CEA cell adhesion molecule 5 enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment.

Hematopoietic stem cell (HSC) surface markers improve the understanding of cell identity and function. Here, we report that human HSCs can be distinguished by their expression of the CEA Cell Adhesion Molecule 5 (CEACAM5, CD66e), which serves as a marker and a regulator of HSC function. CD66e+ cells exhibited a 5.5-fold enrichment for functional long term HSCs compared to CD66e- cells. CD66e+CD34+CD90+CD45RA- cells displayed robust multi-lineage repopulation and serial reconstitution ability in immunodeficient mice compared to CD66e-CD34+CD90+CD45RA-cells. CD66e expression also identified almost all repopulating HSCs within the CD34+CD90+CD45RA- population. Together, these results indicated that CEACAM5 is a marker that enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment.

Aortic Root Reinforcement Combined with Vascular Grafts Eversion and Built-in Procedure (XJ-Procedure) for Acute Type A Aortic Dissection Surgery.

INTRODUCTION: Current root reinforcement methods for acute type A aortic dissection (ATAAD) risk the tearing of endothelial tissue by sutures. This study proposed a novel technique for aortic root reinforcement and evaluated its effectiveness. METHODS: Patients who diagnosed with ATAAD and had mild to moderate aortic root involvement, combined with aortic arch involvement undergoing Sun's procedure in the First Affiliated Hospital of Xi'an Jiaotong University from January 2020 to December 2021, were retrospectively enrolled. They were divided into two groups according to their surgical procedures of aortic root: continuous aortic root suture group (CARS group) and aortic root reinforcement combined with vascular grafts eversion and built-in procedure (XJ-procedure) group. The 30-day mortality rates and incidence of operation-related complications were evaluated. RESULTS: The study cohort comprised 183 patients, including 114 in the XJ-procedure group. The 30-day mortality rates were 7.2% in the CARS group and 6.9% in the XJ-procedure group (P = 1.000). The incidence of residual aortic root dissection in the XJ-procedure group was lower than that in the CARS group before discharge (1.8% vs. 10.1%, P = 0.028), at 3-month (0% vs. 8.7%, P = 0.002) and 6-month (0% vs. 7.2%, P = 0.007) follow-up. In the CARS group, the incidence of anastomotic pseudoaneurysm was 2.9%, 2.9%, and 2.9% compared with none in the XJ-procedure group before discharge, at 3 and 6 months. The XJ-procedure group also showed less chest tube drainage in the first 24-h after the surgery, with lower incidence of hemodialysis and sepsis during hospitalization. No differences were observed in the incidence of bleeding necessitating reoperation and severe aortic regurgitation between the two groups. CONCLUSIONS: The XJ-procedure did not increase 30-day mortality and effectively reduced the incidence of residual aortic root dissection during the 6-month follow-up. Subsequent studies with larger samples and prolonged follow-up are needed to evaluate it. TRIAL REGISTRATION: NCT05751200. The video showed the partial process of the XJ-procedure in managing the aortic root in the ATAAD surgery. The vascular graft was folded outward about 15 mm, and the eversion was intermittently sutured to the full layers aortic wall using 2-0 pad polyester sutures. Then, the eversion of the graft and aortic wall were continuously sutured in one more turn using 3-0 polypropylene sutures. (XJ-procedure, aortic root reinforcement combined with vascular grafts eversion and built-in procedure; ATAAD, acute type A aortic dissection.). (MP4 297097 kb).

Utilizing AAV-mediated LEAPER 2.0 for programmable RNA editing in non-human primates and nonsense mutation correction in humanized Hurler syndrome mice.

