undergoes adaptive changes in both structure and function, which are known as Golgi stress. Although certain signal pathway responses or post-translational modifications have been observed following Golgi stress, further research is needed to comprehensively summarize and understand the related mechanisms. Currently, there is evidence linking Golgi stress to neurodegenerative diseases; however, the role of Golgi stress in the progression of neurodegenerative diseases such as Alzheimer's disease remains largely unexplored. This review focuses on the structural and functional alterations of the Golgi apparatus during stress, elucidating potential mechanisms underlying the involvement of Golgi stress in regulating immunity, autophagy, and metabolic processes. Additionally, it highlights the pivotal role of Golgi stress as an early signaling event implicated in the pathogenesis and progression of neurodegenerative diseases. Furthermore, this study summarizes prospective targets that can be therapeutically exploited to mitigate neurodegenerative diseases by targeting Golgi stress. These findings provide a theoretical foundation for identifying novel breakthroughs in preventing and treating neurodegenerative diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Eggs are a vital dietary component for humans, and it is beneficial to increase egg production to support poultry farming. Initially, the egg production rate rises rapidly with young hens until it reaches its peak, and then it declines gradually. By extending the duration of peak egg production, the hens' performance can be enhanced significantly. Previous studies found dynamic changes in gut microbiota during egg-laying, and several species of microbiota isolated from the chicken gut improved egg-laying performance. However, the interaction between microbes and host gene expression is still unclear. This study provides a more comprehensive understanding of chicken egg-laying by examining dynamic alterations in the microbiota of the entire intestinal tract (i.e., duodenum, jejunum, and ileum) and gene expression. The microbial community in the intestine underwent significant changes during different egg-laying periods (i.e., pre-, peak-, and late-laying periods). Metagenomic functional analysis showed that the relative abundance of biosynthesis of amino acids, secondary metabolites, and cofactors decreased significantly in the duodenum, jejunum, and ileum of aging hens. The relative levels of aldosterone, GnRH, insulin, growth hormone, and other hormone-related pathways increased dramatically in the intestinal microbiota during egg-laying, but only in the microbiota located in the duodenum and ileum. Transcriptome analysis suggested that genes associated with various transport processes were upregulated consistently in the small intestine during egg-laying; genes involved in the development of intestinal structure were down-regulated; and genes involved in response to DNA damage and stress were consistent with changes in laying rate. The abundance of Lactobacillus was related to the expression of ANGPTRL1 , ANGPTRL2 , ANGPT1L , and NOXO1 in the duodenum; Muricomes was correlated significantly with NFKBIZ , LYG2 , and IRG1L expression in the jejunum; and Campylobacter was correlated positively with the expression of KMT2A and USF3 in the ileum. These results indicated that the intestinal microbiota and host gene expression may influence egg production jointly.

Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking., Objective: To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke., Design, Setting, and Participants: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome., Interventions: Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio., Main Outcomes and Measures: The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points., Results: Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups., Conclusions and Relevance: Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke., Trial Registration: ClinicalTrials.gov Identifier: NCT02869009.

Recurrent spontaneous abortion (RSA) is a pregnancy-related condition with complex etiology. Trophoblast dysfunction and abnormal macrophage polarization and metabolism are associated with RSA; however, the underlying mechanisms remain unknown. Jupiter microtubule-associated homolog 2 (JPT2) is essential for calcium mobilization; however, its role in RSA remains unclear. In this study, it is found that the expression levels of JPT2, a nicotinic acid adenine dinucleotide phosphate-binding protein, are decreased in the villous tissues of patients with RSA and placental tissues of miscarried mice. Mechanistically, it is unexpectedly found that abnormal JPT2 expression regulates trophoblast function and thus involvement in RSA via c-Jun N-terminal kinase (JNK) signaling, but not via calcium mobilization. Specifically, on the one hand, JPT2 deficiency inhibits trophoblast adhesion, migration, and invasion by inhibiting the JNK/atypical chemokine receptor 3 axis. On the other hand, trophoblast JPT2 deficiency contributes to M1 macrophage polarization by promoting the accumulation of citrate and reactive oxygen species via inhibition of the JNK/interleukin-6 axis. Self-complementary adeno-associated virus 9-JPT2 treatment alleviates embryonic resorption in abortion-prone mice. In summary, this study reveals that JPT2 mediates the remodeling of the immune microenvironment at the maternal-fetal interface, suggesting its potential as a therapeutic target for RSA., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Adenomyosis is a benign uterine disorder that is associated with female infertility, a reduced clinical pregnancy rate and a high risk of miscarriage. Solute carrier family 38 member a2 (SLC38A2) is a glutamine (Gln) transporter that serves roles in various medical conditions. The present study aimed to reveal the role of SLC38A2 in adenomyosis. The mRNA expression levels of SLC38A2 in eutopic endometrial (EU) and ectopic endometrial (EC) tissues from adenomyotic patients were examined by reverse transcription-quantitative PCR. EU and EC cell proliferation and invasion were analyzed by Cell Counting Kit-8 and Transwell assays. Changes in the oxygen consumption rate (OCR) were determined to indicate the mitochondrial respiratory function and observed using a Seahorse analyzer. SLC38A2 expression in EC tissues was upregulated compared with that in normal endometrial tissues. SLC38A2 knockdown repressed EC cell proliferation and invasion. In addition, the Gln content and OCR were decreased in EC cells transfected with SLC38A2-knockdown lentivirus, whereas SLC38A2 overexpression had the opposite effect in EU cells. Furthermore, the increased proliferation and invasion rates and Gln level induced by SLC38A2 overexpression in EU cells were alleviated by CB-839, a glutaminase inhibitor. SLC38A2 overexpression promoted Gln metabolism and oxygen consumption rate, resulting in an increase in cell proliferation and invasion in the adenomyosis context. The present study indicated that reduction of SLC38A2 expression could be a novel target for adenomyosis therapy, and SLC38A2 may be a valuable clinical diagnostic molecule for adenomyosis., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Wu et al.)

