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The impact of microplastics on antibiotic resistance has attracted widespread attention. However, previous studies primarily focused on the effects of individual microplastics. In reality, diverse microplastic types accumulate in soil, and it remains less well studied whether microplastic diversity (i.e., variations in color, shape or polymer type) can be an important driver of increased antibiotic resistance gene (ARG) abundance. Here, we employed microcosm studies to investigate the effects of microplastic diversity on soil ARG dynamics through metagenomic analysis. Additionally, we evaluated the associated potential health risks by profiling virulence factor genes (VFGs) and mobile genetic elements (MGEs). Our findings reveal that as microplastic diversity increases, there is a corresponding rise in the abundance of soil ARGs, VFGs and MGEs. We further identified microbial adaptive strategies involving genes (changed genetic diversity), community (increased specific microbes), and functions (enriched metabolic pathways) that correlate with increased ARG abundance and may thus contribute to ARG dissemination. Additional global change factors, including fungicide application and plant diversity reduction, also contributed to elevated ARG abundance. Our findings suggest that, in addition to considering contamination levels, it is crucial to monitor microplastic diversity in ecosystems due to their potential role in driving the dissemination of antibiotic resistance through multiple pathways. The effects of microplastics (MPs) on soil microbial communities and antimicrobial resistance genes are not well understood. Here, the authors used microcosm studies to show that MP diversity, and partially fungicide treatment and reduced plant diversity, correlate with higher levels of ARG and related genetic factors. [ABSTRACT FROM AUTHOR]

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The heavy metal cadmium (Cd) is a toxic and bioaccumulative metal that can be enriched in the tissues and organs of living organisms through the digestive tract. However, more research is needed to determine whether food-sourced Cd affects the homeostasis of host gut microflora. In this study, the snail Bradybaena ravida (Benson) was used as a model organism fed with mulberry leaves spiked with different concentrations of Cd (0, 0.052, 0.71, and 1.94 mg kg−1). By combining 16S rRNA high-throughput sequencing with biochemical characterization, it was found that there were increases in the overall microbial diversity and abundances of pathogenic bacteria such as Corynebacterium, Enterococcus, Aeromonas, and Rickettsia in the gut of B. ravida after exposure to Cd. However, the abundances of potential Cd-resistant microbes in the host's gut, including Sphingobacterium, Lactococcus, and Chryseobacterium, decreased with increasing Cd concentrations in the mulberry leaves. In addition, there was a significant reduction in activities of energy, nutrient metabolism, and antioxidant enzymes for gut microbiota of snails treated with high concentrations of Cd compared to those with low ones. These findings highlight the interaction of snail gut microbiota with Cd exposure, indicating the potential role of terrestrial animal gut microbiota in environmental monitoring through rapid recognition and response to environmental pollution. [ABSTRACT FROM AUTHOR]

Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1–C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice. [ABSTRACT FROM AUTHOR]

α-Synuclein forms amyloid fibrils that are critical in the progression of Parkinson's disease and serves as the pathological hallmark of this condition. Different posttranslational modifications have been identified at multiple sites of α-synuclein, influencing its conformation, aggregation and function. Here, we investigate how disease-related phosphorylation and O-GlcNAcylation at the same α-synuclein site (S87) affect fibril structure and neuropathology. Using semi-synthesis, we obtained homogenous α-synuclein monomer with site-specific phosphorylation (pS87) and O-GlcNAcylation (gS87) at S87, respectively. Cryo-EM revealed that pS87 and gS87 α-synuclein form two distinct fibril structures. The GlcNAc situated at S87 establishes interactions with K80 and E61, inducing a unique iron-like fold with the GlcNAc molecule on the iron handle. Phosphorylation at the same site prevents a lengthy C-terminal region including residues 73 to 140 from incorporating into the fibril core due to electrostatic repulsion. Instead, the N-terminal half of the fibril (1–72) takes on an arch-like fibril structure. We further show that both pS87 and gS87 α-synuclein fibrils display reduced neurotoxicity and propagation activity compared with unmodified α-synuclein fibrils. Our findings demonstrate that different posttranslational modifications at the same site can produce distinct fibril structures, which emphasizes link between posttranslational modifications and amyloid fibril formation and pathology. Here, the authors use cryo-EM to show that phosphorylating or O-GlcNAcylating α-synuclein on serine 87 leads to the formation of two distinct fibril structures. Both structures display reduced neurotoxicity and propagation activity. [ABSTRACT FROM AUTHOR]

The process of extracting aluminum with sulfuric acid from high-alumina fly ash activated by roasting with Na2CO3 and NaOH as raw materials ware studied. The results revealed that the aluminum in fly ash activated by sodium carbonate reached 93.2% under the optimum conditions (30% H2SO4, 90°C, 120 min, and liquid-to-solid ratio was 5:1). Simultaneously, the leaching rate of aluminum in fly ash activated by sodium hydroxide reached 92%. The study of kinetics suggested that the leaching process with sulfuric acid was controlled through chemical reactions; it conformed to the kinetic equation: 1 − (1 − X) 1/3 = 22.924 exp[− 25174/(RT)]t. Extracting aluminum with sulfuric acid from high-alumina fly ash activated by roasting with Na2CO3 and NaOH as raw materials. [ABSTRACT FROM AUTHOR]

