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The purpose of this study was to explore the effect of Semaglutide on intrauterine adhesions and discover new drugs for such adhesions. In this study, the cell model was simulated by TGF-β1-induced human endometrial epithelial cells, and the animal model was established through mechanical curettage and inflammatory stimulation. After co-culturing with TGF-β1 with or without different concentrations of Semaglutide for 48 h, cells were collected for RT-qPCR and Western blotting analyses. Three doses were subcutaneously injected into experimental mice once a day for two weeks, while the control group received sterile ddH2O. The serum and uterine tissues of the mice were collected. HE and Masson staining were used for the uterine histomorphological and pathological analyses. RT-qPCR and Western blotting were used for mRNA and protein expression analyses. Serum indicators were detected using ELISA kits. The results showed that Semaglutide significantly reduced the mRNA levels of fibrosis indicators ACTA2, COL1A1, and FN and inflammatory indicators TNF-α, IL-6, and NF-κB in the two models. Semaglutide improved endometrium morphology, increased the number of endometrial glands, and reduced collagen deposition in IUA mice. The results also showed that Semaglutide could inhibit vimentin, E-Cadherin, and N-Cadherin in the two models. In summary, Semaglutide can ameliorate fibrosis and inflammation of intrauterine adhesions as well as inhibit epithelial–mesenchymal transition in IUA models. [ABSTRACT FROM AUTHOR]

Context Cushing syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut microbial dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear. Objective The objective of this work is to examine the alteration of gut microbiota in patients with CS. Methods We performed shotgun metagenomic sequencing of fecal samples from 78 patients with CS and 78 healthy controls matched for age and body mass index. Furthermore, we verify the cortisol degradation capacity of Ruminococcus gnavus in vitro and identify the potential metabolite by LC-MC/MS. Results We observed significant differences in microbial composition between CS and controls in both sexes, with CS showing reduced Bacteroidetes (Bacteroides vulgatus) and elevated Firmicutes (Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (Enterobacter cloacae). Despite distinct causes of hypercortisolism in ACTH-dependent and ACTH-independent CS, we found no significant differences in metabolic profiles or gut microbiota between the 2 subgroups. Furthermore, we identified a group of gut species, including R. gnavus , that were positively correlated with cortisol levels in CS. These bacteria were found to harbor cortisol-degrading desAB genes and were consistently enriched in CS. Moreover, we demonstrated the efficient capacity of R. gnavus to degrade cortisol to 11-oxygenated androgens in vitro. Conclusion This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health. [ABSTRACT FROM AUTHOR]

Environmental processes in cities and suburbs are significantly impacted by climate change. The development of reliable ecological models may successfully direct agricultural activities. Numerous models have been put forth as of late; however, because to the complexity of environmental microorganisms, their use in complex systems is still restricted. For a better understanding of the ecological restoration of an urban lake system that had been disturbed by rainfall, an improved ecological dynamic model that took into account inundation plants, phytoplankton and microorganisms was proposed based on the field survey. Observed data from a shallow urban lake with a surface area of approximately 66 600 m2 in the heart of Shunde district, Foshan, in South China, was used to validate the model. In this model, five hypotheses—phytoplankton, microorganisms, NH3‐N, COD and TP in water—were selected as experimental variables. To assess the model's correctness and dependability, the correlation coefficients (R) and root mean square error‐observations standard deviation ratio (RSR) were computed. The results from the establish model (0.446 < R < 0.985, RSR < 0.7) are very similar to those of actual observations. In addition, four microbe species (Aquabacium, Bradyrhizobium japonicum, Curvibacter and Cyanobacteria) multiplied when pollutant concentration dropped. Our model provides a useful tool for managing urban shallow water lakes by properly simulating the dynamic changes of aquatic species and microbes in urban shallow water lakes. Key Points: An improved ecological dynamic model was proposed based on the field survey.Observed data from a shallow urban lake were used to validate the model.Five hypotheses were selected as experimental variables.Both R and RSR were computed to assess the model's correctness and dependability.The results from the establish model are very similar to those of actual observations. [ABSTRACT FROM AUTHOR]

Beta zeolite, a crystal material with a three-dimensional twelve-ring cross-channel structure, has many advantages, such as high Brønsted acid concentration, high Si/Al ratio, thermal/hydrothermal stability, and large surface area. Due to these advantages, beta zeolite shows excellent catalytic performance in petroleum refining and petrochemical processes. However, traditionally microporous beta zeolite has strong steric hindrance and diffusion restrictions, which hinder large molecules from passing through its internal channels. In addition, carbon deposition occurs, resulting in catalyst deactivation. The main strategy to solve this problem is to prepare nanosized or hierarchical beta zeolites, which allow for large molecule conversion and shortening diffusion pathways. Therefore, researchers have explored different synthesis strategies to prepare beta zeolite with different particle sizes and porosities to obtain better zeolite catalysts. This paper briefly describes the recent research progress in the preparation of nanosized and hierarchical beta zeolite. Additionally, the mechanisms of various preparation methods, structural characteristics, and applications of the materials are introduced in detail. Furthermore, the main problems existing in its industrial application are describing by comparing the advantages and disadvantages of the different methods to prepare optimally nanosized and hierarchical zeolite to meet the requirements of industrial development. [ABSTRACT FROM AUTHOR]