BACKGROUND: The endogenous adenosine deaminases acting on RNA (ADAR) have been harnessed to facilitate precise adenosine-to-inosine editing on RNAs. However, the practicability of this approach for therapeutic purposes is still ambiguous due to the variable expression of intrinsic ADAR across various tissues and species, as well as the absence of all-encompassing confirmation for delivery methods. RESULTS: In this study, we demonstrate that AAV-mediated delivery of circular ADAR-recruiting RNAs (arRNAs) achieves effective RNA editing in non-human primates at dosages suitable for therapy. Within a time frame of 4 to 13 weeks following infection, the editing efficiency in AAV-infected cells can reach approximately 80%, with no discernible toxicity, even at elevated dosages. In addition, when AAV-delivered circular arRNAs are systematically administered to a humanized mouse model of Hurler syndrome, it rectifies the premature stop codon precisely and restores the functionality of IDUA enzyme encoded by the Hurler causative gene in multiple organs. CONCLUSIONS: These discoveries considerably bolster the prospects of employing AAV-borne circular arRNAs for therapeutic applications and exploratory translational research.

Left epigastric isolated tumor fed by the inferior phrenic artery diagnosed as ectopic hepatocellular carcinoma: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the main cause of cancer-related death worldwide. Ectopic HCC, an extremely rare type of HCC, exhibits a wide range of clinical signs and radiographic features, making preoperative identification challenging. CASE SUMMARY: A 47-year-old man underwent routine abdominal color ultrasonography, which identified an asymptomatic tumor in the left upper abdomen. The patient had no history of hepatitis, did not drink alcohol, and had no family history of cancer. Abdominal contrast-enhanced computed tomography (CT) revealed a heterogeneously enhanced lesion between the spleen and stomach that had invaded the diaphragm, with blood supplied by the left inferior phrenic artery. The patient underwent laparoscopic surgery, and HCC was identified by postoperative pathology. Additionally, specific immunohistochemical staining was performed to assess the molecular biological characteristics of the HCC. The patient underwent two rounds of hepatic arterial interventional chemotherapy after surgery. Abdominal plain and enhanced magnetic resonance imaging and lung CT 3 mo postoperatively revealed no signs of local recurrence or distant metastasis. CONCLUSION: This asymptomatic ectopic HCC case described achieved an excellent result due to early detection, radical resection, and systematic surveillance.

Elevated Serum Total Bilirubin Might Indicate Poor Coronary Conditions for Unstable Angina Pectoris Patients beyond as a Cardiovascular Protector.

Backgrounds: Serum total bilirubin (STB) is recently more regarded as an antioxidant with vascular protective effects. However, we noticed that elevated STB appeared in unstable angina pectoris (UAP) patients with diffused coronary lesions. We aimed to explore STB's roles in UAP patients, which have not been reported by articles. Methods and Results: 1120 UAP patients were retrospectively screened, and 296 patients were finally enrolled. They were grouped by Canadian Cardiovascular Society (CCS) angina grades. The synergy between PCI with TAXUS stent and cardiac surgery score (SYNTAX score) and corrected thrombolysis in myocardial infarction flow count (CTFC) were adopted to profile coronary features. The results showed that STB, mean platelet volume (MPV), hs-CRP, fasting blood glucose (FBG), red blood cell width (RDW), and CTFC elevated significantly in the CCS high-risk group. STB (B = 0.59, 95% CI: 0.39-0.74, P < 0.01) and MPV (B = 0.86, 95% CI: 0.42-1.31, P < 0.01) could indicate SYNTAX score changes for these patients. STB (≥21.7 µmol/L) could even indicate a coronary slow flow condition (AUC: 0.88, 95% CI: 0.84-0.93, P < 0.01). Moreover, UAP patients with elevated STB had a lower event-free survival rate by the Kaplan-Meier curve. STB ≥21.7 µmol/L could reflect a poor coronary flow status and indicate 1-year poor outcomes for these patients (HR: 2.01, 95% CI: 1.06-3.84, P < 0.01). Conclusion: Elevated STB in UAP patients has a close relationship with changes in SYNTAX score. STB (over 21.7 µmol/L) could even indicate a coronary slow flow condition and poor outcomes for the UAP patients.

E2F8 knockdown suppresses cell proliferation and induces cell cycle arrest via Wnt/ß-Catenin pathway in ovarian cancer.

