Ginger inhibits the invasion of ovarian cancer cells SKOV3 through CLDN7, CLDN11 and CD274 m6A methylation modifications.

BACKGROUND: Ginger is a common aromatic vegetable with a wide range of functional ingredients and considerable medicinal and nutritional properties. Numerous studies have shown that ginger and its active ingredients have suppressive effects on manifold tumours, including ovarian cancer (OC). However, the molecular mechanism by which ginger inhibits OC is not clear. The aim of this study was to investigate the function and mechanism of ginger in OC. METHODS: The estimation of n6-methyladenosine (m6A) levels was performed using the m6A RNA Methylation Quantification Kit, and RT-qPCR was used to determine the expression of m6A-related genes and proteins. The m6A methylationome was detected by MeRIP-seq, following analysis of the data. Differential methylation of genes was assessed utilizing RT-qPCR and Western Blotting. The effect of ginger on SKOV3 invasion in ovarian cancer cells was investigated using the wound healing assay and transwell assays. RESULTS: Ginger significantly reduced the m6A level of OC cells SKOV3. The 3'UTR region is the major site of modification for m6A methylation, and its key molecular activities include Cell Adhesion Molecules, according to meRIP-seq results. Moreover, it was observed that Ginger aids significantly in downregulating the CLDN7, CLDN11 mRNA, and protein expression. The results of wound healing assay and transwell assay showed that ginger significantly inhibited the invasion of OC cells SKOV3. CONCLUSIONS: Ginger inhibits ovarian cancer cells' SKOV3 invasion by regulating m6A methylation through CLDN7, CLDN11, and CD274.

Drug repositioning and ovarian cancer, a study based on Mendelian randomisation analysis.

Background: The role of drug repositioning in the treatment of ovarian cancer has received increasing attention. Although promising results have been achieved, there are also major controversies. Methods: In this study, we conducted a drug-target Mendelian randomisation (MR) analysis to systematically investigate the reported effects and relevance of traditional drugs in the treatment of ovarian cancer. The inverse-variance weighted (IVW) method was used in the main analysis to estimate the causal effect. Several MR methods were used simultaneously to test the robustness of the results. Results: By screening 31 drugs with 110 targets, FNTA, HSPA5, NEU1, CCND1, CASP1, CASP3 were negatively correlated with ovarian cancer, and HMGCR, PLA2G4A, ITGAL, PTGS1, FNTB were positively correlated with ovarian cancer. Conclusion: Statins (HMGCR blockers), lonafarnib (farnesyltransferase inhibitors), the anti-inflammatory drug aspirin, and the anti-malarial drug adiponectin all have potential therapeutic roles in ovarian cancer treatment.

Riveting technique in percutaneous balloon compression for trigeminal neuralgia remedy.

BACKGROUND: The percutaneous balloon compression (PBC) is a safe and simple treatment for trigeminal neuralgia. It works by compressing the Gasserian ganglion to block pain signals from the trigeminal nerve. To ensure effectiveness, it is important to focus the compression on the lower part of the balloon. OBJECTIVE: To validate the efficacy of a riveting technique, specifically pulling an inflated balloon, in order to apply enhanced compression on the ganglion. METHODS: To compare this novel technique with the conventional approach, a retrospective investigation was conducted on consecutive PBCs performed in our department between 2019 and 2022. For postoperative outcome assessment, efficacy was defined as achieving a VAS score of 0 or an improvement exceeding 5 points. Postoperative numbness was graded as none, mild, or severe based on its impact on daily life and tolerance level. RESULTS: Excluding cases with missed follow-up, a total of 179 participants were included in the study, and their follow-up period ranged up to 40 months. Postoperatively, symptomatic remission was achieved by 98.1% (52/53) of patients in the riveting technique group compared to 87.3% (110/126) in the conventional group (P<0.05). At the last follow-up period, with recurrence observed over time, the long-term efficacy of riveting and conventional groups were 94.3% and 74.6%, respectively (P<0.05). The majority of cases in both groups experienced ipsilateral facial numbness immediately following PBC, which appeared to diminish after 3 months in both groups without significant difference between them (P>0.05).

