OBJECTIVE: To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus (SLE) and lupus nephritis (LN) in children, as well as their diagnostic value for active SLE and LN.
METHODS: A retrospective selection of 90 hospitalized children with SLE at the Children\'s Medical Center of Second Xiangya Hospital, Central South University from January 2016 to March 2019 as the SLE group, all of whom were tested for anti-C1q antibodies. A control group was formed by collecting 70 hospitalized children with other autoimmune diseases (OAD) during the same period. The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed, and the diagnostic value of anti-C1q in SLE and LN was evaluated.
RESULTS: The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group (P<0.05). The SLE disease activity index score was positively correlated with anti-C1q antibodies (rs=0.371, P<0.001) and positively correlated with anti-double-stranded DNA antibodies (rs=0.370, P<0.001). The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90% and 53.90%, respectively, with an area under the curve of 0.720 (P<0.05) and a critical value of 5.45 U/mL. The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50% and 85.00%, respectively, with an area under the curve of 0.675 (P<0.05) and a critical value of 22.05 U/mL.
CONCLUSIONS: Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.
目的: 研究抗C1q抗体与儿童活动性系统性红斑狼疮（systemic lupus erythematosus, SLE）和狼疮性肾炎（lupus nephritis, LN）的相关性，以及对活动性SLE和活动性LN的诊断价值。方法: 回顾性选择2016年1月—2019年3月中南大学湘雅二医院儿童医学中心住院的SLE患儿90例为SLE组，所有患儿均检测抗C1q抗体。收集同期住院的70例其他自身免疫性疾病（other autoimmune diseases, OAD）患儿为OAD组，比较两组抗C1q抗体水平差异，分析抗C1q抗体与SLE和LN各指标的相关性，评价抗C1q在SLE和LN中的诊断价值。结果: SLE组患儿血清抗C1q抗体水平高于OAD组（P<0.05）。SLE疾病活动性指数与抗C1q抗体呈正相关（rs=0.371，P<0.001），与抗双链DNA抗体呈正相关（rs=0.370，P<0.001）。抗C1q抗体诊断活动性SLE的灵敏度和特异度分别为89.90%和53.90%，曲线下面积为0.720（P<0.05），临界值为5.45 U/mL。抗C1q抗体水平对诊断活动性LN的灵敏度和特异度分别为58.50%和85.00%，曲线下面积为0.675（P<0.05），临界值为22.05 U/mL。结论: 抗C1q抗体可作为评价儿童SLE疾病活动性或预测LN活动性的无创生物学指标之一。.

In both mammals and flies, circadian brain neurons orchestrate physiological oscillations and behaviors like wake and sleep-these neurons can be subdivided by morphology and by gene expression patterns. Recent single-cell sequencing studies identified 17 Drosophila circadian neuron groups. One of these includes only two lateral neurons (LNs), which are marked by the expression of the neuropeptide ion transport peptide (ITP). Although these two ITP+ LNs have long been grouped with five other circadian evening activity cells, inhibiting the two neurons alone strongly reduces morning activity, indicating that they also have a prominent morning function. As dopamine signaling promotes activity in Drosophila, like in mammals, we considered that dopamine might influence this morning activity function. Moreover, the ITP+ LNs express higher mRNA levels than other LNs of the type 1-like dopamine receptor Dop1R1. Consistent with the importance of Dop1R1, cell-specific CRISPR-Cas9 mutagenesis of this receptor in the two ITP+ LNs renders flies significantly less active in the morning, and ex vivo live imaging shows Dop1R1-dependent cyclic AMP (cAMP) responses to dopamine in these two neurons. Notably, the response is more robust in the morning, reflecting higher morning Dop1R1 mRNA levels in the two neurons. As mRNA levels are not elevated in constant darkness, this suggests light-dependent upregulation of morning Dop1R1 transcript levels. Taken together with the enhanced morning cAMP response to dopamine, the data indicate how light and dopamine promote morning wakefulness in flies, mimicking the important effect of light on morning wakefulness in humans.

The intensities of the hydrogen Balmer lines of solar-like stars are investigated for stellar chromospheric activity by using the co-source spectral data of the LAMOST Low-Resolution Spectroscopic Survey (LRS) and Medium-Resolution Spectroscopic Survey (MRS). The Balmer H α , H β , H γ , and H δ lines in the LRS data and the H α line in the MRS data are analyzed. The absolute flux indexes, defined as the ratios of the absolute fluxes at the centers of the Balmer lines to the stellar bolometric flux, are employed to indicate the intensity magnitudes of the Balmer lines in response to stellar activity. The H α indexes derived from the LRS data and the MRS data, respectively, are calibrated to be quantitatively consistent with each other. It is found that, as the H α index increases, the H β , H γ , and H δ indexes first present trend of increasing and then decreasing, and finally increase synchronously with the H α index. The distributions of the Balmer line indexes also reveal the three distinct stages of stellar activity (normal stage, intense stage, and extremely intense stage), in which the extremely intense stage is characterized by the synchronous growth of the indexes of the four Balmer lines. The different behaviors of the H β , H γ , and H δ lines from that of the H α line can be interpreted by the different mechanisms by which the line-core intensities are formed, and the three distinct activity stages imply the very different magnetic field environments and physical conditions of solar-like stars.