Purpose: The main objectives of this study were to investigate the distribution characteristics and evaluate the potential ecological hazard associated with rare earth elements (REEs) within the Pearl River Estuary (PRE) sediment. Furthermore, we still have not fully understood the contamination and potential ecological risks of REEs in aquatic sediments. Moreover, the factors influencing their distribution remain unidentified. Hence, we selected the PRE as the central focus for our case study in this paper. Materials and methods: Sediment samples in this study (0–20 cm) were collected from 156 locations. The total organic carbon (TOC) and grain size were measured. The concentrations of REEs were determined by inductively coupled plasma mass spectrometry (ICP-MS). Furthermore, contamination models, including geoaccumulation index (Igeo), enrichment factor (EF), contamination factor ( C f i ), and pollution load index (PLI), along with ecological risk assessment models potential ecological risk factors ( E r i ) and ecological risk index (RI) have been employed to evaluate pollution levels and ecological risks. Results: The concentrations of sum REEs (ΣREEs) were in the range of 51.21 to 567.08 mg kg−1, with an average of 299.06 mg kg−1. We identified two accumulation centers for REEs, indicating that these elements primarily originated from these two centers. It can be seen from the values of EF of REEs that these elements showed minimal enrichment. Moreover, the pollution load index (PLI), which assesses the combined contamination of REEs, was computed to evaluate the collective contamination in the study area. The PLI results indicate a slight multi-element contamination in the research region. Furthermore, based on the E r i values, it is evident that all studied REEs pose a low ecological risk. Conclusions: The distributions of REEs were mainly controlled by TOC and median grain size. The RI was also calculated to assess the combined potential risks on the ecology. The study's findings indicate that the PRE's sediments produce low ecological risks. [ABSTRACT FROM AUTHOR]

The present study examined potential association between the daily intake and serum levels of copper (Cu), selenium (Se), and zinc (Zn) and the risk of osteoarthritis (OA) and rheumatoid arthritis (RA) using data from the National Health and Nutrition Examination Survey (NHANES). Daily intake and serum concentrations of Cu, Zn, and Se in 4200 adults from the 2011–2016 NHANES were examined and divided into normal, OA patients, and RA patients. The level of serum Cu was higher in OA and RA than in non-arthritis, while the levels of serum Se and Zn were no different in the three groups. Serum Se and Zn, but not Cu, concentrations were highly correlated with daily intake. Cu, Se, and Zn intake was independently associated with increased risk of OA, but not with RA. And there was a trend for higher odds of OA among participants in the higher Cu, Se, and Zn intake. Future large longitudinal studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Restoration of HBV-specific T cell immunity is a promising approach for the functional cure of chronic Hepatitis B (CHB), necessitating the development of valid assays to boost and monitor HBV-specific T cell responses in patients with CHB. Methods: We analyzed hepatitis B virus (HBV) core- and envelope (env)-specific T cell responses using in vitro expanded peripheral blood mononuclear cells (PBMCs) from patients with CHB exhibiting different immunological phases, including immune tolerance (IT), immune activation (IA), inactive carrier (IC), and HBeAg-negative hepatitis (ENEG). Additionally, we evaluated the effects of metabolic interventions, including mitochondria-targeted antioxidants (MTA), polyphenolic compounds, and ACAT inhibitors (iACAT), on HBV-specific T-cell functionality. Results: We found that HBV core- and env-specific T cell responses were finely coordinated and more profound in IC and ENEG than in the IT and IA stages. HBV env-specific T cells were more dysfunctional but prone to respond to metabolic interventions using MTA, iACAT, and polyphenolic compounds than HBV core-specific T-cells. The responsiveness of HBV env-specific T cells to metabolic interventions can be predicted by the eosinophil (EO) count and the coefficient of variation of red blood cell distribution width (RDW-CV). Conclusion: These findings may provide valuable information for metabolically invigorating HBV-specific T-cells to treat CHB. [ABSTRACT FROM AUTHOR]

Glutathione peroxidase (GPx) is an important antioxidant enzyme. Selenocysteine (Sec)-containing GPxs (Sec-GPxs) are usually superior to their conventional cysteine-containing counterparts (Cys-GPxs), which make up the majority of the natural GPxs but display unsuitable activity and stability for industrial applications. This study first heterologously expressed and characterized a Cys-GPx from Lactococcus lactis (LlGPx), systematically exchanged all the three Cys to Sec and introduced an extra Sec. The results showed that the insertion of Sec at the active site could effectively increase the enzyme activity and confer a lower optimal pH value on the mutants. The double mutant C36U/L157U increased by 2.65 times (5.12 U/mg). The thermal stability of the C81U mutant was significantly improved. These results suggest that site-directed Sec incorporation can effectively improve the enzymatic properties of LlGPx, which may be also used for the protein engineering of other industrial enzymes containing catalytic or other functional cysteine residues. [ABSTRACT FROM AUTHOR]

Protecting the ecological security of the Qinghai-Tibet Plateau (QTP) is of great importance for global ecology and climate. Over the past few decades, climate extremes have posed a significant challenge to the ecological environment of the QTP. However, there are few studies that explored the effects of climate extremes on ecological environment quality of the QTP, and few researchers have made quantitative analysis. Hereby, this paper proposed the Ecological Environmental Quality Index (EEQI) for analyzing the spatial and temporal variation of ecological environment quality on the QTP from 2000 to 2020, and explored the effects of climate extremes on EEQI based on Geographically and Temporally Weighted Regression (GTWR) model. The results showed that the ecological environment quality in QTP was poor in the west, but good in the east. Between 2000 and 2020, the area of EEQI variation was large (34.61% of the total area), but the intensity of EEQI variation was relatively low and occurred mainly by a slightly increasing level (EEQI change range of 0.05–0.1). The overall ecological environment quality of the QTP exhibited spatial and temporal fluctuations, which may be attributed to climate extremes. Significant spatial heterogeneity was observed in the effects of the climate extremes on ecological environment quality. Specifically, the effects of daily temperature range (DTR), number of frost days (FD0), maximum 5-day precipitation (RX5day), and moderate precipitation days (R10) on ecological environment quality were positive in most regions. Furthermore, there were significant temporal differences in the effects of consecutive dry days (CDD), consecutive wet days (CWD), R10, and FD0 on ecological environment quality. These differences may be attributed to variances in ecological environment quality, climate extremes, and vegetation types across different regions. In conclusion, the impact of climate extremes on ecological environment quality exhibits complex patterns. These findings will assist managers in identifying changes in the ecological environment quality of the QTP and addressing the effects of climate extremes. [ABSTRACT FROM AUTHOR]

CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH. Analysis of plasma metabolites in virologically suppressed individuals infected with HIV-1 and controls, reveals an association between metabolic plasticity and CD8 + T cell-mediated HIV infection control. [ABSTRACT FROM AUTHOR]

The adsorption process is regarded as a promising technology for removing organics and heavy metals. In this study, we used orange peels as biomass feedstock and used nickel-manganese ferrite (Ni1-x MnxFe2O4) as the precursor solution to prepare magnetic mesoporous biochar (MBC). Using a Box-Behnken design response, we investigated the adsorption of 2,4-difluoroaniline (2,4-DFA), as well as the influence of four preparation parameters (activation temperature, the molar mass of Mn in Ni1-x MnxFe2O4, activation time, and impregnation ratio). Based on the adsorption rate of 2,4-DFA, we obtained the following optimal preparation parameters of MBC: a temperature of 180 °C, a molar mass of Ni0.75 Mn0.25Fe2O4, an activation time of 8 h, and an impregnation ratio of 3. Then, we investigated the adsorption capacity of MBC and the mutual effect of 2,4-DFA and copper (II) [Cu(II)] through single and binary systems. The adsorption processes of 2,4-DFA and Cu(II) could be satisfactorily fitted to a pseudo-second-order kinetic model. The adsorption amount of 2,4-DFA was comparable in both single and binary systems. However, the adsorption of Cu(II) in the binary system was inhibited, with the adsorption capacity decreasing by 19.55%. The adsorption isotherms of 2,4-DFA and Cu(II) to MBC fitted the Freundlich model. The maximum adsorption capacity of 2,4-DFA and Cu(II) could reach 66.30 mg/g and 10.44 mg/g at 313 K, respectively. MBC exhibited good regeneration performance through the combination of 90% ethanol and 1 M NaOH solution. The adsorption mechanism mainly included electrostatic interactions, hydrogen bonds, ion exchange, and π-π interactions. [ABSTRACT FROM AUTHOR]

A generalized single-variable shear deformation plate theory (GSSDPT) is proposed. Compared with other single-variable vibration theories, GSSDPT discards the assumption that the shear component has zero effect on the bending moment. This makes the simplification process more reasonable. GSSDPT takes into account the inhomogeneous distribution of material properties, which makes it suitable for many new composite materials, such as functionally graded materials. Compared with higher-order shear deformation plate theories and first-order shear deformation plate theory, GSSDPT has only one governing equation, which significantly simplifies the calculation. GSSDPT takes into account the parabolic distribution of shear stress in the thickness direction. Therefore, it does not require shear correction. In this paper, the free vibration behavior of functionally graded plates under three pore distribution forms is investigated. The convenience and effectiveness of GSSDPT are verified by comparing it with existing literature. In addition, the effects of the porosity parameter, side-to-thickness ratio, aspect ratio, power-law index, and pore distribution forms are investigated based on GSSDPT. [ABSTRACT FROM AUTHOR]

In this paper, the waterborne aluminum pigments with intelligent anticorrosion properties and bright colors were prepared by encapsulating multifunctional composite layers, which were composed of zeolitic imidazole framework (ZIF) and silica. With the results of the micropores and microcracks generated in the silica layer, the penetration of acidic corrosion into the inner layer caused the ZIF layer to release the linker as the corrosion inhibitor and construct a new barrier on the metal surface due to the high corrosion inhibitor content in ZIF. After the pH response, the highest impedance of the aluminum pigments was up to 4.35 × 105 Ω cm2. The aluminum pigments with the multifunctional composite layers (Al@ZIF-B@SiO2) could maintain stability at pH = 1. Meanwhile, the excellent adsorption and porosity of ZIF were applied to sorb the dye, which endowed the aluminum pigments with bright colors. The functional composite layers on the aluminum pigments eliminated the hydrogen emission, which proved the excellent chemical stability of the prepared samples. The sensitive pH responsiveness of Al@ZIF-B@SiO2 was also testified. [ABSTRACT FROM AUTHOR]