Comparison of the efficacy and safety between intravenous thrombolysis, direct endovascular therapy, and bridging therapy for acute basilar artery occlusion in cerebral infarction patients.

OBJECTIVE: To compare the efficacy and safety of intravenous thrombolysis (IVT), direct endovascular therapy (EVT), and bridging therapy (BT=IVT+EVT) for acute basilar artery occlusion cerebral infarction. METHODS: One hundred and fourteen patients with acute basilar artery occlusion cerebral infarctions admitted between January 2020 and August 2023 were selected. Differences in the reperfusion rate, prognosis, incidence of stroke-associated pneumonia, and mortality rate were compared among the three groups. RESULTS: There was no statistically significant difference in the percentage of patients who achieved successful reperfusion (86.8% vs. 84.2%) or complete reperfusion (72.1% vs. 68.4%) between the direct EVT and BT groups (both P>0.05). There were no statistically significant differences in the rates of symptomatic intracranial haemorrhage (3.7% vs. 10.3% vs. 10.5%, P=0.763). There were statistically significant differences in the rates of good prognosis (mRS score 0-2) (59.3% vs. 30.9% vs. 26.3%, P=0.021), stroke-related pneumonia (29.6% vs. 66.2% vs. 36.8%, P=0.002), and mortality (14.8% vs. 48.5% vs. 42.1%, P=0.010) among the three treatment groups. According to the binary logistic regression analysis, a good prognosis was independently associated with a baseline National Institutes of Health Stroke Scale (NIHSS) score <=10 (odds ratio [OR], 3.714; 95% confidence interval [CI], 1.207-11.430; P =0.022) and the incidence of stroke-associated pneumonia (OR, 0.640; 95% CI, 0.484-0.845; P=0.002). CONCLUSION: Although there were differences in prognosis, mortality, and incidence of complications among the three treatment groups, after adjusting for confounding factors, prognosis was independently correlated only with the baseline NIHSS score and stroke-associated pneumonia but not with treatment methods.

Prevalence and associated factors of depression, anxiety and stress among clinical therapists in China in the context of early COVID-19 pandemic.

Objectives: To study the socio-demographic characteristics and the prevalence of depression, anxiety, and stress among clinical therapists in China during the early Coronavirus disease 2019 (COVID-19) pandemic and to identify associated factors. Method: This cross-sectional study was part of a multicenter, nationally representative survey conducted through WeChat from January 2021 to March 2021. Data, including socio-demographics, health-related behaviors, and information on whether they participated in the frontline work of treating COVID-19, were collected anonymously. Respondents also completed the Depression Anxiety Stress Scales-21 (DASS-21). Results: In total, 396 clinical therapists in the selected hospitals completed the questionnaires, with a response rate of 89.0%. Respondents were predominantly female (77.3%). About 6.6% of the participants were current tobacco users, and 20.7% had participated in the frontline work of treating COVID-19. Overall, 22.0%, 17.9%, and 8.8% of participants were classified as having clinically meaningful depression, anxiety, and stress, respectively, based on DASS-21 scores. Multiple logistic regression in Model 1 and Model 2 showed that depression, anxiety, and stress were associated with regular physical activity and frequent insomnia (all, p < 0.05). In anxiety model 2, the associated factors for anxiety during the pandemic were identified as education (master's degree or more, OR=0.520; 95% CI=0.283-0.955), marital status (single, OR=2.064; 95% CI=1.022-4.168), tobacco use (OR=4.265; 95% CI=1.352-13.454), regular physical activity (OR=0.357; 95% CI=0.192-0.663), frequent insomnia (OR=6.298; 95% CI =2.522-15.729), and participation in the frontline work of treating COVID-19 (OR=3.179; 95% CI=1.697-5.954). The COVID-19 epidemic did not significantly increase the depression and stress levels among clinical therapists, but it did significantly increase anxiety levels. Conclusion: During the COVID-19 pandemic, depression, anxiety and stress were relatively common among clinical therapists in China. Regular physical activity and good sleep were important protective factors against emotional problems. Therefore, encouraging regular physical activity and actively addressing clinical therapists' sleep problems is beneficial to improving the ability to cope with negative emotions. The COVID-19 epidemic significantly increased anxiety, and awareness and interventions should be recommended to reduce anxiety among clinical therapists during the COVID-19 pandemic.

