Subtle Structural Differences Affect the Inhibitory Potency of RGD-Containing Cyclic Peptide Inhibitors Targeting SPSB Proteins.

The SPRY domain-containing SOCS box proteins SPSB1, SPSB2, and SPSB4 utilize their SPRY/B30.2 domain to interact with a short region in the N-terminus of inducible nitric oxide synthase (iNOS), and recruit an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in the proteasomal degradation of iNOS. Inhibitors that can disrupt the endogenous SPSB-iNOS interactions could be used to augment cellular NO production, and may have antimicrobial and anticancer activities. We previously reported the rational design of a cyclic peptide inhibitor, cR8, cyclo(RGDINNNV), which bound to SPSB2 with moderate affinity. We, therefore, sought to develop SPSB inhibitors with higher affinity. Here, we show that cyclic peptides cR7, cyclo(RGDINNN), and cR9, cyclo(RGDINNNVE), have ~6.5-fold and ~2-fold, respectively, higher SPSB2-bindng affinities than cR8. We determined high-resolution crystal structures of the SPSB2-cR7 and SPSB2-cR9 complexes, which enabled a good understanding of the structure-activity relationships for these cyclic peptide inhibitors. Moreover, we show that these cyclic peptides displace full-length iNOS from SPSB2, SPSB1, and SPSB4, and that their inhibitory potencies correlate well with their SPSB2-binding affinities. The strongest inhibition was observed for cR7 against all three iNOS-binding SPSB proteins.

Exploring the role of CD8+ T cells in clear renal cell carcinoma metastasis.

Clear cell renal cell carcinoma (ccRCC) accounts for approximately 75-80% of all patients with renal cell carcinoma. Despite its prevalence, little is known regarding the key components involved in ccRCC metastasis. In this study, scRNA-seq analysis was employed to classify CD8+ T cells into four sub-clusters based on their genetic profiles and immunofluorescence experiments were used to validate two key clusters. Through gene set enrichment analysis, these newly identified sub-clusters were found to exhibit distinct biological characteristics. Notably, TYMP, TOP2A, CHI3L2, CDKN3, CENPM, and RZH2 were highly expressed in these sub-clusters, indicating a correlation with poor prognosis. Among these sub-clusters, CD8+ T cells (MT-ND4) were identified as potentially playing a critical role in mediating ccRCC metastasis. These results contribute to our understanding of CD8+ T cell heterogeneity in ccRCC and shed light on the mechanisms underlying the loss of immune response against cancer.

Pd(II)/Pd(IV) redox shuttle to suppress vacancy defects at grain boundaries for efficient kesterite solar cells.

Charge loss at grain boundaries of kesterite Cu2ZnSn(S, Se)4 polycrystalline absorbers is an important cause limiting the performance of this emerging thin-film solar cell. Herein, we report a Pd element assisted reaction strategy to suppress atomic vacancy defects in GB regions. The Pd, on one hand in the form of PdSex compounds, can heterogeneously cover the GBs of the absorber film, suppressing Sn and Se volatilization loss and the formation of their vacancy defects (i.e. VSn and VSe), and on the other hand, in the form of Pd(II)/Pd(IV) redox shuttle, can assist the capture and exchange of Se atoms, thus contributing to eliminating the already-existing VSe defects within GBs. These collective effects have effectively reduced charge recombination loss and enhanced p-type characteristics of the kesterite absorber. As a result, high-performance kesterite solar cells with a total-area efficiency of 14.5% (certified at 14.3%) have been achieved.

Ultrasound-Based Deep Learning Radiomics Nomogram for the Assessment of Lymphovascular Invasion in Invasive Breast Cancer: A Multicenter Study.