Purpose: Phytostabilization is known to be a promising technique to prevent the off-site movement of cadmium (Cd) from severely contaminated arable soils. Previous studies have recognized plants and amendments that could be potentially used for phytostabilization, such as non-edible fiber and energy crops and biochar. However, there is a paucity of information on the performance of these candidate crops and amendments for the application in the field. Methods: Twelve plant-amendment systems were established on the farmland severely contaminated with Cd in the South China karst area, which comprises cash crops kenaf (Hibiscus cannabinus), ramie (Boehmeria nivea), and sorghum (Sorghum bicolor) together with the application of lime, coconut shell biochar, and rice straw biochar at different rates. A comprehensive score was introduced to evaluate the performance of the studied plant-amendment systems, considering not only the indicators related to soil Cd mobility but also the costs. Results: After one crop cycle, a 40% median rate of reduction was achieved in soil available Cd. An intensive application of biochar lowered the comprehensive performance since a significantly increased cost gained only a slight improvement in the reduction of soil available Cd. Sorghum with 0.5% (w/w) rice straw biochar showed the best performance in the study site, which effectively sequestrated Cd in the roots and reduced soil available Cd at a relatively low cost. Conclusion: This work shows the performance and the comprehensive evaluation of candidate plant-amendment systems for the in situ phytostabilization. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and aims: Natural killer (NK) cells are critical innate effectors that respond to viral infections and contribute to immunopathology. Here, we aimed to investigate the role of NK cells in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and elucidate the underlying mechanism by examining their phenotypic and functional profiles. Methods: We included patients with HBV-ACLF (n = 37) and chronic hepatitis B (n = 19), and healthy controls (n = 13) in our study. We examined the phenotype and function of different subsets of peripheral NK cells using flow cytometry and RNA-sequencing analysis, and screened liver NK cells using immunohistochemistry. We detected inflammatory cytokines using a Luminex assay. In addition, we analyzed the relationships between these parameters and disease severity. Results: Peripheral NK cells were decreased and characterized by high expression of caspase-3, Ki67, CXCR3, NKG2D, NKp46, CD107a, and GM-CSF, and typified by higher cell migration and immune response by RNA-sequencing analysis in patients with HBV-ACLF than in those with chronic hepatitis B. Accumulations of CXCL-10 and NK cells were found in the liver, and excessive production of CXCL-10 in the peripheral blood contributed to the apoptosis of NK cells in vitro. The decrease in NK cells was associated with the level of HBV DNA and disease severity and had good prognostic performance in predicting the outcome of patients with HBV-ACLF through AUROC analysis. Conclusion: NK cells were significantly decreased and showed dysfunction of phenotypic and functional profiles across distinct subsets in the peripheral blood of patients with ACLF. Crosstalk between CXCL-10 and NK cells may mediate the unbalanced distribution of NK cells. Understanding the dysfunction and decrease in NK cells may provide new insights into ACLF pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: Endoplasmic reticulum stress (ERS) and long non-coding RNAs (lncRNAs) are important in melanoma development and progression. This study aimed to explore the prognostic value of ERS-associated lncRNA profiles in cutaneous melanoma (CM). Methods: The Cancer Genome Atlas (TCGA) provides the raw data of CM. GSEA website was used to obtain ERS-related genes, and mRNA and LncRNA co-expression network were used to obtain ERS-related lncRNAs. A Lasso regression analysis was used to identify a prognostic risk model for the composition of ERS-related lncRNAs. Patients were divided into high- and low-risk groups based on the model's risk score. The researchers then compared the two groups' survival rates, immune infiltration, chemotherapeutic drug sensitivity, and immune checkpoint gene expression. Results: Thirty-nine ERS-related lncRNAs were discovered to be prognostic. A prognostic risk model made up of ten ERS-related lncRNAs was discovered. Patients in the low-risk group had a better prognosis than those in the high-risk group. An examination of tumor microenvironment revealed that risk scores correlated with immune cell infiltration in eight cases. Dacarbazine, paclitaxel, and cisplatin, three chemotherapy drugs, were more sensitive in the low-risk group than in the high-risk group. Conclusion: This study identified a risk model of ten ERS-related lncRNAs that have significant prognostic value in CM and could help guide clinical treatment. [ABSTRACT FROM AUTHOR]

A novel missense variant (NM_005327.7: c.99C>G, p.Ile33Met) was discovered in 3-hydroxyacyl-CoA dehydrogenase (HADH), which is involved in congenital hyperinsulinism (CHI). This variant may be damaging or deleterious, as assessed using protein prediction software. This study aimed at the impact of this variant on islets and if it caused the leu-sensitive insulin secretion. The adeno-associated virus containing the HADH missense variant (p.Ile33Met), wild-type (WT) HADH or empty vector (EV) was constructed, and the rats were infected with it. Three weeks after the transfection, 15 rats were dissected to observe the effect of the variant on the islet tissue. Then we treated the remaining rats with leucine or sodium carboxymethyl cellulose (CMC-Na) by gavage and drew blood from the rat tail vein to detect the variations in blood glucose, serum insulin and serum glucagon. Further, we dissected the rats to observe the fluctuation of insulin and glucagon contents in pancreatic islets under the combined action of leucine and p.Ile33Met. Insulin and glucagon were observed in the islet tissue under an inverted fluorescence microscope, serum insulin and glucagon were detected by ELISA, and the blood glucose value was determined using a Roche glucometer. The positive area and average gray value of islet fluorescence pictures were analysed using the software Image J (USA). Rats expressing p.Ile33Met showed significantly higher insulin and glucagon content, as well as the islet area, compared to WT and EV rats. Moreover, after intragastric administration of leucine, the serum insulin content of the variant rats increased but the blood sugar level decreased significantly. Meanwhile, there was an appreciable decrease in the insulin content in rat pancreatic islet tissues. Our results suggest that the variant NM_005327.7: c.99C>G promotes the proliferation of pancreatic islets, enhances the secretion of insulin, and induces leu-sensitive hyperinsulinaemia. [ABSTRACT FROM AUTHOR]

