A two-amino-acid substitution in the transcription factor RORγt disrupts its function in TH17 differentiation but not in thymocyte development.

The transcription factor RORγt regulates differentiation of the TH17 subset of helper T cells, thymic T cell development and lymph-node genesis. Although elimination of RORγt prevents TH17 cell-mediated experimental autoimmune encephalomyelitis (EAE), it also disrupts thymocyte development, which could lead to lethal thymic lymphoma. Here we identified a two-amino-acid substitution in RORγt (RORγtM) that 'preferentially' disrupted TH17 differentiation but not thymocyte development. Mice expressing RORγtM were resistant to EAE associated with defective TH17 differentiation but maintained normal thymocyte development and normal lymph-node genesis, except for Peyer's patches. RORγtM showed less ubiquitination at Lys69 that was selectively required for TH17 differentiation but not T cell development. This study will inform the development of treatments that selectively target TH17 cell-mediated autoimmunity but do not affect thymocyte development or induce lymphoma.

Chronic atrophic gastritis and risk of incident upper gastrointestinal cancers: a systematic review and meta-analysis.

BACKGROUND: Previous literature has explored the relationship between chronic atrophic gastritis (CAG) and isolated cancers within the upper gastrointestinal cancers; However, an integrative synthesis across the totality of upper gastrointestinal cancers was conspicuously absent. The research objective was to assess the relationship between CAG and the risk of incident upper gastrointestinal cancers, specifically including gastric cancer, oesophageal cancer, and oesophagogastric junction cancer. METHODS: Rigorous systematic searches were conducted across three major databases, namely PubMed, Embase and Web of Science, encompassing the timeline from database inception until August 10, 2023. We extracted the necessary odds ratio (OR) and their corresponding 95% confidence interval (CI) for subsequent meta-analysis. Statistical analyses were conducted using Stata 17.0 software. RESULTS: This meta-analysis included a total of 23 articles encompassing 5858 patients diagnosed with upper gastrointestinal cancers. CAG resulted in a statistically significant 4.12-fold elevated risk of incident gastric cancer (OR = 4.12, 95% CI 3.20-5.30). Likewise, CAG was linked to a 2.08-fold increased risk of incident oesophageal cancer (OR = 2.08, 95%CI 1.60-2.72). Intriguingly, a specific correlation was found between CAG and the risk of incident oesophageal squamous cell carcinoma (OR = 2.29, 95%CI 1.77-2.95), while no significant association was detected for oesophageal adenocarcinoma (OR = 0.62, 95%CI 0.17-2.26). Moreover, CAG was correlated with a 2.77-fold heightened risk of oesophagogastric junction cancer (OR = 2.77, 95%CI 2.21-3.46). Notably, for the same type of upper gastrointestinal cancer, it was observed that diagnosing CAG through histological methods was linked to a 33-77% higher risk of developing cancer compared to diagnosing CAG through serological methods. CONCLUSION: This meta-analysis indicated a two- to fourfold increased risk of gastric cancer, oesophageal cancer, and oesophagogastric junction cancer in patients with CAG. Importantly, for the same upper gastrointestinal cancer, the risk of incident cancer was higher when CAG was diagnosed histologically compared to serological diagnosis. Further rigorous study designs are required to explore the impact of CAG diagnosed through both diagnostic methods on the risk of upper gastrointestinal cancers.

