Angiostrongylus cantonensis induces energy imbalance and dyskinesia in mice by reducing the expression of melanin-concentrating hormone.

BACKGROUND: Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical. METHODS: We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT-qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice's energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration. RESULTS: Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex. CONCLUSIONS: Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection.

Hematochezia due to rectal invasion by an internal iliac artery aneurysm: A case report.

BACKGROUND: This case report presents the rare occurrence of hematochezia due to an internal iliac artery aneurysm leading to an arterioenteric fistula, expanding the differential diagnosis for gastrointestinal bleeding. It emphasizes the importance of considering vascular origins in cases of atypical hematochezia, particularly in the absence of common gastrointestinal causes, and highlights the role of imaging and multidisciplinary management in diagnosing and treating such unusual presentations. CASE SUMMARY: A 75-year-old man with a history of hypertension presented with 12 d of hematochezia, experiencing bloody stools 7-8 times per day. Initial computed tomography (CT) scans revealed an aneurysmal rupture near the right internal iliac artery with suspected hematoma development. Hemoglobin levels progressively decreased to 7 g/dL. Emergency arterial angiography and iliac artery-covered stent placement were performed, followed by balloon angioplasty. Despite initial stabilization, minor rectal bleeding and abdominal pain persisted, leading to further diagnostic colonoscopy. This identified a neoplasm and potential perforation at the proximal rectum. An exploratory laparotomy confirmed the presence of a hematoma and an aneurysm invading the rectal wall, necessitating partial rectal resection, intestinal anastomosis, and ileostomy. Postoperative recovery was successful, with no further bleeding incidents and normal follow-up CT and colonoscopy results after six months. CONCLUSION: In cases of unusual gastrointestinal bleeding, it is necessary to consider vascular causes for effective diagnosis and intervention.

Unprecedented Spatial Manipulation and Transformation of Dynamic Thermal Radiation Based on Vanadium Dioxide.

Reconfigurable infrared (IR) materials have widespread applications in thermal management and smart IR concealment. Although various reconfigurable IR materials can be customized by positive or negative differential VO2-based resonators, their insightful mechanism remains unknown. Here, we comprehensively investigate the fundamental design rule of reconfigurable thermal radiation between positive and negative differential thermal radiation properties for the first time. Importantly, the skin depth of VO2 film in the metal state is investigated to clarify the transformation from positive to negative differential thermal radiation properties, and the critical thickness is further derived, providing important guidance in designing the reconfigurable thermal radiation regulator. Furthermore, the reconfigurable multistate thermal images had been presented into one plate. The resulting emittance variation (△ε8-14 µm) of the VO2-based resonator can change from 0.61 to -0.53, which consummates the ability for diverse demands such as infrared concealment, thermal illusion, and thermal management. This work constitutes a promising and universal route toward designing whole smart devices and may create new scientific and technological opportunities for platforms that can benefit from reconfigurable electromagnetic manipulation.

Inclusion complex of turmeric essential oil with hydroxypropyl-ß-cyclodextrin: Preparation, characterization and release kinetics.

The application of turmeric essential oil (TEO), a natural effective antibacterial agent, in food preservation is limited due to high volatility and low stability. This study aimed to improve its stability and release behavior by synthesizing TEO/hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex (IC) in a saturated aqueous solution. An orthogonal experimental design was used to determine the optimal process conditions (HP-ß-CD to TEO, g/mL), 16:1; stirring speed, 850 r/min; encapsulation time, 2 h), achieving a comprehensive score value of 85.62% for TEO/HP-ß-CD-IC. Through comprehensive characterization, the results showed that TEO was completely embedded in HP-ß-CD with increased stability. Free TEO exhibited a weight loss of 67.64% between 30 and 300 °C, while TEO/HP-ß-CD-IC had a mass loss of only 9.33%. HP-ß-CD and TEO/HP-ß-CD-IC showed positive ZP values that were 124.76 mV and 132.16 mV, respectively. The release behavior and release kinetics of TEO/HP-ß-CD-ICs were also studied, and the results showed that TEO/HP-ß-CD-IC release rate increased under higher temperature and relative humidity-consistent with Fick's diffusion.

