Alternating bilateral sensory stimulation alleviates alcohol-induced conditioned place preference via a superior colliculus-VTA circuit.

Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current treatments have yet to identify effective methods for reducing cravings and preventing relapse. In this study, we find that 4-Hz alternating bilateral sensory stimulation (ABS) effectively reduces ethanol-induced conditioned place preference (CPP) in male mice, while 4-Hz flash light does not exhibit therapeutic effects. Whole-brain c-Fos mapping demonstrates that 4-Hz ABS triggers notable activation in superior colliculus GABAergic neurons (SCGABA). SCGABA forms monosynaptic connections with ventral tegmental area dopaminergic neurons (VTADA), which is implicated in ethanol-induced CPP. Bidirectional chemogenetic manipulation of SC-VTA circuit either replicates or blocks the therapeutic effects of 4-Hz ABS on ethanol-induced CPP. These findings elucidate the role of SC-VTA circuit for alleviating ethanol-related CPP by 4-Hz ABS and point to a non-drug and non-invasive approach that might have potential for treating alcohol use disorder.

A Model to Predict Prognosis of Renal Cell Clear Cell Carcinoma Based on 3 Angiogenesis-related Long Non-coding RNAs.

Background: Tumor angiogenesis is closely related to the progression of clear cell renal cell carcinoma (ccRCC). Long non-coding RNAs (lncRNAs) regulating angiogenesis could be potential biomarkers for predicting ccRCC prognosis. With this study, we aimed to construct a prognostic model based on lncRNAs and explore its underlying mechanisms. Methods: RNA data and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Angiogenesis-related genes (ARGs) were extracted from the Molecular Signatures database. Pearson correlation and LASSO and COX regression analyses were performed to identify survival-related AR-lncRNAs (sAR-lncRNAs) and construct a prognostic model. The predictive power of the prognostic model was verified according to Kaplan‒Meier curve, receiver operating characteristic (ROC) curve and nomogram analyses. The correlation between the prognostic model and clinicopathological characteristics was assessed via univariate and multivariate analyses. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was subsequently performed to elucidate the mechanisms of the sAR-lncRNAs. In vitro qPCR, immunohistochemistry, migration and invasion assays were conducted to confirm the angiogenic function of sAR-lncRNAs. Results: Three sAR-lncRNAs were used to construct a prognostic model. The model was moderately accurate in predicting 1- , 3- and 5-year ccRCC prognosis, and the risk score according to this model was closely related to clinicopathological characteristics such as T grade and T stage. A nomogram was constructed to precisely estimate the overall survival of ccRCC patients. KEGG enrichment analysis indicated that the MAPK and Notch pathways were highly enriched in high-risk patients. Additionally, we found that the expression of the lncRNAs AC005324.4 and AC104964.4 in the prognostic model was lower in ccRCC cell lines and cancer tissues than in the HK-2 cell line and paracancerous tissues, while the expression of the lncRNA AC087482.1 showed the opposite trend. In a coculture model, knockdown of lncRNA AC005324.4 and lncRNA AC104964.4 significantly promoted the migration and invasion of human umbilical vein endothelial cells (HUVECs), but siR-AC087482.1 transfection alleviated these effects. Conclusions: We constructed a prognostic model based on 3 sAR-lncRNAs and validated its value in clinicopathological characteristics and prognostic prediction of ccRCC patients, providing a new perspective for ccRCC treatment decision making.

Outcomes of fenestrated endovascular abdominal aortic repair in distal entry tears of chronic debakey IIIb aortic dissection.

