Independent and joint relationships of cardiorespiratory fitness and body mass index with liver fat content.

AIMS: To investigate the relationship between cardiorespiratory fitness (CRF) and liver fat content (LFC) in community-based participants and highlight their relationship in people with different body mass indices (BMIs). MATERIALS AND METHODS: Using UK Biobank data, CRF was estimated with bicycle ergometer fitness testing and was evaluated based on physical work capacity at 75% maximum heart rate (PWC75%). LFC was quantified through liver proton density fat fraction (PDFF) on magnetic resonance imaging. Multivariate linear regression models were used to analyse the associations of CRF and BMI with absolute reduction and percentage change in PDFF (%). RESULTS: In total, 5765 participants with a mean age of 55.57 years and a median (range) follow-up of 10.7 (4.0-17.7) years were included. Compared with the lowest PWC75% tertile, the absolute reduction and percentage change in PDFF in the highest PWC75% tertile were -0.450 (95% confidence interval [CI] -0.699 to -0.192) and -4.152 (95% CI -6.044 to -2.104), respectively. These associations were independent of BMI, and individuals with obesity and normal weight had the largest absolute reduction and percentage change in LFC, respectively (p for interaction <0.001). Joint analysis showed that PWC75% and BMI had a negative dose-response relationship with PDFF. These associations were consistent in different sex and age subgroups (p for interaction >0.05). CONCLUSIONS: There was a significant negative association between CRF and LFC, and this association was independent of BMI. The results of this study strongly recommend improving CRF to mitigate LFC.

Lactucopicrin promotes fatty acid ß-oxidation and attenuates lipid accumulation through adenosine monophosphate-activated protein kinase activation in free fatty acid-induced human hepatoblastoma cancer cells.

With its annually increasing prevalence, non-alcoholic fatty liver disease (NAFLD) has become a serious threat to people's life and health. After a preliminary research, we found that Lactucopicrin has pharmacological effects, such as lowering blood lipids and protecting the liver. Further research showed its significant activation for fatty acid ß-oxidase hydroxyacyl-coenzyme A (CoA) dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA), so we hypothesized that Lactucopicrin could ameliorate lipid accumulation in hepatocytes by promoting fatty acid ß-oxidation. In this study, free fatty acid (FFA)-induced human hepatoblastoma cancer cells (HepG2) were used to establish an in vitro NAFLD model to investigate the molecular basis of Lactucopicrin in regulating lipid metabolism. Staining with Oil red O and measurements of triglyceride (TG) content, fatty acid ß-oxidase (FaßO) activity, reactive oxygen species (ROS) content, mitochondrial membrane potential, and adenosine triphosphate (ATP) content were used to assess the extent to which Lactucopicrin ameliorates lipid accumulation and promotes fatty acid ß-oxidation. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot methods were used to explore the regulatory effects of Lactucopicrin on factors related to fatty acid ß-oxidation. Results showed that Lactucopicrin downregulated phosphorylated mammalian target of rapamycin (P-mTOR) by activating the adenosine monophosphate-activated protein kinase (AMPK) pathway and upregulated the messenger RNA (mRNA) and protein expression levels of coactivators (peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)), transcription factors (peroxisome proliferator-activated receptor α (PPARα) and peroxisome proliferator-activated receptor γ (PPARγ)), and oxidative factors (carnitine palmitoyltransferase 1A (CPT1A) and HADHA). This phenomenon resulted in a significant increase in FaßO activity, ATP content, and JC-1 and a significant decrease in ROS level, TG content, and intracellular lipid droplets. With the addition of Dorsomorphin, all the effects of Lactucopicrin intervention were suppressed. In summary, Lactucopicrin promotes fatty acid ß-oxidation by activating the AMPK pathway, thereby ameliorating FFA-induced intracellular lipid accumulation in HepG2 cells.

Natural killer cells promote neutrophil extracellular traps and restrain macular degeneration in mice.

Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Although it is known that nvAMD is associated with focal inflammation, understanding of the precise immune components governing this process remains limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization (CNV) lesions in patients with nvAMD and in mouse models. Olink proteomic analysis and single-cell RNA sequencing combined with knockout studies demonstrated the involvement of C-C chemokine receptor 5 (CCR5) in NK cell recruitment and extravasation at the CNV sites of mice. Depletion of NK cells or inhibition of activating receptor NK group 2, member D (NKG2D) inhibited the formation of neutrophil extracellular traps, increased vascular leakage, and exacerbated pathological angiogenesis, indicating that NK cells restrain pathogenesis in this mouse model. Age is the strongest risk factor for AMD, and we show that NK cells from aged human donors exhibited a less cytotoxic phenotype. NK cells from old mice exhibited compromised protective effects in the CNV mouse model. In addition, interleukin-2 complex-mediated expansion of NK cells improved CNV formation in mice. Collectively, our study highlights NK cells as a potential therapeutic target for patients with nvAMD.

Advances in diffuse glioma assessment: preoperative and postoperative applications of chemical exchange saturation transfer.

Chemical Exchange Saturation Transfer (CEST) is a technique that uses specific off-resonance saturation pulses to pre-saturate targeted substances. This process influences the signal intensity of free water, thereby indirectly providing information about the pre-saturated substance. Among the clinical applications of CEST, Amide Proton Transfer (APT) is currently the most well-established. APT can be utilized for the preoperative grading of gliomas. Tumors with higher APTw signals generally indicate a higher likelihood of malignancy. In predicting preoperative molecular typing, APTw values are typically lower in tumors with favorable molecular phenotypes, such as isocitrate dehydrogenase (IDH) mutations, compared to IDH wild-type tumors. For differential diagnosis, the average APTw values of meningiomas are significantly lower than those of high-grade gliomas. Various APTw measurement indices assist in distinguishing central nervous system lesions with similar imaging features, such as progressive multifocal leukoencephalopathy, central nervous system lymphoma, solitary brain metastases, and glioblastoma. Regarding prognosis, APT effectively differentiates between tumor recurrence and treatment effects, and also possesses predictive capabilities for overall survival (OS) and progression-free survival (PFS).

Analyzing reciprocity dynamics in supply chains of public goods: a stochastic evolutionary game approach.

To start with an infinitely repeated game of supply chains of public goods, a stout reciprocity mechanism is introduced into income games to build a matric dynamic equation. The conventional evolutionary game method is employed to propose a model called the evolutionary game for the cooperative strategy of both the manufacturer and the seller groups in the supply chain of public goods. Also, white Gaussian noise (WGN) is added to reflect random interference in the evolution process. Then, a stochastic dynamic system is established, and Ito's differential equation is used to analyze both sides' strategy evolution in a game, interpret changes in system stability when random disturbance is added, and finally test the influence of different situations on the system stability by running a numerical simulation. The research shows that the stronger the reciprocity coefficient is, and the system is subjected to random interference, the greater the strategy choice change in players' decision-making procedures when the repeated game of public goods is conducted.

Circulating white blood cell traits and prolonged night shifts: a cross-sectional study based on nurses in Guangxi.

This study aimed to elucidate the effects of long day and night shifts on immune cells in a population of nurses. This cross-sectional study in December 2019 was based on a group of nurses. 1568 physically healthy caregivers were included, including 1540 women and 28 men. 1093 nurses had long-term shift work (working in a rotating system for > 1 year). The receiver operating characteristic curve, Ensemble Learning, and Logistic regression analyses were used to evaluate factors related to long-term shift work. The night shift group nurses had significantly higher MPV, PLCR, and WBC and significantly lower BASO%, ELR, MCHC, PLR, RDW-CV, and RDW-SD (P < 0.01). ROC curves showed that WBC, PLR, ELR, RDW_CV, and BASO% were more related to the night shift. Ensemble Learning, combined with the LASSO model, finally filtered out three indicators of night shifts related to ELR, WBC, and RDW_SD. Finally, logistic regression analysis showed that the nurses' night shift situation greatly influenced two peripheral blood ELR and WBC indicators (ELR: log (OR) = - 3.9, 95% CI: - 5.8- - 2.0; WBC: log (OR) = 0.25, 95% CI: 0.18-0.32). Finally, we showed that, unlike WBC, the relative riskiness of ELR showed opposite results among junior nurses and middle-senior nurses (log (OR) 6.5 (95% CI: 1.2, 13) and - 7.1 (95% CI: - 10, - 3.8), respectively). Our study found that prolonged night shifts were associated with abnormal WBC and ELR, but after strict age matching, WBC remained significantly different. These findings help to confirm that COVID-19 and tumorigenesis (e.g., breast cancer) are significantly associated with circadian rhythm disruption. However, more detailed studies are needed to confirm this.