The development of efficient, stable, and economic electrocatalysts are key to the large-scale application of electrochemical energy conversion. Porous carbon-based non-precious metal electrocatalysts are considered to be the most promising materials to replace Pt-based catalysts, which are limited in large-scale applications due to high costs. Because of its high specific surface area and easily regulated structure, a porous carbon matrix is conducive to the dispersion of active sites and mass transfer, showing great potential in electrocatalysis. This review will focus on porous carbon-based non-precious metal electrocatalysts and summarize their new progress, focusing on the synthesis and design of porous carbon matrix, metal-free carbon-based catalysts, non-previous metal monatomic carbon-based catalyst, and non-precious metal nanoparticle carbon-based catalysts. In addition, current challenges and future trends will be discussed for better development of porous carbon-based non-precious metal electrocatalysts. [ABSTRACT FROM AUTHOR]

Nutrition and lifestyle have a great impact on reproduction and infertility in humans, as they are essential for certain processes such as implantation, placental growth, angiogenesis, and the transfer of nutrients from the mother to the fetus. The aim of this review is to provide the interconnection between nutrition and reproductive health through the insight of omics approaches (including metabolomics and nutrigenomics). The effect of various macronutrients, micronutrients, and some food‐associated components on male and female reproduction was discussed. Recent research work was collected through database search from 2010 to 2020 to identify eligible studies. Alterations of metabolic pathways in pregnant women were deliberated with an emphasis on different strategies of lifestyle and dietary interventions. Several nutritional methods, which are important for embryonic and child neurological development, nutritional supplements to lactation, and improved gestational length along with birth weight have been emphasized. Considerable advances in omics strategies show potential technological development for improving human reproductive health. [ABSTRACT FROM AUTHOR]

Formic acid (FA) as a safe and promising hydrogen carrier has attracted widespread attention. The use of solid catalysts in the controllable and efficient dehydrogenation of FA is still a challenge. Here, a series of Au nanoclusters supported on rare earth metal doped ZrO2 catalysts (Au/ReZrO2 (Re = Nd, Ce and Sm)) was prepared. Doping rare earth metals in zirconia stabilizes the mixed-phase zirconia into the tetragonal phase. Meanwhile, the rare earth metal dopants can promote the formation of oxygen vacancies in zirconia, which promotes charge transfer from the support to Au and enhances the metal–support interaction on all the three catalysts. As a result, Au/ReZrO2 (Re = Nd3+, Ce3+ and Sm3+) catalysts exhibited better catalytic performance in the liberation of CO-free H2 from FA, outperforming Au supported on primary ZrO2. Structural and electronic characterization by XPS and H2-TPR further confirmed the contribution of doping rare earth metal cations in Au/ReZrO2, which can enhance the metal–support interaction and accelerate the decomposition of HCOOH into H2, thus resulting in the improvement in catalytic activity for hydrogen production from FA. [ABSTRACT FROM AUTHOR]

A nano-confined pyrolysis approach was developed for constructing highly nitrogen-doped hierarchically porous metal/N/C nanospheres (typically Fe/N/C-HP). Hierarchically porous silica nanospheres (NKM-5) were used as a hard template, and an amorphous Fe/Zn-(MeIm)2 complex was employed as a carbon and nitrogen source. During the pyrolysis process, first, the molten Fe/Zn-(MeIm)2 complex diffused into hierarchically porous tunnels of NKM-5. Secondly, the interface confinement effect of nanopores in NKM-5 could effectively immobilize nitrogen to coordinate with iron atom, prevent the aggregation of Fe-based species and form single-atom Fe sites. After the silica template was removed, the catalyst exhibited a hierarchically porous structure and uniform spherical morphology. This hierarchically porous structure of Fe/N/C-HP can enhance mass transport/electron transfer and greatly improve the accessibility of Fe/N/C sites. As a result, the Fe/N/C-HP catalyst exhibits excellent oxygen reduction performance with a half-wave potential (E1/2) of 0.90 V in alkaline media and 0.78 V in acidic media. A primary Zn–air battery with Fe/N/C-HP as the cathode catalyst exhibits a large peak power density of 181 mW cm−2 and discharge stability. This nano-confined pyrolysis of amorphous M/Zn-(MeIm)2 complex is a general method to construct a hierarchically porous M/N/C (M = Fe, Co, Cu, Mn and Ni) electrocatalyst with well-defined morphology. [ABSTRACT FROM AUTHOR]

