Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study.

BACKGROUND AND AIMS: Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD). METHODS: We included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship. RESULTS: In whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03-1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27-3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10-2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08-1.34]) for LEAD, 1.48 [95% CI 1.28-1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy. CONCLUSIONS: Primary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression.

Down-regulated TINAGL1 in fibroblasts impairs wound healing in diabetes.

Matricellular proteins, a group of extracellular matrix (ECM) proteins, are key regulators of skin repair and their dysregulation impairs wound healing in diabetes. Tubulointerstitial nephritis antigen like 1 (TINAGL1) is a new member of matricellular protein family, and the understanding of its functional role is still relatively limited. In the current study, we detected the expression of TINAGL1 in diabetic skin wound tissues through RT-PCR, ELISA and Western blot analysis, investigated the contribution of TINAGL1 to wound healing through cutaneous administration of recombinant TINAGL1 protein, and characterized its regulation by hyperglycemia through RNA-seq and signal pathway inhibition assay. We showed that TINAGL1 expression has dynamic change and reaching a peak on day-9 after wound during the wound healing process in wild-type (WT) mice. Interestingly, decreased TINAGL1 expression is detected in skin tissues of diabetic patients and mice after wound. Then, we found that high glucose (HG), an important factor that impairs wound healing, reduces the expression of TINAGL1 in fibroblasts through JNK pathway. Notably, the histology analysis, Masson trichrome assay and IHC assay showed that exogenous TINAGL1 promotes wound healing in diabetic mice by accelerating the formation of granulation tissues. Our study provides evidence that TINAGL1 has an essential role in diabetic wound healing, and meanwhile, indicates that manipulation of TINAGL1 might be a possible therapeutic approach.

Extended Application of Inertial Measurement Units in Biomechanics: From Activity Recognition to Force Estimation.

Abnormal posture or movement is generally the indicator of musculoskeletal injuries or diseases. Mechanical forces dominate the injury and recovery processes of musculoskeletal tissue. Using kinematic data collected from wearable sensors (notably IMUs) as input, activity recognition and musculoskeletal force (typically represented by ground reaction force, joint force/torque, and muscle activity/force) estimation approaches based on machine learning models have demonstrated their superior accuracy. The purpose of the present study is to summarize recent achievements in the application of IMUs in biomechanics, with an emphasis on activity recognition and mechanical force estimation. The methodology adopted in such applications, including data pre-processing, noise suppression, classification models, force/torque estimation models, and the corresponding application effects, are reviewed. The extent of the applications of IMUs in daily activity assessment, posture assessment, disease diagnosis, rehabilitation, and exoskeleton control strategy development are illustrated and discussed. More importantly, the technical feasibility and application opportunities of musculoskeletal force prediction using IMU-based wearable devices are indicated and highlighted. With the development and application of novel adaptive networks and deep learning models, the accurate estimation of musculoskeletal forces can become a research field worthy of further attention.

Impaired alpha rhythm in bad sleeper during nap: A high-density electroencephalogram study.

As the pace of life accelerates, poor sleep quality has become a common health problem. A wealth of sleep studies based on electroencephalogram (EEG) have found that poor sleep quality has decreased alpha rhythm during night-time sleep. However, whether the EEG rhythm during an afternoon nap has a similar impairment has seldom been investigated. By recruiting 35 subjects for a 90-min nap, we explored the relationship between sleep quality and the alpha rhythm, and the contribution of naps to subjective sleep experience. We found that the power of alpha rhythm in the occipital lobe negatively correlated with sleep quality. However, there was no correlation between the sleep quality at night and the sleep duration of the nap, nor the sleep quality and the proportion of each sleep period of a nap. Our present results indicated that the quality of night-time sleep did not affect the macrostructure of the nap. Interestingly, the negative correlation between the alpha rhythm of a nap and sleep quality at night continuously existed in Wake, N1 sleep, and N2 sleep, and had the most substantial value during N2 sleep of a nap. This implies that an impaired occipital lobe alpha rhythm is a robust biomarker for poor sleep. The research is of particular significance for developing electrical neural stimulation therapy to improve sleep quality, especially for the stimuli regions for selection and the time windows for implementation.

A cryoprotectant supplemented with pentoxifylline can improve the effect of freezing on the motility of human testicular sperm.

