The effect of goethite aging on Cd adsorption: Constraints of mineral condensation and surface site density.

Iron (hydr)oxides, as natural geosorbents, play a crucial role in retaining toxic heavy metals, and their aging process greatly influences heavy metals distributions and migration in soil systems. However, limited attention has been given to the interaction between heavy metals and crystalline-aged goethite. In this study, we investigated the sorption behavior and sorption mechanism of cadmium (Cd) with freshly synthesized or aged goethite. We quantified the total Cd sorption load, as well as the proportion of Cd with different sorption strengths on minerals. It has been found that in different aged goethite samples, approximately 71.3-84.7 % of Cd is strongly bound (bidentate inner-sphere complexes) and 16.0 % to 26.4 % of Cd is weakly bound (electrostatic adsorption and partially through monodentate inner-sphere complexes) by goethite. This observation is consistent with the distribution characteristics of Cd species fitted by the charge distribution and multisite surface complexation model. Additionally, the total Cd load and strongly bound Cd content on goethite aged at pH 7.5 decreased with extended aging time. Upon combining the mineral characterization analysis and surface hydroxyl density calculation, we found that the morphology transformation and the deterioration in sorption ability on goethite results from a condensation process through a surface hydroxyl oxolation reaction on the {110} facet between adjacent goethite crystals during the aging process at pH 7.5. This condensation process causes goethite to lose many hydroxyl sites, which is the dominant reason for the decrease in inner-sphere complexed Cd. The amount of weakly bound Cd decreases slightly with aging, because the decrease in inner-sphere complexed Cd is not conducive to balancing the positively charged mineral surface, resulting in a slight reduction in the amount of Cd adsorbed through electrostatic attractions.

Efficacy Analysis of Arthroscopic Surgery Combined with Intra-articular Chitosan Injection for Stage II-III Knee Osteoarthritis in Patients with Abnormal Body Weight.

OBJECTIVE: Weight is an influential factor in knee osteoarthritis (KOA). However, the effect of abnormal body weight on chitosan's efficacy in treating KOA is unclear. This study aimed to explore the differences in the effectiveness of arthroscopic surgery combined with intra-articular chitosan injection for KOA in patients with abnormal body weight. METHODS: Patients with stage II-III KOA (Kellgren-Lawrence rating, K-L) undergoing arthroscopic surgery were recruited for this clinical study from January 2020 to September 2021. Based on body mass index (BMI) and intra-articular chitosan injection, patients with KOA undergoing arthroscopic surgery (138 patients) were divided into four groups: low-weight-non-injection (Lw-N, BMI <18.5); low-weight-chitosan injection (Lw-CS, BMI <18.5); overweight-non-injection (Ow-N, BMI ≥25); overweight-chitosan injection (Ow-CS, BMI ≥25). A 2-year follow-up was conducted to evaluate various indicators, including the visual analogue scale (VAS) and the Western Ontario and McMaster Universities osteoarthritis index score (WOMAC). Statistical analyses were performed using relevant parametric or non-parametric tests. RESULTS: In total, 138 patients with KOA were included in this study. There were no significant differences in gender, age, and incidence of chronic residual pain after arthroscopy among the four groups (p > 0.05). The proportion of patients undergoing subsequent knee arthroplasty during the 2-year follow-up period was significantly higher in the Ow-CS group (20/35) than in the Lw-CS group (12/39) (p < 0.05). The K-L rating showed an overall increasing trend over time, with the K-L rating in the Ow-N and Ow-CS groups significantly higher than that in the Lw-CS group at the final follow-up (p < 0.05). VAS and WOMAC scores significantly decreased at 1 and 3 months post-arthroscopy and then increased. One month after arthroscopy, VAS was significantly lower (p < 0.05) in the intra-articular chitosan injection groups (Lw-CS and Ow-CS) compared with the non-injection groups (Lw-N and Ow-N). VAS was lower in the Ow-CS group than in the Lw-CS group (p < 0.05). There was no significant difference in WOMAC between the intra-articular chitosan injection and non-injection groups at each time point (Lw-N vs. Lw-CS, Ow-N vs. Ow-CS, p > 0.05). CONCLUSION: Arthroscopic surgery combined with intra-articular chitosan injection shows short-term positive effects in treating KOA. Intra-articular chitosan injection appears to have a greater short-term pain relief effect in obese patients.

