Factor analysis and evaluation of one-year test-retest reliability of the 33-item Childhood Trauma Questionnaire in Chinese adolescents.

The 33-item Childhood Trauma Questionnaire (CTQ-33) is a recently developed tool expanded from the 28-item Childhood Trauma Questionnaire (CTQ-28) to assess childhood trauma events, which showed good test-retest reliability over 2 weeks. However, little is known regarding the factor structure and long-term test-retest reliability of the CTQ-33. To fill such a gap, this study investigated the factorial validity of the CTQ-33 and test-retest reliability of the scale over a relatively long interval of 1 year. Data on demographics, the CTQ-33 scores, and mental health statuses such as depressive/anxiety symptoms were collected in Chinese adolescents (n = 188) twice across a one-year period. Results of the confirmatory factor analysis (CFA) revealed that the Chinese version of CTQ-33 has close factor validity when compared to the original CTQ-28 in college students. Furthermore, the total and most subscale scores of the CTQ-33 have fair to good test-retest reliability (intra-class correlation coefficients >0.6 for the total score, and > 0.4 for most subscales), except for the physical abuse subscale. Moreover, we replicated previous findings of significant positive relationships between levels of different childhood trauma subtypes using the CTQ-33. These findings provide initial evidence supporting that the CTQ-33 is overall reliable to assess childhood traumatic events in adolescents over relatively long intervals.

Analysis of metastasis­related risk factors and clinical relevance in adult soft­tissue sarcoma.

Metastasis occurs in nearly 50% of cases of adult soft-tissue sarcoma (ASTS), leading to a dismal prognosis, with a 2-year survival rate of ~30%. Consequently, a prognostic model that incorporates metastatic characteristics may be instrumental in predicting survival time and in crafting optimal personalized therapeutic strategies for patients with ASTS. In the present study, a prognostic prediction model for ASTS was developed by examining genes that are differentially expressed between non-metastatic and metastatic patients in the Gene Expression Omnibus dataset. The prognostic model, which includes five featured genes [actin γ2 (ACTG2), apolipoprotein D, coatomer protein complex subunit γ2 imprinted transcript 1, collagen type VI α6 chain and osteomodulin], was further validated in patients with ASTS from the Cancer Genome Atlas dataset. Based on these five-gene signatures, patients were categorized into high- and low-risk groups. Functional and pathway analyses revealed disparities in stemness, extracellular matrix and cell adhesion-related pathways between the two risk groups, particularly noting the activation of the PI3K-Akt pathway in high-risk cases. Analysis of immune infiltration also revealed variations in immune microenvironment changes between the two risk groups. Immunohistochemical staining substantiated the prognostic significance of these gene signatures in a specific sarcoma subtype. Additionally, wound-healing and Transwell assays demonstrated that inhibition of ACTG2 by shRNAs curbed cell migration and invasion in a sarcoma HOS cell line, underscoring its role in sarcoma metastasis. In conclusion, the present study successfully developed and validated a metastasis-based prognosis prediction model. This model not only reliably forecasts the survival of patients with ASTS, but also may pave the way for further investigation into the processes underlying sarcoma metastasis, ultimately aiding in the design of tailored therapeutic regimens.

USP49 promotes adenocarcinoma of the esophagogastric junction malignant progression via activating SHCBP1-ß-catenin-GPX4 axis.

Adenocarcinoma of the esophagogastric junction (AEG) has received widespread attention because of its increasing incidence. However, the molecular mechanism underlying tumor progression remains unclear. Here, we report that the downregulation of Ubiquitin-specific peptidase 49 (USP49) promotes ferroptosis in OE33 and OE19 cells, thereby inhibiting cell proliferation in vitro and in vivo, whereas the overexpression of USP49 had the opposite effect. In addition, USP49 downregulation promoted AEG cell radiotherapy sensitivity. Moreover, overexpression of Glutathione PeroXidase 4 (GPX4) reversed the ferroptosis and proliferation inhibition induced by USP49 knockdown. Mechanistically, USP49 deubiquitinates and stabilizes Shc SH2-domain binding protein 1 (SHCBP1), subsequently facilitating the entry of ß-catenin into the nucleus to enhance GPX4 transcriptional expression. Finally, high USP49 expression was correlated with shorter overall survival in patients with AEG. In summary, our findings identify USP49 as a novel regulator of ferroptosis in AEG cells, indicating that USP49 may be a potential therapeutic target in AEG.