The association of pathological features of cortisol-producing adrenocortical adenomas (ACAs) with somatic driver mutations and their molecular classification remain unclear. In this study, we explored the association between steroidogenic acute regulatory protein (StAR) expression and the driver mutations activating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling to identify the pathological markers of ACAs. Immunohistochemical staining for StAR and mutations in the protein kinase cAMP-activated catalytic subunit alpha (PRKACA), protein kinase cAMP-dependent type I regulatory subunit alpha (PRKAR1A) and guanine nucleotide binding protein, alpha stimulating (GNAS) genes were examined in 97 ACAs. The association of StAR expression with the clinical and mutational features of the ACAs was analyzed. ACAs with mutations in PRKACA, GNAS, and PRKAR1A showed strong immunopositive staining for StAR. The concordance between high StAR expression and mutations activating cAMP/PKA signaling in the ACAs was 99.0%. ACAs with high expression of StAR had significantly smaller tumor volume (P < 0.001) and higher urinary cortisol per tumor volume (P = 0.032) than those with low expression of StAR. Our findings suggest that immunohistochemical staining for StAR is a reliable pathological approach for the diagnosis and classification of ACAs with cAMP/PKA signaling-activating mutations. [ABSTRACT FROM AUTHOR]

The mutually coupled dual three-phase switched reluctance motor (DTPSRM) is a new type of special 12/8 SRMs, which possesses high-reliability and fault-tolerant feature. In the past researches, the model, analysis, and fault-tolerant operation were mainly focused on the classical single three- and four-phase SRMs. This paper is mainly to analyze and investigate the fault-tolerant performances of a 12/8-pole mutually coupled DTPSRM drive under various open-circuit operations. First, the static magnetic characteristics of DTPSRM with single- and two-phase excitations are calculated by finite-element analysis. Then, the mathematic model of the DTPSRM drive under open-circuit condition is developed with a combination of state and fault functions. The simulation model of the DTPSRM drive system with a fault-tolerant control strategy is established for dynamic analysis. The faulty characteristics and fault-tolerant performances of the DTPSRM with diverse open circuits are predicted. Finally, a 12/8 DTPSRM is prototyped and an experimental setup is built for verification. The experimental normal results and diverse open-circuit operations and self-starting capability under lack of phases are presented, validating the accuracy of the analysis and simulation as well as fault-tolerant characteristics of the DTPSRM drive system. [ABSTRACT FROM AUTHOR]

The classical switched reluctance motors (SRMs) often suffer from drawbacks such as low power and torque densities, high torque ripple, mutual coupling, etc., which limit their industrial applications. This paper presents the analysis and development of two novel three-phase SRMs with hybrid magnetic paths comprising six E-shaped modular stators and three segmental common rotors, termed as the modular SRMs (MSRMs), for electric vehicle applications. The machine topologies with different winding arrangements are described. The voltage and output power equations are analytically derived, and some design particularities and parameters are discussed. The field distributions and static magnetic characteristics of an MSRM with double coil are analyzed by using 3-D finite-element method. After that, two MSRMs with different winding arrangements, namely a double-coil MSRM and single-coil MSRM, are analyzed and compared to evaluate the distinct features of this novel MSRM, accompanied with a classical three-phase 6/4 SRM. The comparison includes static magnetic characteristics, mass of iron core, normal dynamic, and fault-tolerant performances. It is shown that the double-coil MSRM appears to have better characteristics such as higher torque production capability, lower torque ripple and cost, higher torque and output power densities, and higher reliability and fault tolerance. For experimental verification, laboratory testing of a double-coil MSRM is developed, and the simulated and measured static inductance characteristics and dynamic performances correlate well. [ABSTRACT FROM PUBLISHER]

