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.

UNASSIGNED: Metabolic syndrome (MetS) in patients with systemic lupus erythematosus (SLE) represents an additional burden and a poor prognostic factor for the onset or worsening of atherosclerosis and cardiovascular complications. In many patients with lupus nephritis (LN), MetS is often already manifested initially. Our work aimed to determine the frequency and characteristics of MetS in patients with LN, as well as the relationship components of MetS and characteristics of disease activity.
UNASSIGNED: The clinical study included 67 patients with LN, 54 (80.59%) female and 13 (19.41%) male, with an average age of 42.86±14.46 years. Patients were divided into two groups: with MetS (35.82%) and without MetS (64.18%), active LN had (34 or 50.74%), and LN in remission (33 or 49.25%). We monitored clinical and biochemical parameters of interest.
UNASSIGNED: Comparing patients with LN collectively, as well as those with MetS and without MetS, we observed that patients with MetS were older (p=0.001), BMI (p<0.001), and systolic arterial pressure was higher (p=0.002), and smokers were more common in this group (p<0.001). In the analysis, increased triglycerides (p<0.001) and creatinine (p=0.027), and decreased albumin (p=0.050) and GFR (p=0.020) were observed in the group with MetS. MetS was present in 44.11% of patients with active LN and in 27.7% with LN in remission. The most common MetS parameter was arterial hypertension (76.6%), which correlated with GFR and creatinine; hypertriglyceridemia (47.8%), which is correlated with anti-ds-DNA Ab, erythrocyturia, proteinuria, and SLEDAI/r index; decreased HDL cholesterol (28.4%) which significantly correlated with albumin, C3 and anti-ds-DNA Ab.
UNASSIGNED: In our patients with LN, MetS was associated with older age, impaired kidney function, and smoking. The most common parameter of MetS was arterial hypertension and dyslipidemia, which were significantly correlated with disease activity parameters, indicating an increased risk of cardiovascular complications in this group of patients.
UNASSIGNED: Metabolički sindrom (MetS) kod bolesnika sa SLE, predstavlja dodatno opterećenje i loš prognostički faktor za nastanak ili pogoršanje ateroskleroze i za kardiovaskularne komplikacije. MetS je često inicijalno već ispoljen kod mnogih bolesnika sa lupus nefritisom (LN). Cilj našeg rada je bio da utvrdimo učestalost i karakteristike MetS kod bolesnika sa LN, kao i odnos komponenti MetS i aktivnosti lupus nefritisa.
UNASSIGNED: Kliničko ispitivanje je obuhvatilo grupu od 67 pacijenata sa LN, 54 (80,59%) ženskog pola i 13 (19,41%) muškaraca, prosečnih godina starosti 42,86±14,46. Pacijenti su podeljeni u dve grupe: prva sa MetS (35,82%) i druga bez MetS (64,18%), pacijenti su imali aktivan LN (34 ili 50,74%) i LN u remisiji (33 ili 49,25%). Pratili smo kliničke i biohemijske parametre od interesa.
UNASSIGNED: Poredeći pacijente sa LN zbirno kao i one sa MetS i bez MetS, utvrdili smo da su pacijenti sa MetS bili stariji (p=0,001), BMI (p<0,001) i sistolni pritisak je bio viši (p=0,002) i pušači su bili zastupljeniji u ovoj grupi (p<0,001). U analizama su zapaženi povišeni trigliceridi (p<0,001) i kreatinin (p=0,027) i snižen albumin (p=0,050) i GFR (p=0,020) u grupi sa MetS. MetS je bio zastupljen kod 44,11% pacijenata sa aktivnim LN i kod 27,7% sa LN u remisiji. Najzastupljeniji parameter MetS je bila arterijska hipertenzija (76,6%) koja značajno korelirala sa GFR i kreatininom; hipertrigliceridemija (47,8%) koja je korelirala sa anti-ds-DNA At, eritrociturijom, proteinurijom i SLEDAI/r indeksom; snižen HDL holesterol (28,4%) koji je korelirao značajno sa albuminom, C3 i anti-ds-DNA At.
UNASSIGNED: Kod naših pacijenata sa LN, MetS je bio povezan sa starijim životnim dobom, poremećajem bubrežne funkcije i pušenjem. Najzastupljeniji parameter MetS kod pacijenata sa LN je bila arterijska hipertenzija i dislipidemija koja je značajno korelirala sa parametrima aktivnosti bolesti, što upućuje na povećan rizik od kardiovaskularnih komplikacija u ovoj grupi bolesnika.