The Micra TPS™ (Medtronic) is the first leadless pacemaker listed in China. The best fluoroscopic angle for the intraoperative fixation test is selected according to different implantation sites to reduce the fluoroscopy duration and radiation dose, and the test is based on the early safety and effectiveness of the device after implantation. A total of 110 patients who underwent Micra TPS™ implantation were selected. Eighty patients were in group A, and 30 patients were in group B. Under the guidance of the conclusions from group A, the fluoroscopy duration, radiation dose and number of fluoroscopic positions of the best fluoroscopic angle of the fixation test according to different positions of the implanted interventricular septum were compared. In 85.0% of the group A implants, these angles were based on the right interior oblique (RAO) angle, with 48.5% cranial (CRA) and 29.4% caudal (CAU) angles. The angle of the tilting head side of the RAO angle was prioritized in group B, and referring to the average angle data, the average fluoroscopy duration for finding the best angle of fixation test was 1.7 ± 0.6 vs. 3.2 ± 1.8 min (P < 0.001), the average radiation dose was 270.4 ± 56.3 vs. 338.1 ± 112.9 mGy (P = 0.002), and the average number of fluoroscopic positions was 2.2 ± 0.6 vs. 4.2 ± 2.1 (P < 0.001), which was significantly less than that in group A. This study found that there was regularity in the fluoroscopic angle for the fixation test during Micra TPS™ operation.Level of Evidence Level 3, local nonrandom sample. [ABSTRACT FROM AUTHOR]

This study reported the cloning, expression, and characterization of a new salt-tolerant leucine dehydrogenase (PrLeuDH) from Pseudoalteromonas rubra DSM 6842. A codon-optimized 1038 bp gene encoding PrLeuDH was successfully expressed on pET-22b(+) in E. coli BL21(DE3). The purified recombinant PrLeuDH showed a single band of about 38.7 kDa on SDS-PAGE. It exhibited the maximum activity at 40 °C and pH 10.5, while kept high activities in the range of 25–45 °C and pH 9.5–12. The Km value and turnover number kcat for leucine of PrLeuDH were 2.23 ± 0.12 mM and 35.39 ± 0.05 s−1, respectively, resulting in a catalytic efficiency kcat/Km of 15.87 s−1/mM. Importantly, PrLeuDH remained 92.1 ± 2.67% active in the presence of 4.0 M NaCl. The study provides the first in-depth understanding of LeuDH from marine Pseudoalteromonas rubra, meanwhile the unique properties of high activity at low temperature and high salt tolerance make it a promising biocatalyst for the synthesis of non-protein amino acids and α-ketoacids under special conditions in pharmaceutical industry. [ABSTRACT FROM AUTHOR]

To obtain a comprehensive scenario of T cell profiles and synergistic immune responses, we performed single-cell RNA sequencing (scRNA-seq) on the peripheral T cells of 14 individuals with chronic human immunodeficiency virus 1 (HIV-1) infection, including nine treatment-naive (TP) and eight antiretroviral therapy (ART) participants (of whom three were paired with TP cases), and compared the results with four healthy donors (HD). Through analyzing the transcriptional profiles of CD4+ and CD8+ T cells, coupled with assembled T cell receptor sequences, we observed the significant loss of naive T cells, prolonged inflammation, and increased response to interferon-α in TP individuals, which could be partially restored by ART. Interestingly, we revealed that CD4+ and CD8+ Effector-GNLY clusters were expanded in TP cases, and persistently increased in ART individuals where they were typically correlated with poor immune restoration. This transcriptional dataset enables a deeper understanding of the pathogenesis of HIV-1 infection and is also a rich resource for developing novel immune targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background and aims: Hepatitis E virus-related acute liver failure (HEV-ALF) rapidly worsens and has a high mortality. However, no simple and specific parameters for predicting short-term mortality are available. Methods: A derivation cohort including 97 patients with HEV-ALF and another validation cohort were enrolled. Laboratory and clinical parameters were recorded. Platelet count, model for end-stage liver disease (MELD), and King's College criteria (KCC) were separately used for predicting mortality, and the levels of cytokines associated with systemic inflammation, platelet production, and platelet activation were measured. Results: Platelet counts were significantly lower in patients with HEV-ALF, and nonsurvivors had lower platelet counts than survivors (p < 0.001). Platelet count was an independent risk factor for predicting 28- and 90-day mortality in patients with HEV-ALF. The AUROC of the baseline platelet count (cutoff, 131 × 109/L) for 28- and 90-day mortality was 0.786 and 0.764, respectively, which was superior to KCC score (p < 0.05) and comparable to MELD score. Furthermore, the platelet counts at 3 and 7 days after ALF diagnosis had similar predictive power for 28- and 90-day mortality. The value of platelet count was also confirmed in the validation cohort. Moreover, platelet-associated cytokines, including thrombopoietin, platelet factor 4, and P-selectin, were increased in patients with HEV-ALF. Conclusions: Decreased platelet count is a simple and reliable indicator for predicting 28- and 90-day mortality in patients with HEV-ALF. Overactivation of platelets is an important risk for platelet counts decrease, and treatment aiming at platelet count recovery may be considered. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cell therapy is a novel therapeutic approach that uses gene editing techniques and lentiviral transduction to engineer T cells so that they can effectively kill tumors. However, CAR T cell therapy still has some drawbacks: many patients who received CAR T cell therapy and achieve remission, still had tumor relapse and treatment resistance, which may be due to tumor immune escape and CAR T cell dysfunction. To overcome tumor relapse, more researches are being done to optimize CAR T cell therapy to make it more precise and personalized, including screening for more specific tumor antigens, developing novel CAR T cells, and combinatorial treatment approaches. In this review, we will discuss the mechanisms as well as the progress of research on overcoming plans. [ABSTRACT FROM AUTHOR]

