Thalassotalea psychrophila sp. nov., Thalassotalea nanhaiensis sp. nov. and Thalassotalea fonticola sp. nov., three psychrophilic bacteria isolated from deep-sea sediment.

Three psychrophilic bacteria, designated as strains SQ149T, SQ345T, and S1-1T, were isolated from deep-sea sediment from the South China Sea. All three strains were the most closely related to Thalassotalea atypica RZG4-3-1T based on the 16S rRNA gene sequence analysis (similarity ranged from 96.45 to 96.67 %). Phylogenetic analysis based on the 16S rRNA gene and core-genome sequences showed that three strains formed a cluster within the genus Thalassotalea. The average amino acid identity, average nucleotide identity, and digital DNA-DNA hybridization values among the three strains and closest Thalassotalea species were far below the cut-off value recommended for delineating species, indicating they each represented a novel species. All three strains were Gram-stain-negative, rod-shaped, and contained summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) as the predominant fatty acid, Q-8 as the major respiratory quinone, and phosphatidylethanolamine and phosphatidylglycerol as predominant polar lipids. Based on the genomic, phylogenetic, and phenotypic characterizations, each strain is considered to represent a novel species within the genus Thalassotalea, for which the names Thalassotalea psychrophila sp. nov. (type strain SQ149T=MCCC 1K04231T=JCM 33807T), Thalassotalea nanhaiensis sp. nov. (type strain SQ345T=MCCC 1K04232T=JCM 33808T), and Thalassotalea fonticola sp. nov. (type strain S1-1T=MCCC 1K06879T=JCM 34824T) are proposed.

Association of Valproic Acid and Its Main Metabolites' Plasma Concentrations with Clinical Outcomes among Epilepsy Patients: A 10-Year Retrospective Study Based on Therapeutic Drug Monitoring.

Valproic acid (VPA) is a first-line antiepileptic drug with broad efficacy. Due to significant individual differences in its metabolism, therapeutic drug monitoring is commonly used. However, the recommended therapeutic range (50-100 µg/mL) is inadequate for predicting clinical outcomes. Additionally, the relationship between VPA metabolites and clinical outcomes remains unclear. In this retrospective study, 485 Chinese Southern Han epilepsy patients receiving VPA monotherapy were analyzed after reaching steady-state levels. Plasma concentrations of VPA and its five main metabolites were determined by liquid chromatography-mass spectrometry (LC-MS). We assessed the relevance of the recommended therapeutic VPA range for clinical outcomes and explored the association between VPA/metabolites levels and treatment efficacy/adverse effects. Vitro experiments were conducted to assess 4-ene-VPA hepatotoxicity. The therapeutic range of VPA exhibited no significant correlation with clinical outcomes, and plasma concentrations of VPA failed to serve as predictive indicators for treatment response/adverse effects. Treatment responders had higher 2-PGA concentrations (median, 26.39 ng/mL versus 13.68 ng/mL), with a threshold of 36.5 ng/mL for optimal epilepsy treatment. Patients with abnormal liver function had a higher 4-ene-VPA median concentration (6.41 µg/mL versus 4.83 µg/mL), and the ratio of 4-ene-VPA to VPA better predicted VPA-induced hepatotoxicity (area under the curve, 0.718) than 4-ene-VPA concentration. Vitro experiments revealed that 4-ene-VPA was more hepatotoxic than VPA in HepaRG and L02 cell lines. Total plasma VPA concentration does not serve as a predictor of clinical outcomes. 2-PGA concentrations may be associated with efficacy, whereas the ratio of 4-ene-VPA to VPA may be considered a better biomarker (threshold 10.03%) for VPA-induced hepatotoxicity. SIGNIFICANCE STATEMENT: This was the first and largest observational cohort in China to explore the relationship between patients' parent and metabolites concentrations of VPA and clinical outcomes during the maintenance of VPA monotherapy in epileptic patients. This study provided feasible references of VPA for epilepsy clinical treatment with a larger sample of patients compared with previous studies for a more definitive conclusion based on real-world situations. We found two potential biomarkers in predicting efficacy and liver injury, respectively. This breakthrough has the potential to assist in the rational use of VPA.

A nomogram for predicting mild cognitive impairment in older adults with hypertension.