Lineage 1 PRRSVs infection induces hemorrhagic injury in intestines of piglets: Effects on complement and coagulation cascades.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly transmissible disease of significant concern in the pig industry. Previous studies have demonstrated that the XM-2020 strain (a lineage 1.8 PRRSV IA/2012/NADC30) can induce special hemorrhagic injury in the small intestines. However, the specific mechanism underlying this injurious effect remains incompletely understood. In this study, we examined the pathogenic properties of XM-2020 and YC-2020 strains (a lineage 1.5 PRRSV IA/2014/NADC34) in piglets. Animal pathogenic tests revealed that with either Lineage 1 PRRSVs strains XM-2020 or YC-2020 demonstrated pronounced intestinal hemorrhage and suppression of peripheral immunological organs, comparing to JXA1 infection. Transcriptome analysis of diseased small intestines unveiled that PRRSV infection stimulated oxidative and inflammatory reactions. Remarkably, we also observed activation of the complement system alongside a notable down-regulation of complement and coagulation cascade pathways in the Lineage 1 PRRSVs infection group. Based on these findings, we propose that the primary mechanism driving the hemorrhagic injury of the small intestine caused by Lineage 1 PRRSVs is the suppression of complement and coagulation cascades resulting from immunosuppression. This discovery deepens our understanding of the pathogenicity of PRRSV in the small intestine and provides promising ways out for the development of innovative strategies aimed at controlling PRRSV.

Risk factors for pterygium: Latest research progress on major pathogenesis.

A pterygium is a wedge-shaped fibrovascular growth of the conjunctiva membrane that extends onto the cornea, which is the outer layer of the eye. It is also known as surfer's eye. Growth of a pterygium can also occur on the either side of the eye, attaching firmly to the sclera. Pterygia are one of the world's most common ocular diseases. However, the pathogenesis remains unsolved to date. As the pathogenesis of pterygium is closely related to finding the ideal treatment, a clear understanding of the pathogenesis will lead to better treatment and lower the recurrence rate, which is notably high and more difficult to treat than a primary pterygium. Massive studies have recently been conducted to determine the exact causes and mechanism of pterygia. We evaluated the pathogenetic factors ultraviolet radiation, viral infection, tumor suppressor genes p53, growth factors, oxidative stress, apoptosis and neuropeptides in the progression of the disease. The heightened expression of TRPV1 suggests its potential contribution in the occurrence of pterygium, promoting its inflammation and modulating sensory responses in ocular tissues. Subsequently, the developmental mechanism of pterygium, along with its correlation with dry eye disease is proposed to facilitate the identification of pathogenetic factors for pterygia, contributing to the advancement of understanding in this area and may lead to improved surgical outcomes.

Impact of body mass index on long-term outcomes in patients undergoing percutaneous coronary intervention stratified by diabetes mellitus: a retrospective cohort study.

BACKGROUND: Patients with diabetes mellitus (DM) caused by obesity have increased in recent years. The impact of obesity on long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) with or without DM remains unclear. METHODS: We retrospectively analysed data from 1918 patients who underwent PCI. Patients were categorized into four groups based on body mass index (BMI, normal weight: BMI < 25 kg/m2; overweight and obese: BMI ≥ 25 kg/m2) and DM status (presence or absence). The primary endpoint was the occurrence of major adverse cardiac and cerebrovascular events (MACCE; defined as all-cause death, myocardial infarction, stroke, and unplanned repeat revascularization). RESULTS: During a median follow-up of 7.0 years, no significant differences in MACCE, myocardial infarction, or stroke were observed among the four groups. Overweight and obese individuals exhibited lower all-cause mortality rates compared with normal-weight patients (without DM: hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.37 to 0.78; with DM: HR: 0.57, 95% CI: 0.38 to 0.86). In non-diabetic patients, the overweight and obese group demonstrated a higher risk of unplanned repeat revascularization than the normal-weight group (HR:1.23, 95% CI:1.03 to 1.46). After multivariable adjustment, overweight and obesity were not significantly associated with MACCE, all-cause death, myocardial infarction, stroke, or unplanned repeat revascularization in patients with and without diabetes undergoing PCI. CONCLUSION: Overweight and obesity did not demonstrate a significant protective effect on long-term outcomes in patients with and without diabetes undergoing PCI.

Histograms of computed tomography values in differential diagnosis of benign and malignant osteogenic lesions.