RATIONALE AND OBJECTIVES: The aim of this study was to develop a deep learning radiomics nomogram (DLRN) based on B-mode ultrasound (BMUS) and color doppler flow imaging (CDFI) images for preoperative assessment of lymphovascular invasion (LVI) status in invasive breast cancer (IBC). MATERIALS AND METHODS: In this multicenter, retrospective study, 832 pathologically confirmed IBC patients were recruited from eight hospitals. The samples were divided into training, internal test, and external test sets. Deep learning and handcrafted radiomics features reflecting tumor phenotypes on BMUS and CDFI images were extracted. The BMUS score and CDFI score were calculated after radiomics feature selection. Subsequently, a DLRN was developed based on the scores and independent clinic-ultrasonic risk variables. The performance of the DLRN was evaluated for calibration, discrimination, and clinical usefulness. RESULTS: The DLRN predicted the LVI with accuracy, achieving an area under the receiver operating characteristic curve of 0.93 (95% CI 0.90-0.95), 0.91 (95% CI 0.87-0.95), and 0.91 (95% CI 0.86-0.94) in the training, internal test, and external test sets, respectively, with good calibration. The DLRN demonstrated superior performance compared to the clinical model and single scores across all three sets (p < 0.05). Decision curve analysis and clinical impact curve confirmed the clinical utility of the model. Furthermore, significant enhancements in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indicated that the two scores could serve as highly valuable biomarkers for assessing LVI. CONCLUSION: The DLRN exhibited strong predictive value for LVI in IBC, providing valuable information for individualized treatment decisions.

Corrigendum: Functional metagenomic and metabolomics analysis of gut dysbiosis induced by hyperoxia.

[This corrects the article DOI: 10.3389/fmicb.2023.1197970.].

Impact of hyperoxia on the gut during critical illnesses.

Molecular oxygen is typically delivered to patients via oxygen inhalation or extracorporeal membrane oxygenation (ECMO), potentially resulting in systemic hyperoxia from liberal oxygen inhalation or localized hyperoxia in the lower body from peripheral venoarterial (VA) ECMO. Consequently, this exposes the gastrointestinal tract to excessive oxygen levels. Hyperoxia can trigger organ damage due to the overproduction of reactive oxygen species and is associated with increased mortality. The gut and gut microbiome play pivotal roles in critical illnesses and even small variations in oxygen levels can have a dramatic influence on the physiology and ecology of gut microbes. Here, we reviewed the emerging preclinical evidence which highlights how excessive inhaled oxygen can provoke diffuse villous damage, barrier dysfunction in the gut, and gut dysbiosis. The hallmark of this dysbiosis includes the expansion of oxygen-tolerant pathogens (e.g., Enterobacteriaceae) and the depletion of beneficial oxygen-intolerant microbes (e.g., Muribaculaceae). Furthermore, we discussed potential impact of oxygen on the gut in various underlying critical illnesses involving inspiratory oxygen and peripheral VA-ECMO. Currently, the available findings in this area are somewhat controversial, and a consensus has not yet to be reached. It appears that targeting near-physiological oxygenation levels may offer a means to avoid hyperoxia-induced gut injury and hypoxia-induced mesenteric ischemia. However, the optimal oxygenation target may vary depending on special clinical conditions, including acute hypoxia in adults and neonates, as well as particular patients undergoing gastrointestinal surgery or VA-ECMO support. Last, we outlined the current challenges and the need for future studies in this area. Insights into this vital ongoing research can assist clinicians in optimizing oxygenation for critically ill patients.

Association between atherogenic index of plasma control level and incident cardiovascular disease in middle-aged and elderly Chinese individuals with abnormal glucose metabolism.

