68Ga labeled EphA2-targeted cyclic peptide: a novel positron imaging tracer for triple-negative breast cancer?

The absence of better biomarkers currently limits early diagnosis and treatment of triple-negative breast cancer (TNBC). Our previously published study reported that the cyclic-peptide SD01 exhibited specific binding to EphA2 (Ephrin type-A receptor 2) on TNBC. To develop a novel PET imaging agent, we prepared gallium-68 (68Ga) labeled-DOTA-SD01 and evaluated its specificity and effectiveness through micro PET/CT imaging in a TNBC-bearing mouse model. SD01 and a control linear peptide YSA were conjugated to DOTA and subsequently labeled with 68Ga, obtaining 68Ga-DOTA-SD01 and 68Ga-DOTA-YSA. Both showed high radiochemical purity, stability, good hydrophilicity, and high binding affinity to 4T1 cells. Micro PET/CT imaging showed high radioactivity accumulation in tumors; SUVmean (mean standardized uptake value) of tumors in the group of 68Ga-DOTA-SD01 was 3.34 ± 0.25 and 2.65 ± 0.32 in the group of 68Ga-DOTA-YSA; T/NT ratios (target to non-target, SUVmean ratios of tumor to muscle) were 3.12 ± 0.06 and 2.77 ± 0.11 at 30 min, respectively (p < 0.05). The biodistribution study showed that tumor uptake % ID per g (percentage of injected dose per gram of tissue) in the group of 68Ga-DOTA-SD01 was 2.73 ± 0.34, and 1.77 ± 0.38 in the group of 68Ga-DOTA-YSA; T/NT ratios (radioactivity of tumor to muscle) were 3.55 ± 0.12 and 3.05 ± 0.10 for both groups at 30 min, respectively (p < 0.05). All these suggest that 68Ga-DOTA-SD01 may act as a better novel PET imaging agent for EphA2 positive tumors, such as TNBC.

An integrated electrode material based on corn straw cellulose biochar with three-dimensional network porous structure for boosting electrochemical performance of lithium batteries.

In this work an integrated electrode material based on the VS4 nanoparticles grow on three-dimensional network porous biochar is put forward, forming a heterostructure that significantly boost the rate and cycle performance in lithium batteries. Biochar derives from two-steps treatment removing partial cellulose and hemicellulose, possessing three-dimensional network porous structure and naturally nitrogenous. The integrated electrode material constructs the continuous electrons transfer network, accommodates the volume expansion and traps the polar polysulfides efficiently. After 100 cycles at 1C, the integrated electrode with biochar shows the highest specific discharge capacity. Even at 2C, the three-dimensional electrode can display a high specific discharge capacity of 798.6 mAh·g-1. Thus, our study has pointed the innovations approach of constructing integrated electrode materials with porous structure biochar to enhance the electrochemical performance of lithium batteries.

miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2.

Metabolic reprogramming plays a critical role in hepatocarcinogenesis. However, the mechanisms regulating metabolic reprogramming in primary liver cancer (PLC) are unknown. Differentially expressed miRNAs between PLC and normal tissues were identified using bioinformatic analysis. RT-qPCR was used to determine miR-10b-5p and SCL38A2 expression levels. IHC, WB, and TUNEL assays were used to assess the proliferation and apoptosis of the tissues. The proliferation, migration, invasion, and apoptosis of PLC cells were determined using the CCK-8 assay, Transwell assay, and flow cytometry. The interaction between miR-10b-5p and SLC38A2 was determined using dual-luciferase reporter assay. A PLC xenograft model in BALB/c nude mice was established, and tumorigenicity and SLC38A2 expression were estimated. Finally, liquid chromatography - mass spectrometry (LC-MS) untargeted metabolomics was used to analyze the metabolic profiles of xenograft PLC tissues in nude mice. miR-10b-5p was a key molecule in the regulation of PLC. Compared with para-carcinoma tissues, miR-10b-5p expression was increased in tumor tissues. miR-10b-5p facilitated proliferation, migration, and invasion of PLC cells. Mechanistically, miR-10b-5p targeted SLC38A2 to promote PLC tumor growth. Additionally, miR-10b-5p altered the metabolic features of PLC in vivo. Overexpression of miR-10b-5p resulted in remarkably higher amounts of lumichrome, folic acid, octanoylcarnitine, and Beta-Nicotinamide adenine dinucleotide, but lower levels of 2-methylpropanal, glycyl-leucine, and 2-hydroxycaproic acid. miR-10b-5p facilitates the metabolic reprogramming of PLC by targeting SLC38A2, which ultimately boosts the proliferation, migration, and invasion of PLC cells. Therefore, miR-10b-5p and SLC38A2 are potential targets for PLC diagnosis and treatment.

