Prospective study of the association between chronotypes and depressive symptoms in Chinese university students: Moderating effects of PER1 gene DNA methylation.

Most studies have shown a link between chronotypes and mental health and have identified evening chronotypes (E-types) as a potential risk for depressive symptoms. However, the mechanisms behind this association remain unknown. Abnormal expression of the PER1 gene was not only associated with circadian rhythm disturbance, but also closely related to mental illness. Therefore, this study aimed to examine the association of chronotype with depressive symptoms, and further explore the moderating effects of the PER1 gene DNA methylation on chronotypes and depressive symptoms in Chinese university students. In a stratified cluster sampling design, chronotype and depressive symptoms were assessed in 1 042 university students from 2 universities in a two-year prospective survey from April 2019 to October 2020. The survey was conducted once every 6 months, corresponding to the time points in April 2019 (T0), October 2019 (T1), April 2020 (T2), and October 2020 (T3). At T0, the Morning and Evening Questionnaire 5 (MEQ-5) was adopted to assess chronotype. At T0-T3, the Patient Health Questionnaire 9 (PHQ-9) was adopted to investigate depressive symptoms. Meanwhile, at T0, participants were subjected to a health check-up trip in the hospital, and blood samples were taken from the students to measure the PER1 gene DNA methylation levels. Binary logistic regression was used to analyze the association of chronotypes with depressive symptoms. The depression/total depression group was coded as 1, while the remaining participants was defined as one group, and was coded as 0. The PROCESS plug-in of SPSS software was used to analyze the moderating effects of PER1 gene DNA methylation on the association of chronotype with depressive symptoms. After adjusting for covariates, the results indicated that T0 E-types were positively correlated with T0-T3 depression/total depression in female university students. Furthermore, the PER1 gene DNA methylation has negative moderating effects between T0 chronotype and T3 depressive symptoms and has a sex difference. This study can provide more favorable scientific value for the prevention and control of depression in university students.

Microstructure and Mechanical Properties of Refill Friction Stir Spot-Welded Joints of 2A12Al and 7B04Al: Effects of Tool Size and Welding Parameters.

To solve problems in dissimilarly light metal joints, refilled friction stir spot welding (RFSSW) is proposed instead of resistance spot welding. However, rotation speed, dwell time, plunge depth, and the diameter of welding tools all have a great influence on joints, which brings great challenges in optimizing welding parameters to ensure their mechanical properties. In this study, the 1.5 mm thick 2A12Al and 2 mm thick 7B04Al lap joints were prepared by Taguchi orthogonal experiment design and RFSSW. The welding tool (shoulder) diameters were 5 mm and 7 mm, respectively. The macro/microstructures of the cross-section, the geometrical characteristics of the effective welding depth (EWD), the stir zone area (SZA), and the stir zone volume (SZV) were characterized. The shear strength and failure mode of the lap joint were analyzed using an optical microscope. It was found that EWD, SZA, and SZV had a good correlation with tensile-shear force. The optimal welding parameters of 5 mm diameter joints are 1500 rpm of rotation speed, 2.5 mm of plunge depth, and 0 s of dwell time, which for 7 mm joints are 1200 rpm, 1.5 mm, and 2 s. The tensile-shear force of 5 mm and 7 mm joints welded with these optical parameters was 4965 N and 5920 N, respectively. At the same time, the 5 mm diameter joints had better strength and strength stability.

Clinical significance and different strategies for re-elevation of plasma EBV-DNA during treatment in pediatric EBV-associated hemophagocytic lymphohistiocytosis.