BACKGROUND: The atherogenic index of plasma (AIP) and cardiovascular disease (CVD) in participants with abnormal glucose metabolism have been linked in previous studies. However, it was unclear whether AIP control level affects the further CVD incidence among with diabetes and pre-diabetes. Therefore, our study aimed to investigate the association between AIP control level with risk of CVD in individuals with abnormal glucose metabolism. METHODS: Participants with abnormal glucose metabolism were included from the China Health and Retirement Longitudinal Study. CVD was defined as self-reporting heart disease and/or stroke. Using k-means clustering analysis, AIP control level, which was the log-transformed ratio of triglyceride to high-density lipoprotein cholesterol in molar concentration, was divided into five classes. The association between AIP control level and incident CVD among individuals with abnormal glucose metabolism was investigated multivariable logistic regression analysis and application of restricted cubic spline analysis. RESULTS: 398 (14.97%) of 2,659 participants eventually progressed to CVD within 3 years. After adjusting for various confounding factors, comparing to class 1 with the best control of the AIP, the OR for class 2 with good control was 1.31 (95% CI, 0.90-1.90), the OR for class 3 with moderate control was 1.38 (95% CI, 0.99-1.93), the OR for class 4 with worse control was 1.46 (95% CI, 1.01-2.10), and the OR for class 5 with consistently high levels was 1.56 (95% CI, 1.03-2.37). In restricted cubic spline regression, the relationship between cumulative AIP index and CVD is linear. Further subgroup analysis demonstrated that the similar results were observed in the individuals with agricultural Hukou, history of smoking, diastolic blood pressure ≥ 80mmHg, and normal body mass index. In addition, there was no interaction between the AIP control level and the subgroup variables. CONCLUSIONS: In middle-aged and elderly participants with abnormal glucose metabolism, constant higher AIP with worst control may have a higher incidence of CVD. Monitoring long-term AIP change will contribute to early identification of high risk of CVD among individuals with abnormal glucose metabolism.

Systemic inflammation and oxidative stress markers in patients with unipolar and bipolar depression: A large-scale study.

OBJECTIVE: Numerous studies have demonstrated that neutrophil/HDL ratio (NHR), lymphocyte/HDL ratio (LHR), monocyte/HDL (MHR) ratio, platelet/HDL ratio (PHR), neutrophil/ALB ratio (NAR) and platelet/ALB ratio (PAR) can serve as systemic inflammation and oxidative stress markers in a variety of diseases. However, few studies have estimated the associations of these markers with unipolar depression (UD) and bipolar depression (BD), as well as psychotic symptoms in UD and BD. METHODS: 6297 UD patients, 1828 BD patients and 7630 healthy subjects were recruited. The differences in these indicators among different groups were compared, and the influencing factors for the occurrence of UD or BD and psychotic symptoms were analyzed. RESULTS: These ratios displayed unique variation patterns across different diagnostic groups. BD group exhibited higher NHR, LHR, MHR, NAR and lower PAR than UD and HC groups, UD group showed higher MHR than HC group. The psychotic UD group had higher NHR, LHR, MHR and NAR than non-psychotic UD group. Higher LHR, MHR, NAR and lower PAR were risk factors in BD when compared to UD group. CONCLUSIONS: Our study demonstrated differences in inflammation and oxidative stress profile between UD and BD patients, as well as between subjects with or without psychotic symptom exist, highlighting the role of inflammation and oxidative stress in the pathophysiology of UD and BD.

Functional metagenomic and metabolomics analysis of gut dysbiosis induced by hyperoxia.