Aims: FoxO1 is an important target in the treatment of Alzheimer's disease (AD). However, FoxO1-specific agonists and their effects on AD have not yet been reported. This study aimed to identify small molecules that upregulate the activity of FoxO1 to attenuate the symptoms of AD., Methods: FoxO1 agonists were identified by in silico screening and molecular dynamics simulation. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to assess protein and gene expression levels of P21, BIM, and PPARγ downstream of FoxO1 in SH-SY5Y cells, respectively. Western blotting and enzyme-linked immunoassays were performed to explore the effect of FoxO1 agonists on APP metabolism., Results: N-(3-methylisothiazol-5-yl)-2-(2-oxobenzo[d]oxazol-3(2H)-yl) acetamide (compound D) had the highest affinity for FoxO1. Compound D activated FoxO1 and regulated the expression of its downstream target genes, P21, BIM, and PPARγ. In SH-SY5Y cells treated with compound D, BACE1 expression levels were downregulated, and the levels of Aβ 1-40 and Aβ 1-42 were also reduced., Conclusions: We present a novel small-molecule FoxO1 agonist with good anti-AD effects. This study highlights a promising strategy for new drug discovery for AD., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Objectives: Smoking susceptibility is defined as a lack of firm decision against smoking, usually starts in the preparation and/or initiation stages of smoking behavior, and is a strong predictor of smoking experimentation during adolescence. However, the recent global prevalence and trends in smoking susceptibility among adolescents are not well documented. This study assessed global smoking susceptibility and secular trends among nonsmoking adolescents., Methods: Smoking susceptibility was analyzed using the most recent data from the Global Youth Tobacco Survey from 129 countries, where the data from each country were drawn from at least 1 survey conducted at any time between 1999 and 2020. Moreover, data from 82 countries were used to assess the average annual rate of change (AARC) in smoking susceptibility over time., Results: Smoking susceptibility among nonsmoking adolescents was 19.6%. A U-shaped relationship was observed between susceptibility and a country's economic level. Most countries showed no changes in susceptibility over time. Countries with a significant upward trend in susceptibility were primarily high-income and upper middle-income countries in the American region. At the World Health Organization regional level, susceptibility significantly decreased in the European region (AARC: -3.5%; 95% confidence interval, -5.8 to -0.8); however, it significantly increased in the American region (AARC: 2.2%; 95% confidence interval, 1.3-3.1)., Conclusions: Smoking susceptibility remains a serious public health challenge among adolescents worldwide. More public health policies are needed to reduce susceptibility and to control its upward trend in the American region and high-income countries., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Cross-sectional evidence suggests that persistently short or long sleep duration is associated with sensory impairment. Thus, this study was conducted to investigate the associations between sleep duration and altered sleep duration with sensory impairment in Chinese older adults., Methods: Longitudinal data (2008-2014) obtained through the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Sleep duration was classified as normal (7-8 h), short (<7 h), or long (≥9 h). Sensory impairment was assessed using individuals' self-reported data on visual and hearing functions. Cox regression was performed to evaluate the effects of sleep duration and altered sleep duration on sensory impairment, including visual impairment (VI) and hearing impairment (HI)., Results: This study included 3,578 older adults (mean age: 78.12 ± 9.59 years). Among them, 2,690 (75.2%) were aged 65-84 years and 1798 (50.3%) were women. The risks of VI (hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.02-1.29), HI (HR: 1.14; 95% CI: 1.00-1.30), and dual sensory impairment (both VI and HI; HR: 1.26; 95% CI: 1.03-1.55) were high in older adults with long sleep duration. In addition, the risks of VI, HI, and dual sensory impairment were high in individuals whose sleep duration changed from normal to short or long (HR: 1.20 [95% CI: 1.02-1.42], 1.26 [95% CI: 1.03-1.53], and 1.54 [95% CI: 1.11-2.12], respectively) and those with persistently short or long sleep duration (HR: 1.25 [95% CI: 1.07-1.46], 1.34 [95% CI: 1.11-1.61], and 1.67 [95% CI: 1.22-2.27], respectively)., Conclusion: A prospective association was identified between altered sleep duration and sensory impairment in Chinese older adults. Our findings highlight the importance of optimal sleep duration and healthy sleep habits in preventing sensory impairment in older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Du, Duan, Cui, Qi, Liu and Liu.)

