Synergetic Enzyme-Incorporated Metal-Organic Framework and Polyoxometalate Nanozyme: Achieving Stable Tandem Catalysis for Organic Photoelectrochemical Transistor Bioanalysis.

Organic photoelectrochemical transistor (OPECT) has emerged as a promising technique for biomolecule detection, yet its operational rationale remains limited due to its short development time. This study introduces a stable tandem catalysis protocol by synergizing the enzyme-incorporated metal-organic frameworks (E-MOFs) with polyoxometalate (POM) nanozyme for sensitive OPECT bioanalysis. The zeolitic imidazolate framework-8 (ZIF-8) acts as the skeleton to protect the encapsulated glucose oxidase (GOx), allowing the stable catalytic generation of H2O2. With peroxidase-like activity, a phosphotungstic acid hydrate (PW12) is then able to utilize the H2O2 to induce the biomimetic precipitation on the photogate, ultimately resulting in the altered device characteristics for quantitative detection. This work reveals the potential and versatility of an engineered enzymatic system as a key enabler to achieve novel OPECT bioanalysis, which is believed to offer a feasible framework to explore new operational rationale in optoelectronic and bioelectronic detection.

Irisin mitigates salt-sensitive hypertension via regulating renal AMPK-Rac1 pathway.

BACKGROUND: Irisin, as a myokine, plays a protective role against cardiovascular disease, including myocardial infarction, atherosclerosis and hypertension. However, whether irisin attenuates salt-sensitive hypertension and the related underlying mechanisms is unknown. METHODS: Male Dahl salt-resistant (DSR) and Dahl salt-sensitive (DSS) (12 weeks) rats were fed a high salt diet (8% NaCl) with or without irisin treatment by intraperitoneal injection for 8 weeks. RESULTS: Compared with DSR rats, DSS rats showed higher systolic blood pressure (SBP), impaired natriuresis and diuresis and renal dysfunction. In addition, it was accompanied by downregulation of renal p-AMPKα and upregulation of renal RAC1 and nuclear mineralocorticoid receptor (MR). Irisin intervention could significantly up-regulated renal p-AMPKα level and down-regulated renal RAC1-MR signal, thereby improving renal sodium excretion and renal function, and ultimately reducing blood pressure in DSS rats. Ex vivo treatment with irisin reduced the expression of RAC1 and nuclear MR in primary renal distal convoluted tubule cells from DSS rats and the effects of irisin were abolished by cotreatment of compound C (AMPK inhibitor), indicating that the regulation of RAC1-MR signals by irisin depended on the activation of AMPK. CONCLUSIONS: Irisin administration lowered salt-sensitive hypertension through regulating RAC1-MR signaling via activation of AMPK, which may be a promising therapeutic approach for salt-sensitive hypertension.

Locus coeruleus microstructural integrity is associated with vigilance vulnerability to sleep deprivation.

Insufficient sleep compromises cognitive performance, diminishes vigilance, and disrupts daily functioning in hundreds of millions of people worldwide. Despite extensive research revealing significant variability in vigilance vulnerability to sleep deprivation, the underlying mechanisms of these individual differences remain elusive. Locus coeruleus (LC) plays a crucial role in the regulation of sleep-wake cycles and has emerged as a potential marker for vigilance vulnerability to sleep deprivation. In this study, we investigate whether LC microstructural integrity, assessed by fractional anisotropy (FA) through diffusion tensor imaging (DTI) at baseline before sleep deprivation, can predict impaired psychomotor vigilance test (PVT) performance during sleep deprivation in a cohort of 60 healthy individuals subjected to a rigorously controlled in-laboratory sleep study. The findings indicate that individuals with high LC FA experience less vigilance impairment from sleep deprivation compared with those with low LC FA. LC FA accounts for 10.8% of the variance in sleep-deprived PVT lapses. Importantly, the relationship between LC FA and impaired PVT performance during sleep deprivation is anatomically specific, suggesting that LC microstructural integrity may serve as a biomarker for vigilance vulnerability to sleep loss.

Molecule Engineering Metal-Organic Framework-Based Organic Photoelectrochemical Transistor Sensor for Ultrasensitive Bilirubin Detection.