Dataset on the effects of psychological care on depression and suicide ideation in underrepresented children.

Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and "left-behind" and "single-parenting" children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.

Macroscopic inhibition of DNA damage repair pathways by targeting AP-2α with LEI110 eradicates hepatocellular carcinoma.

DNA damage repair (DDR) genes are known to be closely associated with the progression of Hepatocellular carcinoma (HCC). Here we report a unique cluster of "deletion-up" genes in HCC, which are accordantly overexpressed in HCC patients and predict the unfavorable prognosis. Binding motif analysis and further validation with ChIP-qPCR unveil that the AP-2α directly modulate the transcription of critical DNA repair genes including TOP2A, NUDT1, POLD1, and PARP1, which facilitates the sanitation of oxidized DNA lesions. Structural analysis and the following validation identify LEI110 as a potent AP-2α inhibitor. Together, we demonstrate that LEI110 stabilizes AP-2α and sensitizes HCC cells toward DNA-damaging reagents. Altogether, we identify AP-2α as a crucial transcription modulator in HCC and propose small-molecule inhibitors targeting AP-2α are a promising novel class of anticancer agents. Our study provides insights into the concept of macroscopic inhibition of DNA damage repair-related genes in cancer treatment.

Hematological and inflammatory markers in Han Chinese patients with drug-free schizophrenia: relationship with symptom severity.

Background: There is a growing amount of evidence suggesting that immunity and inflammation play an important role in the pathophysiology of schizophrenia. In this study, we aimed to examine the relationship between hematological and inflammatory markers with symptom severity in Han Chinese patients with drug-free schizophrenia. Methods: This retrospective study was conducted at Chaohu Hospital of Anhui Medical University and data were extracted from the electronic medical record system over a 5-year period (May 2017 to April 2022), including participants' general and clinical information as well as Brief Psychiatric Rating Scale (BPRS) scores and hematological parameters. Results: A total of 2,899 patients with schizophrenia were identified through the initial search. After screening, 91 patients and 141 healthy controls (HCs) were included. The patients had a higher value of neutrophils/lymphocytes ratio (NLR), monocyte/lymphocyte ratio (MLR), and platelet/lymphocyte ratio (PLR) than HCs (all P < 0.001). MLR was positively correlated with BPRS total score (r = 0.337, P = 0.001) and resistance subscale score (r = 0.350, P = 0.001). Binary logistic regression analyses revealed that severely ill was significantly associated with being male and a higher value of MLR (Natural Logaruthm, Ln) (all P < 0.05), and the receiver operating characteristic (ROC) analysis showed good performance of a regression model with an area under the curve (AUC) value of 0.787. Conclusion: Patients with drug-free schizophrenia have an unbalanced distribution of peripheral blood granulocytes, and elevated NLR, MLR and PLR. Patients with higher value of MLR tend to have more psychotic symptoms, especially those symptoms of hostility, uncooperativeness, and suspiciousness. Our study gives a preliminary indication that MLR is a potential predictor of disease severity in patients with drug-free schizophrenia.

PMSeeker: A Scheme Based on the Greedy Algorithm and the Exhaustive Algorithm to Screen Low-Redundancy Marker Sets for Large-Scale Parentage Assignment with Full Parental Genotyping.

