Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS). Using this newly developed method, we screened the RNA-binding proteins that regulate PABPN1 phase separation and identified the tumor suppressor QKI as a promoter of PABPN1 phase separation. Furthermore, QKI exhibits decreased expression levels and diminished nuclear localization in colorectal cancer cells, resulting in reduced PABPN1 phase separation, which, in turn, promotes alternative polyadenylation (APA), cell proliferation, and migration in colorectal cancer.
Humans ; Colorectal Neoplasms/genetics* ; RNA-Binding Proteins/genetics* ; Poly(A)-Binding Protein I/genetics* ; CRISPR-Cas Systems ; Flow Cytometry ; Cell Proliferation ; Cell Line, Tumor ; Cell Movement

Objective To explore adverse event(AE)signals of sunitinib and to provide a reference for rational drug monitoring based on the Food and Drug Administration Adverse Event Reporting System(FAERS)database.Methods Report odds ratio method(ROR),proportional report ratio method(PRR),polynomial gamma Poisson distribution reduction method(MGPS),and Bayesian confidence interval progressive neural network method(BCPNN)were used to detect the data risk signal strength of sunitinib from the first quarter of 2006 to the third quarter of 2023.Results A total of 35 720 AE reports of sunitinib were retrieved,with 310 positive signals.Most AEs occurred in the first 30 days after treatment(39.71％).Serious AE accounted for 76.37％;27 system organ classifications(SOCs)were involved in positive signals,and the top three were systemic diseases,various reactions at the administration site,gastrointestinal system diseases,and various examinations.High frequency of death,diarrhea,disease progression,and fatigue;65％of the top 20 AEs were new adverse reactions,such as tumor rupture and diffuse proliferation of uveal melanocytes.Conclusion The evaluation of sunitinib should be improved,and medication monitoring should be strengthened to ensure the safety of patients.

Objective To explore adverse event(AE)signals of sunitinib and to provide a reference for rational drug monitoring based on the Food and Drug Administration Adverse Event Reporting System(FAERS)database.Methods Report odds ratio method(ROR),proportional report ratio method(PRR),polynomial gamma Poisson distribution reduction method(MGPS),and Bayesian confidence interval progressive neural network method(BCPNN)were used to detect the data risk signal strength of sunitinib from the first quarter of 2006 to the third quarter of 2023.Results A total of 35 720 AE reports of sunitinib were retrieved,with 310 positive signals.Most AEs occurred in the first 30 days after treatment(39.71％).Serious AE accounted for 76.37％;27 system organ classifications(SOCs)were involved in positive signals,and the top three were systemic diseases,various reactions at the administration site,gastrointestinal system diseases,and various examinations.High frequency of death,diarrhea,disease progression,and fatigue;65％of the top 20 AEs were new adverse reactions,such as tumor rupture and diffuse proliferation of uveal melanocytes.Conclusion The evaluation of sunitinib should be improved,and medication monitoring should be strengthened to ensure the safety of patients.