Path analysis for controlling climate change in global aviation.

The aviation industry's emissions have had a significant impact on global climate change. This study focuses on carbon emission trading schemes, sustainable aviation fuels (SAFs), and hydrogen energy, as vital means for the aviation industry to reduce emissions. To evaluate the climate effects of global routes under four scenarios (24 sub-scenarios) until 2100, this study proposes the Aviation-FAIR (Aviation-Finite Amplitude Impulse Response) method. The findings reveal that while CO2 emissions and concentrations are significant, other emissions, such as N2O and CH4, have a greater effective radiative forcing (ERF) and contribute significantly to climate change. Moreover, SAFs are more effective in mitigating airline pollutant emissions than relying solely on carbon trading schemes. The effectiveness of hydrogen fuel cells may be hindered by technical limitations compared to hydrogen turbine engines. The findings of this study provide reference for the global aviation industry to adopt emission reduction measures.

Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach.

Mulberry is a common crop rich in flavonoids, and its leaves (ML), fruits (M), and branches (Ramulus Mori, RM) have medicinal value. In the present study, a total of 118 flavonoid metabolites (47 flavone, 23 flavonol, 16 flavonoid, 8 anthocyanins, 8 isoflavone, 14 flavanone, and 2 proanthocyanidins) and 12 polyphenols were identified by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. The most abundant in ML were 8-C-hexosyl-hesperetin O-hexoside and astragalin, the most abundant in M were 8-C-hexosyl-hesperetin O-hexoside and naringenin, and the most abundant in RM were cyanidin 3-O-galactoside and gallocatechin-gallocatechin. The total flavonoid compositions of ML and RM were essentially the same, but the contents of flavonoid metabolite in more than half of them were higher than those in M. Compared with ML, the contents of flavone and flavonoid in RM and M were generally down-regulated. Each tissue part had a unique flavonoid, which could be used as a marker to distinguish different tissue parts. In this study, the differences between flavonoid metabolite among RM, ML, and M were studied, which provided a theoretical basis for making full use of mulberry resources.

Conceptual-level disgust conditioning in contamination-based obsessive-compulsive disorder.

Pavlovian fear conditioning and extinction represent learning mechanisms underlying exposure-based interventions. While increasing evidence indicates a pivotal role of disgust in the development of contamination-based obsessive-compulsive disorder (C-OCD), dysregulations in conditioned disgust acquisition and maintenance, in particular driven by higher-order conceptual processes, have not been examined. Here, we address this gap by exposing individuals with high (HCC, n = 41) or low (LCC, n = 41) contamination concern to a conceptual-level disgust conditioning and extinction paradigm. Conditioned stimuli (CS+) were images from one conceptual category partially reinforced by unconditioned disgust-eliciting stimuli (US), while images from another category served as non-reinforced conditioned stimuli (CS-). Skin conductance responses (SCRs), US expectancy and CS valence ratings served as primary outcomes to quantify conditioned disgust responses. Relative to LCC, HCC individuals exhibited increased US expectancy and CS+ disgust experience, but comparable SCR levels following disgust acquisition. Despite a decrease in conditioned responses from the acquisition phase to the extinction phase, both groups did not fully extinguish the learned disgust. Importantly, the extinction resilience of acquired disgust was more pronounced in HCC individuals. Together, our findings suggest that individuals with high self-reported contamination concern exhibit increased disgust acquisition and resistance to extinction. The findings provide preliminary evidence on how dysregulated disgust learning mechanism across semantically related concepts may contribute to C-OCD.

Antibody Production and Immunoassay Development for Authenticating Chlorpheniramine Maleate Adulteration in Herbal Tea.

