The evolution of constitutively active humoral immune defenses in Drosophila populations under high parasite pressure.

Both constitutive and inducible immune mechanisms are employed by hosts for defense against infection. Constitutive immunity allows for a faster response, but it comes with an associated cost that is always present. This trade-off between speed and fitness costs leads to the theoretical prediction that constitutive immunity will be favored where parasite exposure is frequent. We selected populations of Drosophila melanogaster under high parasite pressure from the parasitoid wasp Leptopilina boulardi. With RNA sequencing, we found the evolution of resistance in these populations was associated with them developing constitutively active humoral immunity, mediated by the larval fat body. Furthermore, these evolved populations were also able to induce gene expression in response to infection to a greater level, which indicates an overall more activated humoral immune response to parasitization. The anti-parasitoid immune response also relies on the JAK/STAT signaling pathway being activated in muscles following infection, and this induced response was only seen in populations that had evolved under high parasite pressure. We found that the cytokine Upd3, which induces this JAK/STAT response, is being expressed by immature lamellocytes. Furthermore, these immune cells became constitutively present when populations evolved resistance, potentially explaining why they gained the ability to activate JAK/STAT signaling. Thus, under intense parasitism, populations evolved resistance by increasing both constitutive and induced immune defenses, and there is likely an interplay between these two forms of immunity.

Hunting Drosophila viruses from wild populations: A novel isolation approach and characterisation of viruses.

Metagenomic studies have demonstrated that viruses are extremely diverse and abundant in insects, but the difficulty of isolating them means little is known about the biology of these newly discovered viruses. To overcome this challenge in Drosophila, we created a cell line that was more permissive to infection and detected novel viruses by the presence of double-stranded RNA. We demonstrate the utility of these tools by isolating La Jolla virus (LJV) and Newfield virus (NFV) from several wild Drosophila populations. These viruses have different potential host ranges, with distinct abilities to replicate in five Drosophila species. Similarly, in some species they cause high mortality and in others they are comparatively benign. In three species, NFV but not LJV caused large declines in female fecundity. This sterilization effect was associated with differences in tissue tropism, as NFV but not LJV was able to infect Drosophila melanogaster follicular epithelium and induce follicular degeneration in the ovary. We saw a similar effect in the invasive pest of fruit crops Drosophila suzukii, where oral infection with NFV caused reductions in the fecundity, suggesting it has potential as a biocontrol agent. In conclusion, a simple protocol allowed us to isolate new viruses and demonstrate that viruses identified by metagenomics have a large effect on the fitness of the model organism D. melanogaster and related species.

Trans-regulatory changes underpin the evolution of the Drosophila immune response.

When an animal is infected, the expression of a large suite of genes is changed, resulting in an immune response that can defend the host. Despite much evidence that the sequence of proteins in the immune system can evolve rapidly, the evolution of gene expression is comparatively poorly understood. We therefore investigated the transcriptional response to parasitoid wasp infection in Drosophila simulans and D. sechellia. Although these species are closely related, there has been a large scale divergence in the expression of immune-responsive genes in their two main immune tissues, the fat body and hemocytes. Many genes, including those encoding molecules that directly kill pathogens, have cis regulatory changes, frequently resulting in large differences in their expression in the two species. However, these changes in cis regulation overwhelmingly affected gene expression in immune-challenged and uninfected animals alike. Divergence in the response to infection was controlled in trans. We argue that altering trans-regulatory factors, such as signalling pathways or immune modulators, may allow natural selection to alter the expression of large numbers of immune-responsive genes in a coordinated fashion.

Rapid and Complete Digestion of Refractory Geological Samples Using Ultrafine Powder for Accurate Analyses of Trace Elements.

