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Abstract Background This dynamic nomogram model was developed to predict the probability of fetal loss in pregnant patients with systemic lupus erythematosus (SLE) with mild disease severity before conception. Methods An analysis was conducted on 314 pregnancy records of patients with SLE who were hospitalized between January 2015 and January 2022 at Shenzhen People's Hospital, and the Longhua Branch of Shenzhen People's Hospital. Data from the Longhua Branch of the Shenzhen People's Hospital were utilized as an independent external validation cohort. The nomogram, a widely used statistical visualization tool to predict disease onset, progression, prognosis, and survival, was created after feature selection using multivariate logistic regression analysis. To evaluate the model prediction performance, we employed the receiver operating characteristic curve, calibration curve, and decision curve analysis. Results Lupus nephritis, complement 3, immunoglobulin G, serum albumin, C-reactive protein, and hydroxychloroquine were all included in the nomogram model. The model demonstrated good calibration and discriminatory power, with an area under the curve of 0.867 (95% confidence interval: 0.787–0.947). According to decision curve analysis, the nomogram model exhibited clinical importance when the probability of fetal loss in patients with SLE ranged between 10 and 70%. The predictive ability of the model was demonstrated through external validation. Conclusion The predictive nomogram approach may facilitate precise management of pregnant patients with SLE with mild disease severity before conception.

Objective: To explore the effects and possible mechanisms of the drug pair Cornus officinalis and Radix achyranthis bidentatae (SYR-NX) on improving hypertensive kidney damage. Method: SYR-NX, a formulation of Cornus officinalis and Radix Achyranthis Bidentatae with a dose ratio 1:2.5, was used in this experiment. We investigated the effects of SYR-NX on spontaneously hypertensive rats (SHR) fed with a high-salt diet and Human Kidney-2 (HK2) cells exposed to hypoxia. After 8 weeks of treatment with SYR-NX, blood pressure was tested, and β 2-Microglobulin(β2-MG), blood creatinine (S-cr), endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate (NADPH), M2 pyruvate kinase (PKM2), adenosine triphosphate (ATP), pyruvate, lactate, connective tissue growth factor (CTGF) and tumor necrosis factor-α (TNF-α)were measured. HK2 cells pre-treated with SYR-NX were cultured in a three-gas hypoxic incubator chamber (5 % CO2, 1 % O2, 94 % N2) for 12 h, and then eNOS, PKM2, NADPH, ATP, pyruvate, lactate, CTGF and TNF-α were assessed. Results: SYR-NX significantly reduced SBP, DBP, β2-MG, S-cr, PKM2, pyruvate, lactate, CTGF and TNF-α, and increased eNOS, NADPH, and ATP. Conclusion: SYR-NX can regulate metabolic reprogramming through eNOS and improves hypertensive kidney injury.

ChatGPT, a chatbot developed by OpenAI, has gained widespread popularity and media attention since its release in November 2022. However, little hard evidence is available regarding its perception in various sources. In this paper, we analyze over 300,000 tweets and more than 150 scientific papers to investigate how ChatGPT is perceived and discussed. Our findings show that ChatGPT is generally viewed as of high quality, with positive sentiment and emotions of joy dominating social media. Its perception has slightly decreased since its debut, however, with joy decreasing and (negative) surprise on the rise, and it is perceived more negatively in languages other than English. In recent scientific papers, ChatGPT is characterized as a great opportunity across various fields including the medical domain, but also as a threat concerning ethics and receives mixed assessments for education. Our comprehensive meta-analysis of ChatGPT’s perception after 2.5 months since its release can contribute to shaping the public debate and informing its future development. We make our data available.11 https://github.com/NL2G/ChatGPTReview.

Summary: The conserved WD40-repeat protein WDR5 interacts with multiple proteins both inside and outside the nucleus. However, it is currently unclear whether and how the distribution of WDR5 between complexes is regulated. Here, we show that an unannotated microprotein EMBOW (endogenous microprotein binder of WDR5) dually encoded in the human SCRIB gene interacts with WDR5 and regulates its binding to multiple interaction partners, including KMT2A and KIF2A. EMBOW is cell cycle regulated, with two expression maxima at late G1 phase and G2/M phase. Loss of EMBOW decreases WDR5 interaction with KIF2A, aberrantly shortens mitotic spindle length, prolongs G2/M phase, and delays cell proliferation. In contrast, loss of EMBOW increases WDR5 interaction with KMT2A, leading to WDR5 binding to off-target genes, erroneously increasing H3K4me3 levels, and activating transcription of these genes. Together, these results implicate EMBOW as a regulator of WDR5 that regulates its interactions and prevents its off-target binding in multiple contexts.

