bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the frequency and phenotypic profile of Mycobacterium tuberculosis-specific CD4 T cells between the site of disease and blood in pericardial tuberculosis
Authors: Du Bruyn Elsa , Ruzive Sheena , Howlett Patrick , Cerrone Maddalena. , Jacobs Ashley J. , Arlehamn Cecilia S. Lindestam , Sette Alessandro , Sher Alan , Mayer-Barber Katrin D. , Barber Daniel L. , Mayosi Bongani , Ntsekhe Mpiko , Wilkinson Robert J. , Riou Catherine
Published: November 2022

Studies of the immune response at the site of disease in extra-pulmonary tuberculosis (EPTB) disease are scarce. In this study, we compared the cellular profile of Mycobacterium tuberculosis (Mtb)-specific T cells in pericardial fluid and peripheral blood in patients with pericardial TB (PCTB). Whole blood and pericardial fluid (PCF) samples were collected at the time of diagnostic sampling, with repeat blood sampling after completion of anti-tubercular treatment (ATT) in 16 PCTB patients, most of them being HIV-1 infected (n=14). These samples were stimulated ex vivo and the phenotypic and functional cellular profile of PCF and blood was assessed by flow cytometry. We found that lymphocytes were the predominant cell type in PCF in PCTB, with a preferential influx of CD4 T cells. The frequencies of TNF-α producing Mtb-specific granulocytes and Mtb-specific CD4 T cells were significantly higher in PCF compared to blood. Mtb-specific CD4 T cells in PCF exhibited a distinct phenotype compared to those in blood, with greater GrB expression and lower CD27 and KLRG1 expression. We observed no difference in the production IFNγ, TNF or IL-2 by Mtb-specific CD4 T cells between the two compartments, but MIP-1β production was lower in the PCF T cells. Bacterial loads were not associated with alterations in the phenotype or function of Mtb-specific CD4 T cells. Upon ATT completion, HLA-DR, Ki-67 and GrB expression was significantly decreased, and relative IL-2 production was increased in peripheral Mtb-specific CD4 T cells. Overall, using an ex vivo assay to compare the immune response towards Mtb in PCF and in blood, we identified significant difference in the phenotypic profile of Mtb-specific CD4 T response between these two compartments. Moreover, we show that the activation profile of peripheral Mtb-specific CD4 T cells could be used to monitor treatment response in PCTB.
Spatiotemporal characteristics of P-selectin-induced β2 integrin activation of human neutrophils under flow
Authors: Sun Xiaoxi , Huang Bing , Pan Yuping , Fang Jinhua , Wang Hefeng , Ji Yanru , Ling Yingchen , Guo Pei , Lin Jiangguo , Li Quhuan , Fang Ying , Wu Jianhua
Published: November 2022

Activation of integrins is crucial for recruitment of flowing leukocytes to inflammatory or injured vascular sites, but their spatiotemporal characteristics are incompletely understood. We discovered that β2-integrin activation over the entire surface of neutrophils on immobilized P-selectin occurred via mitogen-activated protein kinase (MAPK) or non-MAPK signaling with a minute-level timescale in a force-dependent manner. In flow, MAPK signaling required intracellular Ca2+ release to activate integrin within 2 min. Integrin activation via non-MAPK signaling occurred first locally in the vicinity of ligated P-selectin glycoprotein ligand-1 (PSGL-1) within sub-seconds, and then over the entire cell surface within 1 min in an extracellular Ca2+ influx-dependent manner. The transition from a local (but rapid) to global (but slow) activation mode was triggered by ligating the freshly activated integrin. Lipid rafts, moesin, actin, and talin were involved in non-MAPK signaling. Fluid loads had a slight effect on local integrin activation with a second-level timescale, but served as enhancers of global integrin activation.
Inhibition of the CD47-SIRPα axis for cancer therapy: A systematic review and meta-analysis of emerging clinical data
Authors: Son Ji , Hsieh Rodney Cheng-En , Lin Heather Y. , Krause Kate J. , Yuan Ying , Biter Amadeo B. , Welsh James , Curran Michael A. , Hong David S.
Published: November 2022

CD47-SIRPα interaction acts as a “don’t eat me” signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). Of these, 6.4% experienced complete response, 10.4% partial response, and 26.1% stable disease for a 16.7% objective response rate (ORR), 42.8% disease control rate, and 4.8-month median duration of response. ORR was significantly higher for hematologic cancers (25.3%) than solid cancers (9.1%, p=0.042). Comparing by mechanism, seven CD47 monoclonal antibodies (mAbs) and six selective SIRPα blockers were given alone or combined with checkpoint inhibitors, targeted therapy, and/or chemotherapy. In solid cancers, selective SIRPα blockade showed a higher ORR (16.2%) than anti-CD47 mAbs (2.8%, p=0.079), which was significant for combination therapies (ORR 28.3% vs 3.0%, respectively, p=0.010). Responses were seen in head and neck, colorectal, endometrial, ovarian, hepatocellular, non-small cell lung, and HER2+gastroesophageal cancers. Dose-limiting toxicity (DLT) was seen in 3.3% of patients (5.4% anti-CD47 mAbs, 1.4% selective SIRPα blockers; p=0.01). The frequency of treatment-related adverse events (TRAEs) ≥grade 3 was 18.0%, similar between the two groups (p=0.082), and mostly laboratory abnormalities. For anti-CD47 mAbs, the most common toxicities included grade 1-2 fatigue (27.2%), headache (21.0%), and anemia (20.5%). For selective SIRPα blockers, these included grade 1-2 infusion reaction (23.1%) and fatigue (15.8%). Anti-CD47 mAbs were significantly more likely than selective SIRPα blockers to cause grade 1-2 fever, chills, nausea/vomiting, headache, and anemia. In conclusion, combination therapies using selective SIRPα blockade had higher response rates in solid tumors than anti-CD47 mAb combinations. Hematologic changes were the main TRAEs, and selective SIRPα blockers seemed to have a better grade 1-2 toxicity profile. Treatment was well-tolerated with minimal DLTs.
Impact of selenium on the intestinal microbiome-eCBome axis in the context of diet-related metabolic health in mice
Authors: Guevara Agudelo Fredy Alexander , Leblanc Nadine , Bourdeau-Julien Isabelle , St-Arnaud Gabrielle , Lacroix Sébastien , Martin Cyril , Flamand Nicolas , Veilleux Alain , Di Marzo Vincenzo , Raymond Frédéric
Published: November 2022