Background: Youth mental health problems are a public health priority. Multiple healthy lifestyle behaviors may cluster into healthy lifestyle behavioral patterns (HLBPs) that increase mental health risks in adolescents and older adults, but little is known regarding young adults. This study aimed to explore the associations between cluster HLBPs and mental health problems in young adults., Methods: We selected 161,744 young adults aged 20-39 as participants from the database of a Chinese general hospital health management center for the years 2015-2020. The latent class analysis was used to identify HLBPs., Results: A total of 15.0 % of young adults have at least one mental health problem. Five clusters of HLBPs were identified, characterized as low-risk class (1.6 %), moderate-risk class 1 (12.0 %), moderate-risk class 2 (2.1 %), moderate-risk class 3 (56.8 %), and high-risk class (27.4 %). The odds ratios (ORs) for young adults with two mental health problems increased with the risk grade of HLBPs, while the ORs for young adults with one or three mental health problems ranged from high to low according to the risk grade of HLBPs: high-risk class, moderate-risk class 2, moderate-risk class 3, moderate-risk class 1., Limitations: Cross-sectional design and no causal conclusions could be drawn., Conclusion: Young adults demonstrated a cluster phenomenon of healthy lifestyle behaviors and significant associations between HLBPs and mental health problems. Young adults with a higher risk grade for HLBPs were more likely to have mental health problems. Different HLBPs should be taken into account when implementing mental health interventions., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The study characterized the aroma-active compounds produced by sesame hulls at three roasting temperatures and analyzed the similarities and differences in the aroma profile of sesame hulls with whole seeds and kernels after roasting. Roasting hulls produced mainly furans, aldehydes, and ketones volatiles. 140 Compounds were identified as aroma-active compounds, including 36 key aroma compounds (odor activity value, OAV ≥ 1). Among them, furanone (caramel-like, OAV = 80), 3-methylbutanal (fruity, OAV = 124), and 2-methoxy-4-vinylphenol (burnt, smoky, OAV = 160) gave hulls (180 °C) sweet, burnt, and smoky aroma. Due to the contribution of vanillin (fatty, sweet milk, OAV = 45), 2-hydroxy-3-butanone (caramel-like, roast, OAV = 46), and 2-methoxy-4-vinylphenol (OAV = 78), hulls (200 °C) shown strong sweet and roast note. These results identified compounds that contributed significantly to the aroma of sesame hulls and elucidated the contribution of sesame hulls to the flavor of roasted whole seeds and sesame oil., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Indoor air pollution causes severe psychological stress and promotes depression. A better understanding of the impact of solid fuel consumption and socioeconomic indicators on mental health is critical to promote successful aging. In this study, we analyzed the relationship of depression with socioeconomic status (SES) and solid fuel use, and illustrated the mediating role of solid fuel use in the relationship between SES and depression., Methods: 9250 participants from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey were included in this study. A logistic regression analysis was used to calculate odds ratio (OR) and 95% confidence interval (CI) of depression for different types of fuel consumption. The stepwise approach and the Sobel test were used to test the mediation effect., Results: Older people who reported the consumption of solid fuels showed higher odds of having depressive symptoms (OR = 1.16, 95% CI:1.03, 1.31). In model with depression as the outcome variable, the ORs of low education level and low annual household income level were 1.30 (95% CI: 1.15, 1.47) and 1.43 (95% CI: 1.28, 1.59) respectively. Solid fuel consumption accounted for 38.40% of the effect of a low education level and 54.73% of the effect of low income on depression., Conclusions: Solid fuel use and SES are associated with depression, and solid fuel use may act as a potential mediator connecting socioeconomic indicators and depression., (© 2024. The Author(s).)