Currently, there have been very few reports within the literature which specifically address using fenestrated and branched stent grafts to completely isolate and repair distal entry tears of chronic DeBakey IIIb aortic dissection. This study aimed to evaluate the clinical outcomes of a 3-dimensional (3D) printed aortic model-guided fenestrated stent in the treatment of distal tears of chronic DeBakey IIIb aortic dissection after thoracic endovascular aortic repair (TEVAR). The study was a one-center retrospective study comprising 36 patients who underwent TEVAR and fenestrated endovascular abdominal aortic repair (F-EVAR) between April 2014 and December 2022. Patient data was compiled and analysed for preoperative, intraoperative, and perioperative characteristics. In total, 36 patients (12 females and 24 males) were incorporated into this study. All of the patients included in this study had hypertension, and among them, the leading cause for undergoing II-stage F-EVAR was the progression of a false lumen, accounting for 24 cases (66.7% of the total). The technical success rate was 97.2% and there were no cases of 30-day mortality, myocardial infarction, permanent paraparesis, or organ failure. One year post-F-EVAR treatment, surviving patients showed significant false and true lumen remodelling with 100% complete false-lumen thrombosis. A total of five patients died during the follow-up, two patients died related to aorta complications and three patients died of heart failure, multiple organ failure, or septic shock. II-stage F-EVAR was safe and feasible operation to repair all distal tears of chronic DeBakey IIIb aortic dissection.

Basolateral Amygdala Cannabinoid CB1 Receptor Controls Formation and Elimination of Social Fear Memory.

Patients with post-traumatic stress disorder (PTSD) usually manifest persistence of the traumatic memory for a long time after the event, also known as resistance to extinction learning. Numerous studies have shown that the endocannabinoid system, specifically the cannabinoid type-1 receptor (CB1R), plays an important role in traumatic memory. However, the effect of basolateral amygdala (BLA) CB1R in social fear memory formation and elimination is still unclear. Here, we built a mouse model of social avoidance induced by acute social defeat stress to investigate the role of BLA CB1R in social fear memory formation and anxiety- and depression-like behavior. Anterograde knockout of CB1R in BLA neurons facilitates social fear memory formation and manifests an anxiolytic effect but does not influence sociability and social novelty. Retrograde knockout of CB1R in BLA promotes social fear memory formation and shows an anxiogenic effect but does not affect sociability and social novelty. Moreover, intracerebral injection of the CB1R antagonist AM251 in BLA during the memory reconsolidation time window eliminates social fear memory. Our findings suggest the CB1R of BLA can be used as a novel molecular target in social fear memory formation and elimination and potential PTSD therapy with memory retrieval and AM251.

Amygdalo-nigral circuit mediates stress-induced vulnerability to the parkinsonian toxin MPTP.

AIMS: The aim was to investigate the effect of mood disorders on parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor disability, substantia nigra pars compacta (SNc) dopaminergic (DA) neurons loss. Also, the neural circuit mechanism was elucidated. METHODS: The depression-like (physical stress, PS) and anxiety-like (emotional stress, ES) mouse models were established by the three-chamber social defeat stress (SDS). The features of Parkinson's disease were reproduced by MPTP injection. Viral-based whole-brain mapping was utilized to resolve the stress-induced global changes in direct inputs onto SNc DA neurons. Calcium imaging and chemogenetic techniques were applied to verify the function of the related neural pathway. RESULTS: We found that PS mice, but not ES mice, showed worse movement performance and more SNc DA neuronal loss than control mice after MPTP administration. The projection from the central amygdala (CeA) to the SNcDA was significantly increased in PS mice. The activity of SNc-projected CeA neurons was enhanced in PS mice. Activating or inhibiting the CeA-SNcDA pathway could mimic or block PS-induced vulnerability to MPTP. CONCLUSIONS: These results indicated that projections from CeA to SNc DA neurons contribute to SDS-induced vulnerability to MPTP in mice.

Galectin-3 and peripheral artery disease: a Mendelian randomization study.