Ovarian cancer is one of the leading causes of death in female reproductive system cancers. However, the pathogenesis of ovarian cancer remains elusive. Our aim is to investigate the potential targets for ovarian cancer. Two microarray datasets were obtained from the Gene Expression Omnibus public database. Using R package limma, the differentially expressed genes (DEGs) were identified from the datasets. There were 95 overlapping DEGs in two microarray datasets. GO, KEGG pathway analysis, and protein-protein interaction (PPI) network analysis were carried out based on the DEGs. Wnt signaling pathway and cell cycle were enriched in the KEGG pathway analysis. Moreover, the top 10 hub genes with the most nodes were determined by PPI network analysis. E2F8, one of hub genes was positively linked to a bad outcome in ovarian cancer patients. Furthermore, E2F8 knockdown suppressed cell proliferation and induced cell cycle arrest in ovarian cancer. In addition, we found that silencing E2F8 inhibited the Wnt/ß-catenin signaling pathway. In ovarian cancer cells with E2F8 knockdown, overexpressing ß-catenin restored both the suppressed capacity of cell proliferation and cell cycle progression. Therefore, our results revealed that E2F8 had an involvement in the development of ovarian cancer which might act as a therapeutic target.

LncRNA AFAP1-AS1 Induces Gefitinib Resistance of Lung Adenocarcinoma Through the miR-653-5p/AGR2 Axis.

Purpose: Gefitinib resistance limits the therapeutic efficacy of gefitinib to lung adenocarcinoma (LUAD). The goal of this research is to learn more about the lncRNA AFAP1-AS1 and how it functions in gefitinib-resistant LUAD cells. Methods: RT-qPCR was performed to test the expression of AFAP1-AS1, miR-653-5p and AGR2 in LUAD tissues with acquired resistance to gefitinib or not as well as in gefitinib-resistant LUAD cells. Cell proliferation, invasion and apoptosis were measured by CCK8 assays, transwell invasion assays and flow cytometry, respectively. Luciferase reporter assay showed that miR-653-5p and AFAP1-AS1 or AGR2 interactions. Results: In gefitinib-resistant LUAD cells and tissues, AFAP1-AS1 was overexpressed. Meanwhile, silencing AFAP1-AS1 reduced proliferation and migration while increasing apoptosis and gefitinib sensitivity. Mechanically, AFAP1-AS1 sequestered the miR-653-5p and blocked the inhibition of miR-653-5p to AGR2 and stepwise upregulated AGR2 overexpression in LUAD gefitinib resistant cells, resulting gefitinib resistance in LUAD. Conclusion: AFAP1-AS1 promotes gefitinib-resistance LUAD cells through a previously unrecognized miR-653-5p/AGR2 axis, suggesting targeting AFAP1-AS1/miR-653-5p/AGR2 axis might be a promising way for LUAD intervention.

Identification of a Recurrence Gene Signature for Ovarian Cancer Prognosis by Integrating Single-Cell RNA Sequencing and Bulk Expression Datasets.

Ovarian cancer is one of the most common gynecological malignancies in women, with a poor prognosis and high mortality. With the expansion of single-cell RNA sequencing technologies, the inner biological mechanism involved in tumor recurrence should be explored at the single-cell level, and novel prognostic signatures derived from recurrence events were urgently identified. In this study, we identified recurrence-related genes for ovarian cancer by integrating two Gene Expression Omnibus datasets, including an ovarian cancer single-cell RNA sequencing dataset (GSE146026) and a bulk expression dataset (GSE44104). Based on these recurrence genes, we further utilized the merged expression dataset containing a total of 524 ovarian cancer samples to identify prognostic signatures and constructed a 13-gene risk model, named RMGS (recurrence marker gene signature). Based on the RMGS score, the samples were stratified into high-risk and low-risk groups, and these two groups displayed significant survival difference in two independent validation cohorts including The Cancer Genome Atlas (TCGA). Also, the RMGS score remained significantly independent in multivariate analysis after adjusting for clinical factors, including the tumor grade and stage. Furthermore, there existed close associations between the RMGS score and immune characterizations, including checkpoint inhibition, EMT signature, and T-cell infiltration. Finally, the associations between RMGS scores and molecular subtypes revealed that samples with mesenchymal subtypes displayed higher RMGS scores. In the meanwhile, the genomics characterization from these two risk groups was also identified. In conclusion, the recurrence-related RMGS model we identified could provide a new understanding of ovarian cancer prognosis at the single-cell level and offer a reference for therapy decisions for patient treatment.