PIEZO1-mediated mechanosensing governs NK-cell killing efficiency and infiltration in three-dimensional matrices.

Natural killer (NK) cells play a vital role in eliminating tumorigenic cells. Efficient locating and killing of target cells in complex three-dimensional (3D) environments are critical for their functions under physiological conditions. However, the role of mechanosensing in regulating NK-cell killing efficiency in physiologically relevant scenarios is poorly understood. Here, we report that the responsiveness of NK cells is regulated by tumor cell stiffness. NK-cell killing efficiency in 3D is impaired against softened tumor cells, whereas it is enhanced against stiffened tumor cells. Notably, the durations required for NK-cell killing and detachment are significantly shortened for stiffened tumor cells. Furthermore, we have identified PIEZO1 as the predominantly expressed mechanosensitive ion channel among the examined candidates in NK cells. Perturbation of PIEZO1 abolishes stiffness-dependent NK-cell responsiveness, significantly impairs the killing efficiency of NK cells in 3D, and substantially reduces NK-cell infiltration into 3D collagen matrices. Conversely, PIEZO1 activation enhances NK killing efficiency as well as infiltration. In conclusion, our findings demonstrate that PIEZO1-mediated mechanosensing is crucial for NK killing functions, highlighting the role of mechanosensing in NK-cell killing efficiency under 3D physiological conditions and the influence of environmental physical cues on NK-cell functions.

Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain.

Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.

Effect of empathy nursing combined with SBAR communication system on the negative emotions and nursing quality of children with tracheotomy.

BACKGROUND: Situation, Background, Assessment, and Recommendation (SBAR) is a structured method for communicating critical information that requires immediate attention and action. OBJECTIVE: To study the effects of empathy nursing combined with the SBAR communication system on the negative emotions and nursing quality of children undergoing tracheotomy. METHODS: This is a clinical observational study. A total of 100 tracheotomy patients who were cared for in the pediatric intensive care unit (subsequent treatment in the tracheotomy clinic or otolaryngology ward) of our hospital from September 2021 to June 2022 were recruited and assigned at a ratio of 1:1 either into a control group (empathic care) or an observation group (empathic care combined with SBAR) using a randomized method. Further, the postoperative anxiety self-rating scale scores, negative emotions, hope index, and nursing quality were compared between the two groups. RESULTS: After nursing, the psychological resilience scale score of the observation group was higher than that of the control group, whereas the anxiety self-rating scale score was significantly lower than that of the control group (all P< 0.05). Basic and special nursing, knowledge awareness, and safety management of the two groups of patients improved significantly, with higher results in the observation group than in the control group (P< 0.05). CONCLUSION: Empathy nursing combined with the SBAR communication system considerably improves postoperative negative emotions and enhances the quality of nursing care for patients undergoing tracheotomy.

CircCDK17 promotes the proliferation and metastasis of ovarian cancer cells by sponging miR-22-3p to regulate CD147 expression.

Ovarian cancer (OC) is a common malignancy in women of reproductive age. Circular RNAs (circRNAs) are emerging players in OC progression. We investigated the function and mechanism of circular RNA hsa_circ_0027803 (circCDK17) in OC pathogenesis. Real­time PCR (RT-qPCR) and western blot were utilized for gene and protein expression analysis, respectively. Cell counting kit­8 (CCK-8), EdU and Transwell assays investigated OC cell proliferation, migration and invasion. The associations between circCDK17, miR-22-3p and CD147 were examined by dual-luciferase reporter and RNA-protein immunoprecipitation (RIP) assays. The in vivo model of OC nude mice was constructed to explore the role of circCDK17. CircCDK17 was increased in OC tissue and cells, and patients with higher expression of circCDK17 had a shorter survival. CircCDK17 downregulation inhibited OC cell proliferation, migration and invasion, and reduced epithelial-mesenchymal transition (EMT)-related markers. In vivo experiments showed that circCDK17 silencing inhibited OC tumor growth and metastasis. CircCDK17 depletion reduced CD147 level via sponging miR-22-3p. MiR-22-3p knockdown overturned effect of circCDK17 depletion on OC cell proliferation, migration and invasion. Meanwhile, overexpressed CD147 restored functions of circCDK17 downregulation on OC development. CircCDK17 is an important molecule that regulates OC pathogenic process through miR-22-3p/CD147.