Clinical application of a modified wiltse approach in middle and lower thoracic vertebrae: a case-control study of thoracic fracture patients.

BACKGROUND: The Wiltse approach has been extensively employed in thoracolumbar surgeries due to its minimal muscle damage. However, in the middle and lower thoracic spine, the conventional Wiltse approach necessitates the severance of the latissimus dorsi and trapezius muscles, potentially leading to muscular injury. Consequently, we propose a modified Wiltse approach for the middle and lower thoracic vertebrae, which may further mitigate muscular damage. METHODS: From May 2018 to April 2022, 60 patients with spinal fractures in the middle and lower thoracic vertebrae (T5-12) were enrolled in this study. Thirty patients underwent surgery using the modified Wiltse approach (Group A), while the remaining 30 patients received traditional posterior surgery (Group B). The observation indices included operation time, intraoperative blood loss, incision length, number of C-arm exposures, postoperative drainage, postoperative ambulation time, discharge time, as well as preoperative and postoperative Cobb's angle, percentage of anterior vertebral body height (PAVBH), visual analog scale (VAS) Score, and Oswestry disability index (ODI). RESULTS: Compared to the traditional posterior approach, the modified Wiltse approach demonstrated significant advantages in operation time, intraoperative blood loss, length of incision, postoperative ambulation time, postoperative drainage, and discharge time, as well as postoperative VAS and ODI scores. No significant differences were observed between the two groups in terms of number of C-arm exposures, postoperative Cobb's angle, or postoperative PAVBH. CONCLUSION: We propose a modification of the Wiltse approach for the middle and lower thoracic vertebral regions, which may further minimize muscular damage and facilitate the recovery of patients who have undergone surgery in the middle and lower thoracic vertebrae.

Comparisons of clinical characteristics, treatments, and outcomes among different pathological subtypes of chondrosarcoma in the spine.

INTRODUCTION: Spinal chondrosarcoma exhibits higher invasiveness and a worse prognosis compared to chondrosarcoma in the extremities. The prognosis and therapeutic plan vary greatly among different pathological subtypes of chondrosarcoma. This study aimed to analyze the differences in clinical characteristics, molecular features, therapeutic effects, and prognostic factors among the subtypes of chondrosarcoma in the spine. METHODS: A retrospective review was conducted on 205 patients with spinal chondrosarcoma. The clinical features and immunohistochemical (IHC) markers were compared among the pathological subtypes of chondrosarcoma grade 1, grade 2, grade 3, mesenchymal chondrosarcoma (MCS), dedifferentiated chondrosarcoma (DCS), and clear cell chondrosarcoma (CCCS). Chondrosarcoma grade 1/2/3 are collectively referred to as conventional chondrosarcoma (CCS) for multivariate survival analysis. Univariate and multivariate analyses were performed to investigate independent prognostic factors for overall survival (OS) and recurrence-free survival (RFS) in patients with spinal chondrosarcoma. Furthermore, independent prognostic factors for OS and RFS were identified in CCS and MCS. RESULTS: MCS patients were younger than the other subtypes. Patients with chondrosarcoma grade 1/2 had better OS than those with chondrosarcoma grade 3, MCS and DCS, while only chondrosarcoma grade 1 patients showed better RFS than chondrosarcoma grade 2/3, MCS and DCS patients. Ki-67 index was higher in chondrosarcoma grade 3, MCS and DCS than chondrosarcoma grade 1/2. The comparison of IHC markers further highlighted the overexpression of P53/MDM2 in MCS and DCS. Gross total resection, including en-bloc and piecemeal resection, significantly improved OS and RFS for CCS patients, while only en-bloc resection significantly improved the prognosis of MCS patients. Chemotherapy appeared to be important for the OS of MCS patients. CONCLUSION: P53/MDM2 pathway was upregulated in MCS and DCS compared to chondrosarcoma grade 1/2. Radical tumor resection is crucial for the treatment of spinal chondrosarcoma, while MCS patients require further comprehensive treatments perioperatively.