OBJECTIVE: Monitoring the disease status of Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH) patients is crucial. This study aimed to investigate the different strategies and outcomes of patients with EBV-HLH and re-elevated EBV-DNA. METHOD: A retrospective analysis was conducted on 20 patients diagnosed with EBV-HLH. Clinical features, laboratory tests, treatments, plasma EBV-DNA levels, and outcomes were assessed. Three cases were highlighted for detailed analysis. RESULTS: Nine of the 20 patients had a re-elevation of EBV-DNA during treatment, and 55.5 % (5/9) experienced relapses. Patients with persistently positive plasma EBV-DNA (n = 4) and those with re-elevated EBV-DNA after conversion (n = 9) showed a significantly higher relapse rate compared to those with persistently negative EBV-HLH (n = 7) (p < 0.05). Among the highlighted cases, Case 1 exhibited plasma EBV-DNA re-elevation after four weeks of treatment without relapse, maintaining stability with the original treatment regimen, and eventually, his plasma EBV-DNA turned negative. In Case 2, plasma EBV-DNA was elevated again with a recurrence of HLH after L-DEP. Consequently, she underwent allogeneic hematopoietic stem cell transplantation and eventually achieved complete remission (CR) with negative plasma EBV-DNA. Case 3 experienced plasma EBV-DNA re-elevation after L-DEP but remained in CR, discontinuing chemotherapy without relapse. CONCLUSION: The re-elevation of plasma EBV-DNA during EBV-HLH treatment poses challenges in determining disease status and treatment strategies. Optimal management decisions require a combination of the level of elevated EBV-DNA, the intensity of hyperinflammation, and the patient's immune function.

SYN1 variant causes X-linked neurodevelopmental disorders: a case report of variable clinical phenotypes in siblings.

The SYN1 gene encodes synapsin I, variants within the SYN1 gene are linked to X-linked neurodevelopmental disorders with high clinical heterogeneity, with reflex epilepsies (REs) being a representative clinical manifestation. This report analyzes a Chinese pedigree affected by seizures associated with SYN1 variants and explores the genotype-phenotype correlation. The proband, a 9-year-old boy, experienced seizures triggered by bathing at the age of 3, followed by recurrent absence seizures, behavioral issues, and learning difficulties. His elder brother exhibited a distinct clinical phenotype, experiencing sudden seizures during sleep at the age of 16, accompanied by hippocampal sclerosis. Whole exome sequencing (WES) confirmed a pathogenic SYN1 variant, c.1647_1650dup (p. Ser551Argfs*134), inherited in an X-linked manner from their mother. Notably, this variant displayed diverse clinical phenotypes in the two brothers and one previously reported case in the literature. Retrospective examination of SYN1 variants revealed an association between truncating variants and the pathogenicity of REs, and non-truncating variants are more related to developmental delay/intellectual disability (DD/ID). In summary, this study contributes to understanding complex neurodevelopmental disorders associated with SYN1, highlighting the clinical heterogeneity of gene variants and emphasizing the necessity for comprehensive genetic analysis in elucidating the pathogenic mechanisms of such diseases.

Effect of respiratory muscle training in patients with stable chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Objectives: Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disorder characterized by progressive airflow limitation. This meta-analysis aims to evaluate the effectiveness of respiratory muscle training (RMT) on key pulmonary function parameters, inspiratory muscle strength and quality of life in patients with stable COPD. Methods: A comprehensive search was conducted in the databases including PubMed, Cochrane, Web of Science, Embase, and ClinicalTrials.gov, from their inception to June 12, 2023. Randomized controlled trials (RCTs) evaluating the impact of RMT on stable COPD were included for meta-analysis. Results: In total, 12 RCTs involving 453 participants were included in the meta-analysis. RMT demonstrated a significant increase in maximal inspiratory pressure (PImax, MD, 95% CI: 14.34, 8.17 to 20.51, P < 0.001) but not on maximal expiratory pressure (PEmax). No significant improvement was observed in 6-Min walk test (6MWT), dyspnea, forced expiratory volume in 1 s (FEV1), forced vital capacity ratio (FVC) and quality of life between RMT and control groups. However, subgroup analysis revealed a significant negative effect of RMT alone on FEV1/FVC (MD, 95% CI: 2.59, -5.11 to -0.06, P = 0.04). When RMT was combined with other interventions, improvements in FEV1/FVC and FEV1 were found, although not statistically significant. Conclusion: RMT can effectively improve maximal inspiratory pressure in stable COPD patients, but the effect is slight in improving lung function, dyspnea and quality of life. It is recommended to combine with other treatment strategies to comprehensively improve the prognosis of COPD patients.

Development of (2-(Benzyloxy)phenyl)methanamine Derivatives as Potent and Selective Inhibitors of CARM1 for the Treatment of Melanoma.