Study of efficient catalytic electrode for hydrogen evolution reaction from seawater based on low tortuosity corn straw cellulose biochar/Mo2C with porous channels.

Porosity and channel structure has important effects on the performance of hydrogen evolution reaction (HER) of nanostructured electrocatalysts in acid solution and seawater. Mesopore usually helps to enhance the reaction kinetics and mass transfer, while the macroporous channel structure also affects the electrocatalyst. Traditional graphene materials do not have such structure. Therefore, this paper designs a method to synthesize Mo2C composite nanomaterial in situ on corn straw biochar, inspires by the natural channel structure of conducting water, salt and organic matter in plants. Characteristic characterization shows that the material also has a large number of mesoporous and vertical distribution of large porous channel structure, through the decrease of tortuosity and porosity, ensure the catalyst surface electrolyte transport and hydrogen timely escape, alleviate the process of metal ion precipitation blocking pore channel, so as to improve the rate of hydrogen evolution reaction. The results shows that the overpotential of the catalyst was 48 mV and 251 mV under 10 mA cm-2 acidic electrolyte and simulated seawater electrolyte, respectively. This method provides new ideas for the design of efficient electrocatalysts for seawater decomposition, then the HER performance in alkaline and neutral environments needs to be further explored.

What Works for Controlling Meningitis Outbreaks: A Case Study from China.

The meningococcal meningitis (MM) vaccine reduces the incidence of MM significantly; however, outbreaks still occur in communities with high vaccine coverage. We aimed to analyze the driving factors of infection from a community outbreak. A total of 266 children aged 9 to 15 years old from the three junior high schools of Tongzi county were identified. We documented infection cases using laboratory tests and analyzed attack rates, infection rates and risk factors for transmission. The index case in School A was identified, and the attack rate in School A was 0.03%. Children showed a significantly low infection rate of MenC in School A (13.2% vs. 19.5% in total children, p = 0.002), while exhibiting significantly high infection rates of MenA in School B (44.1% vs. 24.8% in total children, p < 0.001) and MenB in School C (11.1% vs. 4.1% in total children, p = 0.015). The infection rate of MenA for females (30.0%) was higher (p = 0.055) than for males (19.9%). In School A, 63.19% of children were vaccinated against MenC, while in School B the rate was 42.65% and in School C, it was 59.26%. Three male MenC infection cases were detected as breakthrough infection cases in addition to the index case. The findings suggest that the current full-course immunization has limited long-term effectiveness and is inefficient in preventing the transmission of MM among older children.

Green and chemical-free pretreatment of corn straw using cold isostatic pressure for methane production.

In this study, the effect of cold isostatic pressure (CIP) pretreatment on the physicochemical properties and subsequent anaerobic digestion (AD) performance of corn straw (CS) was explored. The CS was subjected to CIP pretreatment by pressures of 200, 400 and 600 MPa, respectively, while AD was carried out at medium temperature (35 ± 2 °C). The results showed that CIP pretreatment disrupted the dense structure of the CS and altered the crystallinity index and surface hydrophobicity of the CS, thereby affecting the AD process. The presence of CIP pretreatment increased the initial reducing sugar concentration by 0.11-0.27 g/L and increased the maximum volatile fatty acids content by 112.82-436.64 mg/L, which facilitated the process of acidification and hydrolysis of the AD. It was also observed that the CIP pretreatment maintained the pH in the range of 6.37-7.30, maintaining the stability of the overall system. Moreover, the cumulative methane production in the CIP pretreatment group increased by 27.17 %-64.90 % compared to the control group. Analysis of the microbial results showed that CIP pretreatment increased the abundance of cellulose degrading bacteria Ruminofilibacter from 21.50 % to 27.53 % and acetoclastic methanogen Methanosaeta from 45.48 % to 56.92 %, thus facilitating the hydrolysis and methanogenic stages. The energy conversion analysis showed that CIP is a green and non-polluting pretreatment strategy for the efficient AD of CS to methane.

Effects of cold isostatic press pretreatment of rice straw on microstructure and efficiency of anaerobic digestion for methane production.