Key message: A novel mutation in the BnaA03.IAA7 protein reduces plant height and enhances gibberellin signaling in Brassica napus L. Rapeseed (Brassica napus) is an excellent and important source for vegetable oil production, but its production is severely affected by lodging. Lodging hinders mechanization and decreases yield, and an ideal solution is semidwarf breeding. Limited by germplasm resources, semidwarf breeding developed slowly in rapeseed. In the current study, a mutant called sdA03 was isolated from EMS-mutagenized lines of Zhongshuang 11 (ZS11). The inheritance analysis showed that phenotypes of sdA03 were controlled by a single semidominant gene. Genetic mapping, RNA-seq and candidate gene analysis identified BnaA03.IAA7 as a candidate gene, and a function test confirmed that the mutated BnaA03.iaa7 regulates plant architecture in a dose-dependent manner. Yeast two-hybrid and transient expression experiments illustrated the P87L substitution in the GWPPV/I degron motif of BnaA03.iaa7 impaired the interaction between BnaA03.IAA7 and TIR1 proteins, and BnaA03.iaa7 prevented ARF from activating the auxin signaling pathway.The gibberellin (GA) content was higher in sdA03 hypocotyls than in those of ZS11. Further expression analysis showed more active gibberellin signaling in hypocotyl and richer expression of GA synthetic genes in root and cotyledon of sdA03 seedlings. Finally, a marker was developed based on the SNP found in BnaA03.iaa7 and used in molecular breeding. The study enriched our understanding of the architectural regulation of rapeseed and provided germplasm resources for breeding. [ABSTRACT FROM AUTHOR]

Threat and extinction memories are crucial for organisms' survival in changing environments. These memories are believed to be encoded by separate ensembles of neurons in the brain, but their whereabouts remain elusive. Using an auditory fear-conditioning and extinction paradigm in male mice, here we discovered that two distinct projection neuron subpopulations in physical proximity within the insular cortex (IC), targeting the central amygdala (CeA) and nucleus accumbens (NAc), respectively, to encode fear and extinction memories. Reciprocal intracortical inhibition of these two IC subpopulations gates the emergence of either fear or extinction memory. Using rabies-virus-assisted tracing, we found IC-NAc projection neurons to be preferentially innervated by intercortical inputs from the orbitofrontal cortex (OFC), specifically enhancing extinction to override fear memory. These results demonstrate that IC serves as an operation node harboring distinct projection neurons that decipher fear or extinction memory under the top-down executive control from OFC. Ensembles of fear and extinction memories compete and interact to drive opposing behaviors. Here the authors identified insular cortical circuits as an executive gateway that decipher between fear and extinction memories via distinct subcortical pathways. [ABSTRACT FROM AUTHOR]

Immunostimulatory therapies based on pattern recognition receptors (PRRs) have emerged as an effective approach in the fight against cancer, with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment. The agonist cyclic dinucleotides (CDNs) of the stimulator of interferon gene (STING) are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity. However, the tumor immune efficacy of CDNs is limited by several factors, including relatively narrow cytokine production, inefficient delivery to STING, and rapid clearance. In addition, a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect. To address this problem, two or more agonist molecules are often used together to synergistically enhance immune efficacy. In this work, we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8 (TLR7/8) agonist 522 produced a broader cytokine response. Subsequently, we developed multicomponent nanovaccines (MCNVs) consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules. These MCNVs activate bone marrow-derived dendritic cells (BMDCs) to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor T-cell responses. In in vivo experiments, we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes, resulting in significant tumor regression and, notably, a 100% survival rate in mice through 25 days without other partnering therapies. These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency. [ABSTRACT FROM AUTHOR]

To impart self-healing polymers largely adjustable dynamicity and mechanical performance, here we develop libraries of catalyst-free reversible polythioureas directly from commodity 1,4-phenylene diisothiocyanate and amines via facile click chemistry based modular assembly. By using the amine modules with various steric hindrances and flexibilities, the reversible thiourea units acquire triggering temperatures from room temperature to 120 °C. Accordingly, the derived self-healable, recyclable and controlled degradable dynamically crosslinked polythioureas can take effect within wide temperature range. Moreover, mechanical properties of the materials can be tuned covering plastics, elastomers and fibers using (i) different assemble modules or (ii) solid-state stretching. Particularly, unidirectional stretching leads to the record-high tensile strength of 266 MPa, while bidirectional stretching provides the materials with biaxial strengths up to over 120 MPa. The molecular mechanism and technological innovations discussed in this work may benefit promotion and application of self-healing polymers towards greatly diverse demands and scenarios. Intrinsic self-healing polymers attract increasing attention but often suffer from a narrow self-healing temperature range and unsatisfactory mechanical performance. Here, the authors use click chemistry to develop a library of catalyst-free reversible polythioureas and demonstrate that the self-healing temperature and mechanical properties can be adjusted by controlling the flexibility and the steric environment. [ABSTRACT FROM AUTHOR]

Hyperglycemia aggravates cerebral ischemia/reperfusion (I/R) injury via vascular injury. There is still a lack of effective pharmaceutical preparations for cerebral I/R injury under hyperglycemia. This study aimed to investigate the effects of oxymatrine (OMT) on hyperglycemia-exacerbated cerebral I/R injury in vitro and in vivo. The middle cerebral artery occlusion (MCAO) and reperfusion was established in the rats under hyperglycemia. Meanwhile, oxygen–glucose deprivation and reoxygenation (OGD/R) with high glucose was used as an in vitro model of hyperglycemic cerebral I/R injury. The results showed that the neurological deficit score, mortality, infarct volume and penumbra apoptosis in hyperglycemia group were significantly higher than those in normal glucose group. OMT pre-treated obviously reduced the degree of neurological deficit, mortality, infarct volume, improve cerebral blood flow after I/R in rats with hyperglycemia, and increase the survival rate of human brain microvascular endothelial cells (HBMECs) in high glucose and OGD/R group. OMT significantly improved the ultrastructure changes of endothelial cells, and maintain the migration and angiogenesis potency of HBMECs in high glucose and OGD/R group. OMT obviously alleviated the down-regulating CD31 and CD105 expression in cerebral microvessels caused by hyperglycemia. It is concluded that OMT treatment might alleviate cerebral I/R injury under hyperglycemia via protecting microvessels. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with several antigenic variants, has grown into a global challenge, and the rapid establishment of an immune barrier is crucial to achieving long-term control of the virus. This has led to a great demand for easy preparation and scalable vaccines, especially in low-income countries. Here, we present an inhalable nanovaccine comprising chitosan and SARS-CoV-2 spike protein. The chitosan-mediated nanovaccine enabled a strong spike-specific antibody immune response and augmented local mucosal immunity in bronchoalveolar lavage and lungs, which might be capable of protecting the host from infection without systemic toxicity. In addition, the enhanced adaptive immunity stimulated by chitosan showed potential protection against SARS-CoV-2. Furthermore, inhalation of the nanovaccine induced a comparable antibody response compared to intramuscular injection. This inhalable nanovaccine against SARS-CoV-2 offers a convenient and compliant strategy to reduce the use of needles and the need for medical staff. [ABSTRACT FROM AUTHOR]