Coactivator-associated arginine methyltransferase 1 (CARM1), an important member of type I protein arginine methyltransferases (PRMTs), has emerged as a promising therapeutic target for various cancer types. In our previous study, we have identified a series of type I PRMT inhibitors, among which ZL-28-6 (6) exhibited increased activity against CARM1 while displaying decreased potency against other type I PRMTs. In this work, we conducted chemical modifications on compound 6, resulting in a series of (2-(benzyloxy)phenyl)methanamine derivatives as potent inhibitors of CARM1. Among them, compound 17e displayed remarkable potency and selectivity for CARM1 (IC50 = 2 ± 1 nM), along with notable antiproliferative effects against melanoma cell lines. Cellular thermal shift assay and western blot experiments confirmed that compound 6 effectively targets CARM1 within cells. Furthermore, compound 17e displayed good antitumor efficacy in a melanoma xenograft model, indicating that this compound warrants further investigation as a potential anticancer agent.

circRNAs as prognostic markers in pediatric acute myeloid leukemia.

Circular RNAs (circRNAs) arise from precursor mRNA processing through back-splicing and have been increasingly recognized for their functions in various cancers including acute myeloid leukemia (AML). However, the prognostic implications of circRNA in AML remain unclear. We conducted a comprehensive genome-wide analysis of circRNAs using RNA-seq data in pediatric AML. We revealed a group of circRNAs associated with inferior outcomes, exerting effects on cancer-related pathways. Several of these circRNAs were transcribed directly from genes with established functions in AML, such as circRUNX1, circWHSC1, and circFLT3. Further investigations indicated the increased number of circRNAs and linear RNAs splicing were significantly correlated with inferior clinical outcomes, highlighting the pivotal role of splicing dysregulation. Subsequent analysis identified a group of upregulated RNA binding proteins in AMLs associated with high number of circRNAs, with TROVE2 being a prominent candidate, suggesting their involvement in circRNA associated prognosis. Through the integration of drug sensitivity data, we pinpointed 25 drugs that could target high-risk AMLs characterized by aberrant circRNA transcription. These findings underscore prognostic significance of circRNAs in pediatric AML and offer an alternative perspective for treating high-risk cases in this malignancy.

Colorimetric aptasensor based on magnetic beads and gold nanoparticles for detecting mucin 1.

In this work, a colorimetric aptasensor based on magnetic beads (MBs), gold nanoparticles (AuNPs) and Horseradish Peroxidase (HRP) was prepared for the detection of mucin 1 (MUC1). Complementary DNA of the MUC1 aptamer (Apt) immobilized on the MBs was combined with the prepared AuNPs-Apt-HRP complex (AuNPs@Apt-HRP). In the presence of MUC1, it specifically bound to Apt, resulting in the detachment of gold nanoparticles from the MBs. After magnetic separation, AuNPs@Apt-HRP was separated into the supernatant and reacted with 3,3',5,5'-Tetramethylbenzidine (TMB) to produce color reaction from colorless to blue. The linear range of MUC1 was from 75 to 500 µg/mL (R2 = 0.9878), and the detection limit was 41.95 µg/mL. The recovery rate of MUC1 in human serum was 99.18 %∼101.15 %. This method is simple and convenient. Moreover, it does not require complex and expensive equipment for detection of MUC1. It provides value for the development of MUC1 colorimetric sensors and a promising strategy for the determination of MUC1 in clinical diagnosis.

Optimizing Transseptal Puncture Guided by Three-Dimensional Mapping: Role of Unipolar Electrogram on Needle Tip.

BACKGROUND AND AIMS: A three-dimensional electroanatomic mapping system-guided transseptal puncture (3D-TSP), without fluoroscopy or echocardiography, was insufficiently reported. Indications for 3D-TSP remain unclear. This study aimed to establish a precise technique and create a workflow for validating and selecting eligible patients for fluoroless 3D-TSP. METHODS AND RESULTS: We developed a new methodology for 3D-TSP based on the unipolar electrogram derived from transseptal needle tip (UEGM-tip) in 102 cases (the derivation cohort) with intracardiac echocardiography (ICE) from March 2018 to February 2019. The apparent current of injury (COI) was recorded at the muscular limbus of the foramen ovalis (FO) on UEGM-tip (sinus rhythm: 2.57 ± 0.95 mV, atrial fibrillation: 1.92 ± 0.77 mV), which then disappeared or significantly reduced at central FO. Changes in COI, serving as a major criterion to establish 3D-TSP workflow, proved to be the most valuable indicator for identifying FO in 99% (101/102) of patients compared to three previous techniques (3 minor criteria) of reduction in atrial unipolar or bipolar potential and FO protrusion.A total of 1042 patients in the validation cohort underwent successful 3D-TSP through the workflow from March 2019 to July 2023. ICE guidance was required for 6.6% (69/1042) of cases. All four criteria were met in 740 patients, resulting in a 100% pure fluoroless 3D-TSP success rate. CONCLUSION: Most cases successfully achieved fluoroless 3D-TSP using changes of COI on UEGM tip. Patients who met all four criteria were suitable for 3D-TSP, while those who met none required ICE guidance.