OBJECTIVE To evaluate the mechanisms underlying the antidepressant effect of ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor(SNRI),in general and its ability to enhance monoaminergic transmission and suppress neuroinflammation in particular.METHODS① Male ICR mice were divided into vehicle(distilled water),duloxetine(DLX,10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following ig administration,the antidepressant effect of ZBH2012001 was evaluated using the tail suspension test(TST)and forced swimming test(FST).② Radioligand binding assay was conducted to evaluate the affinity of ZBH2012001 for human serotonin transporters(hSERTs)and human norepinephrine transporters(hNETs).③ Mice were divided into vehicle(distilled water),DLX(10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following drug administration,the 5-hydroxytryptophan(5-HTP)-induced head-twitch test or yohimbine-induced lethality test were performed to evaluate the effect of ZBH2012001 on the function of the 5-hydroxytryptamine(5-HT)and norepinephrine(NE)systems.④ Mice were divided into vehicle(distilled water+0.1%acetic acid),reserpine model(distilled water+reserpine 5 mg·kg-1),DLX(DLX 20 mg·kg-1+reserpine 5 mg·kg-1)and ZBH2012001(ZBH2012001 5,10 and 20 mg·kg-1+reserpine 5 mg·kg-1)groups.One hour following drug administration,reserpine was injected intraperitoneally to establish a monoamine-depletion model.The ptosis,akinesia,and hypothermia assays were performed to evaluate the effect of ZBH2012001 on the down-regulation of the reserpine-induced monoamine system.The TST in mice was used to evaluate the effect of ZBH2012001 on reserpine-induced depressive-like behavior while high-performance liquid chromatography with electrochemical detection(HPLC-ECD)was used to measure the levels of monoamines and their metabolites in the hippocampal tissue of reserpine-induced monoamine-depletion mice.ELISA was employed to detect the contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.Western blotting was used to assess the expressions of ionized calcium-binding adapter molecule-1(Iba-1)and nuclear factor-kappa B(NF-κB)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.RESULTS ① Compared with the vehicle group,ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the immobility time both in the TST in mice(P<0.01,respectively),and ZBH2012001(20 mg·kg-1)and in the FST in mice(P<0.05).② ZBH2012001 competitively inhibited the binding of[3H]-imipramine to hSERTs and[3H]-nisoxetine to hNETs,with the half maximal inhibitory concentration(IC50)values of 84.95 and 712.90 nmol·L-1,respectively.③Com-pared with the vehicle group,ZBH2012001(10 and 20 mg·kg-1)significantly increased the head twitches induced by 5-HTP in mice(P<0.01,respectively)and increased the mortality rate in mice induced by yohimbine(P<0.05,P<0.01).④ In the reserpine-induced monoamine-depletion model in mice,compared with the vehicle group,mice in the reserpine model group exhibited ptosis,akinesia and hypothermia feature(P<0.01,respectively),significantly prolonged immobility time in the TST(P<0.01),significantly decreased the levels of NE,5-HT and dopamine(DA)(P<0.05,P<0.01),significantly increased the metabolic conversion rate of 5-HT and DA(P<0.01,respectively),significantly elevated levels of TNF-α and IL-6(P<0.05,respectively),and significantly increased expressions of Iba-1 and NF-κB(P<0.05,respectively)in the hippocampus.Compared with the model group,ZBH2012001(5,10 and 20 mg·kg-1)significantly antagonized ptosis and hypothermia behaviors induced by reserpine(P<0.01,respectively),ZBH2012001(10 and 20 mg·kg-1)significantly shortened the immobility time in reserpine-treated mice(P<0.05,P<0.01),ZBH2012001(20 mg·kg-1)significantly increased the levels of NE and 5-HT in the hippocampus of reserpine-treated mice(P<0.05,respectively),decreased the metabolic conversion rate of 5-HT(P<0.05),significantly reduced the contents of TNF-α and IL-6 in the hippocampus of reserpine-treated mice(P<0.05,respectively),ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the expression of Iba-1 protein in the hippocampus of reserpine-treated mice(P<0.01,respec-tively),and ZBH2012001(20 mg·kg-1)significantly reduced the expression of NF-κB protein in the hippocampus of reserpine-treated mice(P<0.05).CONCLUSION ZBH2012001 exerts its antidepres-sant effect through a dual mechanism involving monoamine enhancement and inflammation suppres-sion.

Purpose To investigate the clinicopathological features,molecular genetics and prognosis of high grade B cell lymphoma with concurrent MYC rearrangement and 11q aberra-tions(HGBCL-MYC-11q).MethodsThree cases of HGBCL-MYC-11q were reviewed and analyzed using hematoxylin-eosin staining,immunohistochemistry,EBER in situ hybridization and fluorescence in situ hybridization.Clinical data were collected with follow-up.Results All three patients were male,age was 10,61,and 74 years,respectively.All patients had Ann Arbor stage Ⅳ disease.All three cases were biopsies occurring in the nasopharynx,upper pharynx and ileocecus,respectively.Three cases were morphologically similar to diffuse infiltrative growth of tumor cells,moderate or moderately large cells,round to slightly irregular nuclei and easily visible mitotic figures.Focal necrosis was noted in one case.One case exhibited the distinct"starry sky"pattern.All cases expressed CD20,BCL6 and MUM1 and high Ki67 index,two cases expressed CD10 and two cases ex-pressed BCL2.CD3,CD30 and TDT were all negative.EBER in situ hybridization was all negative.FISH analyses using C-MYC break-apart probes were all positive and all cases had 11q aberrations.One case only had the 11q23.3 amplification;and one case only had the 11q24.3 loss.After a follow-up for 1-18 months,one patient died and two patients survived with disease.ConclusionHGBCL-MYC-11q is rare,morphologically similar to BL/HGBCL,with MYC rearrangement and 11q abnormali-ties.We should enhance awareness of the disease and improve more accurate diagnosis and differential diagnosis of the disease.

Objective To investigate the incidence and influencing factors of aggressive behavior in adolescent inpatients with mental disorders.Methods A total of 372 patients with mental disorders admitted to the Department of Child and Adolescent Psychiatry of the Second Affiliated Hospital of Xinxiang Medical University from January to December 2022 were selected as research subjects.The occurrence of aggressive behavior and its influencing factors were analyzed.Results Among the 372 patients,38(10.2％)cases had aggressive behavior during hospitalization.Univariate and multivariate logistic regression results showed that the history of aggressive behavior,only child,and high irritation factor scores were the risk factors of aggressive behavior in hospitalized adolescents with mental disorders(P＜0.05).Mild,outgoing,insecure and isolated personalities before the onset were protective factors of aggressive behavior in hospitalized adolescents with mental disorders(P＜0.05).Conclusion Adolescent inpatients with mental disorders are likely to have aggressive behavior.Those who have aggressive behavior before,are the only child in their family and get a high score of irritant factors need more attention.Corresponding nursing interventions should be taken in time through nursing assessment to reduce the occurrence of aggressive behavior.