Analysis of the relationship between drug susceptibility of Cryptococcus neoformans isolates and mortality in HIV-negative cryptococcal meningitis.

OBJECTIVES: The relationship between antifungal susceptibility and mortality of cryptococcal meningitis (CM) in HIV-negative patients is poorly understood. METHODS: We conducted a retrospective analysis of 1-year follow-up of 200 HIV-negative CM patients with an initial cerebrospinal fluid (CSF) culture for Cryptococcus neoformans. According to the cut-off values of minimum inhibitory concentration (MIC), two groups of five antifungal agents were classified: amphotericin B (AmB), ≤0.5 µg/mL, >0.5 µg/mL; 5-flucytosine (5-FC), ≤4 µg/mL, >4 µg/mL; fluconazole (FLU), ≤4 µg/mL, >4 µg/mL; itraconazole (ITR), ≤0.125 µg/mL, >0.125 µg/mL; and voriconazole (VOR), <0.25 µg/mL, ≥0.25 µg/mL. Comparisons were performed to analyse clinical features, laboratory, modified Rankin Scale (mRS) scores, and CSF findings under different prognosis outcomes in 1-year. RESULTS: All of Cryptococcus neoformans isolates were sensitive to AmB and VOR, most of them were sensitive to 5-FC and FLU (95.5% and 90.5%, respectively) while only 55.0% of them were susceptible to ITR. Minimum inhibitory concentrations of ITR and VOR were significantly related to baseline mRS scores. All-cause mortality was not significantly related to MICs in Cryptococcus neoformans strains. The combination of actual antifungal agents and two groups of the MICs values for antifungal agents had no significant effects on all-cause mortality. CONCLUSION: Most Cryptococcus neoformans isolates were sensitive to AmB, VOR, 5-FC, and FLU. Because of the small number of deaths, we are not able to comment on whether MIC is associated with mortality of CM in HIV-negative patients.

Momordica anti-HIV protein MAP30 abrogates the Epstein-Barr virus nuclear antigen 1 dependent functions in host cells.

Originally extracted from Momordica charantia seeds, the antiviral and anti-tumor activities of Momordica anti-HIV protein MAP30 have become well known. Although MAP30 has been reported to possess antiviral activity against several human viruses, the current understanding of the MAP30-mediated antiviral response is mainly derived from the previous research work on anti-HIV herbal medicines; the mechanistic insight of its effects on other viruses remains largely unknown. In this study, we showed that both ectopically expressed and purified recombinant MAP30 (rMAP30) impeded Epstein-Barr virus Nuclear Antigen 1 (EBNA1)-mediated transcription from the viral latent replication origin. Mechanistically, in vivo and in vitro studies revealed that MAP30 caused EBNA1 to dissociate from the cognate binding sites, which disrupted downstream EBNA1-dependent viral epigenome accumulation and cell maintenance of Epstein-Barr virus (EBV)-associated neoplastic cells. Finally, mutational analysis indicated that the N-terminal ricin A homologous domain shared by ricin-like proteins was implicated in the anti-EBV response. Our study provides evidence to support that MAP30 has a unique property to combat EBV latent infection, suggesting a potential to develop this herbal protein to be an alternative medicine for EBV associated diseases.

CD45- erythroid progenitor cells promote lymph node metastasis in gastric cancer by inducing a hybrid epithelial/mesenchymal state in lymphatic endothelial cells.