Parentage assignment is a genetic test that utilizes genetic characteristics, such as molecular markers, to identify the parental relationships within populations, which, in commercial fish farming, are almost always large and where full information on potential parents is known. To accurately find the true parents, the genotypes of all loci in the parentage marker set (PMS) are required for each individual being tested. With the same accuracy, a PMS containing a smaller number of markers will undoubtedly save experimental costs. Thus, this study established a scheme to screen low-redundancy PMSs using the exhaustive algorithm and greedy algorithm. When screening PMSs, the greedy algorithm selects markers based on the parental dispersity index (PDI), a uniquely defined metric that outperforms the probability of exclusion (PE). With the conjunctive use of the two algorithms, non-redundant PMSs were found for more than 99.7% of solvable cases in three groups of random sample experiments in this study. Then, a low-redundancy PMS can be composed using two or more of these non-redundant PMSs. This scheme effectively reduces the number of markers in PMSs, thus conserving human and experimental resources and laying the groundwork for the widespread implementation of parentage assignment technology in economic species breeding.

miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1-containing AMPA receptors in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aß accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Cortical gradient perturbation in attention deficit hyperactivity disorder correlates with neurotransmitter-, cell type-specific and chromosome- transcriptomic signatures.

AIMS: This study aimed to illuminate the neuropathological landscape of attention deficit hyperactivity disorder (ADHD) by a multiscale macro-micro-molecular perspective from in vivo neuroimaging data. METHODS: The "ADHD-200 initiative" repository provided multi-site high-quality resting-state functional connectivity (rsfc-) neuroimaging for ADHD children and matched typically developing (TD) cohort. Diffusion mapping embedding model to derive the functional connectome gradient detecting biologically plausible neural pattern was built, and the multivariate partial least square method to uncover the enrichment of neurotransmitomic, cellular and chromosomal gradient-transcriptional signatures of AHBA enrichment and meta-analytic decoding. RESULTS: Compared to TD, ADHD children presented connectopic cortical gradient perturbations in almost all the cognition-involved brain macroscale networks (all pBH <0.001), but not in the brain global topology. As an intermediate phenotypic variant, such gradient perturbation was spatially enriched into distributions of GABAA/BZ and 5-HT2A receptors (all pBH <0.01) and co-varied with genetic transcriptional expressions (e.g. DYDC2, ATOH7, all pBH <0.01), associated with phenotypic variants in episodic memory and emotional regulations. Enrichment models demonstrated such gradient-transcriptional variants indicated the risk of both cell-specific and chromosome- dysfunctions, especially in enriched expression of oligodendrocyte precursors and endothelial cells (all pperm <0.05) as well enrichment into chromosome 18, 19 and X (pperm <0.05). CONCLUSIONS: Our findings bridged brain macroscale neuropathological patterns to microscale/cellular biological architectures for ADHD children, demonstrating the neurobiologically pathological mechanism of ADHD into the genetic and molecular variants in GABA and 5-HT systems as well brain-derived enrichment of specific cellular/chromosomal expressions.

Development and external validation of a prediction model for digit replantation failure after traumatic amputations based on a prospective multicenter cohort.

BACKGROUND: Failure of digit replantation after traumatic amputation is difficult to predict. We aimed to develop a prognostic model to better identify factors that better predict replantation failure following traumatic digit amputation. MATERIALS AND METHODS: In this multicenter prospective cohort, we identified patients who had received digit replantation between January 1, 2015, and January 1, 2019. Univariable and multivariable analyses were performed successively to identify independently predictive factors for failure of replanted digit. To reduce overfitting, the Bayesian information criterion was used to reduce variables in the original model. Nomograms were created with the reduced model after model selection. This model was then internally validated with bootstrap resampling and further externally validated in validation cohort. RESULTS: Digit replantation was failed in 101 of 1062 (9.5%) digits and 146 of 1156 digits (12.6%) in the training and validation cohorts, respectively. We found that six independent prognostic variables were associated with digit replantation failure: age, mechanism of injury, ischemia duration, smoking status, amputation pattern (complete or incomplete), and surgeon's experience. The prediction model achieved good discrimination, with concordance indexes of 0.81 (95% CI, 0.76-0.85) and 0.70 (95% CI, 0.65-0.74) in predicting digit failure in the training and validation cohorts, respectively. Calibration curves were well-fitted for both training and validation cohorts. CONCLUSIONS: The proposed prediction model effectively predicted the failure rate of digit replantation for individual digits of all patients. It could assist in selecting the most suitable surgical plan for the patient.

