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A 56-year-old male patient was diagnosed with a submucosal tumor in the fundus of the stomach. The conventional operation method is endoscopic submucosal dissection. We present a case of rapid tumor resection without employing traditional endoscopic submucosal dissection instruments such as a mucotomy knife and endoscopic injection needle, resulting in substantial cost savings for the patients.

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Climate warming and drying has led to a sharp increase in nitrogen (N) emissions from the boreal peatland soils, but the underlying microbial-mediated mechanism is still unclear. We reviewed the responses of soil N transformation and emission in alpine peatland to temperature increases and water table changes, the interaction between soil anaerobic ammonia oxidation (Anammox) and NO3- dissimilatory reduction processes, and soil N2O production pathways and their contributions. There are several knowledge gaps. First, the amount of N loss in peatlands in alpine areas is seriously underestimated because most studies focused only on soil N2O emissions and ignored the release of N2. Second, the contribution of Anammox process to N2 emissions from peatlands is not quantified. Third, there is a lack of quantification of the relative contributions of Anammox, bacterial denitrification, and fungal co-denitrification processes to N2 loss. Finally, the decoupling mechanism of Anammox and NO3- reduction processes under a warming and drying climate scenario is not clear. Considering aforementioned shortages in previous studies, we proposed the directions and contents for future research. Through building an experimental platform with field warming and water level controlling, combining stable isotope, molecular biology, and metagenomics technology, the magnitude, composition ratio and main controlling factors of N emissions (N2O, NO, and N2) in boreal peatlands should be systematically investigated. The interaction among the main N loss processes in soils as well as the relative contributions of nitrification, anaerobic ammonia oxidation, and denitrification to N2O and N2 productions should be investigated and quantified. Furthermore, the sensitive microbial groups and the coupling between soil N transformations and microbial community succession should be clarified to reveal the microbiological mechanism underlying the responses of soil N turnover process to climate warming and drying.

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BACKGROUND: Dysregulation of vascular homeostasis can induce cardiovascular diseases and increase global mortality rates. Although lineage tracing studies have confirmed the pivotal role of modulated vascular smooth muscle cells (VSMCs) in the progression of pathological vascular remodeling, the underlying mechanisms are still unclear. METHODS: The expression of Tudor-SN was determined in VSMCs of artery stenosis, PDGF-BB-treated VSMCs and atherosclerotic plaque. Loss- and gain-of-function approaches were used to explore the role of Tudor-SN in the modulation of VSMCs phenotype both in vivo and in vitro. RESULTS: In this study, we demonstrate that Tudor-SN expression is significantly elevated in injury-induced arteries, atherosclerotic plaques, and PDGF-BB-stimulated VSMCs. Tudor-SN deficiency attenuates, but overexpression aggravates the synthetic phenotypic switching of VSMCs and pathological vascular remodeling. Loss of Tudor-SN also reduces atherosclerotic plaque formation and increases plaque stability. Mechanistically, PTEN, the major regulator of the MAPK and PI3K-AKT signaling pathways, plays a vital role in Tudor-SN-mediated regulation on proliferation and migration of VSMCs. Tudor-SN facilitates the polyubiquitination and degradation of PTEN via NEDD4-1, thus exacerbating vascular remodeling under pathological conditions. BpV (HOpic), a specific inhibitor of PTEN, not only counteracts the protective effect of Tudor-SN deficiency on proliferation and migration of VSMCs, but also abrogates the negative effect of carotid artery injury-induced vascular remodeling in mice. CONCLUSIONS: Our findings reveal that Tudor-SN deficiency significantly ameliorated pathological vascular remodeling by reducing NEDD4-1-dependent PTEN polyubiquitination, suggesting that Tudor-SN may be a novel target for preventing vascular diseases.

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Background: The microbial signatures in diabetes with pneumonia and the risk factors of severe pneumonia (SP) in diabetic patients are not clear. Our study explored microbial signatures and the association between clinical characteristics and SP then constructed a risk model to find effective biomarkers for predicting pneumonia severity. Methods: Our study was conducted among 273 patients with pneumonia diagnosed and treated in our hospital from January 2018 to May 2021. Bronchoalveolar lavage fluid (BALF) samples and clinical data were collected. Metagenomic sequencing was applied after extracting the DNA from samples. Appropriate statistical methods were used to compare the microbial signatures and clinical characteristics in patients with or without diabetes mellitus (DM). Results: In total, sixty-one pneumonia patients with diabetes and 212 pneumonia patients without diabetes were included. Sixty-six differential microorganisms were found to be associated with SP in diabetic patients. Some microbes correlated with clinical indicators of SP. The prediction model for SP was established and the receiver operating characteristic (ROC) curve demonstrated its accuracy, with the sensitivity and specificity of 0.82 and 0.91, respectively. Conclusions: Some microorganisms affect the severity of pneumonia. We identified the microbial signatures in the lower airways and the association between clinical characteristics and SP. The predictive model was more accurate in predicting SP by combining microbiological indicators and clinical characteristics, which might be beneficial to the early identification and management of patients with SP.