To date, the benefit of intravenous thrombolysis is confined to within 4.5 h of onset for acute ischemic stroke (AIS) without advanced neuroimaging selection. The current trial aimed to investigate the safety and efficacy of intravenous tenecteplase (TNK) plus Dl-3-n-Butylphthalide (NBP) in AIS within 4.5 to 6 h of onset. In this randomized, multicenter trial, eligible AIS patients were randomly assigned to receive intravenous TNK (0.25 mg/kg) plus NBP or NBP within 4.5 to 6 h of onset. The primary endpoint was symptomatic intracranial hemorrhage (sICH). Secondary endpoints included excellent functional outcome defined as a modified Rankin Scale score of 0 to 1 at 90 days. 100 patients diagnosed by non-contrast CT (NCCT) were enrolled, including 50 in TNK group and 50 in control group. sICH occurred in 2.0% (1/50) in TNK group and 0.0% (0/49) in control group with no difference (unadjusted P = 0.998). The proportion of excellent functional outcome was 77.6% (38/49) in TNK group and 69.4% (34/49) in control group with non-significance (absolute difference 8.2%, P = 0.36). A significant decrease in NIHSS score at 24 h (P = 0.004) and more early neurological improvement (20.4% vs 4.1%; P = 0.026) was observed in TNK vs control group, but there was no difference in other secondary outcomes. This phase 2 study suggests that intravenous TNK with adjuvant NBP seems safe, feasible and may improve early neurological function in AIS patients within 4.5 to 6 h of symptom onset selected using NCCT.Clinical Trials Registration: This trial was registered with ClinicalTrials.gov (NCT05189509)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Egg-laying is an important trait in chickens, and it is affected by many factors, such as hormones regulated by the hypothalamic-pituitary axis and precursors synthesized by the liver. Recent studies showed that gut microbiota was associated with egg-laying, however, its underlying mechanism remains unclear. We comprehensively analyzed the host transcriptome, gut microbiota, and metabolome in broiler breeder hens during the pre-laying, peak-laying, and late-laying periods. The transcriptome analysis of the tissues related to the hypothalamic-pituitary-liver (HPL) axis revealed dynamic gene expression during egg-laying periods. Differentially expressed genes (DEGs) (i.e., PENK, NPY, AVP, PRL, RLN3, and FST) from the hypothalamus and pituitary gland were involved in female gonadal development, hormone secretion, response to endogenous stimulus, liver development, and amide metabolism. In liver, DEGs (i.e., FABP3, VTG1, LPL, APOA5, APOV1, and RBP5) were enriched in efferocytosis, sphingolipid metabolism, amide, and peptide biosynthesis. Alpha and beta diversity changed significantly in cecum microbiota during different laying periods. The abundance of Firmicutes was decreased and the abundance of Bacteroidota was increased during the peak-laying period. Functional analysis showed that the biosynthesis of secondary metabolites, amino acids, purine, and steroid hormones was altered during laying. The metabolome analysis from cecal contents showed that amino acid metabolism and steroid hormone biosynthesis changed during laying. Integrated analysis of the cecal microbiota and metabolites showed the genus Megasphaera was involved in amino acid metabolism, which included 3-phenyllatic acid, quinic acid, caffeic acid, and folic acid, and the genus Hungatella participated in steroid hormone biosynthesis through its strong correlation with estradiol. These results explored the dynamic changes in tissues related to the HPL axis and cecal microbiota and provided new insights into the interaction between the host and microbiota during egg-laying in chickens., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Silver nanoparticles (AgNPs) are widely used in daily life and industry because of their excellent antibacterial properties. AgNPs can exist in wastewater in various forms, such as Ag + , Ag 2 SO 4 , Ag 2 CO 3 , Ag 2 S, Ag 2 O, and AgCl. To assess the potential environmental risk of AgNPs and various forms of Ag, their toxic effects were investigated using the common denitrifier species Pseudomonas stutzeri (P. stutzeri). The inhibitory effect of AgNPs and various forms of Ag on P. stutzeri growth and its denitrification performance occurred in a concentration-dependent manner. The denitrification efficiency of P. stutzeri decreased from 95%∼97% to 89∼95%, 74∼95%, and 56∼85% under low, medium, and high exposure doses, respectively, of AgNPs and various forms of Ag. The changes in cell membrane morphology and increases in lactate dehydrogenase (LDH) release indicated that AgNPs and various forms of Ag damaged the cell membrane of P. stutzeri. Oxidative stress caused by excessive accumulation of reactive oxygen species (ROS) increased superoxide dismutase (SOD) and catalase (CAT) activities and decreased glutathione (GSH) levels. Overall, this study will help elucidate the impact of AgNPs and their transformation products on nitrogen removal efficiency in wastewater biological treatment systems., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xinping Yang reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) stands as the predominant age-related neurodegenerative disorder, for which efficacious treatment remains elusive. An auspicious avenue for this disease lies in natural compounds sourced from tranditional medicine and plant origins. Parthenolide (PTN) is a natural product with multiple biological functionsand. Recent investigations have illuminated PTN's protective properties against neurological maladies; however, its potential therapeutic role against AD remains uncharted. This study aims to explore the role of PTN in treating AD. Our in vitro findings underscore PTN's bioactivity, as