Background: Adrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy, remains challenging, thus underscoring the significance to predict mitotane response prior to treatment and seek other effective therapeutic strategies., Objective: We aimed to determine the efficacy of mitotane via an in vitro assay using patient-derived ACC cells (PDCs), identify molecular biomarkers associated with mitotane response and preliminarily explore potential agents for ACC., Methods: In vitro mitotane sensitivity testing was performed in 17 PDCs and high-throughput screening against 40 compounds was conducted in 8 PDCs. Genetic features were evaluated in 9 samples using exomic and transcriptomic sequencing., Results: PDCs exhibited variable sensitivity to mitotane treatment. The median cell viability inhibition rate was 48.4% (IQR: 39.3-59.3%) and -1.2% (IQR: -26.4-22.1%) in responders (n=8) and non-responders (n=9), respectively. Median IC50 and AUC were remarkably lower in responders (IC50: 53.4 µM vs 74.7 µM, P<0.0001; AUC: 158.0 vs 213.5, P<0.0001). Genomic analysis revealed CTNNB1 somatic alterations were only found in responders (3/5) while ZNRF3 alterations only in non-responders (3/4). Transcriptomic profiling found pathways associated with lipid metabolism were upregulated in responder tumors whilst CYP27A1 and ABCA1 expression were positively correlated to in vitro mitotane sensitivity. Furthermore, pharmacologic analysis identified that compounds including disulfiram, niclosamide and bortezomib exhibited efficacy against PDCs., Conclusion: ACC PDCs could be useful for testing drug response, drug repurposing and guiding personalized therapies. Our results suggested response to mitotane might be associated with the dependency on lipid metabolism. CYP27A1 and ABCA1 expression could be predictive markers for mitotane response, and disulfiram, niclosamide and bortezomib could be potential therapeutics, both warranting further investigation., 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 Zhang, Wu, Su, Liu, Jiang, Jiang, Wu, Chen, Li, Zheng, Sun, Peng, Han, Ning, Ye and Wang.)

Context: The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically., Objective: To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population., Design: Retrospective cohort study., Methods: We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion., Results: UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery., Conclusions: UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA., 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 Jiang, Zhou, Zhang, Su, Jiang, Zhou, Zhong, Wu and Wang.)

Context: Adrenocortical carcinoma (ACC) is rare and have high rates of recurrence and mortality. The role of adjuvant radiation therapy (RT) in localized ACC was controversial., Methods: We conducted a retrospective study in our center between 2015 and 2021 to evaluate the efficacy and safety of adjuvant RT in localized ACC. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to estimate the independent risk factors. Adverse events associated with RT were documented according to the toxicity criteria of the radiation therapy oncology group (RTOG) and the common terminology criteria for adverse events (CTCAE v5.0)., Results: Of 105 patients with localized ACC, 46 (43.8%) received adjuvant RT after surgery. The median radiation dose was 45.0Gy (range:30.0-50.4) and median follow up time was 36.5 (IQR: 19.7-51.8) months. In comparison to the no adjuvant RT group, patients with adjuvant RT had better 3-year OS (87.9% vs 79.5%, P=0.039), especially for patients with ENSAT I/II stage (P=0.004). Adjuvant RT also improved the median DFS time from 16.5months (95%CI, 12.0-20.9) to 34.6months (95%CI, 16.1-53.0). Toxicity of RT was generally mild and moderate with six grade 3 events., Conclusions: Postoperative adjuvant RT significantly improved OS and DFS compared with the use of surgery alone in resected ACC patients. Although this retrospective study on RT in localized ACC indicates that RT is effective in ACC, its findings need to be prospectively confirmed., 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 Wu, Chen, Su, Jiang, Han, Zhang, Zhou, Jiang, Zhong and Wang.)

Context: Preoperative inflammatory markers, such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), have recently been proposed as prognostic markers in different tumors. However, their predictive values in patients with pheochromocytomas and paragangliomas (PPGLs) are uncertain., Objective: This study aimed to investigate the prognostic significance of inflammatory biomarkers in PPGL patients., Methods: Data from 1247 consecutive PPGL patients between 2002 and 2020 were evaluated. The preoperative inflammatory markers were evaluated. The prognostic roles were identified by X-tile software, Kaplan-Meier curves, and Cox regression models., Results: A total of 728 patients were included in the analysis, with a median follow-up of 63 months (IQR, 31-111 months); 31 individuals died, 28 patients developed metastases, and 12 patients developed recurrence. Our study showed that deaths were observed significantly more frequently in patients with high NLR(≥3.5) and high PLR (≥217.4) than those with low NLR (<3.5) (P = .003) and low PLR (<217.4) (P = .005). Elevated NLR (≥3.5) and elevated PLR (≥217.4) was significantly associated with decreased overall survival (OS) (P = .005), and elevated PLR (≥238.3) was significantly associated with decreased metastasis-free survival (MFS) (P = .021). Cox models illustrated that NLR and PLR were independent prognostic factors for OS, and PLR was an independent prognostic factor for MFS., Conclusion: Both elevated NLR and PLR are associated with poor prognosis in PPGLs. They are convenient predictive markers that could be used in daily clinical practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Adrenal incidentaloma (AI) is commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion is the most common functional disorder detected in AI., Objective: To delineate the association between radiological characteristics of benign adrenocortical tumors and hypothalamus-pituitary-adrenal (HPA) axis., Methods: In the study, 494 patients diagnosed with benign unilateral adrenocortical tumors were included. Mild autonomous cortisol secretion (MACS) was diagnosed when cortisol after 1mg-dexamethasone suppression test (1-mg DST) was in the range of 1.8-5ug/dl. Non-functional adrenocortical tumor (NFAT) was diagnosed as cortisol following 1-mg DST less than 1.8ug/dL. We performed Logistics regression and causal mediation analyses, looking for associations between radiological characteristics and the HPA axis., Results: Of 494 patients, 352 (71.3%) with NFAT and 142 (28.7%) with MACS were included. Patients with MACS had a higher tumor diameter, thinner contralateral adrenal gland, and lower plasma ACTH and serum DHEAS than those with NFAT. ACTH (OR 0.978, 0.962-0.993) and tumor diameter (OR 1.857, 95%CI, 1.357-2.540) were independent factors associated with decreased serum DHEAS (all P<0.05). ACTH was also associated with decreased contralateral adrenal diameter significantly (OR 0.973, 95%CI, 0.957-0.988, P=0.001). Causal mediation analysis showed ACTH mediated the effect significantly for the association between 1-mg DST results and DHEAS level (P mediation< 0.001, proportion=22.3%). Meanwhile, we found ACTH mediated 39.7% of the effects of 1-mg DST on contralateral adrenal diameter (P mediation =0.012)., Conclusions: Patients with MACS had thinner contralateral adrenal glands and disturbed HPA axes compared with NFAT. ACTH may partially be involved in mediating the mild autonomous cortisol secretion to DHEAS and the contralateral adrenal gland., 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 Zhu, Wu, Su, Jiang, Zhou, Jiang, Zhang, Zhong and Wang.)

