Regulating the activity of GABAergic neurons in the ventral pallidum alters the general anesthesia effect of propofol.

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia.

Development of a Bio-Hybrid Mosquito Stinger-Based Atomic Force Microscopy Probe.

Mosquitoes, notorious as the deadliest animals to humans due to their capacity to transmit diseases, pose a persistent challenge to public health. The primary prevention strategy currently in use involves chemical repellents, which often prove ineffective as mosquitoes rapidly develop resistance. Consequently, the invention of new preventive methods is crucial. Such development hinges on a thorough understanding of mosquito biting behaviors, necessitating an experimental setup that accurately replicates actual biting scenarios with controllable testing parameters and quantitative measurements. To bridge this gap, a bio-hybrid atomic force microscopy (AFM) probe was engineered, featuring a biological stinger - specifically, a mosquito labrum - as its tip. This bio-hybrid probe, compatible with standard AFM systems, enables a near-authentic simulation of mosquito penetration behaviors. This method marks a step forward in the quantitative study of biting mechanisms, potentially leading to the creation of effective barriers against vector-borne diseases (VBDs) and opening new avenues in the fight against mosquito-transmitted illnesses.

Construction of S100 family members prognosis prediction model and analysis of immune microenvironment landscape at single-cell level in pancreatic adenocarcinoma: a tumor marker prognostic study.

Pancreatic adenocarcinoma characterized by a mere 10% 5-year survival rate, poses a formidable challenge due to its specific anatomical location, making tumor tissue acquisition difficult. This limitation underscores the critical need for novel biomarkers to stratify this patient population. Accordingly, this study aimed to construct a prognosis prediction model centered on S100 family members. Leveraging six S100 genes and their corresponding coefficients, an S100 score was calculated to predict survival outcomes. The present study provided comprehensive internal and external validation along with power evaluation results, substantiating the efficacy of the proposed model. Additionally, the study explored the S100-driven potential mechanisms underlying malignant progression. By comparing immune cell infiltration proportions in distinct patient groups with varying prognoses, the research identified differences driven by S100 expression. Furthermore, the analysis explored significant ligand-receptor pairs between malignant cells and immune cells influenced by S100 genes, uncovering crucial insights. Notably, the study identified a novel biomarker capable of predicting the sensitivity of neoadjuvant chemotherapy, offering promising avenues for further research and clinical application.

Hepatic Involvement in Acquired Immunodeficiency Syndrome-Associated Kaposi's Sarcoma: A Descriptive Analysis on CT, MRI, and Ultrasound.

Purpose: To retrospectively analyse the different imaging manifestations of acquired immunodeficiency syndrome-associated hepatic Kaposi's sarcoma (AIDS-HKS) on CT, MRI, and Ultrasound. Patients and Methods: Eight patients were enrolled in the study. Laboratory tests of liver function were performed. The CT, MRI, and Ultrasound manifestations were reviewed by two radiologists and two sonographers, respectively. The distribution and imaging signs of AIDS-HKS were evaluated. Results: AIDS-HKS patients commonly presented multiple lesions, mainly distributed around the portal vein on CT, MRI, and Ultrasound. AIDS-HKS presented as ring enhancement in the arterial phase on contrast-enhanced CT and MRI scanning, and nodules gradually strengthen in the portal venous phase and the delayed phase. AIDS-HKS presented as intrahepatic bile duct dilatation and bile duct wall thickening around the lesion. Five patients (62.5%, 5/8) were followed up. After chemotherapy, the lesions were completely relieved (60.0%), or decreased (40.0%). Conclusion: AIDS-HKS presented as multiple nodular lesions with different imaging features. The combination of different imaging methods was helpful for the imaging diagnosis of AIDS-HKS.

Optimizing LI-RADS: ancillary features screened from LR-3/4 categories can improve the diagnosis of HCC on MRI.