The functionalization of metal-organic frameworks (MOFs) with organic small molecules by in situ postsynthetic modification has garnered considerable attention. However, the precise engineering of recognition sites using this method remains rarely explored in optically controlled bioelectronics. Herein, employing the Schiff base reaction to embed the small molecule (THBA) into a Zr-MOF, we fabricated a hydroxyl-rich MOF on the surface of titanium dioxide nanorod arrays (U6H@TiO2 NRs) to develop light-sensitive gate electrodes with tailored recognition capabilities. The U6H@TiO2 NR gate electrodes were integrated into organic photoelectrochemical transistor (OPECT) sensing systems to tailor a sensitive device for bilirubin (I-Bil) detection. In the presence of I-Bil, coordination effects, hydrogen bonding, and π-π interactions facilitated strong binding between U6H@TiO2 NRs and the target I-Bil. The electron-donating property of I-Bil influenced the gate voltage, enabling precise control of the channel status and modulation of the channel current. The OPECT device exhibited exceptional analytical performance toward I-Bil with wide linearity ranging from 1 × 10-16 to 1 × 10-9 M and a low limit detection of 0.022 fM. Leveraging the versatility of small molecules for boosting the functionalization of materials, this work demonstrates the great potential of the small molecule family for OPECT bioanalysis and holds promise for the advancement of OPECT sensors.

Single-cell transcriptome analysis revealed heterogeneity in glycolysis and identified IGF2 as a therapeutic target for ovarian cancer subtypes.

BACKGROUND: As the most malignant tumor of the female reproductive system, ovarian cancer (OC) has garnered increasing attention. The Warburg effect, driven by glycolysis, accounts for tumor cell proliferation under aerobic conditions. However, the metabolic heterogeneity linked to glycolysis in OC remains elusive. METHODS: We integrated single-cell data with OC to score glycolysis level in tumor cell subclusters. This led to the identification of a subcluster predominantly characterized by glycolysis, with a strong correlation to patient prognosis. Core transcription factors were pinpointed using hdWGCNA and metaVIPER. A specific transcription factor regulatory network was then constructed. A glycolysis-related prognostic model was developed and tested for estimating OC prognosis with a total of 85 machine-learning combinations, focusing on specific upregulated genes of two subtypes. We identified IGF2 as a key within the prognostic model and investigated its impact on OC progression and drug resistance through in vitro experiments, including the transwell assay, lactate production detection, and the CCK-8 assay. RESULTS: Analysis showed that the Malignant 7 subcluster was primarily related to glycolysis. Two OC molecular subtypes, CS1 and CS2, were identified with distinct clinical, biological, and microenvironmental traits. A prognostic model was built, and IGF2 emerged as a key gene linked to prognosis. Experiments have proven that IGF2 can promote the glycolysis pathway and the malignant biological progression of OC cells. CONCLUSIONS: We developed two novel OC subtypes based on glycolysis score, established a stable prognostic model, and identified IGF2 as the marker gene. These insights provided a new avenue for exploring OC's molecular mechanisms and personalized treatment approaches.

Relationships among self-esteem, depression and self-injury in adolescents: a longitudinal study.

Objective: Non-suicidal self-injury is a widespread mental health concern among adolescents. This study aimed to examine the relationship between self-esteem, depression, and self-injury among adolescents using a longitudinal research design. Methods: The Self-Esteem Scale (SES), Child Depression Inventory (CDI), and Adolescent Self-Injury Scale (ASIS) were used to follow up 1,265 junior middle school students on three occasions with six-month intervals. Results: At all three time points, there were significant gender differences in self-esteem, depression, and self-injury. Self-esteem was negatively correlated with depression and self-injury at all three time points, while depression and self-injury were significantly positively correlated. Cross-lagged analysis revealed that self-esteem at Time 1 (T1) did not significantly predict self-injury at Time 2 (T2), but self-esteem (T2) significantly predicted self-injury at Time 3 (T3; ß = -0.079, p < 0.05). Similarly, self-injury (T1) significantly predicted self-esteem (T2; ß = -0.140, p < 0.001), and self-injury (T2) significantly predicted self-esteem (T3; ß = -0.071, p < 0.01). Horizontal and longitudinal mediating analysis showed that depression served as a complete mediator in both the pathway from self-esteem to self-injury and from self-injury to self-esteem. Cross-lagged analysis showed that self-esteem (T1) significantly predicts depression (T2; ß = -0.070, p < 0.05), which in turn predict self-injury (T3; ß = 0.126, p < 0.001). Similarly, self-injury (T1) predicted depression (T2; ß = 0.055, p < 0.05), which further predicted self-esteem (T3; ß = -0.218, p < 0.001). Conclusion: The self-esteem, depression, and self-injury of adolescents are closely related; self-esteem and self-injury predict each other; self-esteem indirectly affects self-injury through depression; and self-injury indirectly affects self-esteem through depression. Based on the relationship of bi-directional prediction of self-esteem and self-injury mediated by depression, this study proposes a theoretical model of depression-mediated self-esteem and self-injury cycle.