Background: Idiopathic hyperaldosteronism (IHA) is one of the most common types of primary aldosteronism (PA), an important cause of hypertension. Although high dietary sodium is a major risk factor for hypertension, there is no consensus on the recommended dietary sodium intake for IHA., Objective: This study investigated the effect of a low-sodium diet on hemodynamic variables and relevant disease biomarkers in IHA patients, with the aim of providing a useful reference for clinical treatment., Methods: Fifty IHA patients were evenly randomized into two groups and provided, after a 7-day run-in period (100 mmol/d sodium), either a low-sodium diet (50 mmol/d sodium) or a normal sodium diet (100 mmol/d sodium) for an additional 7 days. After the 14-day intervention (conducted without potassium supplementation), changes in blood pressure (BP) and serum potassium were evaluated in both groups., Results: After the dietary intervention, the low sodium group exhibited, compared to the normal sodium group, decreased BP (SBP: 121.8 ± 12.8 vs . 129.9 ± 12.1 mmHg, p < 0.05; DBP: 82.6 ± 7.6 vs . 86.4 ± 8.2 mmHg, p < 0.05; MAP: 95.7 ± 8.8 vs . 100.9 ± 8.4 mmHg, p < 0.05) and increased serum potassium levels (3.38 ± 0.33 vs . 3.07 ± 0.27 mmol/L, p < 0.001). The low sodium group showed also better control of both BP and serum potassium: BP <140/90 mmHg in 70.0% of total patients (76.0% vs . 64.0%, in the low and normal sodium groups, respectively; p > 0.05), BP <130/85 mmHg in 38.0% of total patients (56.0% vs . 20.0%, p < 0.05), BP <120/80 mmHg in 28.0% of total patients (44.0% vs . 12.0%, p < 0.05); serum potassium ≥3.5 mmol/L in 22.0% of total patients (32.0% vs . 12.0% in the low and normal sodium groups, respectively; p = 0.088). There were differences between the controlled BP group (<120/80 mmHg) and the non-controlled BP group (≥120/80 mmHg) in gender, BP at baseline, and type of diet (low vs . normal sodium). Female gender and low-sodium diet were protective factors for BP control., Conclusions: A low-sodium diet is effective in lowering BP and elevating serum potassium in IHA patients. Female patients on a low-sodium diet are more likely to achieve BP control (<120/80 mmHg). We advocate a dietary sodium intake of 50 mmol/d for IHA patients., Clinical Trial Registration: https://clinicaltrials.gov, Identifier NCT05649631., 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 Zhou, Jiang, Zhang, Su, Jiang, Zhou, Zhong, Wu and Wang.)

