A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Aim To investigate the effect of linarin on improving cognitive behavior of APP/PS1 mice,and to explore the therapeutic effect of linarin on A β deposi-tion and neuroinflammation and its correlation.Meth-ods APP/PS1 transgenic mice were randomly divid-ed into the model group,high-dose group,medium-dose group,low-dose group and positive control group.C57BL/6J mice were set as the normal group.Morris water maze was used to evaluate the learning and mem-ory abilities of mice.TUNEL staining was used to de-tect the apoptosis of neurons in the CA1 region of mice.IHC was used to detect the expression levels of Aβ42 and GFAP.Western blot was used to detect the expression levels of BACE1 and PS-1.Results Com-pared with the normal group,mice of the model group showed lower NCP,shorter target quadrant travel,less target quadrant residence time percentage(all P＜0.01),higher apoptosis rate of neurons in the CA1 re-gion(P＜0.01),significantly higher protein expres-sion levels of A β42 and GFAP(all P＜0.01),and significantly higher protein expression levels of BACE1 and PS-1(all P＜0.01).Compared with the model group,the medium-dose group,high-dose group and positive control group showed higher NCP,longer tar-get quadrant travel,more target quadrant residence time percentage(all P＜0.05),lower apoptosis rate of neurons in the CA1 region(P＜0.01),significantly lower protein expression levels of A β42 and GFAP(all P＜0.01),and significantly lower protein expression levels of BACE1 and PS-1(all P＜0.01).Conclu-sions Linarin can inhibit two key enzymes to reduce the decomposition of APP and the generation of A β42,thereby inhibiting the activation of astrocytes,allevia-ting neuroinflammation,improving the core pathologi-cal features of AD,and thus significantly improving learning and memory impairment in APP/PS1 mice.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

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 identify the developmental trajectories of internet use and well-being among the elderly in China,and to explore the dynamic relationship between these trajectories and the moderating role of intergenerational support from children.Methods:Group-Based Trajectory Modeling was employed to identify developmental trajectories,and moderated generalized logits models were used to analyze the relationship between trajectories and the moderating effect of intergenerational support from children.Results:Both internet use and well-being among the elderly exhibited differentiated developmental trajectories.Internet use trajectories had a significant positive impact on well-being trajectories.Compared with the low-level group,the elderly in the moderate internet use group being classified into the medium-and high-level well-being groups were 1.550 times(P<0.01)and 1.539 times(P<0.05)those of the offline group respectively,while those in the high-frequency internet use group were 9.560 times(P<0.01)and 9.030 times(P<0.01),respectively.Intergenerational support from children negatively moderated this relationship(medium-level well-being group:OR=0.768,P<0.05;high-level well-being group:OR=0.733,P<0.05).Conclusions:Internet use can sustainably enhance the well-being of the elderly over the long term,with this effect being more pronounced among those receiving less intergenerational support from children.It is recommended to establish a dual-track service system integrating online and offline channels,and to prioritize internet empowerment as a targeted social support strategy for the elderly with insufficient intergenerational support from children.