Network analysis of the relationship between non-suicidal self-injury, depression, and childhood trauma in adolescents.

BACKGROUND: Non-suicidal self-injury seriously harm the physical and mental health of adolescents. The aim of the current study was to explore the relationship between non-suicide self-injury, depression, and childhood trauma from the perspective of symptoms in adolescents. METHODS: A cross-sectional survey was conducted in four junior high middle schools and collected 2640 valid questionnaires. There were 1329 male students and 1311 female students. The age of the participants ranged from 11 to 17 years old, with a mean age of 13.3 (± 0.94) years. Non-suicidal self-injury (NSSI), depressive symptoms, and childhood trauma were assessed using the Adolescent Self-Harm Scale, the Childhood Depression Scale, and the Childhood Trauma Questionnaire, respectively. A network analysis was performed. RESULTS: In the network, NSSI, depressive symptoms, and childhood trauma were closely related. Negative self-esteem in the depressive symptoms and emotional abuse in childhood were the most central nodes. Negative self-esteem and negative mood were directly connected to NSSI, other nodes of depressive symptoms appeared to be indirectly connected to NSSI through these two nodes. Emotional abuse was the only node in childhood trauma categories directly connected to NSSI. Nodes of other categories of childhood trauma (physical neglect, physical abuse, emotional neglect, and sexual abuse) were indirectly connected to NSSI through emotional abuse. CONCLUSIONS: NSSI, depression, and childhood trauma of teenagers were closely related. Individuals who have suffered emotional abuse in childhood were more likely to have depressive symptoms and NSSI. Improving negative self-esteem and negative emotions and reducing emotional abuse may be beneficial in alleviating depression and reducing NSSI in adolescents.

Icariin regulates RANKL-induced osteoclast differentiation via the ERα/c-Src/RANK signaling.

Osteoporosis (OP) is a common metabolic bone disease. Excessive osteoclastic activity significantly contributes to the development of OP. Icariin (ICA) is a flavonol glycoside derived from herbal plants and possesses curative effects on postmenopausal OP and bone fracture. This study aimed to investigate the effects of ICA on osteoclast differentiation induced by receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) and the involvement of estrogen receptorα(ERα) and RANK signaling cascade in this process. RANKL was used to induce the differentiation of RAW264.7 cells to into osteoclasts. Small interfering RNA technique was used to knockdown ERαin cells. Cell counting kit-8 assay was performed to determine the cytotoxicity of ICA. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells was quantified by TRAP staining. RANKL induced the differentiation of RAW264.7 cells into osteoclasts, while ICA abolished the pro-osteoporotic effect of RANKL. Moreover, ERαknockdown abolished the effects of ICA on RANKL-induced osteoclastogenesis. Further exploration revealed that ICA inhibited the phosphorylation ofc-Src in osteoclasts via regulating ERα, while inactivation ofc-Src reversed ERαknockdown-promoted osteoclastogenesis. Lastly, ICA inhibited the activation of the mitogen-activated protein kinase signaling pathway and downregulated the expressions of target osteoclastogenic proteins in RANKL-treated RAW 264.7 cells, while ERαknockdown almost completely diminished the effects of ICA. ICA inhibited RANKL-induced osteoclast differentiation via regulating the ERα/c-Src/RANK signaling. These findings elucidated a novel mechanism by which ICA exerts an anti-osteoporotic effect.