This study examined the effect of a cryoprotectant with and without pentoxifylline supplementation on the motility and viability of human testicular sperm, both before and after freezing. Testicular samples were obtained from 68 patients with azoospermia who came to the Andrology Service of West China Second University Hospital, Sichuan University, for testicular biopsies from December 2019 to April 2020. All patients were assigned randomly to two groups: experimental, whose testicular sperm were added to the cryoprotectant with pentoxifylline, and the control, whose testicular sperm were added to the cryoprotectant without pentoxifylline. Both groups used the same freezing and thawing methods. Testicular sperm motility in the experimental group was significantly higher than that of the control group, both before and after cryopreservation. The recovery rate of sperm motility in the experimental group was significantly higher than that of the control group. The percentage of samples with motile testicular sperm in the experimental group was significantly higher than that of the control group after thawing. Sperm viability was unchanged between the experimental and control groups, both before and after freezing. Overall, a pentoxifylline-supplemented cryoprotectant can significantly improve the motility of testicular sperm before and after cryopreservation.

Rapid cryopreservation of small quantities of human spermatozoa by a self-prepared cryoprotectant without animal component.

Cryopreservation of small quantities of human spermatozoa whilst maintaining adequate post-thawing motility has been found an essential challenge for male fertility preservation. Therefore, the study used an effective, and convenient rapid-freezing method to freeze small amounts of human spermatozoa by adding self-prepared cryoprotectant (SPC) without animal component. In the feasibility experiment, no significant differences in progressive motility, normal sperm morphology, vitality or DNA fragmentation index between the conventional slow freezing and rapid freezing were realised. The present study prospectively analysed the effects of sperm freezing and resuscitation in 175 patients with severe oligozoospermia (sperm concentration <1 × 106 /ml). We observed the 120 severe oligozoospermia specimens had a mean recovery rate of 60.19% ± 10.43% and a mean cryosurvival rate of 68.0% ± 9.17%. In addition, 55 cryptozoospermia specimens were analysed. The small-volume cryopreservation showed advantages. The total sperm recovery, motility recovery and sperm loss rates were 98.48%, 50.17% and 1.52% respectively. In short, the SPC is safe and effective, and can be used to rapidly freeze severe oligozoospermia specimens. That is useful for successful sperm freezing whilst avoiding the risk of azoospermia in the later stages and promoting comprehensive fertility preservation.

Critical values of soil solution Al3+ activity and pH for canola and maize cultivation in two acidic soils.

BACKGROUND: Aluminum (Al) toxicity caused by soil acidification is the main constraint for crop growth in tropical and subtropical areas of southern China. The critical values of soil solution Al3+ activity and pH for crops in acidic soils can provide a useful reference for soil acidity amelioration. RESULTS: A pot experiment in a greenhouse was conducted to investigate the critical values of soil solution Al3+ activity and pH for canola and maize in an Ultisol and an Alfisol. The critical values of soil solution Al3+ activity in Ultisol and Alfisol for canola were 1.5 and 10.0 µmol L-1 , and 13.9 and 30.4 µmol L-1 for maize, respectively. The Al tolerance varied with soil type for the same variety of crop. There was more biomass of roots and shoots and higher plant height under the same Al3+ activity, and thus greater critical values of soil solution Al3+ activity for both crops in Alfisol than those in Ultisol, owing to higher Ca2+ /Al3+ , Mg2+ /Al3+ and K+ /Al3+ ratios in soil solution caused by higher cation exchange capacity and exchangeable base cations in Alfisol, when compared with those in Ultisol. The critical values of soil solution pH for canola and maize in Ultisol were 5.09 and 4.72, respectively; while those in Alfisol were 4.87 and 4.54, respectively. CONCLUSION: The critical values of Al3+ activity were higher for maize than for canola and the critical values for both crops were higher in Alfisol than in Ultisol. The critical soil pH for both crops showed opposite trends to soil Al3+ activity. © 2022 Society of Chemical Industry.

Chemical doping of organic semiconductors for thermoelectric applications.

Doping is essential to manipulate the electrical performance of both thermoelectric (TE) materials and organic semiconductors (OSCs). Although organic thermoelectric (OTE) materials have experienced a rapid development over the past decade, the chemical doping of OSCs for TE applications lags behind, which has limited further breakthroughs in this cutting-edge field. Recently, increasing efforts have been devoted to the development of energetically matched host and dopant molecules, exploring novel doping methods and revealing the doping mechanisms. This tutorial review covers the basic mechanisms, fundamental requirements, recent advances and remaining challenges of chemical doping in OSCs for TE applications. We first present the basic knowledge of the trade-off relationship in TE materials and its critical requirements for doped OSCs, followed by a brief introduction of recent advances in the molecular design of OSCs and dopants. Moreover, we provide an overview of the existing categories of doping mechanisms and methods, and more importantly, emphasize the summarized doping strategies for the state-of-the-art OTE materials. Finally, challenges and perspectives on the chemical doping of OSCs are proposed to highlight the research directions that deserve attention towards a bright future of OTE materials.