Complete sample digestion is a prerequisite for acquiring high-quality analytical results for geological samples. Closed-vessel acid digestion (bomb) has typically been used for the total digestion of refractory geological samples. However, the long digestion time (4-5 days) and insoluble fluoride complexes still pose challenges for digesting refractory geological samples using this approach. In this study, an efficient and simplified digestion technique combining ultrafine powders from planetary ball milling with bomb digestion was developed for trace element analysis of refractory geological samples: peridotite and granitoid. The method shows two significant improvements compared with previous approaches. (1) By performing dry planetary ultrafine milling, the initial 200 mesh peridotite (<74 µm) could be reduced to 800 mesh (<20 µm) in 6 min at a ball-to-powder mass ratio of approximately 15 using 3 mm tungsten carbide milling balls. (2) Complete peridotite and granitoid dissolution were achieved in approximately 2 h, 60 times faster than what is achievable using previous methods (2 h vs 120 h). Moreover, ultrafine powders effectively suppressed insoluble fluoride formation during bomb digestion. A suite of peridotite and granitoid reference materials were measured to evaluate the stability of this method. This efficient, simple, and reliable sample digestion method could benefit geological, food, environmental, and other fields requiring solid sample decomposition via wet acid, fusion, combustion, or dry ashing.

A Triboelectric-Electromagnetic Hybrid Nanogenerator with Magnetic Coupling Assisted Waterproof Encapsulation for Long-Lasting Energy Harvesting.

Ocean energy harvesting based on a triboelectric nanogenerator (TENG) has great application potential, while the encapsulation of triboelectric devices in water poses a critical issue. Herein, a triboelectric-electromagnetic hybrid nanogenerator (TE-HNG) consisting of TENGs and electromagnetic generators (EMGs) is proposed to harvest water flow energy. A magnetic coupling transmission component is applied to replace traditional bearing structures, which can realize the fully enclosed packaging of the TENG devices and achieve long-lasting energy harvesting from water flow. Under the intense water impact, magnetic coupling reduces the possibility of internal gear damage due to excessive torque, indicating superior stability and robustness compared to conventional TENG. At the waterwheel rotates speed of 75 rpm, the TE-HNG can generate an output peak power of 114.83 mW, corresponding to a peak power density of 37.105 W m-3. After 5 h of continuous operation, the electrical output attenuation of TENG is less than 3%, demonstrating excellent device durability. Moreover, a self-powered temperature sensing system and a self-powered cathodic protection system based on the TE-HNG are developed and illustrated. This work provides a prospective strategy for improving the output stability of TENGs, which benefits the practical applications of the TENGs in large-scale blue energy harvesting.

A TrkB cleavage fragment in hippocampus promotes Depressive-Like behavior in mice.

Decreased hippocampal tropomyosin receptor kinase B (TrkB) level is implicated in the pathophysiology of stress-induced mood disorder and cognitive decline. However, how TrkB is modified and mediates behavioral responses to chronic stress remains largely unknown. Here the effects and mechanisms of TrkB cleavage by asparagine endopeptidase (AEP) were examined on a preclinical murine model of chronic restraint stress (CRS)-induced depression. CRS activated IL-1ß-C/EBPß-AEP pathway in mice hippocampus, accompanied by elevated TrkB 1-486 fragment generated by AEP. Specifi.c overexpression or suppression of AEP-TrkB axis in hippocampal CaMKIIα-positive cells aggravated or relieved depressive-like behaviors, respectively. Mechanistically, in addition to facilitating AMPARs internalization, TrkB 1-486 interacted with peroxisome proliferator-activated receptor-δ (PPAR-δ) and sequestered it in cytoplasm, repressing PPAR-δ-mediated transactivation and mitochondrial function. Moreover, co-administration of 7,8-dihydroxyflavone and a peptide disrupting the binding of TrkB 1-486 with PPAR-δ attenuated depression-like symptoms not only in CRS animals, but also in Alzheimer's disease and aged mice. These findings reveal a novel role for TrkB cleavage in promoting depressive-like phenotype.

Persistence of dissolved organic matter in sediments influenced by environmental factors：Implication for nutrition and carbon cycle.