In this study, rice straw was pretreated using by cold isostatic pressure to disrupt its microstructure and improve the performance of anaerobic digestion, and the optimal process parameters were optimized using the response surface methodology. The results showed that cold isostatic pressure pretreatment under optimal conditions (pressure of 400 MPa and holding time of 9 min) was effective in disrupting the structure of rice straw and improving its biodegradability. The cumulative methane production of the cold isostatic pressure pretreatment group increased by 76% compared to the untreated group. In addition, microbial community analysis showed that the relative abundance of Firmicutes, Halobacterota, DMER64 and Methanosaeta was higher in groups pretreated with cold isostatic pressure than in untreated groups. This study demonstrated the potential of pretreatment of rice straw with cold isostatic pressure to increase methane production during anaerobic digestion.

A high-throughput 3D kinetic killing assay.

Our work presents a high-throughput kinetic killing assay in the 3D matrix using high-content imaging that is a robust and powerful cytotoxicity assay for evaluating the killing efficiency of immune killer cells or conducting drug screening under physiologically and pathologically relevant scenarios, particularly in the context of solid tumors.

In vitro evaluation of immune responses to bacterial hydrogels for the development of living therapeutic materials.

In living therapeutic materials (LTMs), organisms genetically programmed to produce and deliver drugs are encapsulated in porous matrices acting as physical barriers between the therapeutic organisms and the host cells. LTMs consisting of engineered E. coli encapsulated in Pluronic F127-based hydrogels have been frequently used in LTM designs but their immunogenicity has not been tested. In this study, we investigate the response of human peripheral blood mononuclear cells (PBMCs) exposed to this bacteria/hydrogel combination. The release of inflammation-related cytokines and cytotoxic proteins and the subsets of natural killer cells and T cells were examined. Encapsulation of the bacteria in hydrogels considerably lowers their immunogenicity. ClearColi, an endotoxin-free variant of E. coli, did not polarize NK cells into the more cytolytic CD16dim subset as E. coli. Our results demonstrate that ClearColi-encapsulated hydrogels generate low immunogenic response and are suitable candidates for the development of LTMs for in vivo testing to assess a potential clinical use. Nevertheless, we observed a stronger immune response (elevated levels of IFNγ, IL-6 and cytotoxic proteins) in pro-inflammatory PBMCs characterized by a high spontaneous release of IL-2. This highlights the need to identify recipients who have a higher likelihood of experiencing undesired immune responses to LTMs with IL-2 serving as a potential predictive marker. Additionally, including anti-inflammatory measures in living therapeutic material designs could be beneficial for such recipients.

Interleukin-27 potentiates CD8+ T-cell-mediated antitumor immunity in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) cells are highly dependent on interactions with the immunosuppressive tumor microenvironment (TME) for survival and proliferation. In the search for novel treatments, pro-inflammatory cytokines have emerged as candidates to reactivate the immune system. Among those, interleukin 27 (IL-27) has recently gained attention, but its effects differ among malignancies. Here, we utilized the Eµ-TCL1 and EBI3 knock-out mouse models as well as clinical samples from patients to investigate the role of IL-27 in CLL. Characterization of murine leukemic spleens revealed that the absence of IL-27 leads to enhanced CLL development and a more immunosuppressive TME in transgenic mice. Gene-profiling of T-cell subsets from EBI3 knock-out highlighted transcriptional changes in the CD8+ T-cell population associated with T-cell activation, proliferation, and cytotoxicity. We also observed an increased anti-tumor activity of CD8+ T cells in the presence of IL-27 ex vivo with murine and clinical samples. Notably, IL-27 treatment led to the reactivation of autologous T cells from CLL patients. Finally, we detected a decrease in IL-27 serum levels during CLL development in both pre-clinical and patient samples. Altogether, we demonstrated that IL-27 has a strong anti-tumorigenic role in CLL and postulate this cytokine as a promising treatment or adjuvant for this malignancy.

Research progress of applications for nano-materials in improved QuEChERS method.