Since 2020, many compounds have been investigated for their potential use in the treatment of SARS-CoV-2 infection. Among these agents, a huge number of natural products and FDA-approved drugs have been evaluated as potential therapeutics for SARS-CoV-2 using virtual screening and docking studies. However, the identification of the molecular targets involved in viral replication led to the development of rationally designed anti-SARS-CoV-2 agents. Among these targets, the main protease (Mpro) is one of the key enzymes needed in the replication of the virus. The data gleaned from the crystal structures of SARS-CoV-2 Mpro complexes with small-molecule covalent inhibitors has been used in the design and discovery of many highly potent and broad-spectrum Mpro inhibitors. The current review focuses mainly on the covalent type of SARS-CoV-2 Mpro inhibitors. The design, chemistry, and classification of these inhibitors were also in focus. The biological activity of these inhibitors, including their inhibitory activities against Mpro, their antiviral activities, and the SAR studies, were discussed. The review also describes the potential mechanism of the interaction between these inhibitors and the catalytic Cys145 residue in Mpro. Moreover, the binding modes and key binding interactions of these covalent inhibitors were also illustrated. The covalent inhibitors discussed in this review were of diverse chemical nature and origin. Their antiviral activity was mediated mainly by the inhibition of SARS-CoV-2 Mpro, with IC50 values in the micromolar to the nanomolar range. Many of these inhibitors exhibited broad-spectrum inhibitory activity against the Mpro enzymes of other coronaviruses (SARS-CoV-1 and MERS-CoV). The dual inhibition of the Mpro and PLpro enzymes of SARS-CoV-2 could also provide higher therapeutic benefits than Mpro inhibition. Despite the approval of nirmatrelvir by the FDA, many mutations in the Mpro enzyme of SARS-CoV-2 have been reported. Although some of these mutations did not affect the potency of nirmatrelvir, there is an urgent need to develop a second generation of Mpro inhibitors. We hope that the data summarized in this review could help researchers in the design of a new potent generation of SARS-CoV-2 Mpro inhibitors.

Enzymes serve as pivotal components in various biotechnological applications across several industries. Understanding enzyme inhibition sheds light on how certain compounds disrupt biochemical pathways, facilitating the design of targeted drugs for combating diseases. On the other hand, reversible inhibition or enhancement of activity can unlock new ways of controlling industrial reactions and boosting the catalytic activity of native enzymes that are taken out of their natural environments. Over the last two decades, immobilizing enzymes on nanomaterial-based solid supports has emerged as an especially promising approach for tuning enzyme activity. Nanomaterials not only inhibit enzymes but also enhance their performance, showcasing their versatility.  This Concept highlights significant advancements in utilizing nanomaterials for enzyme modulation and discusses future prospects for leveraging this phenomenon in developing sophisticated molecular systems and downstream applications.

MicroRNA-146a (miR-146a) has been involved in the pathophysiology of inflammatory bowel disease (IBD). However, the precise processes are still not entirely understood. Contradictory studies suggest that miR-146a expression could be influenced by the miR-146a rs2910164 C > G polymorphism. This case-control study aimed to investigate the association of miR-146a rs2910164 C > G gene polymorphism and its impact on circulating miR-146a expression levels in Egyptian IBD patients. We included 40 IBD patients and 30 matched healthy controls. Genotyping of miR-146a rs2910164 polymorphism and assessment of miR-146a expression level were done using quantitative real-time PCR in all participants. MiR-146a rs2910164 GG genotype and the G allele were reported in 47% and 70% of the IBD patient group, respectively. And they were associated with increased IBD risk. All the IBD patients with the CC genotype (100%) and most of those with the CG genotype (66.67%) had an inactive disease, while most IBD patients with the GG genotype (73.68%) had an active disease. The miR-146a expression level was the highest with the CC genotype and the lowest with the GG genotype. Also, miR-146a expression level decreased significantly in IBD patients than controls and with disease activity. Combined detection of fecal calprotectin with miR-146a expression level improved the diagnostic sensitivity and the negative predictive value in differentiating IBD patients with active disease from those inactive. Our study identified a strong association of miR-146a rs2910164 GG genotype and G allele with IBD-increased susceptibility and activity in the Egyptian population. The miR-146a rs2910164 polymorphism can reduce miR-146a expression levels in these patients as well. Further research on a larger sample size and different ethnic populations can be the key to progress in establishing this genetic association.

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.