Introduction: Pheochromocytomas and paragangliomas (PCC/PGL) are rare neuroendocrine tumors and can secrete catecholamine. Previous studies have found that SDHB immunohistochemistry (IHC) can predict SDHB germline gene mutation, and SDHB mutation is closely associated with tumor progression and metastasis. This study aimed to clarify the potential effect of SDHB IHC as a predictive marker for tumor progression in PCC/PGL patients., Methods: We included PCC/PGL patients diagnosed in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from 2002 to 2014 for retrospective analysis and discovered that SDHB (-) staining patients had poorer prognoses. Then we examined SDHB protein expression by IHC on all tumors in the prospective series, which was composed of patients from 2015 to 2020 in our center., Results: In the retrospective series, the median follow-up was 167 months, and during follow-up, 14.4% (38/264) patients developed metastasis or recurrence, and 8.0% (22/274) patients died. Retrospective analysis revealed that 66.7% (6/9) of participants in the SDHB (-) group and 15.7% (40/255) of those in the SDHB (+) group developed progressive tumors (OR: 10.75, 95% CI: 2.72-52.60, P=0.001), and SDHB (-) was independently associated with poor outcomes after adjusting by other clinicopathological parameters (OR: 11.68, 95% CI: 2.58-64.45, P=0.002). SDHB (-) patients had shorter disease-free survival (DFS) and overall survival (OS) (P<0.001) and SDHB (-) was significantly associated with shorter median DFS (HR: 6.89, 95% CI: 2.41-19.70, P<0.001) in multivariate cox proportional hazard analysis. In the prospective series, the median follow-up was 28 months, 4.7% (10/213) patients developed metastasis or recurrence, and 0.5% (1/217) patient died. For the prospective analysis, 18.8% (3/16) of participants in the SDHB (-) group had progressive tumors compared with 3.6% (7/197) in the SDHB (+) group (RR: 5.28, 95% CI: 1.51-18.47, P=0.009), statistical significance remained (RR: 3.35, 95% CI: 1.20-9.38, P=0.021) after adjusting for other clinicopathological factors., Conclusions: Our findings demonstrated patients with SDHB (-) tumors had a higher possibility of poor outcomes, and SDHB IHC can be regarded as an independent biomarker of prognosis in PCC/PGL., 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 Su, Yang, Jiang, Xie, Zhong, Wu, Jiang, Zhang, Zhou, Ye, Ning and Wang.)

Adrenal incidentalomas are the most frequent human neoplasms. Recent genomic investigations on functional adrenocortical tumors have demonstrated that somatic mutations in PRKACA and KCNJ5 responsible for the development of adrenocortical adenomas (ACAs) are associated with hypercortisolism and aldosteronism, respectively. Several studies have identified CTNNB1 mutations in ACAs and have been mostly involved in the tumorigenesis of non-functional ACA (NFACA). However, integrated genomic characterization of NFACAs is lacking. In the current study, we utilized pan-genomic methods to comprehensively analyze 60 NFACA samples. A total of 1264 somatic mutations in coding regions among the 60 samples were identified, with a median of 15 non-silent mutations per tumor. Twenty-two NFACAs (36.67%) had genetic alterations in CTNNB1. We also identified several somatic mutations in genes of the cAMP/PKA pathway and KCNJ5. Histone modification genes (KMT2A, KMT2C, and KMT2D) were altered in 10% of cases. Germline mutations of MEN1 and RET were also found. Finally, by comparison of our transcriptome data with those available in the TCGA, we illustrated the molecular characterization of NFACA. We revealed the genetic profiling and molecular landscape of NFACA. Wnt/β-catenin pathway activation as shown ssby nuclear and/or cytoplasmic β-catenin accumulation is frequent, occurring in about one-third of ACA cases. cytochrome P450 enzymes could be markers to reveal the functional status of adrenocortical tumors. These observations strongly suggest the involvement of the Wnt/β-catenin pathway in benign adrenal tumorigenesis and possibly in the regulation of steroid secretion.

Objective: Unilateral primary aldosteronism (PA) includes aldosterone-producing adenoma (APA), unilateral adrenal hyperplasia, and unilateral multiple nodules. The correlation of multiple nodules, especially genotypic and pathological characteristics, remains unknown. KCNJ5 mutation accounts for 60-80% of unilateral PA, so we aimed to explore the correlation of KCNJ5 somatic mutation and CYP11B1/CYP11B2 staining in multiple nodules in unilateral PA., Design and Methods: A total of 56 microdissected nodules from 24 patients with unilateral PA were included. We assessed somatic KCNJ5 mutations, immunohistochemistry for aldosterone synthase (CYP11B2)/cortisol synthase (CYP11B1), and histological cellular composition of nodules together with adjacent adrenal cortical statements., Results: KCNJ5 mutations were identified in 17 (17/56, 30.4%) nodules from 11 adrenals (11/24, 45.8%). All KCNJ5-mutant nodules were positive for CYP11B2 staining, 6 cases (6/11) had only one KCNJ5-mutant nodular, and the other 5 cases (5/11) had more than one KCNJ5-mutant nodules. Three cases (3/11) had different KCNJ5 mutations in individual nodules. Compared with KCNJ5-positive adrenals, the cortices adjacent to the nodules in KCNJ5-negative adrenals showed significant proliferation ( p = 0.004). CYP11B2/CYP11B1 expression patterns revealed great heterogeneity in intensity and range both in KCNJ5-mutant nodules and KCNJ5-WT ones., Conclusion: There is great heterogeneity among nodules from patients with unilateral PA. Countable nodules could be considered as multiple APAs, featuring somatic KCNJ5 mutation, positive CYP11B2 staining, and lack of adjacent cortical proliferation in unilateral multiple nodules., 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 © 2022 Xie, Zhang, Wang, Jiang, Wu, Ye, Wang, Xie, Xu and Wang.)