BACKGROUND AND AIMS: Specific mechanisms of lymph node (LN) metastasis in early-stage gastric cancer (GC) have not been elucidated. The role of anemia, a vital clinical feature of GC, in LN metastasis is also unclear. Since the number of erythroid progenitor cells (EPCs) is increased in chronic anemia, we investigated its association with LN metastasis in GC. METHODS: Flow cytometry and immunofluorescence analyses were performed to sort and study EPCs from the circulation and tumors of patients with stage I-III GC. The effect of these EPCs on the activation of T and B cells and on the functions of lymphatic endothelial cells (LECs) was determined, and their ability to promote LN metastasis was evaluated using a footpad-popliteal LN metastasis model based on two human adenocarcinoma GC cell lines in nude mice. The prognostic value of EPCs was also analyzed. RESULTS: The proportion of CD45- EPCs was higher in the mononuclear cells in the circulation, tumors, and LNs of GC patients with LN metastasis (N+) than in those of GC patients without LN metastasis (N0). In N+ patients, CD45- EPCs were more abundant in metastatic LNs than in non-metastatic LNs. Lymphatic vessel endothelial hyaluronan receptor 1 immunoreactivity in tumors revealed that CD45- EPCs were positively associated with nodal stages and lymph vessel density. Furthermore, CD45- EPCs increased LEC proliferation and migration through their S100A8/A9 heterodimer-induced hybrid epithelial/mesenchymal (E/M) state; however, they did not influence the invasion and tubulogenesis of LECs or T and B cell proliferation. CD45- EPCs promoted LN metastasis in vivo; the S100A8/A9 heterodimer mimicked this phenomenon. Finally, CD45- EPCs predicted the overall and disease-free survival of stage I-III GC patients after radical resection. CONCLUSIONS: The CD45- EPCs accumulated in GC tissues and metastatic LNs and promoted LN metastasis via the S100A8/9-induced hybrid E/M state of LECs, which was the specific mechanism of LN metastasis in the early stages of GC.

Erythroid-transdifferentiated myeloid cells promote portal vein tumor thrombus in hepatocellular carcinoma.

Rationale: Hepatocellular carcinoma (HCC) is primarily characterized by a high incidence of vascular invasion. However, the specific mechanism underlying portal vein tumor thrombus (PVTT) in HCC remains unclear. As a consequence of myeloid cell developmental arrest, CD71+ erythroid progenitor cells (EPCs) and myeloid-derived suppressor cells play important roles in HCC; however, their roles in PVTT remain unclear. Methods: The role of CD71+ EPCs in the HCC tumor microenvironment (TME) was evaluated via morphological, RNA-sequencing, enzyme-linked immunosorbent assay, and flow cytometric analyses. Co-culture techniques were employed to assess the CD45+ EPCs and their vascular compromising effect. Additionally, the PVTT-promoting function of CD45+ EPCs was explored in vivo in a murine model. Results: The CD45+EPCs in HCC tissues exhibited increased myeloid cell features, including morphology, surface markers, transforming growth factor (TGF)-ß generation, and gene expression, compared with those in circulation. Hence, a large proportion of CD45+EPCs, particularly those in TMEs, comprise erythroid-transdifferentiated myeloid cells (EDMCs). Additionally, the expression of C-C chemokine receptor type 2 (CCR2) mRNA was upregulated in CD45+EPCs within the TME. Tumor macrophages from HCC tissues induced substantial migration of CD45+EPCs in a dose-dependent manner. Meanwhile, results from immunofluorescence analyses revealed that these two cell types are positively associated in the TME and circulation. That is, EDMCs are chemoattracted by HCC macrophages mainly via CCR2 from CD45+ EPCs in the circulation. Additionally, the expressions of FX, FVII, FGB, C4b, CFB, and CFH were elevated in CD45+EPCs within the TME compared with those in the spleen. The CD45+EPCs from the HCC TME promoted vessel endothelial cell migration and compromised tube formation through TGF-ß and FGB, respectively. Additionally, CD45+EPCs from the TME induced HCC cell migration. HCC macrophage-induced CD45+EPCs to exhibit higher levels of FX, FVII, FGB, and TGF-ß. Meanwhile, upregulation of CCAAT/enhancer binding protein beta expression induced FGB and TGF-ß generation in CD45+EPCs in the TME. WTAP, a major RNA m6A writer, stabilized FX and FVII mRNA and enhanced their nuclear export in CD45+EPCs from the TME. CD45+EPCs from the TME were positively associated with PVTT and poor prognosis. Splenectomy reduced the level of CD45+EPCs in the circulation and TME, as well as the incidence of microvascular invasion. The incidence of microvascular invasion increased following the transfer of HCC tissue CD45+EPCs to splenectomized HCC-bearing mice. Conclusions: The CD45+EPCs enriched in the HCC microenvironment are EDMCs, which are induced by HCC macrophages to migrate from the circulation to the TME. Subsequently, EDMCs promote PVTT by compromising the blood vessel endothelium, aggravating coagulation, and promoting HCC cell migration.