Unveiling the activity origin of electrochemical oxygen evolution on heteroatom-decorated carbon matrix.

Chemical modification via functional dopants in carbon materials holds great promise for elevating catalytic activity and stability. To gain comprehensive insights into the pivotal mechanisms and establish structure-performance relationships, especially concerning the roles of dopants, remains a pressing need. Herein, we employ computational simulations to unravel the catalytic function of heteroatoms in the acidic oxygen evolution reaction (OER), focusing on a physical model of high-electronegative F and N co-doped carbon matrix. Theoretical and experimental findings elucidate that the enhanced activity originates from the F and pyridinic-N (Py-N) species that achieve carbon activation. This activated carbon significantly lowers the conversion energy barrier from O* to OOH*, shifts the potential-limiting step from OOH* formation to O* generation, and ultimately optimizes the energy barrier of the potential-limiting step. This wok elucidates that the critical role of heteroatoms in catalyzing the reaction and unlocks the potential of carbon materials for acidic OER.

Efficient optimization parameter calibration method-based DEM simulation for compacted loess slope under dry-wet cycling.

Dry-wet cycles can cause significant deterioration of compacted loess and thus affect the safety of fill slopes. The discrete element method (DEM) can take into account the non-homogeneous, discontinuous, and anisotropic nature of the geotechnical medium, which is more capable of reflecting the mechanism and process of instability in slope stability analysis. Therefore, this paper proposes to use the DEM to analyze the stability of compacted loess slopes under dry-wet cycles. Firstly, to solve the complex calibration problem between macro and mesoscopic parameters in DEM models, an efficient parameter optimization method was proposed by introducing the chaotic particle swarm optimization with sigmoid-based acceleration coefficients algorithm (CPSOS). Secondly, during the parameter calibration, a new indicator, the bonding ratio (BR), was proposed to characterize the development of pores and cracks in compacted loess during dry-wet cycles, to reflect the impact of dry-wet action on the degradation of bonding between loess aggregates. Finally, according to the results of parameter calibration, the stability analysis model of compacted loess slope under dry-wet cycling was established. The results show that the proposed optimization calibration method can accurately reflect the trend of the stress-strain curve and strength of the actual test results under dry-wet cycles, and the BR also reflects the degradation effect of dry-wet cycles on compacted loess. The slope stability analysis shows that the DEM reflects the negative effect of dry-wet cycles on the safety factor of compacted loess slopes, as well as the trend of gradual stabilization with dry-wet cycles. The comparison with the finite element analysis results verified the accuracy of the discrete element slope stability analysis.

PLK-3-mediated phosphorylation of BAP1 prevents diabetic retinopathy.

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus, and its main clinical manifestation is retinal vascular dysfunction. DR causes blindness and is a problem with significant global health implications. However, treating DR is still challenging. In this study, we aimed to explore the role of polo-like kinase-3 (PLK-3) and the potential regulatory mechanism in DR. Sprague-Dawley rats were injected intraperitoneally with streptozotocin (STZ, 60 mg/kg) to induce a rat model of DR, and rat retinal microvascular endothelial cells (RRMECs) were treated with high glucose (HG, 25 mmol/L glucose) to develop a cell model of DR. We found that PLK-3 was significantly downregulated in the retinal tissues of STZ-induced diabetic rats and HG-induced RRMECs. Lentivirus-mediated PLK-3 overexpression alleviated the histological damages in DR rats. After HG stimulation, cell proliferation, migration, and angiogenesis in RRMECs were inhibited after PLK-3 upregulation. By using label-free proteomics, we identified 82 differentially expressed proteins downstream of PLK-3, including BRCA1-associated protein 1 (BAP1), which was significantly upregulated in PLK-3-overexpressed RRMECs compared to control cells under the HG condition. In vivo and in vitro assays indicated that the forced expression of PLK-3 increased the phosphorylation of BAP1 at serine 592 and caspase-8 expression. Detailed evidence showed that BAP1-shRNA-mediated knockdown restored the cell function in HG-treated RRMECs when PLK-3 was overexpressed. Collectively, this study shows that PLK-3 alleviates retinal vascular dysfunction in DR by inhibiting the phosphorylation of BAP1. Thus, PLK-3 may develop as a promising target for the therapy of DR.