Preparation of flexible and UV-blocking films from lignin-containing cellulose incorporated with tea polyphenol/citric acid.

Lignin-containing bamboo cellulose, fractionated from a pilot-scale microwave liquefaction of bamboo was dissolved in tetrabutylammonium acetate/dimethyl sulfoxide (TBAA/DMSO) for the fabrication of highly flexible, transparent and UV-blocking films. Tea polyphenol (TP) or citric acid (CA) was added during the dissolving process in order to modify the film's properties. The results showed that the addition of TP obviously improved the elongation at break (triple that of the control) and UV-blocking ability of the films. Both the addition of TP and CA could increase the water contact angle of the films. The films incorporated with TP and CA were much more thermal stable than previously reported similar films. The proposed film fabrication mechanism revealed that stable hydrogen bonds formed between the lignin-cellulose matrix and TP/CA, resulting in the enhancement on the properties of the films. This present study showed that lignin-containing cellulose with the incorporation of TP/CA had great potential in the preparation of films in place of plastic.

CTRP9 Mitigates the Progression of Arteriovenous Shunt-Induced Pulmonary Artery Hypertension in Rats.

The present study is aimed at investigating the molecular mechanism of C1q/TNF-related protein 9 (CTRP9) and providing a new perspective in arteriovenous shunt-induced pulmonary arterial hypertension (PAH). PAH was established by an arteriovenous shunt placement performed in rats. Adenovirus(Ad)-CTRP9 and Ad-green fluorescent protein viral particles were injected into the rats through the tail vein. Following 12 weeks, the mean pulmonary arterial pressure (mPAP) and right ventricular systolic pressure (RVSP) were measured and morphological analysis was conducted to confirm the establishment of the PAH model. The systemic elevation of CTRP9 maintained pulmonary vascular homeostasis and protected the rats from dysfunctional and abnormal remodeling. CTRP9 attenuated the pulmonary vascular remodeling in the shunt group by decreasing the mPAP and RVSP, which was associated with suppressed inflammation, apoptosis, and extracellular matrix injury. In addition, CTRP9 dramatically increased the phosphorylation of AKT and p38-MAPK in the lung tissues of shunt-operated animals. These findings suggest a previously unrecognized effect of CTRP9 in pulmonary vascular homeostasis during PAH pathogenesis.

circSNX6 (hsa_circ_0031608) enhances drug resistance of non-small cell lung cancer (NSCLC) via miR-137.

circRNAs have been suggested to modulate NSCLC tumorigenesis and drug resistance. Whether circSNX6 affects NSCLC remains unclear. In this study, we aim to investigate the role of circSNX6 in drug resistance of NSCLC exposed to cisplatin. RT-qPCR method was used to investigate expression levels of circSNX6, miR-137 and CXCL12. MTT, cell colony formation and TUNEL assays were utilized to assess cell viability, proliferation, apoptosis, respectively. Xenograft assay was conducted to examinein vivotumor growth. circSNX6 overexpression caused enhanced cell viability and proliferation of H1299 and Calu-1, while it inhibited apoptosis under cisplatin treatment. miR-137 inhibitor greatly rescued cell viability, proliferation and apoptosis of circSNX6 knockdown H1299 cells. miR-137 mimic increased ROS generation, as well as reduced GSH and SOD levels, whereas miR-137 inhibitor exerted opposing effect. circSNX6 knockdown also enhanced ROS generation, as well as decreased GSH and SOD levels. CXCL12 partially restored miR-137 mimic-modulated cell viability, proliferation and apoptosis. Herein, our group proposes circSNX6 as key regulator for drug resistance of NSCLC. The findings provide solid groundings for understanding of NSCLC pathogenesis and development of therapeutics.

Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model.

BACKGROUND: Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation. METHODS: The active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension. RESULTS: A total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C-C motif chemokine 2 (CCL2), IL-1ß, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1ß, MMP-2 and MMP-9 in rats. CONCLUSION: The potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.

Circular RNA circE2F2 promotes malignant progression of ovarian cancer cells by upregulating the expression of E2F2 protein via binding to HuR protein.