BACKGROUND: Hyper- and hypotension increase the risk of cognitive dysfunction. As effective control of blood pressure can reduce the risk of mild cognitive impairment (MCI), early risk assessment is necessary to identify MCI in senile hypertension as soon as possible and reduce the risk of developing dementia. No perfect risk-prediction model or nomogram has been developed to evaluate the risk of MCI in older adults with hypertension. We aimed to develop a nomogram model for predicting MCI in older patients with hypertension. METHODS: We selected 345 older patients with hypertension in Xixiangtang District, Nanning City, as the modeling group and divided into the MCI (n = 197) and non-MCI groups (n = 148). Comparing the general conditions, lifestyle, disease factors, psychosocial and other indicators. Logistic regression was used to analyze risk factors for MCI in older hypertensive patients, and R Programming Language was used to draw the nomogram. We selected 146 older patients with hypertension in Qingxiu District, Nanning City, as the verification group. The effectiveness and discrimination ability of the nomogram was evaluated through internal and external verification. RESULTS: Multivariate logistic regression analysis identified 11 factors, including hypertension grade, education level, complicated diabetes, hypertension years, stress history, smoking, physical exercise, reading, social support, sleep disorders, and medication compliance, as risk factors for MCI in older patients with hypertension. To develop a nomogram model, the validity of the prediction model was evaluated by fitting the curve, which revealed a good fit for both the modeling (P = 0.98) and verification groups (P = 0.96). The discrimination of the nomogram model was evaluated in the modeling group using a receiver operating characteristic curve. The area under the curve was 0.795, and the Hosmer-Lemeshow test yielded P = 0.703. In the validation group, the area under the curve was 0.765, and the Hosmer-Lemeshow test yielded P = 0.234. CONCLUSIONS: We developed a nomogram to help clinicians identify high-risk groups for MCI among older patients with hypertension. This model demonstrated good discrimination and validity, providing a scientific basis for community medical staff to evaluate and identify the risk of MCI in these patients at an early stage.

Synthesis of graphene anchored with atomically isolated cobalt from a promising graphite-like supramolecule.

The application of heteroatom-doped graphene for photochemical and electrochemical reactions is primarily hindered by the lack of a controllable and facile synthesis strategy. In this work, few-layer CoN-graphene (1.8 nm thickness) with atomic Co has been fabricated via pyrolysis exfoliation. The half wave potential of CoN-graphene reaches 0.875 V vs. RHE, and the corresponding direct methanol fuel cell performance is 100% (higher than that of the commercial Pt/C catalyst), demonstrating potential for practical application in energy conversion devices.

Spatial-temporal variation of the carbon sequestration rate of afforestation in China: Implications for carbon trade and planning.

Afforestation and reforestation (A&R) are nature-based and cost-effective solutions for enhancing terrestrial carbon sinks and facilitating faster carbon neutrality. However, the lack of hierarchical spatial-temporal maps for the carbon sequestration rate (CSR) from A&R at the national scale impedes the scientific implementation of forest management planning to a large extent. Here, we assessed the spatial-temporal CSR per area for A&R at the provincial, prefectural, and county levels in China using a forest carbon sequestration model under three climate scenarios. Results showed that the CSR of vegetation (CSRVeg), soil (CSRSoil), and the ecosystem (CSREco) significantly varied across space and time. In China, the CSRVeg, CSRSoil, and CSREco were primarily regulated by the spatial variations in temperature and precipitation. Additionally, CSRVeg was found to be positively influenced by precipitation and temperature, whereas temperature had a negative influence on CSRSoil. Therefore, the differences between the CSRVeg and CSRSoil should be emphasized in the future. These information on the spatiotemporal variation of CSR of A&R (vegetation, soil, and ecosystem) on unit area basis and at levels of province, prefecture, and county in China, can be used as a comparable protocol to estimate the carbon sinks of A&R at different scales. Overall, these hierarchical spatiotemporal maps for CSR on A&R may help to identify priority areas of forest management planning and carbon trade policy to achieve faster carbon neutrality for China in the future.

Defect-Rich Glassy IrTe2 with Dual Enzyme-Mimic Activities for Sono-Photosynergistic-Enhanced Oncotherapy.