The quick, easy, cheap, effective, rugged, and safe (QuEChERS) approach is widely used in sample pretreatment in agricultural products, food, environment, etc. And nano-materials are widely used in QuEChERS method due to its small size and large specific surface area. In this review, we examine the typical applications of several commonly used nano-materials in improved QuEChERS method. These materials include multi-walled carbon nanotubes (MWCNTs) and their derivatives, magnetic nanoparticles (MNPs), metal organic frameworks (MOFs), covalent organic frameworks (COFs), graphene oxide (GO), lipid and protein adsorbent (LPAS), cucurbituril (CBs), and carbon nano-cages (CNCs), and so on. The strengths and weaknesses of each nano-material are presented, as well as the challenging aspects that need to be addressed in future research. By comparing the applications and the current technology development, this review suggests utilizing artificial intelligence (AI) to screen suitable combinations of purification agents and performing virtual simulation experiments to verify the reliability of this methodology. By doing so, we aim to accelerate the development of new products and decrease the cost of innovation. It also recommends designing smarter pretreatment instruments to enhance the convenience and automation of the sample pretreatment process and reduce the margin for human error.

Hsa_circ_0023826 protects against glaucoma by regulating miR-188-3p/MDM4 axis.

OBJECTIVE: Circular RNAs (circRNAs) are characterized as a class of covalently closed circRNA transcripts and are associated with various cellular processes and neurological diseases by sponging microRNAs. The most common feature of glaucoma, a form of retinal neuropathy, is the loss of retinal ganglion cells. Although the pathogenesis of glaucoma is not fully understood, elevated intraocular pressure is undoubtedly the only proven modifiable factor in the classic glaucoma model. This study investigated the role of circ_0023826 in glaucoma-induced retinal neurodegeneration by modifying the miR-188-3p/mouse double minute 4 (MDM4) axis. METHODS: The expression pattern of circ_0023826 was analyzed during retinal neurodegeneration. The effect of circ_0023826, miR-188-3p, and MDM4 on retinal neurodegeneration in vivo was assessed by visual behavioral testing and HandE staining in glaucoma rats, while that on in vitro retinal ganglion cells (RGCs) was evaluated by MTT assay, flow cytometry, Western blot, and ELISA. Bioinformatics analysis, RNA pull-down assay, luciferase reporter assay were performed to reveal the regulatory mechanism of circ_0023826-mediated retinal neurodegeneration. RESULTS: Circ_0023826 expression was downregulated during retinal neurodegeneration. Upregulating circ_0023826 attenuated the visual impairment in rats and promoted the survival of RGCs in vitro. Circ_0023826 acted as a sponge of miR-188-3p sponge, resulting in increased expression of MDM4. MDM4 silencing or miR-188-3p upregulation reversed the protective effect of upregulated circ_0023826 on glaucoma-induced neuroretinal degeneration in vitro and in vivo. CONCLUSION: Overall, circ_0023826 protects against glaucoma by regulating the miR-188-3p/MDM4 axis, and targeted intervention of circ_0023826 expression is a promising therapeutic strategy for the treatment of retinal neurodegeneration.

Serum disease-specific IgG Fc glycosylation as potential biomarkers for nonproliferative diabetic retinopathy using mass spectrometry.

OBJECTIVE: To explore the potential of serum disease-specific immunoglobulin G (DSIgG) glycosylation as a biomarker for the diagnosis of nonproliferative diabetic retinopathy (NPDR). METHODS: A total of 387 consecutive diabetic patients presenting in an eye clinic without proliferative diabetic retinopathy (DR) were included and divided into those with nondiabetic retinopathy (NDR) (n = 181) and NPDR (n = 206) groups. Serum was collected from all patients for DSIgG separation. The enriched glycopeptides of the tryptic digests of DSIgG were detected using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Patients were randomly divided into discovery and validation sets (1:1). The differences in glycopeptide ratios between the groups were compared by using Student's t-test or the Mann-Whitney U test. The predictive ability of the model was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: DSIgG1 G1FN/G0FN, G2N/G2, G2FN/G2N and DSIgG2 G1F/G0F, G1FN/G0FN, G2N/G1N, G2S/G2 were significantly different between NDR and NPDR patients (p < 0.05) in both the discovery and validation sets. The prediction model that was built comprising the seven glycopeptide ratios showed good NPDR prediction performance with an AUC of 0.85 in the discovery set and 0.87 in the validation set. CONCLUSION: DSIgG Fc N-glycosylation ratios were associated with NPDR and can be used as potential biomarkers for the early diagnosis of DR.

Bioactive Constituents of Verbena officinalis Alleviate Inflammation and Enhance Killing Efficiency of Natural Killer Cells.