Background: Inhaled oxygen is the first-line therapeutic approach for maintaining tissue oxygenation in critically ill patients, but usually exposes patients to damaging hyperoxia. Hyperoxia adversely increases the oxygen tension in the gut lumen which harbors the trillions of microorganisms playing an important role in host metabolism and immunity. Nevertheless, the effects of hyperoxia on gut microbiome and metabolome remain unclear, and metagenomic and metabolomics analysis were performed in this mouse study. Methods: C57BL/6 mice were randomly divided into a control (CON) group exposed to room air with fractional inspired oxygen (FiO2) of 21% and a hyperoxia (OXY) group exposed to FiO2 of 80% for 7 days, respectively. Fecal pellets were collected on day 7 and subjected to metagenomic sequencing. Another experiment with the same design was performed to explore the impact of hyperoxia on gut and serum metabolome. Fecal pellets and blood were collected and high-performance liquid chromatography with mass spectrometric analysis was carried out. Results: At the phylum level, hyperoxia increased the ratio of Firmicutes/Bacteroidetes (p = 0.049). At the species level, hyperoxia reduced the abundance of Muribaculaceae bacterium Isolate-037 (p = 0.007), Isolate-114 (p = 0.010), and Isolate-043 (p = 0.011) etc. Linear discriminant analysis effect size (LEfSe) revealed that Muribaculaceae and Muribaculaceae bacterium Isolate-037, both belonging to Bacteroidetes, were the marker microbes of the CON group, while Firmicutes was the marker microbes of the OXY group. Metagenomic analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-Active enZYmes (CAZy) revealed that hyperoxia provoked disturbances in carbohydrate and lipid metabolism. Fecal metabolomics analysis showed hyperoxia reduced 11-dehydro Thromboxane B2-d4 biosynthesis (p = 1.10 × 10-11). Hyperoxia blunted fecal linoleic acid metabolism (p = 0.008) and alpha-linolenic acid metabolism (p = 0.014). We showed that 1-docosanoyl-glycer-3-phosphate (p = 1.58 × 10-10) was the most significant differential serum metabolite inhibited by hyperoxia. In addition, hyperoxia suppressed serum hypoxia-inducible factor-1 (HIF-1, p = 0.007) and glucagon signaling pathways (p = 0.007). Conclusion: Hyperoxia leads to gut dysbiosis by eliminating beneficial and oxygen strictly intolerant Muribaculaceae with genomic dysfunction of carbohydrate and lipid metabolism. In addition, hyperoxia suppresses unsaturated fatty acid metabolism in the gut and inhibits the HIF-1 and glucagon signaling pathways in the serum.

Controlling Selenization Equilibrium Enables High-Quality Kesterite Absorbers for Efficient Solar Cells.

Kesterite Cu2ZnSn(S, Se)4 is considered one of the most competitive photovoltaic materials due to its earth-abundant and nontoxic constituent elements, environmental friendliness, and high stability. However, the preparation of high-quality Kesterite absorbers for photovoltaics is still challenging for the uncontrollability and complexity of selenization reactions between metal element precursors and selenium. In this study, we propose a solid-liquid/solid-gas (solid precursor and liquid/vapor Se) synergistic reaction strategy to precisely control the selenization process. By pre-depositing excess liquid selenium, we provide the high chemical potential of selenium to facilitate the direct and rapid formation of the Kesterite phase. The further optimization of selenium condensation and subsequent volatilization enables the efficient removal of organic compounds and thus improves charge transport in the absorber film. As a result, we achieve high-performance Kesterite solar cells with total-area efficiency of 13.6% (certified at 13.44%) and 1.09 cm2-area efficiency of 12.0% (certified at 12.1%).

Adaptive Dynamic Event-Triggered Distributed Output Observer for Leader-Follower Multiagent Systems Under Directed Graphs.

Leader-follower consensus problem for multiagent systems (MASs) is an important research hotspot. However, the existing methods take the leader system matrix as a priori knowledge for each agent to design the controller and use the leader's state information. In fact, only the output information may be available in some practical applications. On this basis, this article first designs a novel adaptive distributed dynamic event-triggered observer for each follower to learn the minimum polynomial coefficients of the leader system matrix instead of the leader system matrix. The proposed method is scalable and suitable for large-scale MASs and can reduce the information transmission dimension in observer design. Then, an adaptive dynamic event-triggered compensator based on the observer and leader output information is designed for each follower, thereby solving the leader-follower consensus problem. Finally, several simulation examples are given to verify the effectiveness of the proposed scheme.

Current status and progress in research on dressing management for diabetic foot ulcer.