BACKGROUND: The use of histogram analysis of computed tomography (CT) values is a potential method for differentiating between benign osteoblastic lesions (BOLs) and malignant osteoblastic lesions (MOLs). PURPOSE: To explore the diagnostic efficacy of histogram analysis in accurately distinguishing between BOLs and MOLs based on CT values. MATERIAL AND METHODS: A total of 25 BOLs and 25 MOLs, which were confirmed through pathology or imaging follow-up, were included in this study. FireVoxel software was used to process the lesions and obtain various histogram parameters, including mean value, standard deviation, variance, coefficient of variation, skewness, kurtosis, entropy value, and percentiles ranging from 1st to 99th. Statistical tests, such as two independent-sample t-tests and the Mann-Whitney U test with Bonferroni correction, were employed to compare the differences in histogram parameters between BOLs and MOLs. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of each parameter. RESULTS: Significant differences were observed in several histogram parameters between BOLs and MOLs, including the mean value, coefficient of variation, skewness, and various percentiles. Notably, the 25th percentile demonstrated the highest diagnostic efficacy, as indicated by the largest area under the curve in the ROC curve analysis. CONCLUSION: Histogram analysis of CT values provides valuable diagnostic information for accurately differentiating between BOLs and MOLs. Among the different parameters, the 25th percentile parameter proves to be the most effective in this discrimination process.

Metabolic Profile and Lipid Metabolism Phenotype in Mice with Conditional Deletion of Hepatic BMAL1.

The disruption of circadian rhythms (CRs) has been linked to metabolic disorders, yet the role of hepatic BMAL1, a key circadian regulator, in the whole-body metabolism and the associated lipid metabolic phenotype in the liver remains unclear. Bmal1 floxed (Bmal1f/f) and hepatocyte-specific Bmal1 knockout (Bmal1hep-/-) C57BL/6J mice underwent a regular feeding regimen. Hepatic CR, lipid content, mitochondrial function, and systemic metabolism were assessed at zeitgeber time (ZT) 0 and ZT12. Relevant molecules were examined to elucidate the metabolic phenotype. Hepatocyte-specific knockout of Bmal1 disrupted the expression of rhythmic genes in the liver. Bmal1hep-/- mice exhibited decreased hepatic TG content at ZT0, primarily due to enhanced lipolysis, reduced lipogenesis, and diminished lipid uptake. The ß-oxidation function of liver mitochondria decreased at both ZT0 and ZT12. Our findings on the metabolic profile and associated hepatic lipid metabolism in the absence of Bmal1 in hepatocytes provides new insights into metabolic syndromes from the perspective of liver CR disturbances.

Nanomaterials for fluorescent assay of bilirubin.

The accumulation of bilirubin in blood is associated with many diseases. Sensitive and accurate detection of bilirubin is of great significance for personal health care. The rapid development of fluorescent nanomaterials promotes rapid development in the bilirubin assay. In this review, traditional methods for detection of bilirubin are briefly presented to compare with fluorescent nanosensors. Subsequently, the recent progress of different types of fluorescent nanomaterials for determination of bilirubin is summarized. Further, the performance of fluorescent nanosensors and conventional techniques for sensing bilirubin are compared. To this end, the challenges and prospects concerning the topics are discussed. This review will provide some introductory knowledge for researchers to understand the status and importance of fluorescent nanosensors for sensing bilirubin.

Prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit.