Ovarian cancer (OC) is a gynecological malignancy with a poor prognosis and low survival rate. E2F2 is a transcription activator that plays an indispensable role in cell proliferation and cell cycle progression. The preliminary analysis indicated that the E2F2 gene could produce three circular RNAs (circRNAs). This study aimed to investigate whether these circRNAs would be involved in OC tumorigenesis. The results showed that one of the circRNAs (termed circE2F2) was significantly upregulated in OC tissues and cell lines, and high circE2F2 expression was associated with poor survival in OC patients. The knockdown of circE2F2 in OC cells suppressed cell proliferation, migration, invasion, and cellular glucose metabolism. In circE2F2-deficient cells, the half-life of the E2F2 mRNA was significantly shorter than that in the control group, indicating that sufficient circE2F2 expression could strengthen the stability of the E2F2 mRNA. Further analysis revealed that circE2F2 could bind to RNA-binding protein Hu antigen R (HuR). Moreover, circE2F2 enhanced the stability of the E2F2 mRNA via binding to the HuR protein. Also, E2F2 overexpression significantly enhanced the mobility, invasiveness, and glucose metabolism of OC cells with insufficient circE2F2 expression, suggesting that circE2F2 induced OC cell growth and metastasis by upregulating E2F2. In conclusion, circE2F2 promoted OC cell proliferation, metastasis, and glucose metabolism by stabilizing the E2F2 mRNA via binding to the HuR protein. These findings suggest a novel regulatory mechanism for the oncogenic effects of circE2F2, E2F2, and HuR on ovarian carcinogenesis.

Coronary computed tomography angiography before on-pump cardiac surgery does not reduce the risk of postoperative acute kidney injury compared to coronary angiography.

OBJECTIVES: Cardiac surgery and contrast media are both related to acute kidney injury. We investigated whether undergoing coronary computed tomography angiography, which uses less contrast medium, before on-pump cardiac surgery could reduce the risk of postoperative acute kidney injury compared to coronary angiography. METHODS: In this retrospective study, 745 and 171 patients underwent coronary angiography and coronary computed tomography angiography, respectively, within 30 days before on-pump cardiac surgery. Postoperative acute kidney injury was defined according to Kidney Disease Improving Global Outcomes Definition and Staging criteria. RESULTS: Age, hypertension, cardiopulmonary bypass time, and performing cardiac surgery within 24 h of preoperative angiography (odds ratio: 1.507, 95% confidence interval: 1.111‒2.045, P = 0.008) independently predicted postoperative acute kidney injury on multivariable analysis. After propensity score matching, the acute kidney injury incidence in coronary angiography and computed tomography angiography groups was 43% and 46%, respectively (P = 0.65), and the groups had similar intensive care unit stay (2 days vs. 2 days, P = 0.209), postoperative hospital stay (11 days vs. 12 days, P = 0.084), postoperative continuous renal replacement therapy use (0.6% vs 1.9%, P = 0.314), and in-hospital mortality (0 vs. 1.3%, P = 0.156). In-hospital outcomes were similar among patients who underwent preoperative coronary angiography or computed tomography angiography within 24 h before cardiac surgery. CONCLUSION: Although coronary computed tomography angiography uses less contrast medium, it does not reduce the risk of postoperative acute kidney injury or improve in-hospital outcomes compared to coronary angiography.

Pharmacological corrections of the mutant hERG channels by posaconazole.