Dietary micronutrients act at the intestinal level, thereby influencing microbial communities, the host endocannabinoidome, and immune and anti-oxidative response. Selenium (Se) is a trace element with several health benefits. Indeed, Se plays an important role in the regulation of enzymes with antioxidative and anti-inflammatory activity as well as indicators of the level of oxidative stress, which, together with chronic low-grade inflammation, is associated to obesity. To understand how Se variations affect diet-related metabolic health, we fed female and male mice for 28 days with Se-depleted or Se-enriched diets combined with low- and high-fat/sucrose diets. We quantified the plasma and intestinal endocannabinoidome, profiled the gut microbiota, and measured intestinal gene expression related to the immune and the antioxidant responses in the intestinal microenvironment. Overall, we show that intestinal segment-specific microbiota alterations occur following high-fat or low-fat diets enriched or depleted in Se, concomitantly with modifications of circulating endocannabinoidome mediators and changes in cytokine and antioxidant enzyme expression. Specifically, Se enrichment was associated with increased circulating plasma levels of 2-docosahexaenoyl-glycerol (2-DHG), a mediator with putative beneficial actions on metabolism and inflammation. Others eCBome mediators also responded to the diets. Concomitantly, changes in gut microbiota were observed in Se-enriched diets following a high-fat diet, including an increase in the relative abundance of Peptostreptococcaceae and Lactobacillaceae. With respect to the intestinal immune response and anti-oxidative gene expression, we observed a decrease in the expression of proinflammatory genes Il1β and Tnfα in high-fat Se-enriched diets in caecum, while in ileum an increase in the expression levels of the antioxidant gene Gpx4 was observed following Se depletion. The sex of the animal influenced the response to the diet of both the gut microbiota and endocannabinoid mediators. These results identify Se as a regulator of the gut microbiome and endocannabinoidome in conjunction with high-fat diet, and might be relevant to the development of new nutritional strategies to improve metabolic health and chronic low-grade inflammation associated to metabolic disorders.
Indoleamine 2,3-dioxygenase 1 signaling orchestrates immune tolerance in Echinococcus multilocularis-infected mice
Authors: Meng Ru , Fu Yong , Zhang Yaogang , Mou Yalin , Liu Gongguan , Fan Haining
Published: November 2022

The cestode Echinococcus multilocularis larva infection causes lethal zoonotic alveolar echinococcosis (AE), a disease posing a great threat to the public health worldwide. This persistent hepatic tumor-like disease in AE patients has been largely attributed to aberrant T cell responses, of which Th1 responses are impeded, whilst Th2 and regulatory T cell responses are elevated, creating an immune tolerogenic microenvironment in the liver. However, the immune tolerance mechanisms are not fully understood. Dendritic cells (DCs) are key cellular components in facilitating immune tolerance in chronic diseases, including AE. Here, we demonstrate that indoleamine 2,3-dioxygenase 1-deficient (IDO1-/-) mice display less severe AE as compared to wild-type (WT) mice during the infection. Mechanistically, IDO1 prevents optimal T cells responses by programming DCs into a tolerogenic state. Specifically, IDO1 prevents the maturation and migration potential of DCs, as shown by the significantly enhanced expression of the antigen-presenting molecule (MHC II), costimulatory molecules (CD80 and CD86), and chemokine receptors (CXCR4 and CCR7) in infected IDO1-/- mice as compared to infected wild-type mice. More importantly, the tolerogenic phenotype of DCs is partly reverted in IDO1-/- mice, as indicated by enhanced activation, proliferation, and differentiation of both CD4+ and CD8+ - T cells upon infection with Echinococcus multilocularis, in comparison with WT mice. Interestingly, in absence of IDO1, CD4+ T cells are prone to differentiate to effector memory cells (CD44+CD62L-); in contrast, CD8+ T cells are highly biased to the central memory phenotype (CD44+CD62L+). Overall, these data are the first to demonstrate the essential role of IDO1 signaling in inducing immunosuppression in mice infected with Echinococcus multilocularis.
Exploring the molecular mechanism of hepatitis virus inducing hepatocellular carcinoma by microarray data and immune infiltrates analysis
Authors: Zhang Yong-Zheng , Zeb Amir , Cheng Lu-Feng
Published: November 2022