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OBJECTIVES: To explore early diagnostic biological markers for Leigh syndrome caused by the m.8993T>G mutation. METHODS: A retrospective analysis was performed on the clinical data of four children diagnosed with m.8993T>G mutation-related mitochondrial disease at the Children's Hospital of Chongqing Medical University from January 2014 to January 2024. Additionally, a literature review was conducted. RESULTS: All four children had plasma amino acid and acylcarnitine analyses that revealed decreased citrulline levels, and one child was initially identified through neonatal genetic metabolic disease screening. According to the literature review, there were 26 children with mitochondrial disease and hypocitrullinemia caused by the m.8993T>G mutation (including the four children in this study). Among these, 12 children exhibited clinical phenotypes of Leigh syndrome or Leigh-like syndrome, while 18 children were identified with hypocitrullinemia and/or elevated levels of 3-hydroxyisovalerylcarnitine (C5-OH) during neonatal genetic metabolic disease screening. CONCLUSIONS: Hypocitrullinemia may serve as a potential biomarker for the early diagnosis of m.8993T>G mutation-associated Leigh syndrome, detectable as early as during neonatal genetic metabolic disease screening.

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Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.

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Objective: Osteoarticular tuberculosis (OATB) is one of the most common forms of extrapulmonary tuberculosis; however, limited epidemiological data are available on this public health concern worldwide, especially in developing countries. This study aimed to analyze the clinical epidemiology and drug resistance characteristics of OATB cases in Hunan province which located in South-central China. Methods: We retrospectively enrolled OATB patients with Mycobacterium tuberculosis culture positive at Hunan Chest Hospital from January 2013 through March 31, 2022. The multiple demographic, clinical variables and drug susceptibility data of the patients were collected from the hospital's electronic patient records. Descriptive statistical methods, Chi-square test and logistic regression analysis were employed as statistical methods. Results: Of the 269 OATB cases, 197 (73.23%) were males, 206 (76.85%) were farmers; patients' ages ranged from 5 to 85 years, 57 (21.19%) aged at 20-29 years old and 52 (19.33%) aged at 60-69 years old. In terms of the disease, 177 (65.80%) had spinal TB with most occurrence in lumbar vertebrae (26.02%, 70/269), multiple spinal sites (18.96%, 51/269) and thoracic vertebrae (15.24%, 41/269). Outside of the spine, OATB mainly occurred in the lower limb (13.38%, 36/269). In terms of drug resistance, 40 (14.87%) and 72 (26.77%) were resistant to rifampicin (RFP) and isoniazid (INH) respectively; 38 (14.13%) were multi-drug resistant (MDR), and a total of 78 (29.00%) isolates were drug resistant. OATB patients aged 40-49 years old (compared to those aged ≥70 years) and from the west of Hunan province, China (compared to those from the center of Hunan) were at risk for developing RR/MDR (ORs were 5.057 and 4.942, respectively; 95% CIs were 1.009-25.342 and 1.458-16.750, respectively). Conclusion: In South-central China, OATB mainly affected males, farmers and those aged 20-29 and 60-69 years old. Spinal TB is prone to occur in the lumbar and multiple spinal sites. The resistance situation of OATB was serious, and people aged 40-49 years old and patients from the west of Hunan were risk factors of RR/MDR. All these findings will help to improve the prevention, diagnosis and treatment strategies of OATB.

