Mulberry Leaf Lipid Nanoparticles: a Naturally Targeted CRISPR/Cas9 Oral Delivery Platform for Alleviation of Colon Diseases.

Oral treatment of colon diseases with the CRISPR/Cas9 system has been hampered by the lack of a safe and efficient delivery platform. Overexpressed CD98 plays a crucial role in the progression of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). In this study, lipid nanoparticles (LNPs) derived from mulberry leaves are functionalized with Pluronic copolymers and optimized to deliver the CRISPR/Cas gene editing machinery for CD98 knockdown. The obtained LNPs possessed a hydrodynamic diameter of 267.2 nm, a narrow size distribution, and a negative surface charge (-25.6 mV). Incorporating Pluronic F127 into LNPs improved their stability in the gastrointestinal tract and facilitated their penetration through the colonic mucus barrier. The galactose end groups promoted endocytosis of the LNPs by macrophages via asialoglycoprotein receptor-mediated endocytosis, with a transfection efficiency of 2.2-fold higher than Lipofectamine 6000. The LNPs significantly decreased CD98 expression, down-regulated pro-inflammatory cytokines (TNF-α and IL-6), up-regulated anti-inflammatory factors (IL-10), and polarized macrophages to M2 phenotype. Oral administration of LNPs mitigated UC and CAC by alleviating inflammation, restoring the colonic barrier, and modulating intestinal microbiota. As the first oral CRISPR/Cas9 delivery LNP, this system offers a precise and efficient platform for the oral treatment of colon diseases.

Circulating microRNAs as diagnostic biomarkers for melanoma: a systematic review and meta-analysis.

BACKGROUND: Recent studies have shown that circulating microRNAs (miRNAs) can be used as diagnostic biomarkers for melanoma. This study aimed to evaluate the diagnostic value of circulating miRNAs for melanoma. METHODS: A comprehensive literature search was conducted and the quality of the included literature was evaluated using QUADAS-2 (Quality Assessment for diagnostic accuracy studies), and the diagnostic accuracy was assessed by pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). We used Deeks' funnel plot to evaluate publication bias. RESULTS: The meta-analysis included 10 articles covering 16 studies, and the results showed that circulating miRNAs provide high diagnostic accuracy for melanoma. The overall pooled sensitivity was 0.87 (95% CI: 0.82-0.91), specificity was 0.81 (95% CI: 0.77-0.85), PLR was 4.6 (95% CI: 3.7-5.8), NLR was 0.16 (95% CI: 0.11-0.23), DOR was 29 (95% CI: 18-49), and AUC was 0.90 (95% CI: 0.87-0.92), respectively. Subgroup analysis showed better diagnostic value in miRNA clusters, European population, plasma miRNAs, and upregulated miRNAs compared to other subgroups. CONCLUSIONS: The results indicated that circulating microRNAs can be used as a non-invasive biomarker for the diagnosis of melanoma.

Associations between abnormal electroencephalogram microstates and childhood emotional abuse in adolescent depression. / é’å°‘å¹´æŠ‘éƒç—‡é™æ¯æ€è„‘ç”µå¾®çŠ¶æ€ä¸Žç«¥å¹´æœŸæƒ æ„Ÿè™å¾ çš„ç›¸å ³æ€§.

OBJECTIVES: Childhood traumatic experiences greatly influenced the brain network activities of patients with depression, and there is an urgent need to explore the temporal dynamics for these changes. This study aims to investigate the abnormalities of resting-state electroencephalogram (EEG) microstates in eye-open state of depressed adolescents and to explore the correlations between their EEG microstates and the childhood traumatic experience. METHODS: Using resting-state EEG microstate analysis, we explored the temporal dynamics of brain activity in patients with adolescent depression. This study selected 66 adolescents with depression as a patient group, and 27 healthy adolescents as a healthy control group. A modified k-means clustering algorithm was used to classify the 64-channel resting-state EEG data into different microstates. Independent sample t-tests were used to compare the microstate parameters between the 2 groups and further assciations between these parameters and childhood traumatic experience in patients were explored via using Spearman correlation. RESULTS: In this study, significant differences were observed in the occurrence and transition probabilities of EEG microstates between the healthy control and the patient group. Notably, there was a statistically significant difference (P<0.05) in the occurrence of microstate A across 2 groups, exhibiting a negative correlation with the emotional abuse component within the childhood trauma scores (Spearman's rho=-0.31, P=0.013). Furthermore, patient-specific, non-random transitions from microstate B to A (Spearman's rho=-0.30, P=0.015) and C to A (Spearman's rho=-0.31, P=0.013) were inversely associated with the scores of emotional abuse factors from childhood trauma in the patient group, showing statistically significant differences when comparing to the healthy controls (P<0.05). Upon stratification into quartiles based on the emotional abuse factor scores, the occurrence of microstate A, as well as the transition rates from microstates B to A and C to A, retained statistical significance following adjustment for multiple comparisons (all P<0.05). CONCLUSIONS: The abnormal temporal dynamics in brain networks of adolescents with depression are linked to childhood emotional abuse. Those who have suffered severe emotional abuse may show greater impairments in the brain's visual and central executive networks. EEG microstate analysis could be a potential tool for detecting adolescent depression with severe childhood trauma.

