Three-dimensional flower-like Ni-S/Co-MOF grown on Ni foam as a bifunctional electrocatalyst for efficient overall water splitting.

Poor conductivity of the metal-organic frameworks (MOFs) limits their applications in overall water splitting. Surface sulfur (S) doping transition metal hydroxides would effectively improve the conductivity and adjust the electronic structure to generate additional electroactive sites. Herein, we fabricated a Ni-S/Co-MOF/NF catalyst by electroplating a Ni-S film on the 3D flower-like Co-MOF. Because the 3D flower-like structures are covered in Ni foam, the high exposure of active sites and good conductivity are obtained. Moreover, the synergistic effect between Ni-S and Co-MOF contributes to the redistribution of electrons in the catalyst, which can then optimize the catalytic performance of the material. The obtained 3D flower-like Ni-S/Co-MOF/NF demonstrates excellent activity toward both the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) in 1 M KOH, which only requires a low overpotential of 248 mV@10 mA cm-2 for the OER and 127 mV@10 mA cm-2 for the HER, respectively. At a current density of 10 mA cm-2, the Ni-S/Co-MOF/NF‖Ni-S/Co-MOF/NF requires a low cell voltage of 1.59 V to split overall water splitting.

Microplastics footprint in nature reserves-a case study on the microplastics in the guano from Yancheng Wetland Rare Birds National Nature Reserve, China.

Bio-ingestion of microplastics poses a global threat to ecosystems, yet studies within nature reserves, crucial habitats for birds, remain scarce despite the well-documented ingestion of microplastics by avian species. Located in Jiangsu Province, China, the Yancheng Wetland Rare Birds Nature Reserve is home to diverse bird species, including many rare ones. This study aimed to assess the abundance and characteristics of microplastics in common bird species within the reserve, investigate microplastic enrichment across different species, and establish links between birds' habitat types and microplastic ingestion. Microplastics were extracted from the feces of 110 birds, with 84 particles identified from 37.27% of samples. Among 8 species studied, the average microplastic abundance ranged from 0.97 ± 0.47 to 43.43 ± 61.98 items per gram of feces, or 1.5 ± 0.87 to 3.4 ± 1.50 items per individual. The Swan goose (Anser cygnoides) exhibited the highest microplastic abundance per gram of feces, while the black-billed gull (Larus saundersi) had the highest abundance per individual. The predominant form of ingested microplastics among birds in the reserve was fibers, with polyethylene being the most common polymer type. Significant variations in plastic exposure were observed among species and between aquatic and terrestrial birds. This study represents the first quantitative assessment of microplastic concentrations in birds within the reserve, filling a crucial gap in research and providing insights for assessing microplastic pollution and guiding bird conservation efforts in aquatic and terrestrial environments.

p32/OPA1 axis-mediated mitochondrial dynamics contributes to cisplatin resistance in non-small cell lung cancer.

Cisplatin resistance is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). p32 and OPA1 are the key regulators of mitochondrial morphology and function. This study aims to investigate the role of the p32/OPA1 axis in cisplatin resistance in NSCLC and its underlying mechanism. The levels of p32 protein and mitochondrial fusion protein OPA1 are higher in cisplatin-resistant A549/DDP cells than in cisplatin-sensitive A549 cells, which facilitates mitochondrial fusion in A549/DDP cells. In addition, the expression of p32 and OPA1 protein is also upregulated in A549 cells during the development of cisplatin resistance. Moreover, p32 knockdown effectively downregulates the expression of OPA1, stimulates mitochondrial fission, decreases ATP generation and sensitizes A549/DDP cells to cisplatin-induced apoptosis. Furthermore, metformin significantly downregulates the expressions of p32 and OPA1 and induces mitochondrial fission and a decrease in ATP level in A549/DDP cells. The co-administration of metformin and cisplatin shows a significantly greater decrease in A549/DDP cell viability than cisplatin treatment alone. Moreover, D-erythro-Sphingosine, a potent p32 kinase activator, counteracts the metformin-induced downregulation of OPA1 and mitochondrial fission in A549/DDP cells. Taken together, these findings indicate that p32/OPA1 axis-mediated mitochondrial dynamics contributes to the acquired cisplatin resistance in NSCLC and that metformin resensitizes NSCLC to cisplatin, suggesting that targeting p32 and mitochondrial dynamics is an effective strategy for the prevention of cisplatin resistance.