OBJECTIVE: To determine the high-efficiency ancillary features (AFs) screened from LR-3/4 lesions and the HCC/non-HCC group and the diagnostic performance of LR3/4 observations. MATERIALS AND METHODS: We retrospectively analyzed a total of 460 patients (with 473 nodules) classified into LR-3-LR-5 categories, including 311 cases of hepatocellular carcinoma (HCC), 6 cases of non-HCC malignant tumors, and 156 cases of benign lesions. Two faculty abdominal radiologists with experience in hepatic imaging reviewed and recorded the major features (MFs) and AFs of the Liver Imaging Reporting and Data System (LI-RADS). The frequency of the features and diagnostic performance were calculated with a logistic regression model. After applying the above AFs to LR-3/LR-4 observations, the sensitivity and specificity for HCC were compared. RESULTS: The average age of all patients was 54.24 ± 11.32 years, and the biochemical indicators ALT (P = 0.044), TBIL (P = 0.000), PLT (P = 0.004), AFP (P = 0.000) and Child‒Pugh class were significantly higher in the HCC group. MFs, mild-moderate T2 hyperintensity, restricted diffusion and AFs favoring HCC in addition to nodule-in-nodule appearance were common in the HCC group and LR-5 category. AFs screened from the HCC/non-HCC group (AF-HCC) were mild-moderate T2 hyperintensity, restricted diffusion, TP hypointensity, marked T2 hyperintensity and HBP isointensity (P = 0.005, < 0.001, = 0. 032, p < 0.001, = 0.013), and the AFs screened from LR-3/4 lesions (AF-LR) were restricted diffusion, mosaic architecture, fat in mass, marked T2 hyperintensity and HBP isointensity (P < 0.001, = 0.020, = 0.036, < 0.001, = 0.016), which were not exactly the same. After applying AF-HCC and AF-LR to LR-3 and LR-4 observations in HCC group and Non-HCC group, After the above grades changed, the diagnostic sensitivity for HCC were 84.96% using AF-HCC and 85.71% using AF-LR, the specificity were 89.26% using AF-HCC and 90.60% using AF-LR, which made a significant difference (P = 0.000). And the kappa value for the two methods of AF-HCC and AF-LR were 0.695, reaching a substantial agreement. CONCLUSION: When adjusting for LR-3/LR-4 lesions, the screened AFs with high diagnostic ability can be used to optimize LI-RADS v2018; among them, AF-LR is recommended for better diagnostic capabilities.

Establishment and evaluation of a CT-based radiomic model for AIDS-associated pulmonary cryptococcosis.

BACKGROUND: Establish a CT-based diagnostic radiomic model for AIDS complicated with pulmonary cryptococcosis and evaluate the diagnostic efficacy of this model. METHODS: This retrospective study enrolled 98 AIDS patients with pulmonary cryptococcosis and 103 AIDS patients with other infections or neoplastic lesions, comprising a total of 699 lesions. Patients were randomly divided into a training group and test group at a ratio of 2.75:1. Features from all lesions, cavity lesions and solid nodule lesions were extracted, and two kinds of radiomic models (6 types) were established. ROC curves were drawn, and the sensitivity and specificity were calculated to compare the SVM model and LR model, radiologists' empirical diagnoses and the combination of these empirical diagnoses with the radiomic model. RESULTS: The AUCs of senior radiologist for all lesions and cavity lesions were lower than those of the SVM and LR models. The diagnostic efficacy of primary radiologist was lower than that of both of the other model types. The diagnostic efficacy of the LR model was relatively stable, with the highest diagnostic efficiency of the 3 model/radiologist groups. The AUCs of intermediate radiologist in combination with the LR radiomic model for all lesions, nodular lesions and cavity lesions were 0.88, 0.84, and 0.9, respectively, which were the highest among all models and radiologists. CONCLUSIONS: The CT-based radiomic LR model of AIDS-associated pulmonary cryptococcosis exhibits good diagnostic performance, which was similar to that of senior radiologists and higher than that of the primary radiologist. With the help of a radiomic model, radiologists can achieve improved diagnostic accuracy compared to that when only an empirical diagnosis is used.