Luteolin as a phytogenic algicide can inhibit the growth and microcystins (MCs) release of Microcystis, a dominant genus during cyanobacterial blooms, but how phosphorus (P) level impacts luteolin effect on its growth and MC-pollution risk is unclear. By employing Microcystis aeruginosa as test alga, this study addressed this concern and explored response mechanisms from novel insights of relationship between extracellular polysaccharide (ex-poly) and protein (ex-pro) contents and MC-production/release. At each P level (0.05–5 mg/L), rising luteolin dose more greatly inhibited Microcystis growth and MC-pollution risk, with growth inhibition ratio of around 10%–30%, 20%–50% and 40%–90% for 3, 6 and 12 mg/L luteolin, respectively, but almost increasingly enhanced cellular ability of MC-production/conservation and total and bound ex-poly/ex-pro production. Rising P level promoted Microcystis growth and intracellular/extracellular MCs content (IMC, EMC) in test system at each luteolin dose, thus higher P level weakened algicidal and MC-removal effects of luteolin, indicating that P-decrease was required for stronger application outcome of luteolin. Total and bound ex-poly/ex-pro amount were positively correlated with cellular MC-production/conservation ability, IMC and EMC, which constituted cooperative stress-defense of Microcystis at each P level. Besides, rising luteolin dose posed stronger algicidal effect by inactivating gene expression involving peroxidase synthesis (especially at P-limitation), photosynthesis and P acquisition, while rising P level alleviated algicidal and MC-pollution inhibition effects of luteolin by enhancing gene expression involving N acquisition and peroxidase synthesis. This study shed novel insights for P-dependent effect and mechanisms of luteolin on toxigenic Microcystis growth and MC-pollution control, which guided to mitigating toxigenic Microcystis-dominated cyanobacterial blooms in different P-level water areas.

RIBO-seq and proteogenomics have revealed that mammalian genomes harbor thousands of unannotated small and alternative open reading frames (smORFs, 100 amino acids, respectively). Several dozen mammalian smORF-encoded proteins (SEPs) and alt-ORF-encoded proteins (alt-proteins) have been shown to play important biological roles, while the overwhelming majority of smORFs and alt-ORFs remain uncharacterized, particularly at the molecular level. Functional proteomics has the potential to reveal key properties of unannotated SEPs and alt-proteins in high throughput, and an approach to identify SEPs and alt-proteins undergoing regulated synthesis should be of broad utility. Here, we introduce a chemoproteomic pipeline based on bio-orthogonal non-canonical amino acid tagging (BONCAT) (Dieterich et al., 2006) to profile nascent SEPs and alt-proteins in human cells. This approach is able to identify cellular stress-induced and cell-cycle regulated SEPs and alt-proteins in cells. Graphical abstract Schematic overview of BONCAT-based chemoproteomic profiling of nascent, unannotated small and alternative open reading frame-encoded proteins (SEPs and alt-proteins)

Immune checkpoint inhibitors (ICIs) have significantly improved the survival of patients with advanced tumors. However, immune-related adverse events (irAEs) caused by ICIs, especially high-grade irAEs, are of growing concern. High-grade multisystem irAEs due to toripalimab, a programmed cell death-1 (PD-1) inhibitor, have been rarely reported. Two patients with malignant metastatic tumors were treated with anti-PD-1 immunotherapy. However, both patients developed high-grade multisystem irAEs based on myocarditis, with chest discomfort and malaise as the main clinical manifestation. Both patients had an elevation of cardiac enzymes, abnormal electrocardiography and left ventricular wall motion. Patient 2 was also diagnosed with organizing pneumonia. Immunotherapy was suspended. High-dose intravenous methylprednisolone was immediately initiated. The patients’ symptoms were significantly relieved in a short period of time. Immunosuppressants were discontinued at the 6th month follow-up in patient 1 without relapse. However, patient 2 was lost to follow up due to financial reasons. To the best of our knowledge, this is the first report regarding ICI-associated myocarditis-pneumonia due to toripalimab, indicating the significance of early recognition and management of high-grade multisystem irAEs in clinical practice.

Group creation is the process by which group members collaborate to produce novel and useful ideas or products, including ideas generation and evaluation. However, the interpersonal neural mechanism of group creation during natural communication remains unclear. In this study, two groups of same-sex dyads with similar individual creativity collaborated to complete the Product Improvement Task (creative condition) and the Item Purchase Plan Task (control condition), respectively. Functional near-infrared spectroscopy (fNIRS) was used to record both members’ neural activity in the left prefrontal (lPFC) and right temporal-parietal junction (rTPJ) regions during the task. Considering that the role asymmetry of group members may have an impact on interpersonal neural patterns, we identified leaders and followers in the dyads based on participant performance. The results showed that leaders and followers in the creative condition had significantly lower interpersonal neural synchronization (INS) in the right superior temporal gyrus-left superior frontal gyrus, right supramarginal gyrus-left superior frontal gyrus, and right supramarginal gyrus-left middle frontal gyrus than in the control condition. Partial multivariate Granger causality analyses revealed the influence between dyads was bidirectional but was significantly stronger from the leaders to the followers than the other direction. In addition, in the creative task, the INS was significantly associated with novelty, appropriateness, and conflict of views. All these findings suggest that the ideas generation and ideas evaluation process in group creation have poor interpersonal neural activity coupling due to factors such as the difficulty of understanding novel ideas. However, performances may be improved when groups can better integrate views and reach collective understanding, intentions, and goals. Furthermore, we found that there are differences in the dynamics of INS in different brain regions. The INS related to the novelty of the group creation decreased in the early stages, while the INS related to the appropriateness decreased in the middle stages. Our findings reveal a unique interpersonal neural pattern of group creation processes in the context of natural communication.