Oral Nanomotor-Enabled Mucus Traverse and Tumor Penetration for Targeted Chemo-Sono-Immunotherapy against Colon Cancer.

The therapeutic outcomes of oral nanomedicines against colon cancer are heavily compromised by their lack of specific penetration into the internal tumor, favorable anti-tumor activity, and activation of anti-tumor immunity. Herein, hydrogen peroxide (H2 O2 )/ultrasound (US)-driven mesoporous manganese oxide (MnOx )-based nanomotors are constructed by loading mitochondrial sonosensitizers into their mesoporous channels and orderly dual-functionalizing their surface with silk fibroin and chondroitin sulfate. The locomotory activities and tumor-targeting capacities of the resultant nanomotors (CS-ID@NMs) are greatly improved in the presence of H2 O2 and US irradiation, inducing efficient mucus-traversing and deep tumor penetration. The excess H2 O2 in the tumor microenvironment (TME) is decomposed into hydroxyl radicals and oxygen by an Mn2+ -mediated Fenton-like reaction, and the produced oxygen participates in sonodynamic therapy (SDT), yielding abundant singlet oxygen. The combined Mn2+ -mediated chemodynamic therapy and SDT cause effective ferropotosis of tumor cells and accelerate the release of tumor antigens. Importantly, animal experiments reveal that the treatment of combining oral hydrogel (chitosan/alginate)-embedding CS-ID@NMs and immune checkpoint inhibitors can simultaneously suppress the growth of primary and distal tumors through direct killing, reversion of immunosuppressive TME, and potentiation of systemic anti-tumor immunity, demonstrating that the CS-ID@NM-based platform is a robust oral system for synergistic treatment of colon cancer.

Enhanced biodegradation of oil-contaminated soil oil in shale gas exploitation by biochar immobilization.

The enhanced biodegradation of oil-contaminated soil by fixing microorganisms with corn cob biochar was investigated. It was found that the components of oil in the test soil were mainly straight-chain alkanes and branched alkanes. When using corn cob biochar as a carrier to immobilize microorganisms, the best particle size of corn cob biochar as an immobilization carrier was 0.08 mm, and the best immobilization time was 18 h. SEM analysis confirmed that the microorganisms were immobilized on the corn cob biochar. Immobilized microorganisms exhibited high biodegradability under stress to high concentrations of petroleum pollutants, heavy metals, and organic pollutants. Infrared spectroscopy analysis showed that oxygen-containing groups such as hydroxyl, carboxyl, and methoxy on the surface of biochar were involved in the complexation of heavy metals. The mechanism of immobilization promoted microbial degradation of oil contamination was explained by gas chromatography mass. First, alkanes and aromatics were adsorbed by corn cob biochar and passed to immobilized microorganisms to promote their degradation. Their bioavailability increased, especially for aromatics. Second, biochar provided a more suitable environment for microorganisms to degrade. Third, the conversion of ketones to acids was accelerated during the biodegradation of alkanes, and the biodegradation of alkanes was accelerated by immobilization. The biodegradable efficiency of oil by immobilized microorganisms in soil was 70.10% within 60 days, 28.80% higher than that of free microorganisms. The degradation of immobilized microorganisms was highly correlated with the activities of catalase, urease, and polyphenol oxidase.

Photoluminescence Properties of SrMoO4:Eu3+, Sm3+ Nanophosphors Prepared by Sol-Gel Method.

Novel red light-emitting nanophosphors of SrMoO4:Eu3+, Sm3+ were synthesized by a facile sol-gel method. Particles have sizes in the range of 50-80 nm. The structures, morphologies and optical properties of as-prepared products were characterized by means of X-ray diffraction (XRD), transmission electron microscope (TEM) and photo luminescent (PL). The results indicate that the red emission intensity was enhanced significantly with the increase of Sm3+ doping concentrations. When the mole fraction of Sm3+ is 2%, the emission intensity of red light is the strongest. It has been found that the incorporation of R+(Li+, Na+) into SrMoO4:Eu3+, Sm3+ phosphor could lead to a remarkable increase of photoluminescence. Thus, it is considered to be efficient red-emitting phosphors.