[Effects of RPA1 down-regulation on the invasion and migration and cell cycle of human nasopharyngeal carcinoma CNE-2R cells with radio resistance].

Objective: To investigate the effects of RPA1 silencing on the invasion, migration and cell cycle of human nasopharyngeal carcinoma CNE-2R cells. Methods: shRNA technology was used to construct CNE-2R cell lines with RPA1 low-expression, which were verified by RT-PCR and Western blotting. The following assays were performed using the three 3 groups: control group(CNE-2),negative control group(NC-shRNA) and RPA1 down-regulation group(RPA1-shRNA). The effects of RPA silence on the proliferation, invasion, migration, and cell cycle of CNE-2R cells were detected using Cell Counting Kit-8, clone formation experiment, Transwell, scratch test and flow cytometry, respectively. The expressions of Chk2, p-Chk2, Cdc 25c and p-cdc25c were tested by Western blot assay. Results: The expressions of RPA1 mRNA and protein in the RPA1-shRNA group were lower than those in the CNE-2 and NC-shRNA groups significantly (P＜0.01 and 0.05). Compared with CNE-2 and NC-shRNA groups, the abilities of proliferation, invasion and migration of RPA1-shRNA group were decreased and the cell cycle in the RPA1-shRNA group was blocked in the G2/M phase (P＜0.01). The expressions of Chk2 and Cdc25c in RPA1-shRNA group cells were lower than those in CNE-2R and NC-shRNA group cells (P＜0.05), while the expressions of p-Chk2 and p-cdc25c were higher than those in the other groups (P＜0.05). Conclusion: After RPA1 silenced, the proliferation and migration of radio resistant human nasopharyngeal carcinoma CNE-2R cells was inhibited, resulting in cell cycle arrested in the G2/M phase.

CT findings of COVID-19 in follow-up: comparison between progression and recovery.

PURPOSE: We aimed to retrospectively analyze the imaging changes detected in the follow-up of coronavirus disease 2019 (COVID-19) patients on thin-section computed tomography (CT). METHODS: We included 54 patients diagnosed with COVID-19. The mean interval between the initial and follow-up CT scans was 7.82±3.74 days. Patients were divided into progression and recovery groups according to their outcomes. We evaluated CT images in terms of distribution of lesions and imaging manifestations. The manifestations included ground-glass opacity (GGO), crazy-paving pattern, consolidation, irregular line, and air bronchogram sign. RESULTS: COVID-19 lesions showed mainly subpleural distribution, which was accompanied by bronchovascular bundle distribution in nearly 30% of the patients. The lower lobes of both lungs were the most commonly involved. In the follow-up, the progression group showed more involvement of the upper lobe of the left lung than the recovery group. GGO was the most common sign. As the disease progressed, round GGO decreased and patchy GGO increased. On follow-up CT, consolidation increased in the progression group while decreasing in the recovery group. Air bronchogram sign was more commonly observed at the initial examination (90.9%) than at follow-up (30%) in the recovery group, but there was no significant change in the progression group. Pleural effusion and lymphadenopathy were absent in the initial examination, but pleural effusion was observed in three cases after follow-up. CONCLUSION: As COVID-19 progressed, round GGOs tended to evolve into patchy GGOs, consolidation increased, and pleural effusion could be occasionally observed. As COVID-19 resolved, the crazy-paving pattern and air bronchogram significantly decreased.

Transcriptome Based System Biology Exploration Reveals Homogeneous Tumorigenicity of Alimentary Tract Malignancy.