evidenced by its capacity to curtail apoptosis, reduce reactive oxygen species (ROS) production, and restore mitochondrial membrane potential in PC12 cells. Moreover, PTN treatment demonstrates a capacity to ameliorate deficits in spatial learning and memory in the 3 ×Tg-AD murine model. Notably, PTN's therapeutic efficacy surpasses that of a clinical agent, donepezil. Mechanistically, PTN's neuroprotective effects stem from its adept regulation of the AMPK/GSK3β(ser9)/Nrf2 signaling pathway and protection on neuronal cells from ROS-related apoptosis. Although the molecular target and the pre-clinical evaluations of PTN need to be further explored, this study indicates PTN as a potential agent or lead compound for the drug development against AD., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Primary adrenal insufficiency (PAI) is a rare but life-threatening condition. Differential diagnosis of numerous causes of PAI requires a thorough understanding of the condition., Methods: To describe the genetic composition and presentations of PAI. The following data were collected retrospectively from 111 patients with non-21OHD with defined genetic diagnoses: demographic information, onset age, clinical manifestations, laboratory findings and genetic results. Patients were divided into four groups based on the underlying pathogenesis: (1) impaired steroidogenesis, (2) adrenal hypoplasia, (3) resistance to adrenocorticotropic hormone (ACTH) and (4) adrenal destruction. The age of onset was compared within the groups., Results: Mutations in the following genes were identified: NR0B1 (n=39), STAR (n=33), CYP11B1 (n=12), ABCD1 (n=8), CYP17A1 (n=5), HSD3B2 (n=4), POR (n=4), MRAP (n=2), MC2R (n=1), CYP11A1 (n=1), LIPA (n=1) and SAMD9 (n=1). Frequent clinical manifestations included hyperpigmentation (73.0%), dehydration (49.5%), vomiting (37.8%) and abnormal external genitalia (23.4%). Patients with adrenal hypoplasia typically presented manifestations earlier than those with adrenal destruction but later than those with impaired steroidogenesis (both p<0.01). The elevated ACTH (92.6%) and decreased cortisol (73.5%) were the most common laboratory findings. We generated a differential diagnosis flowchart for PAI using the following clinical features: 17-hydroxyprogesterone, very-long-chain fatty acid, external genitalia, hypertension and skeletal malformation. This flowchart identified 84.8% of patients with PAI before next-generation DNA sequencing., Conclusions: STAR and NR0B1 were the most frequently mutated genes in patients with non-21OHD PAI. Age of onset and clinical characteristics were dependent on aetiology. Combining clinical features and molecular tests facilitates accurate diagnosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Although the negative effects coming along with opiate withdrawal are in part modulated by L-type calcium channels (LTCCs), the distinctive physiological properties and functions of LTCCs subtypes suggest differential roles of subtypes during withdrawal. The present study aimed to examine the contributions of LTCC subtypes, Ca v 1.2 and Ca v 1.3, within the dorsal hippocampus (DH) in naloxone-precipitated morphine withdrawal using the conditioned place aversion (CPA) paradigm. Firstly, we injected the non-specific LTCCs antagonist verapamil into the DH of morphine-dependent rats before conditioning an environment with naloxone-precipitated withdrawal. Our results showed that verapamil blocked the acquisition of CPA. Then, to explore the molecular mechanisms of LTCCs subtypes during withdrawal, we measured the protein expression of Ca v 1.2 and Ca v 1.3 in morphine-dependent rats under different conditions. In morphine-dependent rats, conditioning with withdrawal increased Ca v 1.2 expression in the membrane, while only acute naloxone injection increased the membrane expression of Ca v 1.3. To further determine the causal roles of LTCCs subtypes in the withdrawal process, we used Ca v 1.2 siRNA or Ca v 1.3 shRNA to knock down the expression of subtypes and detected the effects on CPA and somatic withdrawal signs in morphine-dependent rats. Ca v 1.2 siRNA, but not Ca v 1.3 shRNA, inhibited the acquirement of CPA and relieved somatic withdrawal symptoms. Together, our findings reveal that Ca v 1.2, but not Ca v 1.3 plays an important role in mediating morphine withdrawal, suggesting this subtype may serve as a potential therapeutic target for the treatment of negative effects in opiate dependence., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

FK506-binding protein 5 (FKBP5) contributes to many diseases; However, it remains unclear whether FKBP5 is relevant to recurrent spontaneous abortion (RSA) and the mechanisms by which it is involved in maternal-fetal immunological tolerance. Placental tissue was collected in women with normal pregnancy and RSA and examined for FKBP5 expression. Human trophoblast cell lines and THP-1-derived M0 macrophages were used to explore the role of FKBP5 in RSA and its mechanism. The role of FKBP5 on pregnancy outcomes was assessed using a mouse model of miscarriage. This study found that upregulation of FKBP5 at the placental interface is involved in the pathogenesis of RSA by depressing trophoblast function and promoting M1-type macrophage polarization. First, FKBP5 expression was upregulated in the villi of RSA, and FKBP5 regulated trophoblast function by inhibiting HAPLN1 expression through suppression of PI3K/AKT signaling. In addition, FKBP5 inhibited trophoblast IL-6 secretion by suppressing PI3K/AKT signaling, thereby promoting macrophage polarization toward the M1 phenotype. Meanwhile, FKBP5 was significantly elevated in decidual macrophages from patients with RSA and promoted M1 macrophage polarization via ROS/NF-κB signaling and