The complexity, diversity, and heterogeneity of malignant tumors pose a formidable challenge for antitumor therapy. To achieve the goal of significantly enhancing the antitumor effect, nanomedicine-based synergistic therapy is one of the important strategies. Herein, we innovatively report a defect-rich glassy IrTe2 (G-IrTe2) with weak Ir-Te bond strength for synergistic sonodynamic therapy (SDT), chemodynamic therapy (CDT), and mild photothermal therapy (PTT). G-IrTe2 sonosensitizer under ultrasound (US) stimuli exhibits excellent reactive oxygen species (ROS) production performance. Besides, catalase (CAT)-like activity of G-IrTe2 can provide abundant oxygen to enhance the SDT effect. Then, the theoretical calculation verifies that US stimuli can easily make the irregular Ir-Te bond to be broken in amorphous IrTe2 and free electrons will be released to combine with the oxygen and further form singlet oxygen (1O2). Meanwhile, G-IrTe2 with peroxidase (POD)-like activity can also catalyze endogenous H2O2 to produce more ROS for chemodynamic therapy (CDT), which is conducive to better tumor ablation. Furthermore, the ROS produced by sono-/chemodynamic processes can cause mitochondrial dysfunction and further give rise to heat shock protein (HSP) downregulated expression, maximizing the efficiency of mild PTT. Therefore, such glassy IrTe2 with rich defect could be significantly involved in synergistic oncotherapy and then effectively achieve outstanding antitumor efficacy. This study provides a new research idea for expanding the application of inorganic glassy nanomaterials in promoting the therapeutic effect of tumors.

Spatial-Temporal Variation and Influencing Factors of Regional Tourism Carbon Emission Efficiency in China Based on Calculating Tourism Value Added.

Tourism-related carbon emission efficiency is an important indicator that reflects the sustainable development of tourism and can better balance the relationship between negative environmental impact and economic value. According to panel data of 30 provincial regions, "the tourism value added coefficient" (not including the Tibet Autonomous Region) in mainland China from 2000 to 2019, we estimate the tourism of each provincial administrative unit carbon emissions, measure the tourism carbon efficiency value, and analyze the measurement results of the change trend, spatial differentiation characteristics, and influencing factors. The results show that (1) the carbon emission efficiency of regional tourism in China increased significantly from 2000 to 2019, but there was a significant difference in the carbon emission efficiency of tourism among regions, and the sustainable development level of regional tourism was still unbalanced. (2) The spatial pattern of provincial administrative units in China has the adjacent characteristics of High-High agglomeration and Low-Low agglomeration, the difference in the tourism eco-efficiency development level among regions gradually decreases with time, and there is a dynamic convergence characteristic. (3) The q value represents the intensity of the impact factor on tourism carbon emission efficiency. According to the q value, the factors affecting tourism carbon emission efficiency were divided into dominant factors (0.5 ≤ q ≤ 1), inducing factors (0.2 ≤ q < 0.5) and driving factors (0 ≤ q < 0.2), among which the level of technological development was the dominant factor. The level of opening-up to the outside world is the inducing factor; environmental regulation intensity, urbanization level, regional economic development level, tourism industry environment, and tourism infrastructure are the driving factors. (4) The influence degree of influencing factors on the spatial differentiation of tourism carbon emission efficiency is significantly different in different periods. The degree of influence of the urbanization level and tourism industry environment shows an upward trend over time, and the influence degree of other factors shows a "V-shaped" trend. (5) The two-factor interaction will significantly enhance the spatial differentiation of regional tourism carbon emission efficiency, and the interaction between the level of scientific and technological innovation and other influencing factors has a deeper impact on tourism carbon emission efficiency.

Cu Single Atom Nanozyme Based High-Efficiency Mild Photothermal Therapy through Cellular Metabolic Regulation.

Upregulation of heat shock proteins (HSPs) drastically compromises the treatment effect of mild photothermal therapy (PTT). Herein, we designed a polyporous Cu single atom nanozyme (Cu SAzyme) loaded with licogliflozin (LIK066) for HSP-silencing induced mild PTT. On one hand, LIK066 inhibits glucose uptake by shutting sodium-dependent glucose transporter (SGLT) "valve", effectively blocking the energy source for adenosine triphosphate (ATP) generation. Without sufficient energy, cancer cells cannot synthesize HSPs. On the other hand, Cu SAzyme presents extraordinary multienzyme activities to induce reactive oxygen species (ROS) storm formation, which can damage the existing HSPs in cancer cells. Through a two-pronged strategy of SGLT inhibitor and ROS storm, LIK066-loaded Cu SAzyme shows high efficiency for comprehensive removal of HSPs to realize mild PTT.

