Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Objective　To understand the impact of early and timely treatment and initial antiviral treatment regimen on mortality and attrition of antiretroviral therapy. Methods A retrospective cohort study was conducted using download data on antiretroviral therapy for HIV-infected patients in Liuzhou City, Guangxi Province, from the database of the Basic Information System for AIDS Control and Prevention (BISAC) from 2010 to 2020. The Cox proportional risk regression model was used to analyze the influencing factors of mortality and attrition. Results A total of 15 713 infected patients were included, including 53.4% aged 18-<50 years, 69.4% male, 61.0% farmer, 75.1% CD4 count <350 cells /μL before initial antiviral treatment, the overall mortality rate was 4.30/100 person-years, and the overall attrition was 2.42/100 person-years. The results of Cox regression analysis showed that the influencing factors of mortality were pretreatment CD4 counts of 350-<500 cells/μL(AHR=0.72, 95%CI: 0.63-0.81) and ≥500 cells/μL (AHR= 0.64, 95%CI: 0.55-0.76); duration from diagnosis to initial antiviral treatment 91-180 days (AHR=1.25, 95%CI: 1.08-1.45), 181-365 days (AHR=1.26, 95%CI: 1.08-1.47), and ≥365 days (AHR=1.26, 95%CI: 1.11-1.44); initial antiviral treatment regimens of D4T+3TC+EFV/NVP (AHR=1.47, 95%CI: 1.32-1.63) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.73, 95%CI: 1.50-1.99). Factors affecting attrition were pretreatment CD4 counts of 350-499 cells/μL (AHR=1.32, 95%CI: 1.16-1.50) and ≥500 cells/μL (AHR=1.28, 95%CI: 1.10-1.50); interval from HIV positivity confirmation to initial dosing ≥365 days (AHR=1.21, 95%CI: 1.04-1.40), initial antiviral treatment regimens of TDF+3TC+NVP (AHR=1.32, 95%CI: 1.13-1.55), AZT+3TC+EFV/NVP (AHR=1.43, 95%CI: 1.26-1.62) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.33, 95CI%: 1.06-1.67). Conclusions　Early and timely treatment and the initial antiviral treatment regimen of TDF+3TC+EFV have good efficacy, but attention should be paid to the high risk of attrition of HIV-infected people with high CD4 count before treatment.

BACKGROUND:Trauma-induced coagulopathy(TIC)due to serious injuries significantly leads to increased mortality and morbidity among elderly patients.However,the risk factors of TIC are not well elucidated.This study aimed to explore the risk factors of TIC in elderly patients who have major trauma. METHODS:In this retrospective study,the risk factors for TIC in elderly trauma patients at a single trauma center were investigated between January 2015 and September 2020.The demographic information including gender,age,trauma parts,injury severity,use of blood products,use of vasopressors,need of emergency surgery,duration of mechanical ventilation,length of stay in the intensive care unit(ICU)and hospital,and clinical outcomes were extracted from electric medical records.Multivariate logistic regression analysis was performed to differentiate risk factors,and the performance of the model was evaluated using receiver operating characteristics(ROC)curves. RESULTS:Among the 371 elderly trauma patients,248(66.8%)were male,with the age of 72.5±6.8 years,median injury severity score(ISS)of 24(IQR:17-29),and Glasgow coma score(GCS)of 14(IQR:7-15).Of these patients,129(34.8%)were diagnosed with TIC,whereas 242(65.2%)were diagnosed with non-TIC.The severity scores such as ISS(25[20-34]vs.21[16-29],P<0.001)and shock index(SI),(0.90±0.66 vs.0.58±0.18,P<0.001)was significantly higher in the TIC group than in the non-TIC group.Serum calcium levels(1.97±0.19 mmol/L vs.2.15±0.16 mmol/L,P<0.001),fibrinogen levels(1.7±0.8 g/L vs.2.8±0.9 g/L,P<0.001),and base excess(BE,-4.9±4.6 mmol/L vs.-1.2±3.1 mmol/L,P<0.001)were significantly lower in the TIC group than in the non-TIC group.Multivariate logistic regression analysis revealed that ISS>16(OR:3.404,95%CI:1.471-7.880;P=0.004),SI>1(OR:5.641,95%CI:1.700-18.719;P=0.005),low BE(OR:0.868,95%CI:0.760-0.991;P=0.037),hypocalcemia(OR:0.060,95%CI:0.009-0.392;P=0.003),and hypofibrinogenemia(OR:0.266,95%CI:0.168-0.419;P<0.001)were independent risk factors for TIC in elderly trauma patients.The AUC of the prediction model included all these risk factors was 0.887(95%CI:0.851-0.923)with a sensitivity and specificity of 83.6%and 82.6%,respectively. CONCLUSION:Higher ISS(more than 16),higher SI(more than 1),acidosis,hypocalcemia,and hypofibrinogenemia emerged as independent risk factors for TIC in elderly trauma patients.