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Objective: To evaluate the efficacy and safety of Apatinib combined with epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) in the treatment of patients with non-small cell lung cancer (NSCLC) and acquired EGFR-TKI resistance. Methods: Clinical records of 106 patients with NSCLC at Shanxi Tumor Hospital of the Chinese Academy of Medical Sciences Cancer Hospital from January 2017 to October 2020, with acquired drug resistance after EGFR-TKI treatment were retrospectively analyzed. Among them, 52 patients received Apatinib combined with EGFR-TKI (Apatinib group), and 54 patients received a standard chemotherapy (pemetrexed combined with platinum) (chemotherapy group). Clinical efficacy indicators, follow-up results, and adverse reactions in both groups were compared. Results: There was no significant difference in the objective response rate and disease control rate between the two groups (P>0.05). The progression free survival (PFS) of the Apatinib group was significantly longer than that of the chemotherapy group (10.5 months vs. 5.7 months; P<0.05). There was no significant difference in adverse reactions between the two groups (P>0.05). Conclusions: Compared with standard chemotherapy, Apatinib combined with EGFR-TKI has the same efficacy in treating NSCLC patients with EGFR-TKI resistance, and was associated with longer PFS with no significant increase in adverse reactions.

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BACKGROUND: Pre-dialysis nephrology care and kidney replacement therapy (KRT)-directed education (KDE) are essential for incident home dialysis use. However, there are substantial disparities in these care parameters among patients with advanced CKD. The impact of these disparities on home dialysis underuse has not been examined. METHODS: We analyzed the 2021 US Renal Database System to identify all adult kidney failure patients with over six months of pre-dialysis Medicare coverage initiating their first-ever dialysis between 2010 and 2019. We used a mediation analysis to dissect the attributable influence of disparities in pre-dialysis nephrology care and KDE on incident home dialysis use. Additionally, we conducted sensitivity analyses using graded levels of mediators and sustained impact on home dialysis outcomes. RESULTS: We identified 464,310 Medicare recipients: 428,301 using incenter hemodialysis and 35,416 using home dialysis as their first-ever dialysis modality during the study period. Compared to non-Hispanic White patients (n=294,914), adjusted odds ratio (95% confidence intervals) for receiving pre-dialysis nephrology care, KDE service, and incident home dialysis were 0.62(0.61, 0.64), 0.58(0.52, 0.63) and 0.76(0.73, 0.79) respectively among Hispanic individuals (n=49,734), and 0.74(0.73, 0.76), 0.84(0.79, 0.89), and 0.63(95%CI:0.61, 0.65) respectively among Black individuals (n=98,992). Mediation analyses showed that compared to non-Hispanic White individuals, lack of nephrology care explained 30% and 14% of incident home dialysis underuse among Hispanic and Black individuals, respectively (p<0.001). Sensitivity analyses using a longer duration of nephrology care and KDE services and the sustained impact on home dialysis underuse through the first-year post-kidney failure showed congruent and consolidating findings. CONCLUSIONS: Disparities in pre-dialysis nephrology care were significantly associated with lower home dialysis among Hispanic and Black individuals.

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Background: Recent studies showed increased mortality risks after hot nights, but their effect on hospitalizations, especially in vulnerable populations, remains under-studied. Methods: Daily hospitalization, meteorological (including hourly), and air pollution data were collected for the hot seasons (May-October) of 2000-19 in Hong Kong. We derived three hot-night metrics: HNday28 °C, daily minimum temperature ≥28 °C, the governmental definition of hot nights; HNe, hot night excess calculated by summing heat excess of hourly temperatures above 28 °C at night; and HNday90th, hot nights classified using the 90th percentile HNe (17.7 °C⋅h) as a cutoff. We fitted time-series regression with distributed lag nonlinear models to examine the associations of hot-night metrics with various hospitalizations. Findings: During the 3680 study days, 5,002,114 non-cancer non-external (NCNE) hospitalizations were recorded. Half (1874) of the days experienced excess nighttime heat (HNe>0) with a mean (SD) of 8.0 (6.8) °C⋅h; 499 and 187 hot nights were identified by HNday28 °C and HNday90th, respectively. Extreme HNe (99th percentile vs 0 °C⋅h) was significantly associated with increased NCNE hospitalizations over lag 0-4 days by 3.1% [95% confidence interval: 1.5%, 4.8%] overall, with enhanced effects in elderly (5.3% [3.2%, 7.4%]), low-SES individuals (5.3% [2.8%, 8.0%]), and circulatory admissions (3.4% [0.2%, 6.8%]). HNday90th, reflecting extreme HNe, better identified hazardous hot nights than the official HNday28 °C. Interpretation: Excessive nighttime heat is significantly associated with increased hospitalizations, particularly affecting the elderly and socioeconomically disadvantaged individuals. Nighttime heat intensity should be incorporated in defining hot nights with public health relevance. Funding: British Heart Foundation.