Properties of mutant human ether-à-go-go-related gene (hERG) channels can be modified by some antibiotics. However, the pharmacological effects of posaconazole on cardiomyocyte hERG channels remain unclear. Whole-cell patch clamping, western blotting and laser confocal scanning microscopy were used to evaluate the effects of posaconazole on wild-type (WT)-, A561V- and L539 fs/47-hERG channels expressed in human embryonic kidney (HEK) 293 cells. In electrophysiological experiments, HEK 293 cells were transiently co-transfected with equal amounts of WT-hERG, WT+A561 V-hERG and WT+L539 fs/47-hERG plasmids to mimic a heterozygous genotype. Posaconazole (30 µM) increased tail currents in cells expressing WT-hERG, WT+A561 V-hERG and WT+L539 fs/47-hERG by 82.65%, 147.72% and 134.73%, respectively, compared to controls. Posaconazole increased hERG protein expression in cells expressing WT-hERG, WT+A561 V-hERG and WT+L539 fs/47-hERG compared to controls condition as well as their trafficking to the cell membrane. To our knowledge, this is the first study to show that antifungal agent posaconazole rescues the mutant A561 V-hERG and L539 fs/47-hERG channels by altering the gating kinetics, enhancing the expression and trafficking of hERG channels. The results demonstrate that posaconazole could be a promising candidate for the prevention and treatment of long QT syndrome and other arrhythmia-related diseases.

Integrated analysis of a competing endogenous RNA network reveals an 11-lncRNA prognostic signature in ovarian cancer.

Long noncoding RNA (lncRNA) can function as a competing endogenous RNA (ceRNA) involved in tumor initiation and progression. However, the prognostic roles of lncRNAs in the integrated analysis of the ceRNA network in ovarian cancer (OVC) are still lacking. This study aimed to identify lncRNAs associated with the prognosis of OVC. Differential expression analysis and WGCNA were used to screen OVC-specific RNAs. A lncRNA-miRNA-mRNA regulatory network consisting of 201 lncRNAs, 85 miRNA and 146 mRNAs was constructed, and functional enrichment and protein-protein network analyses were performed. Then, the OVC-specific RNAs were submitted to Cox regression analysis. Twelve differentially expressed lncRNAs and mRNAs were identified as significantly associated with OS of OVC patients. Meanwhile, 11 lncRNAs (including C4A-AS1, LINC02408, LINC00488) were established as prognostic risk formulas. The low-risk group had better OS and DFS than the high-risk group (P <0.01). Univariate and multivariate Cox regression analyses revealed the 11-lncRNA risk score as an independent prognostic factor. A prognostic nomogram was developed based on independent prognostic factors. Our data provide evidence that the 11-lncRNA signature could serve as an independent prognostic indicator. This study also suggests that these 11 lncRNAs potentially participate in the progression of OVC.

H2O2-Triggered Rapid Deposition of Poly(caffeic acid) Coatings: A Mechanism-Based Entry to Versatile and High-Efficient Molecular Separation.

Plant-derived polyphenol coating offers a promising route to fabricate functional surfaces for different substrate materials. However, almost all of the deposition approaches are time-consuming and involve inefficient processes, and the mechanisms behind the coating deposition are rarely understood. Herein, we report a rational methodology to achieve the rapid deposition of poly(caffeic acid) (PCA) by using H2O2 as a trigger under the assistance of copper sulfate (CuSO4). The comparative monomer structure of PCA oxidation polymerization has illustrated a significant distinction in the reaction path for PCA coating deposition which has never been reported before. Until now, the unprecedented fast velocity for polyphenol coating has been obtained, and the PCA coating exhibits excellent homogeneity, spatiotemporal tunability, and firm stability. Moreover, three different types of filtration membranes, poly(vinylidene fluoride) microfiltration membrane (PVDF MF membrane), poly(ether sulfone) (PES) ultrafiltration (UF) hollow fiber membrane, and PCA-coated PES nanofiltration (NF) membrane, are all successfully dip-coated using H2O2-triggered PCA coating. Without synthetic complexities and intricate procedures, the formation of hydrophilic and homogeneous PCA aggregates on the surface and/or inside pore walls resulted in various membranes. The as-prepared PCA-coated PVDF MF membrane demonstrates excellent oil/water separation efficiency of less than 150 ppm and a flux recovery rate of approximately 90% even after five cycles. By one-step co-deposition of PCA and poly(2-ethyl-2-oxazoline) (PEtOx) on the PES UF membrane surface, hydrophilicity and biofouling resistance are implemented for efficient protein filtration. The PES NF membrane formed by the PCA layer exhibits high mono-/divalent ion selectivity and excellent chlorine resistance. Overall, these results represent a rapid and sustainable approach to tailor PCA coatings for versatile liquid separation processes.

Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant.