Malignancies of alimentary tract include esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ). Despite of their similarities in cancer development and progression, there are numerous researches concentrating on single tumor but relatively little on their common mechanisms. Our study explored the transcriptomic data of digestive tract cancers from The Cancer Genome Atlas database, yielding their common differentially expressed genes including 1,700 mRNAs, 29 miRNAs, and 362 long non-coding RNAs (lncRNAs). There were 12 mRNAs, 5 miRNAs, and 16 lncRNAs in the core competitive endogenous RNAs network by RNA-RNA interactions, highlighting the prognostic nodes of SERPINE1, hsa-mir-145, and SNHG1. In addition, the weighted gene co-expression network analysis (WGCNA) illustrated 20 gene modules associated with clinical traits. By taking intersections of modules related to the same trait, we got 67 common genes shared by ESCA and READ and screened 5 hub genes, including ADCY6, CXCL3, NPBWR1, TAS2R38, and PTGDR2. In conclusion, the present study found that SERPINE1/has-mir-145/SNHG1 axis acted as promising targets and the hub genes reasoned the similarity between ESCA and READ, which revealed the homogeneous tumorigenicity of digestive tract cancers at the transcriptome level and led to further comprehension and therapeutics for digestive tract cancers.

Relationship between Structural Characteristics and Plant Sources along with Pharmacology Research of Quassinoids.

Quassinoids, one kind of triterpenoids with multiple bioactivities such as anti-cancer, anti-malarial, anti-oxidative, anti-microbial, anti-diabetic, anti-viral, and anti-inflammatory effects, have drawn much attention in recent years. Between 2004 and 2018, the structural characteristics and plant sources of 190 quassinoids were reported. Herein, the structure-activity relationships (SARs) of quassinoids along with the anti-cancer mechanisms of four representative quassinoids, eurycomanone, bruceine D, dehydrobruceine B, and brusatol are discussed. This review might be useful for further research and development of quassinoids.

Clinical analysis of antithrombotic treatment and occurrence of stroke in elderly patients with nonvalvular persistent atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is common in elderly patients and is associated with ischemic stroke. We sought to explore the current status of antithrombotic therapy in elderly patients with nonvalvular persistent AF. METHODS: This is a retrospective study and data were collected from the First Hospital of China Medical University. A total of 300 patients were enrolled from January 2015 to June 2017. Patients were divided into two groups: Group 1 (from 65-74) and Group 2 (older than 75). The status of antithrombotic treatment was recorded. Follow-ups were done at 7, 90 , 180, and 360 days after discharge. The occurrence of stroke was recorded. RESULTS: For 287 patients with a CHA2 DS2 -VASc score ≥2, 41.10% received oral anticoagulants (OAC), 27.20% received new oral anticoagulants (NOAC), 42.20% received antiplatelet agents, 16.70% received no antithrombotic treatment. From 2015 to the first half 2017, the ratio of OAC was 25.90%, 51.89%, and 49.30%, respectively; ratio of NOAC were 16.90%, 30.19%, and 39.10%, respectively. During the four times follow-up, percentage of patients who had good treatment compliance was 65%, 49.2%, 38.5%, and 25% stroke rate was 6.7% in total 300 patients. Logistic regression analysis showed age older than 75 (odds ratio [OR] 4.812), prior stroke (OR 4.109) were risk factors of stroke, and OAC treatment (OR 0.021) could prevent stroke. CONCLUSION: Ratio of antithrombotic therapy in elderly patients with nonvalvular persistent AF was low and drug compliance was poor. Age, prior history of stroke, and OAC treatment are the important predictive factors of stoke in elderly patients.

Hantavirus Gc induces long-term immune protection via LAMP-targeting DNA vaccine strategy.