Detection of alkaline phosphatase activity with a CsPbBr3/Y6 heterojunction-based photoelectrochemical sensor.

An ultra-sensitive photoelectrochemical (PEC) sensor based on perovskite composite was developed for the determination of alkaline phosphatase (ALP) in human serum. In contrast to CsPbBr3 or Y6 that generated anodic current, the heterojunction of CsPbBr3/Y6 promoted photocarriers to separate and generated cathodic photocurrent. Ascorbic acid (AA) was produced by ALP hydrolyzing L-ascorbic acid 2-phosphate trisodium salt (AAP), which can combine with the holes on the photoelectrode surface, accelerating the transmission of photogenerated carriers, leading to enhanced photocurrent intensity. Thus, the enhancement of PEC current was linked to ALP activity. The PEC sensor exhibits good sensitivity for detection of ALP owing to the unique photoelectric properties of the CsPbBr3/Y6 heterojunction. The detection limit of the sensor was 0.012 U·L-1 with a linear dynamic range of 0.02-2000 U·L-1. Therefore, this PEC sensing platform shows great potential for the development of different PEC sensors.

Nanoparticles as Drug Delivery Systems for the Targeted Treatment of Atherosclerosis.

Atherosclerosis continues to be a leading cause of morbidity and mortality globally. The precise evaluation of the extent of an atherosclerotic plaque is essential for forecasting its likelihood of causing health concerns and tracking treatment outcomes. When compared to conventional methods used, nanoparticles offer clear benefits and excellent development opportunities for the detection and characterisation of susceptible atherosclerotic plaques. In this review, we analyse the recent advancements of nanoparticles as theranostics in the management of atherosclerosis, with an emphasis on applications in drug delivery. Furthermore, the main issues that must be resolved in order to advance clinical utility and future developments of NP research are discussed. It is anticipated that medical NPs will develop into complex and advanced next-generation nanobotics that can carry out a variety of functions in the bloodstream.

Cost-effectiveness analysis of tislelizumab plus chemotherapy as the first-line treatment for advanced or metastatic esophageal squamous cell carcinoma in China.

Introduction: First-line treatment with tislelizumab plus chemotherapy has shown clinical benefits for patients with advanced or metastatic esophageal squamous cell carcinoma (OSCC) in China, while its economic burden is unknown. This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy from the perspective of the Chinese healthcare system. Methods: We constructed a partitioned survival model to compare the cost-effectiveness of tislelizumab plus chemotherapy with chemotherapy in patients with advanced OSCC. Patient characteristics and clinical outcomes were extracted from RATIONALE-306. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were selected as the study outcomes. Sensitivity analysis and subgroup analysis were conducted to test the stability of the results. Results: Tislelizumab plus chemotherapy provided additional 0.48 QALYs with the incremental cost of $16,587.2 than chemotherapy, of which ICER was $34,699.72 per QALY. When the willingness-to-pay threshold was set as $37,260, the novel therapy had a probability of 77% to be cost-effective. Our base-case analysis results were sensitive to utilities of progression-free survival and progression of disease. Our subgroup analysis showed that the novel therapy was associated with cost-effectiveness in patients with a high expression of PD-L1. Conclusion: Tislelizumab plus chemotherapy was likely to be more cost-effective compared with chemotherapy in the first-line therapy of advanced OSCC from the perspective of the Chinese healthcare system. Our findings can provide clinicians and decision-makers with evidence of the cost-effectiveness of tislelizumab.