A Mettl16/m6A/mybl2b/Igf2bp1 axis ensures cell cycle progression of embryonic hematopoietic stem and progenitor cells.

Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (m6A) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA m6A modification in early embryonic development. Here, using cross-species single-cell RNA sequencing analysis, we found that during early embryonic development, METTL16 is more highly expressed in vertebrate hematopoietic stem and progenitor cells (HSPCs) than other methyltransferases. In Mettl16-deficient zebrafish, proliferation capacity of embryonic HSPCs is compromised due to G1/S cell cycle arrest, an effect whose rescue requires Mettl16 with intact methyltransferase activity. We further identify the cell-cycle transcription factor mybl2b as a directly regulated by Mettl16-mediated m6A modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the m6A reader Igf2bp1 in vivo. Moreover, we found that the METTL16-m6A-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated m6A modification in HSPC cell cycle progression during early embryonic development.

Observing heroic behavior and its influencing factors in immersive virtual environments.

Studying heroism in controlled settings presents challenges and ethical controversies due to its association with physical risk. Leveraging virtual reality (VR) technology, we conducted a three-study series with 397 participants from China to investigate heroic actions. Participants unexpectedly witnessed a criminal event in a simulated scenario, allowing observation of their tendency to physically intercept a thief. We examined situational factors (voluntariness, authority, and risk) and personal variables [gender, impulsivity, empathy, and social value orientation (SVO)] that may influence heroism. Also, the potential association between heroism and social conformity was explored. In terms of situational variables, voluntariness modulated participants' tendency to intercept the escaping thief, while perceived risk demonstrated its impact by interacting with gender. That is, in study 3 where the perceived risk was expected to be higher (as supported by an online study 5), males exhibited a greater inclination toward heroic behavior compared to females. Regarding other personal variables, the tendency to engage in heroic behavior decreased as empathy levels rose among males, whereas the opposite trend was observed for females. SVO influenced heroic behavior but without a gender interaction. Finally, an inverse relationship between heroism and social conformity was observed. The robustness of these findings was partly supported by the Chinese sample (but not the international sample) of an online study 4 that provided written descriptions of VR scenarios, indicating cultural variations. These results advance insights into motivational factors influencing heroism in the context of restoring order and highlight the power of VR technology in examining social psychological hypotheses beyond ethical constraints.

Biosynthesis of Scopoletin in Sweet Potato Confers Resistance against Fusarium oxysporum.

Fusarium wilt is a severe fungal disease caused by Fusarium oxysporum in sweet potato. We conducted transcriptome analysis to explore the resistance mechanism of sweet potato against F. oxysporum. Our findings highlighted the role of scopoletin, a hydroxycoumarin, in enhancing resistance. In vitro experiments confirmed that scopoletin and umbelliferone had inhibitory effects on the F. oxysporum growth. We identified hydroxycoumarin synthase genes IbF6'H2 and IbCOSY that are responsible for scopoletin production in sweet potatoes. The co-overexpression of IbF6'H2 and IbCOSY in tobacco plants produced the highest scopoletin levels and disease resistance. This study provides insights into the molecular basis of sweet potato defense against Fusarium wilt and identifies valuable genes for breeding wilt-resistant cultivars.