Hemorrhagic fever with renal syndrome (HFRS) occurs widely throughout Eurasia. Unfortunately, there is no effective treatment, and prophylaxis remains the best option against the major pathogenic agent, hantaan virus (HTNV), which is an Old World hantavirus. However, the absence of cellular immune responses and immunological memory hampers acceptance of the current inactivated HFRS vaccine. Previous studies revealed that a lysosome-associated membrane protein 1 (LAMP1)-targeting strategy involving a DNA vaccine based on the HTNV glycoprotein Gn successfully conferred long-term immunity, and indicated that further research on Gc, another HTNV antigen, was warranted. Plasmids encoding Gc and lysosome-targeted Gc, designated pVAX-Gc and pVAX-LAMP/Gc, respectively, were constructed. Proteins of interest were identified by fluorescence microscopy following cell line transfection. Five groups of 20 female BALB/c mice were subjected to the following inoculations: inactivated HTNV vaccine, pVAX-LAMP/Gc, pVAX-Gc, and, as the negative controls, pVAX-LAMP or the blank vector pVAX1. Humoral and cellular immunity were assessed by enzyme-linked immunosorbent assays (ELISAs) and 15-mer peptide enzyme-linked immunospot (ELISpot) epitope mapping assays. Repeated immunization with pVAX-LAMP/Gc enhanced adaptive immune responses, as demonstrated by the specific and neutralizing antibody titers and increased IFN-γ production. The inactivated vaccine induced a comparable humoral reaction, but the negative controls only elicited insignificant responses. Using a mouse model of HTNV challenge, the in vivo protection conferred by the inactivated vaccine and Gc-based constructs (with/without LAMP recombination) was confirmed. Evidence of pan-epitope reactions highlighted the long-term cellular response to the LAMP-targeting strategy, and histological observations indicated the safety of the LAMP-targeting vaccines. The long-term protective immune responses induced by pVAX-LAMP/Gc may be due to the advantage afforded by lysosomal targeting after exogenous antigen processing initiation and major histocompatibility complex (MHC) class II antigen presentation trafficking. MHC II-restricted antigen recognition effectively primes HTNV-specific CD4+ T-cells, leading to the promotion of significant immune responses and immunological memory. An epitope-spreading phenomenon was observed, which mirrors the previous result from the Gn study, in which the dominant IFN-γ-responsive hot-spot epitopes were shared between HLA-II and H2d. Importantly, the pan-epitope reaction to Gc indicated that Gc should be with potential for use in further hantavirus DNA vaccine investigations.

Discovery of putative capsaicin biosynthetic genes by RNA-Seq and digital gene expression analysis of pepper.

The Indian pepper 'Guijiangwang' (Capsicum frutescens L.), one of the world's hottest chili peppers, is rich in capsaicinoids. The accumulation of the alkaloid capsaicin and its analogs in the epidermal cells of the placenta contribute to the pungency of Capsicum fruits. To identify putative genes involved in capsaicin biosynthesis, RNA-Seq was used to analyze the pepper's expression profiles over five developmental stages. Five cDNA libraries were constructed from the total RNA of placental tissue and sequenced using an Illumina HiSeq 2000. More than 19 million clean reads were obtained from each library, and greater than 50% of the reads were assignable to reference genes. Digital gene expression (DGE) profile analysis using Solexa sequencing was performed at five fruit developmental stages and resulted in the identification of 135 genes of known function; their expression patterns were compared to the capsaicin accumulation pattern. Ten genes of known function were identified as most likely to be involved in regulating capsaicin synthesis. Additionally, 20 new candidate genes were identified related to capsaicin synthesis. We use a combination of RNA-Seq and DGE analyses to contribute to the understanding of the biosynthetic regulatory mechanism(s) of secondary metabolites in a nonmodel plant and to identify candidate enzyme-encoding genes.

[Pitavastatin enhances angiogenesis and perfusion in a murine mode of limb ischemia].

OBJECTIVE: We investigated the effects of pitavastatin on angiogenesis and perfusion in C3H/He mice with unilateral hind limb ischemia. METHODS: C3H/He mice treated with saline (n = 15) or pitavastatin (1 mg.kg(-1).d(-1), n = 15) per gavage for 1 week underwent unilateral hind limb ischemia surgery and were treated for another 5 weeks. Hind-limb blood flow was measured by Laser Doppler perfusion imager (LDPI, ischemic/nonischemic limb, %) at baseline, immediately after ischemia and weekly thereafter for 5 weeks. Endpoints included local vessel counts by immunofluorescence, phospho-Akt positive cell counts by immunoenzyme histochemical technique, vascular endothelial growth factors (VEGFs) expression in ischemic limbs by Western blot and serum nitric oxide metabolite (NOx) by chrome dioxide Griess method. RESULTS: Lower extremity perfusion was significantly improved in pitavastatin treated mice vs. controls as measured by LDPI% at 1 week post ischemia and thereafter (P < 0.05). Pitavastatin treatment was associated with significantly increased capillary count [(47 +/- 11) vs. (26 +/- 14)/per high-power field (x 200), P < 0.05] and greater percentage of phospho-Akt positive cells [(6 +/- 1) vs. (2 +/- 0)/per high-power field (x 200), P < 0.05] in ischemic limbs. Serum NOx [(77.3 +/- 21.8) vs. (52.1 +/- 11.2) mol/L, P < 0.05) and VEGF protein expression in ischemic limbs were also significantly increased in pitavastatin group than those in control group. CONCLUSIONS: Pitavastatin enhances angiogenesis and perfusion in CsH/He mice with limb ischemia.