The Impact of Regulatory Reforms in China on Drug Lag: The Role of Clinical Development Strategies.

In recent years, there has been significant focus on China's new drug lag, but relevant research is limited. This study explores the reasons for drug lag by assessing the impact of reforms in China's drug review system, particularly focusing on the influence of clinical development strategies. This study selected drugs first launched in the United States between 2017 and 2022, examining absolute and relative lag between China and the first-launch country (including submission and review lag). These delays with drugs approved in the European Union and Japan during the same period were compared with uncover the roots of delays in China, further identifying potential factors that could reduce these delays. The results indicate that the National Medical Products Administration (NMPA) has a longer relative lag compared with the European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency (PMDA). The submission lag time of the NMPA significantly surpasses that of the EMA and PMDA, whereas the review lag time of the NMPA exceeds that of the PMDA but falls short of the EMA. Focusing on clinical trial strategies, bridging trials and multiregional clinical trials (MRCTs) are typically required by the NMPA in East Asia, resulting in longer clinical delay time. Whereas the EMA and PMDA primarily require international MRCTs in Europe and America, with a clinical delay of < 5 months. It is evident that there is a significant gap in clinical trial durations between China and other countries. Further optimization of clinical trial management is necessary to address the lag for new drugs in China.

Application of Northern Goshawk Back-Propagation Artificial Neural Network in the Prediction of Monohydroxycarbazepine Concentration in Patients with Epilepsy.

INTRODUCTION: A northern goshawk back-propagation artificial neural network (NGO-BPANN) model was established to predict monohydroxycarbazepine (MHD) concentration in patients with epilepsy. METHODS: The data were collected from 108 Han Chinese patients with epilepsy on oxcarbazepine monotherapy. The results of 14 genotype variates were selected as the input layer in the first BPANN model, and the variables that had a more significant impact on the plasma concentration of MHD were retained. With demographic characteristics and clinical laboratory test results, the genotypes of SCN1A rs2298771 and SCN2A rs17183814 were used to construct the BPANN model. The BPANN model was comprehensively validated and used to predict the MHD plasma concentration of five patients with epilepsy in our hospital. RESULTS: The model demonstrated favorable fitness metrics, including a mean squared error of 0.00662, a gradient magnitude of 0.00753, an absence of validation tests amounting to zero, and a correlation coefficient of 0.980. Sex, BMI, and the genotype SCN1A rs2298771 were ranked highest by the absolute mean impact value (MIV), which is primarily associated with the concentration of MHD. The test group exhibited a range of - 20.84% to 31.03% bias between the predicted and measured values, with a correlation coefficient of 0.941 between the two. With BPANN, the MHD nadir concentration could be predicted precisely. CONCLUSION: The NGO-BPANN model exhibits exceptional predictive capability and can be a practical instrument for forecasting MHD concentration in patients with epilepsy. CLINICAL TRIAL REGISTRATION: www.chiCTR-OOC-17012141 .

[Contralateral endoscopic approach for lumbar foraminal stenosis using unilateral biportal endoscopic surgery].