Impact of Gestational Exposure to Individual and Combined Per- and Polyfluoroalkyl Substances on a Placental Structure and Efficiency: Findings from the Ma'anshan Birth Cohort.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is inevitable among pregnant women. Nevertheless, there is a scarcity of research investigating the connections between prenatal PFAS exposure and the placental structure and efficiency. Based on 712 maternal-fetal dyads in the Ma'anshan Birth Cohort, we analyzed associations between individual and mixed PFAS exposure and placental measures. We repeatedly measured 12 PFAS in the maternal serum during pregnancy. Placental weight, scaling exponent, chorionic disc area, and disc eccentricity were used as the outcome variables. Upon adjusting for confounders and implementing corrections for multiple comparisons, we identified positive associations between branched perfluorohexane sulfonate (br-PFHxS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) with placental weight. Additionally, a positive association was observed between br-PFHxS and the scaling exponent, where a higher scaling exponent signified reduced placental efficiency. Based on neonatal sex stratification, female infants were found to be more susceptible to the adverse effects of PFAS exposure. Mixed exposure modeling revealed that mixed PFAS exposure was positively associated with placental weight and scaling exponent, particularly during the second and third trimesters. Furthermore, br-PFHxS and 6:2 Cl-PFESA played major roles in the placental measures. This study provides the first epidemiological evidence of the relationship between prenatal PFAS exposure and placental measures.

Ablation of Brg1 in fibroblast/myofibroblast lineages attenuates renal fibrosis in mice with diabetic nephropathy.

AIMS: Diabetic nephropathy (DN) is one of the most common complications of diabetes and represents a prototypical form of chronic kidney disease (CKD). Interstitial fibrosis is a key pathological feature of DN. During DN-associated renal fibrosis, resident fibroblasts trans-differentiate into myofibroblasts to remodel the extracellular matrix, the underlying epigenetic mechanism of which is not entirely clear. METHODS: Diabetic nephropathy was induced in C57B6/j mice by a single injection with streptozotocin (STZ). Gene expression was examined by quantitative PCR and Western blotting. Renal fibrosis was evaluated by PicroSirius Red staining. RESULTS: We report that expression of Brg1, a chromatin remodeling protein, in renal fibroblasts was up-regulated during DN pathogenesis as assessed by single-cell RNA-seq. Treatment with high glucose similarly augmented Brg1 expression in primary renal fibroblasts in vitro. Importantly, Brg1 ablation in quiescent renal fibroblasts or in mature myofibroblasts equivalently attenuated renal fibrosis in the context of diabetic nephropathy in mice. Additionally, administration with a small-molecule Brg1 inhibitor PFI-3 ameliorated renal fibrosis and improved renal function in mice induced to develop DN. SIGNIFICANCE: In conclusion, our data provide novel genetic evidence that links Brg1 to fibroblast-myofibroblast transition and renewed rationale for targeting Brg1 in the intervention of DN-associated renal fibrosis.

Elucidating the impacts of cobalt (II) ions on extracellular electron transfer and pollutant degradation by anodic biofilms in bioelectrochemical systems during industrial wastewater treatment.

Electrogenic biofilms in bioelectrochemical systems (BES) are critical in wastewater treatment. Industrial effluents often contain cobalt (Co2+); however, its impact on biofilms is unknown. This study investigated how increasing Co2+ concentrations (0-30 mg/L) affect BES biofilm community dynamics, extracellular polymeric substances, microbial metabolism, electron transfer gene expression, and electrochemical performance. The research revealed that as Co2+ concentrations increased, power generation progressively declined, from 345.43 ± 4.07 mW/m2 at 0 mg/L to 160.51 ± 0.86 mW/m2 at 30 mg/L Co2+. However, 5 mg/L Co2+ had less effect. The Co2+ removal efficiency in the reactors fed with 5 and 10 mg/L concentrations exceeded 99% and 94%, respectively. However, at 20 and 30 mg/L, the removal efficiency decreased substantially, likely because of reduced biofilm viability. FTIR indicated the participation of biofilm functional groups in Co2+ uptake. XPS revealed Co2+ presence in biofilms as CoO and Co(OH)2, indicating precipitation also aided removal. Cyclic voltammetry and electrochemical impedance spectroscopy tests revealed that 5 mg/L Co2+ had little impact on the electrocatalytic activity, while higher concentrations impaired it. Furthermore, at a concentration of 5 mg/L Co2+, there was an increase in the proportion of the genus Anaeromusa-Anaeroarcus, while the genus Geobacter declined at all tested Co2+ concentrations. Additionally, higher concentrations of Co2+ suppressed the expression of extracellular electron transfer genes but increased the expression of Co2+-resistance genes. Overall, this study establishes how Co2+ impacts electrogenic biofilm composition, function, and treatment efficacy, laying the groundwork for the optimized application of BES in remediating Co2+-contaminated wastewater.