BACKGROUND:Trauma-induced coagulopathy(TIC)due to serious injuries significantly leads to increased mortality and morbidity among elderly patients.However,the risk factors of TIC are not well elucidated.This study aimed to explore the risk factors of TIC in elderly patients who have major trauma. METHODS:In this retrospective study,the risk factors for TIC in elderly trauma patients at a single trauma center were investigated between January 2015 and September 2020.The demographic information including gender,age,trauma parts,injury severity,use of blood products,use of vasopressors,need of emergency surgery,duration of mechanical ventilation,length of stay in the intensive care unit(ICU)and hospital,and clinical outcomes were extracted from electric medical records.Multivariate logistic regression analysis was performed to differentiate risk factors,and the performance of the model was evaluated using receiver operating characteristics(ROC)curves. RESULTS:Among the 371 elderly trauma patients,248(66.8%)were male,with the age of 72.5±6.8 years,median injury severity score(ISS)of 24(IQR:17-29),and Glasgow coma score(GCS)of 14(IQR:7-15).Of these patients,129(34.8%)were diagnosed with TIC,whereas 242(65.2%)were diagnosed with non-TIC.The severity scores such as ISS(25[20-34]vs.21[16-29],P<0.001)and shock index(SI),(0.90±0.66 vs.0.58±0.18,P<0.001)was significantly higher in the TIC group than in the non-TIC group.Serum calcium levels(1.97±0.19 mmol/L vs.2.15±0.16 mmol/L,P<0.001),fibrinogen levels(1.7±0.8 g/L vs.2.8±0.9 g/L,P<0.001),and base excess(BE,-4.9±4.6 mmol/L vs.-1.2±3.1 mmol/L,P<0.001)were significantly lower in the TIC group than in the non-TIC group.Multivariate logistic regression analysis revealed that ISS>16(OR:3.404,95%CI:1.471-7.880;P=0.004),SI>1(OR:5.641,95%CI:1.700-18.719;P=0.005),low BE(OR:0.868,95%CI:0.760-0.991;P=0.037),hypocalcemia(OR:0.060,95%CI:0.009-0.392;P=0.003),and hypofibrinogenemia(OR:0.266,95%CI:0.168-0.419;P<0.001)were independent risk factors for TIC in elderly trauma patients.The AUC of the prediction model included all these risk factors was 0.887(95%CI:0.851-0.923)with a sensitivity and specificity of 83.6%and 82.6%,respectively. CONCLUSION:Higher ISS(more than 16),higher SI(more than 1),acidosis,hypocalcemia,and hypofibrinogenemia emerged as independent risk factors for TIC in elderly trauma patients.

BACKGROUND:Trauma-induced coagulopathy(TIC)due to serious injuries significantly leads to increased mortality and morbidity among elderly patients.However,the risk factors of TIC are not well elucidated.This study aimed to explore the risk factors of TIC in elderly patients who have major trauma. METHODS:In this retrospective study,the risk factors for TIC in elderly trauma patients at a single trauma center were investigated between January 2015 and September 2020.The demographic information including gender,age,trauma parts,injury severity,use of blood products,use of vasopressors,need of emergency surgery,duration of mechanical ventilation,length of stay in the intensive care unit(ICU)and hospital,and clinical outcomes were extracted from electric medical records.Multivariate logistic regression analysis was performed to differentiate risk factors,and the performance of the model was evaluated using receiver operating characteristics(ROC)curves. RESULTS:Among the 371 elderly trauma patients,248(66.8%)were male,with the age of 72.5±6.8 years,median injury severity score(ISS)of 24(IQR:17-29),and Glasgow coma score(GCS)of 14(IQR:7-15).Of these patients,129(34.8%)were diagnosed with TIC,whereas 242(65.2%)were diagnosed with non-TIC.The severity scores such as ISS(25[20-34]vs.21[16-29],P<0.001)and shock index(SI),(0.90±0.66 vs.0.58±0.18,P<0.001)was significantly higher in the TIC group than in the non-TIC group.Serum calcium levels(1.97±0.19 mmol/L vs.2.15±0.16 mmol/L,P<0.001),fibrinogen levels(1.7±0.8 g/L vs.2.8±0.9 g/L,P<0.001),and base excess(BE,-4.9±4.6 mmol/L vs.-1.2±3.1 mmol/L,P<0.001)were significantly lower in the TIC group than in the non-TIC group.Multivariate logistic regression analysis revealed that ISS>16(OR:3.404,95%CI:1.471-7.880;P=0.004),SI>1(OR:5.641,95%CI:1.700-18.719;P=0.005),low BE(OR:0.868,95%CI:0.760-0.991;P=0.037),hypocalcemia(OR:0.060,95%CI:0.009-0.392;P=0.003),and hypofibrinogenemia(OR:0.266,95%CI:0.168-0.419;P<0.001)were independent risk factors for TIC in elderly trauma patients.The AUC of the prediction model included all these risk factors was 0.887(95%CI:0.851-0.923)with a sensitivity and specificity of 83.6%and 82.6%,respectively. CONCLUSION:Higher ISS(more than 16),higher SI(more than 1),acidosis,hypocalcemia,and hypofibrinogenemia emerged as independent risk factors for TIC in elderly trauma patients.