Diabetic foot ulcer (DFU) is a major complication of diabetes and is associated with a high risk of lower limb amputation and mortality. During their lifetime, 19%-34% of patients with diabetes can develop DFU. It is estimated that 61% of DFU become infected and 15% of those with DFU require amputation. Furthermore, developing a DFU increases the risk of mortality by 50%-68% at 5 years, higher than some cancers. Current standard management of DFU includes surgical debridement, the use of topical dressings and wound decompression, vascular assessment, and glycemic control. Among these methods, local treatment with dressings builds a protective physical barrier, maintains a moist environment, and drains the exudate from DFU wounds. This review summarizes the development, pathophysiology, and healing mechanisms of DFU. The latest research progress and the main application of dressings in laboratory and clinical stage are also summarized. The dressings discussed in this review include traditional dressings (gauze, oil yarn, traditional Chinese medicine, and others), basic dressings (hydrogel, hydrocolloid, sponge, foam, film agents, and others), bacteriostatic dressings, composite dressings (collagen, nanomaterials, chitosan dressings, and others), bioactive dressings (scaffold dressings with stem cells, decellularized wound matrix, autologous platelet enrichment plasma, and others), and dressings that use modern technology (3D bioprinting, photothermal effects, bioelectric dressings, microneedle dressings, smart bandages, orthopedic prosthetics and regenerative medicine). The dressing management challenges and limitations are also summarized. The purpose of this review is to help readers understand the pathogenesis and healing mechanism of DFU, help physicians select dressings correctly, provide an updated overview of the potential of biomaterials and devices and their application in DFU management, and provide ideas for further exploration and development of dressings. Proper use of dressings can promote DFU healing, reduce the cost of treating DFU, and reduce patient pain.

Life Events, Boredom Proneness and Mobile Phone Addiction Tendency: A Longitudinal Mediation Analysis Based on Latent Growth Modeling (LGM).

Purpose: Mobile phone addiction has motivated a widespread concern in recent years. From a developmental perspective, this study explored the predictive relations between life events, boredom proneness (BP), and mobile phone addiction tendency (MPAT) among undergraduate students. It also tested the longitudinal mediation of BP between life events and MPAT. Methods: Five hundred and eighty-four undergraduate students completed the Mobile Phone Addiction Tendency Scale, the Adolescent Self-Rating Life Events Checklist, and the Boredom Proneness Scale-Short Form. A longitudinal mediation analysis based on latent growth modeling was conducted to test the hypothesized relationships among life events, BP and MPAT. Results: Latent growth modeling (LGM) showed that the BP and MPAT of undergraduate students both increased linearly. A longitudinal model based on LGM showed that negative life events both directly and indirectly affected the initial level and the growth rate of the MPAT through the mediating effect of the initial level of BP. Conclusion: These results reveal that negative life events are an indicator of the development of MPAT. It has practical implications for calling for adopting health coping styles when facing negative life events. Supported for reducing college students' boredom proneness in order to lessen the tendency towards mobile phone addiction to improve their mental health.

Expanding the mutational spectrum of ZTTK syndrome: A de novo variant with global developmental delay and malnutrition in a Chinese patient.

BACKGROUND: Zhu-Tokita-Takenouchi-Kim (ZTTK, OMIM 617140) syndrome is a severe multisystem developmental disorder characterized by intellectual disability, developmental delay, cortical malformations, epilepsy, visual problems, musculoskeletal abnormalities, and congenital malformations. ZTTK syndrome is caused by a heterozygous pathogenic variant of the SON gene (NM_138927) at chromosome 21q22.1. The purpose of this study was to investigate the pathogenesis of a 6-month-old Chinese child who exhibited global developmental delay, muscle weakness, malnutrition, weight loss, and strabismus, brain abnormality, immunological system abnormalities. METHODS: The little girl was tested for medical exome sequencing (MES) and mtDNA sequencing in trio. And, the mutation was validated by Sanger sequencing. RESULTS: A novel de novo frameshift variant, c.1845_1870del26 (p.G616Sfs*61), in the SON gene was found in the proband. CONCLUSION: We described a 6-month-old Chinese child with global developmental delay caused by pathogenic de novo mutation c.1845_1870del26 (p.G616Sfs*61) in the SON. Apart from a founder mutation, we reviewed the phenotypic abnormalities and genotypes in 79 individuals. The data showed that global developmental delay is accompanied by other system disorders. Our findings expanded the mutational spectrum of ZTTK syndrome and provide genetic counseling of baby with global developmental delay.

Exploring psychological and psychosocial correlates of non-suicidal self-injury and suicide in college students using network analysis.