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Knowledge distillation (KD) has shown great potential for transferring knowledge from a complex teacher model to a simple student model in which the heavy learning task can be accomplished efficiently and without losing too much prediction accuracy. Recently, many attempts have been made by applying the KD mechanism to graph representation learning models such as graph neural networks (GNNs) to accelerate the model's inference speed via student models. However, many existing KD-based GNNs utilize multilayer perceptron (MLP) as a universal approximator in the student model to imitate the teacher model's process without considering the graph knowledge from the teacher model. In this work, we provide a KD-based framework on multiscaled GNNs, known as graph framelet, and prove that by adequately utilizing the graph knowledge in a multiscaled manner provided by graph framelet decomposition, the student model is capable of adapting both homophilic and heterophilic graphs and has the potential of alleviating the oversquashing issue with a simple yet effective graph surgery. Furthermore, we show how the graph knowledge supplied by the teacher is learned and digested by the student model via both algebra and geometry. Comprehensive experiments show that our proposed model can generate learning accuracy identical to or even surpass the teacher model while maintaining the high speed of inference.

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OBJECTIVE: To study body mass index (BMI) changes among individuals aged 18-99 years with and without SARS-CoV-2 infection. SUBJECTS/METHODS: Using real-world data from the OneFlorida+ Clinical Research Network of the National Patient-Centered Clinical Research Network, we compared changes over time in BMI in an Exposed cohort (positive SARS-CoV-2 test between March 2020-January 2022), to a contemporary Unexposed cohort (negative SARS-CoV-2 tests), and an age/sex-matched Historical control cohort (March 2018-January 2020). BMI (kg/m2) was retrieved from objective measures of height and weight in electronic health records. We used target trial approaches to estimate BMI at start of follow-up and change per 100 days of follow-up for Unexposed and Historical cohorts relative to the Exposed cohort by categories of sex, race & ethnicity, age, and hospitalization status. RESULTS: The study sample consisted of 249,743 participants (19.2% Exposed, 61.5% Unexposed, 19.3% Historical cohort) of whom 62% were women, 21.5% Non-Hispanic Black, 21.4% Hispanic and 5.6% Non-Hispanic other and had an average age of 51.9 years (SD: 18.9). At start of follow-up, relative to the Unexposed cohort (mean BMI: 29.3 kg/m2 [95% CI: 29.1, 29.4]), the Exposed (0.07 kg/m2 [95% CI; 0.01, 0.12]) had higher mean BMI and Historical controls (-0.20 kg/m2 [95% CI; -0.25, -0.15]) had lower mean BMI. Over 100 days, BMI did not change (0 kg/m2 [95% CI: -0.03, 0.03]) for the Exposed cohort, decreased (-0.04 kg/m2 [95% CI; -0.05, -0.02]) for the Unexposed cohort and increased (0.03 kg/m2 [95% CI; 0.01, 0.04]) for the Historical cohort. Observed differences in BMI at start of follow-up and over 100 days were consistent between Unexposed and Exposed cohorts for most subgroups, except at start of follow-up period among Males and those 65 years or older who had lower BMI among Exposed. CONCLUSIONS: In a diverse real-world cohort of adults, mean BMI of those with and without SARS-CoV2 infection varied in their trajectories. The mechanisms and implications of weight retention following SARS-CoV-2 infection remain unclear.

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IMPORTANCE: Diabetes increases the risk of Parkinson disease (PD). Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new glucose-lowering therapeutic class, have shown neuroprotective effects in mechanistic studies. However, the association between SGLT2 inhibitors and PD risk in real-world populations with type 2 diabetes (T2D) remains unclear. OBJECTIVE: The aim was to assess the association between SGLT2 inhibitors and the risk of PD in older populations with T2D. DESIGN, SETTING AND PARTICIPANTS: This retrospective cohort analysis used Medicare claims data from 2016 to 2020 to identify fee-for-service beneficiaries ≥65 years diagnosed with T2D and without pre-existing PD. EXPOSURES: The initiation of an SGLT2 inhibitor was compared with that of a dipeptidyl peptidase-4 (DPP4) inhibitor. MAIN OUTCOMES AND MEASURES: The outcome was the first incident PD ever since the date initiating either an SGLT2 inhibitor or a DPP4 inhibitor. We employed a 1:1 propensity score matching to balance the baseline covariates between treatment groups, including sociodemographics, comorbidities and co-medications. We applied Cox regression models to assess the effect of SGLT2 inhibitors versus DPP4 inhibitors on incident PD. RESULTS: Of 89 330 eligible Medicare beneficiaries (mean age: 75 ± 7 years, 52% women), 0.6% (n = 537) had incident PD over the follow-up. After 1:1 propensity matching, the PD incidence was 2.5 and 3.5 events per 1000 person-years in the SGLT2 inhibitor group and DPP4 inhibitor group, respectively. The SGLT2 inhibitor group was associated with a significantly lower risk of incident PD than the DPP4 inhibitor group (hazard ratio: 0.70 [95% confidence interval: 0.55-0.89]). There is a potential trend that the risk reduction in incident PD was profound in non-Hispanic Black individuals and insulin users. CONCLUSION AND RELEVANCE: Compared to DPP4 inhibitors, SGLT2 inhibitors were associated with a significantly lower risk of incident PD in older populations with T2D.