Comparing ameliorative effects of biomass ash and alkaline slag on an acidic Ultisol under artificial Masson pine: A field experiment.

Forest soil acidification caused by acid deposition is a serious threat to the forest ecosystem. To investigate the liming effects of biomass ash (BA) and alkaline slag (AS) on the acidic topsoil and subsoil, a three-year field experiment under artificial Masson pine was conducted at Langxi, Anhui province in Southern China. The surface application of BA and AS significantly increased the soil pH, and thus decreased exchangeable acidity and active Al in the topsoil. Soil exchangeable Ca2+ and Mg2+ in topsoil were significantly increased by the surface application of BA and AS, while an increase in soil exchangeable K+ was only observed in BA treatments. The soil acidity and active Al in subsoil were decreased by the surface application of AS. Compared with the control, soluble monomeric and exchangeable Al in the subsoil was decreased by 38.0% and 29.4% after 3 years of AS surface application. There was a minimal effect on soluble monomeric and exchangeable Al after the application of BA. The soil exchangeable Ca2+ and Mg2+ in the subsoil increased respectively by 54% and 141% after surface application of 10 t ha-1 AS. The decrease of soil active Al and increase of base cations in subsoil were mainly attributed to the high migration capacity of base cations in AS. In conclusion, the effect of surface application of AS was superior to BA in ameliorating soil acidity and alleviating soil Al toxicity in the subsoil of this Ultisol.

Method for initially selecting Al-tolerant rice varieties based on the charge characteristics of their roots.

To explore the relationship between charge characteristics of rice roots and aluminum (Al) tolerance of rice, roots of 47 different rice genotypes were obtained by hydroponic experiment. The zeta potentials of roots were determined by streaming potential method, and the Al tolerance and the functional groups of rice were measured by relative root elongation and infrared spectroscopy (ATR-FTIR), respectively. The exchangeable, complexed and precipitated Al(III) sorbed on the root surface of rice was extracted with 1 mol L-1 KNO3, 0.05 mol L-1 EDTA-2Na and 0.01 mol L-1 HCl, respectively. There was a significant correlation between the zeta potentials and the relative elongation of rice roots, indicating that the zeta potentials of rice roots could be used to characterize rice tolerance to Al toxicity. Twelve Al-tolerant rice varieties, 25 medium Al-tolerant rice varieties, and 10 Al-sensitive rice varieties were obtained. The Al-tolerant rice varieties sorbed less complexed Al(III) and total Al(III) because there was lower negative charge on their roots compared to less tolerant genotypes. A correlation analysis showed that there were significant negative correlations between the zeta potential, relative root elongation, and the total Al(III) sorption capacity of the roots, which further confirmed the reliability of using the root zeta potential to characterize rice tolerance to Al toxicity. The results of this paper provide a new method for screening Al-tolerant rice varieties.

A risk prediction model of sperm retrieval failure with fine needle aspiration in males with non-obstructive azoospermia.