BACKGROUND: Non-suicidal self-injury (NSSI) and suicide are a serious health concern in young people. Remarkable progress has been made in understanding the correlates and risk factors for suicidality. However, it remains unclear the complex interplay between different factors and which factors are most saliently associated with NSSI and suicide risk and should be targeted for interventions. METHODS: This study utilized network analysis to examine the interrelationship between NSSI, suicide and a variety of psychological (e.g., depression, psychotic-like experiences) and psychosocial (e.g., childhood maltreatment, family dysfunction, being bullied and social support) correlates in a sample of Chinese first year college students (n = 2328). RESULTS: The severity of depressive symptoms was the only factor connected to both NSSI and suicide. Other psychiatric factors like psychotic experiences could only act in an indirect way via the bridging effect of depression. Emotional abuse, compared with other forms of childhood adversities, was found to be the most influential maltreatment form associated with suicidal ideation and attempts. Finally, social support showed the potential to lower the risk of self-injury and suicide in young people. LIMITATIONS: Only a subset of risk and resilience factors of NSSI and suicide were included. Causal inference was impossible due to the cross-sectional design. CONCLUSIONS: Our findings highlighted the importance of identifying risk groups with mental illnesses or negative childhood events, and providing additional support during the key time of transitioning into higher education.

Constructing an Interfacial Gradient Heterostructure Enables Efficient CsPbI3 Perovskite Solar Cells and Printed Minimodules.

Severe nonradiative recombination originating from interfacial defects together with the pervasive energy level mismatch at the interface remarkably limits the performance of CsPbI3 perovskite solar cells (PSCs). These issues need to be addressed urgently for high-performance cells and their applications. Herein, an interfacial gradient heterostructure based on low-temperature post-treatment of quaternary bromide salts for efficient CsPbI3 PSCs with an impressive efficiency of 21.31% and an extraordinary fill factor of 0.854 is demonstrated. Further investigation reveals that Br- ions diffuse into the perovskite films to heal undercoordinated Pb2+ and inhibit Pb cluster formation, thus suppressing nonradiative recombination in CsPbI3 . Meanwhile, a more compatible interfacial energy level alignment resulting from Br- gradient distribution and organic cations surface termination is also achieved, hence promoting charge separation and collection. Consequently, the printed small-size cell with an efficiency of 20.28% and 12 cm2 printed CsPbI3 minimodules with a record efficiency of 16.60% are also demonstrated. Moreover, the unencapsulated CsPbI3 films and devices exhibit superior stability.

Photoelectric properties of the layered raspberry sandwich amorphous ZnCo2S4@MnCo2S4/CP composite counter electrode in semiconductor-sensitized solar cells.

Multistage amorphous materials have promising applications in the catalytic performance of dye-sensitized solar cells (DSSCs). Herein, an amorphous sheet-raspberry sandwich-like ZnCo2S4@MnCo2S4/CP composite material was rationally designed and developed as a counter electrode (CE) for DSSCs by applying a three-step hydrothermal method. The first development of the amorphous composites as CEs resulted in lower charge transfer resistance at the CE/electrolyte interface and improved the fill factor and short-circuit current density. The excellent catalytic performance is mainly attributed to the large number of unsaturated coordination sites generated by the undirected structure of the lamellar-raspberry intercalated amorphous material, the smooth ion transport interface with a self-built corrosion-resistant layer, coupled with the dual catalytic performance of the Zn, Co, and Mn composites, and the good electrical conductivity of the C substrate. When ZnCo2S4@MnCo2S4/CP was used as the CE on a Ti substrate, the photoelectric conversion efficiency was as high as 11.68% (Voc = 0.821, Jsc = 20.14 mA cm-2, and FF = 0.71) under 100 mW cm-2 light illumination. This paper provides a design idea for amorphous materials in terms of catalytic performance and a method for developing alternatives to Pt electrodes.

Dynamic Event-Based Control for Stochastic Optimal Regulation of Nonlinear Networked Control Systems.