Sex-specific resting state brain network dynamics in patients with major depressive disorder.

Sex-specific neurobiological changes have been implicated in Major Depressive Disorder (MDD). Dysfunctions of the default mode network (DMN), salience network (SN) and frontoparietal network (FPN) are critical neural characteristics of MDD, however, the potential moderating role of sex on resting-state network dynamics in MDD has not been sufficiently evaluated. Thus, resting-state functional magnetic resonance imaging (fMRI) data were collected from 138 unmedicated patients with first-episode MDD (55 males) and 243 healthy controls (HCs; 106 males). Recurring functional network co-activation patterns (CAPs) were extracted, and time spent in each CAP (the total amount of volumes associated to a CAP), persistence (the average number of consecutive volumes linked to a CAP), and transitions across CAPs involving the SN, DMN and FPN were quantified. Relative to HCs, MDD patients exhibited greater persistence in a CAP involving activation of the DMN and deactivation of the FPN (DMN + FPN-). In addition, relative to the sex-matched HCs, the male MDD group spent more time in two CAPs involving the SN and DMN (i.e., DMN + SN- and DMN-SN + ) and transitioned more frequently from the DMN + FPN- CAP to the DMN + SN- CAP relative to the male HC group. Conversely, the female MDD group showed less persistence in the DMN + SN- CAP relative to the female HC group. Our findings highlight that the imbalance between SN and DMN could be a neurobiological marker supporting sex differences in MDD. Moreover, the dominance of the DMN accompanied by the deactivation of the FPN could be a sex-independent neurobiological correlate related to depression.

Mitophagy-related long non-coding RNA signature predicts prognosis and drug response in Ovarian Cancer.

BACKGROUND: Ovarian cancer (OC) is the most malignant tumor with the worst prognosis in female reproductive system. Mitophagy and long non-coding RNAs (lncRNAs) play pivotal roles in tumorigenesis, development, and drug resistance. The effects of mitophagy-related lncRNAs on OC prognosis and therapeutic response remain unelucidated. METHODS: We retrieved OC-related RNA sequence, copy number variation, somatic mutation, and clinicopathological information from The Cancer Genome Atlas database and mitophagy-related gene sets from the Reactome database. Pearson's correlation analysis was used to distinguish mitophagy-related lncRNAs. A prognostic lncRNA signature was constructed using UniCox, LASSO, and forward stepwise regression analysis. Individuals with a risk score above or below the median were classified as high- or low-risk groups, respectively. The risk model was analyzed using the Kaplan-Meier estimator, receiver operating characteristic curve, decision curve analysis, and Cox regression analysis and validated using an internal dataset. LINC00174 was validated in clinical samples and OC cell lines. We also reviewed reports on the role of LINC00174 in cancer. Subsequently, a nomogram model was constructed. Furthermore, the Genomics of Drug Sensitivity in Cancer database was used to explore the relationship between the risk model and anti-tumor drug sensitivity. Gene set variation analysis was performed to assess potential differences in biological functions between the two groups. Finally, a lncRNA prognostic signature-related competing endogenous RNA (ceRNA) network was constructed. RESULTS: The prognostic signature showed that patients in the high-risk group had a poorer prognosis. The nomogram exhibited satisfactory accuracy and predictive potential. LINC00174 mainly acts as an oncogene in cancer and is upregulated in OC; its knockdown inhibited the proliferation and migration, and promoted apoptosis of OC cells. High-risk patients were more insensitive to cisplatin and olaparib than low-risk patients. The ceRNA network may help explore the potential regulatory mechanisms of lncRNAs. CONCLUSION: The mitophagy-related lncRNA signature can help estimate the survival and drug sensitivity, the ceRNA network may provide novel therapeutic targets for patients with OC.

Enhanced amygdala-cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation.