Background: Multiple clinical studies have found a significant correlation between elevated galectin-3 (Gal-3) in circulation and the diagnosis and severity of peripheral arterial disease (PAD). The current study used the Mendelian randomization (MR) technique to evaluate the possible causal relationship between Gal-3 and PAD. Methods: Genome-wide association study (GWAS) data of Gal-3 and PAD were obtained through the MR-Base platform. Then, using Gal-3 as the exposure and PAD as the outcome, a two-sample MR analysis was performed utilizing several regression techniques, including MR-Egger regression, inverse variance weighted (IVW), weighted median, and weighted mode. Results: Six single-nucleotide polymorphisms (SNPs) were identified and designated as instrumental variables (IVs) that exhibited significant correlations with Gal-3 (linkage disequilibrium r2 < 0.001; P < 5 × 10-8). Various statistical methods showed that there was an absence of a significant link between Gal-3 and PAD (IVW: odds ratio (OR) = 0.9869, 95% confidence interval (CI) = 0.8792-1.1078, P = 0.8232). In addition, the presence of genetic pleiotropy did impact the putative causal relationship between PAD and Gal-3 (MR-Egger intercept = 0.0099, P = 0.659). Conclusions: There is no current evidence to establish a causal relationship between the level of Gal-3 in circulation and PAD.

A zona incerta-basomedial amygdala circuit modulates aversive expectation in emotional stress-induced aversive learning deficits.

A previously published study showed that stress may interfere with associative aversive learning and facilitate mood-related disorders. However, whether emotional stress alone affects aversive learning is unknown. Using three chamber-vicarious social defeat stress (3C-VSDS) model mice, we investigated the effect of emotional stress on aversive learning. An important origin of dopamine (DA) neurons, the zona incerta (ZI), is expected to be a novel target for the modulation of aversive learning. However, less is known about the circuit mechanism of ZI DA neurons in aversive learning. Here, we subjected mice to a fear-conditioning system (FCS) and observed an increased calcium activity of ZI TH+ neurons in aversive expectation during the conditioning phase, especially during the late stage of the conditional stimulus (CS) when CS and unconditional stimulus (US) pairings were used. Optogenetic inhibition of ZI TH+ neurons at the late stage of CS disrupted conditioned fear learning in mice. We further identified a TH+ projection from the ZI to the basomedial amygdala (BMA) and found that optogenetic inhibition of the ZI-BMA circuit could also block aversive learning. Finally, we used 3C-VSDS mice as a model of emotional stress. We found that the 3C-VSDS model mice demonstrated reduced aversive expectation associated with ZI TH+ neurons in the late stage of CS and impaired aversive learning in FCS. Optogenetic activation of ZI-BMA TH+ projections in the late stage of CS significantly reversed the aversive FCS learning disability of 3C-VSDS model mice. These data suggest that a TH+ circuit from the ZI to the BMA is required for aversive expectation, both at baseline and in 3C-VSDS-induced aversive learning deficits and that this circuit is a potential target for the modulation of aversive learning. Low activity of ZI-BMA TH+ projections is one reason for 3C-VSDS-induced aversive learning deficits.

Serum Autoantibodies against LRDD, STC1, and FOXA1 as Biomarkers in the Detection of Ovarian Cancer.

Purpose: This study is aimed at evaluating serum autoantibodies against four tumor-associated antigens, including LRDD, STC1, FOXA1, and EDNRB, as biomarkers in the immunodiagnosis of ovarian cancer (OC). Methods: The autoantibodies against LRDD, STC1, FOXA1, and EDNRB were measured using an enzyme-linked immunosorbent assay (ELISA) in 94 OC patients and 94 normal healthy controls (NHC) in the research group. In addition, the diagnostic values of different autoantibodies were validated in another independent validation group, which comprised 136 OC patients, 136 NHC, and 181 patients with benign ovarian diseases (BOD). Results: In the research group, autoantibodies against LRDD, STC1, and FOXA1 had higher serum titer in OC patients than NHC (P < 0.001). The area under receiver operating characteristic curves (AUCs) of these three autoantibodies were 0.910, 0.879, and 0.817, respectively. In the validation group, they showed AUCs of 0.759, 0.762, and 0.817 and sensitivities of 49.3%, 42.7%, and 48.5%, respectively, at specificity over 90% for discriminating OC patients from NHC. For discriminating OC patients from BOD, they showed AUCs of 0.718, 0.729, and 0.814 and sensitivities of 47.1%, 39.0%, and 51.5%, respectively, at specificity over 90%. The parallel analyses demonstrated that the combination of anti-LRDD and anti-FOXA1 autoantibodies achieved the optimal diagnostic performance with the sensitivity of 58.1% at 87.5% specificity and accuracy of 72.8%. The positive rate of the optimal autoantibody panel improved from 62.4% to 87.1% when combined with CA125 in detecting OC patients. Conclusion: Serum autoantibodies against LRDD, STC1, and FOXA1 have potential diagnostic values in detecting OC.