Objective: This study is the first to adopt a cultural and contextual coping model to examine the impact of forbearance coping on compliance and psychological health and unravel the psychosocial mediator and moderator among community-dwelling residents in the post-pandemic era in China. Methods: A multistage cluster convenience sampling strategy was conducted to recruit 402 community-dwelling residents of ten cities in Guangdong province who completed an online survey measuring forbearance coping, anti-pandemic compliance behaviours, family resilience, community resilience and psychological distress. Results: The study results showed an unexpected negative influence of forbearance coping on psychological distress. Nevertheless, forbearance coping facilitated personal compliance with coronavirus disease-2019 mitigation measures and improved psychological health. More importantly, meaning-making of adversity within families partially mediated the negative effect of forbearance on mental health only when respondents perceived higher levels of community resilience. Conclusion This study is the first to apply the cultural and contextual model of coping to Chinese individuals during a significant public health crisis. It expands the model by uncovering mechanisms like behavioural compliance and family meaning-making, and highlights the moderating role of community resilience. The findings emphasize the importance of building resilient communities and supporting mental health, providing evidence for future policy interventions and pandemic/disaster prevention measures in China.

Objective: This study is the first to adopt a cultural and contextual coping model to examine the impact of forbearance coping on compliance and psychological health and unravel the psychosocial mediator and moderator among community-dwelling residents in the post-pandemic era in China. Methods: A multistage cluster convenience sampling strategy was conducted to recruit 402 community-dwelling residents of ten cities in Guangdong province who completed an online survey measuring forbearance coping, anti-pandemic compliance behaviours, family resilience, community resilience and psychological distress. Results: The study results showed an unexpected negative influence of forbearance coping on psychological distress. Nevertheless, forbearance coping facilitated personal compliance with coronavirus disease-2019 mitigation measures and improved psychological health. More importantly, meaning-making of adversity within families partially mediated the negative effect of forbearance on mental health only when respondents perceived higher levels of community resilience. Conclusion This study is the first to apply the cultural and contextual model of coping to Chinese individuals during a significant public health crisis. It expands the model by uncovering mechanisms like behavioural compliance and family meaning-making, and highlights the moderating role of community resilience. The findings emphasize the importance of building resilient communities and supporting mental health, providing evidence for future policy interventions and pandemic/disaster prevention measures in China.

Objective: This study is the first to adopt a cultural and contextual coping model to examine the impact of forbearance coping on compliance and psychological health and unravel the psychosocial mediator and moderator among community-dwelling residents in the post-pandemic era in China. Methods: A multistage cluster convenience sampling strategy was conducted to recruit 402 community-dwelling residents of ten cities in Guangdong province who completed an online survey measuring forbearance coping, anti-pandemic compliance behaviours, family resilience, community resilience and psychological distress. Results: The study results showed an unexpected negative influence of forbearance coping on psychological distress. Nevertheless, forbearance coping facilitated personal compliance with coronavirus disease-2019 mitigation measures and improved psychological health. More importantly, meaning-making of adversity within families partially mediated the negative effect of forbearance on mental health only when respondents perceived higher levels of community resilience. Conclusion This study is the first to apply the cultural and contextual model of coping to Chinese individuals during a significant public health crisis. It expands the model by uncovering mechanisms like behavioural compliance and family meaning-making, and highlights the moderating role of community resilience. The findings emphasize the importance of building resilient communities and supporting mental health, providing evidence for future policy interventions and pandemic/disaster prevention measures in China.

Objective: This study is the first to adopt a cultural and contextual coping model to examine the impact of forbearance coping on compliance and psychological health and unravel the psychosocial mediator and moderator among community-dwelling residents in the post-pandemic era in China. Methods: A multistage cluster convenience sampling strategy was conducted to recruit 402 community-dwelling residents of ten cities in Guangdong province who completed an online survey measuring forbearance coping, anti-pandemic compliance behaviours, family resilience, community resilience and psychological distress. Results: The study results showed an unexpected negative influence of forbearance coping on psychological distress. Nevertheless, forbearance coping facilitated personal compliance with coronavirus disease-2019 mitigation measures and improved psychological health. More importantly, meaning-making of adversity within families partially mediated the negative effect of forbearance on mental health only when respondents perceived higher levels of community resilience. Conclusion This study is the first to apply the cultural and contextual model of coping to Chinese individuals during a significant public health crisis. It expands the model by uncovering mechanisms like behavioural compliance and family meaning-making, and highlights the moderating role of community resilience. The findings emphasize the importance of building resilient communities and supporting mental health, providing evidence for future policy interventions and pandemic/disaster prevention measures in China.