Traditional craniotomy versus current minimally invasive surgery for spontaneous supratentorial intracerebral haemorrhage: A propensity-matched analysis.

BACKGROUND: Minimally invasive surgery (MIS) and craniotomy (CI) are the current treatments for spontaneous supratentorial cerebral haemorrhage (SSTICH). AIM: To compare the efficacy and safety of MIS and CI for the treatment of SSTICH. METHODS: Clinical and imaging data of 557 consecutive patients with SSTICH who underwent MIS or CI between January 2017 and December 2022 were retrospectively analysed. The patients were divided into two subgroups: The MIS group and CI group. Propensity score matching was performed to minimise case selection bias. The primary outcome was a dichotomous prognostic (favourable or unfavourable) outcome based on the modified Rankin Scale (mRS) score at 3 months; an mRS score of 0-2 was considered favourable. RESULTS: In both conventional statistical and binary logistic regression analyses, the MIS group had a better outcome. The outcome of propensity score matching was unexpected (odds ratio: 0.582; 95%CI: 0.281-1.204; P = 0.144), which indicated that, after excluding the interference of each confounder, different surgical modalities were more effective, and there was no significant difference in their prognosis. CONCLUSION: Deciding between MIS and CI should be made based on the individual patient, considering the hematoma size, degree of midline shift, cerebral swelling, and preoperative Glasgow Coma Scale score.

Does lower extremity stiffness influence change of direction speed in badminton athletes after dynamic loaded warm-up?

This study investigated whether lower extremity stiffness plays a role in the enhancement of change of direction speed (CODS) and the duration of this enhancement after dynamic loaded warm-up (DLWU). Fifteen badminton athletes underwent DLWU, and CODS, individual muscle and tendon stiffness, and vertical stiffness were measured before DLWU and 6, 12, and 18 min after DLWU. The data were analyzed using ANOVA and covariance analysis. Significant improvements in CODS were found at 6, 12, and 18 min post-DLWU compared to pre-DLWU (p < 0.05). The Achilles tendon stiffness of the dominant leg increased at 6 min (p = 0.039) and 18 min (p = 0.024) post-DLWU compared to pre-DLWU. Achilles tendon stiffness of the dominant leg had a significant effect on improving CODS (p > 0.05). CODS improvement lasted up to 18 min after DLWU in badminton athletes, potentially related to increased Achilles tendon stiffness of the dominant leg.

Chloride intracellular channel 4 blockade improves cognition in mice with Alzheimer's disease: CLIC4 protein expression and tau protein hyperphosphorylation.

Numerous academic literature suggests that amyloid-ß (Aß) deposition, tau protein phosphorylation, and irreversible neuronal death are the three major causes of AD. The chloride intracellular channel (CLIC) protein family not only regulates the polarisation of neurons, but also has important implications for neuronal survival. Chloride intracellular channel 4 (CLIC4) can be pathologically activated by cyclin-dependent kinase 5 (Cdk5), which causes a significant increase in the expression of CLIC4 and mediates neuronal apoptosis. CLIC4 knockdown inhibits H2O2-induced neuronal apoptosis; however, the relationship between CLIC4 and AD remains unknown. In the present study, we showed that CLIC4 expression was elevated in the hippocampus of AD mice; knockdown of hippocampal CLIC4 alleviated Aß25-35-induced cognitive impairment in mice; overexpression of hippocampal CLIC4 accelerated Aß deposition and tau protein hyperphosphorylation in young AD mice (APP/PS1 mice at three months of age). CLIC4 overexpressing mice had a longer escape latency compared to controls in behavioural testing (Morris water maze and T-maze tests). By Co-immunoprecipitation/mass spectrometry (Co-IP/MS) of HT22 cells to identify proteins that specifically bind to CLIC4, we found interactions with CCAAT enhancer binding protein (C/EBPß); a critical pathway involved in the development of various neurodegenerative diseases. In addition, the knockdown of hippocampal CLIC4 alleviated AD-like pathology by inhibiting the C/EBPß/AEP signaling pathway. These data suggest an essential role for high CLIC4 expression in the pathophysiology of AD and reveal that inhibition of CLIC4 expression may provide an opportunity for treatment.

