With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

OBJECTIVE: To investigate the expression levels of EZH2 and KMT2D in patients with diffuse large B-cell lymphoma (DLBCL) and their relationship with pathological features. METHODS: 84 patients with DLBCL treated in our hospital from January 2021 to June 2022 were selected as the study subjects, and clinical characteristics such as sex, age and pathological classification of the patients were collected. Immunohistochemistry was used to detecet the expression of KMT2D and EZH2 proteins in tumor tissue cells of the DLBCL patients. The differential expression of KMT2D and EZH2 in subgroups of different sexes, ages, primary sites, clinical stages, Hans subtypes, etc. were compared. The correlation between the expression of KMT2D and EZH2 protein and BCL-6, CD79A was analyzed and validated through the interaction of protein molecular structures. We followed up and recorded the survival status of the patients for 12 months, and analyzed the factors that affect the mortality of DLBCL patients. RESULTS: The positive rate of KMT2D and EZH2 was high (over 95%) in DLBCL patients. There was no significant difference in the expression of EZH2 and KMT2D among subgroups of different sexes, ages and stages (P >0.05). However, patients with different levels of BCL-6 and CD79A expression showed differences in EZH2 and KMT2D expression (P < 0.05). EZH2 and KMT2D were positively correlated with BCL-6 (r =0.391, r =0.332) and CD79A (r =0.309, r =0.258), respectively, and there were interactions in the protein molecular structures. The risk factors for mortality in DLBCL patients include male sex (OR =1.106, 95%CI : 1.082-1.130, P < 0.001), stage II (OR =1.778, 95%CI : 1.567-2.016, P < 0.001), stage IV (OR =2.233, 95%CI : 2.021-2.467, P < 0.001), EZH2 positive (OR =2.762, 95%CI : 1.304-5.850, P =0.008), BCL-6 positive (OR =7.309, 95%CI : 1.340-39.859, P =0.022), age≥74 years (OR =3.080, 95%CI : 1.658-5.723, P < 0.001), and 63-73 years old (OR =2.400, 95%CI : 1.564-3.682, P < 0.001), while KMT2D positive (OR =0.180, 95%CI : 0.054-0.608, P =0.006) and 41-51 years old (OR =0.406, 95%CI : 0.274-0.603, P < 0.001) were factors which could reduce the risk of mortality. CONCLUSION EZH2 and KMT2D are highly expressed in patients with DLBCL, and they are positively correlated with BCL-6 and CD79A, and affect the prognosis of DLBCL patients.
Humans ; Enhancer of Zeste Homolog 2 Protein/metabolism* ; Lymphoma, Large B-Cell, Diffuse/metabolism* ; DNA-Binding Proteins/metabolism* ; Female ; Male ; Middle Aged ; Adult ; Neoplasm Proteins/metabolism* ; Aged ; Immunohistochemistry ; Proto-Oncogene Proteins c-bcl-6/metabolism* ; Prognosis

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Objective:To investigate the efficacy of Saussurea involucrata injection (SII) in alleviating rheumatoid arthritis (RA) and to explore the mechanism of action of SII in alleviating RA through the Toll-like receptor 4 (TLR4)/nuclear factor-kappaBp65 (NF-κBp65) pathway-mediated M1 macrophage polarization.Methods:In vivo experiments were conducted using a collagen-induced arthritis (CIA) rat model. After successful modeling, the CIA rats were randomly assigned into five groups ( n=10 per group): CIA control group, MTX group, low-dose SII (L-SII) group, medium-dose SII (M-SII) group, and high-dose SII (H-SII) group. The efficacy of SII in alleviating RA was evaluated using arthritis index scores, histopathology, and ELISA to measure serum levels of nitric oxide (NO), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Subsequently, Western blot analysis was used to detect the expression of inducible nitric oxide synthase (iNOS) and CD86 proteins in synovial tissue. In vitro experiments involved first isolating and inducing rat bone