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The goal of our research is to elucidate and better assess placental function in rats with preeclampsia through an innovative application of ultrasound-based radiomics. Using a rat model induced with L-NAME, we carefully investigated placental dysfunction via microstructural analysis and immunoprotein level assessment. Employing the Boruta feature selection method on ultrasound images facilitated the identification of crucial features, consequently enabling the development of a robust model for classifying placental dysfunction. Our study included 12 pregnant rats, and thorough placental evaluations were conducted on 160 fetal rats. Distinct alterations in placental microstructure and angiogenic factor expression were evident in rats with preeclampsia. Leveraging high-throughput mining of quantitative image features, we extracted 558 radiomic features, which were subsequently used to construct an impressive evaluation model with an area under the receiver operating curve (AUC) of 0.95. This model also exhibited a remarkable sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 88.7%, 91.5%, 90.2%, 90.4%, and 90.0%, respectively. Our findings highlight the ability of ultrasound-based radiomics to detect abnormal placental features, demonstrating its potential for evaluating both normative and impaired placental function with high precision and reliability.

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Plastids are essential, semi-autonomous organelles in plants that carry out a multitude of functions during development. Plastids existing in different subtypes are derived from proplastids progenitors and interconvert in response to environmental and growth cues. Most efforts focus on the differentiation from proplastid to other forms. However, the studies of proplastid development are insufficient and whether proplastid biogenesis affects plant growth is yet to be determined. Arabidopsis TIC236, a translocon component at the inner membrane of the chloroplast envelope, is critical for importing chloroplast-targeted preproteins and chloroplast division. In this study, we uncovered the fundamental influence of proplastid biogenesis on embryo development by exploring the function of TIC236 during embryogenesis. Widespread and strong expression of TIC236 was observed in leaves and embryos. The null mutant tic236 had an embryo-lethal phenotype, with cell division in the mutant embryos delayed starting at the octant stage and arrested at the globular stage. Transmission electron microscopy revealed enlarged proplastids with an aberrant inner structure at the dermatogen and globular stages that ultimately did not differentiate into chloroplasts. Additionally, the fluorescence signal distribution patterns of tic236 embryos carrying the pDR5rev::3xVENUS-N7, pPIN1::PIN1-GFP, pWOX5::GFP, and pSCR::H2B-YFP reporter systems were altered. Together, we provide genetic evidence supporting proplastid biogenesis plays a vital role in embryo development and TIC236 is identified as an indispensable player, ensuring normal proplastid development.

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Objective: This study aimed to investigate the value of a CT-enhanced scanning radiomics nomogram in distinguishing between early hepatic abscess (EHA) and intrahepatic cholangiocarcinoma (ICC) and to validate its diagnostic efficacy. Materials and Methods: Clinical and imaging data on 112 patients diagnosed with EHA and ICC who underwent double-phase CT-enhanced scanning at our hospital were collected. The contours of the lesions were delineated layer by layer across the three phases of CT scanning and enhancement using 3D Slicer software to define the region of interest (ROI). Subsequently, the contours were merged into 3D models, and radiomics features were extracted using the Radiomics plug-in. The data were randomly divided into training (n = 78) and validation (n = 34) cohorts at a 7:3 ratio, using the R programming language. Standardization was performed using the Z-score method, and LASSO regression was used to select the best λ-value for screening variables, which were then used to establish prediction models. The rad-score was calculated using the best radiomics model, and a joint model was constructed based on the rad-score and clinical scores. A nomogram was developed based on the joint model. The diagnostic efficacy of the models for distinguishing ICC and EHA was assessed using receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses. Calibration curves were used to evaluate the reliability and accuracy of the nomograms, while decision curves and clinical impact curves were utilized to assess their clinical value. Results: Compared with the ICC group, significant differences were observed in clinical data and imaging characteristics in the EHA group, including age, centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement (p < 0.05). Logistic regression analysis identified centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement as independent influencing factors. Three, five, and four radiomics features were retained in the scanning, arterial, and venous phases, respectively. Single-phase models were constructed, with the radiomics model from the arterial phase demonstrating the best diagnostic efficacy. The rad-score was calculated using the arterial-phase radiomics model, and nomograms were drawn in conjunction with the clinical model. The nomogram based on the combined model exhibited the highest differential diagnostic efficacy between EHA and ICC (training cohort: AUC of 0.972; validation cohort: AUC of 0.868). The calibration curves indicated good agreement between the predicted and pathological results, while decision curves and clinical impact curves demonstrated higher clinical utility of the nomograms. Conclusion: The CT-enhanced scanning radiomics nomogram demonstrates high clinical value in distinguishing between EHA and ICC, thereby enhancing the accuracy of preoperative diagnosis.