Background: Primary aldosteronism is caused by aldosterone overproduction. While conventional hematoxylin-eosin staining can demonstrate morphological abnormality, it cannot provide any functional histopathological information. We aimed to identify the diagnostic, functional and prognostic value of CYP11B2, CYP11B1, and β-catenin immunostaining in unilateral hyperaldosteronism. Method: A total of 134 patients with unilateral hyperaldosteronism were recruited in our study. The expression of CYP11B2, CYP11B1, and β-catenin was evaluated semiquantitatively on 134 patients' sections using immunohistochemistry technology and the relationship with clinical data was assessed. Results: Patients were classified into four subtypes based on CYP11B2 staining as below: (1)118 patients with unilateral single aldosterone-producing adenoma (APA), (2)11 with unilateral multiple APA, (3)four with aldosterone-producing cell cluster (APCC), and (4)one with an undefined source. Adjusted CYP11B2 H-score was correlated with serum aldosterone, aldosterone to renin ratio (ARR), and serum potassium. In the abnormal β-catenin staining group, hypertension duration, aldosterone, ARR, cortisol, tumor diameter, tumor area, and CYP11B2 H-score were significantly higher than those of the wild-type group. Serum potassium level was significantly lower in the abnormal β-catenin staining group. Age, gender, BMI, family history of hypertension, adjusted CYP11B2 and CYP11B1 H-scores differed significantly between complete clinical success and incomplete clinical success groups. Age, gender and family history of hypertension were independently associated with complete clinical success based on multivariate logistic regression analysis. Conclusion: CYP11B2 immunostaining could improve the differential diagnosis of unilateral hyperaldosteronism. Adjusted CYP11B2 H-score could be used as a histopathological marker to reflect the severity of unilateral APA. Dysregulation of Wnt/β-catenin signaling and impaired β-catenin degradation may provoke the proliferation and enhance the steroidogenic ability of APA tumor cells, indicating that the Wnt pathway might be a potential, actionable, therapeutic target in the treatment of hyperaldosteronism. Age, sex and family history of hypertension were independent predictors of clinical outcome after adrenalectomy for unilateral hyperaldosteronism., 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 © 2021 Sun, Jiang, Xie, Zhu, Wu, Zhong, Zhou, Su and Wang.)