BACKGROUND: Identifying rheumatoid arthritis patients at higher risk of complications after total hip arthroplasty could make perioperative management more effective. Here we examined whether disease activity is associated with risk of such complications.
METHODS: We retrospectively analyzed data for 337 rheumatoid arthritis patients at our medical center who underwent primary total hip arthroplasty. Rheumatoid arthritis patients were categorized according to the simplified disease activity index (SDAI), the values of which at admission and follow-up were averaged together. Logistic regression was used to examine associations of mean SDAI with rates of dislocation, infection, periprosthetic fracture and aseptic loosening. As controls, 337 osteoarthritis patients who did not have systemic inflammation and who underwent the same procedure were matched across numerous clinicodemographic variables.
RESULTS: Among the 337 rheumatoid arthritis patients, 38 (11.3%) had postoperative complications, the rates of which varied significantly from 0 to 17.5% (p = 0.003) among the four subgroups whose disease activity based on mean SDAI was categorized as high, moderate, low or in remission. Each 1-unit increase in mean SDAI was associated with a significant increase in risk of postoperative complications (OR 1.015, 95% CI 1.001-1.029, p = 0.035). Across all rheumatoid arthritis patients, rate of complications did not differ significantly between patients who received disease-modifying anti-rheumatic drugs or other treatments. Rates of dislocation, of infection or of all postoperative complications combined were significantly lower among osteoarthritis controls than among rheumatoid arthritis patients.
CONCLUSIONS: Greater mean SDAI is associated with higher risk of dislocation, infection and composite postoperative complications after total hip arthroplasty in rheumatoid arthritis patients. These patients show a significantly higher rate of postoperative complications than osteoarthritis patients, likely reflecting the influence of systemic inflammation. Disease activity should be reduced as much as possible in rheumatoid arthritis patients before they undergo total hip arthroplasty.

Heparinases, including heparinases I-III (HepI, HepII, and HepIII, respectively), are important tools for producing low-molecular-weight heparin, an improved anticoagulant. The poor thermostability of heparinases significantly hinders their industrial and laboratory applications. To improve the thermostability of heparinases, we applied a rigid linker (EAAAK)5 (R) and a flexible linker (GGGGS)5 (F) to fuse maltose-binding protein (MBP) and HepI, HepII, and HepIII from Pedobacter heparinus, replacing the original linker from the plasmid pMAL-c2X. Compared with their parental fusion protein, MBP-fused HepIs, HepIIs, and HepIIIs with linkers (EAAAK)5 or (GGGGS)5 all displayed enhanced thermostability (half-lives at 30°C: 242%-464%). MBP-fused HepIs and HepIIs exhibited higher specific activity (127%-324%), whereas MBP-fused HepIIIs displayed activity similar to that of their parental fusion protein. Kinetics analysis revealed that MBP-fused HepIIs showed a significantly decreased affinity toward heparin with increased Km values (397%-480%) after the linker replacement, whereas the substrate affinity did not change significantly for MBP-fused HepIs and HepIIIs. Furthermore, it preliminarily appeared that the depolymerization mechanism of these fusion proteins may not change after linker replacement. These findings suggest the superior enzymatic properties of MBP-fused heparinases with suitable linker designs and their potential for the bioproduction of low-molecular-weight heparin.

Ascorbate peroxidases (APXs) are key components of the ascorbate-glytathione cycle, which plays an important role in removing excess reactive oxygen species (ROS) in plants. Herein, MaAPX1 was verified as being involved in the ripening and senescence of banana fruit, exhibiting responsiveness to the accumulation of ROS and the oxidation of proteins. Site-directed mutation was applied to explore the mechanism of MaAPX1 activity changes. We found that the 32-site cysteine (Cys, C) served as a potential S-nitrosylation site. The mutant MaAPX1C32S activity was decreased significantly when Cys32 was mutated to serine (Ser, S). Intriguingly, the neighboring conserved 36-site methionine (Met, M), which is adjacent to Cys32, displayed an enzyme activity that was approximately five times higher than that of the wild-type MaAPX1 when mutated to lysine (Lys, K). Utilizing LC-MS/MS spectroscopy coupled with stopped-flow analysis showed that the enhanced MaAPX1M36K activity might be due to the increased S-nitrosylation level of Cys32 and the promotion of intermediate (compound I, the first intermediate product of the reaction of APX with H2O2) production. Molecular docking simulations showed that the S-N bond between Cys32 and Lys36 in MaAPX1M36K might have a function in protecting the thiol of Cys32 from oxidation. MaAPX1M36K, a promising mutant, possesses immense potential for improving the antioxidant capabilities of APX in the realm of bioengineering technology research.