Chlorphenamine maleate is a prohibited additive found in herbal teas and health foods. Excessive intake of this substance can result in adverse health effects. In this study, two novel haptens, PEM and bepotastine (PB1), mimicking chlorphenamine maleate structure were designed and synthesized based on molecular simulation for developing two corresponding polyclonal antibodies (PEM-Ab and PB1-Ab), respectively. Afterward, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was developed to quickly and accurately detect chlorphenamine maleate in herbal teas using PB1-Ab, which has a high sensitivity and specificity. For chlorphenamine maleate, the half-maximal inhibitory concentration (IC50) and limit of detection (LOD) of PB1-Ab under ideal circumstances were found to be 1.18 µg/L and 0.07 µg/L, respectively. Besides, an environmentally friendly sample pre-treatment strategy was employed that allowed easy and effective elimination of complex matrices. The ic-ELISA method observed the average recovery rate from 87.7% to 94.0% with the variance coefficient (CV) ranging from 2.2% to 9.4%. Additionally, the identification of 25 commercially available herbal teas using liquid chromatography-tandem mass spectrometry (LC-MS/MS) further confirmed the validity of our detection. The results of the two methods are consistent. Overall, the proposed ic-ELISA could be an ultrasensitive and reliable method for chlorphenamine maleate adulterated in foods or exposure to the environment.

Sleep deprivation increases the generalization of perceptual and concept-based fear: An fNIRS study.

Insufficient sleep can initiate or exacerbate anxiety by triggering excessive fear generalization. In this study, a de novo paradigm was developed and used to examine the neural mechanisms governing the effects of sleep deprivation on processing perceptual and concept-based fear generalizations. A between-subject design was adopted, wherein a control group (who had a typical night's sleep) and a one-night sleep deprivation group completed a fear acquisition task at 9:00 PM on the first day and underwent a generalization test the following morning at 7:00 AM. In the fear acquisition task, navy blue and olive green were used as perceptual cues (P+ and P-, respectively), while animals and furniture items were used as conceptual cues (C+ and C-, respectively). Generalization was tested for four novel generalized categories (C+P+, C+P-, C-P+, and C-P-). Shock expectancy ratings, skin conductance responses, and functional near-infrared spectroscopy were recorded during the fear acquisition and generalization processes. Compared with the group who had a typical night's sleep, the sleep deprived group showed higher shock expectancy ratings (especially for P+ and C-), increased oxygenated hemoglobin in the dorsolateral prefrontal cortex, and increased activation in the triangular inferior frontal gyrus during the generalization test. These findings suggest that sleep deprivation increases the generalization of threat memories, thus providing insights into the overgeneralization characteristics of anxiety and fear-related disorders.

General hapten skeleton motivated duplex-immunoassay for emergent bisoxatin adulterants in slimming foods.

Adulterating hazardous bisoxatin (BSO) and bisoxatin acetate (BSOA) in slimming foods poses a threat to public health. A rapid synchronous detection method is urgently needed. Herein, the precise design of four novel haptens based on the general skeleton of BSO and BSOA was driven by computer-chemical visualization strategy, which was used to raise monoclonal antibody (mAb) toward both target compounds. The generated mAb 1F1 recognized BSO and BSOA with maximal half-inhibitory concentration (IC50) of 0.26 and 16.85 ng/mL, respectively. The molecular mechanism governing the duplex-recognition of mAb was elucidated by homology modeling and molecular docking. Finally, an immunochromatography (ICA) was developed for identifying BSO and BSOA, demonstrating a detection capability for screening (CCß) estimated to be 10-500 ng/g in candy tablets, jellies, and oral liquids. This study provides a robust approach for determining adulteration in food and offers insights into hapten design to improve antibody recognition spectrum.

Prognostic effect of triglyceride glucose-related parameters on all-cause and cardiovascular mortality in the United States adults with metabolic dysfunction-associated steatotic liver disease.