Gout with etiological hyperuricemia deteriorates patient's quality of life, making an urgent need for effective uric acid-lowering drugs. Uric acid-lowering peptides derived from naturally-occurring proteins have great potential therapeutic applications and are found to be rich in aromatic amino acids (AAAs) and branched-chain amino acids (BCAAs). This study proposed a new method to rationally synthesize uric-acid lowering peptides from amino acids mainly composed of AAAs and BCAAs by papain in non-aqueous medium. Firstly, L-tryptophan and L-phenylalanine were screened out for the synthesis of uric acid-lowering peptides from all the 49 possible pairwise combinations of 7 amino acids dominating in reported natural uric-acid lowering peptides, which are 3 AAAs (L-tryptophan, L-phenylalanine, L-tyrosine), 2 BCAAs (L-leucine and L-alanine), 1 L-proline and 1 L-histidine. Secondly, the optimal reaction conditions of 90 mmol/L triethylamine, reaction at pH 6.0 for 1.5 h for the synthesis of uric-acid lowering peptides were determined using single factor method and response surface experiments (RSE). By means of preparative HPLC and LC–MS/MS identification, a newly synthesized tripeptide (FWF) was obtained, which inhibited xanthine oxidase activity by 18.47%. The tripeptide FWF was further confirmed by the chemical synthesis and its underlying XOD inhibition was supported by the computational molecular docking experiments. The newly identified uric acid-lowering tripeptide FWF and its protease-catalyzed rational synthesis in non-aqueous medium method provide alternative choices to developing uric acid-lowering peptides for anti-gout or anti-hyperuricemia treatments. [ABSTRACT FROM AUTHOR]

Utilizing the advantage of decoherence-free (DF) states, two semi-quantum private comparison (SQPC) protocols against the collective-dephasing noise and collective-rotation noise are proposed, respectively. In the protocols, two semi-quantum parties (i.e. participants with limited quantum capabilities) can compare their secrets with the help of a semi-honest third party (TP). Some common outsider's and insider's attacks are also discussed. Moreover, the simulations of our protocols on the IBM Quantum Experience show that our protocols are not only robust under two collective noises, but also feasible under the current quantum technology. [ABSTRACT FROM AUTHOR]

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Purpose: The existing concept suggests early palliative and hospice therapy for a better quality of care (QOC) and less medical expense in terminal cancer patients, but the time points of "early" initiation were defined by pre-set study protocol rather than the real-world data. The study aimed to determine the optimal timing of initiating palliative care for patients with terminal cancer. Methods: This retrospective population-based study was conducted using a nationwide database. We extracted patients with cancer who were in their last year of lives in the period from 1 January 2010 to 31 December 2013 and categorized them into two groups ("hospice-shared care" (HSC) group and "usual care" (UC) group) after a matching process. Subsequently, we used a generalized linear mixed-effects model to compare the QOC and medical expenses between groups. Results: After the selection and matching process, we enrolled 1714 patients (67.7 ± 13.2 years, 62.7% male) categorized into the HSC and UC groups (n = 857 in each group). The HSC groups showed generally better QOC in the four indices (with emergency room visit, hospitalization, intensive care unit admission, and receiving chemotherapy) than the UC group in those who initiated HSC 8–60 days before death. The HSC group also had significantly lower medical expenses than the UC group in those who initiated HSC 15–90 days before death. Conclusions: Among patients with terminal cancer, HSC initiation before the last 8 days and 15 days of lives can effectively improve QOC and save medical expenses, respectively. [ABSTRACT FROM AUTHOR]

Recently, increasing attention has been paid to the effects of air pollutants on autoimmune diseases. The results of relationship between ambient air pollution and multiple sclerosis (MS) showed a variety of differences. Thus, the purpose of this study is to further clarify and quantify the relationship between ambient air pollutants and MS through meta-analysis. Through electronic literature search, literature related to our research topic was collected in Cochrane Library, Embase, and PubMed till August 18, 2020, according to certain criteria. Pooled risk estimate and 95% confidence intervals (95%CI) were calculated by random-effect model analysis. After removing copies, browsing titles and abstracts, and reading full text, 6 studies were finally included. The results showed that only particulate matter (PM) with aerodynamic diameter ≤ 10 (PM10) was related to MS (pooled HR = 1.058, 95% CI = 1.050–1.066), and no correlation was found between PM with aerodynamic diameter < 2.5 (PM2.5), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), benzene (C6H6), major road < 50 m, and MS. There was no publication bias, and the heterogeneity analysis results were stable. PM10 is correlated with the disease MS, while other pollution is not connected with MS. Therefore, it is important for MS patients to take personal protection against particulate pollution and avoid exposure to higher levels of PM. [ABSTRACT FROM AUTHOR]