BACKGROUND:Trauma-induced coagulopathy(TIC)due to serious injuries significantly leads to increased mortality and morbidity among elderly patients.However,the risk factors of TIC are not well elucidated.This study aimed to explore the risk factors of TIC in elderly patients who have major trauma. METHODS:In this retrospective study,the risk factors for TIC in elderly trauma patients at a single trauma center were investigated between January 2015 and September 2020.The demographic information including gender,age,trauma parts,injury severity,use of blood products,use of vasopressors,need of emergency surgery,duration of mechanical ventilation,length of stay in the intensive care unit(ICU)and hospital,and clinical outcomes were extracted from electric medical records.Multivariate logistic regression analysis was performed to differentiate risk factors,and the performance of the model was evaluated using receiver operating characteristics(ROC)curves. RESULTS:Among the 371 elderly trauma patients,248(66.8%)were male,with the age of 72.5±6.8 years,median injury severity score(ISS)of 24(IQR:17-29),and Glasgow coma score(GCS)of 14(IQR:7-15).Of these patients,129(34.8%)were diagnosed with TIC,whereas 242(65.2%)were diagnosed with non-TIC.The severity scores such as ISS(25[20-34]vs.21[16-29],P<0.001)and shock index(SI),(0.90±0.66 vs.0.58±0.18,P<0.001)was significantly higher in the TIC group than in the non-TIC group.Serum calcium levels(1.97±0.19 mmol/L vs.2.15±0.16 mmol/L,P<0.001),fibrinogen levels(1.7±0.8 g/L vs.2.8±0.9 g/L,P<0.001),and base excess(BE,-4.9±4.6 mmol/L vs.-1.2±3.1 mmol/L,P<0.001)were significantly lower in the TIC group than in the non-TIC group.Multivariate logistic regression analysis revealed that ISS>16(OR:3.404,95%CI:1.471-7.880;P=0.004),SI>1(OR:5.641,95%CI:1.700-18.719;P=0.005),low BE(OR:0.868,95%CI:0.760-0.991;P=0.037),hypocalcemia(OR:0.060,95%CI:0.009-0.392;P=0.003),and hypofibrinogenemia(OR:0.266,95%CI:0.168-0.419;P<0.001)were independent risk factors for TIC in elderly trauma patients.The AUC of the prediction model included all these risk factors was 0.887(95%CI:0.851-0.923)with a sensitivity and specificity of 83.6%and 82.6%,respectively. CONCLUSION:Higher ISS(more than 16),higher SI(more than 1),acidosis,hypocalcemia,and hypofibrinogenemia emerged as independent risk factors for TIC in elderly trauma patients.

BACKGROUND:Trauma-induced coagulopathy(TIC)due to serious injuries significantly leads to increased mortality and morbidity among elderly patients.However,the risk factors of TIC are not well elucidated.This study aimed to explore the risk factors of TIC in elderly patients who have major trauma. METHODS:In this retrospective study,the risk factors for TIC in elderly trauma patients at a single trauma center were investigated between January 2015 and September 2020.The demographic information including gender,age,trauma parts,injury severity,use of blood products,use of vasopressors,need of emergency surgery,duration of mechanical ventilation,length of stay in the intensive care unit(ICU)and hospital,and clinical outcomes were extracted from electric medical records.Multivariate logistic regression analysis was performed to differentiate risk factors,and the performance of the model was evaluated using receiver operating characteristics(ROC)curves. RESULTS:Among the 371 elderly trauma patients,248(66.8%)were male,with the age of 72.5±6.8 years,median injury severity score(ISS)of 24(IQR:17-29),and Glasgow coma score(GCS)of 14(IQR:7-15).Of these patients,129(34.8%)were diagnosed with TIC,whereas 242(65.2%)were diagnosed with non-TIC.The severity scores such as ISS(25[20-34]vs.21[16-29],P<0.001)and shock index(SI),(0.90±0.66 vs.0.58±0.18,P<0.001)was significantly higher in the TIC group than in the non-TIC group.Serum calcium levels(1.97±0.19 mmol/L vs.2.15±0.16 mmol/L,P<0.001),fibrinogen levels(1.7±0.8 g/L vs.2.8±0.9 g/L,P<0.001),and base excess(BE,-4.9±4.6 mmol/L vs.-1.2±3.1 mmol/L,P<0.001)were significantly lower in the TIC group than in the non-TIC group.Multivariate logistic regression analysis revealed that ISS>16(OR:3.404,95%CI:1.471-7.880;P=0.004),SI>1(OR:5.641,95%CI:1.700-18.719;P=0.005),low BE(OR:0.868,95%CI:0.760-0.991;P=0.037),hypocalcemia(OR:0.060,95%CI:0.009-0.392;P=0.003),and hypofibrinogenemia(OR:0.266,95%CI:0.168-0.419;P<0.001)were independent risk factors for TIC in elderly trauma patients.The AUC of the prediction model included all these risk factors was 0.887(95%CI:0.851-0.923)with a sensitivity and specificity of 83.6%and 82.6%,respectively. CONCLUSION:Higher ISS(more than 16),higher SI(more than 1),acidosis,hypocalcemia,and hypofibrinogenemia emerged as independent risk factors for TIC in elderly trauma patients.