BACKGROUNDS: Insulin resistance (IR) plays a vital role in the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether triglyceride-glucose (TyG) related parameters, which serve as useful biomarkers to assess IR, have prognostic effects on mortality outcomes of MASLD. METHODS: Participants in the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018 years were included. TyG and its related parameters [TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR)] were calculated. Kaplan-Meier curves, Cox regression analysis, and restricted cubic splines (RCS) were conducted to evaluate the association between TyG-related indices with the all-cause and cardiovascular mortality of adults with MASLD. The concordance index (C-index) was used to evaluate the prediction accuracy of TyG-related indices. RESULTS: A total of 8208 adults (4209 men and 3999 women, median age 49.00 years) with MASLD were included in this study. Multivariate-adjusted Cox regression analysis revealed that high quartile levels of TyG-related indices were significantly associated with the all-cause mortality of participants with MASLD [TyGadjusted hazard ratio (aHR) = 1.25, 95% confidence interval (CI) 1.05-1.50, P = 0.014; TyG-WCaHR for all-cause mortality = 1.28, 95% CI 1.07-1.52, P = 0.006; TyG-WHtRaHR for all-cause mortality = 1.50, 95% CI 1.25-1.80, P < 0.001; TyG-WCaHR for cardiovascular mortality = 1.81, 95% CI 1.28-2.55, P = 0.001; TyG-WHtRaHR for cardiovascular mortality = 2.22, 95% CI 1.55-3.17, P < 0.001]. The C-index of TyG-related indices for predicting all-cause mortality was 0.563 for the TyG index, 0.579 for the TyG-WC index, and 0.585 for the TyG-WHtR index, respectively. Regarding cardiovascular mortality, the C-index was 0.561 for the TyG index, 0.607 for the TyG-WC index, and 0.615 for the TyG-WHtR index, respectively. Nonlinear trends were observed between TyG and TyG-WC indices with all-cause mortality of MASLD (P < 0.001 and = 0.012, respectively). A non-linear relationship was observed between the TyG index and cardiovascular mortality of MASLD (P = 0.025). Subgroup analysis suggested that adults aged < 65 years old and those without comorbidities were more sensitive to the mortality prediction of TyG-related indices. CONCLUSION: Findings of this study highlight the predictive value of TyG-related indices, especially the TyG-WHtR index, in the mortality outcomes of adults with MASLD. TyG-related indices would be surrogate biomarkers for the clinical management of MASLD.

Epitope-Shared Hapten Enhancing Antibody Polyreactivity for Simultaneous Immunochromatography of Oxyphenisatin Adulterants.

Given the significant threat posed by oxyphenisatin adulterants (OPHs) in weight-loss foods, simultaneous analysis of the OPHs is necessary. Herein, four novel haptens based on the general epitope shared among the OPHs were raised by computer-aided chemical modeling prediction, with the expectation of eliciting antibody responses targeting three of the OPHs. One obtained monoclonal antibody (mAb) showed maximal half-inhibitory concentration (IC50) of 0.40-12.11 ng/mL for OPHs. The key interaction forces responsible for the corecognition of the OPHs were revealed by the intrinsic molecular mechanism. The developed immunochromatography (ICA) indicated a detection capability for screening (CCß) for OPHs estimated to be 5-600 ng/g in jelly, candy tablets, and oral liquid. Furthermore, the analysis of 15 real samples by our method showed a good correlation with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Our research not only presented a rapid approach for identifying OPHs adulteration but also proposed an effective hapten prediction strategy to enhance antibody polyreactivity.

Correlation between serum uric acid level and atrial fibrillation in patients with hyperthyroidism on medical data analysis context of IoT.

BACKGROUND: Dysfunctions in metabolism and endocrine systems are outcomes of disruptions in human physiological processes, often leading to disease onset. External factors can hinder the human body's innate capacity for self-regulation and healing, particularly when immune responses are compromised, allowing these factors to interfere with normal bodily functions directly. OBJECTIVE: To explore the effect of uric acid expression water in blood on the occurrence of atrial fibrillation in patients with hyperthyroidism, the expression level of uric acid in the blood and other physiological indexes were compared between patients with no symptoms of atrial fibrillation and patients with hyperthyroidism with symptoms of atrial fibrillation, to find the correlation between them. METHODS: A group of 112 hyperthyroidism patients who were admitted to our hospital from September 2019 to March 2020 were chosen and split into two groups. The control group consisted of 56 individuals (21 men and 35 women) aged between 16 and 86 years old, with an average age of 46.23 years (± 7.63). The observation group consisted of 56 individuals (24 males and 32 females) between 15 and 79 years, with an average age of 53.44 years (± 8.91). RESULTS: In the patients who were not treated with drugs before hospitalization the disease course and symptoms varied. The patients' clinical medical and demographic data were recorded and the patients' physiological indexes were obtained through blood tests and analysis. The differences between the two groups were analyzed by renal function, blood lipid index, thyroid function, and cardiac ultrasound, and these influencing factors were analyzed by regression analysis. The research adhered to ethical norms and ensured clear data presentation by using a rigorous technique to compare uric acid levels and physiological indicators among various patient groups. CONCLUSION: The study concentrated on the validation, repeatability, and contextual interpretation of data to provide a robust and rigorously scientific comparison. The most common is the increase of uric acid in the blood, which can induce other diseases, and atrial fibrillation is one of the most common diseases of cardiovascular diseases.