[Identification of genes involved in biosynthesis of paeoniflorin in Paeonia lactiflora based on transcriptome analysis].

Paeoniflorin, a representative pinane monoterpene glycoside, is the main active component and quality index of Paeoniae Radix Alba and Paeoniae Radix Rubra.The possible biosynthesis of paeoniflorin is as follows: GPP is derived from mevalonate(MVA) and/or 2-C-methyl-D-erythritol 4-phosphate(MEP) pathway(s) followed by the catalysis with terpene synthase, cytochrome P450(CYP450), UDP-glucuronosyltransferase(UGT), and acyltransferase(AT), respectively.This study aims to explore the genes rela-ted to the biosynthesis of paeoniflorin.To be specific, the cDNA libraries for flowers, leaves, and roots of Paeonia lactiflora were established and sequenced.A total of 30 609 open reading frames(ORFs) were yielded.Through functional annotation and expression analysis of all CYP450 genes in the transcriptome, 11 CYP450 genes belonging to CYP71 A and CYP71 D subfamilies and showing expression trend consistent with monoterpene synthase PlPIN that may be involved in paeoniflorin biosynthesis were screened out.Subsequently, 7 UGT genes and 9 AT genes demonstrating the expression trend consistent with PlPIN which were possibly involved in paeoniflorin biosynthesis were further screened by functional annotation analysis, full-length sequence analysis, expression analysis, and phylogeny analysis.This study provided a systematic screening method with smaller number of candidate genes, thus reducing the workload of functional gene verification.The result laid a foundation for analyzing the biosynthesis pathway of paeoniflorin and the formation mechanism.

Compared with Him or Her, I Am Not Good Enough: How to Alleviate Depression Due to Upward Social Comparison?

The present study primarily aims to examine the mediating role of core self-evaluation and the moderating role of personal growth initiative (PGI) in the relationship between upward social comparison and senior high school students' depression and to explore the gender difference in this association. A total of 721 Chinese senior high school students (61.16% boys; M = 16.21 years, SD = 1.07) completed measures of upward social comparison, core self-evaluation, personal growth initiative, and depression. Results showed a significant positive correlation between upward social comparison and depression. Core self-evaluation partially mediated this association, and a gender difference in the indirect effect was revealed; that is, the effect was shown to be stronger for girls than for boys. Moreover, for boys, the mediating effect of core self-evaluation was moderated by PGI, and the effect was more potent for individuals with high PGI than for those with low PGI. However, no moderating effect of PGI on the indirect effect was found for girls. These findings suggest that prevention and interventions focusing on reducing upward social comparison and enhancing core self-evaluation may alleviate adolescents' depression symptoms and that more attention should be given to girls with low core self-evaluation and boys with high PGI.

Optimization design of hump phenomenon of low specific speed centrifugal pump based on CFD and orthogonal test.

Aiming to eliminate the hump phenomenon in a low specific speed centrifugal pump, its structural parameters were optimized using the computational fluid dynamics method. Based on the [Formula: see text] turbulence model, a 3D steady analysis of the internal flow field was carried out. The [Formula: see text] orthogonal table was established, and four structural parameters, including the impeller outlet diameter, impeller outlet width, number of blades, and blade outlet angle, were selected as influencing factors. Nine orthogonal test schemes were developed and the results were analyzed through the weight matrix analysis method, obtaining the weight of the selected factors on the test results. The optimal scheme was selected according to the weight and the weight matrix analysis results have shown that the impeller outlet width had the dominant influence on the head, shaft power, and efficiency. Further, the blade number was the main influencing factor for shaft power and efficiency. The centrifugal pump flow control test bench was built to carry out the numerical simulation and test all the prototype and optimization pump indexes. Through the external characteristic test, it can be seen that the [Formula: see text] of the optimized pump is 87.889, which is 24.89% lower than that of the prototype pump, which effectively optimizes the hump phenomenon of the centrifugal pump. The experimental results have shown that in underrated working conditions, the working performance of the optimized pump was improved significantly. The head size was reduced by 1.424%, and the efficiency was increased by 7.896%. By optimizing the structural pump parameters, its jet-wake hydraulic loss was reduced, and the head curve hump phenomenon was effectively eliminated. All the performance indexes of the optimized pump were higher than those of the prototype, verifying both the accuracy and reliability of the orthogonal test and weight matrix analysis method. Finally, obtained results provide a reference for the structural design of high-performance centrifugal pumps.