Development of Nitric Oxide Releasing Oxoisoaporphines with Antidepressant Activities by Simultaneously Regulating MAO-A and SERT.

The occurrence of depression is closely related to the decrease in serotonin (5-HT) levels in the synaptic cleft. Designing negative regulators aiming at intervening in MAO-A and serotonin transporter (SERT) could work synergistically to elevate synaptic 5-HT levels and thus might exhibit superior antidepressant efficacy. By linking the lead compound oxoisoaporphine to various nitric oxide donors, we endeavored to design and synthesize 10 synergistic negative regulators. The overarching objective was to maintain the original inhibitory effect on MAO-A while concurrently mitigating SERT-mediated reuptake of 5-HT. Within the spectrum of inhibitory compounds, I7 showcased the most formidable neuroprotective efficacy in a cellular depression model. In vivo experiments demonstrated that I7 significantly improved depressive behavior in both zebrafish and mice. Further research indicated that the antidepressant mechanism of I7 was associated with the downregulation of both MAO-A and SERT.

Graphene-skinned alumina fiber fabricated through metalloid-catalytic graphene CVD growth on nonmetallic substrate and its mass production.

Graphene growth on widely used dielectrics/insulators via chemical vapor deposition (CVD) is a strategy toward transfer-free applications of CVD graphene for the realization of advanced composite materials. Here, we develop graphene-skinned alumina fibers/fabrics (GAFs/GAFFs) through graphene CVD growth on commercial alumina fibers/fabrics (AFs/AFFs). We reveal a vapor-surface-solid growth model on a non-metallic substrate, which is distinct from the well-established vapor-solid model on conventional non-catalytic non-metallic substrates, but bears a closer resemblance to that observed on catalytic metallic substrates. The metalloid-catalytic growth of graphene on AFs/AFFs resulted in reduced growth temperature (~200 °C lower) and accelerated growth rate (~3.4 times faster) compared to that obtained on a representative non-metallic counterpart, quartz fiber. The fabricated GAFF features a wide-range tunable electrical conductivity (1-15000 Ω sq-1), high tensile strength (>1.5 GPa), lightweight, flexibility, and a hierarchical macrostructure. These attributes are inherited from both graphene and AFF, making GAFF promising for various applications including electrical heating and electromagnetic interference shielding. Beyond laboratory level preparation, the stable mass production of large-scale GAFF has been achieved through a home-made roll-to-roll system with capacity of 468-93600 m2/year depending on product specifications, providing foundations for the subsequent industrialization of this material, enabling its widespread adoption in various industries.

Controllable preparation of graphene glass fiber fabric towards mass production and its application in self-adaptive thermal management.

Direct synthesis of graphene on nonmetallic substrates via chemical vapor deposition (CVD) has become a frontier research realm targeting transfer-free applications of CVD graphene. However, the stable mass production of graphene with a favorable growth rate and quality remains a grand challenge. Herein, graphene glass fiber fabric (GGFF) was successfully developed through the controllable growth of graphene on non-catalytic glass fiber fabric, employing a synergistic binary-precursor CVD strategy to alleviate the dilemma between growth rate and quality. The binary precursors consisted of acetylene and acetone, where acetylene with high decomposition efficiency fed rapid graphene growth while oxygen-containing acetone was adopted for improving the layer uniformity and quality. Notably, the bifurcating introducing-confluent premixing (BI-CP) system was self-built for the controllable introduction of gas and liquid precursors, enabling the stable production of GGFF. GGFF features solar absorption and infrared emission properties, based on which the self-adaptive dual-mode thermal management film was developed. This film can automatically switch between heating and cooling modes by spontaneously perceiving the temperature, achieving excellent thermal management performances with heating and cooling power of ∼501.2 and ∼108.6 W m-2, respectively. These findings unlock a new strategy for the large-scale batch production of graphene materials and inspire advanced possibilities for further applications.

O-GlcNAcylated RALY Contributes to Hepatocellular Carcinoma Cells Proliferation by Regulating USP22 mRNA Nuclear Export.