NSUN4 mediated RNA 5-methylcytosine promotes the malignant progression of glioma through improving the CDC42 mRNA stabilization.

5-Methylcytosine (m5C) methylation is a significant post-transcriptional modification that play a crucial role in the development and progression of numerous cancers. Whereas the functions and molecular mechanisms underlying m5C methylation in gliomas remain unclear. This study dedicated to explore changes of m5C levels and the clinical significance of the m5C writer NSUN4 in gliomas. We found that high m5C levels were negatively related to prognosis of patients with glioma. Moreover, gain- and loss-of-function experiments revealed the role of NSUN4 in enhancing m5C modification of mRNA to promote the malignant progression of glioma. Mechanistically speaking, NSUN4-mediated m5C alterations regulated ALYREF binding to CDC42 mRNA, thereby impacting the mRNA stability of CDC42. We also demonstrated that CDC42 promoted glioma proliferation, migration, and invasion by activating the PI3K-AKT pathway. Additionally, rescue experiments proved that CDC42 overexpression weaken the inhibitory effect of NSUN4 knockdown on the malignant progression of gliomas in vitro and in vivo. Our findings elucidated that NSUN4-mediated high m5C levels promote ALYREF binding to CDC42 mRNA and regulate its stability, thereby driving the malignant progression of glioma. This provides theoretical support for targeted the treatment of gliomas.

Diffuse tumors: Molecular determinants shared by different cancer types.

Most cancer types have both diffuse and non-diffuse subtypes, which have rather distinct morphologies, namely scattered tiny tumors vs. one solid tumor, and different levels of aggressiveness. However, the causes for forming such distinct subtypes remain largely unknown. Using the diffuse and non-diffuse gastric cancers (GCs) as the illustrative example, we present a computational study based on the transcriptomic data from the TCGA and GEO databases, to address the following questions: (i) What are the key molecular determinants that give rise to the distinct morphologies between diffuse and non-diffuse cancers? (ii) What are the main reasons for diffuse cancers to be generally more aggressive than non-diffuse ones of the same cancer type? (iii) What are the reasons for their distinct immunoactivities? And (iv) why do diffuse cancers on average tend to take place in younger patients? The study is conducted using the framework we have previously developed for elucidation of general drivers cancer formation and development. Our main discoveries are: (a) the level of (poly-) sialic acids deployed on the surface of cancer cells is a significant factor contributing to questions (i) and (ii); (b) poly-sialic acids synthesized by ST8SIA4 are the key to question (iii); and (c) the circulating growth factors specifically needed by the diffuse subtype dictate the answer to question (iv). All these predictions are substantiated by published experimental studies. Our further analyses on breast, prostate, lung, liver, and thyroid cancers reveal that these discoveries generally apply to the diffuse subtypes of these cancer types, hence indicating the generality of our discoveries.

Urban network noise control based on road grade optimization considering comprehensive traffic environment benefit.