further inhibited trophoblast function. Finally, FKBP5 inhibitors improved embryo resorption rate in miscarried mice. In conclusion, FKBP5 is essential in maintaining pregnancy and trophoblast-macrophage crosstalk in the maternal-fetal interface, which may be a potential target for diagnosing and treating RSA., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Autophagy regulates many cell function related to cancer, including cell proliferation, invasion and apoptosis. Therefore, we investigated the potential value of crosstalk between autophagy and apoptosis. The present study demonstrated that seven autophagy related genes were screened from the biological network of salidroside (Sal) acting on liver cancer. The GO analysis showed that these genes were mainly involved in apoptosis and autophagy. The KEGG analysis showed that these genes regulated the process of liver cancer through Th17 cell differentiation, PI3K-Akt signaling pathway and other pathways. Moreover, seven genes were positively correlated with tumor purity, number of B cells, number of CD4 + T cells, number of CD8 + T cells, number of macrophages, number of dendritic cells and number of neutrophils. The overall survival time of liver cancer patients in the high expression group of BIRC5, HSP90AB1 and MTOR was lower than that in the low expression group (P < 0.05), while the overall survival time of the liver cancer patients in the high expression group of DLC1 and FOXO1 was higher than that in the low expression group (P < 0.05). In the pan-cancer analysis, we also found that BIRC5, HSP90AB1, MTOR, and ITGA6 were highly expressed in various cancers, while DLC1, FOXO1, and FOS were low expressed in various cancers. In the molecule docking analysis, we found that FOS, HSP90AB1, and MTOR had the best binding ability. Notably, in the vitro validation experiments, Sal was confirmed to induce autophagy and apoptosis, inhibite invasion and metastasis of liver cancer cells through the PI3K/Akt/mTOR signaling pathway. Meanwhile, inhibition of autophagy by chloroquine diphosphate (CQ) promoted Sal-induced mitochondrial apoptosis via corresponding cell and animal experiments. We speculated that Sal-induced autophagy might be a protective mechanism, inhibition of autophagy could further promote the progression of liver cancer. It may provide important insight into the molecular mechanism of crosstalk between autophagy and apoptosis, and provide a new theoretical basis of Sal combined with autophagy inhibitors as a adjuvant chemotherapeutic strategy for human liver cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

During the outbreak of COVID-19 in China, many health care workers have been involved in the front-line fight against the epidemic and have experienced major psychological challenges. This study was aimed at assessing the mental health of front-line health workers after 2 years of COVID-19 efforts. We recruited front-line health workers from Liaoning province who supported Hubei, the epicenter of the COVID-19 outbreak. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder scale (GAD-7), and Insomnia Severity Index (ISI) were used to assess psychological status. A total of 1101 of 1354 contacted individuals completed the survey (participation rate of 81.31%): 963 (87.5%) were 20-45 years of age, 919 (83.47%) were women, 845 (76.7%) were nurses, and 245 (22.3%) were physicians. After 2 years, the mental health symptoms among survey respondents were as follows: 46.6% had depression, 35.5% had anxiety, and 38.1% had insomnia. Thus, 2 years after the COVID-19 pandemic, the front-line health workers who had assisted Hubei province during the COVID‑19 pandemic in China still had high levels of depression, anxiety, and insomnia. Our findings suggest that the pandemic has had significant long-term effects on the mental health of front-line health workers. Therefore, mental health policies should offer long-term rather than short-term services., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Meng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The study aims to investigate the relationships among oral hygiene behavior, toothache, and depression among Chinese older adults., Methods: We used data came from the 2018 wave of Chinese Longitudinal Healthy Longevity Survey (CLHLS). The Center for Epidemiologic Studies Depression Scale was used to evaluate depression. Binary logistic regression was performed to analyze the relationships among oral hygiene behavior, toothache, and depression., Results: A total of 12,172 older adults were included in the study, of whom 27.2% had depression. Compared with those who did not brush their teeth daily, those who brushed their teeth at least once daily exhibited lower odds of having depressive symptoms (odds ratio [OR] = 0.86, 95% confidence interval [CI] = 0.77-0.97 versus OR = 0.81, 95% CI = 0.71-0.93). Compared with those who did not have toothache, those who had toothache over the past 6 months exhibited higher odds of having depression (OR = 1.49, 95% CI = 1.33-1.68). Living arrangement had a significant effect on the correlation between toothache and depression (p = 0.049), who lived alone and had toothache exhibited higher odds of having depressive symptoms., Conclusions: Oral hygiene behavior and toothache are associated with depression. Taking effective measures to maintain a daily toothbrushing pattern and reduce the occurrence of toothache may mitigate the risk of depression among older adults, especially among those living alone., Clinical Relevance: The present study reports that the potential relationship between different oral hygiene behavior, toothache, and depressive