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly tumors; however, its pathogenic mechanism remains largely elusive. In-depth researches are needed to reveal the expression regulatory mechanisms and functions of the RNA-binding protein RALY in HCC. Here, we identify RALY as a highly expressed oncogenic factor that affects HCC cells proliferation both in vitro and in vivo. O-GlcNAcylation of RALY at Ser176 enhances its stability by protecting RALY from TRIM27-mediated ubiquitination, thus maintaining hyper-expression of the RALY protein. Mechanistically, RALY interacts with USP22 messenger RNA, as revealed by RNA immunoprecipitation, to increase their cytoplasmic localization and protein expression, thereby promoting the proliferation of HCC cells. Furthermore, we develop a novel RALY protein degrader based on peptide proteolysis-targeting chimeras, named RALY-PROTAC, which we chemically synthesize by linking a RALY-targeting peptide with the E3 ubiquitin ligase recruitment ligand pomalidomide. In conclusion, our findings demonstrate a novel mechanism by which O-GlcNAcylation/RALY/USP22 mRNA axis aggravates HCC cells proliferation. RALY-PROTACs as degraders of the RALY protein exhibit potential as therapeutic drugs for RALY-overexpressing HCC.

Study on the fracture propagation of ground fissures with syn-depositional structure in Fenwei Basin, China.

In Fenwei Basin, most of the tectonic ground fissures show characteristics of growth faults on the section. They continue to destroy the engineering properties of soil at different depths. This has introduced significant security risks to the construction processes of deep underground spaces. However, there are few studies have been conducted on syn-depositional ground fissures. Therefore, in this study, a physical simulation test was used to study the fracture propagation of syn-depositional ground fissures. The characteristics of sections and surface fractures were analyzed. The engineering properties of model soil were divided into bad and poor areas. The syn-depositional ground fissure fracture propagation process was divided into five phases. The results show that soil profile exhibited a composite Y-shaped fracture morphology. Syn-deposition affects the fracture angle and healing state of fractures. The soil strain and surface displacement were positively correlated with the number of deposition layers. The conclusions of this study provide a theoretical geological basis and practical engineering significance for design of deep underground space structures.

Rotating Sonotrode Design for Ultrasonic-Assisted Arc Welding of Metal Materials.

In the process of the ultrasonic-assisted arc welding of metal materials, traditional ultrasonic application methods, such as the low-frequency impact of ultrasonic horns on a base material, can easily cause the non-fusion defect. In order to solve this problem, a rotating sonotrode with a groove and double thin ends was designed in this study. The ultrasonic vibration is transmitted into the weld pool by the rolling of the sonotrode on both sides of the weld. The resonant frequency was set at 50 kHz. Firstly, based on the Mindlin theory, a rotating sonotrode without a groove was designed by solving the frequency equation and by conducting a finite element simulation. Secondly, the effects of the groove, perforation, and transition mode on the resonant frequency, stress distribution, and amplification factor were investigated by finite element simulation. Finally, the optimum rotating sonotrode with a groove was obtained. The results show that the size of a rotating sonotrode that has a small frequency error can be obtained by using the discrete interval solver method combined with finite element simulation. The groove can significantly reduce the resonant frequency. The stress concentration can be effectively reduced by using the elliptical transition mode. The resonant frequency and amplification factor of a rotating sonotrode with a groove could be effectively adjusted by a method of double-position joint perforation. The final resonant frequency was 49.721 kHz and the amplification factor was 3.02. This study provides an effective design method for a sonotrode with double thin ends and a groove structure.