marrow-derived macrophages (BMDMs). Then, BMDMs were polarized toward the M1 phenotype using lipopolysaccharide (LPS) combined with interferon-γ (IFN-γ). Concurrently, cells were treated with SII and the TLR4 inhibitor TAK242. Subsequently, ELISA was used to detect NO, IL-1β, TNF-α levels in the cell culture supernatant via ELISA. RT-qPCR was used to detect the expression of IL-1b, IL-6, and TNF-α genes in each group of cells. Western blot analysis was performed to detect the expression of iNOS, CD86, TLR4, myeloid differentiation primary response 88 (MyD88), and p-NF-κBp65/NF-κBp65 proteins in the cells. Data analysis between multiple groups was performed using one-way analysis of variance, and between pairs using LSD- t-tests. Results:In vivo experimental results showed that compared with the CIA group(7.90 ± 0.70), MTX and SII both improved the pathological symptoms of rats and reduced the ankle joint pathological score [MTX (4.40 ± 0.92), L-SII (7.00 ± 0.89), M-SII (5.10 ± 1.30), H-SII (4.90 ± 0.94), t=33.86, P<0.001; t=9.10, P<0.001; t=2.38, P=0.029; t=5.69, P<0.001; t=7.66, P<0.001], while downregulating serum levels of NO, IL-1β, IL-6, and TNF-α levels in serum, as well as iNOS [ t=30.01, P<0.001; t=6.17, P=0.003; t=10.86, P<0.001; t=28.95, P<0.001; t=19.03, P<0.001] and CD86 [ t=65.61, P<0.001; t=8.76, P<0.001; t=13.18, P<0.001; t=13.22, P<0.001; t=18.91, P<0.001] expression. In vitro experimental results showed that compared with BMDMs treated with LPS and IFN-γ, SII and TAK242 treatment reduced the levels of NO, IL-1β, IL-6, and TNF-α in the supernatant and decreased the expression of IL-1b, IL-6, and TNF-α genes. Additionally, SII and TAK242 treatment downregulated the expression of iNOS and CD86 proteins in cells, and simultaneously downregulated TLR4, MYD88, and p-NF-κBp65/NF-κBp65 expression ( t=35.84, P<0.001; t=15.69, P<0.001; t=21.99, P<0.001; t=23.64, P<0.001; t=22.50, P<0.001). Additionally, compared with the TAK242 group alone, TAK242 + H-SII showed no significant differences in the modulation of M1 macrophage polarization and TLR4/NF-κBp65 pathway-related indicators. Conclusion:SII exerts anti-inflammatory and anti-RA effects by inhibiting TLR4/NF-κBp65-mediated M1 macrophage polarization.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To investigate the efficacy of Saussurea involucrata injection (SII) in alleviating rheumatoid arthritis (RA) and to explore the mechanism of action of SII in alleviating RA through the Toll-like receptor 4 (TLR4)/nuclear factor-kappaBp65 (NF-κBp65) pathway-mediated M1 macrophage polarization.Methods:In vivo experiments were conducted using a collagen-induced arthritis (CIA) rat model. After successful modeling, the CIA rats were randomly assigned into five groups ( n=10 per group): CIA control group, MTX group, low-dose SII (L-SII) group, medium-dose SII (M-SII) group, and high-dose SII (H-SII) group. The efficacy of SII in alleviating RA was evaluated using arthritis index scores, histopathology, and ELISA to measure serum levels of nitric oxide (NO), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Subsequently, Western blot analysis was used to detect the expression of inducible nitric oxide synthase (iNOS) and CD86 proteins in synovial tissue. In vitro experiments involved first isolating and inducing rat bone marrow-derived macrophages (BMDMs). Then, BMDMs were polarized toward the M1 phenotype using lipopolysaccharide (LPS) combined with interferon-γ (IFN-γ). Concurrently, cells were treated with SII and the TLR4 inhibitor TAK242. Subsequently, ELISA was used to detect NO, IL-1β, TNF-α levels in the cell culture supernatant via ELISA. RT-qPCR was used to detect the expression of IL-1b, IL-6, and TNF-α genes in each group of cells. Western blot analysis was performed to detect the