The number of new cases of hepatocellular carcinoma (HCC) worldwide reached 910,000, ranking the sixth, 80% HCC is associated with viruses, so exploring the molecular mechanism of viral carcinogenicity is imperative. The study showed that both HBV and HCV associated HCC and non-viral HCC have the same molecular phenotype (low gene expression and inhibition of immune pathways), but in the tumor immune micro-environment, there is excessive M2-type macrophage polarization in virus-associated hepatocellular carcinoma. To address this phenomenon, the data sets were analyzed and identified five hub genes (POLR2A, POLR2B, RPL5, RPS6, RPL23A) involved in viral gene expression and associated with PI3K-Akt-mTOR pathway activation by six algorithms. In addition, numerous studies have reported that M2-type macrophages participate in the hepatic fibro-pathological process of the development of HCC and are regulated by the PI3K-Akt-mTOR pathway. On this basis, the study showed that hepatitis virus causes abnormal expression of hub genes, leading to the activation of the pathway, which in turn promote the differentiation of M2-type macrophages and eventually promote the formation of liver fibrosis, leading to the occurrence of HCC. In addition, these hub genes are regulated by transcription factors and m6A enzyme, and have good prognosis and diagnostic value. With regard to drug reuse, the results suggest that patients with virus-related HCC for whom Cytidine triphosphate disodium salt and Guanosine-5’-Triphosphate are used as supplementary therapy, and may have a better prognosis. In conclusion, the study has identified novel molecules that are carcinogenic to hepatitis viruses and are expected to serve as molecular markers and targets for diagnosis and treatment.
Type I interferon receptor (IFNAR2) deficiency reveals Zika virus cytopathicity in human macrophages and microglia
Authors: Hanrath Aidan T. , Hatton Catherine F. , Gothe Florian , Browne Cathy , Vowles Jane , Leary Peter , Cockell Simon J. , Cowley Sally A. , James William S. , Hambleton Sophie , Duncan Christopher J. A.
Published: November 2022

Macrophages are key target cells of Zika virus (ZIKV) infection, implicated as a viral reservoir seeding sanctuary sites such as the central nervous system and testes. This rests on the apparent ability of macrophages to sustain ZIKV replication without experiencing cytopathic effects. ZIKV infection of macrophages triggers an innate immune response involving type I interferons (IFN-I), key antiviral cytokines that play a complex role in ZIKV pathogenesis in animal models. To investigate the functional role of the IFN-I response we generated human induced pluripotent stem cell (iPSC)-derived macrophages from a patient with complete deficiency of IFNAR2, the high affinity IFN-I receptor subunit. Accompanying the profound defect of IFN-I signalling in IFNAR2 deficient iPS-macrophages we observed significantly enhanced ZIKV replication and cell death, revealing the inherent cytopathicity of ZIKV towards macrophages. These observations were recapitulated by genetic and pharmacological ablation of IFN-I signalling in control iPS-macrophages and extended to a model of iPS-microglia. Thus, the capacity of macrophages to support noncytolytic ZIKV replication depends on an equilibrium set by IFN-I, suggesting that innate antiviral responses might counterintuitively promote ZIKV persistence via the maintenance of tissue viral reservoirs relevant to pathogenesis.
Single-dose of a replication-competent adenovirus-vectored vaccine provides sterilizing protection against Rift Valley fever virus challenge
Authors: Bian Ting , Wang Busen , Fu Guangcheng , Hao Meng , Chen Yi , Fang Ting , Liu Shuling , Yu Changming , Li Jianmin , Chen Wei
Published: November 2022

Rift Valley fever virus (RVFV) is one of the most important virulent pathogens causing severe disease in animals and humans. However, there is currently no approved vaccine to prevent RVFV infection in humans. The use of human adenovirus serotype 4 (Ad4) as a vector for an RVFV vaccine has not been reported. Here, we report the generation of a replication-competent recombinant Ad4 vector expressing codon-optimized forms of the RVFV glycoproteins Gn and Gc (named Ad4-GnGc). Intramuscular immunization with Ad4-GnGc elicited robust neutralizing antibodies against RVFV and cellular immune responses in mice. A single low-dose vaccination with Ad4-GnGc completely protected interferon-α/β receptor-deficient A129 mice from lethal RVFV infection. More importantly, Ad4-GnGc efficacy was not affected by pre-existing immunity to adenovirus serotype 5, which currently exists widely in populations. These results suggest that Ad4-GnGc is a promising vaccine candidate against RVFV.
Association of the retinal vasculature, intrathecal immunity, and disability in multiple sclerosis
Authors: Noll Christina , Hiltensperger Michael , Aly Lilian , Wicklein Rebecca , Afzali Ali Maisam , Mardin Christian , Gasperi Christiane , Berthele Achim , Hemmer Bernhard , Korn Thomas , Knier Benjamin
Published: November 2022

Background

Optical coherence tomography angiography (OCT-A) is a novel technique allowing non-invasive assessment of the retinal vasculature. During relapsing remitting multiple sclerosis (RRMS), retinal vessel loss occurs in eyes suffering from acute optic neuritis and recent data suggest that retinal vessel loss might also be evident in non-affected eyes. We investigated whether alterations of the retinal vasculature are linked to the intrathecal immunity and whether they allow prognostication of the future disease course.