Prognostic Risk Models Using Epithelial Cells Identify ß-Sitosterol as a Potential Therapeutic Target Against Esophageal Squamous Cell Carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is an aggressive and fatal malignancy that leads to epithelial cancer. The association between epithelial cell heterogeneity, prognosis, and immune response in this cancer remains uncertain. This study aimed to investigate epithelial cell heterogeneity in ESCC and develop a predictive risk model using the identified cell types. Methods: Single-cell RNA sequencing (scRNA-seq) and differential ESCC gene data were accessed from the Gene Expression Omnibus. Functional enrichment analysis, inferCNV, cell development trajectories, and intercellular communication were analyzed following epithelial cell characterization. Differentially expressed ESCC (n = 773) and epithelial cell marker genes (n = 3407) were intersected to obtain core genes, and epithelial cell-related prognostic genes were identified. LASSO regression analysis was used to construct a prognostic model. The external dataset GSE53624 was used to further validate the stability of the model. Drug sensitivity predictions, and immune cell infiltration were analyzed. Molecular docking clarified the possible therapeutic role of ß-sitosterol in ESCC. Finally, wound healing assay, cell colony, and transwell assay were constructed to detect the effects of the core gene PDLIM2 on ESCC cell proliferation, invasion, and migration. Results: Eight cell clusters were identified, and epithelial cells were categorized into tumor and paratumor groups. The tumor group possessed more chromosomal variants than the paratumor group. Epithelial cells were associated with multiple cell types and significantly correlated with the Wnt, transforming growth factor, and epidermal growth factor signaling pathways. From 231 intersected genes, five core genes were screened for use in the risk model: CTSL, LAPTM4B, MYO10, NCF2, and PDLIM2. These genes may contribute to the cancerous transformation of normal esophageal epithelial cells and thereby act as biomarkers and potential therapeutic targets in patients with ESCC. ß-Sitosterol furthermore displayed excellent docking potential with these genes. Meanwhile, further experiments demonstrated that the gene PDLIM2 plays a major role in the progression of oesophageal squamous carcinoma. Conclusion: We successfully developed a risk model for the prognosis of ESCC based on epithelial cells that addresses the response of ESCC to immunotherapy and offers novel cancer treatment options.

A one-step process for multi-gradient wettability modification on a polymer surface.

The surface modification technique is applied in microfluidic devices to modify wettability and achieve different flow velocities. Currently available methods for poly(dimethylsiloxane) (PDMS) surfaces may reliably induce wettability changes, but only one area can be altered at a time. This work introduces the controlled gradient oxygen plasma modification (CGPM) technique, which layers several resin masks with varying porosities on top of the PDMS surface. Selective wettability of the PDMS surface can be achieved by varying the oxygen plasma density above the modified material's surface by manipulation of the porosity value. Through the implementation of the COMSOL plasma module, the impact of the mask's porosity, through-hole size, distribution, and distance from the PDMS surface on wettability was studied. The suggested CGPM approach was characterized by contact angle measurements. During the 25-second CGPM procedure, the PDMS surface's contact angle continually changed from 8.77° to 76.98°. An integrated microfluidic device was created and manufactured to identify D-dimers to illustrate this method. In comparison with standard oxygen plasma treatment, the D-dimer assay was finished in 10 minutes and had a dynamic range of 1-1000 ng mL-1, with a peak fluorescence signal augmentation of 78.3% and an average fluorescence intensity enhancement of 31.1%.

The Incidences and Related CT Features of Vascular Lake Phenomenon on Angiography Before Chemoembolization.

PURPOSE: To elucidate incidence rates of vascular lake phenomenon (VLP) in hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatic metastasis (HMT) on transarterial angiography before chemoembolization, and to identity CT features predictive for it. MATERIALS AND METHODS: A comprehensive evaluation involved 665 subjects for incidence analysis, comprising 527 of HCC, 33 of ICC and 105 of HMT. VLP was characterized as intratumoral contrast material pool persisting late into venous phase. Incidences were cataloged on both super-selective and common hepatic artery angiography. For CT features analysis, a subset of 182 cases were analyzed. Enhancement ratio served as an index for comparative analysis of nodule enhancement degrees. RESULTS: In HCC, incidence of VLP ascertained via super-selective angiography was 13.5%, whereas it as 7.8% on common hepatic artery angiography. Remarkably, no incidences of VLP were recorded in either ICC or HMT cases. On pre-interventional CT, the prevalence of pseudocapsule was statistically greater in VLP group than Non-VLP group (66.6% vs. 37.6%, P = 0.015). The Houndsfield units (HU) of tumors in plain scan (P = 0.007), arterial phase (P = 0.001), venous phase (P = 0.041), arterial phase enhancement ratio (P < 0.001) were statistically higher in VLP group compared to Non-VLP group. Arterial phase enhancement ratio (P = 0.025), presence of pseudocapsule (P = 0.001), HU of tumor in plain scan (P = 0.035) serve as independent risk factors for VLP manifestation. CONCLUSION: VLP is a distinct angiography phenomenon uniquely associated with HCC. High arterial phase enhancement ratio, presence of pseudocapsule, high HU of tumor in plain scan are independent risk factors for VLP.