Apigenin, identified as 4′, 5, 7-trihydroxyflavone, is a natural flavonoid compound that has many interesting pharmacological activities and nutraceutical potential including anti-inflammatory and antioxidant functions. Chronic, low-grade inflammation and oxidative stress are involved in both the initiation and progression of hypertension and hypertension-induced cardiac hypertrophy. However, whether or not apigenin improves hypertension and cardiac hypertrophy through modulating NADPH oxidase-dependent reactive oxygen species (ROS) generation and inflammation in hypothalamic paraventricular nucleus (PVN) has not been reported. This study aimed to investigate the effects of apigenin on hypertension in spontaneously hypertensive rats (SHRs) and its possible central mechanism of action. SHRs and Wistar-Kyoto (WKY) rats were randomly assigned and treated with bilateral PVN infusion of apigenin or vehicle (artificial cerebrospinal fluid) via osmotic minipumps (20 μg/h) for 4 weeks. The results showed that after PVN infusion of apigenin, the mean arterial pressure (MAP), heart rate, plasma norepinephrine (NE), Beta 1 receptor in kidneys, level of phosphorylation of PKA in the ventricular tissue and cardiac hypertrophy, perivascular fibrosis, heart level of oxidative stress, PVN levels of oxidative stress, interleukin 1β (IL-1β), interleukin 6 (IL-6), iNOS, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), NOX2 and NOX4 were attenuated and PVN levels of interleukin 10 (IL-10), superoxide dismutase 1 (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67) were increased. These results revealed that apigenin improves hypertension and cardiac hypertrophy in SHRs which are associated with the down-regulation of NADPH oxidase-dependent ROS generation and inflammation in the PVN. [ABSTRACT FROM AUTHOR]

The host and guest supramolecular interactions between symmetric dicyclohexanocucurbit[6]uril (CyH2Q[6]) and 1H-benzotriazole (BTA) were investigated using nuclear magnetic resonance spectroscopy, isothermal titration calorimetry (ITC), MALDI-TOF mass spectrometry and single-crystal X-ray diffraction analysis. From the experimental results, it was concluded that there was a 1:1 mode of inclusion in BTA@CyH2Q[6]. In addition, the benzene ring of the BTA molecule entered the cavity of CyH2Q[6], while the triazole part was at the port of the CyH2Q[6], forming a supramolecular framework. According to ITC, the complexation process for BTA with CyH2Q[6] is exothermic and mainly driven by enthalpy. [ABSTRACT FROM AUTHOR]

Gardenia yellow pigment (GYP) loaded alginate beads were prepared by the ionic gelation technique, and the preparation parameters were optimized by response surface methodology for high encapsulation efficiency. The optimized parameters were alginate concentration of 3.3%, CaCl2 concentration of 2.4%, and GYP concentration of 3.2 mg/mL, under which the encapsulation efficiency was 73.61%. The surface morphology and bead size analysis showed that the GYP-loaded alginate beads had a roughly spherical morphology with a wrinkled surface, and their average diameter was 0.87 mm. In vitro release test revealed that the GYP release had a pH-dependent release profile and a two-step release process. The Rigter-Peppas model was the most proper model to assess the GYP release from alginate beads. The release mechanism of GYP at pH 1.2 and 7.4 was non-Fickian transport and case-II transport, respectively. The 2,2-diphenyl-1-picrylhydrazyl assay indicated that the encapsulated GYP had effectively maintained 82.56% of the antioxidant activity. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in the world, however, no drug treatment has been approved for this disease. Thus, it is urgent to find effective therapeutic targets for clinical intervention. In this study, we find that liver-specific knockout of PPDPF (PPDPF-LKO) leads to spontaneous fatty liver formation in a mouse model at 32 weeks of age on chow diets, which is enhanced by HFD. Mechanistic study reveals that PPDPF negatively regulates mTORC1-S6K-SREBP1 signaling. PPDPF interferes with the interaction between Raptor and CUL4B-DDB1, an E3 ligase complex, which prevents ubiquitination and activation of Raptor. Accordingly, liver-specific PPDPF overexpression effectively inhibits HFD-induced mTOR signaling activation and hepatic steatosis in mice. These results suggest that PPDPF is a regulator of mTORC1 signaling in lipid metabolism, and may be a potential therapeutic candidate for NAFLD. Non-alcoholic fatty liver disease (NAFLD) has become a prevalent chronic liver disease, however, drugs to treat this disease are still lacking. Here, the authors show that PPDPF inhibits the development of hepatic steatosis by negatively regulating mTORC1-S6K-SREBP1 signaling, which provides a potential therapeutic candidate for NAFLD treatment. [ABSTRACT FROM AUTHOR]

In this study, a total of 160 experimental data points of Henry's law constant of CO2 in 32 imidazole ionic liquids (ILs) were collected, with the temperatures range from 283 to 350 K. Herein intuitive and explanatory descriptors related to Henry's law constant (HLC) were suggested from the 2D structural features of the ILs according to experimental experience and laws. Temperature was used as another variable due to its significant effect on Henry's law constant. Three machine learning methods were used to construct models to fast predict the HLC based on suggested descriptors. Multi-layer Perceptrowas mainly used to build the model and compared with the results of Random forest and Multiple Linear Regression after investigating the outliers and variable selection. In addition, if only one data point was left at a similar temperature and the reduced dataset was also used to build models in the same procedure, the results were not as good as those of the full dataset but still satisfactory. [ABSTRACT FROM AUTHOR]