Material and methods

This study includes two different patient cohorts recruited at a tertiary German academic multiple sclerosis center between 2018 and 2020 and a cohort of 40 healthy controls. A total of 90 patients with RRMS undergoing lumbar puncture and OCT-A analysis were enrolled into a cross-sectional cohort study to search for associations between the retinal vasculature and the intrathecal immune compartment. We recruited another 86 RRMS patients into a prospective observational cohort study who underwent clinical examination, OCT-A and cerebral magnetic resonance imaging at baseline and during annual follow-up visits to clarify whether alterations of the retinal vessels are linked to RRMS disease activity. Eyes with a history of optic neuritis were excluded from the analysis.

Results

Rarefication of the superficial vascular complex occured during RRMS and was linked to higher frequencies of activated B cells and higher levels of the pro-inflammatory cytokines interferon-γ, tumor necrosis factor α and interleukin-17 in the cerebrospinal fluid. During a median follow-up of 23 (interquartile range 14 - 25) months, vessel loss within the superficial (hazard ratio [HR] 1.6 for a 1%-point decrease in vessel density, p=0.01) and deep vascular complex (HR 1.6 for a 1%-point decrease, p=0.05) was associated with future disability worsening.

Discussion

Optic neuritis independent rarefication of the retinal vasculature might be linked to neuroinflammatory processes during RRMS and might predict a worse disease course. Thus, OCT-A might be a novel biomarker to monitor disease activity and predict future disability.
Mulberry leaf extract improves non-specific immunity and antioxidant capacity of largemouth bass (Micropterus salmoides) fed a high-starch diet
Authors: Tingsen Jing , Hui Luo , Junwa Huang , Zhe Li , Yu Li , Honghao Jin , Xinxi Zou , Zhenlin Ke , Wenbo Sun , Mengdan Hou , Huijun Yang , Hua Ye
Published: November 2022

A 70-day experiment was conducted to investigate the effects of mulberry leaf extract (MLE) on growth, proximate compositions, antioxidant and plasma biochemical parameters, and indices of non-specific immunity of largemouth bass (Micropterus salmoides) fed a high-starch diet. Two hundred eighty largemouth bass (initial body weight, 68.00 ± 0.19 g) were randomly fed seven diets: basal-starch diet (BSD; 8.88% starch), high-starch diet (HSD; 11.42% starch), and HSD diets supplemented with 0.05%, 0.10%, 0.20%, 0.50%, and 1.00% MLE (MLE1, MLE2, MLE3, MLE4, and MLE5, respectively). The results indicated that HSD and MLE did not significantly affect the growth performance of largemouth bass during the experimental period compared with that of the BSD, but the supplementation with more than 0.20% (MLE3, MLE4, and MLE5) MLE significantly decreased the hepatosomatic index (HSI) values, and 1.00% (MLE5) MLE significantly decreased the viscerosomatic index (VSI) values. The whole-body moisture of fish fed an HSD decreased significantly, while the whole-body lipid content increased significantly in the HSD group compared with the BSD group. Compared with HSD, MLE supplementation significantly decreased the moisture and lipid contents in the whole body. Supplementation with more than 0.20% MLE (MLE3, MLE4, and MLE5) significantly decreased the moisture content in the muscle. Supplementation with 1.00% MLE significantly decreased the content of hepatic and muscle glycogen. The malondialdehyde (MDA) content of the HSD group was significantly increased compared to that of the BSD group, whereas more than 0.10% (MLE2, MLE3, MLE4, and MLE5) MLE significantly decreased the MDA content. Additionally, the total antioxidant capacity (T-AOC), catalase (CAT), and glutathione peroxidase (GSH-Px) activities of MLE5 were significantly higher than those of the HSD group. The complement-3 (C3) content and globulin (GLB) in the plasma of the HSD group were significantly lower than those of the BSD group. Plasma C3 levels in the MLE3, MLE4, and MLE5 groups were significantly higher than those in the HSD group. In addition, glucose (GLU) levels in the MLE3, MLE4, and MLE5 groups were significantly lower than those in the HSD group. Supplementation with 0.50% (MLE4) MLE significantly increased the lysozyme (LYZ) content and decreased the activities of alanine transaminase (ALT) and aspartate transaminase (AST). Supplementation with 1.00% MLE significantly increased complement-4 (C4) and GLB contents and alkaline phosphatase (ALP) activity. Overall, these findings suggest that MLE could improve antioxidant capacity, immune function, and glycolipid metabolism, thereby alleviating the negative effects of a high-starch diet in M. salmoides.
Single underwater image enhancement based on differential attenuation compensation
Authors: Lai Yunting , Zhou Zhuang , Su Binghua , Xuanyuan Zhe , Tang Jialin , Yan Jinghui , Liang Wanxin , Chen Jiongjiang
Published: November 2022