symptoms., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Purpose: Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset., Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5-24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0-1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH)., Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46-2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0-2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group., Conclusion: This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5-24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Unexplained recurrent spontaneous abortion (URSA) has been associated with the dysfunction of trophoblasts and decidual macrophages. Current evidence suggests that profilin1 (PFN1) plays an important role in many biological processes. However, little is known about whether PFN1 is related to URSA. Herein, the location of PFN1 was detected by immunohistochemistry, and the level of PFN1 was detected by quantitative real-time PCR, Western blot analysis, and immunohistochemistry. The proliferation of trophoblasts was detected by CCK8 and 5-ethynyl-2'-deoxyuridine assays, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays were used to detect apoptosis of trophoblasts. The migration and invasion ability of trophoblasts was assessed by using the wound-healing test and transwell test. Polarization of macrophages was detected in macrophages cultured in trophoblast conditioned medium. PFN1 expression was observed in cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts and was decreased in the villous tissue of patients with URSA. The migration and invasion ability and cell viability of trophoblastic cell lines that underwent PFN1 knockdown significantly decreased, and apoptosis increased. Opposite findings were observed after the overexpression of PFN1 in trophoblastic cells. In addition, PFN1 could regulate trophoblast function through phosphatidylinositol 3-kinase/AKT signal transduction rather than mitogen-activated protein kinase signaling pathways. Finally, knockdown of PFN1 in trophoblasts promoted tumor necrosis factor-α secretion to induce macrophage polarization to M1 phenotype, mediated by the NF-κB signaling pathway. These findings indicate that PFN1 has a broad therapeutic potential for patients with URSA., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The catalytic transformation of biomass-based furan compounds (furfural and HMF) for the synthesis of organic chemicals is one of the important ways to utilize renewable biomass resources. Among the numerous high-value products, cyclopentanone derivatives are a kind of valuable compound obtained by the hydrogenation rearrangement of furfural and HMF in the aqueous phase of metal-hydrogen catalysis. Following the vast application of cyclopentanone derivatives, this reaction has attracted wide attention since its discovery, and a large number of catalytic systems have been reported to be effective in this transformation. Among them, the design and synthesis of metal catalysts are at the core of the reaction. This review briefly introduces the application of cyclopentanone derivatives, the transformation mechanism, and the pathway of biomass-based furan compounds for the synthesis of cyclopentanone derivatives. The important progress of metal catalysts in the reaction since the first report in 2012 up to now is emphasized, the characteristics and catalytic performance of different metal catalysts are introduced, and the critical role of metal catalysts in the reaction is discussed. Finally, the future development of this transformation process was prospected.

Epilepsy is a chronic central nervous system disorder characterized by recurrent seizures. Not only does epilepsy severely affect the daily life of the patient, but the risk of premature death in patients with epilepsy is three times higher than that of the normal population. Magnetoencephalography (MEG) is a non-invasive, high temporal and spatial resolution electrophysiological data that provides a valid basis for epilepsy diagnosis, and used in clinical practice to locate epileptic foci in patients with epilepsy. It has been shown that MEG helps to identify MRI-negative epilepsy, contributes to clinical decision-making in recurrent seizures after previous epilepsy surgery, that interictal MEG can provide additional localization information than scalp EEG, and complete excision of the stimulation area defined by the MEG has prognostic significance for postoperative seizure control. However, due to the complexity of the MEG signal, it is often difficult to identify subtle but critical changes in MEG through visual inspection, opening up an important area of research for biomedical engineers to investigate and implement intelligent algorithms for epilepsy recognition. At the same time, the use of manual markers requires significant time and labor costs, necessitating the development and use of computer-aided diagnosis (CAD) systems that use classifiers to automatically identify abnormal activity. In this review, we discuss in detail the results of applying various different feature extraction methods on MEG signals with different classifiers for epilepsy detection, subtype determination, and laterality classification. Finally, we also briefly look at the prospects of using MEG for epilepsy-assisted localization (spike detection, high-frequency oscillation detection) due to the unique advantages of MEG for functional area localization in epilepsy, and discuss the limitation of current research status and suggestions for future research. Overall, it is hoped that our review will facilitate the reader to quickly gain a general understanding of the problem of MEG-based epilepsy classification and provide ideas and directions for subsequent research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pan, Yang, Li, Ren and Duan.)