Characterization, stability and antioxidant activity of curcumin nanocomplexes with soy protein isolate and pectin.

Curcumin (Cur) has antioxidant, anti-inflammatory and other biological activities, but its poor stability, low water solubility and other defects limit the application. Herein, Cur was nanocomposited with soy isolate protein (SPI) and pectin (PE) for the first time and its characterization, bioavailability and antioxidant activity were discussed. The optimal encapsulation process of SPI-Cur-PE was as follow: the addition amount of PE was 4 mg, Cur was 0.6 mg and at pH of 7. It was observed by SEM that SPI-Cur-PE were partially aggregated. The average particle size of SPI-Cur-PE was 210.1 nm and the zeta potential was -31.99 mV. Through XRD, FT-IR and DSC analysis, the SPI-Cur-PE was formed through hydrophobic interaction and electrostatic interaction. The SPI-Cur-PE released more slowly in simulated gastrointestinal treatment and displayed higher photostability and thermal stability. SPI-Cur-PE, SPI-Cur and free Cur had scavenging activities for 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals.

LAG3+ erythroid progenitor cells inhibit HBsAg seroclearance during finite pegylated interferon treatment through LAG3 and TGF-ß.

HBsAg seroclearance, the ideal aim of anti-hepatitis B virus (HBV) treatment, cannot be achieved easily. Anemia is another common issue for chronic hepatitis B (CHB) patients, which leads to elevation of erythroid progenitor cells (EPCs) and immune suppression in cancer. This study investigated the role of EPCs in HBsAg seroclearance following pegylated interferon-α (PEG-IFN) treatment. CD45+EPC accumulation in CHB patients and an AAV/HBV mice model was found in the circulation and liver by flow cytometry and immunofluorescence tests. Wright-Giemsa staining showed that these pathological CD45+EPCs presented elevated erythroid cells with relative immature morphologies and atypical cells compared with the control cells. CD45+EPCs were associated with immune tolerance and decreased HBsAg seroclearance during finite PEG-IFN treatment. CD45+EPCs suppressed antigen non-specific T cell activation and HBV-specific CD8+T cells, partially through transforming growth factor ß (TGF-ß). RNA-seq revealed that CD45+EPCs in patients with CHB presented a distinct gene expression profile compared with CD45-EPCs and CD45+EPCs from cord blood. Notably, CD45+EPCs from patients with CHB expressed high level of Lymphocyte-activation gene 3 (LAG3), an immune checkpoint molecule, and were then defined as LAG3+EPCs. LAG3+EPCs diminished the function of antigen presenting cells through LAG3, which was another mechanism by which LAG3+EPCs' suppressed HBV-specific CD8+T cells. Anti-LAG3 and anti-TGF-ß combination treatment decreased serum HBeAg, HBV DNA levels and HBsAg level, as well as HBsAg-expression in hepatocytes during PEG-IFN treatment in the AAV/HBV mice model. Conclusions: LAG3+EPCs inhibited the efficacy of PEG-IFN treatment on HBsAg seroclearance induced by LAG3 and TGF-ß. Anti-LAG3, anti-TGF-ß and PEG-IFN combination treatment might facilitate HBV clearance.

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study

Introduction: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. Methods: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. Results: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. Conclusion: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Rheumatic valvular heart disease treated with traditional Chinese medicine: A case report.

BACKGROUND: Rheumatic heart disease (RHD) is an autoimmune disease that leads to irreversible valve damage and heart failure. Surgery is an effective treatment; however, it is invasive and carries risks, restricting its broad application. Therefore, it is essential to find alternative nonsurgical treatments for RHD. CASE SUMMARY: A 57-year-old woman was assessed with cardiac color Doppler ultrasound, left heart function tests, and tissue Doppler imaging evaluation at Zhongshan Hospital of Fudan University. The results showed mild mitral valve stenosis with mild to moderate mitral and aortic regurgitation, confirming a diagnosis of rheumatic valve disease. After her symptoms became severe, with frequent ventricular tachycardia and supraventricular tachycardia > 200 beats per minute, her physicians recommended surgery. During a 10-day preoperative waiting period, the patient asked to be treated with traditional Chinese medicine. After 1 week of this treatment, her symptoms improved significantly, including resolution of the ventricular tachycardia, and the surgery was postponed pending further follow-up. At 3 -month follow-up, color Doppler ultrasound showed mild mitral valve stenosis with mild mitral and aortic regurgitation. Therefore, it was determined that no surgical treatment was required. CONCLUSION: Traditional Chinese medicine treatment effectively relieves symptoms of RHD, particularly mitral valve stenosis and mitral and aortic regurgitation.