A double-decision optimization model based on the road grade optimization strategy and considered comprehensive traffic environment benefit is proposed to control the traffic noise. The upper-level model maximizes the comprehensive traffic environment benefit, including network noise emission and traffic efficiency. Adjusting the emphasis on noise optimization benefits and traffic efficiency in road network planning through setting weights. The lower-level resolves the question of network traffic flow assignment using a stochastic user-equilibrium model. The increase of traffic environment demand, network noise emissions decrease and travel time rises. In the case, with a low environmental requirement (weighting with 1.1), the sound pressure emission of the network decreases by 9.23% with only a 4.01% increase in travel time. Under the high environmental requirement (weighting with 0.2), the sound pressure decreases by 26.8%, but the travel time rises by as high as 30.9%. The network is optimized towards road grade degradation and is the first to optimize the arterial roads. In addition, it is found that the influence of speed on traffic noise is greater than that of traffic volume through case validation. This method proposing traffic noise optimization strategies at the road network planning level provides technical support for the proactive governance of traffic noise pollution and the improvement of traffic sound environment quality.

sTREM-1 as a Predictive Biomarker for Disease Severity and Prognosis in COVID-19 Patients.

Background: Research on biomarkers associated with the severity and adverse prognosis of COVID-19 can be beneficial for improving patient outcomes. However, there is limited research on the role of soluble TREM-1 (sTREM-1) in predicting the severity and prognosis of COVID-19 patients. Methods: A total of 115 COVID-19 patients admitted to the emergency department of Beijing Youan Hospital from February to May 2023 were included in the study. Demographic information, laboratory measurements, and blood samples for sTREM-1 levels were collected upon admission. Results: Our study found that sTREM-1 levels in the plasma of COVID-19 patients increased with the severity of the disease (moderate vs mild, p=0.0013; severe vs moderate, p=0.0195). sTREM-1 had good predictive value for disease severity and 28-day mortality (area under the ROC curve was 0.762 and 0.805, respectively). sTREM-1 also exhibited significant correlations with age, body temperature, respiratory rate, PaO2/FiO2, PCT, CRP, and CAR. Ultimately, through multivariate logistic regression analysis, we determined that sTREM-1 (OR 1.008, 95% CI: 1.002-1.013, p=0.005), HGB (OR 0.966, 95% CI: 0.935-0.998, p=0.036), D-dimer (OR 1.001, 95% CI: 1.000-1.001, p=0.009), and CAR (OR 1.761, 95% CI: 1.154-2.688, p=0.009) were independent predictors of 28-day mortality in COVID-19 patients. The combination of these four markers yielded a strong predictive value for 28-day mortality in COVID-19 cases with an AUC of 0.919 (95% CI: 0.857 -0.981). Conclusion: sTREM-1 demonstrated good predictive value for disease severity and 28-day mortality, serving as an independent prognostic factor for adverse patient outcomes. In the future, we anticipate conducting large-scale multicenter studies to validate our research findings.

PSMD11 promotes the proliferation of hepatocellular carcinoma by regulating the ubiquitination degradation of CDK4.

BACKGROUND: The 26S proteasome non-ATPase regulatory subunit 11 is a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins, and PSMD11 plays a key role in the regulation of embryonic stem cell proteasome activity. However, the role of PSMD11 in hepatocellular carcinoma has not been studied. In this study, it was found that the expression of PSMD11 in HCC tissues was significantly higher than that in para-cancerous tissues, and was associated with poor prognosis. The results of in vitro experiments showed that PSMD11 knockdown could effectively inhibit the proliferation and apoptosis of hepatoma cell lines, and flow cytometry showed that the G0/G1 phase was significantly prolonged. Through protein spectrometry, immunoprecipitation and in vitro experiments, it was found that PSMD11 can promote the proliferation of hepatocellular carcinoma through regulating the ubiquitination of CDK4 and enhancing its protein stability. This study explores the mechanism of action of PSMD11 in hepatocellular carcinoma and provides new insights for the treatment of hepatocellular carcinoma.

Comprehensive assessment of enhancing dewaterability of dredged sediments by starch-based flocculant.