Ovarian cancer is the most lethal gynecologic malignancy. Surgery and chemotherapy are the primary treatments for ovarian cancer; however, patients often succumb to recurrence with chemotherapeutic resistance within several years after the initial treatment. In the past two decades, immunotherapy has rapidly developed, and has revolutionized the treatment of various types of cancer. Despite the fact that immunotherapy response rates among ovarian cancer patients remain modest, treatment with immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR)- and TCR-engineered T cells is rapidly developing. Therapeutic efficiency could be improved significantly if immunotherapy is included as an adjuvant therapy, in combination with chemotherapy, radiation therapy, and the use of anti-angiogenesis drugs, and poly ADP ribose polymerase inhibitors (PARPi). Newly developed technologies that identify therapeutic targets, predict treatment efficacy, rapidly screen potential immunotherapy drugs, provide neoadjuvant immunotherapy, and utilize nanomedicine technology provide new opportunities for the treatment of ovarian cancer, and have the potential to prolong patient survival. However, important issues that may hinder the efficacy of such approaches, including hyperprogressive disease (HPD), immunotherapy-resistance, and toxicity of the treatments, including neurotoxicity, must be taken into account and addressed for these therapies to be effective.

CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression.

Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein. We had reported that CPEB3 is involved in hepatocellular carcinoma (HCC) progression. However, the underlying mechanisms of CPEB3 in HCC remain unclear. In this study, we firstly performed RNA immunoprecipitation to uncover the transcriptome-wide CPEB3-bound mRNAs (CPEB3 binder) in HCC. Bioinformatic analysis indicates that CPEB3 binders are closely related to cancer progression, especially HCC metastasis. Further studies confirmed that metadherin (MTDH) is a direct target of CPEB3. CPEB3 can suppress the translation of MTDH mRNA in vivo and in vitro. Besides, luciferase assay demonstrated that CPEB3 interacted with 3'-untranslated region of MTDH mRNA and inhibited its translation. Subsequently, CPEB3 inhibited the epithelial-mesenchymal transition and metastasis of HCC cells through post-transcriptional regulation of MTDH. In addition, cpeb3 knockout mice are more susceptible to carcinogen-induced hepatocarcinogenesis and subsequent lung metastasis. Our results also indicated that CPEB3 was a good prognosis marker, which is downregulated in HCC tissue. In conclusion, our results demonstrated that CPEB3 played an important role in HCC progression and targeting CPEB3-mediated mRNA translation might be a favorable therapeutic approach.

The identification of six risk genes for ovarian cancer platinum response based on global network algorithm and verification analysis.

Ovarian cancer is the most lethal gynaecological cancer, and resistance of platinum-based chemotherapy is the main reason for treatment failure. The aim of the present study was to identify candidate genes involved in ovarian cancer platinum response by analysing genes from homologous recombination and Fanconi anaemia pathways. Associations between these two functional genes were explored in the study, and we performed a random walk algorithm based on reconstructed gene-gene network, including protein-protein interaction and co-expression relations. Following the random walk, all genes were ranked and GSEA analysis showed that the biological functions focused primarily on autophagy, histone modification and gluconeogenesis. Based on three types of seed nodes, the top two genes were utilized as examples. We selected a total of six candidate genes (FANCA, FANCG, POLD1, KDM1A, BLM and BRCA1) for subsequent verification. The validation results of the six candidate genes have significance in three independent ovarian cancer data sets with platinum-resistant and platinum-sensitive information. To explore the correlation between biomarkers and clinical prognostic factors, we performed differential analysis and multivariate clinical subgroup analysis for six candidate genes at both mRNA and protein levels. And each of the six candidate genes and their neighbouring genes with a mutation rate greater than 10% were also analysed by network construction and functional enrichment analysis. In the meanwhile, the survival analysis for platinum-treated patients was performed in the current study. Finally, the RT-qPCR assay was used to determine the performance of candidate genes in ovarian cancer platinum response. Taken together, this research demonstrated that comprehensive bioinformatics methods could help to understand the molecular mechanism of platinum response and provide new strategies for overcoming platinum resistance in ovarian cancer treatment.