Objective: Pancreatic neuroendocrine tumors (pNETs) causing ectopic adrenal corticotropic hormone (ACTH) syndrome (EAS) are rare and aggressive with little known information. We aimed to elucidate the clinical features and molecular mechanisms of pNETs with EAS by methylation analysis., Methods: Seven patients with ectopic ACTH-secreting pNETs who were diagnosed at Shanghai Clinical Endocrine and Metabolic Diseases Center and Pancreatic Disease Center in Ruijin Hospital between 2001 and 2019 were enrolled. Twenty patients with ectopic ACTH-secreting thymic neuroendocrine tumors (TNETs) and 7 with nonfunctional pNETs (nf-pNETs) were also enrolled as controls. We collected clinical data and measured POMC promoter CpG methylation., Results: All 7 patients had elevated ACTH and urinary free cortisol (UFC) levels with positive ACTH staining in the pancreas and were diagnosed with ectopic ACTH-secreting pNET. Of the 7 patients, 6 underwent surgery and 1 underwent transarterial embolization (TAE). Two patients were free of disease after surgery; 2 died within 90 days after surgery; and 3 had metastases and died within 1 year. Compared with ACTH-secreting TNETs, ACTH-secreting pNETs had similar clinical and biochemical features but a significantly poorer prognosis. POMC promoter CpG methylation was significantly lower in ACTH-secreting pNETs than in nf-pNETs and normal pancreas., Conclusions: ACTH-secreting pNETs are aggressive and fatal. Surgery is definitively curative for patients with resectable primary tumors without metastasis. Pro-opiomelanocortin (POMC) promoter hypomethylation caused pNETs to produce ACTH. This study further supplements the genetic features of ACTH-secreting NETs., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Exosomes are extracellular vesicles (EVs) released from cells upon fusion of an intermediate endocytic compartment with the plasma membrane. They refer to the intraluminal vesicles released from the fusion of multivesicular bodies with the plasma membrane. The contents and number of exosomes are related to diseases such as metabolic diseases, cancer and inflammatory diseases. Exosomes have been used in neurological research as a drug delivery tool and also as biomarkers for diseases. Recently, exosomes were observed in the seminal plasma of the one who is asthenozoospermia, which can affect sperm motility and capacitation., Objective: The main objective of this review is to deeply discuss the role of exosomes in spermatozoa after leaving the seminiferous tubule., Methods: We conducted an extensive search of the literature available on relationships between exosomes and exosomes in spermatozoa on the bibliographic database., Conclusion: This review thoroughly discussed the role that exosomes play in the exchange of spermatozoa after leaving the seminiferous tubule and its potential as a drug delivery tool and biomarkers for diseases as well., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ultrafine and highly dispersed PdAu nanoparticles were immobilized on amine functionalized carbon black (VXC-72-NH 2 ) for dehydrogenation of formic acid (FA). The introduction of amines is of vital importance for the formation of ultrafine PdAu nanoparticles (∼1.5 nm). Moreover, the presence of the amino groups also increased the electron density of PdAu nanoparticles, and this effect facilitated the formation of metal-formate, which further enhanced the rate of the catalytic dehydrogenation of FA. The as-prepared Pd 0.6 Au 0.4 /VXC-72-NH 2 exhibited high catalytic activity and 100% H 2 selectivity for dehydrogenation of formic acid without any additive, with turnover frequency (TOF) values of 7385 h -1 at 298 K and 17 724 h -1 at 333 K, which are the highest TOF values ever reported among heterogeneous catalysts for FA dehydrogenation., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Background: Feminizing adrenocortical carcinoma (ACC) is rare. The source of estrogen production and the underlying mechanism remain unclear., Objective: In the current study, we investigated the source and the molecular mechanism of estrogen production in feminizing ACC., Methods: A total of 46 consecutive patients with a diagnosis of ACC were recruited in our center. We described the clinical characteristics and steroid hormone profile of the peripheral and adrenal vein. In both feminizing ACC tissues and cell lines, we investigated the expression of steroidogenic biomarkers and β-catenin pathways by quantitative PCR and immunohistochemical staining. The effects of Wnt inhibitors on steroidogenesis were also analyzed in NCI-H295R cells., Results: A total of 46 consecutive patients with ACC were analyzed, and 25 had functional ACC. Four patients received a diagnosis of feminizing ACC based on feminizing manifestations, high levels of estradiol that were normalized after surgery, and histological Weiss score. Gonadal steroidogenic biomarkers including CYP19A1, HSD17B3, and LHCGR were markedly elevated in the feminizing ACC tissues. Adrenal vein sampling and liquid chromatography-tandem mass spectrometry suggested high CYP19A1 activity in the adrenal mass. β-catenin expression was also elevated. When treated with niclosamide and PNU-74654, the H295R cell line showed a decrease in β-catenin expression, cell proliferation, and steroid secretion. All steroid hormone enzymes were inhibited, whereas CYP19A1, HSD17B3, and LHCGR mRNA increased., Conclusions: Feminizing ACC can express high levels of CYP19A1, thus ectopically producing estrogens. Wnt pathway activation and dedifferentiation toward common adrenal-gonadal precursor cells may be the underlying mechanisms.

Objective: Thymic neuroendocrine tumor is the second-most prevalent cause of ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), which is a rare disease characterized by ectopic ACTH oversecretion from nonpituitary tumors. However, the genetic abnormalities of thymic neuroendocrine tumors with EAS remain largely unknown. We aim to elucidate the genetic abnormalities and identify the somatic mutations of potential tumor-related genes of thymic neuroendocrine tumors with EAS by whole exome sequencing., Design and Methods: Nine patients with thymic neuroendocrine tumors with EAS who were diagnosed at Shanghai Clinical Center for Endocrine and Metabolic Diseases in Ruijin Hospital between 2002 and 2014 were enrolled. We performed whole exome sequencing on the DNA obtained from thymic neuroendocrine tumors and matched peripheral blood using the Hiseq2000 platform., Results: We identified a total of 137 somatic mutations (median of 15.2 per tumor; range, 1-24) with 129 single-nucleotide mutations (SNVs). The predominant substitution in these mutations was C:G > T:A transition. Approximately 80% of detected mutations resulted in amino acid changes. However, we failed to discover any recurrent mutations in these nine patients. By functional predictions, HRAS, PAK1 and MEN1, previously reported in neuroendocrine tumors, were identified as candidate tumor-related genes associated with thymic neuroendocrine tumors., Conclusions: Using whole exome sequencing, we identified genetic abnormalities in thymic neuroendocrine tumors with EAS. Thereby, this study acts as a further supplement of the genetic features of neuroendocrine tumors. Somatic mutations of three potential tumor-related genes (HRAS, PAK1 and MEN1) might contribute to the tumorigenesis of thymic neuroendocrine tumors with EAS., (© 2017 European Society of Endocrinology.)