Oral phages prophylaxis against mixed Escherichia coli O157:H7 and Salmonella Typhimurium infections in weaned piglets.

Escherichia coli and Salmonella Typhimurium are the main pathogens of diarrhea in weaned piglets. The prevention of bacterial diarrhea in weaned piglets by phage is rarely reported. We conducted this study to evaluate the preventive effect of phages on mixed Escherichia coli and Salmonella Typhimurium infections in weaned piglets. A novel phage named NJ12 was isolated by using Salmonella Typhimurium SM022 as host bacteria and characterized by electron microscopy, genomic analysis and in vitro bacteriostatic activity. Phage NJ12 and a previously reported phage EP01 were microencapsulated with sodium alginate to make phage cocktail. Microencapsulated phage cocktail and PBS (Phosphate buffer solution) were used to piglets the phage and phage-free group through oral administration before bacterial infection 2 h, respectively. Piglets of the phage and phage-free group were consumed with feed contaminated with 6 mL (108CFU/mL) Escherichia coli O157:H7 GN07 (GXEC-N07) and 6 mL (108CFU/mL) SM022 every day for seven consecutive days. The results showed that piglets in the phage-free group had more severe diarrhea, larger decreased average weight gain and higher levels of neutrophils compared with piglets in phage group. Meanwhile, piglets in the phage-free group had higher load of SM022 and GN07 in jejunal tissue and more severe intestinal damage compared with piglets in group phage in vivo. In addition, oral administration phage can significant decreased the relative abundance of Enterobacteriaceae but hardly repaired the changes of diversity and composition of gut microbiota caused by the mixed infection of SM022 and GN07. This implies that phage used as a feed additive have a marvelous preventive effect on bacterial diarrhea during weaning of piglets.

Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy.

Accumulating evidence shows that Schwann cells' (SCs) death caused by high glucose (HG) is involved in the pathological process of diabetic peripheral neuropathy (DPN). Ferroptosis is a novel form of regulatory cell death driven by iron-dependent lipid peroxidation. However, it is not clear whether ferroptosis is involved in the death process of SCs induced by HG. The expression of ferroptosis-related indicators in the serum of DPN patients was detected by ELISA. Subsequently, using cell counting kit­8, western blot, real-time PCR, and Ki-67 staining, we investigated the effects of HG on the ferroptosis of SCs and initially explored the underlying mechanism. The results showed that the serum levels of glutathione peroxidase 4 (GPX4) and glutathione in patients with DPN decreased, while malondialdehyde levels increased significantly. Then, we observed that erastin and HG induced ferroptosis in SCs, resulting in the decrease in cell activity and the expression level of GPX4 and SLC7A11, which could be effectively reversed by the ferroptosis inhibitor Fer-1. Mechanistically, HG induced ferroptosis in SCs by inhibiting the NRF2 signaling pathway. Our results showed that ferroptosis was involved in the death process of SCs induced by HG. Inhibition of ferroptosis in SCs might create a new avenue for the treatment of DPN.

pH-Responsive and Actively Targeted Metal-Organic Framework Structures for Multimodal Antitumor Therapy and Inhibition of Tumor Invasion and Metastasis.

Multimodal treatment is an important tool to overcome tumor drug resistance. The reactive oxygen species (ROS) generated by photodynamic therapy (PDT) can directly play a killing role on tumor cells, which has the advantages of repeatable treatment and no drug resistance. However, its therapeutic oxygen consumption and destruction of tumor microvessels lead to hypoxia in tumor tissues, and hypoxia leads to overexpression of the receptor tyrosine kinase (c-MET) and vascular endothelial growth factor receptor (VEGFR). Overexpression of these two receptors leads to increased tumor invasiveness and metastasis. The molecularly targeted drug cabozantinib (CAB) has multiple targets, including anti-c-MET and VEGFR, to inhibit the development of hepatocellular carcinoma (HCC). In this study, our team designed a pH-sensitive nanoparticle CAB/Ce6@ZIF-8@PEG-FA (CCZP) loaded with CAB and Ce6, which exerted a multimodal therapeutic effect of PDT and molecularly targeted therapy by laser irradiation, and the PDT-induced overexpression of MET and VEGFR could also be inhibited by the target of CAB, thus reducing the invasive tumor cells metastasis. In summary, CCZP gives full play to the advantages of both drugs, exerting multimodal treatment while reducing HCC invasion and metastasis, providing a safe, potential approach to clinical treatment.