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BACKGROUND: Adrenal-origin and peripheral tissue-transformed 11-oxygenated androgens are recognized as significant androgens. However, our current understanding of the synthesis of 11-oxygenated androgens, including the organs and cell types involved, remains limited. METHODS: We performed comprehensive analyses on an extensive dataset of normal human tissues, which included bulk RNA data from 30 tissues, single-cell RNA sequencing (scRNA) data from 16 tissues and proteomics data from 29 tissues, to characterize the expression profiles of enzyme-encoding genes. To validate the findings, immunohistochemical and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques were employed. RESULTS: Our investigation revealed that the gene expression levels of the enzymes HSD11B2 and AKR1C3 were notably elevated in the kidney and intestines. Intriguingly, within these organs, we observed an increasing trend in enzyme expression with age in women, while a decreasing trend was apparent in men. scRNA analysis revealed that HSD11B2 was predominantly expressed in collecting duct principal cells in the kidney, while AKR1C3 was primarily expressed in the proximal tubules. Intriguingly, nearly all epithelial cells in the intestine expressed these key enzymes. Further analysis using LC-MS/MS revealed that the kidney exhibited the highest levels of 11-ketoandrostenedione (11KA4) and 11-ketotestosterone (11KT) among the seven tissues examined, and substantial synthesis of 11KA4 and 11KT was also observed in the intestine. Finally, we developed the TransMap website (http://gxmujyzmolab.cn:16245/TransMap/) to provide comprehensive visualization of all currently available transcriptome data. CONCLUSION: This study offers an overarching perspective on tracing the synthesis of 11-oxygenated androgens in peripheral tissues, thereby providing valuable insights into the potential role of these androgens in humans.

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Introduction: Diuretics are the mainstay of maintaining and restoring euvolemia in the management of heart failure. Loop diuretics are often preferred, however, combination diuretic therapy (CDT) with a thiazide diuretic is often used to overcome diuretic resistance and increase diuretic effect. We performed an analysis of the GUIDE-IT study to assess all-cause mortality and time to first hospitalizations in patients necessitating CDT. Methods: Patients from the GUIDE-IT dataset were stratified by their requirement for CDT with a thiazide to achieve euvolemia. A total of 894 patients were analyzed, 733 of which were treated with loop diuretics alone vs 161 used either chlorothiazide or metolazone in addition to loop diuretics. Kaplan-Meir curves were derived with log-rank p-values to evaluate for differences between the groups. Results: There was no significant difference in all-cause mortality regardless of CDT utilization status (mean survival of 612.704 days vs 603.326 days, p = 0.083). On subgroup analysis, there was no significant difference in all-cause mortality amongst those using loop diuretics compared to CDT in the BNP-guided therapy group, (mean survival time 576.385 days vs 620.585 days, p = 0.0523), nor the control group (614.1 days vs 588.9 days; p = 0.5728). Time to first hospitalization was reduced in all using CDT compared to loop diuretics alone (280.5 days vs 407.2 days, p < 0.0001). On subgroup analysis, both the BNP-guided group as well as the control group had reduced time to first hospitalization in the CDT group compared to those who did not require CDT (BNP group: 287.503 days vs 402.475 days, p ≤0.0001; control group 248.698 days vs 399.035 days, p = 0.0009). Conclusion: Use of CDT is associated with earlier time to hospitalization, though no association was identified with increased all-cause mortality. Further prospective studies are likely needed to determine the true risk and benefits of combination diuretic therapy.