The persistence of dissolved organic matter (DOM) plays a crucial role in the cycling and distribution of carbon and nutrients. Nonetheless, our understanding of how environmental alterations affect the persistence of sedimentary DOM remains incomplete. Excitation Emission Fluorescence Matrix-Parallel Factor Analysis (EEM-PARAFAC) was used to examine the fluorescence and compositional characteristics of hydrophilic and hydrophobic DOM (separated using XAD-8 resin) within sediments from twelve lakes and reservoirs. Fluorescence analysis indicated that DOM persistence is dependent on the proportions of the three components derived from PARAFAC. The Mantel test showed that climatic factors had the most significant impact on DOM persistence (Mantel's r = 0.46-0.54, Mantel's p = 0.001-0.007), while anthropogenic (Mantel's r = 0.24-0.32, Mantel's p = 0.03-0.05) and hydrological factors (Mantel's r = 0.03-0.22, Mantel's p = 0.06-0.40) had a somewhat lesser influence. Environmental changes resulted in a consistent decline in DOM persistence from Northeast to Southwest China, accompanied by an increase in gross primary productivity (GPP). Reduced DOM persistence due to climate, hydrological, and anthropogenic factors may lead to elevated concentrations of total phosphorus (TP), contributing to deteriorating water quality and events such as algal blooms. The decline in water quality due to reduced DOM persistence in lakes with high GPP can exacerbate the transition from carbon sinks to carbon sources. Consequently, the persistence of sedimentary DOM significantly influences nutrient and carbon cycling in lakes. Investigating DOM persistence in lakes across diverse geographic locations offers a new perspective on lake eutrophication and carbon emissions. Furthermore, it is crucial to develop targeted recommendations for lake restoration and management.

Enhanced phosphorus fixation in red mud-amended acidic soil subjected to periodic flooding-drying and straw incorporation.

Globally, red mud is a solid waste from the aluminum industry, which is rich in iron oxides. It is an effective soil amendment in agriculture that protects connected waters from legacy diffuse phosphorus (P) soil losses. However, other management practices such as flooding and drying and/or organic carbon inputs could potentially alter P fixation in these red mud-amended soils thereby releasing P to waters. The present study was designed and conducted to monitor the mobilization of P in a red mud-amended acidic soil subjected to periodic flooding-drying, straw incorporation, and a mix of both management practices. Sequential extraction and K edge X-ray absorption near-edge structure spectroscopy (k-XANES) were employed to distinguish P fractions/species and the Langmuir model was fitted to evaluate soil P sorption capacity. The content of labile P indicated by CaCl2-P was increased significantly by 101% and 28.7% in the straw incorporation and periodic flooding-drying treatments, while it decreased significantly by 22.3% in the combined periodic flooding-drying with straw incorporation treatment, compared with Control. The inherent phosphate contained in sorghum straw, and the enhanced iron (Fe) reduction and dissolution of Calcium (Ca)-bound P induced by straw addition contributed to mobilization of P in the straw incorporation treatment. In contrast, the increased poorly crystalline Al/Fe oxides-bound P and occluded Fe-bound P fraction in the combined periodic flooding-drying with straw incorporation treatment explains the decrease in CaCl2-P. Furthermore, the increased soil P sorption capacity and the decreased P desorption rate were also responsible for the reduced P loss risk in the treatment. The results of structural equation modelling (SEM) indicated that organically complexed Fe and Fe-bound P were directly affecting P mobilization in the amended soil. Overall, the present study shows that appropriate flooding-drying events coupled with straw incorporation could be a mitigation practice for stabilizing P in red mud-amended soil. However, before it can be applied on a wide scale, multi-point and field trials should be carried out to further evaluate actual environmental implications.

Factors associated with 25-hydroxyvitamin D level in Chinese hospitalized patients with systemic lupus erythematosus: a retrospective cohort study.

We aimed to investigate the factors associated with vitamin D deficiency and changes in 25 (OH)D levels, as well as the impact of those changes on disease activity and renal function among SLE patients. This retrospective cohort study was based on the medical records of SLE patients hospitalized between 2010 and 2021. We collected relevant information from this patient population. Logistic regression analysis was employed to determine the factors associated with vitamin D deficiency and increased 25 (OH)D levels, and we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) accordingly. At baseline, among the 1257 SLE patients, the median and interquartile range of 25 (OH)D levels were 14 (9, 20) ng/ml, with 953 (75.8%) patients exhibiting 25 (OH)D deficiency (< 20 ng/ml). The presence of 25 (OH)D deficiency was found to be associated with renal involvement and a high glucocorticoid (GC) maintenance dose. Among the 383 patients who were followed up for an average of 18 months, an increase of at least 100% in 25 (OH)D levels was positively associated with a decreased GC maintenance dose and vitamin D3 supplementation, with adjusted odds ratios(OR) (95% confidence interval [CI]) of 2.16 (1.02, 4.59) and 1300 (70, 22300), respectively. Furthermore, an increased level of 25 (OH)D was significantly associated with a decrease in the Disease Activity Index 2000 score and the urinary protein/creatinine ratio. Patients with SLE have low vitamin D levels, especially those with impaired kidney function. Increased 25 (OH)D levels can be achieved through supplementation with high doses of vitamin D3 and are associated with improvements in disease activity and the urinary protein/creatinine ratio.

CRISPR/Cas9-Mediated Genome Editing in Cancer Therapy.

The Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system, an RNA-based adaptive immune system found in bacteria and archaea, has catalyzed the development and application of a new generation of gene editing tools. Numerous studies have shown that this system can precisely target a wide range of human genes, including those associated with diseases such as cancer. In cancer research, the intricate genetic mutations in tumors have promoted extensive utilization of the CRISPR/Cas9 system due to its efficient and accurate gene editing capabilities. This includes improvements in Chimeric Antigen Receptor (CAR)-T-cell therapy, the establishment of tumor models, and gene and drug target screening. Such progress has propelled the investigation of cancer molecular mechanisms and the advancement of precision medicine. However, the therapeutic potential of genome editing remains underexplored, and lingering challenges could elevate the risk of additional genetic mutations. Here, we elucidate the fundamental principles of CRISPR/Cas9 gene editing and its practical applications in tumor research. We also briefly discuss the primary challenges faced by CRISPR technology and existing solutions, intending to enhance the efficacy of this gene editing therapy and shed light on the underlying mechanisms of tumors.

Simultaneous immobilization of ammonia and phosphorous by thermally treated sediment co-modified with hydrophilic organic matter and zeolite.

The use of calcined sediments (CS) for thin-layer capping is an environment-friendly technology for controlling nitrogen (N) or phosphorus (P) release. However, the effects of CS derived materials and efficiency in controlling the sedimentary N/P ratio have not been thoroughly investigated. While zeolite-based materials have been proven efficient to remove ammonia, it is limited by the low adsorption capacity of PO43-. Herein, CS co-modified with zeolite and hydrophilic organic matter (HIM) was synthesized to simultaneously immobilize ammonium-N (NH4+-N) and remove P, due to the superior ecological security of natural HIM. Studies on the influences of calcination temperature and composition ratio indicated that 600 °C and 40% zeolite were the optimal parameters leading to the highest adsorption capacity and lowest equilibrium concentration. Compared with doping with polyaluminum chloride, doping with HIM not only enhanced P removal but also achieved higher NH4+-N immobilization efficacy. The efficiency of zeolite/CS/HIM capping and amendment in prohibiting the discharge of N/P from sediments was assessed via simulation experiments, and the relevant control mechanism was studied at the molecular level. The results indicated that zeolite/CS/HIM can reduce 49.98% and 72.27% of the N flux and 32.10% and 76.47% of the P flux in slightly and highly polluted sediments, respectively. Capping and incubation with zeolite/CS/HIM simultaneously resulted in substantial reductions in NH4+-N and dissolved total P in overlying water and pore water. Chemical state analysis indicated that HIM enhanced the NH4+-N adsorption ability of CS owing to its abundant carbonyl groups and indirectly increased P adsorption by protonating mineral surface groups. This research provides a novel strategy to control sedimentary nutrient release by adopting an efficient and ecologically secure remediation method to rehabilitate eutrophic lake systems.

Effects of calcination on the environmental behavior of sediments by phosphorus speciation and interface characterization.

Dredged sediments derived from eutrophicated lakes poses hardness of sludge disposal and ecological risks. The proper pretreatment and utilization of dredged sediments presented a challenge. In this study, Dianchi Lake sediments were dredged, thermally treated and utilized as particle capping material in batch experiments. The effects of calcination on phosphorus speciation and sediment-water interface environment as well as P immobility mechanism were predominantly explored. The microstructures and chemical compositions of calcined sediments were investigated, indicating the porosity and mineralization components were greatly enhanced. The fractional analysis of phosphorus revealed that the calcination process reduced the percentage of unsteady phosphorus, transforming into stable inert phosphorus fractions (Al-P, Ca-P and Res-P), respectively, thereby minimized its mobility and eutrophication risk. Interestingly, calcination temperatures of 700 °C and 800 °C resulted in smaller releasing potentials and equilibrium phosphorus concentrations, despite having lower adsorption capacities than 550 °C. Furthermore, the results of redox potential monitoring showed that the thermally treated Dianchi Lake sediments could enhance the redox potential and dissolved oxygen in the surface sediment, indicating the amelioration of interfacial environment. The practical monitoring experiments confirmed the capping depressed the DTP to 0.031 mg L-1. The investigation of this study provided explicit evidence of Ca coupled P and aerobic Fe bound P strengthened the immobilization effects, and the development of sediment calcination demonstrates a promising strategy for alleviating the burden of endogenous pollution and improving aerobic environment, which are of great significance for lake ecological remediation.

Heterogeneity of molecular-level and photochemical of dissolved organic matter derived from decomposing submerged macrophyte and algae.

Aquatic macrophytes and algae are the most important sources of autochthonous dissolved organic matter (DOM), and their transformation and reuse significantly affect aquatic ecosystem health. In this study, Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was used to identify the molecular features between submerged macrophyte-derived DOM (SMDOM) and algae-derived DOM (ADOM). The photochemical heterogeneity between SMDOM and ADOM by UV254-irradiation and their molecular mechanism were also discussed. The results showed that the molecular abundance of SMDOM was dominated by lignin/CRAM-like structures, tannins, and concentrated aromatic structures (sum of 91.79%), while that of ADOM was dominated by lipids, proteins, and unsaturated hydrocarbons (sum of 60.30%). UV254-radiation resulted in a net reduction of tyrosine-like, tryptophan-like and terrestrial humic-like, and conversely a net production of marine humic-like. The light decay rate constants obtained by the multiple exponential function model fitting revealed that both tyrosine-like and tryptophan-like components of SMDOM could be rapidly and directly photodegraded, while the photodegradation of tryptophan-like in ADOM depended on the production of photosensitizers. The photo-refractory fractions of both SMDOM and ADOM were as follows: humic-like > tyrosine-like > tryptophan-like. Our results provide new insights into the fate of autochthonous DOM in aquatic ecosystems where "grass-algae" coexist or evolve.

Supplying amendments alleviates aluminum toxicity and regulates cadmium accumulation by spinach in strongly acidic soils.

Al toxicity and Cd pollution are key limiting factors for agricultural production in the acidic soils in China. The application of amendments is an effective and promising measure for remediating strongly acidic Cd-contaminated soils. However, the information on applying amendments for alleviating Al toxicity and regulating plant Cd accumulation is still rare. Here, oyster shell (OS), red mud (RM), hydroxyapatite (HAP), and biochar (BC) at 30 g kg-1 were investigated for alleviating Al toxicity and decreasing Cd accumulation in spinach plants. The results showed that four amendments significantly increased soil pH, and reduced soil exchangeable Al3+ and DTPA-Cd, promoted spinach growth (P < 0.05). Al(OH)30 and Al-HA were the main forms of active Al in soil. The BC and OS were more effective to alleviate Al toxicity but significantly (P < 0.05) increased Cd accumulation in spinach. RM and HAP effectively reduced the uptake of Cd by spinach plants as well as alleviated Al toxicity (P < 0.05). Bivariate correlation analysis and the partial least squares path modeling analysis indicated that soil exchangeable Al3+ was the main limiting factor for biomass production. Our study demonstrated that HAP could significantly alleviate Al toxicity, promote spinach growth, and decrease Cd accumulation in strongly acidic Cd-contaminated soils. Besides, OS and BC effectively alleviated soil Al toxicity leading to promoting the growth of spinach. Compared with CK, RM treatment significantly reduced soil Cd bioavailability (61.2%) and decreased Cd concentration and uptake of spinach plants by 90.0% and 50.7%. These results indicated that RM could be used as an efficient amendment in Cd contaminated.

Characterizing the impact of Three Gorges Dam on the Changjiang (Yangtze River): A story of nitrogen biogeochemical cycling through the lens of nitrogen stable isotopes.

The alterations of nitrogen sources and cycling within the Three Gorges Reservoir (TGR) and downstream the Changjiang were investigated to understand the impacts of the construction of the Three Gorges Dam (TGD) and anthropogenic inputs from the associated watershed. Water samples collected in October 2016 were analyzed for hydrologic parameters, nutrient concentrations, and stable isotopes of nitrate (NO3-), ammonium (NH4+) and particulate matter. Nitrate dual stable isotope values ranged from +5.8‰ to +7.1‰ and -1.9‰ to +0.4‰ for δ15N and δ18O, respectively. δ15N values in particulate nitrogen (PN) ranged from +0.5‰ to +8.5‰, with slightly lower values before the dam. δ15N-NH4+ values ranged between +10.5‰ and +19.4‰, likely reflecting the presence of ammonium assimilation throughout the TGR. The contribution of different nitrogen sources was calculated using a Bayesian mixing model. These sources, including soil organic nitrogen, ammonium fertilizer, and sewage effluent, contributed to elevated DIN concentrations within the TGR (83.2 µM-178.5 µM). The construction of the dam has also likely induced changes in the river environment such as ammonium assimilation in the surface waters and nitrification and/or remineralization within the deep waters of the TGR. Overall, during this investigation period, the TGR acted as a sink of PN (retaining 29%), yet negligibly influenced levels of TDN with ~96.5% of TDN exported to the downstream Changjiang and estuary. It is important to understand the long-term impacts of the TGD on the ecological environment of the Changjiang. This study highlights the influence that anthropogenic nitrogen sources have on the natural biogeochemical cycling within the TGR, showing the urgent need to reduce anthropogenic nitrogen pollution.

Magnetic hydrogel with long in situ retention time for self-regulating temperature hyperthermia.

Aim: Magnetic hydrogels (MHGs) have been proposed to avoid the redistribution and loss of magnetic nanoparticles (MNPs) when administrated by intratumoral injection. However, the requirement of complex cooling systems and temperature monitoring systems still hinder the clinical application of MHGs. This study investigates the feasibility of developing an MHG to realize the self-regulation of hyperthermia temperature. Methods: The MHG was developed by dispersing the MNPs with self-regulating temperature property into the temperature-sensitive hydrogel through physical crosslinking. The MHG's gelation temperature was tested by measuring the storage modulus and loss modulus on a rotational rheometer. The biocompatibility of the MHG and MNPs was characterized by CCK-8 assay against HaCaT cells. The in vivo magnetic heating property was examined through monitoring the temperature in the MHG on mice back upon the application of the alternating magnetic field (400 ± 5 Oe, 100 ± 5 kHz) every week for successive six weeks. Results: The gelation temperature of the MHG falls in 28.4°C-37.4°C. At in vivo applied concentration of 80 mg/mL, the MHG exhibits over 80% cell viability after 72 h, significantly higher than 50% cell viability of the MNPs (p<0.001). The MHG's stable magnetic hyperthermia temperatures in vivo are in the range of 43.4°C-43.8°C. Conclusions: The developed MHG can be injected using a syringe and will solidify upon body temperature. The biocompatibility is improved after the MNPs being made into MHG. The MHG can self-regulate the temperature for six weeks, exhibiting application potential for self-regulating temperature hyperthermia.

Morphometric evaluation of the alveolar bone around central incisors during surgical orthodontic treatment of high-angle skeletal class III malocclusion.

OBJECTIVES: To evaluate morphometric characteristics of alveolar bone around the incisors of high-angle skeletal class III patients receiving surgical orthodontic treatment. SETTING AND SAMPLE POPULATION: Thirty high-angle skeletal class III patients (mean age, 20.94 ± 3.25 years) underwent cone-beam computed tomography before treatment (T0), after pre-surgical orthodontic treatment (T1) and after treatment (T2). MATERIALS AND METHODS: The vertical bone level (VBL), alveolar bone thickness (ABT), alveolar bone area (ABA) and position of upper and lower central incisors (UCIs and LCIs) were evaluated. The ABT included five levels (4, 6, 8 mm from the cemento-enamel junction, midroot and root apex level). One-way repeated measures ANOVA with Bonferroni's multiple-comparison test and matched t test was performed to compare variables. RESULTS: Before treatment, the average labial ABT was approximately 1 mm in UCIs and 0.38 ~ 0.79 mm in LCIs, and the VBL of the LCIs was over 2 mm. After treatment, the VBL increased by 2.19 ± 1.96 mm (P < .001) on the lingual side of UCIs and 2.78 ± 2.29 mm and 3.09 ± 2.52 mm on the labial and lingual sides of LCIs, respectively (all P < .001). ABT at every level decreased significantly, decreasing by 1.66 ± 1.93 mm at the 8 mm level of UCIs and 1.06 ± 1.01 mm at the apex of LCIs (P < .001). The lingual ABA of UCIs and LCIs decreased by over 50% (P < .001). CONCLUSIONS: In high-angle skeletal class III patients, the condition of alveolar bone around UCIs and LCIs was extremely poor before treatment. Further alveolar bone resorption occurred during surgical orthodontic treatment. More attention should be paid to the movement of anterior teeth in cases of severe alveolar bone loss.