High quality underwater images and videos are important for exploitation tasks in the underwater environment, but the complexity of the underwater imaging environment makes the quality of the acquired underwater images generally low. To correct the chromatic aberration and enhance the sharpness of underwater images in order to improve the quality of underwater images, we based on the differential compensation proposed a Differential Attenuation Compensation (DAC) method. The underwater image is contrast stretched to improve the contrast of the image, as well as the underwater image is denoised, for the red channel with serious loss of detail information we choose the blue and green channels with more detail information to compensate for this, and finally the image is restored through the grayscale world to obtain more realistic colors. Our method is qualitatively and quantitatively compared with multiple state-of-the-art methods in the public underwater image dataset, underwater image enhancement benchmark (UIEB) and enhancing underwater visual perception (EUVP), demonstrating that the underwater images processed by our method better resolve the problems of chromatic aberration and blur, with more realistic color, detail and better underwater image quality evaluation indicators
Microplastics in gastric samples from common bottlenose dolphins (Tursiops truncatus) residing in Sarasota Bay FL (USA)
Authors: Hart Leslie B. , Dziobak Miranda , Wells Randall S. , Ertel Bonnie , Weinstein John
Published: November 2022

The oceans contain trillions of plastic particles, mostly microplastics (i.e., particles < 5 mm diameter; 92.4% of plastic particles), which have been detected in organisms at all levels of the marine food web. The ubiquity of marine plastic debris has created a monumental environmental pollution problem with extensive public health consequences, as more than 40% of the world’s population lives near the coast and shares coastal resources. For decades, common bottlenose dolphins (Tursiops truncatus) have been used as sentinels of marine pollution risks for coastal communities that rely on seafood. Recently, prevalent phthalate exposure was documented in bottlenose dolphins residing in Sarasota Bay, FL, at concentrations exceeding those of human reference populations. While the source of their exposure is uncertain, the types of compounds detected suggest a plastic origin. The objective of this study was to screen for plastic ingestion among free-ranging dolphins in Sarasota Bay using gastric samples collected during catch-and-release health assessments. Gastric samples were collected from seven live bottlenose dolphins in 2019, and suspected microplastic particles were detected in all samples. The number of particles per sample ranged from <10 to >100, and the most common types were transparent films and white foams. Similar to other marine mammal studies, fibers were also present. Given that dolphins are likely exposed to microplastics via contaminated prey, findings from this and additional studies will help to evaluate the potential of contaminated seafood as an additional source of microplastic exposure for humans, as well as help to inform intervention and risk communication needs regarding seafood safety.
A determination method for the shear strength of soil-rock mixture considering the size effect and its application
Authors: Zhou Yingbo , Sheng Genlin , Qiao Shihui , Zhou Li , Cai Jie , Xu Hanping
Published: November 2022

The shear strength of the soil-rock mixture (S-RM) is the primary mechanical factor influencing the stability of the deposit slope. The particle size range inside the test sample, however, is not the same as that of the S-RM in the deposit slope due to the limitations of the test device, which results in a variation in the mechanical properties. In this study, computer simulation tests were conducted to examine the impact of particle size on mechanical behaviors under the uniaxial compressive condition, and the size effect was analyzed from both macroscopic and mesoscopic perspectives. Results indicate that when the particle size increases, the anisotropy levels of the S-RM sample also rise, causing the particle displacement difference inside the sample to increase and the rounding rock effect to become more pronounced. The quantitative relationship between the uniaxial compressive strength (UCS) and the maximum particle size (dmax) was proposed, and the accuracy of the prediction formula for the UCS value of S-RM that takes the size effect into account has been confirmed. The improvement of the shear strength determination method was achieved by unifying the particle size range corresponding to the uniaxial compressive and shear test results used in the approach, and the determination method was used to evaluate the stability of a typical deposit slope. The study results can be used as a guide for estimating strength parameters of S-RM throughout the design and construction process of the deposit slope.
Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-β1 signaling in vitro and in vivo
Authors: Gao Haijun , Huo Lele , Mo Xiaojin , Jiang Bin , Luo Yanping , Xu Bin , Li Jingzhong , Ma Xingming , Jing Tao , Feng Zheng , Zhang Ting , Hu Wei
Published: November 2022

Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with severe side effects in long-term use, thus development of new anti-echinococcal drugs is mandated. Pseudolaric acid B (PAB) has long been used to treat fungal-infected dermatosis, and exerted anti-tumor, -fertility, -angiogenesis, -tubulin and antiparasitic activity. However, the effect of PAB against Echinococcus spp. remains unclear. The present study is to understand the effect of PAB against E. multilocularis in vitro and in vivo, and identify potential anti-echinococcal mechanism, as well as its toxicity. After exposure to PAB at 20 μg/ml, significant reduction of the survival rate and substantial ultrastructural destructions in E. multilocularis protoscoleces were observed in vitro. Furthermore, the wet weight of E. multilocularis cysts in the infected mice was significantly decreased after treatment with PAB (40, 20 or 10 mg/kg) for 12 weeks. Meanwhile, significant increase of both protein and mRNA expression of transforming growth factor beta 1 (TGF-β1) was detected in the serum and liver of the infected mice, whereas PAB administration lowered its expression significantly. The toxicity tests demonstrated that PAB displayed lower cytotoxicity to human liver and kidney cells (HL-7702 and HK-2 cell) with IC50 = 25.29 and 42.94 μg/ml than albendazole with IC50 = 3.71 and 21.22 μg/ml in vitro, and caused lower hepatoxicity and nephrotoxicity in mice than ABZ. Our findings indicated that PAB possesses potent anti-echinococcal effect, with lower toxicity than albendazole, implying a potential chemotherapeutic agent for AE. Additionally, the present study demonstrated that the suppressive effect of PAB on the parasite may involve down-regulation of TGF-β1 signaling.
Purification and characterization of cold-adapted and salt-tolerant dextranase from Cellulosimicrobium sp. THN1 and its potential application for treatment of dental plaque
Authors: Xu Linxiang , Zhang Yan , Liu Nannan , Wei Zhen , Wang Zhen , Wang Yonghua , Wang Shujun
Published: November 2022