STUDY QUESTION: Can we predict the risk of sperm retrieval failure among men with non-obstructive azoospermia (NOA) before they undergo fine needle aspiration (FNA)? SUMMARY ANSWER: Our model, which includes FSH level, age and testicular volume as variables, can predict the risk of sperm retrieval failure with FNA. WHAT IS KNOWN ALREADY: Combined with ICSI, testicular sperm aspiration (TESA) can enable patients with NOA to have their own genetic offspring. Nearly all reproductive medicine centres in China have applied FNA, but approximately half of patients with NOA experience testicular sperm retrieval failure. Nevertheless, the models developed to predict the likelihood of obtaining spermatozoa with testicular sperm extraction (TESE) cannot accurately predict sperm retrieval, and few of these models have been sufficiently validated. STUDY DESIGN, SIZE, DURATION: This study involved three cohorts including 597 men with NOA. From 1 January 2015 to 31 July 2017, a retrospective cohort of 317 males with NOA who underwent FNA procedures at a university affiliated hospital were included to build a risk prediction model of sperm retrieval failure with FNA. Then, from 25 October 2017 to 31 March 2018, two prospective cohorts of 61 and 219 males with NOA from the same hospital and one other reproductive specialist hospital respectively, were recruited to validate the risk prediction model. PARTICIPANTS/MATERIALS, SETTING, METHODS: All men with NOA undergoing their first TESE procedure as part of a fertility treatment were included. The primary end-point was the presence of one or more spermatozoa (regardless of their motility) obtained with FNA. A binary multivariable logistic model was built to predict the risk of sperm retrieval failure after TESA using the dataset from the retrospective cohort. A cut-off value for risk was calculated with receiver operating characteristic (ROC) curve analysis. Two validation sets from the prospective cohort were used to validate the risk prediction model by measures including prediction accuracy and the true positive rate. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 327 (54.8%) males with NOA experienced sperm retrieval failure with FNA. FSH level, age and testicular volume were included in the prediction model for sperm retrieval failure risk. The model had an AUC of 82.3% (95% CI: 77.6-87.1%) and a cut-off value of 64.61% with a sensitivity of 0.677 and specificity of 0.863 for predicted risk. The predictive accuracies were 85.25 and 83.56% in the external validation sets from two centres. Specifically, 85.71 and 85.15% of NOA patients from two centres that experienced sperm retrieval failure were correctly identified using our model. LIMITATIONS, REASONS FOR CAUTION: A small proportion of males with NOA in whom sperm were successfully retrieved with FNA were misclassified; therefore, TESA techniques with higher sperm retrieval rates may be attempted in patients with high predicted risks of sperm retrieval failure rather than terminating the efforts to produce a genetic offspring. In addition, the ability to achieve a live birth using sperm retrieved with FNA was not tested in this study. WIDER IMPLICATIONS OF THE FINDINGS: We would recommend the use of micro-TESE for men with NOA and a high predicted risk of FNA failure. STUDY FUNDING/COMPETING INTEREST(S): This study was partly supported by National Key R&D Program of China (No. 2017YFC0907305), the National Natural Science Foundation of China (No.81803332), Sichuan Science & Technology Program (No. 2018SZ0144, 2016SZ0066, 2018SZ0284 and 2018FZ0043), Chengdu Science & Technology Bureau (No. 2018-YF05-01265-SN), Postdoctoral Research foundation of Sichuan University (No. 2018SCU12012) and West China Second University Hospital of Sichuan University (No. kx027). There are no competing interests related to this study. TRIAL REGISTRATION NUMBER: Not applicable.

[The brain imaging studies of obstructive sleep apnea: evidence from resting-state EEG and fMRI].

Obstructive sleep apnea (OSA) is a common clinic sleep disorder, and characterized by obstruction of upper airway during sleep, resulting in sleep fragmentation and intermittent hypoxemia. We reviewed the brain imaging studies in OSA patients compared with healthy subjects, including studies of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). The resting-state EEG studies showed increased power of δ and θ in the front and central regions of the cerebral cortex in OSA patients. While resting-state fMRI studies demonstrated altered large-scale networks in default-mode network (DMN), central executive network (CEN) and salience network (SN). Evidence from resting-state studies of both fMRI and EEG focused on the abnormal activity in prefrontal cortex (PFC), which is correlated with OSA severity. These findings suggested that the PFC may play a key role in the abnormal function of OSA patients. Finally, based on the perspectives of treatment effect, multimodal data acquisition, and comorbidities, we discussed the future research direction of the neuroimaging study of OSA.

Selenium-Substituted Diketopyrrolopyrrole Polymer for High-Performance p-Type Organic Thermoelectric Materials.

Development of high-performance organic thermoelectric (TE) materials is of vital importance for flexible power generation and solid-cooling applications. Demonstrated here is the significant enhancement in TE performance of selenium-substituted diketopyrrolopyrrole (DPP) derivatives. Along with strong intermolecular interactions and high Hall mobilities of 1.0-2.3 cm2 V-1 s-1 in doping-states for polymers, PDPPSe-12 exhibits a maximum power factor and ZT of up to 364 µW m-1 K-2 and 0.25, respectively. The performance is more than twice that of the sulfur-based DPP derivative and represents the highest value for p-type organic thermoelectric materials based on high-mobility polymers. These results reveal that selenium substitution can serve as a powerful strategy towards rationally designed thermoelectric polymers with state-of-the-art performances.

Alpha 5/6 helix domains together with N-terminus determine the apoptotic potency of the Bcl-2 family proteins.