Diagnostic value of RNA for hepatocellular carcinoma: a network meta-analysis.

Aim: The aim of this study was to evaluate the capacity of RNA in the diagnosis of hepatocellular carcinoma (HCC). Methods: A systematic review was conducted from PubMed, Cochrane Library, EMBASE and Web of Science databases via well-designed retrieval strategy. Subsequently, the network meta-analysis was performed by the STATA software. Results: Through statistical analysis, the three hypotheses of the network meta-analysis were established. In view of these hypotheses, the diagnostic efficacy of the three markers in HCC (HCC vs healthy people) may be consistent, and the cumulative ranking results showed such a trend: circular RNA >long noncoding RNA >microRNA. Conclusion: Circular RNA may be most effective for diagnosing HCC across the three types of RNA.

Identification and Evaluation of Autoantibody to a Novel Tumor-Associated Antigen GNA11 as a Biomarker in Esophageal Squamous Cell Carcinoma.

The study aims to explore the diagnostic value of anti-GNA11 autoantibody in esophageal squamous cell carcinoma (ESCC) from multiple levels. Autoantibody against GNA11 with the highest diagnostic performance was screened out from the customized protein microarray. A total of 486 subjects including ESCC patients and matched normal controls were recruited in the verification and validation phases by using enzyme-linked immunosorbent assay (ELISA). Western blotting analysis was used to verify the ELISA results. Immunohistochemistry (IHC) was used to evaluate GNA11 expression in ESCC tissues and para-tumor tissues. In addition, a bioinformatics approach was adopted to investigate the mRNA expression of GNA11 in ESCC. Results indicated that the level of anti-GNA11 autoantibody in ESCC patients was significantly higher than that in the normal controls, and it can be used to distinguish ESCC patients from normal individuals in clinical subgroups (p < 0.05), as revealed by both ELISA and Western blotting. The receiver operating characteristic (ROC) curve analysis showed that anti-GNA11 autoantibody could distinguish ESCC patients from normal controls with an area under the ROC curve (AUC) of 0.653, sensitivity of 10.96%, and specificity of 98.63% in the verification cohort and with an AUC of 0.751, sensitivity of 38.24%, and specificity of 88.82% in the validation cohort. IHC manifested that the expression of GNA11 can differentiate ESCC tissues with para-tumor tissues (p < 0.05), but it cannot be used to differentiate different pathological grades and clinical stages (p > 0.05). The mRNA expression of GNA11 in ESCC patients and normal controls was different with a bioinformatics mining with The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data in Gene Expression Profiling Interactive Analysis (GEPIA). In summary, anti-GNA11 autoantibody has the potential to be a new serological marker in the diagnosis of ESCC.

Identification of Novel Autoantibodies Based on the Human Proteomic Chips and Evaluation of Their Performance in the Detection of Gastric Cancer.