Application of GWAS summary data and drug-induced gene expression profiles of neural progenitor cells in psychiatric drug prioritization analysis.

Common psychiatric disorders constitute one of the most substantial healthcare burdens worldwide. However, drug development in psychiatry remains hampered partially due to the lack of approaches to estimating drugs that can simultaneously modulate the expression of a nontrivial fraction of disease susceptibility genes. We proposed a new drug prioritization strategy under the framework of our previously proposed phenotype-associated tissues estimation approach (DESE) by investigating the drugs' selective perturbation effect on disease susceptibility genes. Based on the genome-wide association study summary data and drug-induced gene expression profiles of neural progenitor cells, we applied this strategy to prioritize candidate drugs for schizophrenia, depression and bipolar I disorder and identified several known therapeutic drugs among the top-ranked drug candidates. Also, our results revealed that the disease susceptibility genes involved in the selective gene perturbation analysis were enriched with many biologically sensible function terms and interacted with known therapeutic drugs. Our results suggested that selective gene perturbation analysis could be a promising starting point to prioritize biologically sensible drug candidates under the "one drug, multiple targets" paradigm for the drug development of common psychiatric disorders.

Course-based intra-articular injection of medical chitosan mitigates excessive deposition of triacylglycerides in the synovial tissue of the knee osteoarthritis.

BACKGROUND: This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue. METHODS: 60 patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), VAS, WOMAC scoring, and AKS scoring were conducted. RESULTS: Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the pre-surgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced a slightly more pronounced decline in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids. CONCLUSION: Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.

Long-term warming and decreased precipitation regulated microbial community structure and potential function through enhanced predator-prey relationships in the Tibetan Plateau.

Global climate change can shape the interactions among soil microbes and, in turn, mediate ecosystem functions. However, how these interactions were regulated remains to be investigated. This study utilized 16S rRNA, ITS, and 18S rRNA high-throughput sequencing to investigate the effects of simulated warming and precipitation changes on the major components of soil micro-food webs in the Qinghai-Tibetan Plateau through a field experiment. Adonis and non-metric multidimensional scaling (NMDS) analyses showed that compositions of bacteria, fungi and protists were all affected by changes in temperature and precipitation. Correlation and cross-trophic network analyses revealed that warming and decreased precipitation, both separately and together, enhanced the relationships between bacteria and protists, especially protistan predators. We found that the modified stochasticity ratio of the bacterial community assembly was best predicted by protists. The potential functional structures of bacteria were positively correlated with protistan predators under warming and decreased precipitation condition, suggesting enhanced predator-prey relationships between protists and bacteria might further influence the potential functional characteristics of bacterial communities. Our study indicated that climate change altered bacterial compositional and functional structure via enhanced predator-prey interactions. Therefore, in the context of global climate change, broader and more comprehensive studies on protist-regulated soil bacterial and fungal communities are imperative.

Self-Cleaning Antibacterial Composite Coating of Fluorinated Acrylic Resin and Ag/SiO2 Nanoparticles with Quaternary Ammonium.

With improvements in living standards, the demand for antibacterial self-cleaning coatings has significantly increased. In this work, self-cleaning coatings with antibacterial properties were fabricated by spray-coating a composite of fluorinated acrylic resin and Ag/SiO2 nanoparticles with quaternary ammonium salts. The synergistic action of the quaternary ammonium salts and silver nanostructures caused the coating to show a dual antibacterial effect. The Ag/SiO2 nanoparticles roughened the coating's surface and, in combination with the fluorinated chains, provided the surface a superhydrophobic self-cleaning property with a contact angle of 156° and a sliding angle of less than 2°. Notably, the composite coating withstood 100 abrasion cycles without losing its superhydrophobicity and the contact angle is still exceeded 150° after 60 h of immersion solutions with different pH values, demonstrating outstanding wear resistance and acid/alkali stability. The incorporation of nanostructured antibacterial agents was effective in improving the roughness and antibacterial properties of the low-surface-energy resin, resulting in a self-cleaning antibacterial composite coating. This method may pave a new route for the design of functional coating materials with excellent overall performance.

Diagnostic value of corneal optical densitometry in keratoconus.

PURPOSE: To investigate the clinical significance of the correlation between optical densitometry and both biomechanical and morphological parameters in keratoconus (KC) and to verify the diagnostic value of optical densitometry in KC. METHOD: This cross-sectional study included 436 eyes of 295 patients with KC. Corneal optical densitometry, morphological parameters and biomechanical parameters were measured. Spearman's correlation analysis was employed to investigate the association between optical densitometry and both biomechanical and morphological parameters. RESULT: Optical densitometry of the anterior (0-2 mm and 2-6 mm), central (0-2 mm), posterior (2-6 mm) and total (2-6 mm) layers correlated positively with SPA1, while the posterior layer (0-2 mm) correlated negatively. Optical densitometry of the anterior layers 2-6 mm, 6-10 mm, and the central layer 6-10 mm negatively affected AL1, while the posterior layer 0-2 mm positively affected it. Optical densitometry of the anterior, central, and posterior layers 0-2 mm and 2-6 mm positively influenced the morphological parameters K1F, K2F, KmF and the absolute values of K1B, K2B, KmB. Optical densitometry of the center (0-2 mm) and posterior (2-6 mm) layers negatively influenced TCT. Optical densitometry of the anterior (0-2 mm and 2-6 mm), center (0-2 mm), posterior (2-6 mm) and total (2-6 mm) layers correlated positively with ACE and PCE, whereas the posterior layer (0-2 mm) correlated negatively. CONCLUSION: Optical densitometry was correlated with biomechanical and morphological parameters in keratoconus, suggesting its potential as a diagnostic indicator for assessing keratoconus progression and treatment efficacy.

A storage mechanism of data access record on consortium chain based on master-slave blocks.

Although data on the blockchain cannot be tampered with, malicious access by insiders can also lead to data leakage. Access records of block are an important basis for tracing the source of data breaches; however, access records themselves may be tampered with. Therefore, it is important to study how to protect the block access records. So far, the protection of block access records has not received much attention. To make block access records a protected data resource as well, this paper proposes a storage mechanism of data access record on consortium chain based on master-slave blocks. In this mechanism, the master block is used to store data resources, and the slave block of the master block is used to store access records of the master block. This method ensures that the slave block has the security characteristics of the single chain block, making the access record traceable and immutable. The storage mechanism's viability is confirmed by real-world experimentation. The proposed mechanism outperforms the single chain in terms of data query performance, according to the testing results on public data sets.

Effects of exercise dose based on the ACSM recommendations on patients with post-stroke cognitive impairment: a systematic review and meta-analyses.

Purpose: This review aimed to assess the impact of different exercise dosages on cognitive function in individuals with post-stroke cognitive impairment (PSCI). Methods: Four electronic databases-Embase, PubMed, Web of Science, and Cochrane Library-were systematically searched from inception to 01 January 2024, focusing on the impact of exercise therapy on cognitive function in individuals with PSCI. Only randomized controlled trials meeting the criteria were included. The exercise therapy dose and adherence were evaluated following the American College of Sports Medicine (ACSM) guidelines, categorized into a high compliance group with ACSM recommendations and a low or uncertain compliance group. A random-effects model compared the effect of ACSM compliance on cognitive function in individuals with PSCI, with the effect size represented by the standardized mean difference (SMD) and a 95% confidence interval (CI). Results: In total, 18 studies meeting the criteria were included, with data from 1,742 participants. The findings suggested a beneficial effect of exercise on cognitive function in individuals with PSCI [SMD = 0.42, 95% CI (0.20, 0.65)]. Ten studies were categorized as the "high adherence group" and eight in the "low or uncertain adherence group" based on the ACSM recommendations. The subgroup analysis revealed that the SMD of the high compliance group was 0.46 (95% CI: 0.10, 0.82) (p = 0.01), while the SMD of the low or uncertain compliance group was 0.38 (95% CI: 0.07, 0.70) (p = 0.02). Conclusion: Our study indicates the beneficial impact of exercise for patients with PSCI over no exercise. Furthermore, high adherence to the exercise dose recommended by ACSM guidelines demonstrated a more substantial improvement in cognitive function than low or uncertain adherence in patients with PSCI. Systematic Review Registration: https:// www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42023487915.