A novel antimicrobial peptide with broad-spectrum and exceptional stability derived from the natural peptide Brevicidine.

The global issue of antibiotic resistance is increasingly severe, highlighting the urgent necessity for the development of new antibiotics. Brevicidine, a natural cyclic lipopeptide, exhibits remarkable antimicrobial activity against Gram-negative bacteria. In this study, a comprehensive structure-activity relationship of Brevicidine was investigated through 20 newly synthesized cyclic lipopeptide analogs, resulting in the identification of an optimal linear analog 22. The sequence of analog 22 consisted of five d-amino acids and four non-natural amino acid 2,5-diaminovaleric acid (Orn) and conjugated with decanoic acid at N-terminal. Compared to Brevicidine, analog 22 was easier to synthesize, and exerted broad spectrum antimicrobial activity and excellent stability (t1/2 = 40.98 h). Additionally, analog 22 demonstrated a rapid bactericidal effect by permeating non-specifically through the bacterial membranes, thereby minimizing the likelihood of inducing resistance. Moreover, it exhibited remarkable efficacy in combating bacterial biofilms and reversing bacterial resistance to conventional antibiotics. Furthermore, it effectively suppressed the growth of bacteria in vital organs of mice infected with S. aureus ATCC 25923. In conclusion, analog 22 may represent a potential antimicrobial peptide for further optimization.

Boron in the Second Coordination Sphere of Fe Single Atom Boosts the Oxygen Reduction Reaction.

Metal single atoms coordinated with four nitrogen atoms (M1N4) are regarded as tremendously promising catalysts for the electrocatalytic oxygen reduction reaction (ORR). Nevertheless, the strong bond intensity between the metal center and the O atom in oxygen-containing intermediates significantly limits the ORR activity of M1N4. Herein, the catalytically active B atom is successfully introduced into the second coordination sphere of the Fe single atom (Fe1N4-B-C) to realize the alternative binding of B and O atoms and thus facilitate the ORR activity. Compared with the pristine Fe1N4 catalyst, the synthesized Fe1N4-B-C catalyst exhibits improved ORR catalytic capability with a half-wave potential (E1/2) of 0.80 V and a kinetic current density (JK) of 5.32 mA cm-2 in acid electrolyte. Moreover, in an alkaline electrolyte, the Fe1N4-B-C catalyst displays remarkable ORR activity with E1/2 of 0.87 V and JK of 8.94 mA cm-2 at 0.85 V, outperforming commercial Pt/C. Notably, the mechanistic study has revealed that the active center is the B atom in the second coordination shell of the Fe1N4-B-C catalyst, which avoids the direct bonding of Fe-O. The B center has a moderate binding force to the ORR intermediate, which flattens the ORR energy diagram and thereby improves the ORR performance. Therefore, this study offers a novel strategy for tailoring catalytic performance by tuning the active center of single-atom catalyst.

Demethylzeylasteral protects against renal interstitial fibrosis by attenuating mitochondrial complex I-mediated oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Renal interstitial fibrosis (RIF) is a main pathological process in chronic kidney disease (CKD). Demethylzeylasteral (DML), a major component of Tripterygium wilfordii Hook. f., has anti-renal fibrosis effects. However, its mechanism of action remains incompletely understood. AIM OF THE STUDY: The present study was designed to comprehensively examine the effects of DML on RIF and the underlying mechanisms. MATERIALS AND METHODS: Pathological experiments were performed to determine the therapeutic effect of DML on a mouse model of UUO-induced RIF. To determine the novel mechanisms underlying the therapeutic effects of DML against RIF, a comprehensive transcriptomics analysis was performed on renal tissues, which was further verified by a series of experiments. RESULTS: Pathological and immunohistochemical staining showed that DML inhibited UUO-induced renal damage and reduced the expression of fibrosis-related proteins in mice. Transcriptomic analysis revealed that the partial subunits of mitochondrial complex (MC) I and II may be targets by which DML protects against RIF. Furthermore, DML treatment reduced mitochondrial reactive oxygen species (ROS) levels, consequently promoting ATP production and mitigating oxidative stress-induced injury in mice and cells. Notably, this protective effect was attributed to the inhibition of MC I activity, suggesting a crucial role for this specific complex in mediating the therapeutic effects of DML against RIF. CONCLUSIONS: This study provides compelling evidence that DML may be used to treat RIF by effectively suppressing mitochondrial oxidative stress injury mediated by MC I. These findings offer valuable insights into the pharmacological mechanisms of DML and its potential clinical application for patients with CKD.