Antiparasitical efficacy of sophoraflavanone G isolated from Sophora flavescens against parasitic protozoa Ichthyophthirius multifiliis.

Ichthyophthirius multifiliis, a global distributed protozoan parasite, causes "White spot disease" and leads to serious mortality of freshwater fish in aquaculture. The present study was conducted to assess the anti-I. multifiliis efficacy of active compound isolated from Sophora flavescens. The isolated active compound was identified as sophoraflavanone G (SG) with ESI-MS and NMR. In vitro tests, SG at concentrations of 0.5 mg/L and 2 mg/L resulted in death of all theronts and tomonts, respectively; SG at concentrations of 0.125 mg/L and 0.25 mg/L notably decreased theronts infectivity (p < 0.05). Additionally, the in vivo test results showed that a cumulative delivery of SG at concentration of 2 mg/L for 7 days protected fish from I. multifiliis infection. The 96-h LC50 (median lethal concentration) and safety concentration of SG to grass carp were 46.6 mg/L and 11.3 mg/L, respectively. The present work indicated that SG was a potential safe and effectively therapeutic agent in treating I. multifiliis.

Individual and mixtures of metal exposures in associations with biomarkers of oxidative stress and global DNA methylation among pregnant women.

BACKGROUND: Prenatal exposure to metals has been linked with adverse pregnancy outcomes. Oxidative stress and epigenetic changes are potential mechanisms of action. OBJECTIVES: We aimed to examine the associations of individual and mixtures of metal exposures with oxidative stress and DNA methylation among pregnant women. METHODS: We measured a panel of 16 metals and 3 oxidative stress biomarkers including 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-isoprostaglandin F2α (8-isoPGF2α) in urine from 113 pregnant women in a Chinese cohort. Biomarkers of global DNA methylation including Alu and long interspersed nucleotide element-1 (LINE-1) in cord blood were measured. Multivariable linear regression and Bayesian kernel machine regression (BKMR) models were separately applied to estimate the associations between individual and mixtures of metal exposures and biomarkers of oxidative stress and global DNA methylation. RESULTS: In single-metal analyses, we observed positive associations between 11 metals [arsenic (As), cadmium (Cd), thallium (Tl), barium (Ba), nickel (Ni), vanadium (V), cobalt (Co), zinc (Zn), copper (Cu), selenium (Se) and molybdenum (Mo)] and at least one of oxidative stress biomarkers (all FDR-adjusted P-values < 0.05). In mixture analyses, we found positive overall associations of metal mixtures with 8-OHdG and 8-isoPGF2α, and Se was the most important predictor. There was no evidence on associations of urinary metals as individual chemicals and mixtures with Alu and LINE-1 methylation. CONCLUSION: Urinary metals as individual chemicals and mixtures were associated with increased oxidative stress, especially Se.

Selenium Vacancy Engineering Using Bi2Se3 Nanodots for Boosting Highly Efficient Photonic Hyperthermia.

Despite bismuth-based energy conversion nanomaterials having attracted extensive attention for nanomedicine, the nanomaterials suffer from major shortcomings including low tumor accumulation, long internal retention time, and undesirable photothermal conversion efficiency (PCE). To combat these challenges, bovine serum albumin and folic acid co-modified Bi2Se3 nanomedicine with rich selenium vacancies (abbreviated as VSe-BS) was fabricated for the second near-infrared (NIR-II) light-triggered photonic hyperthermia. More importantly, selenium vacancies on the crystal planes (0 1 5) and (0 1 11) of VSe-BS with similar formation energies could be distinctively observed via aberration-corrected scanning transmission electron microscopy images. The defect engineering endows VSe-BS with enhanced conductivity, making VSe-BS possess outstanding PCE (54.1%) in the NIR-II biowindow and desirable photoacoustic imaging performance. Tumor ablation studies indicate that VSe-BS possesses satisfactory therapeutic outcomes triggered by NIR-II light. These findings give rise to inspiration for further broadening the biological applications of defect engineering bismuth-based nanomaterials.

Near-Infrared-Light-Responsive Copper Oxide Nanoparticles as Efficient Theranostic Nanoagents for Photothermal Tumor Ablation.

A theranostic nanoagent exhibits great promise to improve diagnostic accuracy and therapy efficacy. Herein, a kind of theranostic nanoagent based on poly(vinylpyrrolidone) (PVP)-protected ultrasmall Cu1.2O nanoparticles (Cu1.2O NPs) is developed by a facile liquid reduction method. Attributed to high near-infrared absorbance and good biocompatibility, Cu1.2O NPs have shown significant potential for photothermal therapy. Moreover, Cu1.2O NPs with a satisfactory T1 relaxivity coefficient (r1) can be well applied as outstanding MRI contrast agents and exhibit excellent magnetic resonance imaging (MRI) ability. In vivo treatments further demonstrate that Cu1.2O NPs could be well used as multifunctional theranostic nanoagents, which achieve precise MRI and a high photothermal antitumor effect. It is expected to further promote the research and application of copper-based nanoparticles as theranostic nanoagents for cancer therapy.

Engineering Gadolinium-Integrated Tellurium Nanorods for Theory-Oriented Photonic Hyperthermia in the NIR-II Biowindow.

Near-infrared (NIR) light-triggered hyperthermia has exhibited promising prospects in oncology therapy due to the unique merits including minimal invasiveness, monitorable, excellent therapeutic effect, and negligible side effects. Especially, the second NIR biowindow (NIR-II, 1000-1700 nm) with less absorbance and scattering by skin tissue, and deep tissue penetration, has received extensive attention for photonic hyperthermia. Unfortunately, the dissatisfactory photothermal conversion efficiency (PCE) and cumbersome preparation process of photo-driven heat conversion nanomaterials seriously hamper the future clinical application. To combat the aforementioned challenges, high imaging performance and desired therapeutic outcome 1D nanorods are constructed based on gadolinium-integrated tellurium nanorods (Te-Gd). In this system, magnetic resonance (MR) imaging and X-ray computed tomography (CT) imaging-guided photonic hyperthermia can be easily implemented in cooperation with Te-Gd. Importantly, Te-Gd possesses high PCE (41%) in the NIR-II biowindow because the transition of the excited electron can easily occur from the valence band (VB) to the conduction band (CB) on (1 0 1) and (1 0 2) crystal planes. Furthermore, the distinctive photostability, high tumor accumulation, as well as low systemic adverse effects of Te-Gd guarantee the potential in the clinic.

Correction to: microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11.

An amendment to this paper has been published and can be accessed via the original article.

Dual Role of Hepatic Macrophages in the Establishment of the Echinococcus multilocularis Metacestode in Mice.

Echinococcus multilocularis larvae, predominantly located in the liver, cause a tumor-like parasitic disease, alveolar echinococcosis (AE), that is characterized by increased infiltration of various immune cells, including macrophages, around the lesion that produces an "immunosuppressive" microenvironment, favoring its persistent infection. However, the role of hepatic macrophages in the host defense against E. multilocularis infection remains poorly defined. Using human liver tissues from patients with AE and a hepatic experimental mouse model of E. multilocularis, we investigated the phenotype and function of hepatic macrophages during the parasite infection. In the present study, we found that a large number of CD68+ macrophages accumulated around the metacestode lesion in the liver of human AE samples and that both S100A9+ proinflammatory (M1 phenotype) and CD163+ anti-inflammatory (M2 phenotype) macrophages were significantly higher in close liver tissue (CLT) than in distant liver tissue (DLT), whereas M2 macrophages represent the dominant macrophage population. Furthermore, E. multilocularis-infected mice exhibited a massive increase in macrophage (F4/80+) infiltration in the liver as early as day 5, and the infiltrated macrophages were mainly monocyte-derived macrophages (CD11bhi F4/80int MoMFs) that preferentially differentiated into the M1 phenotype (iNOS+) at the early stage of E. multilocularis infection and then polarized to anti-inflammatory macrophages of the M2 phenotype (CD206+) at the chronic stage of infection. We further showed that elimination of macrophages by treatment of mice with clodronate-liposomes before E. multilocularis infection impaired worm expulsion and was accompanied by a reduction in liver fibrosis, yielding a high parasite burden. These results suggest that hepatic macrophages may play a dual role in the establishment and development of E. multilocularis metacestodes in which early larvae clearance is promoted by M1 macrophages while persistent metacestode infection is favored by M2 macrophages.

Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway.

BACKGROUND: Larvae of Echinococcus granulosus (sensu lato) dwell in host organs for a long time but elicit only a mild inflammatory response, which indicates that the resolution of host inflammation is necessary for parasite survival. The recruitment of alternatively activated macrophages (AAMs) has been observed in a variety of helminth infections, and emerging evidence indicates that AAMs are critical for the resolution of inflammation. However, whether AAMs can be induced by E. granulosus (s.l.) infection or thioredoxin peroxidase (TPx), one of the important molecules secreted by the parasite, remains unclear. METHODS: The activation status of peritoneal macrophages (PMs) derived from mice infected with E. granulosus (sensu stricto) was analyzed by evaluating the expression of phenotypic markers. PMs were then treated in vivo and in vitro with recombinant EgTPx (rEgTPx) and its variant (rvEgTPx) in combination with parasite excretory-secretory (ES) products, and the resulting activation of the PMs was evaluated by flow cytometry and real-time PCR. The phosphorylation levels of various molecules in the PI3K/AKT/mTOR pathway after parasite infection and antigen stimulation were also detected. RESULTS: The expression of AAM-related genes in PMs was preferentially induced after E. granulosus (s.s.) infection, and phenotypic differences in cell morphology were detected between PMs isolated from E. granulosus (s.s.)-infected mice and control mice. The administration of parasite ES products or rEgTPx induced the recruitment of AAMs to the peritoneum and a notable skewing of the ratio of PM subsets, and these effects are consistent with those obtained after E. granulosus (s.s.) infection. ES products or rEgTPx also induced PMs toward an AAM phenotype in vitro. Interestingly, this immunomodulatory property of rEgTPx was dependent on its antioxidant activity. In addition, the PI3K/AKT/mTOR pathway was activated after parasite infection and antigen stimulation, and the activation of this pathway was suppressed by pre-treatment with an AKT/mTOR inhibitor. CONCLUSIONS: This study demonstrates that E. granulosus (s.s.) infection and ES products, including EgTPx, can induce PM recruitment and alternative activation, at least in part, via the PI3K/AKT/mTOR pathway. These results suggest that EgTPx-induced AAMs might play a key role in the resolution of inflammation and thereby favour the establishment of hydatid cysts in the host.

A highly active (102) surface-induced rapid degradation of a CuS nanotheranostic platform for in situ T1-weighted magnetic resonance imaging-guided synergistic therapy.

Polyvinylpyrrolidone-modified CuS nanocrystals (CuS NCs) with high photothermal conversion efficiency (46%) and pH and near-infrared (NIR) light-triggered degradation properties are a promising nanotheranostic platform for in situ magnetic resonance imaging (MRI)-guided synergistic photothermal and photodynamic therapy. On the one hand, the (102) surface of CuS NCs has a small bandgap based on density functional theory, which leads to high photothermal conversion efficiency. On the other hand, the S vacancy formation energy of the (102) surface is favourable. On entry into tumor cells through endocytosis, the S2- ions on the (102) surface of CuS NCs can be easily oxidized under the tumor microenvironment and 808 nm laser irradiation; then, a large amount of Cu+ ions can be released from CuS NCs and accelerate the degradation of nanocrystals. Cu+ ions can generate reactive oxygen species (ROS) under the tumor microenvironment and 808 nm laser irradiation. Meanwhile, the oxidation product Cu2+ ions can be generated from the oxidized Cu+ ions and applied for in situ T1-weighted magnetic resonance imaging. Moreover, the biodegradable CuS NCs possess a high tumor uptake and can be rapidly excreted with a low long-term retention/toxicity. Therefore, degradable and multifunctional CuS NCs are a safe and efficient candidate for the diagnosis and treatment of cancer.