Associations between insomnia symptoms and inflammatory cytokines in adolescents with first-episode and recurrent major depressive disorder.

BACKGROUND: Insomnia symptoms are often associated with increased levels of inflammatory biomarkers. However, such associations have not been adequately explored in adolescents with major depressive disorder (MDD). This study aimed to examine the associations between insomnia symptoms with inflammatory cytokines in adolescents with first-episode and recurrent MDD. METHODS: From January to December 2021, this study included 164 adolescents with MDD and 76 healthy controls (HCs). The Center for Epidemiological Studies Depression Scale (CES-D) and the Insomnia Severity Index Scale (ISI) were used to assess depressive and insomnia symptoms, respectively. Also, plasma levels of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-17 A and tumor necrosis factor-α (TNF-α) were measured. RESULTS: The prevalence of mild, moderate and severe insomnia in adolescents with MDD was 40.24 %, 36.59 % and 6.71 %, respectively. The patients had higher levels of IL-1ß, IL-6 and TNF-α than HCs (all p < 0.05). ISI score was positively correlated with CES-D score and levels of IL-1ß, IL-6 and TNF-α in first-episode patients but not in recurrent patients. A further multivariate stepwise linear regression analysis showed that ISI score was independently associated with CES-D score (beta = 0.523, t = 5.833, p < 0.001) and TNF-α levels (beta = 0.254, t = 2.832, p = 0.006). LIMITATIONS: The cross-sectional design leads to failure to make causal inferences. CONCLUSION: Insomnia symptoms are common in adolescents with MDD and associated with elevated levels of inflammatory cytokines in first-episode patients. The findings suggest that inflammatory cytokines may relate to the pathogenesis of insomnia symptoms in adolescents with MDD, but further longitudinal studies are needed to explore the causal association between insomnia symptoms and inflammatory cytokines in MDD.

PCSK6 exacerbates Alzheimer's disease pathogenesis by promoting MT5-MMP maturation.

Proprotein convertase subtilisin/kexin type 6 (PCSK6) is a calcium-dependent serine proteinase that regulates the proteolytic activity of various precursor proteins and facilitates protein maturation. Dysregulation of PCSK6 expression or function has been implicated in several pathological processes including nervous system diseases. However, whether and how PCSK6 is involved in the pathogenesis of Alzheimer's disease (AD) remains unclear. In this study, we reported that the expression of PCSK6 was significantly increased in the brain tissues of postmortem AD patients and APP23/PS45 transgenic AD model mice, as well as N2AAPP cells. Genetic knockdown of PCSK6 reduced amyloidogenic processing of APP in N2AAPP cells by suppressing the activation of membrane-type 5-matrix metalloproteinase (MT5-MMP), referred to as η-secretase. We further found that PCSK6 cleaved and activated MT5-MMP by recognizing the RRRNKR sequence in its N-terminal propeptide domain in N2A cells. The mutation or knockout of this cleavage motif prevented PCSK6 from interacting with MT5-MMP and performing cleavage. Importantly, genetic knockdown of PCSK6 with adeno-associated virus (AAV) reduced Aß production and ameliorated hippocampal long-term potentiation (LTP) and long-term spatial learning and memory in APP23/PS45 transgenic mice. Taken together, these results demonstrate that genetic knockdown of PCSK6 effectively alleviate AD-related pathology and cognitive impairments by inactivating MT5-MMP, highlighting its potential as a novel therapeutic target for AD treatment.

Effects of butylphthalide on cerebral vascular circulation, coagulation function, and neurological function in patients with acute severe ischemic stroke following intravenous thrombolysis: a preliminary study.