Relationship between circulating metabolites and diabetic retinopathy: a two-sample Mendelian randomization analysis.

Diabetic retinopathy (DR) is the most frequent microvascular complication of diabetes mellitus, however, its underlying biological mechanisms remain poorly understood. We examined single nucleotide polymorphisms linked to 486 blood metabolites through extensive genome-wide association studies conducted on individuals of European ancestry. The FinnGen Biobank database served as a reference to define DR. Two-sample MR analysis was conducted to reveal the association between the levels of genetically predicted circulating metabolites and the susceptibility to DR. To validate the robustness of the obtained findings, sensitivity analyses with weighted median, weighted mode, and MR-Egger were conducted. 1-oleoylglycerophosphoethanolamine (odds ratio [OR] (OR per one standard deviation [SD] increase) = 0.414; 95% confidence interval [CI] 0.292-0.587; P = 7.613E-07, PFDR = 6.849E-06), pyroglutamine (OR per one SD increase = 0.414; 95% confidence interval [CI] 0.292-0.587; P = 8.31E-04, PFDR = 0.007), phenyllactate (PLA) (OR per one SD increase = 0.591; 95% confidence interval [CI] 0.418-0.836; P = 0.003, PFDR = 0.026), metoprolol acid metabolite (OR per one SD increase = 0.978; 95% confidence interval [CI] 0.962-0.993; P = 0.005, PFDR = 0.042), 10-undecenoate (OR per one SD increase = 0.788; 95% confidence interval [CI] 0.667-0.932; P = 0.005, PFDR = 0.049), erythritol (OR per one SD increase = 0.691; 95% confidence interval [CI] 0.513-0.932; P = 0.015, PFDR = 0.034), 1-stearoylglycerophosphoethanolamine (OR per one SD increase = 0.636; 95% confidence interval [CI] 0.431-0.937; P = 0.022, PFDR = 0.099), 1-arachidonoylglycerophosphoethanolamine (OR per one SD increase = 0.636; 95% confidence interval [CI] 0.431-0.937; P = 0.030, PFDR = 0.099) showed a significant causal relationship with DR and could have protective effects. stachydrine (OR per one SD increase = 1.146; 95% confidence interval [CI] 1.066-1.233; P = 2.270E-04, PFDR = 0.002), butyrylcarnitine (OR per one SD increase = 1.117; 95% confidence interval [CI] 1.023-1.219; P = 0.014, PFDR = 0.062), 5-oxoproline (OR per one SD increase = 1.569; 95% confidence interval [CI] 1.056-2.335; P = 0.026, PFDR = 0.082), and kynurenine (OR = 1.623; 95% CI 1.042-2.526; P = 0.041, PFDR = 0.097) were significantly associated with an increased risk of DR. This study identified metabolites have the potential to be considered prospective compounds for investigating the underlying mechanisms of DR and for selecting appropriate drug targets.

Effects of oral calcium on reproduction and postpartum health in cattle: a meta-analysis and quality assessment.

Postpartum blood calcium (Ca) concentration is related to the reproduction and health of cattle. Oral calcium supplements were given to dairy cows after calving to increase blood Ca concentration and reduce the risk of hypocalcemia. However, studies have shown that oral Ca has different effects in preventing disease. The purposes of this study were (i) to conduct a meta-analysis to evaluate the expected effect of oral Ca on incidence of calving-related diseases, pregnancy risk and milk yield in dairy cows, and (ii) to make a quality assessment of these related studies. In total, 22 eligible studies were included in this review. Meta-analysis showed that oral Ca could significantly reduce the incidence of hypocalcemia (clinical hypocalcemia: relative risk (RR) = 0.67, 95% confidence interval (CI) = [0.52, 0.87]; subclinical hypocalcemia: RR = 0.81, CI = [0.72, 0.91]), and incidence of retained placenta (RR = 0.77, CI = [0.62, 0.95]), improved blood Ca concentrations: mean difference (MD) = 0.08; 95% CI = [0.04, 0.11]. For other results, the meta-analysis revealed a lack of evidence of the correlation between oral Ca and serum magnesium (Mg) / phosphorus (P) concentration (Mg: MD = -0.04; 95% CI = [-0.10, 0.02]; P: MD = 0.05; 95% CI = [-0.10, 0.21]) or incidence of other calving-related disorders (metritis: RR = 1.06, CI = [0.94, 1.19]; ketosis: RR = 1.04, CI = [0.91, 1.18]; mastitis: RR = 1.02, CI = [0.86, 1.21]; displacement of the abomasum: RR = 0.81, CI = [0.57, 1.16]) or pregnancy risk (pregnancy risk at first service: RR = 0.99, CI = [0.94, 1.05]; overall pregnancy rate: RR = 1.03, CI = [0.98, 1.08]) or milk yield (MD = 0.44; 95% CI = [-0.24, 1.13]). The distribution of the funnel plot formed by the included studies was symmetrical, and the Egger's test had a p > 0.05, indicating that there was no significant publication bias. Sensitivity analyses results suggested that the results of meta-analysis are robust. Quality assessment of the included studies revealed that the risk of bias was focused on selection bias, performance bias, detection bias and other sources of bias, and the future research should focus on these aspects.