OBJECTIVE: To analyze the prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit (PICU) and to compare the efficacy of different scoring systems for predicting the outcome of children. METHODS: Patients with an acute leukemia diagnosis admitted to a tertiary care university hospital PICU due to sepsis during chemotherapy between May 2015 and August 2022 were retrospectively analyzed through an electronic medical record system. RESULTS: During this period, 693 children with acute leukemia initially diagnosed were admitted to the center, and 155 (22.3%) of them were transferred to PICU due to deterioration of the disease during treatment. Total 109 (70.3%) patients were transferred to PICU due to sepsis. Here, 17 patients was excluded (prior treatment from another hospital; referring from other hospitals; discontinued treatment; incomplete medical record). Of the 92 patients studied, the mortality rate was 35.9%. Multivariate analysis revealed that remission status, lactate level, invasive mechanical ventilation (IMV), and inotropic support within 48 hours after PICU transfer were independent risk factors for PICU mortality. The pediatric sequential organ failure assessment (PSOFA) score had the greatest predictive validity for hospital mortality (area under the receiver operating characteristic curve [AUROC]: 0.83, 95% confidence intervals [CI]: 0.74-0.92), followed by the pediatric early warning score (PEWS) (0.82, 0.73-0.91) and pediatric critical illness score (PCIS) (0.79, 0.69-0.88). CONCLUSION: The mortality rate among children with acute leukemia complicated with sepsis is high after being transferred to the PICU. Various scoring systems can be used to monitor the clinical status of patients, identify sepsis early, detect critical illness, and determine the optimal time for transfer to the PICU for supportive treatment, thereby improving the prognosis of these patients.

Genetic and pathogenic characterization of an NADC-34-like isolate of porcine reproductive and respiratory syndrome virus.

In this study, an NADC34-like strain of porcine reproductive and respiratory syndrome virus (PRRSV), YC-2020, was isolated from a pig farm in Yuncheng, Shanxi Province, China. Phylogenetic and molecular evolutionary analysis showed that the genome sequence of YC-2020 was very similar to those of NADC34-like PRRSV strains in the ORF2-7 region. However, it was more closely related to NADC30-like PRRSV and highly pathogenic (HP) PRRSV in the NSP2 and NSP3-9 coding regions, respectively, suggesting that recombination had occurred between viruses belonging to lineages 1 and 8. Piglets infected with YC-2020 exhibited mild clinical signs, but they had severe histopathological lesions in their lungs. These findings reveal novel genetic and pathogenic features of this isolate.

Clinical and prognostic profile of SRSF2 and related spliceosome mutations in patients with acute myeloid leukemia.

BACKGROUND: Mutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but their clinical and prognostic relevance in acute myeloid leukemia (AML) have rarely been reported. METHODS: A total of 368 newly diagnosed non-M3 AML patients were included in this study. Next generation sequencing including four SF genes was performed on the genomicDNA. The clinical features and survival were analyzed using statistical analysis. RESULTS: We found that 64 of 368 patients harbored SF mutations. The SF mutations were much more frequently found in older or male patients. SRSF2 mutations were shown obviously co-existed with IDH2 mutation. The level of measurable residual disease after first chemotherapy was higher in SF-mutated patients compared to that in SF-wild patients, while the complete remission rate was significantly decreased. And the overall survival of SF-mutated patients was shorter than that of SF-wild patients. Moreover, our multivariable analysis suggests that the index of male, Kit mutation or ZRSR2 mutation was the independent risk factor for overall survival. SRSF2mut was associated with older age, higher proportion of peripheral blasts or abnormal cell proportion by flow cytometry. CONCLUSION: SF mutation is a distinct subgroup of AML frequently associated with clinic-biological features and poor outcome. SRSF2mut could be potential targets for novel treatment in AML.

Hawthorn total flavonoids ameliorate ambient fine particulate matter-induced insulin resistance and metabolic abnormalities of lipids in mice.