PARP in colorectal cancer: Molecular mechanisms, immunity, clinical trials, and drug combinations.

The changes in cell homeostasis in the tumor microenvironment may affect the development of colorectal cancer (CRC). Genomic instability is an important factor. Persistent genomic instability leads to epigenetic changes, and mutations are a major factor in the progression of CRC. Based on these mechanisms, it is reasonable to link poly (ADP-ribose) polymerase (PARP) with the treatment of CRC. PARP is mainly involved in DNA repair, which has an essential role in the DNA damage response and prevention of DNA damage, and maintains oxidation and superoxide redox homeostasis in the intracellular environment of the tumor. This article reviews the latest research progress on PARP and PARP inhibitors (PARPi) in CRC. It mainly includes molecular mechanisms, immunity, clinical trials, and combination strategies of CRC. The research of PARPi in CRC has broad prospects, and the combinations with other drugs are the main research direction in the future.

TYRO protein tyrosine kinase-binding protein predicts favorable overall survival in osteosarcoma and correlates with antitumor immunity.

To explore the prognostic significance and underlying mechanism of TYRO protein tyrosine kinase-binding protein (TYROBP) in osteosarcoma. Firstly, the expression of TYROBP was analyzed using the t test. The Kaplan-Meier plotter analysis and a receiver operating characteristic curve were performed to evaluate the influence of TYROBP on overall survival (OS). Further, Cox regression analysis was conducted to predict the independent prognostic factors for OS of osteosarcoma patients, and a nomogram was constructed. Then, the relationship between TYROBP and clinicopathological characteristics was determined using statistical methods. Enrichment analyses were conducted to evaluate the biological functions of TYROBP. Finally, the ESTIMATE algorithm was used to assess the association of TYROBP with immune cell infiltration. TYROBP was significantly increased in osteosarcoma (all P < .001). However, the high expression of TYROBP was related to better OS in osteosarcoma patients. Cox regression analysis showed that TYROBP was an independent prognostic factor for predicting OS (P = .005), especially in patients of the male sex, age <18 years, metastasis, and tumor site leg/foot (all P < .05). Besides, TYROBP mRNA expression was significantly associated with the tumor site (P < .01) but had no remarkable relationship with age, gender, and metastasis status (all P > .05). Functional annotation and gene set enrichment analysis (GSEA) revealed that TYROBP was mainly involved in immune-related pathways. Importantly, TYROBP positively correlated with immune scores (P < .001, R = .87). TYROBP served as an independent prognostic biomarker for OS in osteosarcoma. High TYROBP expression might prolong the survival of osteosarcoma patients mainly through promoting antitumor immunity.

Analysis of the association of HLA subtypes with cryptococcal meningitis in HIV-negative immunocompetent patients.

Objective: We aimed to study the possible relationship between cryptococcal meningitis (CM) and HLA genotypes in HIV-negative immunocompetent patients. Methods: HLA loci of 53 HIV-negative immunocompetent Han Chinese CM patients were compared with those in 481 healthy individuals. Results: We found a significant association between DQB1*05:02 and CM patients compared with controls. There were no significant differences in the frequencies of HLA alleles between CM with and without postinfectious inflammatory response syndrome and controls. Correlation analysis showed DQB1*05:02 was correlated with susceptibility to CM. CM patients carrying the DQB1*05:02 allele had more severe focal neurological deficit, higher initial modified Rankin Scale and British Medical Research Council staging scores. Conclusion: This study provides the first evidence for the interaction between specific HLA class II alleles and HIV-negative immunocompetent CM patients.