Differential lncRNA profiles of blood plasma-derived exosomes from systemic lupus erythematosus.

INTRODUCTION: Long non-coding RNAs (lncRNAs) dysregulation is key in the pathogenesis of systemic lupus erythematosus (SLE), but the role of exosomal lncRNAs in SLE has not been well studied. We elucidated the profiles of plasma exosomal lncRNAs expression in patients with SLE and predictd their potential clinical significance in SLE. METHODS: In the screening stage, six newly diagnosed and untreated patients with SLE and six healthy controls were examined by high-throughput sequencing technology, and differential exosomal lncRNA profiles were constructed. In the validation phase, two differentially selected exosomal lncRNAs from 20 patients each with active and stable SLE and 20 healthy controls were verified with RT-qPCR. The correlation between the selected exosomal lncRNAs and SLE clinical indicators was examined. The diagnostic value of the selected exosomal lncRNAs in SLE was analyzed by the receiver operator characteristic (ROC) curve. RESULTS: Exosomes were successfully extracted from the patients and controls. Sequencing-phase sequencing demonstrated 528 upregulated lncRNAs and 7491 downregulated lncRNAs. In the validation stage, exosomal LINC00667 and DANCR were significantly upregulated in the patients, and positively correlated with Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K). Exosomal DANCR expression between the active and stable SLE patients was different. The area under the curve(AUC) of exosomal LINC00667 and DANCR for SLE diagnosis was 0.815 and 0.759, respectively. CONCLUSIONS: Exosomal LINC00667 and DANCR were upregulated in SLE, and might be new biomarkers thereof. Exosomal DANCR was associated with SLE activity.

Changes in P300 amplitude to negative emotional stimuli correlate with treatment responsiveness to sertraline in adolescents with depression.

OBJECTIVE: Adolescents with depression is characterized by high rates of recurrence and functional impairment, with a significant association with suicide risk. Antidepressants are commonly prescribed to treat depression, yet few reproducible neurobiological markers for depression and antidepressant treatment response have been identified. Therefore, discovering a stable and reliable neurobiological marker holds significant value for both the clinical diagnosis and treatment of depression in adolescents. METHODS: One hundred and seven patients with major depressive disorder (MDD group, 30 males, 77 females, mean age: 14.80 years), and 25 healthy subjects (HC group, 13 males, 12 females, mean age: 15.72 years) were recruited to perform a two-choice oddball task related to negative emotional cues. All participants completed a self-administered questionnaire to gather demographic information. A trained psychiatrist administered the Hamilton Depression Scale (HAMD-17) to assess depression severity. Of the 107 adolescents with depression, 61 received antidepressant medication for 8 weeks, and 61 of these patients were followed up. Multichannel EEG was recorded continuously from 64 scalp electrodes using the Curry 8 system. EEG signal preprocessing and analysis was performed offline using the EEGLAB toolbox in MATLAB. The ERP component characteristics associated with emotional processing were extracted from the difference waves and statistically analyzed. RESULTS: Adolescents with depression exhibited significantly larger P300 amplitudes than healthy controls in response to both neutral and negative emotional cues. Following sertraline treatment, both depression scores and P300 amplitudes decreased significantly in adolescents with depression. Moreover, a strong positive correlation was observed between changes in depression scores and changes in P300 amplitude in response to negative emotional cues before and after treatment. CONCLUSIONS: Changes in neural reactivity to negative emotional stimuli among adolescents with depression can be selectively modulated by sertraline and are significantly associated with improvements in depressive symptoms. SIGNIFICANCE: Changes in P300 amplitude to negative emotional stimuli significantly correlate with treatment responsiveness to sertraline in adolescents with depression.