Autoantibodies against tumor-associated antigens (TAAbs) can be used as potential biomarkers in the detection of cancer. Our study aims to identify novel TAAbs for gastric cancer (GC) based on human proteomic chips and construct a diagnostic model to distinguish GC from healthy controls (HCs) based on serum TAAbs. The human proteomic chips were used to screen the candidate TAAbs. Enzyme-linked immunosorbent assay (ELISA) was used to verify and validate the titer of the candidate TAAbs in the verification cohort (80 GC cases and 80 HCs) and validation cohort (192 GC cases, 128 benign gastric disease cases, and 192 HCs), respectively. Then, the diagnostic model was established by Logistic regression analysis based on OD values of candidate autoantibodies with diagnostic value. Eleven candidate TAAbs were identified, including autoantibodies against INPP5A, F8, NRAS, MFGE8, PTP4A1, RRAS2, RGS4, RHOG, SRARP, RAC1, and TMEM243 by proteomic chips. The titer of autoantibodies against INPP5A, F8, NRAS, MFGE8, PTP4A1, and RRAS2 were significantly higher in GC cases while the titer of autoantibodies against RGS4, RHOG, SRARP, RAC1, and TMEM243 showed no difference in the verification group. Next, six potential TAAbs were validated in the validation cohort. The titer of autoantibodies against F8, NRAS, MFGE8, RRAS2, and PTP4A1 was significantly higher in GC cases. Finally, an optimal prediction model with four TAAbs (anti-NRAS, anti-MFGE8, anti-PTP4A1, and anti-RRAS2) showed an optimal diagnostic performance of GC with AUC of 0.87 in the training group and 0.83 in the testing group. The proteomic chip approach is a feasible method to identify TAAbs for the detection of cancer. Moreover, the panel consisting of anti-NRAS, anti-MFGE8, anti-PTP4A1, and anti-RRAS2 may be useful to distinguish GC cases from HCs.

Method of ultrasound-assisted liquid-phase exfoliation to prepare graphene.

Graphene is a two-dimensional material with unique structure and excellent properties. After first being successfully prepared in 2004, it rapidly became a research hotspot in the fields of materials, chemistry, physics, and engineering. Currently, there are many methods for preparing graphene, such as ball milling method, chemical oxidation-reduction, chemical vapor deposition, and liquid-phase exfoliation. Among these methods, liquid-phase exfoliation is the most important preparation method. In this paper, ultrasound-assisted liquid-phase exfoliation is systematically studied. The output power and frequency of the ultrasonic crusher used in the experiment are 100 W and 20 kHz, respectively. Results show that ultrasonic waves can affect the size and thickness distribution of graphene sheets; ultrasound-assisted deoxycholic acid sodium aqueous solution has a good exfoliation effect. In addition, the effects of the 3 liquid-phase systems on preparing graphene are studied, including organic solvent system, aqueous surfactant system, and ionic liquids system; the improvement efforts for ultrasound-assisted liquid-phase exfoliation method are discussed including the exploration of new solvents and optimization of exfoliation process. The application of auxiliary agent-assisted liquid-phase exfoliation method is also discussed.

Surgical bypass and permanent iodine-125 seed implantation vs. surgical bypass for the treatment of pancreatic head cancer.

The present study aimed to investigate the efficacy and safety of Iodine-125 (125I) seed implantation in the treatment of locally advanced unresectable pancreatic head cancer. A prospective nonrandomized study was performed using data collected from patients between January 2009 and December 2012. A total of 34 patients underwent surgical bypass and permanent 125I seed implantation (group A), and 32 patients underwent biliary and gastric bypass (group B). The preoperative variables, operative data, postoperative complications and follow-up information were examined. No significant differences were identified in clinical characteristics, mortality, morbidity and length of hospital stay between the two groups. Tumor responses were significantly different between between patients in group A and B (partial response, 56 vs. 0%, P<0.001; progression, 24 vs. 84%, P=0.013). The time until disease progression was significantly longer in group A compared to group B (8±1 vs. 5±2 months; P<0.001). The median survival time was significantly longer in group A compared to group B (11 vs. 7 months; P<0.001). The quality of life was improved significantly in group A compared to group B. In the first month following surgery, pain scores were improved (24±10 vs. 54±19; P<0.001). Following repeated measure analysis, pain scores were significantly lower in group A compared to group B (P<0.05) at 9 months following surgery. The results of the present study suggest that 125I seed implantation is feasible, safe and effective for the treatment of unresectable pancreatic head cancer.