OBJECTIVE: To assess the feasibility and imaging outcomes of unilateral biportal endoscopic technique in the treatment of lumbar foraminal stenosis through contralateral approach. METHODS: The clinical data of 33 patients with lumbar foraminal stenosis treated with unilateral biportal endoscopic technique from January 2021 to July 2022 were retrospectively analyzed. There were 17 males and 16 females;age ranging from 34 to 72 years old with an average of (56.00±7.89) years old;operation time and perioperative complications were recorded;visual analogue scale (VAS) of pain was recorded, to evaluate the degree of low back pain and lower extremity pain, and Oswestry disability index (ODI) to evaluate the lumbar spine function. At the latest follow-up, the modified Macnab score was used to evaluate the clinical efficacy. RESULTS: All patients successfully completed the operation. The operation time ranged from 47 to 65 minutes, with an average of (56.10±5.19) minutes. The postoperative follow-up ranged from 12 to 18 months, with an average of (14.9±2.3) months. The VAS of low back and lower extermity pain before operation were (7.273±1.442) and (7.697±1.447) scores, ODI was (69.182±9.740)%. Postoperative lumbocrural pain VAS were (3.394±0.966) and (2.818±0.727) scores, ODI was (17.30±4.78) %. At the latest follow-up, VAS of back and lower extermity pain was (2.788±0.650) and (2.394±0.704) scores, ODI was (14.33±350)%. There were significant differences in VAS of low back and lower extremity pain and ODI before and after operation(P<0.05). At the latest follow-up, according to the modified Macnab criteria, 24 patients got excellent result, 5 as good, 2 as fair, and 2 as poor. CONCLUSION: Unilateral biportal endoscopic treatment of lumbar foraminal stenosis through the contralateral approach is a safe and efficient method, with few complications, quick postoperative recovery, and satisfactory clinical outcomes. During the follow-up period, no iatrogenic lumbar instability was observed.

A review on polysaccharide biosynthesis in Cordyceps militaris.

Cordyceps militaris (C. militaris) is an edible parasitic fungus with medicinal properties. Its bioactive polysaccharides are structurally diverse and exhibit various metabolic and biological activities, including antitumor, hypoglycemic, antioxidant, hypolipidemic, anti-inflammatory, immunostimulatory, and anti-atherosclerotic effects. These properties make C. militaris-derived polysaccharides a promising candidate for future development. Recent advancements in microbial fermentation technology have enabled successful laboratory cultivation and extraction of these polysaccharides. These polysaccharides are structurally diverse and exhibit various biological activities, such as immunostimulatory, antioxidant, antitumor, hypolipidemic, and anti-atherosclerotic effects. This review aims to summarize the structure and production mechanisms of polysaccharides from C. militaris, covering extraction methods, key genes and pathways involved in biosynthesis, and fermentation factors that influence yield and activity. Furthermore, the future potential and challenges of utilizing polysaccharides in the development of health foods and pharmaceuticals are addressed. This review serves as a valuable reference in the fields of food and medicine, and provides a theoretical foundation for the study of polysaccharides.

A humanized Anti-YKL-40 antibody inhibits tumor development.

Drugs specifically targeting YKL-40, an over-expressed gene (CHI3L1) in various diseases remain developed. The current study is to create a humanized anti-YKL-40 neutralizing antibody and characterize its potentially therapeutic signature. We utilized in silico CDR-grafting bioinformatics to replace the complementarity determining regions (CDRs) of human IgG1 with mouse CDRs of our previously established anti-YKL-40 antibody (mAY). In fifteen candidates (VL1-3/VH1-5) of heavy and light chain variable region combination, one antibody L3H4 named Rosazumab demonstrated strong binding affinity with YKL-40 (KD = 4.645 × 10-8 M) and high homology with human IgG (80 %). In addition, we established different overlapping amino acid peptides of YKL-40 and found that Rosazumab specifically bound to residues K337, K342, and R344, the KR-rich functional domain of YKL-40. Rosazumab inhibited migration and tube formation of YKL-40-expressing tumor cells and induced tumor cell apoptosis. Mechanistically, Rosazumab induced interaction of N-cadherin with ß-catenin and activation of downstream MST1/RASSF1/Histone H2B axis, leading to chromosomal DNA breakage and cell apoptosis. Treatment of xenografted tumor mice with Rosazumab twice a week for 4 weeks inhibited tumor growth and angiogenesis, but induced tumor apoptosis. Rosazumab injected in mice distributed to blood, tumor, and other multiple organs, but did not impact in function or structure of liver and kidney, indicating non-detectable toxicity in vivo. Collectively, the study is the first one to demonstrate that a humanized YKL-40 neutralizing antibody offers a valuable means to block tumor development.