Skeletal muscle index together with body mass index is associated with secondary osteoporosis in patients with rheumatoid arthritis.

OBJECTIVE: The objective of this study was to explore the associations of body mass index (BMI), fat mass index (FMI), skeletal mass index (SMI) and secondary osteoporosis (OP) in patients with rheumatoid arthritis (RA). METHODS: The bone mineral density (BMD) at sites of the femur neck (Neck), total hip (Hip) and lumbar vertebrae 1-4 (L1-4) was measured by dual-energy X-ray absorptiometry. The skeletal muscle index, body fat percentage and mineral content were measured by biological electrical impedance for calculating BMI, FMI and SMI. RESULTS: A total of 433 patient with RA and 158 healthy controls were enrolled. The BMDs at each site of the RA patients were lower compared with those of the healthy controls (p < 0.0001), and the prevalence of OP (36.1%, 160/443) and sarcopenia (65.2%, 288/443) in the RA patients were higher than those in the controls (12.7%, 20/158, p < 0.0001; 9.0%, 14/156, p < 0.0001). Significant differences in the BMD, FMI, SMI, mineral content, body fat percentage and skeletal muscle mass were found among the RA patients in the different BMI groups (p < 0.05). In RA patients with BMI < 18.5 kg/m2, the prevalence of OP in the RA patients with sarcopenia was similar to that in those without sarcopenia (44.4% vs. 66. 7%, χ2 = 0. 574, p = 0.449). In the RA patients with a normal BMI or who were overweight or obese, prevalence of OP in the RA patients with sarcopenia was significantly higher than that in the RA patients without sarcopenia (42.8% vs. 21.7%, χ2 = 10.951, p = 0.001; 61.1% vs. 13.0%, χ2 = 26.270, p < 0.0001). In the RA patients without sarcopenia, the prevalence of OP in the RA patients in the different BMI groups was different (p = 0.039). In the RA patients with sarcopenia, there was no significant difference in the prevalence of OP among the RA patients in the different BMI groups (p = 0. 128). The linear correlation analysis showed that the SMI in RA patients was positively correlated with the BMD of each site measured and BMI and FMI (p < 0.0001). However, there was a negative linear correlation between SMI and disease duration (p = 0.048). The logistic regression analysis found that SMI (OR = 0.569, p = 0.002, 95% CI 0.399-0.810), BMI (OR = 0.884, p = 0.01, 95% CI 0.805-0.971) and gender (1 = female, 2 = male) (OR = 0.097, p < 0.0001, 95% CI 0.040-0.236) were protective factors for OP in RA, while age (OR = 1.098, p < 0.0001, 95% CI 1.071-1.125) was the risk factor. CONCLUSION: BMI and SMI are associated with the occurrence of OP in RA patients, and both SMI and BMI are important protective factors for OP secondary to RA.

EEG microstate analysis reveals large-scale brain network alterations in depressed adolescents with suicidal ideation.

BACKGROUND: Accumulating evidence showed abnormalities in brain network connectivity in depressive individuals with suicidal ideation (SI). We aimed to investigate the large-scale brain network dynamics in adolescents with SI and major depressive disorder (MDD). METHODS: We recruited 47 first-episode drug-naïve adolescents with MDD and SI, 26 depressed adolescents without SI (noSI), and 26 age-matched healthy controls (HC). The Columbia Suicidal Ideation Severity Scale (C-SSRS) was utilized to assess suicide ideation. We acquired 64-channel resting-state EEG recordings from all subjects and used microstate analysis to investigate the large-scale brain network dynamics. RESULTS: We observed a significant reduction in the occurrence and coverage of microstate B within the SI group when contrasted with the noSI group. Conversely, there was a significant increase in the occurrence and coverage of microstate A in the SI group as compared to the HC group. Additionally, we observed heightened transition probabilities from microstates D and C to microstate A in the SI group; meanwhile, transitions from microstate D to B were more prevalent in the noSI group. Furthermore, the noSI group exhibited a significant decline in the transition probabilities from microstate D to microstate C. LIMITATIONS: The cross-sectional nature limits the capacity to determine whether microstate dynamics have prognostic significance for SI. CONCLUSION: We provided evidence that depressed adolescents with SI have a distinct pattern in microstate dynamics compared to those without SI. These findings suggest that microstate dynamics might serve as a potential neurobiomarker for identifying SI in depressed adolescents.

Impaired behavioral inhibitory control of self-injury cues between adolescents with depression with self-injury behavior and those without during a two-choice oddball task: an event-related potential study.