In this article, a dynamic event-triggered stochastic adaptive dynamic programming (ADP)-based problem is investigated for nonlinear systems with a communication network. First, a novel condition of obtaining stochastic input-to-state stability (SISS) of discrete version is skillfully established. Then, the event-triggered control strategy is devised, and a near-optimal control policy is designed using an identifier-actor-critic neural networks (NNs) with an event-sampled state vector. Above all, an adaptive static event sampling condition is designed by using the Lyapunov technique to ensure ultimate boundedness (UB) for the closed-loop system. However, since the static event-triggered rule only depends on the current state, regardless of previous values, this article presents an explicit dynamic event-triggered rule. Furthermore, we prove that the lower bound of sampling interval for the proposed dynamic event-triggered control strategy is greater than one, which avoids the so-called triviality phenomenon. Finally, the effectiveness of the proposed near-optimal control pattern is verified by a simulation example.

MicroRNA-210-3p mediates trabecular meshwork extracellular matrix accumulation and ocular hypertension - Implication for novel glaucoma therapy.

Elevation of intraocular pressure (IOP) is a major, controllable risk factor of primary open-angle glaucoma (POAG). Transforming growth factor-ß2 (TGF-ß2)-induced excessive accumulation of extracellular matrix (ECM) in the trabecular meshwork (TM) has been demonstrated to contribute significantly to the development of high IOP. We previously showed that treatment with salidroside (Sal), a plant-derived glucoside, can ameliorate the TGF-ß2-induced ECM expression in cultured human TM cells and reduce TGF-ß2-induced ocular hypertension in mice. In the current study, its underlying molecular mechanism associated with microRNA-210-3p (miR-210-3p) was characterized. We discovered that, in TM tissues of POAG patients, there was an increase in miR-210-3p. And miR-210-3p mediated a portion of the pathological effects of TGF-ß2 in vitro (excessive accumulation of ECM in cultured human TM cells) and in vivo (mouse ocular hypertension and ECM accumulation in the TM). Most interestingly, miR-210-3p was down-regulated by Sal, which appeared to mediate a significant portion of its IOP-lowering effect. Thus, these results shed light on the probable molecular mechanisms of TGF-ß2 and Sal and indicate that manipulation of miR-210-3p level/activity represents a potential new therapeutic strategy for POAG.

Chain mediating effect of insomnia, depression, and anxiety on the relationship between nightmares and cognitive deficits in adolescents.

BACKGROUND: The study explored the differences in nightmare, insomnia, depression, anxiety, and cognitive deficits among adolescents and the chain mediating effects of insomnia, depression, and anxiety on the relationship between nightmares and cognitive deficits in adolescents. METHODS: An online survey was used to collect demographic data of 6014 adolescents and assess nightmare, insomnia, depression, anxiety, and cognitive deficits using the Chinese Version of Nightmare Distress Questionnaire, Insomnia Severity Index, Patient Health Questionnaire 9, Generalized Anxiety Disorder 7, and Perceived Deficits Questionnaire-Depression. Spearman correlation analysis and the SPSS function "PROCESS macro" were used for correlation and mediation analyses, respectively. RESULTS: Female adolescents, senior high school, and poor academic performance had higher nightmare, insomnia, and cognitive deficit scores; those living in the city had higher depression and anxiety scores. Cognitive deficits were positively correlated with nightmares, insomnia, depression, and anxiety. Further, insomnia, depression, and anxiety had a chain mediating effect between nightmares and cognitive deficits in adolescents. Nightmares indirectly affect cognition deficits by affecting insomnia and then depression and anxiety symptoms. LIMITATIONS: As this was a cross-sectional study, the causal relationship between the variables could not be determined. Moreover, reporting bias and volunteer bias might be present. CONCLUSIONS: These findings suggest that clinicians should identify adolescents with frequent nightmares early and provide timely treatment to minimize negative outcomes and possibly limit the chronicity of nightmare disorder. It is significant to maintain the physical and mental health development of adolescents to reduce the risk of insomnia, depression, anxiety, and cognitive deficits.