Inulin alters gut microbiota to alleviate post-stroke depressive-like behavior associated with the IGF-1-mediated MAPK signaling pathway.

INTRODUCTION: Gut microbiota dysbiosis is a key factor of the pathogenesis of post-stroke depression (PSD). PSD is associated with increased hippocampal neuronal apoptosis and decreased synaptic connectivity. Inulin can be involved in hippocampal neuron protection through the microbiome-gut-brain axis. However, the neuroprotective effects of inulin in PSD are still to be further investigated. METHODS: By utilizing the GEO public database, we identify differentially expressed genes in the hippocampus following inulin intake. This can help us discover key signaling pathways through functional enrichment analysis. Furthermore, we validate the expression levels of signaling molecules in a rat model of PSD and examine the effects of inulin on behavioral changes and body weight. Additionally, conducting a microbiome analysis to identify significantly different microbial populations and perform correlation analysis. RESULTS: The intake of inulin significantly up-regulated mitogen-activated protein kinase signaling pathway in the hippocampus. Inulin changed in the gut microbiota structure, leading to an increase in the abundance of Lactobacillus and Clostridium_sensu_stricto_1 in the intestines of PSD rats, while decreasing the abundance of Ruminococcus UCG_005, Prevotella_9, Oscillospiraceae, and Clostridia UCG_014. Furthermore, the inulin diet elevated levels of insulin-like growth factor 1 in the serum, which showed a positive correlation with the abundance of Lactobacillus. Notably, the consumption of inulin-enriched diet increased activity levels and preference for sugar water in PSD rats, while also reducing body weight. CONCLUSION: These findings highlight the potential therapeutic benefits of inulin in the management of depression and emphasize the importance of maintaining a healthy gut microbiota for PSD.

Anticancer and anti-angiogenic activities of mannooligosaccharides extracted from coconut meal on colorectal carcinoma cells in vitro.

Colorectal carcinoma (CRC) is one of the most common malignancies, though there are no effective therapeutic regimens at present. This study aimed to investigate the inhibitory effects of mannooligosaccharides extracted from coconut meal (CMOSs) on the proliferation and migration of human colorectal cancer HCT116 cells in vitro. The results showed that CMOSs exhibited significant inhibitory activity against HCT116 cell proliferation in a concentration-dependent manner with less cytotoxic effects on the Vero normal cells. CMOSs displayed the ability to increase the activation of caspase-8, -9, and -3/7, as well as the generation of reactive oxygen species (ROS). Moreover, CMOSs suppressed HCT116 cell migration in vitro. Interestingly, treatment of human microvascular endothelial cells (HMVECs) with CMOSs resulted in the inhibition of cell proliferation, cell migration, and capillary-like tube formation, suggesting its anti-vascular angiogenesis. In summary, the results of this study indicate that CMOSs could be a valuable therapeutic candidate for CRC treatment.

Protocol for photocatalytic upcycling of non-biodegradable plastics into platform chemicals at ambient conditions.

Upcycling plastics presents an opportunity not only to reduce plastic waste, but also to provide an alternative carbon source to fossil fuels. Herein, we present a protocol to upcycle plastics with resin codes 2-7 using a commercially available base-metal photocatalyst. We first conducted batch reactions, followed by a continuous, segmented flow system for gram-scale upcycling into value-added platform chemicals. This protocol, employing tandem carbon-hydrogen bond oxidation/carbon-carbon bond cleavage reactions, can be useful for photocatalytically transforming plastics at ambient conditions. For complete details on the use and execution of this protocol, please refer to Li et al. (2023).1.

[Simultaneous detection of lower aliphatic amines and conventional cations in atmospheric PM2.5 particulates by ion chromatography].