Background: This study aimed to objectively evaluate the severity of impulsivity [behavior inhibitory control (BIC) impairment] among adolescents with depression. In particular, those involved in non-suicidal self-injury (NSSI) behaviors, compared with those engaged in suicidal behaviors and adolescents without any self-injury behavior, using event-related potentials (ERPs) and event-related spectral perturbation (ERSP) within the two-choice oddball paradigm. Methods: Participants with a current diagnosis of major depressive disorder (MDD) engaged in repetitive NSSI for five or more days in the past year (n = 53) or having a history of at least one prior complete suicidal behavior (n = 31) were recruited in the self-injury group. Those without self-injury behavior were recruited in the MDD group (n = 40). They completed self-report scales and a computer-based two-choice oddball paradigm during which a continuous electroencephalogram was recorded. The difference waves in P3d were derived from the deviant minus standard wave, and the target index was the difference between the two conditions. We focused on latency and amplitude, and time-frequency analyses were conducted in addition to the conventional index. Results: Participants with self-injury, compared to those with depression but without self-injury, exhibited specific deficits in BIC impairment, showing a significantly larger amplitude. Specifically, the NSSI group showed the highest value in amplitude and theta power, and suicidal behavior showed a high value in amplitude but the lowest value in theta power. These results may potentially predict the onset of suicide following repetitive NSSI. Conclusion: These findings contribute to substantial progress in exploring neuro-electrophysiological evidence of self-injury behaviors. Furthermore, the difference between the NSSI and suicide groups might be the direction of prediction of suicidality.

Changes in emotion-related EEG components and brain lateralization response to negative emotions in adolescents with nonsuicidal self-injury: An ERP study.

Nonsuicidal self-injury (NSSI) is a serious risk behavior in adolescents and is a high risk factor for suicide, while negative emotions can lead to increased NSSI behaviors. In this study, we investigated the altered behavioral performance and neural reactivity of adolescents with NSSI by using a two-choice oddball paradigm when exposed to negative emotional stimuli, and analyzed the brain lateralization effect. Our data indicated that adolescents with NSSI exhibit more pronounced N250, P300, and LPP components during negative emotional face stimulation, as evidenced by a smaller N250 wave amplitude, larger P300 wave amplitude, steeper LPP waveform, and faster fallback baseline; and the presence of brain lateralization responses in both the N250 component and the LPP component. These results suggested that adolescents with NSSI showed significant alterations in cognitive EEG components associated with emotional processing during negative emotional face stimulation, particularly in EEG components representing inhibitory control, and there was a lateralization effect on emotional processing in the brain, with different processing stages and different dominance of the left and right brain.

Neurophysiological biomarkers for depression classification: Utilizing microstate k-mers and a bag-of-words model.

Microstates are analogous to characters in a language, and short fragments consisting of several microstates (k-mers) are analogous to words. We aimed to investigate whether microstate k-mers could be used as neurophysiological biomarkers to differentiate between depressed patients and normal controls. We utilized a bag-of-words model to process microstate sequences, using k-mers with a k range of 1-10 as terms, and the term frequency (TF) with or without inverse-document-frequency (IDF) as features. We performed nested cross-validation on Dataset 1 (27 patients and 26 controls) and Dataset 2 (34 patients and 30 controls) separately and then trained on one dataset and tested on the other. The best area under the curve (AUC) of 81.5% was achieved for the model with L1 regularization using the TF of 4-mers as features in Dataset 1, and the best AUC of 88.9% was achieved for the model with L1 regularization using the TF of 9-mers as features in Dataset 2. When Dataset 1 was used as the training set, the best AUC of predicting Dataset 2 was 74.1% for the model with L2 regularization using the TF-IDF of 9-mers as features, while the best AUC of predicting Dataset 1 was 70.2% for the model with L1 regularization using the TF of 8-mers as features. Our study provided novel insights into the potential of microstate k-mers as neurophysiological biomarkers for individual-level classification of depression. These may facilitate further exploration of microstate sequences using natural language processing techniques.

Changes in microstates of first-episode untreated nonsuicidal self-injury adolescents exposed to negative emotional stimuli and after receiving rTMS intervention.