expression of iNOS, CD86, TLR4, myeloid differentiation primary response 88 (MyD88), and p-NF-κBp65/NF-κBp65 proteins in the cells. Data analysis between multiple groups was performed using one-way analysis of variance, and between pairs using LSD- t-tests. Results:In vivo experimental results showed that compared with the CIA group(7.90 ± 0.70), MTX and SII both improved the pathological symptoms of rats and reduced the ankle joint pathological score [MTX (4.40 ± 0.92), L-SII (7.00 ± 0.89), M-SII (5.10 ± 1.30), H-SII (4.90 ± 0.94), t=33.86, P<0.001; t=9.10, P<0.001; t=2.38, P=0.029; t=5.69, P<0.001; t=7.66, P<0.001], while downregulating serum levels of NO, IL-1β, IL-6, and TNF-α levels in serum, as well as iNOS [ t=30.01, P<0.001; t=6.17, P=0.003; t=10.86, P<0.001; t=28.95, P<0.001; t=19.03, P<0.001] and CD86 [ t=65.61, P<0.001; t=8.76, P<0.001; t=13.18, P<0.001; t=13.22, P<0.001; t=18.91, P<0.001] expression. In vitro experimental results showed that compared with BMDMs treated with LPS and IFN-γ, SII and TAK242 treatment reduced the levels of NO, IL-1β, IL-6, and TNF-α in the supernatant and decreased the expression of IL-1b, IL-6, and TNF-α genes. Additionally, SII and TAK242 treatment downregulated the expression of iNOS and CD86 proteins in cells, and simultaneously downregulated TLR4, MYD88, and p-NF-κBp65/NF-κBp65 expression ( t=35.84, P<0.001; t=15.69, P<0.001; t=21.99, P<0.001; t=23.64, P<0.001; t=22.50, P<0.001). Additionally, compared with the TAK242 group alone, TAK242 + H-SII showed no significant differences in the modulation of M1 macrophage polarization and TLR4/NF-κBp65 pathway-related indicators. Conclusion:SII exerts anti-inflammatory and anti-RA effects by inhibiting TLR4/NF-κBp65-mediated M1 macrophage polarization.

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male

Aim To explore the protective effects of Xiyanping injection against lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice,and investi-gate the underlying mechanism.Methods In the LPS-induced ALI mouse model,the protective effect of Xiyanping injection against ALI was evaluated by ob-serving the pathological indicators of lung tissue.Net-work pharmacology and molecular docking were used to explore its mechanism.Western blot method was used to validate the predicted target proteins.Results Xiy-anping injection significantly improved the pathological injury and alleviated inflammatory reactions in lungs of ALI mice.Four active ingredients were identified in Xiyanping injection,namely,14-deoxy-11-oxo-an-drographolide,14-deoxyandrographolide,14-deoxy-12-methoxyandrographolide,and andrographolide-19-β-D-glucoside.A total of 288 corresponding drug targets and 4 960 ALI-related targets were obtained,with 192 genes overlapping.The ten core targets associated with Xiyanping injection were identified as STAT3,EGFR,PIK3R1,MAPK1,PIK3CA,NFKB1,ESR1,MAPK8,JAK2,and FYN.GO enrichment analysis re-vealed 310 biological processes(BP),65 cellular components(CC),and 80 molecular functions(MF)associated with the overlapping genes.KEGG pathway enrichment analysis identified 141 pathways related to ALI,with the top 20 pathways including MAPK,TNF-α,VEGF,cAMP,mTOR,AMPK,NOD,JAK-STAT,IL-17,and NF-κB.Molecular docking results demonstrated strong binding affinity between core tar-gets(MAPK1,MAPK8,NFKB1)and active ingredi-ents(14-deoxy-12-methoxyandrographolide and 14-de-oxyandrographolide).Western blotting showed that medium and high doses of Xiyanping injection signifi-cantly downregulated p38,JNK,ERKl/2,NF-κB p65 protein expression in lung tissue of ALI mice(P＜0.01).Conclusions Xiyanping injection has a cer-tain protective effect against ALI,and the mechanism is related to regulating MAPK and NF-κB signaling pathways.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.