OBJECTIVE: To analyze the effects of Butylphthalide on cerebral vascular circulation, coagulation function, and neurological function in patients with acute severe ischemic stroke following intravenous thrombolysis. METHODS: Clinical efficacy, cerebral vascular circulation indicators [anterior cerebral artery (ACA), middle cerebral artery (MCA), vertebral artery (VA) blood flow velocity], coagulation function indicators [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB)], neurological function indicators [Activities of Daily Living (ADL) score. RESULTS: The total effective rate of treatment in the control group was 76.47%, while in the observation group, it was 96.08%, with the observation group showing a significantly higher total effective rate than the control group (p < 0.05). Before treatment, there was no significant difference in ACA, MCA, and VA blood flow velocity between the two groups (p > 0.05). However, after treatment, the ACA, MCA, and VA blood flow velocity in the observation group were significantly higher than those in the control group (p < 0.05). Before treatment, there was no significant difference in PT, APTT, TT, and FIB levels between the two groups (p > 0.05). CONCLUSION: In patients with acute severe ischemic stroke undergoing intravenous thrombolysis, the addition of Butylphthalide to the treatment regimen yields favorable clinical outcomes. Compared to Alteplase alone, the addition of Butylphthalide further improves cerebral vascular circulation and coagulation function, promoting the recovery and reconstruction of neurological function in patients. Importantly, the addition of Butylphthalide does not increase the risk of adverse reactions, making it a safe and ideal option for clinical application.

Modulating nickel-iron active species via dealloying to boost the oxygen evolution reaction.

The surface structure and composition of pre-catalysts play a critical role in the surface reconstruction process toward active species during the anodic oxygen evolution reaction (OER). Surface modified methods can accelerate the OER process of alloy ribbons, but the understanding of pre-catalysts and the structure/reactivity of the reconstruction (active) species is still insufficient. Herein, we report a two-step dealloyed Ni-Fe-P alloy ribbon as a highly efficient OER electrocatalyst. By adjusting the surface-derived component, we could regulate Ni/Fe hydroxide active species on the Ni-Fe-P alloy ribbon, enhancing the OER performance. The oxidation and release of P driven by dealloying plays a key role in constructing optimal ß-NiOOH/FeOOH catalytic species on Ni-Fe-P. The optimal ß-NiOOH/FeOOH active species enables Ni-Fe-P alloy to obtain a 104 mV of reduction in overpotential (at 10 mA cm-2) and a 78-fold increase in current density (at overpotential: 300 mV) compared to undealloyed Ni-Fe-P. Our work provides valuable insights into the relationship between the surface structure/composition of alloy bulk electrocatalysts and surface-reconstructed species and a rational design of a surface treatment process.

Sulforaphane Attenuates AOM/DSS-Induced Colorectal Tumorigenesis in Mice via Inhibition of Intestinal Inflammation.

Sulforaphane (SFN) is a compound derived from cruciferous plants. It has received considerable attention in recent years due to its effectiveness in cancer prevention and anti-inflammatory properties. The purpose of this study was to evaluate the antitumor potential of sulforaphane on colitis-associated carcinogenesis (CAC) through the establishment of a mouse model with AOM/DSS. First, AOM/DSS and DSS-induced model were established and administered SFN for 10 wk, and then the severity of colitis-associated colon cancer was examined macroscopically and histologically. Subsequently, immune cells and cytokines in the tumor microenvironment (TME) were quantified. Finally, the influence of sulforaphane was also investigated using different colon cell lines. We found that sulforaphane treatment decreased tumor volume, myeloid-derived suppressor cells (MDSC) expansion, the expression of the proinflammatory cytokine IL-1ß, and the level of IL-10 in serum. Also, it enhanced the antitumor activities of CD8+ T cells and significantly reduced tumorigenesis as induced by AOM/DSS. SFN also attenuated intestinal inflammation in DSS-induced chronic colitis by reshaping the inflammatory microenvironment. This work demonstrates that sulforaphane suppresses carcinogenesis-associated intestinal inflammation and prevents AOM/DSS-induced intestinal tumorigenesis and progression.

Identifying risk loci for obsessive-compulsive disorder and shared genetic component with schizophrenia: A large-scale multi-trait association analysis with summary statistics.