Background: Nonsuicidal self-injury (NSSI) is a common mental health threat in adolescents, peaking in adolescence with a lifetime prevalence of ~17%-60%, making it a high-risk risk factor for suicide. In this study, we compared changes in microstate parameters in depressed adolescents with NSSI, depressed adolescents, and healthy adolescents during exposure to negative emotional stimuli, and further explored the improvement of clinical symptoms and the effect of microstate parameters of repetitive transcranial magnetic stimulation (rTMS) in depressed adolescents with NSSI, and more evidence was provided for potential mechanisms and treatment optimization for the occurrence of NSSI behaviors in adolescents. Methods: Sixty-six patients with major depressive disorder (MDD) exhibiting NSSI behavior (MDD + NSSI group), 52 patients with MDD (MDD group), and 20 healthy subjects (HC group) were recruited to perform neutral and negative emotional stimulation task. The age range of all subjects was 12-17 years. All participants completed the Hamilton Depression Scale, the Patient Health Questionnaire-9, the Ottawa Self-Injury Scale and a self-administered questionnaire to collect demographic information. We provided two different treatments to 66 MDD adolescents with NSSI; 31 patients received medication and completed post-treatment scale assessments and EEG acquisitions, and 21 patients received medication combined with rTMS and completed post-treatment scale assessments and EEG acquisitions. Multichannel EEG was recorded continuously from 64 scalp electrodes using the Curry 8 system. EEG signal preprocessing and analysis was performed offline, using the EEGLAB toolbox in MATLAB. Use the Microstate Analysis Toolbox in EEGLAB for segmentation and computation of microstates, and calculate a topographic map of the microstate segmentation of the EEG signal for a single subject in each dataset, and four parameters were obtained for each microstate classification: global explained variance (GEV), mean duration (Duration), average number of occurrences per second (Occurrence), and average percentage of total analysis time occupied (Coverage), which were then statistically analyzed. Results: Our results indicate that MDD adolescents with NSSI exhibit abnormalities in MS 3, MS 4, and MS 6 parameters when exposed to negative emotional stimuli compared to MDD adolescents and healthy adolescents. The results also showed that medication combined with rTMS treatment improved depressive symptoms and NSSI performance more significantly in MDD adolescents with NSSI compared to medication treatment, and affected MS 1, MS 2, and MS 4 parameters in MDD adolescents with NSSI, providing microstate evidence for the moderating effect of rTMS. Conclusion: MDD adolescents with NSSI showed abnormal changes in several microstate parameters when receiving negative emotional stimuli, and compared to those not receiving rTMS treatment, MDD adolescents with NSSI treated with rTMS showed more significant improvements in depressive symptoms and NSSI performance, as well as improvements in EEG microstate abnormalities.

Circulating MicroRNAs as Potential Diagnostic Biomarkers for Diabetic Retinopathy: A Meta-Analysis.

Objective: Diabetic retinopathy (DR) is a common diabetic microvascular complication and a major cause of acquired vision loss. Finding effective biomarkers for the early identification and diagnosis of DR is crucial. This study aimed to comprehensively evaluate the accuracy of microRNAs (miRNAs) in the diagnosis of DR via a meta-analysis of previously published diagnostic studies. This study has been registered on the PROSPERO website, with the number CRD42022323238. Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, China Wanfang database, and China Knowledge Network database to identify relevant articles published from the time of database creation to April 10, 2022. Stata 14.0 software was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the summary receiver operating characteristic (ROC) curve to assess the accuracy of miRNAs in the diagnosis of DR. Heterogeneity between studies was assessed using Cochran-Q test and I2 statistic for quantitative analysis. The random-effect model was selected due to significant heterogeneity. Subgroup analysis and regression analysis were also performed to determine the potential sources of heterogeneity. Results: We included 25 articles detailing 52 studies with 1987 patients with DR and 1771 non-DR controls. The findings demonstrated overall sensitivity (0.82, 95% CI: 0.78 ~ 0.85), specificity (0.84, 95% CI: 0.81 ~ 0.86), PLR (5.0, 95% CI: 4.2 ~ 5.9), NLR (0.22, 95% CI: 0.18 ~ 0.26), and the area under the summary ROC curve (0.90, 95% CI: 0.87 ~ 0.92). Furthermore, we performed subgroup analysis and found that panels of multiple miRNAs could enhance the pooled sensitivity (sensitivity, specificity, and AUC values were 0.89, 0.87, and 0.94, respectively). Conclusion: The meta-analysis showed that miRNAs can be used as potential diagnostic markers for DR, with high accuracy of diagnoses observed with the detection of miRNAs in plasma and serum.

Oral antimicrobial peptide-EGCG nanomedicines for synergistic treatment of ulcerative colitis.