Cryptococcus neoformans is a pathogen that mainly causes infections in patients with a weakened immune system. The most common manifestation of C. neoformans infection is cryptococcal meningitis (CM), inflammation of the membranes that surround the brain and spinal cord. CM is a leading fungal cause of human disease and death worldwide. It mainly occurs in patients who are HIV positive, but is also an important cause of disease in individuals with immune systems that are working normally. However, little is known about the cause and development of the disease in HIV-negative individuals who have normally functioning immune systems. Human proteins called HLA molecules are associated with various infectious diseases, so we wondered whether HLA subtypes are associated with CM. Our study found that an HLA subtype called HLA-DQB1*05:02 was involved in C. neoformans infections that lead to CM. Patients with HLA-DQB1*05:02 had a significantly worse level of disability and problems with nerve, spinal cord or brain function. This study will be useful for exploring the influence of different forms of the HLA molecule on susceptibility to CM in HIV-negative individuals with a normally functioning immune system.

Evaluation of Adenosine A2A receptor gene polymorphisms as risk factors of methamphetamine use disorder susceptibility and predictors of craving degree.

The adenosine A2A receptor (ADORA2A) is highly expressed in the central nervous system and plays vital roles in drug addiction. In this study, we aimed to explore the susceptibility of ADORA2A to methamphetamine use disorder (MUD) and the craving degree based on a two-stage association analysis. A total of 3,542 (1,216 patients with MUD and 2,326 controls) and 1,740 participants (580 patients with MUD and 1,160 controls) were recruited in discovery and replication stage, respectively. Significant SNPs identified in the discovery stage were genotyped in the replication samples. Serum levels of ADORA2A were measured using enzyme-linked immunosorbent assay kits. The genetic association signal of each SNP was examined using Plink. A linear model was fitted to investigate the relationship between craving scores and genotypes of significant SNPs. SNP rs5751876 was significantly associated with MUD in the discovery samples and this association signal was then further replicated in the replication samples. Significant associations were also identified between serum levels of ADORA2A and the genotypes of rs5751876 (P = 0.0002). The craving scores in patients with MUD were strongly correlated with rs5751876 genotypes. Our results suggest that polymorphisms of the ADORA2A gene could affect the susceptibility to MUD and its craving degree.

Immunological Predictors of Post Infectious Inflammatory Response Syndrome in HIV-Negative Immunocompetent Cryptococcal Meningitis.

Objective: This research aims to study the correlation between serum immune factors and post-infectious inflammatory response syndrome (PIIRS) in immunocompetent cryptococcal meningitis (CM), and explore whether serum immune factors could be used to predict the development of PIIRS. Methods: A cohort of 30 patients with PIIRS and 87 patients without PIIRS was selected from 347 CM patients. We analyzed the general clinical information and immunological indexes (cytokines, complement, immunoglobulin, inflammation, related cytological and biochemical indexes). Spearman correlation analysis and principal component analysis were used to explore the effects of the variables on PIIRS. Additionally, the variables were identified by a random forest-based classifier for predicting the development of PIIRS. The clinical value of predictors was verified by survival analysis. Results: Compared with patients without PIIRS, patients with PIIRS had lower baseline serum interleukin-6 (IL-6, P = 0.006), immunoglobulin M (IgM, P = 0.004), and a higher baseline neutrophil ratio (P <0.001). The baseline neutrophil ratio (r = 0.359, P = 0.001), IgM (r = -0.272, P = 0.025), and IL-6 (r = -0.259, P = 0.027) were significantly correlated with PIIRS. Combining principal component analysis and random forest results, neutrophil ratio, neutrophil count, IgM, IL-6, and D-dimer were useful predictors. The accuracy of random forest prediction was 75.00%, AUC, and sensitivity were 0.76 and 70%, respectively. Further survival analysis of the time from treatment to PIIRS revealed that the development of PIIRS was associated with IgM (more than 98 days of treatment) and neutrophil ratio/count. Conclusion: Baseline neutrophils ratio, neutrophil count, IgM, IL-6, and D-dimer may be clinically useful predictors of PIIRS in HIV-negative immunocompetent CM patients.

Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis.

Angiostrongylus cantonensis (AC) is well-documented that parasitizes the host brain and causes eosinophilic meningitis. The migration route of AC in permissive hosts is well demonstrated, while in nonpermissive hosts, it remains to be fully defined. In the present study, we exploited live imaging technology, morphological and pathological configuration analysis, and molecular biological technologies to explore the migration route of AC and the accompanying tissue damage in nonpermissive and permissive hosts. Our data indicated that, in nonpermissive host mouse, AC larvae migrated from intestinal wall to liver at 2 hours post-infection (hpi), from liver to lung at 4 hpi and then from lung to brain at 8 hpi. AC larval migration caused fatal lung injury (pneumonia) during acute and early infection phases, along with significant activation of Stat3/IL-6 signaling. In addition, AC induce sustained interstitial pneumonia in mouse and rat and pulmonary fibrosis only in rat during late infection phase. Moreover, during the early and late infection phases, Th2 cytokine expression and Stat3 and IL-6 signaling were persistently enhanced and myeloid macrophage cells were notably enriched in host lung, and administration of Stat3 and IL-6 inhibitors (C188-9 and LMT-28) attenuated AC infection-induced acute pneumonia in mice. Overall, we are the first to provide direct and systemic laboratory evidence of AC migration route in a nonpermissive host and report that infection with a high dose of AC larvae could result in acute and fatal pneumonia through Stat3/IL-6 signaling in mice. These findings may present a feasible to rational strategy to minimize the pathogenesis induced by AC.

Effect of applying persulfate on the accumulation of arsenic in rice plants grown in arsenic-contaminated paddy soil.

Arsenic is known to be a notorious human carcinogen and rice consumption is becoming the primary human exposure route for As, especially in many Asian countries. As one of redox-sensitive elements in soil, sulfur plays an indisputable role in controlling As behaviors. However, information on the effects of persulfe (PS) on the toxicity and accumulation of As in rice plant under flooded conditions is limited. Therefore, a pot experiment was conducted to investigate the effects of PS amendment on the growth and accumulation of As species in rice plants grown in As-contaminated paddy soil. Results revealed that PS application increased the As, Fe, and Mn in porewater at the early stage, and then declined. Application of PS increased the biomass of stem and root, while inhibited the formation of iron plaque on the root surface. The As translocation from root to rice above tissues and accumulation of As species in brown rice were declined by amendment with PS. The inorganic arsenic (iAs) and DMA were the two main species in brown rice, and decreased by 13~26% and 40~60% respectively upon PS application. The results suggested that amendment with PS might be feasible for reducing the accumulation of As in rice grains grown in As-contaminated paddy soil. However, further detailed studies on the potential soil biogeochemical and physiological mechanisms are recommended.

Successful apatinib treatment for advanced clear cell renal carcinoma as a first-line palliative treatment: A case report.

BACKGROUND: Apatinib is an orally bioavailable small-molecule receptor tyrosine kinase inhibitor. In December 2014, the China Food and Drug Administration made it the first anti-angiogenic therapy to be approved for treating metastatic gastric cancer. It was specifically designated as a third-line or later treatment for metastatic gastric cancer. CASE SUMMARY: Here, we present a case of advanced renal cell carcinoma (RCC) with multiple metastases (Stage IV) in a 48-year-old male with an extremely poor general status (Karnofsky 30%). He was initially given pazopanib as a targeted therapeutic. However, he experienced severe adverse reactions within two weeks, including grade IV oral mucositis. We, thus, tried switching his targeted treatment to an apatinib dose of 250 mg once daily since April 2018. The patient demonstrated striking benefits from this switch to the apatinib palliative treatment. Nearly one month later, his pain and other associated symptoms were alleviated. The patient was able to move freely and had an excellent general status (Karnofsky 90%). His progress has been followed up with regularly, allowing for a documented progression-free survival interval of approximately 32 mo. CONCLUSION: This case suggests that, like other multi-target drugs, apatinib may be a useful first-line therapeutic drug for advanced RCC. It may be a particularly helpful curative option when patients are found to be intolerant of other targeted drugs.