Due to limited samples, no genetic loci have been identified for obsessive-compulsive disorder (OCD) in genome-wide association studies. Additionally, although co-morbidities between OCD and schizophrenia (SCZ) were observed, their common genetic etiology was not completely known. Here, we conducted a comprehensive investigation regarding the genetic architecture of OCD and the common genetic foundation shared by OCD and SCZ using summary statistics data (2688 cases and 7037 controls for OCD; 53,386 cases and 77,258 controls for SCZ). We discovered significant genetic correlation between OCD and SCZ (r̂g=0.296, P = 2.82 × 10-11). We then performed two multi-trait association analyses to detect OCD-associated loci and colocalization analysis to detect causal variants. Parallel gene-level analyses were also implemented. We identified 323 OCD-relevant variants located within 12 loci, with four loci shared the same causal variants between OCD and SCZ. Further, the gene-level analyses discovered 8 OCD-associated genes. Finally, multiple functional analyses at both SNP and gene levels showed that these genetic association signals had significant enrichments in the regions of left ventricle and anterior cingulate cortex, and suggested an important role of pathways involving regulation of telomere maintenance, histone phosphorylation, and GnRH secretion. Overall, this study identified new genetic loci for OCD and provided substantial evidence supporting common genetic foundation underlying OCD and SCZ. The findings advanced our understanding of genetic architecture and pathophysiology of OCD as well as shedding light on shared genetic etiology of the two disorders.

Altered EEG Microstates Dynamics in Individuals with Subthreshold Depression When Generating Negative Future Events.

Negative bias in prospection may play a crucial role in driving and maintaining depression. Recent research suggests abnormal activation and functional connectivity in regions of the default mode network (DMN) during future event generation in depressed individuals. However, the neural dynamics during prospection in these individuals remain unknown. To capture network dynamics at high temporal resolution, we employed electroencephalogram (EEG) microstate analysis. We examined microstate properties during both positive and negative prospection in 35 individuals with subthreshold depression (SD) and 35 controls. We identified similar sets of four canonical microstates (A-D) across groups and conditions. Source analysis indicated that each microstate map partially overlapped with a subsystem of the DMN (A: verbal; B: visual-spatial; C: self-referential; and D: modulation). Notably, alterations in EEG microstates were primarily observed in negative prospection of individuals with SD. Specifically, when generating negative future events, the coverage, occurrence, and duration of microstate A increased, while the coverage and duration of microstates B and D decreased in the SD group compared to controls. Furthermore, we observed altered transitions, particularly involving microstate C, during negative prospection in the SD group. These altered dynamics suggest dysconnectivity between subsystems of the DMN during negative prospection in individuals with SD. In conclusion, we provide novel insights into the neural mechanisms of negative bias in depression. These alterations could serve as specific markers for depression and potential targets for future interventions.

A H2 S-Generated Supramolecular Photosensitizer for Enhanced Photodynamic Antibacterial Infection and Relieving Inflammation.

Photodynamic therapy (PDT) is a promising treatment against bacteria-caused infections. By producing large amounts of reactive oxygen species (ROS), PDT can effectively eliminate pathogenic bacteria, without causing drug resistance. However, excessive ROS may also impose an oxidative stress on surrounding tissues, resulting in local inflammation. To avoid this major drawback and limit pro-inflammation during PDT, this work prepared a supramolecular photosensitizer (TPP-CN/CP5) based on host-guest interactions between a cysteine-responsive cyano-tetraphenylporphyrin (TPP-CN) and a water-soluble carboxylatopillar[5]arene (CP5). TPP-CN/CP5 not only possesses excellent photodynamic antibacterial properties, but also shows good anti-inflammatory and cell protection capabilities. Under 660 nm light irradiation, TPP-CN/CP5 could rapidly produce abundant ROS for sterilization. After the PDT process, the addition of cysteine (Cys) triggers the release of H2 S from TPP-CN. H2 S then stops the induced inflammation by inhibiting the production of related inflammatory factors. Both in vitro and in vivo experiments show the excellent antibacterial effects and anti-inflammatory abilities of TPP-CN/CP5. These results will certainly promote the clinical application of PDT in the treatment of bacterial infectious diseases.