The pathogenesis of ulcerative colitis (UC) is associated with severe inflammation, damaged colonic barriers, increased oxidative stress, and intestinal dysbiosis. The majority of current medications strive to alleviate inflammation but fail to target additional disease pathologies. Addressing multiple symptoms using a single 'magic bullet' remains a challenge. To overcome this, a smart epigallocatechin-3-gallate (EGCG)-loaded silk fibroin-based nanoparticle (NP) with the surface functionalization of antimicrobial peptides (Cathelicidin-BF, CBF) was constructed, which could be internalized by Colon-26 cells and RAW 264.7 macrophages with high efficiencies. The resulting CBF-EGCG-NPs efficiently restored colonic epithelial barriers by relieving oxidative stress and promoting epithelium migration. They also alleviated immune responses through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and lipopolysaccharide (LPS) elimination. Interestingly, oral administration of hydrogel (chitosan/alginate)-embedding CBF-EGCG-NPs could not only retard progression and treat UC, but also modulate intestinal microbiota by increasing their overall diversity and richness and augmenting the abundance of beneficial bacteria (e.g., Firmicutes and Lactobacillaceae). Our work provides a "many birds with one stone" strategy for addressing UC symptoms using a single NP-based oral platform that targets immune microenvironment modulation, LPS clearance, and microbial remodeling.

Altered Neural Reactivity in Adolescents With Nonsuicidal Self-Injury During Exposure to Self-Injury Related Cues: Electrophysiological Evidence From a Two-Choice Oddball Paradigm.

Background: Nonsuicidal self-injury (NSSI) may be a type of addiction, that is characterized by cue reactivity. We aimed to explore the behavioral performance and neural reactivity during exposure to self-injury cues in adolescents with NSSI and major depressive disorder (MDD). Methods: Eighteen MDD patients, 18 MDD patients with NSSI, and 19 healthy controls (HC) were recruited to perform a two-choice oddball paradigm. All subjects were 12-18 years old. Neutral cues and self-injury related cues separately served as deviant stimuli. Difference waves in N2 and P3 (N2d and P3d) were derived from deviant waves minus standard waves. Accuracy cost and reaction time (RT) cost were used as behavioral indexes, while the N2d and P3d were used as electrophysiological indexes; the N2d reflects early conflict detection, and the P3d reflects the process of response inhibition. Results: No significant main effects of group or cue or an effect of their interaction were observed on accuracy cost and P3d latency. For RT cost, N2d amplitude, and N2d latency, there was a significant main effect of cue. For P3d amplitude, there was a significant main effect of cue and a significant group × cue interaction. In the NSSI group, the P3d amplitude with self-injury cues was significantly larger than that with neutral cues. However, there was no such effect in the MDD and HC groups. Conclusions: Adolescents with NSSI showed altered neural reactivity during exposure to self-injury cue. Further studies with larger sample sizes are needed to confirm our results.

Immunization Against Inhibin Promotes Fertility in Cattle: A Meta-Analysis and Quality Assessment.

Superovulation and embryo transfer techniques are important methods in cattle breeding. Combined with traditional superovulation protocols, immunization against inhibin can further improve follicular development and embryo yield. The aim of this study is to determine the efficacy of immunization against inhibin in improving the fertility of cattle through meta-analysis and to provide better clinical veterinary practice guidance. Three English databases (PubMed, EMBASE, Web of Science) were searched for research articles of immunizations against inhibin influence on cattle fertility. Literature screening, data extraction, and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In addition, the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias (RoB) tool was used to assess the risk of bias of the included animal studies. Potentially relevant studies (317) were identified, and finally 14 eligible studies (all in English) were included. The results of meta-analysis revealed that immunization against inhibin has significant effects on improving the number of ovulations [mean difference (MD) = 0.44, 95% confidence interval (CI) = (0.31, 0.56)], embryos and unfertilized ova [MD = 4.51, 95% CI = (2.28, 6.74)], follicles of the three size categories, the incidence of multiple ovulations [OR = 22.50, 95% CI = (8.13, 62.27)], and the conception rate [OR = 2.36, 95% CI = (1.26, 4.40)]. Moreover, it improved the production of embryos [grades 1 embryos: MD = 3.84, (3.54, 4.15); grade 2 embryos: MD = -0.73, (-0.89, -0.57); grade 3 embryos: MD = -0.50, (-0.75, -0.25); degenerated embryos: MD = 1.16, (-0.51, 2.82); transferable embryos: MD = 2.67, (2.03, 3.31)] and the number of corpora lutea [MD = 1.25, 95% CI = (0.79, 1.71)]. In the above indicators, the differences between the two groups were statistically significant (all p < 0.0001). Additionally, according to the quality evaluation results, the risk of bias in the included studies is relatively high. The quality evaluation of the results of the included studies showed that the risk of bias mainly concentrated in the selective, performance, detection, and reporting of bias aspects.