Natural killer (NK) cells play key roles in eliminating pathogen-infected cells. Verbena officinalis (V. officinalis) has been used as a medical plant in traditional and modern medicine for its anti-tumor and anti-inflammatory activities, but its effects on immune responses remain largely elusive. This study aimed to investigate the potential of V. officinalis extract (VO extract) to regulate inflammation and NK cell functions. We examined the effects of VO extract on lung injury in a mouse model of influenza virus infection. We also investigated the impact of five bioactive components of VO extract on NK killing functions using primary human NK cells. Our results showed that oral administration of VO extract reduced lung injury, promoted the maturation and activation of NK cells in the lung, and decreased the levels of inflammatory cytokines (IL-6, TNF-α and IL-1ß) in the serum. Among five bioactive components of VO extract, Verbenalin significantly enhanced NK killing efficiency in vitro, as determined by real-time killing assays based on plate-reader or high-content live-cell imaging in 3D using primary human NK cells. Further investigation showed that treatment of Verbenalin accelerated the killing process by reducing the contact time of NK cells with their target cells without affecting NK cell proliferation, expression of cytotoxic proteins, or lytic granule degranulation. Together, our findings suggest that VO extract has a satisfactory anti-inflammatory effect against viral infection in vivo, and regulates the activation, maturation, and killing functions of NK cells. Verbenalin from V. officinalis enhances NK killing efficiency, suggesting its potential as a promising therapeutic to fight viral infection.

E2F1-mediated KDM4A-AS1 up-regulation promotes EMT of hepatocellular carcinoma cells by recruiting ILF3 to stabilize AURKA mRNA.

Hepatocellular carcinoma (HCC) is a gastrointestinal tumor with high clinical incidence. Long non-coding RNAs (lncRNAs) play vital roles in modulating the growth and epithelial-mesenchymal transition (EMT) of HCC. However, the underlying mechanism of lncRNA KDM4A antisense RNA 1 (KDM4A-AS1) in HCC remains elusive. In our study, the role of KDM4A-AS1 in HCC was systematically investigated. The levels of KDM4A-AS1, interleukin enhancer-binding factor 3 (ILF3), Aurora kinase A (AURKA), and E2F transcription factor 1 (E2F1) were determined by RT-qPCR or western blot. ChIP and dual luciferase reporter experiments were performed to detect the binding relationship between E2F1 and KDM4A-AS1 promoter sequence. RIP and RNA-pull down confirmed the interaction of ILF3 with KDM4A-AS1/AURKA. Cellular functions were analyzed by MTT, flow cytometry, wound healing and transwell assays. IHC was performed to detect Ki67 in vivo. We found that KDM4A-AS1 was increased in HCC tissues and cells. Elevated KDM4A-AS1 level was correlated to poor prognosis of HCC. Knockdown of KDM4A-AS1 inhibited the proliferation, migration, invasion and EMT of HCC cells. ILF3 bound to KDM4A-AS1 and AURKA. KDM4A-AS1 maintained the stability of AURKA mRNA by recruiting ILF3. E2F1 transcriptionally activated KDM4A-AS1. Overexpressed KDM4A-AS1 reversed the contribution of E2F1 depletion to AURKA expression and EMT in HCC cells. KDM4A-AS1 promoted tumor formation in vivo through the PI3K/AKT pathway. These results revealed that E2F1 transcriptionally activated KDM4A-AS1 to regulate HCC progression via the PI3K/AKT pathway. E2F1 and KDM4A-AS1 may serve as good prognostic targets for HCC treatment.

Practical aspects of the diagnosis and management of pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare autoinflammatory ulcerative neutrophilic skin disease. Its clinical presentation is a rapidly progressing painful skin ulcer with ill-defined borders and surrounding erythema. The pathogenesis of PG is complex and not fully understood. Clinically, patients with PG often have various systemic diseases, the most common being inflammatory bowel disease (IBD) and arthritis. Due to the lack of specific biological markers, diagnosing PG remains difficult, which easily resulting in misdiagnosis. Some validated diagnostic criteria have been applied in clinical practice that facilitate its diagnosis. The treatment of PG currently consists mainly of immunosuppressive and immunomodulatory agents, especially biological agents, which have bright prospects for PG therapy. After the systemic inflammatory response is controlled, the problem of wounds becomes the main contradiction in PG treatment. Surgery is not controversial for PG, increasing evidence shows that with adequate systemic treatment, the benefits of reconstructive surgery for patients are increasing.