The cold-adapted and/or salt-tolerant enzymes from marine microorganisms were confirmed to be meritorious tools to enhance the efficiency of biocatalysis in industrial biotechnology. We purified and characterized a dextranase CeDex from the marine bacterium Cellulosimicrobium sp. THN1. CeDex acted in alkaline pHs (7.5–8.5) and a broad temperature range (10–50°C) with sufficient pH stability and thermostability. Remarkably, CeDex retained approximately 40% of its maximal activities at 4°C and increased its activity to 150% in 4 M NaCl, displaying prominently cold adaptation and salt tolerance. Moreover, CeDex was greatly stimulated by Mg2+, Na+, Ba2+, Ca2+ and Sr2+, and sugarcane juice always contains K+, Ca2+, Mg2+ and Na+, so CeDex will be suitable for removing dextran in the sugar industry. The main hydrolysate of CeDex was isomaltotriose, accompanied by isomaltotetraose, long-chain IOMs, and a small amount of isomaltose. The amino acid sequence of CeDex was identified from the THN1 genomic sequence by Nano LC–MS/MS and classified into the GH49 family. Notably, CeDex could prevent the formation of Streptococcus mutans biofilm and disassemble existing biofilms at 10 U/ml concentration and would have great potential to defeat biofilm-related dental caries.
The determinants regulating Toxoplasma gondii bradyzoite development
Authors: Pan Ming , Ge Ceng-Ceng , Fan Yi-Min , Jin Qi-Wang , Shen Bang , Huang Si-Yang
Published: November 2022

Toxoplasma gondii is an obligate intracellular zoonotic pathogen capable of infecting almost all cells of warm-blooded vertebrates. In intermediate hosts, this parasite reproduces asexually in two forms, the tachyzoite form during acute infection that proliferates rapidly and the bradyzoite form during chronic infection that grows slowly. Depending on the growth condition, the two forms can interconvert. The conversion of tachyzoites to bradyzoites is critical for T. gondii transmission, and the reactivation of persistent bradyzoites in intermediate hosts may lead to symptomatic toxoplasmosis. However, the mechanisms that control bradyzoite differentiation have not been well studied. Here, we review recent advances in the study of bradyzoite biology and stage conversion, aiming to highlight the determinants associated with bradyzoite development and provide insights to design better strategies for controlling toxoplasmosis.
Sociability in a non-captive macaque population is associated with beneficial gut bacteria
Authors: Johnson Katerina V.-A. , Watson Karli K. , Dunbar Robin I. M. , Burnet Philip W. J.
Published: November 2022

The relationship between social behaviour and the microbiome is known to be reciprocal. Research in wild animal populations, particularly in primate social groups, has revealed the role that social interactions play in microbial transmission, whilst studies in laboratory animals have demonstrated that the gut microbiome can affect multiple aspects of behaviour, including social behaviour. Here we explore behavioural variation in a non-captive animal population with respect to the abundance of specific bacterial genera. Social behaviour based on grooming interactions is assessed in a population of rhesus macaques (Macaca mulatta), and combined with gut microbiome data. We focus our analyses on microbiome genera previously linked to sociability and autistic behaviours in rodents and humans. We show in this macaque population that some of these genera are also related to an individual’s propensity to engage in social interactions. Interestingly, we find that several of the genera positively related to sociability, such asFaecalibacterium, are well known for their beneficial effects on health and their anti-inflammatory properties. In contrast, the genusStreptococcus, which includes pathogenic species, is more abundant in less sociable macaques. Our results indicate that microorganisms whose abundance varies with individual social behaviour also have functional links to host immune status. Overall, these findings highlight the connections between social behaviour, microbiome composition, and health in an animal population.
Attenuated Streptococcus agalactiae WC1535 ∆Sia perturbs the gut microbiota of Oreochromis niloticus, massively colonizes the intestine, and induces intestinal mucosal immunity after intraperitoneal inoculation
Authors: Hao Jingwen , Wang Shuyi , Yang Jicheng , Zhang Qianqian , Wu Zhenbing , Zhang Defeng , Li Aihua
Published: November 2022