Lipid Metabolism in Tumor-Associated Myeloid-Derived Suppressor Cells.

Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of myeloid cells with immature phenotypes and immunosuppressive functions. This population of cells has been extensively studied over the past decade owing to an increasing recognition of their pivotal role in pathological conditions including cancers, infectious diseases, sepsis, and autoimmune diseases. Various treatments targeting MDSCs are currently under development or in clinical trials with the aim to restore functional immunity against tumors or pathogens. Recent advances in immune metabolism demonstrate the role of metabolic pathways, especially lipid metabolism, in the differentiation and function of MDSCs in tumor environments. Therefore, a comprehensive understanding of lipid metabolism in MDSCs would facilitate the development of novel therapies against tumors through metabolic reprograming of MDSCs.

Circular RNA hsa_circ_0005909 modulates osteosarcoma progression via the miR-936/HMGB1 axis.

BACKGROUND: Osteosarcoma (OS) is the most common bone malignant tumor in children, youth, and adolescents. Circular RNA hsa_circ_0005909 (circ_0005909) is involved in the progression of OS. Nevertheless, there are few reports on the role and mechanism of circ_0005909 in OS. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was executed to examine the expression of circ_0005909, miR-936, and High Mobility Group Box 1 (HMGB1) mRNA in OS tissues and cells. Cell viability, colony formation, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8), cell colony formation, or transwell assays. Cell epithelial-mesenchymal transition (EMT) and HMGB1 protein levels were assessed through western blot analysis. The role of circ_0005909 on tumor growth in vivo was verified by xenograft assay. The relationship between circ_0005909 or HMGB1 and miR-936 was confirmed with the dual-luciferase reporter or RNA pull-down assays. RESULTS: Circ_0005909 level was upregulated in OS tissues and cells. OS patients with high circ_0005909 expression had a lower survival rate. Circ_0005909 inhibition reduced tumor growth in vivo and constrained cell viability, colony formation, migration, invasion, and EMT of OS cells in vitro. Furthermore, circ_0005909 served as a sponge for miR-936 and the repressive impacts of circ_0005909 silencing on malignant behaviors of OS cells were abolished by miR-936 inhibitors. Also, HMGB1 acted as a target for miR-936 and was modulated by circ_0005909 via miR-936. Additionally, HMGB1 overexpression restored the inhibitory influence on the malignant behaviors of OS cells mediated by circ_0005909 inhibition. CONCLUSIONS: Circ_0005909 inhibition impeded the progression of OS via downregulating HMGB1 via sponging miR-936.

Histamine releasing factor and elongation factor 1 alpha secreted via malaria parasites extracellular vesicles promote immune evasion by inhibiting specific T cell responses.

Protozoan pathogens secrete nanosized particles called extracellular vesicles (EVs) to facilitate their survival and chronic infection. Here, we show the inhibition by Plasmodium berghei NK65 blood stage-derived EVs of the proliferative response of CD4+ T cells in response to antigen presentation. Importantly, these results were confirmed in vivo by the capacity of EVs to diminish the ovalbumin-specific delayed type hypersensitivity response. We identified two proteins associated with EVs, the histamine releasing factor (HRF) and the elongation factor 1α (EF-1α) that were found to have immunosuppressive activities. Interestingly, in contrast to WT parasites, EVs from genetically HRF- and EF-1α-deficient parasites failed to inhibit T cell responses in vitro and in vivo. At the level of T cells, we demonstrated that EVs from WT parasites dephosphorylate key molecules (PLCγ1, Akt, and ERK) of the T cell receptor signalling cascade. Remarkably, immunisation with EF-1α alone or in combination with HRF conferred a long-lasting antiparasite protection and immune memory. In conclusion, we identified a new mechanism by which P. berghei-derived EVs exert their immunosuppressive functions by altering T cell responses. The identification of two highly conserved immune suppressive factors offers new conceptual strategies to overcome EV-mediated immune suppression in malaria-infected individuals.