Recent studies have shown a strong correlation between ambient fine particulate matter (PM2.5) exposure and diabetes risk, including abnormal lipid accumulation and systemic insulin resistance (IR). Hawthorn total flavonoids (HF) are the main groups of active substances in Hawthorn, which showed anti-hyperlipidemic and anti-hyperglycemic effects. Therefore, we hypothesized that HF may attenuate PM2.5-induced IR and abnormal lipid accumulation. Female C57BL/6 N mice were randomly assigned to the filtered air exposure (FA) group, concentrated PM2.5 exposure (PM) group, PM2.5 exposure maintained on a low-dose HF diet (LHF) group, and PM2.5 exposure maintained on a high-dose HF diet (HHF) group for an 8-week PM2.5 exposure using a whole-body exposure device. Body glucose homeostasis, lipid profiles in the liver and serum, and enzymes responsible for hepatic lipid metabolism were measured. We found that exposure to PM2.5 impaired glucose tolerance and insulin sensitivity. In addition, triacylglycerol (TAG) in serum elevated, whereas hepatic TAG levels were decreased after PM2.5 exposure, accompanied by inhibited fatty acid uptake, lipogenesis, and lipolysis in the liver. HF administration, on the other hand, balanced the hepatic TAG levels by increasing fatty acid uptake and decreasing lipid export, leading to alleviated systemic IR and hyperlipidemia in PM2.5-exposed mice. Therefore, HF administration may be an effective strategy to protect against PM2.5-induced IR and metabolic abnormalities of lipids.

A Method of DDoS Attack Detection and Mitigation for the Comprehensive Coordinated Protection of SDN Controllers.

Software defined networking (SDN) improves the flexibility and programmability of the network by separating the control plane and the data plane and effectively realizes the global control of the network infrastructure. However, the centralized structure design of SDN exposes the controller to potential threats. Attackers have used the active flow table delivery mode to launch distributed denial of service (DDoS) attacks on the SDN controller, resulting in the controller failure and seriously affecting the network performance. To overcome this problem, this paper proposes a defense framework called CC-Guard. The framework consists of four modules: attack detection triggering, switch migration, anomaly detection, and mitigation. Among them, the attack detection trigger module improves the system's timely response to DDoS attacks. The switch migration module effectively unclogs the controller congestion problem and provides convenience for network flow transmission. The anomaly detection module uses a coarse-grained method for two-stage detection, which improves the detection accuracy. The mitigation module uses the idea of cross-domain cooperation of the controller to clear the abnormal flow in the blacklist. Experimental results show that our proposed CC-Guard has real-time DDoS attack defense capability and high detection accuracy, as well as efficient network resource utilization.

Directional Assembly of ZnO Nanowires via Three-Dimensional Laser Direct Writing.

The precise placement of semiconductor nanowires (NWs) into two- or three-dimensional (2D/3D) micro-/nanoarchitectures is a key for the construction of integrated functional devices. However, long-pending challenges still exist in high-resolution 3D assembly of semiconductor NWs. Here, we have achieved directional assembly of zinc oxide (ZnO) NWs into nearly arbitrary 3D architectures with high spatial resolution using two-photon polymerization. The NWs can regularly align in any desired direction along the laser scanning pathway. Through theoretical calculation and control experiments, we unveiled the laser-induced assembly mechanism and found that the nonoptical forces are the dominant factor leading to the directional assembly of ZnO NWs. A ZnO-NW-based polarization-resolved UV photodetector of excellent photoresponsivity was fabricated to demonstrate the potential application of the assembled ZnO NWs. This work is expected to promote the research on NW-based integrated devices such as photonic integrated circuits, sensors, and metamaterial with unprecedented controllability of the NW's placement in three dimensions.

Polarized second-harmonic generation optical microscopy for laser-directed assembly of ZnO nanowires.

Two-photon polymerization (TPP) based on laser direct writing is currently one of the most prevailing 3D micro/nano fabrication techniques. Nanomaterials can be doped in resins and assembled by TPP for developing advanced 3D functional devices. However, there lacks an effective visualization tool to determine the distribution and orientation of the nanomaterials as-doped in the composite resins. Herein, we present a nondestructive, in situ, and rapid characterization method to determine the orientation and distribution of the nanomaterials within cured resins using polarized second-harmonic generation (p-SHG). The directional assembly of the ZnO nanowires within micro/nanostructures fabricated by TPP is, for the first time to the best of our knowledge, characterized by p-SHG optical microscopy with a fast imaging speed by two orders of magnitude higher than that of the Raman mapping technique. Our method opens a window for nondestructive, rapid, in situ, and polarization-resolved characterization of functional devices made by TPP micro/nanofabrication.