We previously developed and assessed the effectiveness of the attenuated Streptococcus agalactiae (Group B Streptococcus, GBS) strain WC1535 ∆Sia (with neuA-D gene cluster deletion) vaccine in tilapia (Oreochromis niloticus). In this study, we characterized the bacterial communities of the tilapia intestines by 16S rRNA high-throughput sequencing and assessed the serum antibody response, expression of immune-related genes, and histological changes following formalin-killed GBS vaccine (FKV) and the live attenuated vaccine ∆Sia (LAV). Results showed that FKV and LAV induced robust systemic and intestinal mucosal immune responses in tilapia without causing obvious pathological changes in the hindgut, spleen, and head kidney but exerted different effects on intestinal bacterial communities. The richness or diversity of the intestinal bacterial community of FKV tilapia showed no significant changes compared with that of the control fish (p > 0.05) at either day 21 post-initial vaccination (21 dpiv) or day 35 (day 14 after the second immunization) (35 dpiv). The community composition of FKV tilapia and controls was significantly similar, although the relative abundance of some genera was significantly altered. Relative to control fish, the gut ecosystem of LAV tilapia was significantly disturbed with a substantial increase in community diversity at 21 dpiv (p < 0.05) and a significant decrease at 35 dpiv in fish with high serum antibody response (ΔSia35H) (p < 0.05). However, there was no significant difference between ΔSia35H and ΔSia35L (low serum antibody response) fish (p > 0.05). Moreover, the community composition of LAV tilapia at 21 dpiv or 35 dpiv was considerably different from that of the controls. Particularly, GBS ∆Sia was found to be abundant in the intestine at 21 and 35 dpiv. This result suggested that the parenteral administration of the LAV (∆Sia) may also have the effect of oral vaccination in addition to the immune effect of injection vaccination. In addition, a significant correlation was found between the expression of immune-related genes and certain bacterial species in the intestinal mucosal flora. Our findings will contribute to a better understanding of the effects of inactivated and attenuated vaccines on gut microbiota and their relationship with the immune response.
Screening low-methanol and high-aroma produced yeasts for cider fermentation by transcriptive characterization
Authors: Liu Liang , Zhao Peng Tao , Hu Ching Yuan , Tian Dan , Deng Hong , Meng Yong Hong
Published: November 2022

The commercial active dry yeast strains used for cider production in China are far behind the requirements of the cider industry development in recent decades. In this study, eight yeasts, including Saccharomyces cerevisiae, Schizosaccharomyces pombe, Pichia bruneiensis, and Pichia kudriavzevii, were screened and assessed by growth performance, methanol production, aroma analysis, and their transcriptive characterization. Saccharomyces cerevisiae strains WFC-SC-071 and WFC-SC-072 were identified as promising alternatives for cider production. Strains WFC-SC-071 and WFC-SC-072 showed an excellent growth capacity characterized by 91.6 and 88.8% sugar utilization, respectively. Methanol production by both strains was below 200 mg/L. Key aroma compounds imparting cider appreciably characteristic aroma increased in cider fermented by strains WFC-SC-071 and WFC-SC-072. RT-qPCR analysis suggested that most genes associated with growth capacity, carbohydrate uptake, and aroma production were upregulated in WFC-SC-071 and WFC-SC-072. Overall, two Saccharomyces cerevisiae strains are the optimal starters for cider production to enable the diversification of cider, satisfy the differences in consumer demand, and promote cider industry development.
Inventa: A computational tool to discover structural novelty in natural extracts libraries
Authors: Quiros-Guerrero Luis-Manuel , Nothias Louis-Félix , Gaudry Arnaud , Marcourt Laurence , Allard Pierre-Marie , Rutz Adriano , David Bruno , Queiroz Emerson Ferreira , Wolfender Jean-Luc
Published: November 2022

Collections of natural extracts hold potential for the discovery of novel natural products with original modes of action. The prioritization of extracts from collections remains challenging due to the lack of a workflow that combines multiple-source information to facilitate the data interpretation. Results from different analytical techniques and literature reports need to be organized, processed, and interpreted to enable optimal decision-making for extracts prioritization. Here, we introduce Inventa, a computational tool that highlights the structural novelty potential within extracts, considering untargeted mass spectrometry data, spectral annotation, and literature reports. Based on this information, Inventa calculates multiple scores that inform their structural potential. Thus, Inventa has the potential to accelerate new natural products discovery. Inventa was applied to a set of plants from the Celastraceae family as a proof of concept. The Pristimera indica (Willd.) A.C.Sm roots extract was highlighted as a promising source of potentially novel compounds. Its phytochemical investigation resulted in the isolation and de novo characterization of thirteen new dihydro-β-agarofuran sesquiterpenes, five of them presenting a new 9-oxodihydro-β-agarofuran base scaffold.
Comprehensive analysis of the prognostic value and functions of prefoldins in hepatocellular carcinoma
Authors: Ke Shanjia , Lu Shounan , Wang Chaoqun , Xu Yanan , Bai Miaoyu , Yu Hongjun , Feng Zhigang , Yin Bing , Li Zihao , Huang Jingjing , Li Xinglong , Qian Baolin , Hua Yongliang , Pan Shangha , Wu Yaohua , Ma Yong
Published: November 2022

Prefoldins (PFDNs), a group of proteins known to be associated with cytoskeletal rearrangement, are involved in tumor progression in various cancer types. However, little is known about the roles of PFDNs in hepatocellular carcinoma (HCC). Herein, we investigated the transcriptional and survival data of PFDNs from The Cancer Genome Atlas (TCGA) database. Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and single-sample gene set enrichment analysis (ssGSEA) were used to evaluate the potential functions of PFDN1/2/3/4. We also detected the expression of PFDN1/2/3/4 via immunohistochemistry (IHC), Western blotting, and real-time PCR in our clinical samples. We found that the PFDN family showed elevated expression in HCC tissues, while only PFDN1/2/3/4 were found to be significantly correlated with poor prognosis of patients with HCC in the TCGA database. Further investigation was associated with PFDN1–4. We found that the expression of PFDN1/2/3/4 was significantly associated with advanced clinicopathologic features. Apart from the TCGA database, IHC, real-time PCR, and immunoblotting identified the overexpression of PFDN1/2/3/4 in HCC tissues and HCC cell lines. Taken together, these results indicated that PFDN1/2/3/4 might be novel prognostic biomarkers and treatment targets for patients with HCC.
Preliminary findings of accelerated visual memory decline and baseline brain correlates in middle-age and older adults with autism: The case for hippocampal free-water
Authors: Walsh Melissa J. M. , Ofori Edward , Pagni Broc A. , Chen Kewei , Sullivan Georgia , Braden B. Blair
Published: November 2022