Simultaneous mitigation of heterocyclic aromatic amines and advanced glycation end products in roasted beef patties by plasma-activated water: Effects and mechanisms.

Heterocyclic aromatic amines (HAAs) and advanced glycation end products (AGEs) are hazardous substances produced when food is heated. In this study, the ability of plasma-activated water (PAW) to simultaneously mitigate production of HAAs and AGEs in roasted beef patties was investigated. Assays of free radicals, lipid peroxidation, and active carbonyls were used to analyze the mechanisms. PAW treatment decreased the contents of free HAAs, free AGEs, bound HAAs, and bound AGEs to 12.65 ng/g, 0.10 µg/g, 297.74 ng/g, and 4.32 µg/g, with the inhibition rates of 23.88%, 23.08%, 11.02%, and 8.47%, respectively. PAW treatment decreased HAAs and AGEs and mitigated their increase during storage. The decrease of HAAs and AGEs in PAW-treated samples was correlated with the enhancement of antioxidant capacity. The increase of free radical scavenging ability by PAW treatment led to the decrease of lipid peroxidation and the decrease of active carbonyls, HAAs, and AGEs in meat products.

Time-varying similarity of neural responses to musical tension is shaped by physical features and musical themes.

The similarity of understanding is important for music experience and communication, but little is understood about the sources of this common knowledge. Although neural responses to the same piece of music are known to be similar across listeners, it remains unclear whether this neural response similarity is linked to musical understanding and the role of dynamic musical attributes in shaping it. Our study addresses this gap by investigating the relationship between neural response similarity, musical tension, and dynamic musical attributes. Using electroencephalography-based inter-subject correlation (EEG-ISC), we examined how the neural response similarity among listeners varies throughout the evaluation of musical tension in the first movement of Beethoven's Piano Sonata No. 8. Participants continuously rated the degree of alignment between musical events and their expectations, while neural activity was recorded using electroencephalography (EEG). The results showed that neural response similarity fluctuated in tandem with musical tension, with increased similarity observed during moments of heightened tension. This time-varying neural response similarity was influenced by two dynamic attributes contributing to musical tension: physical features and musical themes. Specifically, its fluctuation was driven by physical features, and the patterns of its variation were modulated by musical themes, with similar time-varying patterns observed across similar thematic materials. These findings offer valuable insight into the role of dynamic musical attributes in shaping neural response similarity, and reveal an important source and mechanism of shared musical understandings.

R-MFE-TCN: A correlation prediction model between body surface and tumor during respiratory movement.

BACKGROUND: 2D CT image-guided radiofrequency ablation (RFA) is an exciting minimally invasive treatment that can destroy liver tumors without removing them. However, CT images can only provide limited static information, and the tumor will move with the patient's respiratory movement. Therefore, how to accurately locate tumors under free conditions is an urgent problem to be solved at present. PURPOSE: The purpose of this study is to propose a respiratory correlation prediction model for mixed reality surgical assistance system, Riemannian and Multivariate Feature Enhanced Temporal Convolutional Network (R-MFE-TCN), and to achieve accurate respiratory correlation prediction. METHODS: The model adopts a respiration-oriented Riemannian information enhancement strategy to expand the diversity of the dataset. A new Multivariate Feature Enhancement module (MFE) is proposed to retain respiratory data information, so that the network can fully explore the correlation of internal and external data information, the dual-channel is used to retain multivariate respiratory feature, and the Multi-headed Self-attention obtains respiratory peak-to-valley value periodic information. This information significantly improves the prediction performance of the network. At the same time, the PSO algorithm is used for hyperparameter optimization. In the experiment, a total of seven patients' internal and external respiratory motion trajectories were obtained from the dataset, and the first six patients were selected as the training set. The respiratory signal collection frequency was 21 Hz. RESULTS: A large number of experiments on the dataset prove the good performance of this method, which improves the prediction accuracy while also having strong robustness. This method can reduce the delay deviation under long window prediction and achieve good performance. In the case of 400 ms, the average RMSE and MAE are 0.0453  and 0.0361 mm, respectively, which is better than other research methods. CONCLUSION: The R-MFE-TCN can be extended to respiratory correlation prediction in different clinical situations, meeting the accuracy requirements for respiratory delay prediction in surgical assistance.