A novel measurement approach to dynamic change of limb length discrepancy using deep learning and wearable sensors.

The accurate identification of dynamic change of limb length discrepancy (LLD) in non-clinical settings is of great significance for monitoring gait function change in people's everyday lives. How to search for advanced techniques to measure LLD changes in non-clinical settings has always been a challenging endeavor in recent related research. In this study, we have proposed a novel approach to accurately measure the dynamic change of LLD outdoors by using deep learning and wearable sensors. The basic idea is that the measurement of dynamic change of LLD was considered as a multiple gait classification task based on LLD change that is clearly associated with its gait pattern. A hybrid deep learning model of convolutional neural network and long short-term memory (CNN-LSTM) was developed to precisely classify LLD gait patterns by discovering the most representative spatial-temporal LLD dynamic change features. Twenty-three healthy subjects were recruited to simulate four levels of LLD by wearing a shoe lift with different heights. The Delsys TrignoTM system was implemented to simultaneously acquire gait data from six sensors positioned on the hip, knee and ankle joint of two lower limbs respectively. The experimental results showed that the developed CNN-LSTM model could reach a higher accuracy of 93.24% and F1-score of 93.48% to classify four different LLD gait patterns when compared with CNN, LSTM, and CNN-gated recurrent unit(CNN-GRU), and gain better recall and precision (more than 92%) to detect each LLD gait pattern accurately. Our model could achieve excellent learning ability to discover the most representative LLD dynamic change features for classifying LLD gait patterns accurately. Our technical solution would help not only to accurately measure LLD dynamic change in non-clinical settings, but also to potentially find out lower limb joints with more abnormal compensatory change caused by LLD.

Deep metagenomic characterization of the gut virome in pregnant women with preeclampsia.

Preeclampsia (PE), a pregnancy-specific syndrome, has been associated with the gut bacteriome. Here, to investigate the impact of the gut virome on the development of PE, we identified over 8,000 nonredundant viruses from the fecal metagenomes of 40 early-onset PE and 37 healthy pregnant women and profiled their abundances. Comparison and correlation analysis showed that PE-enriched viruses frequently connected to Blautia species enriched in PE. By contrast, bacteria linked to PE-depleted viruses were often the Bacteroidaceae members such as Bacteroides spp., Phocaeicola spp., Parabacteroides spp., and Alistipes shahii. In terms of viral function, PE-depleted viruses had auxiliary metabolic genes that participated in the metabolism of simple and complex polysaccharides, sulfur metabolism, lipopolysaccharide biosynthesis, and peptidoglycan biosynthesis, while PE-enriched viruses had a gene encoding cyclic pyranopterin monophosphate synthase, which seemed to be special, that participates in the biosynthesis of the molybdenum cofactor. Furthermore, the classification model based on gut viral signatures was developed to discriminate PE patients from healthy controls and showed an area under the receiver operating characteristic curve of 0.922 that was better than that of the bacterium-based model. This study opens up new avenues for further research, providing valuable insights into the PE gut virome and offering potential directions for future mechanistic and therapeutic investigations, with the ultimate goal of improving the diagnosis and management of PE.IMPORTANCEThe importance of this study lies in its exploration of the previously overlooked but potentially critical role of the gut virome in preeclampsia (PE). While the association between PE and the gut bacteriome has been recognized, this research takes a pioneering step into understanding how the gut virome, represented by over 8,000 nonredundant viruses, contributes to this condition. The findings reveal intriguing connections between PE-enriched viruses and specific gut bacteria, such as the prevalence of Blautia species in individuals with PE, contrasting with bacteria linked to PE-depleted viruses, including members of the Bacteroidaceae family. These viral interactions and associations provide a deeper understanding of the complex dynamics at play in PE.