Oral phage therapy with microencapsulated phage A221 against Escherichia coli infections in weaned piglets.

BACKGROUND: Escherichia coli (E. coli) is a common pathogen that often causes diarrhea in piglets. Since bacteria are becoming more and more resistant to antibiotics, phages have become a promising alternative therapy. However, the therapy of oral phage often fails to achieve the desired effect. A novel phage named A221 was isolated by using E. coli GXXW-1103 as host strain, characterized by electron microscopy, genomic sequencing and analyzed by measuring lysis ability in vitro. RESULTS: Phage A221 was identified as a member of Ackermannviridae, Aglimvirinae, Agtrevirus with 153297 bp genome and effectively inhibited bacterial growth in vitro for 16 h. This study was conducted to evaluate the therapeutic effect of oral microencapsulated phage A221 on E. coli GXXW-1103 infections in weaned piglets. The protective effect of phage was evaluated by body weight analysis, bacterial load and histopathological changes. The results showed that with the treatment of phage A221, the body weight of piglets increased, the percentage of Enterobacteriaceae in duodenum decreased to 0.64%, the lesions in cecum and duodenum were alleviated, and the bacterial load in the jejunal lymph nodes, cecum and spleen were also significantly different with infected group (P < 0.001). CONCLUSIONS: The results showed that phage A221 significantly increased the daily weight gain of piglets, reduced the bacterial load of tissues and the intestinal lesions, achieved the same therapeutic effect as antibiotic Florfenicol. Taken together, oral microencapsulated phage A221 has a good therapeutic effect on bacterial diarrhea of weaned piglets, which provides guidance for the clinical application of phage therapy in the future.

ALDOC promotes non-small cell lung cancer through affecting MYC-mediated UBE2N transcription and regulating Wnt/ß-catenin pathway.

Despite advancements in therapeutic options, the overall prognosis for non-small cell lung cancer (NSCLC) remains poor. Therefore, it is crucial to further explore the etiology and targets for novel treatments to effectively manage NSCLC. In this study, immunohistochemistry was used to analyze the expression of aldolase, fructose-bisphosphate C (ALDOC) protein in tumor tissues and adjacent non-malignant tissues from 79 NSCLC patients. Our findings revealed that ALDOC was overexpressed in NSCLC tissues. ALDOC expression was associated with lymph node metastasis, lymphatic metastasis and pathological stage. In addition, Kaplan-Meier analysis showed that higher ALDOC levels were indicative of a poorer prognosis. Additionally, we observed elevated ALDOC mRNA levels in NSCLC cell lines relative to normal cells. To investigate the functional roles of ALDOC, we infected cells with small interfering RNA against ALDOC, which led to attenuated proliferation and migration, as well as ameliorated apoptosis. Furthermore, through our investigations, we discovered that ubiquitin-conjugating enzyme E2N (UBE2N) acts as a downstream factor of ALDOC. ALDOC promoted NSCLC through affecting MYC-mediated UBE2N transcription and regulating the Wnt pathway. More importantly, we found that downregulation of UBE2N or the use of Wnt pathway inhibitor could reverse the promoting effects of ALDOC elevation on NSCLC development in vitro and in vivo. Based on these findings, our study highlights the potential of ALDOC as a future therapeutic target for NSCLC.

N6-methyladenosine with immune infiltration and PD-L1 in hepatocellular carcinoma: novel perspective to personalized diagnosis and treatment.