ZIF-8 Used for the Selective Recovery of Heavy Rare Earth Elements from Mining Wastewater.

In this study, a sample of 2-methylimidazole zinc salt (ZIF-8) demonstrated high selectivity for the recovery of heavy rare earth elements (REEs) from real rare earth mining wastewater. Results show that the distribution coefficient values of Y3+ (4.02 × 104 mL·g-1), Gd3+ (7.8 × 104 mL·g-1), and Dy3+ (6.8 × 104 mL·g-1) are orders of magnitude higher than those of K+ (359.51 mL·g-1), Mn2+ (266.67 mL·g-1), Ca2+ (396.42 mL·g-1), and Mg2+ (239.48 mL·g-1). Moreover, the desorption efficiency of heavy REEs exceeded 40%. Advanced characterizations and density functional theory (DFT) calculations were utilized to elucidate that the heavy REEs were more likely to bind to the nitrogen atoms of imidazole groups on ZIF-8 compared to non-REEs. Furthermore, the adsorption and desorption of heavy REEs primarily depend on the chemical interaction confirmed by adsorption kinetics, isotherm model, and thermodynamic analysis, which involves the dissociation of water and the formation of REE-O bonds. Finally, the ZIF-8 exhibits a remarkable recovery efficiency of over 40% for heavy REEs in column tests conducted over 7h. The findings reported here provide new insights into the selective recovery of heavy REEs from real mining wastewater.

Terrestrial vegetation carbon sink analysis and driving mechanism identification in the Qinghai-Tibet Plateau.

The estimation of terrestrial carbon sinks in the Qinghai-Tibet Plateau (QTP) still faces significant uncertainties, and the spatiotemporal dynamics of terrestrial carbon sinks along altitudinal gradients remain unexplored. Moreover, the driving mechanisms of terrestrial carbon sinks at the watershed scale in the QTP continue to be lacking. To address these research gaps, based on multi-source remote sensing data and meteorological data, this study calculated the Net Ecosystem Productivity (NEP) in the QTP from 2000 to 2020 using the Modis NPP-soil respiration model. Through the coefficient of variation (CV), the Mann-Kendall test (MK), and the spatial autocorrelation methods, the spatial distribution pattern and spatiotemporal trends of NEP were investigated. Employing a pixel accumulation method, the variation of NEP along altitudinal gradients was explored. Grey relation analysis, Pearson correlation analysis, and Geographical detector (GD) were used to investigate the driving mechanisms of NEP at the watershed scale. Results showed that: (1) the terrestrial ecosystem in the QTP served as a carbon sink, which produced a total of 2.04 Pg C from 2000 to 2020, and the multi-year average of total carbon sinks was 96.92 Tg C; (2) the spatial distribution of NEP shows a decreasing change from southeast to northwest, and the clustering characteristic of NEP is significant at the watershed scale; (3) the elevation of 4507 m we proposed is likely to be a key threshold for biophysical processes of the terrestrial ecosystems in the QTP; (4) the fluctuation and change trend of carbon sources and carbon sinks show significant differences between the East and West; (5) at the watershed scale, precipitation and temperature play a dominant role in the variation of NEP, while the impact of human activities on NEP variation is weak. Our study aims to address the existing knowledge gaps and provide valuable insights into the management of terrestrial carbon sinks in QTP.

Bioinspired Superhydrophobic All-In-One Coating for Adaptive Thermoregulation.