Many amine pollutants exist in the atmosphere. Lower aliphatic amines promote the formation and growth of particles into PM2.5, which damages the heart, lungs, and kidneys of the human body. PM2.5, a common atmospheric particulate pollutant with complex compositions, is the main cause of haze weather. Therefore, measuring the contents of lower aliphatic amines and cations in PM2.5 is of great significance for monitoring environmental air quality and protecting human health. This study established a suppressed ion-chromatographic method with conductivity for the simultaneous detection of four lower aliphatic amines (methylamine, dimethylamine, trimethylamine, and ethylamine) and five cations (Na+, N[Formula: see text], and Ca2+ showed high concentrations. The contents of the four lower aliphatic amines were low; however, the ethylamine content in some samples was high. The results indicate that the proposed method meets the quantification requirements for cations and lower aliphatic amines in PM2.5, with simple processing, high sensitivity, and good accuracy. It can quickly and accurately detect a large number of samples and be used to assess the pollution of small particles in the air as well as trace pollution sources to protect human health.

[Environmental regulation of water use efficiency in Artemisia ordosica in Mu Us Sandy Land: From leaf to ecosystem]. / æ¯›ä¹Œç´ æ²™åœ°é»‘æ²™è’¿æ°´åˆ†åˆ©ç”¨æ•ˆçŽ‡çŽ¯å¢ƒè°ƒæŽ§:从叶片到生态系统.

Water use efficiency (WUE) is a key indicator for predicting the impacts of climate change on ecosystem carbon and water cycles. Most studies have explored the changes in the response environment of WUE at a particular scale. Few studies have examined how WUE responds to environments at multiple scales, thus limiting our in-depth understanding of the cross-scale carbon and water cycles. In this study, we measured photosynthesis and transpiration in situ periodically and continuously from June to October 2022 in a community dominated by Artemisia ordosica in Mu Us Sandy Land, and analyzed the seasonal variations in WUE at leaf, canopy, and ecosystem scales. The results showed there were significant seasonal variations in leaf water use efficiency (WUEL), canopy water use efficiency (WUET), and ecosystem water use efficiency (WUEE). WUEL was large in June and small in both August and September, ranging from 0.73-2.98 µmol·mmol-1. Both WUET and WUEE were lowest in June and highest in July and August, ranging from 0.10-7.00 and 0.06-6.25 µmol·mmol-1. WUEL was significantly negatively correlated with stomatal conductance. WUET was significantly positively correlated with canopy conduc-tance and soil water content, and negatively correlated with vapor pressure deficit (VPD). There was a significant positive correlation between WUEE and soil water content (SWC10) in 10 cm soil depth. The structural equation model showed that SWC10 and air temperature affected net photosynthetic rate and transpiration rate by modifying stomatal conductance, and thus affecting WUEL. VPD and SWC10 affected WUET by altering transpiration. SWC10, air temperature, and VPD affected WUEE by regulating ecosystem gross primary productivity. The modelling of carbon and water cycles should thoroughly consider the path and intensity of the effect of environmental factors on WUE at multiple scales.

Highly reflective silver mirror enhanced by several dielectric films prepared under the low substrate temperature.

Optical paths in telescopes frequently incorporate silver mirrors for high sensitivity. Unfortunately, silver mirrors without protective coatings are susceptible to sulfurization and oxidation, compromising their quality. Even with protective layers, insufficient adhesion between the coating and the silver film can lead to peeling, exposing the silver to external environments and affecting its quality. This study aimed to identify dielectric materials with superior adhesion to silver, rendering them ideal choices for silver coating applications. By electron gun evaporation, different dielectric layers were deposited on the top and bottom of the silver film under a substrate temperature below 150 °C. These coatings were composed of materials with desired refractive indices, including aluminum oxide (Al2O3), aluminum-doped silicon, magnesium fluoride (MgF2), and other dielectrics. Following the deposition, a tape adhesion test was conducted to evaluate the bond strength of the samples. X-ray photoelectron spectroscopy (XPS) analysis was carried out to investigate the interaction between silver and its neighboring layers. The results revealed that Al2O3 and MgF2 exhibited exceptional adhesion to silver. Moreover, these multilayer coatings can effectively enhance the reflectance of silver in the visible (VIS) wavelength ranges.