As a natural polyphenolic compound, chlorogenic acid (CGA) has attracted increasing attention for its various biological activities, such as antioxidant, liver protection, intestinal barrier protection, and effective treatment of obesity and type II diabetes. However, the poor solubility of CGA in hydrophobic media limits its application in the food, drug and cosmetic industries. In order to obtain new hydrophobic derivatives, a highly efficient synthesis approach of CGA oleyl alcohol ester (CGOA) under non-catalytic and solvent-free conditions was developed in this study. The influences of reaction temperature, reaction time, substrate molar ratio, and stirring rate on the CGA conversion were investigated. The results showed that the optimal conditions were as follows: reaction temperature 200 °C, reaction time 3 h, molar ratio of CGA to oleyl alcohol 1:20, and stirring rate 200 rpm. Under these conditions, the CGA conversion could reach 93.59%. Then, the obtained crude product was purified by solvent extraction and column chromatography, and the purify of CGOA was improved to 98.72%. Finally, the structure of CGOA was identified by FT-IR, HPLC-MS and NMR. This study provides a simple and efficient strategy for the preparation of CGOA with the avoidance of catalysts and solvents.

With the growing and aging population round the world, it becomes increasingly important to understand what factors impact the mental health and cognition of the older generations in order to design effective interventions. In this paper, we investigate the effect of a child’s gender on parental mental health and cognition in the context of one of the world’s largest developing countries and the unique one-child policy, using China Family Panel Studies (CFPS). We exploit the exogeneity of the first child’s gender and find that having a son has significant protective effects on parents’ mathematics performance and memory functions in one-child families, but such effects are absent in multi-child families. Moreover, we find that the protective effect is more pronounced among one-child families in rural areas than urban areas. Our results suggest the existence of gender inequality in China and reveal the hidden long-term social cost of the one-child policy.

Summary: Histone methyl groups can be removed by demethylases. Although LSD1 and JmjC domain-containing proteins have been identified as histone demethylases, enzymes for many histone methylation states or sites are still unknown. Here, we perform a screening of a cDNA library containing 2,500 nuclear proteins and identify hHR23A as a histone H4K20 demethylase. Overexpression of hHR23A reduces the levels of H4K20me1/2/3 in cells. In vitro, hHR23A specifically demethylates H4K20me1/2/3 and generates formaldehyde. The enzymatic activity requires Fe(II) and α-ketoglutarate as cofactors and the UBA domains of hHR23A. hHR23B, a protein homologous to hHR23A, also demethylates H4K20me1/2/3 in vitro and in vivo. We further demonstrate that hHR23A/B activate the transcription of coding genes by demethylating H4K20me1 and the transcription of repetitive elements by demethylating H4K20me3. Nuclear magnetic resonance (NMR) analyses demonstrate that an HxxxE motif in the UBA1 domain is crucial for iron binding and demethylase activity. Thus, we identify two hHR23 proteins as histone demethylases. : Cao et al. screen 2,500 nuclear proteins and find that hHR23A/B are histone H4K20 demethylases. They also show that hHR23A/B activate transcription via demethylation. Keywords: histone demethylase, H4K20 demethylase, H4K20 methylation, UBA domain-containing proteins

The current standards related to live working provide no determined path for equal potential working, in which only safety distance is referred, so that the works are often executed relying on the line maintenance experience. As high-voltage and strong space electrical field intensity exist in 1000 kV ultra-high voltage transmission lines, the real-time safe distance measurement is difficult to be conducted and the exhaustive full-scale experiments are difficult to accomplish due to the varied true tower models and lines. Simulation calculation is aroused for improving the efficiency of safety distance calculation and safety path planning during the process of importing and exporting the potential according to the different kind of tower and the actual line situation. Here, with the cup type iron tower and hanging basket mode, the electrical field intensity in and outside of screening clothes at different part of body while climbing tower and during equal-potential process are calculated, and then the safety distance, the combination gap, and the optimal path planning are carried out. The simulation results demonstrate that electrical field intensity meet safety requirements using the proposed planning path, which enriches the theoretical basis for the safety operation of ultra-high voltage live working.