Sleep loss robustly disrupts mood and emotion regulation in healthy individuals but can have a transient antidepressant effect in a subset of patients with depression. The neural mechanisms underlying this paradoxical effect remain unclear. Previous studies suggest that the amygdala and dorsal nexus (DN) play key roles in depressive mood regulation. Here, we used functional MRI to examine associations between amygdala- and DN-related resting-state connectivity alterations and mood changes after one night of total sleep deprivation (TSD) in both healthy adults and patients with major depressive disorder using strictly controlled in-laboratory studies. Behavioral data showed that TSD increased negative mood in healthy participants but reduced depressive symptoms in 43% of patients. Imaging data showed that TSD enhanced both amygdala- and DN-related connectivity in healthy participants. Moreover, enhanced amygdala connectivity to the anterior cingulate cortex (ACC) after TSD associated with better mood in healthy participants and antidepressant effects in depressed patients. These findings support the key role of the amygdala-cingulate circuit in mood regulation in both healthy and depressed populations and suggest that rapid antidepressant treatment may target the enhancement of amygdala-ACC connectivity.

Effects of Kinesio Taping for Chronic Nonspecific Low Back Pain: A Systematic Review and Meta-analysis.

Context: Chronic nonspecific low back pain (CNLBP) is a common musculoskeletal disorder that seriously affects patients' quality of life (QoL). Clinicians have used Kinesio Taping (KT) in the treatment of CNLBP patients, but evidence is still lacking on the benefits of KT for CNLBP. Objective: The study aimed to perform a systematic review and meta-analysis of the currently published randomized controlled trails (RCTs) to determine KT's efficacy for CNLBP patients. Design: The research team performed a literature search using five major electronic databases-PubMed, Embase, Web of science, Cochrane Library, MEDLINE and OpenGrey-and included studies form inception to January 2018. The search used the keywords "kinesio tap*", "kinesio*", and "chronic low back pain (CLBP)" or "CNLBP". Setting: The study took place in the 942 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army. Outcome Measures: The research team performed the meta-analysis using RevMan 5.3 software. The team selected studies that used pain intensity and disability as the primary outcome measures, and if the study used other outcomes, they had to be the secondary outcomes. Results: The systematic review included nine RCTs in the meta-analysis. KT can significantly reduce pain intensity between baseline and immediately postintervention (SMD = -0.47, 95% CI -0.93 to -0.02, P = .04) and between baseline and the short-term follow-up period (SMD = -0.67, 95% CI -0.44 to -0.20, P = .03). However, no significant differences existed between KT's ability to relieve other symptoms of CNLBP-disability, trunk flexion range of motion (ROM), change in status, fear of movement, isometric endurance of the trunk muscles, or extension-when compared to either sham taping or KT as an adjunct to physical therapy. Conclusions: KT can have immediate and short-term positive effects on reducing pain intensity, but existing evidence doesn't support KT's superiority to other interventions in improving functions for individuals with CNLBP.

Test-Retest Reliability of Resting Brain Small-World Network Properties across Different Data Processing and Modeling Strategies.

Resting-state functional magnetic resonance imaging (fMRI) with graph theoretical modeling has been increasingly applied for assessing whole brain network topological organization, yet its reproducibility remains controversial. In this study, we acquired three repeated resting-state fMRI scans from 16 healthy controls during a strictly controlled in-laboratory study and examined the test-retest reliability of seven global and three nodal brain network metrics using different data processing and modeling strategies. Among the global network metrics, the characteristic path length exhibited the highest reliability, whereas the network small-worldness performed the poorest. Nodal efficiency was the most reliable nodal metric, whereas betweenness centrality showed the lowest reliability. Weighted global network metrics provided better reliability than binary metrics, and reliability from the AAL90 atlas outweighed those from the Power264 parcellation. Although global signal regression had no consistent effects on the reliability of global network metrics, it slightly impaired the reliability of nodal metrics. These findings provide important implications for the future utility of graph theoretical modeling in brain network analyses.

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OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS: Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.

Persistent Ventral Anterior Cingulate Cortex and Resolved Amygdala Hyper-responses to Negative Outcomes After Depression Remission: A Combined Cross-sectional and Longitudinal Study.