The development of scalable and passive coatings that can adapt to seasonal temperature changes while maintaining superhydrophobic self-cleaning functions is crucial for their practical applications. However, the incorporation of passive cooling and heating functions with conflicting optical properties in a superhydrophobic coating is still challenging. Herein, an all-in-one coating inspired by the hierarchical structure of a lotus leaf that combines surface wettability, optical structure, and temperature self-adaptation is obtained through a simple one-step phase separation process. This coating exhibits an asymmetrical gradient structure with surface-embedded hydrophobic SiO2 particles and subsurface thermochromic microcapsules within vertically distributed hierarchical porous structures. Moreover, the coating imparts superhydrophobicity, high infrared emission, and thermo-switchable sunlight reflectivity, enabling autonomous transitions between radiative cooling and solar warming. The all-in-one coating prevents contamination and over-cooling caused by traditional radiative cooling materials, opening up new prospects for the large-scale manufacturing of intelligent thermoregulatory coatings.

Degradation of Complex Carbon Sources in Organic Fertilizers Facilitates Nitrogen Fixation.

Biological nitrogen fixation is crucial for agriculture and improving fertilizer efficiency, but organic fertilizers in enhancing this process remain debated. Here, we investigate the impact of organic fertilizers on biological nitrogen fixation through experiments and propose a new model where bacterial interactions with complex carbon sources enhance nitrogen fixation. Field experiments showed that adding organic fertilizers increased the nitrogenase activity by 57.85%. Subculture experiments revealed that organic fertilizer addition enriched genes corresponding to complex carbon and energy metabolism, as well as nifJ involved in electron transfer for nitrogenase. It also enhanced bacterial interactions and enhanced connectors associated with complex carbon degradation. Validation experiments demonstrated that combinations increased nitrogenase activity by 2.98 times compared to the single. Our findings suggest that organic fertilizers promoted nitrogen fixation by enhancing microbial cooperation, improved the degradation of complex carbon sources, and thereby provided utilizable carbon sources, energy, and electrons to N-fixers, thus increasing nitrogenase activity and nitrogen fixation.

High-Efficiency Effect-Directed Analysis Leveraging Five High Level Advancements: A Critical Review.

Organic contaminants are ubiquitous in the environment, with mounting evidence unequivocally connecting them to aquatic toxicity, illness, and increased mortality, underscoring their substantial impacts on ecological security and environmental health. The intricate composition of sample mixtures and uncertain physicochemical features of potential toxic substances pose challenges to identify key toxicants in environmental samples. Effect-directed analysis (EDA), establishing a connection between key toxicants found in environmental samples and associated hazards, enables the identification of toxicants that can streamline research efforts and inform management action. Nevertheless, the advancement of EDA is constrained by the following factors: inadequate extraction and fractionation of environmental samples, limited bioassay endpoints and unknown linkage to higher order impacts, limited coverage of chemical analysis (i.e., high-resolution mass spectrometry, HRMS), and lacking effective linkage between bioassays and chemical analysis. This review proposes five key advancements to enhance the efficiency of EDA in addressing these challenges: (1) multiple adsorbents for comprehensive coverage of chemical extraction, (2) high-resolution microfractionation and multidimensional fractionation for refined fractionation, (3) robust in vivo/vitro bioassays and omics, (4) high-performance configurations for HRMS analysis, and (5) chemical-, data-, and knowledge-driven approaches for streamlined toxicant identification and validation. We envision that future EDA will integrate big data and artificial intelligence based on the development of quantitative omics, cutting-edge multidimensional microfractionation, and ultraperformance MS to identify environmental hazard factors, serving for broader environmental governance.

Blockade of CCR5 and CXCR3 attenuates murine acute graft-versus-host disease through modulating donor-derived T cell distribution and function.

BACKGROUND: Lymphocyte trafficking via chemokine receptors such as CCR5 and CXCR3 plays a critical role in the pathogenesis of aGVHD. Our previous studies showed that addition of CCR5 or CXCR3 antagonist could only slightly alleviate the development of aGVHD. Given the specificity of T lymphocytes bearing CXCR3 and CCR5, we investigated whether combined CCR5 and CXCR3 blockade could further attenuate murine aGVHD. METHODS: A mouse model of aGVHD was established to assess the efficacy of CCR5 or/and CXCR3 blockade on the development of aGVHD. The distribution of lymphocytes was calculated by quantification of immunostaining cells. The immunomodulatory effect on T cells were assessed by evaluating T- cell proliferation, viability, and differentiation. RESULTS: Using murine allo-HSCT model, we demonstrated that blockade of both CCR5 and CXCR3 could efficiently alleviate the development of aGVHD. Further investigation on the immune mechanisms for this prophylactic effect showed that more T cells were detained into secondary lymphoid organs (SLOs), which may lead to reduced infiltration of T cells into GVHD target organs. Our study also showed that T cells detained into SLOs dampened the activation, suppressed the polarization toward Th1 and Tc1, and induced the production of Treg cells. CONCLUSION: These data suggest that concurrent blockade of CCR5 and CXCR3 attenuates murine aGVHD through modulating donor-derived T cell distribution and function, and this might be applicable for aGVHD prophylaxis in clinical settings.