Cichorium glandulosum Ameliorates HFD-Induced Obesity in Mice by Modulating Gut Microbiota and Bile Acids.

Obesity is an ongoing global health problem, and Cichorium glandulosum (CG, chicory) is traditionally used as a hepatoprotective and lipid-lowering drug. However, there is still a lack of research on the role of CG in the treatment of obesity. In the present study, we found that CG significantly delayed weight gain and positively affected glucolipid metabolism disorders, serum metabolism levels, and the degree of liver and kidney oxidative stress in high-fat diet (HFD) mice. Further examination of the effects of CG on intestinal microenvironmental dysregulation and its metabolites in HFD mice revealed that the CG ethanol extract high-dose group (CGH) did not have a significant regulatory effect on short-chain fatty acids. Still, CGH significantly decreased the levels of 12α-OH/non-12α-OH bile acids and also found significant upregulation of proteobacteria and downregulation of cyanobacteria at the phylum level. CG may have ameliorated obesity and metabolic abnormalities in mice by repairing gut microbiota dysbiosis and modulating bile acid biosynthesis.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Emerging trends in small molecule inhibitors targeting aldosterone synthase: A new paradigm in cardiovascular disease treatment.

Aldosterone synthase (CYP11B2) is the rate-limiting enzyme in aldosterone production. In recent years, CYP11B2 has become an appealing target for treating conditions associated with excess aldosterone, such as hypertension, heart failure, and cardiometabolic diseases. Several small-molecule inhibitors of CYP11B2 have demonstrated efficacy in both preclinical studies and clinical trials. Among them, the tetrahydroisoquinoline derivative Baxdrostat has entered clinical trial phases and demonstrated efficacy in treating patients with hypertension. However, the high homology (>93 %) between CYP11B2 and steroid-11ß-hydroxylase (CYP11B1), which catalyzes cortisol production, implies that insufficient drug specificity can lead to severe side effects. Developing selective inhibitors for CYP11B2 remains a considerable challenge that requires ongoing attention. This review summarizes recent research progress on small-molecule inhibitors targeting CYP11B2, focusing on structure-activity relationships (SAR) and structural optimization. It discusses strategies for enhancing the specificity and inhibitory activity of inhibitors, while also exploring potential applications and future prospects for CYP11B2 inhibitors, providing a theoretical foundation for developing the new generation of CYP11B2-targeted medications.

circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC).

BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.

Investigating the effects and efficacy of self-compassion intervention on generalized anxiety disorders.

BACKGROUND: Generalized anxiety disorder (GAD) is the least successfully treated anxiety disorder. This clinical trial investigated the effects and efficacy of a novel self-compassion intervention in GAD. METHODS: A total of 75 GAD patients were assigned to a self-compassion intervention group (n = 25), a mindfulness intervention group (n = 25), or a treat-as-usual group (n = 25). Patients in the two active groups received eight intervention sessions in two weeks in addition to usual treatment i.e., pharmacotherapy. Primary outcomes were anxiety and worry, assessed at pre-intervention, post-intervention, and three-month follow-up. Secondary outcomes included depression, sleep, as well as self-compassion and mindfulness. RESULTS: Both the self-compassion and mindfulness intervention induced a more rapid decrease in anxiety and depression than pharmacological treatment alone with excellent response and remission rate. Self-compassion intervention also induced a more rapid improvement in sleep quality compared to mindfulness intervention and pharmacological treatment alone. We also presented a mechanism for the self-compassion intervention in which decreased anxiety led to improvement in sleep quality. There was also a higher pleasure, acceptance, and willingness to re-attend in the self-compassion compared to the mindfulness intervention. LIMITATIONS: This study was single blinded and nonrandomized which may bring risks of bias. CONCLUSIONS: Overall, we provided novel evidence that self-compassion intervention is an alternative psychotherapy for GAD with excellent response and acceptability.