Multifunctional Polymer Sponge with Molecule Recognition: Facile Mechanic Induced Separation.

Polymer sponges with molecular recognition provide a facile approach to water purification and industrial separation with easy operation, but its fabrication is still challenging because some critical issues of selective adsorption, high mechanical strength, and easy collection/re-use are difficult to be achieved in one material. Here, inspired by natural sponges, novel multifunctional polymer sponges were developed which were fabricated by ice-templating with multifunctional amine polyethylenimine and diepoxide cross-linker poly(ethylene glycol) diglycidyl ether for highly efficient harvesting of dyes and simultaneous pure water recovery both in mechanic pressing and filtration processes. The as-prepared sponge (SP-1) was further modified by poly(caffeic acid) through a simple dipping-cross-linking process to obtain the hybrid polymer sponge (SP-2), which showed higher compressive strength than SP-1. These sponges possessed a cross-linked three-dimensional macroporous structure with quick water absorbing properties over ten times of their own weight within 20 s directed by capillary. The adsorption behavior of the obtained polymer sponges to 11 hydrophilic dyes was studied in detail by mechanic induced separation. All these polymer sponges exhibited a high selective adsorption to hydrophilic dyes in water. For example, SP-1 has high adsorption capacity over 150 µmol/g to erythrosin B, which is 20 times higher than that of calcein. With the modified poly(caffeic acid) layer, SP-2 exhibited different adsorption properties for methylene blue (180 µmol/g) to SP-1 (∼0 µmol/g), indicating that the tailorable structures of the sponge can regulate their selectivity to guest molecules. Based on the unique recognition to guest molecules, the methodology of dynamic separation of the dye's mixture in water was demonstrated by using these sponges through mechanical pressing or fast filtration, which provides a facile alternative with easy operation for water purification.

Ultralarge Nanosheets Fabricated by the Hierarchical Self-Assembly of Porphyrin-Ended Hyperbranched Poly (ether amine) (TPP-hPEA).

An ultralarge sheet with remarkable lateral dimensions of 10 µm × 10 µm-20 µm × 20 µm is fabricated by the hierarchical self-assembly of porphyrin-ended hyperbranched poly(ether amine) (tetraphenylporphyrin (TPP)-hPEA) in solution. The obtained TPP-hPEA amphiphiles can self-assemble from ultrathin single-layered nanosheets with a thickness of 4 nm to ultralarge multilayered nanosheets with thicknesses from 30 to 70 nm. The lateral dimensions increase from 2 × 2 µm to 5 × 5 µm, and eventually to 10 × 10 µm. In-situ dynamic light scattering and UV-vis spectroscopy studies suggest a hierarchical growth self-assembly mechanism with a self-assembly process that relies on π-π stacking. This 2D self-assembly method provides a significant potential guide for the preparation of ultralarge nanosheets in solution.

Genetic polymorphisms of IL-18 rs1946518 and IL-1ß rs16944 are associated with prognosis and survival of acute myeloid leukemia.

BACKGROUND: Though the pathogenesis of AML is still unknown, accumulating evidence revealed that immune response plays a vital part in it. NLRP3 inflammasome as a component of immune system has been found related to several cancers. The single nucleotide polymorphisms (SNPs) of NLRP3 inflammasome genes may be related to pathogenesis and prognosis of AML. METHODS AND RESULTS: We determined polymorphisms of NLRP3 (rs35829419), CARD8 (rs2043211), IL-1ß (rs16944), IL-18 (rs1946518) and NF-κB -94 ins/del ATTG in de novo AML patients to find out whether they play roles in the susceptibility and severity of AML. In our study, 383 AML cases and 300 randomly selected healthy individuals were examined for the polymorphisms and expression of NLRP3 genes. IL-1ß (rs16944) polymorphism in different risk AML subgroups was found statistically different, with more GA genotype in favorable-risk cytogenetics group. We also demonstrated that the bone marrow blasts of patients carrying IL-18 (rs1946518) GG or GT genotype were higher than patients of TT genotype. IL-18 plasma level of patients with IL-18 (rs1946518) GT or TT genotype was higher than GG genotype. Moreover, the GT genotype of IL-18 (rs1946518) led to statistically poorer AML-specific survival. CONCLUSION: IL-1ß (rs16944) and IL-18 (rs1946518) may be served as potential predictors for AML.

Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems.

Phytosterols are a kind of natural component including sitosterol, campesterol, avenasterol, ergosterol (Er) and others. Their main natural sources are vegetable oils and their processed products, followed by grains, by-products of cereals and nuts, and small amounts of fruits, vegetables and mushrooms. In this study, three new Er monoester derivatives were obtained from the reflux reaction with Er: organic acids (furoic acid, salicylic acid and 2-naphthoic acid), 1-Ethylethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) in dichloromethane. Their chemical structures were defined by IR and NMR. The present study was also undertaken to investigate the antidepressant-like effects of Er and its derivatives in male adult mice models of depression, and their probable involvement of GABAergic and glutamatergic systems by the forced swim test (FST). The results indicated that Er and its derivatives display antidepressant effects. Moreover, one derivative of Er, ergosteryl 2-naphthoate (ErN), exhibited stronger antidepressant activity in vivo compared to Er. Acute administration of ErN (5 mg/kg, i.p.) and a combination of ErN (0.5 mg/kg, i.p.), reboxetine (2.5 mg/kg, i.p.), and tianeptine (15 mg/kg, i.p.) reduced the immobility time in the FST. Pretreatment with bicuculline (a competitive γ-aminobutyric acid (GABA) antagonist, 4 mg/kg, i.p.) and N-methyl-d-aspartic acid (NMDA, an agonist at the glutamate site, 75 mg/kg, i.p.) effectively reversed the antidepressant-like effect of ErN (5 mg/kg, i.p.). However, prazosin (a α1-adrenoceptor antagonist, 1 mg/kg, i.p.) and haloperidol (a non-selective D2 receptor antagonist, 0.2 mg/kg, i.p.) did not eliminate the reduced immobility time. Altogether, these results indicated that ErN produced antidepressant-like activity, which might be mediated by GABAergic and glutamatergic systems.

Molecular epidemiology of hepatitis C infections in Ningxia, China: genotype, phylogeny and mutation analysis.

BACKGROUND: Current prevalence and genotype distribution of hepatitis C virus (HCV) infection remain unknown in Ningxia, northwest China. METHODS: From June to December 2013, 13,022 individuals were screened in Ningxia HIV/AIDS Sentinel Surveillance System, with their demographic features collected and serum samples tested for HCV antibody. Sero-positive drug users were further subjected to sequencing of NS5B and Core regions of HCV. RESULTS: The anti-HCV prevalence was 0.34 % among individuals without history of drug use, while it was 15.80 % among drug users. Of 79 NS5B sequences amplified from drug users, 64 (81.0 %) were male and 51 (64.0 %) were injection drug users (IDUs). Subtype 3a (40.5 %) and 1b (25.3 %) were the most predominant subtypes, followed in frequency by 3b (10.1 %) and 2a (7.6 %). Subtype distribution has no significant difference between injection and non-injection drug users. Based on phylogeographic analysis, HCV strains in Ningxia IDUs were mainly originated from two sites, Yunnan province (in southwest China bordering Myanmar, also known as Burma) and Xinjiang Autonomous Region (in northwest China on the border of Central Asia), which are the two major drug trafficking originates in China. Previously reported drug-resistance mutations were also scanned in this treatment-naïve population. Amino acid substitutions (C316N) associated with direct anti-viral agents (DAA) resistance were identified in the NS5B region in seven samples. CONCLUSION: This study is the first to reveal the existence of multiple genotypes of HCV in Ningxia, an inland province in northwest China, suggesting the rapid spreading of the virus.