Association between CBL gene polymorphism and susceptibility of microscopic polyangiitis in a Chinese population: A case-control analysis.

OBJECTIVE: To assess whether Casitas B-lineage lymphoma (CBL) gene polymorphism influences the risk of microscopic polyangiitis (MPA) in Chinese populations. METHODS: In total, 266 MPA patients and 297 healthy controls were recruited for a case-control study. Five CBL SNPs were genotyped using multiplex polymerase chain reaction and high-throughput sequencing. The relationship between SNPs and the risk of MPA under different genetic models was evaluated by SNPstats. SNP-SNP interaction was analyzed by generalized multifactor dimensionality reduction (GMDR). Finally, the association between CBL SNPs and treatment effects were assessed. RESULTS: The results showed that CBL rs2276083 was associated with decreasing MPA risk under dominant (OR: 0.53; p = 0.014) and recessive models (OR: 0.52; p = 0.0034). Stratification analysis indicated that rs2276083 and rs2509671 in age < 60 years, rs2276083 in female or in Han population were protective factors for MPA. The CBL haplotype (A-A-G-C-T) was associated with an increased risk of MPA. GMDR suggested that CBL rs2276083, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PI3KCA) rs1607237, and autophagy-related gene 7 (ATG7) rs7549008 might interact with each other in MPA development (p = 0.0107). CBL rs1047417 with AG genotype and rs11217234 with AG genotype had better clinical treatment effects than other two genotypes (p = 0.048 and p = 0.025, respectively). CONCLUSION: The genetic polymorphism of CBL had a potential association with the risk of MPA and clinical treatment effects in Guangxi population in China.

Molecular mechanisms of cytochrome P450-mediated detoxification of tetraniliprole, spinetoram, and emamectin benzoate in the fall armyworm, Spodoptera frugiperda (J.E. Smith).

The fall armyworm (FAW) Spodoptera frugiperda (J.E. Smith) is a highly damaging invasive omnivorous pest that has developed varying degrees of resistance to commonly used insecticides. To investigate the molecular mechanisms of tolerance to tetraniliprole, spinetoram, and emamectin benzoate, the enzyme activity, synergistic effect, and RNA interference were implemented in S. frugiperda. The functions of cytochrome P450 monooxygenase (P450) in the tolerance to tetraniliprole, spinetoram, and emamectin benzoate in S. frugiperda was determined by analysing changes in detoxification metabolic enzyme activity and the effects of enzyme inhibitors on susceptibility to the three insecticides. 102 P450 genes were screened via transcriptome and genome, of which 67 P450 genes were differentially expressed in response to tetraniliprole, spinetoram, and emamectin benzoate and validated by quantitative real-time PCR. The expression patterns of CYP9A75, CYP340AA4, CYP340AX8v2, CYP340L16, CYP341B15v2, and CYP341B17v2 were analysed in different tissues and at different developmental stages in S. frugiperda. Silencing CYP340L16 significantly increased the susceptibility of S. frugiperda to tetraniliprole, spinetoram, and emamectin benzoate. Furthermore, knockdown of CYP340AX8v2, CYP9A75, and CYP341B17v2 significantly increased the sensitivity of S. frugiperda to tetraniliprole. Knockdown of CYP340AX8v2 and CYP340AA4 significantly increased mortality of S. frugiperda to spinetoram. Knockdown of CYP9A75 and CYP341B15v2 significantly increased the susceptibility of S. frugiperda to emamectin benzoate. These results may help to elucidate the mechanisms of tolerance to tetraniliprole, spinetoram and emamectin benzoate in S. frugiperda.