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent mood disorder affecting more than 300 million people worldwide. Biased processing of negative information and neural hyper-responses to negative events are hallmarks of depression. This study combined cross-sectional and longitudinal experiments to explore both persistent and resolved neural hyper-responses to negative outcomes from risky decision making in patients with current MDD (cMDD) and remitted MDD (rMDD). METHODS: A total of 264 subjects participated in the cross-sectional study, including 117 patients with medication-naïve, first-episode current depression; 45 patients with rMDD with only 1 episode of depression; and 102 healthy control subjects. Participants completed a modified balloon analog risk task during functional magnetic resonance imaging. In the longitudinal arm of the study, 42 patients with cMDD were followed and 26 patients with rMDD were studied again after 8 weeks of antidepressant treatment. RESULTS: Patients with cMDD showed hyper-responses to loss outcomes in multiple limbic regions including the amygdala and ventral anterior cingulate cortex (vACC). Amygdala but not vACC hyperactivity correlated with depression scores in patients with cMDD. Furthermore, amygdala hyperactivity resolved while vACC hyperactivity persisted in patients with rMDD in both cross-sectional and longitudinal studies. CONCLUSIONS: These findings provide consistent evidence supporting differential patterns of amygdala and vACC hyper-responses to negative outcomes during depression remission. Amygdala hyperactivity may be a symptomatic and state-dependent marker of depressive neural responses, while vACC hyperactivity may reflect a persistent and state-independent effect of depression on brain function. These findings offer new insights into the neural underpinnings of depression remission and prevention of depression recurrence.

Decision-making biases in suicide attempters with major depressive disorder: A computational modeling study using the balloon analog risk task (BART).

BACKGROUND: In the last decade, suicidality has been increasingly theorized as a distinct phenomenon from major depressive disorder (MDD), with unique psychological and neural mechanisms, rather than being mostly a severe symptom of MDD. Although decision-making biases have been widely reported in suicide attempters with MDD, little is known regarding what components of these biases can be distinguished from depressiveness itself. METHODS: Ninety-three patients with current MDD (40 with suicide attempts [SA group] and 53 without suicide attempts [NS group]) and 65 healthy controls (HCs) completed psychometric assessments and the balloon analog risk task (BART). To analyze and compare decision-making components among the three groups, we applied a five-parameter Bayesian computational modeling. RESULTS: Psychological assessments showed that the SA group had greater suicidal ideation and psychological pain avoidance than the NS group. Computational modeling showed that both MDD groups had higher risk preference and lower ability to learn and adapt from within-task observations than HCs, without differences between the SA and NS patient groups. The SA group also had higher loss aversion than the NS and HC groups, which had similar loss aversion. CONCLUSIONS: Our BART and computational modeling findings suggest that psychological pain avoidance and loss aversion may be important suicide risk factor that are distinguishable from depression illness itself.

FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2.

Fat mass and obesity-associated protein (FTO) regulates critical pathways in various diseases, including malignant tumours. However, the functional link between FTO and its target genes in epithelial ovarian cancer (EOC) development remains to be elucidated. In this study, the biological functions of FTO were verified in vitro and in vivo. The m6A modification and the binding sites of SNAI1 mRNA were confirmed by m6A RNA immunoprecipitation (MeRIP) and RIP experiments. The actinomycin D assay was used to test the stability of RNA. We found that FTO was downregulated with increased m6A levels in EOC. Reduced expression of FTO was associated with a higher FIGO stage in patients with EOC. Mechanistically, FTO decreased the m6A level and stability of SNAI1 mRNA, causing downregulation of SNAI1 and inhibiting epithelial-mesenchymal transition (EMT). Furthermore, FTO-mediated downregulation of SNAI1 expression depended on IGF2BP2, which acted as an m6A reader binding to the 3' UTR region of SNAI1 mRNA to promote its stability. In conclusion, FTO inhibits SNAI1 expression to attenuate the growth and metastasis of EOC cells in an m6A-IGF2BP2-dependent manner. Our findings suggest that the FTO-IGF2BP2-SNAI1 axis is a potential therapeutic target in EOC.

PHGDH Inhibitor CBR-5884 Inhibits Epithelial Ovarian Cancer Progression via ROS/Wnt/ß-Catenin Pathway and Plays a Synergistic Role with PARP Inhibitor Olaparib.