[The pro-angiogenesis effect of Pitavastatin in the Klotho gene-knockout mice].

AIM: To discuss the effect of Pitavastatin on angiogenesis in vivo and its mechanism in Klotho heterozygous deficient mice. METHODS: The heterozygous deficient Klotho mice (kl +/-) and wild mice (kl +/+) from the same litter were used to establish the animal model of hind-limb ischemia and grouped into control and Pitavastatin group, respectively. Hind-limb blood flow was evaluated using Laser Doppler perfusion imager (LDPI) before treatment and after operation of hind-limbs. The capillaries in muscle of limbs were counted by means of CD-31 labeled immuno-fluorescence. The phosphorylation of Akt (Protein kinase B) in cells was measured by direct immunohistochemical technique. The expression of vascular endothelial growth factors (VEGFs) in muscle of limbs was assessed using Western blotting. RESULTS: After treatment of Pitavastatin, the blood flow in ischemic limbs of the Kl +/- and wild mice improved obviously, the ratio of blood flow area in ischemic limb to that in non-ischemic limb increased and the density of capillaries increased in ischemic limbs of the Kl +/- and wild mice. Pitavastatin enhanced the phosphorylation of Akt and the expression of VEGF in ischemic limbs of the Kl +/- and wild mice. CONCLUSION: Pitavastatin has the pro-angiogenesis effect in vivo and the VEGF-p-Akt-NO pathway may be involved in the mechanism of the effect of Pitavastatin.

[Effect of human plasma on preservation of red blood cells].

In order to study whether plasma can affect the structure and function of red blood cells during their storage period, the differences of pH value, concentration of K(+), Na(+), osmotic fragility, plasma hemoglobin, AchE, ATP, 2.3-DPG, P50 in suspended RBC, washed RBC, and RBC with various plasma volume at different storage times were compared. The results showed that plasma helped the blood to keep the RBC at high pH value, low K(+), high Na(+) and maintain RBC-ATP, oxygen carry capacity and deformability, but no effect on maintenance of osmotic fragility, and levels of plasma hemoglobin, AchE, ATP and 2.3-DPG was found in preservated blood. In conclusion, human plasma may be in favour of the preservation of red blood cells.

[Methoxypolyethylene glycol-modified HLA-A2 antigen on lymphocytes].

OBJECTIVE: To modify the HLA-A2 antigen on the lymphocytes with methoxypolyethylene glycol (mPEG) so as to block the specific binding site for antibody. METHOD: Different types of mPEG (all with final concentration of 12 mmol/L) were used at different temperatures in PBS with varied pH values for the modification of the HLA-A2 antigen. RESULT: The modification of the antigen was not obviously affected when it was carried out at 4 degrees Celsius or room temperature, but higher temperatures of 30 and 37 degrees Celsius significantly hampered the modification. Better antigen modification was observed with high-concentration mPEG in basic PBS, depending also on the type of mPEGs used for this purpose. CONCLUSION: The specific HLA-A2 binding on the lymphocytes is completely blocked by benzotriazole carbonate-mPEG(mPEG-BTC), which is superior to N-hydroxysuccinimidyl ester of mPEG(mPEG-SPA). Maleimide-mPEG(mPEG-MAL) is incapable of blocking the HLA-A2 ligand-binding site with antibody.