Dredged sediment poses significant challenges for transportation and subsequent treatment due to its high water content and large volume. Coagulation, a common method of dewatering, can significantly enhance the dewatering performance of dredged sediment. This study synthesized a cationic starch-based flocculant [starch-3-chloro-2-hydroxypropyl trimethylammonium chloride (St-CTA)] through etherification for the flocculation dewatering of dredged sediment. The effectiveness and mechanism of St-CTA as a dewatering flocculant for dredged sediment were investigated. The results demonstrated that when the dosage of St-CTA was 12 mg g-1 TSS (total suspended solids), the dehydration property of dredged sediment substantially improved, with the specific resistance to filtration (SRF) decreasing by 93.3%, the capillary suction time (CST) by 93.5%, and the water content of the filter cake (WC) by 9.7%. The removal rate of turbidity of the supernatant from the conditioned dredged sediment reached 99.6%, accelerating the settling speed and effectively capturing and separating fine particles from the sediment. St-CTA significantly increased the median particle size (D50), altered the microstructure and extracellular polymeric substances (EPS) of the flocs, and increased the fractal dimension of the flocs, making them more compact and conducive to the formation of drainage channels. These findings confirm the feasibility of using potentially environmentally friendly St-CTA as a rapid dewatering conditioning agent for sediment.

APEX-pHLA: A novel method for accurate prediction of the binding between exogenous short peptides and HLA class I molecules.

Human leukocyte antigen (HLA) molecules play critically significant role within the realm of immunotherapy due to their capacities to recognize and bind exogenous antigens such as peptides, subsequently delivering them to immune cells. Predicting the binding between peptides and HLA molecules (pHLA) can expedite the screening of immunogenic peptides and facilitate vaccine design. However, traditional experimental methods are time-consuming and inefficient. In this study, an efficient method based on deep learning was developed for predicting peptide-HLA binding, which treated peptide sequences as linguistic entities. It combined the architectures of textCNN and BiLSTM to create a deep neural network model called APEX-pHLA. This model operated without limitations related to HLA class I allele variants and peptide segment lengths, enabling efficient encoding of sequence features for both HLA and peptide segments. On the independent test set, the model achieved Accuracy, ROC_AUC, F1, and MCC is 0.9449, 0.9850, 0.9453, and 0.8899, respectively. Similarly, on an external test set, the results were 0.9803, 0.9574, 0.8835, and 0.7863, respectively. These findings outperformed fifteen methods previously reported in the literature. The accurate prediction capability of the APEX-pHLA model in peptide-HLA binding might provide valuable insights for future HLA vaccine design.

Discovery of Sovleplenib, a Selective Inhibitor of Syk in Clinical Development for Autoimmune Diseases and Cancers.

Herein we describe the medicinal chemistry efforts that led to the discovery of the clinical-staged Syk inhibitor sovleplenib (41) via a structure-activity relationship investigation and pharmacokinetics (PK) optimization of a pyrido[3,4-b]pyrazine scaffold. Sovleplenib is a potent and selective Syk inhibitor with favorable preclinical PK profiles and robust anti-inflammation efficacy in a preclinical collagen-induced arthritis model. Sovleplenib is now being developed for treating autoimmune diseases such as immune thrombocytopenic purpura and warm antibody hemolytic anemia as well as hematological malignancies.

Mitophagy in mammalian follicle development and health.

Mitophagy, the cellular process that removes damaged mitochondria, plays a crucial role in maintaining normal cell functions. It is deeply involved in the entire process of follicle development and is associated with various ovarian diseases. This review aims to provide a comprehensive overview of mitophagy regulation, emphasizing its role at different stages of follicular development. Additionally, the study illuminates the relationship between mitophagy and ovarian diseases, including ovary aging (OA), primary ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS). A detailed understanding of mitophagy could reveal valuable insights and novel strategies for managing female ovarian reproductive health.

The Value of Chemokine and Chemokine Receptors in Diagnosis, Prognosis, and Immunotherapy of Hepatocellular Carcinoma.