PHGDH attaches importance to serine biosynthesis in cancer cells and maintaining mitochondrial redox homeostasis. However, the role of PHGDH inhibitor CBR-5884 in cell ROS level and its downstream pathways has not been explored in epithelial ovarian cancer. Thus, we investigated the function and possible mechanism of PHGDH inhibitor CBR-5884 on epithelial ovarian cancer in vitro and in vivo. A2780, OVCAR3, and ES-2 were treated with CBR-5884 at different concentrations or different time points. Results showed that CBR-5884 inhibited epithelial ovarian cancer cell proliferation, migration, and invasion and increases cell ROS level. Meanwhile, CBR-5884 exerts antitumor effect through activating ROS/Wnt/ß-catenin pathway. Besides, CBR-5884 exerts antitumor effect in vivo. What's more, we explored the effect of CBR-5884 with or without PARP inhibitor Olaparib, which showed that the two together had a larger effect. In conclusion, PHGDH inhibitor CBR-5884 inhibits epithelial ovarian cancer proliferation, migration, and invasion through activating ROS/Wnt/ß-catenin pathway and plays a synergistic role with PARP inhibitor olaparib, which provided a theoretical basis for PHGDH inhibitor CBR-5884 in clinical treatment.

An Immune-Related lncRNA Pairing Model for Predicting the Prognosis and Immune-Infiltrating Cell Condition in Human Ovarian Cancer.

Ovarian cancer is the second common cancer among the gynecological tumors. It is difficult to be found and diagnosed in the early stage and easy to relapse due to chemoresistance and deficiency in choices of treatment. Therefore, future exploring the biomarkers for diagnosis, treatment, and prognosis prediction of ovarian cancer is significant to women in the world. We downloaded data from TCGA and GTEx and used R "limma" package for analyzing the differentially expressed immune-related lncRNA in ovarian cancer and finally got 7 downregulated and 171 upregulated lncRNA. Then, we paired the differentially expressed immune-related lncRNA and constructed a novel lncRNA pairing model containing 7 lncRNA pairs. Based on the cut-off point with the highest AUC value, 102 patients were selected in high-risk group and 272 in low-risk group. The KM analysis suggested that the patients in the low-risk group had a longer overall survival. Future analysis showed the correlations between risk scores and clinicopathological parameters and infiltrating immune cells. In conclusion, we identified an immune-related lncRNA pairing model for predicting the prognosis and immune-infiltrating cell condition in human ovarian cancer, which thus further can instruct immunotherapy.

Social Media Disorder, Mental Health, and Validation of the Chinese Version of 27-Item Social Media Disorder Scale in Chinese College Students.

Objective: With the widespread use of social media, excessive use of social media may lead to problematic behaviors such as social media disorder, which has a negative impact on teenagers' mental health. Thus, it is an urgent need to provide a measurement tool to assess social media addiction in different cultures. The aim of this study was to assess the psychometric properties of the Chinese version of 27-item Social Media Disorder (SMD) Scale (developed using the diagnostic criteria of DSM-V Internet Gaming Disorder) in college students, and to verify its impact on mental health. Methods: Two online surveys were conducted among a total of 1,539 Chinese college students, including 1,316 subjects in sample 1 and 223 subjects in sample 2. The discrimination, criterion validity, construct validity and reliability of the Chinese version of SMD-27 scale were examined. Results: The Chinese version of SMD-27 scale showed excellent psychometric properties. The item-total correlation coefficients of the scale ranged from 0.31 to 0.56, and the item-dimension correlations of the scale ranged from 0.459 to 0.834. Findings from confirmatory factor analysis indicated a great fit of the model of the Chinese version of SMD-27, with CFI = 0.956, TLI = 0.951, RMSEA = 0.036 in sample one and CFI = 0.970, TLI = 0.967, RMSEA = 0.040 in sample two, thus confirming the second-order factor structure of the scale. The SMD-27 scale showed good internal consistency between two different samples with their respective Cronbach's alpha of 0.87 and 0.92, and good test-retest reliability over a period of 1 month. In addition, multiple regression results generally supported the impact of social media addiction on mental health. Conclusion: This study provides evidence that the Chinese version of SMD-27 scale is applicable to Chinese college populations, and it is a promising tool for the study of social media addiction in China.