The combined impact of initial state, pressure, and freezing on peroxidase denaturation during high-pressure freezing (HPF) processing of enzyme-containing foods remains unclear. This study investigated solid-liquid (initial low/high concentration) biphasic peroxidase using spectroscopic and computer simulation techniques to analyze structural changes affecting peroxidase (POD) activity under HPF. The results indicate that the primary factors determining POD activity during HPF treatment can be ranked as follows: concentration > physical state > pressure > freezing. Higher initial concentrations strengthen protein interactions, leading to a 1% increase in the molecular diameter and a 34% increase in molecular height of HL-POD, thereby increasing aggregation likelihood during crystallization and facilitating structural changes that activate enzymes by 6-17%. The amide I peak proves to be a reliable indicator for monitoring both POD activity and structural alterations. This study offers valuable insights for optimizing HPF technology in food processing.

The lithium-rich manganese-based layer oxide (LRMO) with high specific capacity (∼300 mAh g-1) and economic feasibility is accepted as the cathode material for high energy density rechargeable batteries. Accompanied by the additional anionic redox reactions during the initial charging process, LRMO presents oxygen release, sluggish Li+ diffusion, and irreversible transition metal ion (TM) migration, which is responsible for its severe structural deterioration and rapid capacity/voltage decay. Here, the N doping strategy is proposed via feasible treatment of oxygen-vacancy-containing Li1.16Ni0.21Mn0.63O2-δ (LNMO) particles. The as obtained LNMO-N samples demonstrate doping N, partially reduced Mn/Ni cations, and oxygen vacancies on the surface. The DFT calculations and experimental results demonstrate that N replacing the crystal oxygen sites on the surface reduces the energy barrier for diffusion, thereby enhancing the kinetics of Li+ diffusion and improving the reversibility of transition metal migration. Furthermore, N doping induces stacking faults and a more flexible structure. Therefore, LNMO-N exhibits a significantly improved anionic-cationic redox reaction reversibility with a high discharge specific capacity of 296.6 mAh g-1 at 20 mA g-1 within the range of 2.0 to 4.8 V and an impressive initial Coulombic efficiency of 85.9%. Moreover, the rate capability is obviously improved with a remarkable capacity of 215.1 mAh g-1 at 200 mA g-1 in 200 cycles with a capacity retention of 72.52% and exceptional performance of 141.4 mAh g-1 even at a higher current density of 1000 mA g-1.

Nanozymes, with their versatile composition and structural adaptability, present distinct advantages over natural enzymes including heightened stability, customizable catalytic activity, cost-effectiveness, and simplified synthesis process, making them as promising alternatives in various applications. Recent advancements in nanozyme research have shifted focus from serendipitous discovery toward a more systematic approach, leveraging machine learning, theoretical calculations, and mechanistic explorations to engineer nanomaterial structures with tailored catalytic functions. Despite its pivotal role, electron transfer, a fundamental process in catalysis, has often been overlooked in previous reviews. This review comprehensively summarizes recent strategies for modulating electron transfer processes to fine-tune the catalytic activity and specificity of nanozymes, including electron-hole separation and carrier transfer. Furthermore, the bioapplications of these engineered nanozymes, including antimicrobial treatments, cancer therapy, and biosensing are also introduced. Ultimately, this review aims to offer invaluable insights for the design and synthesis of nanozymes with enhanced performance, thereby advancing the field of nanozyme research.

Infectious diseases have been jeopardized problem that threaten public health over a long period of time. The growing prevalence of drug-resistant pathogens and infectious cases have led to a decrease in the number of effective antibiotics, which highlights the urgent need for the development of new antibacterial agents. Serine acetyltransferase (SAT), also known as CysE in certain bacterial species, and O-acetylserine sulfhydrylase (OASS), also known as CysK in select bacteria, are indispensable enzymes within the cysteine biosynthesis pathway of various pathogenic microorganisms. These enzymes play a crucial role in the survival of these pathogens, making SAT and OASS promising targets for the development of novel anti-infective agents. In this comprehensive review, we present an introduction to the structure and function of SAT and OASS, along with an overview of existing inhibitors for SAT and OASS as potential antibacterial agents. Our primary focus is on elucidating the inhibitory activities, structure-activity relationships, and mechanisms of action of these inhibitors. Through this exploration, we aim to provide insights into promising strategies and prospects in the development of antibacterial agents that target these essential enzymes.