Galactomannan inhibits Trichinella spiralis invasion of intestinal epithelium cells and enhances antibody-dependent cellular cytotoxicity related killing of larvae by driving macrophage polarization.

Previous studies have shown that recombinant Trichinella spiralis galectin (rTsgal) is characterized by a carbohydrate recognition domain sequence motif binding to beta-galactoside, and that rTsgal promotes larval invasion of intestinal epithelial cells. Galactomannan is an immunostimulatory polysaccharide composed of a mannan backbone with galactose residues. The aim of this study was to investigate whether galactomannan inhibits larval intrusion of intestinal epithelial cells and enhances antibody-dependent cellular cytotoxicity (ADCC), killing newborn larvae by polarizing macrophages to the M1 phenotype. The results showed that galactomannan specially binds to rTsgal, and abrogated rTsgal facilitation of larval invasion of intestinal epithelial cells. The results of qPCR, Western blotting, and flow cytometry showed that galactomannan and rTsgal activated macrophage M1 polarization, as demonstrated by high expression of iNOS (M1 marker) and M1 related genes (IL-1ß, IL-6, and TNF-α), and increased CD86+ macrophages. Galactomannan and rTsgal also increased NO production. The killing ability of macrophage-mediated ADCC on larvae was also significantly enhanced in galactomannan- and rTsgal-treated macrophages. The results demonstrated that Tsgal may be considered a potential vaccine target molecule against T. spiralis invasion, and galactomannan may be a novel adjuvant therapeutic agent and potential vaccine adjuvant against T. spiralis infection.

Title: Le galactomannane inhibe l'invasion par Trichinella spiralis des cellules de l'épithélium intestinal et améliore la cytotoxicité cellulaire dépendante des anticorps tuant les larves en activant la polarisation des macrophages. Abstract: Des études antérieures ont montré que la galectine recombinante de Trichinella spiralis (rTsgal) est caractérisée par un motif de séquence de domaines de reconnaissance des glucides se liant au bêta-galactoside, et que la rTsgal favorise l'invasion larvaire des cellules épithéliales intestinales. Le galactomannane est un polysaccharide immunostimulateur composé d'un squelette mannane avec des résidus galactose. Le but de cette étude était de déterminer si le galactomannane inhibe l'intrusion larvaire des cellules épithéliales intestinales et améliore la cytotoxicité cellulaire dépendante des anticorps (CCDA) tuant les larves nouvelles-nées en polarisant les macrophages au phénotype M1. Les résultats ont montré que le galactomannane se liait spécialement au rTsgal et supprimait la facilitation du rTsgal sur l'invasion larvaire des cellules épithéliales intestinales. Les résultats de la qPCR, du Western blot et de la cytométrie en flux ont montré que le galactomannane et le rTsgal activaient la polarisation des macrophages M1, comme le démontre la forte expression de l'iNOS (marqueur de M1) et des gènes liés à M1 (IL-1ß, IL-6 et TNF-α), et l'augmentation des macrophages CD86+. Le galactomannane et le rTsgal ont également augmenté la production de NO. La capacité de destruction de la CCDA médiée par les macrophages sur les larves était également significativement améliorée dans les macrophages traités au galactomannane et au rTsgal. Les résultats ont démontré que Tsgal pourrait être considéré comme une molécule cible potentielle d'un vaccin contre l'invasion par T. spiralis, et que le galactomannane pourrait être un nouvel agent thérapeutique adjuvant et un adjuvant vaccinal potentiel contre l'infection à T. spiralis.

Characterization of a novel dipeptidyl peptidase 1 of Trichinella spiralis and its participation in larval invasion.