A critical process in apoptosis is the permeabilization of the mitochondrial outer membrane (MOM). This process is known to be regulated by the multi-domain Bcl-2 family proteins. For example, the pro-apoptotic proteins Bax and Bak are responsible for forming pores at MOM. The anti-apoptotic proteins (including Bcl-2, Mcl-1 and Bcl-xL), on the other hand, can inhibit this pore-forming process. Interestingly, although these two subgroups of proteins perform opposite apoptotic functions, their structures are very similar. This raises two highly interesting questions: (1) Why do these structurally similar proteins play opposite roles in apoptosis? (2) What are the roles of different functional domains of a Bcl-2 family protein in determining its apoptotic property? In this study, we generated a series of deletion mutants and substitution chimera, and used a combination of molecular biology, bio-informatics and living cell imaging techniques to answer these questions. Our major findings are: (1) All of the Bcl-2 family proteins appear to possess an intrinsic pro-apoptotic property. (2) The N-termini of these proteins play an active role in suppressing their pro-apoptotic function. (3) The apoptotic potency is positively correlated with membrane affinity of the alpha 5/6 helix domains. (4) Charge distribution flanking the alpha 5/6 helices is also important for the apoptotic potency. These findings explain why different members of Bcl-2 family proteins with similar domain composition can function oppositely in the apoptotic process.

Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis.

BACKGROUND: Gallium-68 somatostatin receptor positron emission tomography (PET) has been used in the diagnosis of neuroendocrine tumors (NETs). The compounds often used in molecular imaging of NETs with PET are 68Ga-DOTATOC, 68Ga-DOTATATE, and 68Ga-DOTANOC. There is varying affinity to different somatostatin receptors. PURPOSE: To systematically review and perform a meta-analysis of published data regarding the diagnostic role of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. MATERIAL AND METHODS: A comprehensive literature search of studies published through 30 April 2013 regarding 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs was performed using the PubMed/MEDLINE, Embase, and Scopus databases. Pooled sensitivity and specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. RESULTS: Ten studies comprising 416 patients with NETs were included in this meta-analysis. The pooled sensitivity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs calculated on a per-patient-based analysis was 93% (95% confidence interval [CI] 89-96%) and 96% (95% CI 91-99%). The pooled specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in diagnosing NETs was 85% (95% CI 74-93%) and 100% (95% CI 82-100%). The area under the ROC curve of 68Ga-DOTATOC and 68Ga-DOTATATE PET was 0.96 and 0.98, respectively, on a per-patient-based analysis. CONCLUSION: The molecular imaging agents 68Ga-DOTATOC and 68Ga-DOTATATE demonstrated high sensitivity and specificity in the diagnosis of NETs on PET scan. Although both are accurate tools in the diagnosis of NETs, 68Ga-DOTATATE PET may be more sensitive and specific than 68Ga-DOTATOC PET scan.

Identifying the insomnia-related psychological issues associated with hyperarousal: A network perspective.

Hyperarousal, recognized as a fundamental characteristic of insomnia for decades, has yielded limited evidence concerning its direct psychological associations. This study aimed to explore the psychological factors linked to hyperarousal within the framework of interrelated variables. Two independent samples, comprising n = 917 and n = 652 young adults, were included in the study. Employing the first dataset as a discovery sample and the second dataset as a replication sample, network analyses were conducted using 26 variables derived from 17 scales. The objective was to estimate the direct and indirect associations between psychological issues, including hyperarousal and insomnia. Additionally, linear regression analysis was employed to assess the convergence of findings obtained from the network analysis. Network analyses in both samples converged to reveal direct associations between insomnia severity and several psychological factors, including negative sleep beliefs, physical fatigue, insomnia response to stress, hyperarousal, self-reported depression, and mental fatigue. Notably, the nodes with relative importance within the network include trait anxiety, depressive rumination, hyperarousal, perfectionism sub-dimension of concern over mistakes, and private self-consciousness. Hyperarousal is one of the key factors linking insomnia with a variety of psychological issues, including emotion-related factors (rumination, perveived stress), sleep-related factors (dysfunctional sleep beliefs and attitudes, insomnia response to stress, fatigue, chronotype), and self-related factors (self-consciousness, perfectionism). The results suggest that forthcoming strategies for enhancing the treatment efficacy of insomnia could consider supplementary interventions that specifically address hyperarousal, other factors directly linked to insomnia, or the hub nodes within the network.

Binary-amplifying electrochemiluminescence sensor for sensitive assay of catechol and luteolin based on HKUST-1 derived CuO nanoneedles as a novel luminophore.