Background: Chemokines and chemokine receptors (CCRs) are involved in a variety of anti-tumour and pro-tumour immune processes in vivo, such as angiogenesis, metastasis, proliferation and invasiveness, and influence patient prognosis and response to therapy. Methods: CCRs differentially expressed in HCC and associated with prognosis were extracted from TCGA and GEO databases, and the obtained CCRs were then used to construct signature genes, and the signature gene were selected for expression validation as well as functional experiments to explore the role of CCRs in the treatment and prognosis of HCC. Results: We constructed a prognostic model including five CCRs (CCL20, CCL23, CCR3, CCR10, and CXCR3) and validated the expression of signature genes. The model's risk score is an independent prognostic factor for HCC. We have also developed prognostic model nomograms for clinical use. In addition, we validated that CCR3 expression is associated with poor prognosis in HCC, and the proliferation and migration ability of HCC cells was significantly inhibited after interfering with the expression of CCR3 in MHCC-LM3. We also looked at differences in pathway enrichment, immune infiltration and immune checkpoints. Finally, we found that risk scores were also correlated with drug sensitivity, the high-risk group had a better sensitivity to sorafenib. Conclusion: The CCRs-related gene signature may better assess HCC prognosis and response to immunotherapy and tyrosine kinase inhibitors such as sorafenib in HCC, providing prospective solutions for diagnosis and treatment.

Presepsin as a prognostic biomarker in COVID-19 patients: combining clinical scoring systems and laboratory inflammatory markers for outcome prediction.

BACKGROUND: There is still limited research on the prognostic value of Presepsin as a biomarker for predicting the outcome of COVID-19 patients. Additionally, research on the combined predictive value of Presepsin with clinical scoring systems and inflammation markers for disease prognosis is lacking. METHODS: A total of 226 COVID-19 patients admitted to Beijing Youan Hospital's emergency department from May to November 2022 were screened. Demographic information, laboratory measurements, and blood samples for Presepsin levels were collected upon admission. The predictive value of Presepsin, clinical scoring systems, and inflammation markers for 28-day mortality was analyzed. RESULTS: A total of 190 patients were analyzed, 83 (43.7%) were mild, 61 (32.1%) were moderate, and 46 (24.2%) were severe/critically ill. 23 (12.1%) patients died within 28 days. The Presepsin levels in severe/critical patients were significantly higher compared to moderate and mild patients (p < 0.001). Presepsin showed significant predictive value for 28-day mortality in COVID-19 patients, with an area under the ROC curve of 0.828 (95% CI: 0.737-0.920). Clinical scoring systems and inflammation markers also played a significant role in predicting 28-day outcomes. After Cox regression adjustment, Presepsin, qSOFA, NEWS2, PSI, CURB-65, CRP, NLR, CAR, and LCR were identified as independent predictors of 28-day mortality in COVID-19 patients (all p-values < 0.05). Combining Presepsin with clinical scoring systems and inflammation markers further enhanced the predictive value for patient prognosis. CONCLUSION: Presepsin is a favorable indicator for the prognosis of COVID-19 patients, and its combination with clinical scoring systems and inflammation markers improved prognostic assessment.

PAFAH1B3 is a KLF9 target gene that promotes proliferation and metastasis in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. Uncontrolled cell proliferation, invasion and migration of pancreatic cancer cells are the fundamental causes of death in PDAC patients. Our previous studies showed that KLF9 inhibits the proliferation, invasion and migration of pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In this study, we found that platelet-activating factor acetylhydrolase IB3 (PAFAH1B3) is highly expressed in pancreatic cancer tissues and cells. In vitro and in vivo studies showed that overexpression of PAFAH1B3 promoted the proliferation and invasion of pancreatic cancer cells, while downregulation of PAFAH1B3 inhibited these processes. We found that KLF9 expression is negatively correlated with PAFAH1B3 expression in pancreatic cancer tissues and cells. Western blotting revealed that KLF9 negatively regulates the expression of PAFAH1B3 in pancreatic cancer tissues and cells. Rescue experiments showed that overexpression of PAFAH1B3 could partially attenuate the suppression of pancreatic cancer cell proliferation, invasion and migration induced by KLF9 overexpression. Finally, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were carried out, and the results showed that KLF9 directly binds to the promoter of PAFAH1B3 and inhibits its transcriptional activity. In conclusion, our study indicated that KLF9 can inhibit the proliferation, invasion, migration and metastasis of pancreatic cancer cells by inhibiting PAFAH1B3.