The research aimed to describe a new Trichinella spiralis dipeptidyl peptidase 1 (TsDPP1) and investigate its functions in the larval invasion of intestinal epithelial cells (IECs). The gene TsDPP1 was successfully replicated and produced in Escherichia coli BL21 (DE3), showing a strong immune response. TsDPP1 was detected in diverse stages of T. spiralis and showed significant expression in the intestine infective larvae (IIL) and adult worms at 6 days post infection, as confirmed by qPCR and Western blot analysis. The primary localization of TsDPP1 in this parasite was observed in cuticles, stichosomes, and embryos by using the indirect immunofluorescence assay (IIFA). rTsDPP1 exhibited the enzymatic function of natural dipeptidyl peptidase and showed specific binding to IECs, and the binding site was found to be localized on cell membrane. Following transfection with dsRNA-TsDPP1, the expression of TsDPP1 mRNA and protein in muscle larvae (ML) were decreased by approximately 63.52 % and 58.68 %, correspondingly. The activity of TsDPP1 in the ML and IIL treated with dsRNA-TsDPP1 was reduced by 42.98 % and 45.07 %, respectively. The acceleration of larval invasion of IECs was observed with rTsDPP1, while the invasion was suppressed by anti-rTsDPP1 serum. The ability of the larvae treated with dsRNA-TsDPP1 to invade IECs was hindered by 31.23 %. In mice infected with dsRNA-treated ML, the intestinal IIL, and adults experienced a significant decrease in worm burdens and a noticeable reduction in adult female length and fecundity compared to the PBS group. These findings indicated that TsDPP1 significantly impedes the invasion, growth, and reproductive capacity of T. spiralis in intestines, suggesting its potential as a target for anti-Trichinella vaccines.

A new diagnostic technique for identifying Angiostrongylus spp. larvae in intermediate snail species by examining the buccal cavity.

BACKGROUND: Angiostrongyliasis is a zoonotic parasitic disease caused by the rat lungworm Angiostrongylus cantonensis. The intermediate hosts of A. cantonensis are gastropods, and snail species such as Pomacea canaliculata play a key role in the transmission of human angiostrongyliasis. Detecting A. cantonensis infection in snails is an important component of epidemiological surveillance and the control of angiostrongyliasis. METHODS: In this study, a new method for diagnosing A. cantonensis infection in gastropods was developed by recovering larvae from the buccal cavity of three snail species. The entire buccal cavity of a snail was extracted, and the tissue was pressed between two microscope slides to observe whether A. cantonensis larvae were present. Our new method was compared with traditional pathogenic detection methods of lung microscopy, tissue homogenization, and artificial digestion. We artificially infected 160 P. canaliculata, 160 Cipangopaludina chinensis, and 160 Bellamya aeruginosa snails with A. cantonensis. Then, the four different detection methods were used to diagnose infection in each snail species at 7, 14, 21, and 28 days post exposure. RESULTS: We found no significant difference in the percentages of infected P. canaliculata snails using the four methods to detect A. cantonensis larvae. The radula pressing method had a mean detection rate of 80%, while the lung microscopy (81.3%), tissue homogenization (83.8%), and artificial digestion (85%) methods had slightly greater detection rates. Similarly, the percentages of infected C. chinensis snails that were detected using the radula pressing (80%), tissue homogenization (82.1%), and artificial digestion (83.8%) methods were not significantly different. Finally, the percentages of infected B. aeruginosa snails that were detected using the radula pressing (81.3%), tissue homogenization (81.9%), and artificial digestion (81.4%) methods were not significantly different. These results showed that the radula pressing method had a similar detection rate to traditional lung microscopy, tissue homogenization, or artificial digestion methods. CONCLUSIONS: This study demonstrates a new method for the qualitative screening of gastropods that act as intermediate hosts of A. cantonensis (and other Angiostrongylus species), provides technical support for the control of human angiostrongyliasis, and furthers research on A. cantonensis.