Assessment of the safety and efficacy of bedside ultrasound guidance for inferior vena cava filter placement in critically ill intensive care unit patients.

Inferior vena cava filters (IVCFs) have been used clinically for approximately 45 y, but only a few studies of these devices have involved intensive care unit (ICU) patients who were critically ill and had multiple-organ dysfunction or were otherwise too unstable for transport. The purpose of this research was to assess the tolerability and efficacy of bedside ultrasound-guided IVCF placement in ICU patients. A retrospective analysis of both bedside ultrasound-guided and X-ray-guided ICVF placement was performed from November of 2011 to August of 2013. The total success rate for ultrasound-guided IVCF placement was 93.4%, which included a 96.0% success rate in 25 ICU patients with an average age of 69.46 y. Six-month follow-up studies revealed no significant differences in long-term complications between the ultrasound- and X-ray-guided groups. IVCFs may be safely implanted under ultrasound guidance in a monitored ICU environment. Our conclusion is that patients should be fasting and should receive an enema and that pre-operative surface marking and dynamic monitoring should be employed. Further research is needed to develop specific ultrasound guidelines.

[Research on the threshold of Chl-a in Lake Taihu based on microcystins].

Water samples were collected in Lake Taihu from June to October in 2013 in order to investigate the threshold of chlorophyll a (Chl-a). The concentrations of three microcystins isomers (MC-LR, MC-RR, MC-YR) were detected by means of solid phase extraction and high performance liquid chromatography-tandem mass spectrometry. The correlations between various MCs and eutrophication factors, for instance of total nitrogen (TN), total phosphorus (TP), chlorophyll a, permanganate index etc were analyzed. The threshold of Chl-a was studied based on the relationships between MC-LR, MCs and Chl-a. The results showed that Lake Taihu was severely polluted by MCs and its spatial distribution could be described as follows: the concentration in Meiliang Bay was the highest, followed by Gonghu Bay and Western Lake, and Lake Center; the least polluted areas were in Lake Xuhu and Southern Lake. The concentration of MC-LR was the highest among the 3 MCs. The correlation analysis indicated that MC-LR, MC-RR, MC-YR and MCs had very positive correlation with permanganate index, TN, TP and Chl-a (P < 0.01). The threshold value of Chl-a was 12.26 mg x m(-3) according to the standard thresholds of MC-LR and MCs in drinking water. The threshold value of Chl-a in Lake Taihu was very close to the standard in the State of North Carolina, which demonstrated that the threshold value provided in this study was reasonable.

Quantifying the astrocytoma cell response to candidate pharmaceutical from F-ACTIN image analysis.

The distribution, directionality and motility of the actin fibers control cell shape, affect cell function and are different in cancer versus normal cells. Quantification of actin structural changes is important for further understanding differences between cell types and for elucidation of the effects and dynamics of drug interactions. We have developed an image analysis framework for quantifying F-actin organization patterns in confocal microscope images in response to different candidate pharmaceutical treatments. The main problem solved was to determine which quantitative features to compute from the images that both capture the visually-observed F-actin patterns and correlate with predicted biological outcomes. The resultant numerical features were effective to quantitatively profile the changes in the spatial distribution of F-actin and facilitate the comparison of different pharmaceuticals. The validation for the segmentation was done through visual inspection and correlation to expected biological outcomes. This is the first study quantifying different structural formations of the same protein in intact cells. Preliminary results show uniquely significant increases in cortical F-actin to stress fiber ratio for increasing doses of OSW-1 and Schweinfurthin A(SA) and a less marked increase for cephalostatin 1 derivative (ceph). This increase was not observed for the actin inhibitors: cytochalasin B (cytoB) and Y-27632 (Y). Ongoing studies are further validating the algorithms, elucidating the underlying molecular pathways and will utilize the algorithms for understanding the kinetics of the F-actin changes. Since many anti-cancer drugs target the cytoskeleton, we believe that the quantitative image analysis method reported here will have broad applications to understanding the mechanisms of action of candidate pharmaceuticals.