Herein, a highly novel and effective electrochemiluminescence (ECL) sensor based on metal-organic framework (MOF, HKUST-1) derived CuO nanoneedles (HKUST-1 derived CuO NNs), gold nanoparticles (AuNPs) and TiO2 was developed for ultrasensitive detection of catechol and luteolin. The HKUST-1 derived CuO NNs were employed as luminophore for the first time, which were successfully fabricated by using HKUST-1 as precursor. The results revealed that the HKUST-1 derived CuO NNs exhibit excellent ECL activity ascribed to its abundant active site and the high specific surface area, thus obviously promoting the separation and transfer of charge and further improving the current density of ECL sensor. To binary-amplify the signal of the ECL sensor, the AuNPs and TiO2 nano-materials with good biocompatibility, great electron transport efficiency and high catalytic activity were used as co-reaction accelerators in the ECL process. Dependent on the above brilliant strategy, the proposed ECL sensor achieved wide linear ranges from 3 × 10-9 - 1 × 10-4 M for catechol and 1 × 10-8 - 2 × 10-4 M for luteolin, with the detection limits of 1.5 × 10-9 M for catechol and 5.3 × 10-9 M for luteolin, respectively. Furthermore, the ECL sensor exhibited outstanding selectivity, repeatability, stability and obtained great feedback on determination of catechol and luteolin in actual samples. The method not only filled a gap in the ECL application of MOF-derived materials but also provided a novel sight for design other highly efficient luminescent materials.

Investigating Novel Therapeutic Approaches for Idiopathic Short Stature: Targeting siRNA and Growth Hormone Delivery to the Growth Plate Using Exosome Nanoparticles.

Idiopathic short stature (ISS) is a common childhood condition with largely unknown underlying causes. Recent research highlights the role of circulating exosomes in the pathogenesis of various disorders, but their connection to ISS remains unexplored. In the experiments, human chondrocytes are cocultured with plasma exosomes from ISS patients, leading to impaired chondrocyte growth and bone formation. Elevated levels of a specific long non-coding RNA (lncRNA), ISSRL, are identified as a distinguishing factor in ISS, boasting high specificity and sensitivity. Silencing ISSRL in ISS plasma exosomes reverses the inhibition of chondrocyte proliferation and bone formation. Conversely, overexpression of ISSRL in chondrocytes impedes their growth and bone formation, revealing its mechanism of action through the miR-877-3p/GZMB axis. Subsequently, exosomes (CT-Exo-siISSRL-oeGH) with precise cartilage-targeting abilities are engineered, loaded with customized siRNA for ISSRL and growth hormone. This innovative approach offers a therapeutic strategy to address ISS by rectifying abnormal non-coding RNA expression in growth plate cartilage and delivering growth hormone with precision to promote bone growth. This research provides valuable insights into ISS diagnosis and treatment, highlighting the potential of engineered exosomes.

Non-invasive prediction of preeclampsia using the maternal plasma cell-free DNA profile and clinical risk factors.

Background: Preeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors. Methods: We retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24-45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher's exact test and Mann-Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors. Results: By using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively. Conclusion: Incorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

Functional connectivity between dorsal attention and default mode networks mediates subjective sleep duration and depression in young females.

BACKGROUND: Depression prevails throughout the world. Young females are more likely to suffer from depression because of lack of sleep. METHODS: We recruited 405 young female participants to assess their subjective sleep duration and self-rating depression. The resting-state magnetic resonance imaging (rs-fMRI) data were collected to identify the brain regions related to sleep duration and depression, and a mediating model was established among sleep duration, depression and functional connectivity (FC) of rs-fMRI. RESULTS: Correlation analysis indicated that subjective sleep duration was negatively associated with self-rating depression in young females (r = -0.22, p < .001). The network connectivity between dorsal attention network (DAN) and default mode network (DMN) positively correlated with self-rating depression (r = 0.13, p < .05), and negatively correlated with subjective sleep duration (r = -0.14, p < .01). Furthermore, the mediation analysis revealed that the FC of DAN-DMN significantly mediated the effect of sleep duration on depression. LIMITATIONS: The study was a cross-section design and the sleep duration of the participants was subjectively reported. Future studies should consider to track the participants longitudinally and to measure the objective sleep duration by actigraph or polysomnography. CONCLUSIONS: The participants with less sleep duration are more prone to develop depression feelings. The FC of DAN-DMN mediated the effect of sleep duration on depression. Thus, the FC of DAN-DMN could be consider as a neural target to relieve depression by increasing sleep duration in young females.