Research aimed at understanding cognitive and brain aging in adults with autism spectrum disorder (ASD) is growing, but critical longitudinal work is scant. Adults with ASD struggle with tasks involving visual memory compared with neurotypical adults (NT). This may be related to differences in size or integrity of the hippocampus and its’ primary structural connectivity pathway, the fornix. The aim of this study was to describe preliminary findings of longitudinal aging trajectories in short- and long-term visual memory abilities in middle-age and older adults with ASD, compared with matched NT adults. We then evaluated baseline multi-modal imaging metrics of the hippocampal system, including the relatively novel metric of free-water, as potential correlates of longitudinal memory change in the ASD group. Middle-age and older adults with ASD (n = 25) and matched NT adults (n = 25) between the ages of 40 and 70 years were followed longitudinally at ~2-year intervals (range 2–5 years). Participants completed the Wechsler Memory Scale III Visual Reproduction task. Longitudinal mixed models were utilized to detect group differences in memory change with baseline age and sex as covariates. Hippocampal volume was measuredviaT1-weighted MRI images with FreeSurfer. Fornix fractional anisotropy and hippocampal and fornix free-water were measured from diffusion tensor imaging scans. Exploratory correlations were run between individual hippocampal system metrics and longitudinal slopes of visual memory change. There was a significant group by time interaction for long-term visual memory, such that middle-age and older adults with ASD declined faster than matched NT adults. There was no group by time interaction for short-term visual memory. Baseline hippocampal free-water was the only hippocampal system metric that correlated with long-term visual memory change in the ASD group. As one of the first longitudinal cognitive and brain aging studies in middle-age and older adults with ASD, our findings suggest vulnerabilities for accelerated long-term visual memory decline, compared to matched NT adults. Further, baseline hippocampal free-water may be a predictor of visual memory change in middle-age and older adults with ASD. These preliminary findings lay the groundwork for future prognostic applications of MRI for cognitive aging in middle-age and older adults with ASD.
Subtyping of early-onset Parkinson’s disease using cluster analysis: A large cohort study
Authors: Zhou Zhou , Zhou Xiaoxia , Xiang Yaqin , Zhao Yuwen , Pan Hongxu , Wu Juan , Xu Qian , Chen Yase , Sun Qiying , Wu Xinyin , Zhu Jianping , Wu Xuehong , Li Jianhua , Yan Xinxiang , Guo Jifeng , Tang Beisha , Lei Lifang , Liu Zhenhua
Published: November 2022

Background

Increasing evidence suggests that early-onset Parkinson’s disease (EOPD) is heterogeneous in its clinical presentation and progression. Defining subtypes of EOPD is needed to better understand underlying mechanisms, predict disease course, and eventually design more efficient personalized management strategies.

Objective

To identify clinical subtypes of EOPD, assess the clinical characteristics of each EOPD subtype, and compare the progression between EOPD subtypes.

Materials and methods

A total of 1,217 patients were enrolled from a large EOPD cohort of the Parkinson’s Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) between January 2017 and September 2021. A comprehensive spectrum of motor and non-motor features were assessed at baseline. Cluster analysis was performed using data on demographics, motor symptoms and signs, and other non-motor manifestations. In 454 out of total patients were reassessed after a mean follow-up time of 1.5 years to compare progression between different subtypes.

Results

Three subtypes were defined: mild motor and non-motor dysfunction/slow progression, intermediate and severe motor and non-motor dysfunction/malignant. Compared to patients with mild subtype, patients with the severe subtype were more likely to have rapid eye movement sleep behavior disorder, wearing-off, and dyskinesia, after adjusting for age and disease duration at baseline, and showed a more rapid progression in Unified Parkinson’s Disease Rating Scale (UPDRS) total score (P = 0.002), UPDRS part II (P = 0.014), and III (P = 0.001) scores, Hoehn and Yahr stage (P = 0.001), and Parkinson’s disease questionnaire-39 item version score (P = 0.012) at prospective follow-up.

Conclusion

We identified three different clinical subtypes (mild, intermediate, and severe) using cluster analysis in a large EOPD cohort for the first time, which is important for tailoring therapy to individuals with EOPD.
The spatial frequency domain designated watermarking framework uses linear blind source separation for intelligent visual signal processing
Authors: Kumari Rani , Mustafi Abhijit
Published: November 2022

This paper develops a digital watermarking algorithm using an informed watermark retrieval architecture. The developed method uses the fractional Fourier transform to embed the watermark in the space-frequency domain and extracts the watermark using blind source separation techniques. The watermark embedding is further enhanced using a heuristic algorithm to increase the strength of the watermarking system. We use genetic algorithm to find the optimal fractional domain by minimizing the coefficient of RMSE between the input image and the watermarked image. The algorithm's performance against various common attacks, e.g., JPEG compression and Gaussian noise, is presented to estimate the algorithm's robustness.