Resting-state functional connectivity, constructed via functional magnetic resonance imaging, has become an essential tool for exploring brain functions. Aside from the methods focusing on the static state, investigating dynamic functional connectivity can better uncover the fundamental properties of brain networks. Hilbert-Huang transform (HHT) is a novel time-frequency technique that can adapt to both non-linear and non-stationary signals, which may be an effective tool for investigating dynamic functional connectivity. To perform the present study, we investigated time-frequency dynamic functional connectivity among 11 brain regions of the default mode network by first projecting the coherence into the time and frequency domains, and subsequently by identifying clusters in the time-frequency domain using k-means clustering. Experiments on 14 temporal lobe epilepsy (TLE) patients and 21 age and sex-matched healthy controls were performed. The results show that functional connections in the brain regions of the hippocampal formation, parahippocampal gyrus, and retrosplenial cortex (Rsp) were reduced in the TLE group. However, the connections in the brain regions of the posterior inferior parietal lobule, ventral medial prefrontal cortex, and the core subsystem could hardly be detected in TLE patients. The findings not only demonstrate the feasibility of utilizing HHT in dynamic functional connectivity for epilepsy research, but also indicate that TLE may cause damage to memory functions, disorders of processing self-related tasks, and impairment of constructing a mental scene., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Temporal Lobe Epilepsy (TLE) is the most common subtype of focal epilepsy and the most refractory to drug treatment. Roughly 30% of patients do not have easily identifiable structural abnormalities. In other words, MRI-negative TLE has normal MRI scans on visual inspection. Thus, MRI-negative TLE is a diagnostic and therapeutic challenge. In this study, we investigate the cortical morphological brain network to identify MRI-negative TLE. The 210 cortical ROIs based on the Brainnetome atlas were used to define the network nodes. The least absolute shrinkage and selection operator (LASSO) algorithm and Pearson correlation methods were used to calculate the inter-regional morphometric features vector correlation respectively. As a result, two types of networks were constructed. The topological characteristics of networks were calculated by graph theory. Then after, a two-stage feature selection strategy, including a two-sample t-test and support vector machine-based recursive feature elimination (SVM-RFE), was performed in feature selection. Finally, classification with support vector machine (SVM) and leave-one-out cross-validation (LOOCV) was employed for the training and evaluation of the classifiers. The performance of two constructed brain networks was compared in MRI-negative TLE classification. The results indicated that the LASSO algorithm achieved better performance than the Pearson pairwise correlation method. The LASSO algorithm provides a robust method of individual morphological network construction for distinguishing patients with MRI-negative TLE from normal controls., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Neoadjuvant chemotherapy (NAC) plays an important role in the treatment and prognosis of breast cancer. The early identification of patients who can truly benefit from preoperative NAC is crucial in clinical practice. The purpose of this study was to explore whether the ultrasound features and clinical characteristics combined with tumor-infiltrating lymphocyte(TIL) levels can improve the performance of predicting NAC efficacy in breast cancer patients., Material and Methods: In this retrospective study, 202 invasive breast cancer patients who underwent NAC followed by surgery were included. The baseline ultrasound features were reviewed by two radiologists. Miller-Payne Grading (MPG) was used to assess pathological response, and MPG 4-5 was defined as major histologic responders (MHR). Multivariable logistic regression analysis was used to evaluate independent predictors for MHR and build the prediction models. The receiver operating characteristic (ROC) curve was used to evaluate the performance of the models., Results: Of the 202 patients, 104 patients achieved MHR and 98 patients achieved non-MHR. Multivariate logistic regression analysis showed the US size (p=0.042), molecular subtypes (p=0.001), TIL levels (p<0.001), shape (p=0.030), and posterior features (p=0.018) were independent predictors for MHR. The model combined the US features, clinical characteristics, and TIL levels had a better performance with an area under the curve (AUC) of 0.811, a sensitivity of 0.663, and a specificity of 0.847., Conclusion: The model combined US features, clinical characteristics, and TIL levels had a better performance in predicting pathological response to NAC in breast cancer.

Background: X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency (PAI) and hypogonadotropic hypogonadism (HH), with limited clinical and genetic characterization., Methods: The clinical, biochemical, genetic, therapeutic, and follow-up data of 42 patients diagnosed with X-linked AHC were retrospectively analysed., Results: Hyperpigmentation (38/42, 90%), vomiting/diarrhoea (20/42, 48%), failure to thrive (13/42, 31%), and convulsions (7/42, 17%) were the most common symptoms of X-linked AHC at onset. Increased adrenocorticotropic hormone (ACTH) (42/42, 100%) and decreased cortisol (37/42, 88%) were the most common laboratory findings, followed by hyponatremia (32/42, 76%) and hyperkalaemia (29/42, 69%). Thirty-one patients presented with PAI within the first year of life, and 11 presented after three years of age. Three of the thirteen patients over the age of 14 exhibited spontaneous pubertal development, and ten of them experienced delayed puberty due to HH. Six patients receiving human chorionic gonadotropin (hCG) therapy exhibited a slight increase in testicular size and had rising testosterone levels (both P < 0.05). The testicular volumes of the three patients with pulsatile gonadotropin-releasing hormone (GnRH) therapy were larger than those of the six patients undergoing hCG therapy (P < 0.05), and they also exhibited some growth in terms of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Of the 42 patients, three had an Xp21 deletion, and 39 had an isolated DAX1 defect. Most patients (9/10) with entire DAX1 deletion accounting for 23.8% (10/42) of the total variants had early onset age of less than one year., Conclusions: This study details the clinical features and genetic spectra of X-linked AHC. Patients with X-linked AHC show a bimodal distribution of the age of onset, with approximately 70% presenting within the first year of life. Pulsatile GnRH may be recommended for HH when hCG therapy is not satisfactory, although it is difficult to achieve normal testicular volume. The combination of clinical features and molecular tests provides information for an accurate diagnosis., (© 2023. The Author(s).)