Background: Increasing evidence elucidated N6-methyladenosine (m6A) dysregulation participated in regulating RNA maturation, stability, and translation. This study aimed to demystify the crosstalk between m6A regulators and the immune microenvironment, providing a potential therapeutic target for patients with hepatocellular carcinoma (HCC). Methods: Totals of 371 HCC and 50 normal patients were included in this study. GSE121248 and GSE40367 datasets were used to validate the expression of HNRNPC. The R package "ConsensusClusterPlus" was performed to screen consensus clustering types based on the expression of m6A regulators in HCC. The R package "pheatmap", "immunedeconv", "survival", "survminer" and "RMS" were applied to investigate the expression, immunity, overall survival, and clinical application in different clusters and expression groups. Comprehensive analysis of HNRNPC in pan-cancer was conducted by TIMER2 database. Besides, HNRNPC mRNA and protein expression were verified by qRT-PCR and immunohistochemistry analysis. Results: Most of m6A regulators were over-expressed excerpt for ZC3H13 in HCC. Three independent clusters were screened based on m6A regulators expression, and the cluster 2 had a favorable prognosis in HCC. Then, the cluster 2 was positively expression in macrophage, hematopoietic stem cell, endothelial cell, and stroma score, while negatively in T cell CD4+ memory and mast cell. We identified HNRNPC was an independent prognostic factor in HCC, and nomogram performed superior application value for clinical decision making. Moreover, PD-L1 was significantly up-regulated in HCC tissues, cluster 1, and cluster 3, and we found PD-L1 expression was positively correlated with HNRNPC. Patients with HCC in high-expression groups was associated with tumor-promoting cells. Besides, HNRNPC was correlated with prognosis, TMB, and immune checkpoints in cancers. Particularly, the experiments confirmed that HNRNPC was positively expression in HCC cells and tissues. Conclusion: The m6A regulators play irreplaceable roles in prognosis and immune infiltration in HCC, and the relationship of HNRNPC and PD-L1 possesses a promising direction for therapeutic targets of immunotherapy response. Exploration of m6A regulators pattern could be build the prognostic stratification of individual patients and move toward to personalized treatment.

Biological characteristics and genomic analysis of a novel Escherichia phage Kayfunavirus CY1.

As the problem of bacterial resistance becomes serious day by day, bacteriophage as a potential antibiotic substitute attracts more and more researchers' interest. In this study, Escherichia phage Kayfunavirus CY1 was isolated from sewage samples of swine farms and identified by biological characteristics and genomic analysis. One-step growth curve showed that the latent period of phage CY1 was about 10 min, the outbreak period was about 40 min and the burst size was 35 PFU/cell. Analysis of the electron microscopy and whole-genome sequence showed that the phage should be classified as a member of the Autographiviridae family, Studiervirinae subfamily. Genomic analysis of phage CY1 (GenBank accession no. OM937123) revealed a genome size of 39,173 bp with an average GC content of 50.51% and 46 coding domain sequences (CDSs). Eight CDSs encoding proteins involved in the replication and regulation of phage DNA, 2 CDSs encoded lysis proteins, 14 CDSs encoded packing and morphogenesis proteins. Genomic and proteomic analysis identified no sequence that encoded for virulence factor, integration-related proteins or antibiotic resistance genes. In summary, morphological and genomics suggest that phage CY1 is more likely a novel Escherichia phage.

Downregulated liver-elevated long intergenic noncoding RNA (LINC02428) is a tumor suppressor that blocks KDM5B/IGF2BP1 positive feedback loop in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and poor prognoses worldwide. Many studies have reported that long noncoding RNAs (lncRNAs) are related to the progression and prognosis of HCC. However, the functions of downregulated liver-elevated (LE) lncRNAs in HCC remain elusive. Here we report the roles and mechanisms of downregulated LE LINC02428 in HCC. Downregulated LE lncRNAs played significant roles in HCC genesis and development. LINC02428 was upregulated in liver tissues compared with other normal tissues and showed low expression in HCC. The low expression of LINC02428 was attributed to poor HCC prognosis. Overexpressed LINC02428 suppressed the proliferation and metastasis of HCC in vitro and in vivo. LINC02428 was predominantly located in the cytoplasm and bound to insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) to prevent it from binding to lysine demethylase 5B (KDM5B) mRNA, which decreased the stability of KDM5B mRNA. KDM5B was found to preferentially bind to the promoter region of IGF2BP1 to upregulate its transcription. Therefore, LINC02428 interrupts the KDM5B/IGF2BP1 positive feedback loops to inhibit HCC progression. The KDM5B/IGF2BP1 positive feedback loop is involved in tumorigenesis and progression of HCC.