Objective:To explore the neuroprotective effect of α7 nicotinic acetylcholine receptor (α7nAChR) on rat models of Parkinson's disease (PD) and its underlying mechanism.Methods:Forty-eight 8-week-old SPF-grade SD rats were randomly divided into a normal control group, a PD model group, an α7nAChR empty vector group and an α7nAChR overexpression group, with 12 rats in each group. PD models in the latter 3 groups of rats were established by 6-hydroxydopamine (6-OHDA). Four weeks after modeling, rats in the latter 2 groups were injected with 2 μL α7nAChR overexpression lentivirus or empty vector lentivirus through stereotactic intracerebral injection, while rats in the normal control group did not receive any treatment. Two weeks after injection, the behavioral changes of these rats were detected by apomorphine-induced rotation test; the right substantia nigra pars compacta (SNc) was prepared and performed the following experiments: hematoxylin-eosin (HE) staining and Nissl staining were used to detect the neuron morphological changes, TUNEL was used to detect the neuron apoptosis, fluorescent double labeling was used to detect the expressions of tyrosine hydroxylase (TH) and α-synuclein (α-Syn), ELISA was used to detect the expressions of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), and Western blotting was used to detect the expressions of ferroptosis-related proteins (ferritin heavy chain 1 [FTH1], Sigma receptor 1 [S1R], glutathione peroxidase 4 [GPX4], long chain acyl-coa synthetase 4 [ACSL4], solute carrier family 7 member11 [SLC7A11]), and the expressions of proteins related to CAMKII/ERK pathway (phosphorylated calmodulin kinase Ⅱ [p-CAMK Ⅱ], phosphorylated extracellular signal regulated kinase [p-ERK], and phosphorylated Kirsten rat sarcoma viral oncogene homolog [p-KRAS]).Results:(1) Compared with the normal control group, the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly larger number of rotations ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly smaller number of rotations ( P<0.05). (2) HE staining and Nissl staining showed that the PD model group had decreased number of dopaminergic neurons and Nissl bodies, accompanied by neuronal distribution disorder, nuclear condensation or swelling; the α7nAChR-overexpression group had obviously improved appearance of dopaminergic neurons, with normal morphology and less cell degeneration. (3) TUNEL results showed that compared with the normal control group, the PD model group, α7nAChR empty vector group, and α7nAChR overexpression group had significantly higher apoptosis rate ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had statistically lower apoptosis rate ( P<0.05). (4) Double immunofluorescent staining results showed that compared with the normal control group (303.61±48.40, 13 985.80±1 956.06), the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly increased α-Syn expression (4 310.40±518.43, 3 846.60±524.47 and 1 033.55±59.98) and statistically decreased TH expression (760.97±57.26, 842.55±113.41 and 8 101.82±1 171.85) in the right SNc ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly decreased α-Syn expression and increased TH expression in the right SNc ( P<0.05). (5) ELISA results showed that the 4-HNE and MDA expressions in the right SNc of the PD model group, α7nAChR empty vector group and α7nAChR overexpression group were significantly higher than those in the normal control group ( P<0.05); the 4-HNE and MDA expressions in the α7nAChR overexpression group were significantly lower than those in the PD model group ( P<0.05). (6) Western blotting results showed that compared with the normal control group, the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly decreased FTH1, S1R, GPX4, and SLC7A11 protein expressions, and statistically increased ACSL4 protein expression in the right SNc ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly increased FTH1, S1R, GPX4, and SLC7A11 protein expressions and decreased ACSL4 protein expression in the right SNc ( P<0.05). Compared with the normal control group, the PD model group, α7nAChR empty vector group and α7nAChR overexpression group had significantly increased p-KRAS, p-CAMKII, and p-ERK protein expressions in the right SNc ( P<0.05); compared with the PD model group, the α7nAChR overexpression group had significantly decreased p-KRAS, p-CAMKII, and p-ERK protein expressions in the right SNc ( P<0.05). Conclusion:The α7nAChR may exert neuroprotective effect on PD rat models by regulating the CAMKII/ERK pathway and ferroptosis-related proteins.

Objective:To systematically evaluate the unmet needs and challenges of caregivers of cancer patients at home and clarify their unmet needs.Methods:A computerized search was conducted in PubMed, Web of Science, Embase, Cochrane Library, ProQuest, Scopus, CINAHL, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine disc for qualitative studies on the unmet needs and challenges of caregivers of cancer patients in the home environment. The search time limit was from the establishment of the databases to April 30, 2024. The Joanna Briggs Institute Centre for Evidence-Based Healthcare's quality assessment criteria for qualitative research were used to evaluate the quality of the literatures, and the aggregative integration method was used to summarize and integrate the research results.Results:A total of 17 articles were finally included, which were summarized into eight new categories. Further synthesis yielded three integrated results: caregivers in the home environment face multi-dimensional unmet needs and challenges related to patients; caregivers in the home environment face challenges and unmet needs in self-care; caregivers in the home environment are hesitant to obtain external support, and continuity and sustainability are hindered.Conclusions:Medical staff should accurately assess the unmet needs of caregivers of cancer patients at home, pay attention to their negative experiences, promote positive coping, optimize the patient-and family-centered cancer care model, and strengthen social support.

Objective:To identify the developmental trajectories of internet use and well-being among the elderly in China,and to explore the dynamic relationship between these trajectories and the moderating role of intergenerational support from children.Methods:Group-Based Trajectory Modeling was employed to identify developmental trajectories,and moderated generalized logits models were used to analyze the relationship between trajectories and the moderating effect of intergenerational support from children.Results:Both internet use and well-being among the elderly exhibited differentiated developmental trajectories.Internet use trajectories had a significant positive impact on well-being trajectories.Compared with the low-level group,the elderly in the moderate internet use group being classified into the medium-and high-level well-being groups were 1.550 times(P<0.01)and 1.539 times(P<0.05)those of the offline group respectively,while those in the high-frequency internet use group were 9.560 times(P<0.01)and 9.030 times(P<0.01),respectively.Intergenerational support from children negatively moderated this relationship(medium-level well-being group:OR=0.768,P<0.05;high-level well-being group:OR=0.733,P<0.05).Conclusions:Internet use can sustainably enhance the well-being of the elderly over the long term,with this effect being more pronounced among those receiving less intergenerational support from children.It is recommended to establish a dual-track service system integrating online and offline channels,and to prioritize internet empowerment as a targeted social support strategy for the elderly with insufficient intergenerational support from children.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis