Guiding function of positron emission tomography-computed tomography examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma.

AIM: To explore the role of positron emission tomography-computed tomography (PET-CT) examination in the diagnosis and treatment of ocular adnexal mucosa associated lymphoid tissue lymphoma (OAML). METHODS: The general clinical data, postoperative PET-CT results, treatment regimens, and the prognosis of 21 histopathologically confirmed OAML patients between October 2017 and September 2021 were collected. Among the 21 patients, five patients underwent surgical treatment alone, 13 patients underwent surgical treatment combined with radiotherapy, and three patients underwent surgical treatment combined with chemotherapy. RESULTS: The follow-up period ranged from 8 to 79mo, with four cases of recurrence and no deaths. Through PET-CT examination, two patients exhibited both local ocular metabolic elevation and systemic metastasis, and one of these patients had cervical lymph node metastasis, while the other had submandibular and parotid gland metastasis. Nine patients showed only local ocular metabolic elevation, while 10 patients had no abnormal metabolic activity locally. CONCLUSION: PET-CT examination plays a crucial role in detecting residual lesions and recurrence following tumor resection, aiding in precise disease staging, and facilitating the development of personalized treatment plans, ultimately improving patient prognosis.

A new classification for surgical NEC during exploratory laparotomy: introduction and reproducibility assessment.

PURPOSE: Variability in necrosis patterns and operative techniques in surgical necrotizing enterocolitis (NEC) necessitates a standardized classification system for consistent assessment and comparison. This study introduces a novel intraoperative reporting system for surgical NEC, focusing on reliability and reproducibility. METHODS: Analyzing surgical NEC cases from January 2018 to June 2023 at two tertiary neonatal and pediatric surgery units, a new classification system incorporating anatomical details and intestinal involvement extent was developed. Its reproducibility was quantified using kappa coefficients (κ) for interobserver and intraobserver reliability, assessed by four specialists. Furthermore, following surgery, the occurrence of mortality and enteric autonomy were evaluated on the basis of surgical decision-making of the novel intraoperative classification system for surgical NEC. RESULTS: In total, 95 patients with surgical NEC were included in this analysis. The mean κ value of the intra-observer reliability was 0.889 (range, 0.790-0.941) for the new classification, indicating excellent agreement and the inter-observer reliability was 0.806 (range, 0.718-0.883), indicating substantial agreement. CONCLUSION: The introduced classification system for surgical NEC shows high reliability, deepening the understanding of NEC's intraoperative exploration aspects. It promises to indicate operative strategies, enhance prognosis prediction, and substantially facilitate scholarly communication in pediatric surgery. Importantly, it explores the potential for a standardized report and may represent a step forward in classifying surgical NEC, if pediatric surgeons are open to change.

Natural Amino Acid-Bearing Carbamate Prodrugs of Daidzein Increase Water Solubility and Improve Phase II Metabolic Stability for Enhanced Oral Bioavailability.

Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4'-O-CO-N-isoleucine, D-4'-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma. In addition, unlike the passive transport of DAN, D-4'-I maintained high permeability via organic anion-transporting polypeptide 2B1 (OATP2B1)-mediated transport. Importantly, D-4'-I increased the oral bioavailability by 15.5-fold, reduced the gender difference, and extended the linear absorption capacity in the pharmacokinetics of DAN in rats. Furthermore, D-4'-I exhibited dose-dependent protection against liver injury. Thus, the natural amino acid-bearing carbamate prodrug strategy shows potential in increasing water solubility and improving phase II metabolic stability to enhance the oral bioavailability of DAN.

Effect of Body Mass Index on Cecal Intubation Time During Unsedated Colonoscopy: Variation Across the Learning Stages of an Endoscopist.

BACKGROUND Body mass index (BMI) and endoscopists' experiences can be associated with cecal intubation time (CIT), but such associations are controversial. This study aimed to clarify the association between BMI and CIT during unsedated colonoscopy at 3 learning stages of a single endoscopist. MATERIAL AND METHODS A total of 1500 consecutive patients undergoing unsedated colonoscopy by 1 endoscopist at our department from December 11, 2020, to August 21, 2022, were reviewed. They were divided into 3 learning stages according to the number of colonoscopies performed by 1 endoscopist, including intermediate (501-1000 colonoscopies), experienced (1001-1500 colonoscopies), and senior stages (1501-2000 colonoscopies). Variables that significantly correlated with CIT were identified by Spearman rank correlation analyses and then included in multiple linear regression analysis. RESULTS Overall, 1233 patients were included. Among them, 392, 420, and 421 patients were divided into intermediate, experienced, and senior stages, respectively. Median CIT was 7.83, 6.38, and 5.58 min at intermediate, experienced, and senior stages, respectively (P.

Excellent Bowel Preparation Quality Is Not Superior to Good Bowel Preparation Quality for Improving Adenoma/Polyp Detection Rate.

Background: Adequate bowel preparation quality is essential for high-quality colonoscopy according to the current guidelines. However, the excellent effect of bowel preparation on adenoma/polyp detection rate (ADR/PDR) remained controversial. Methods: During the period from December 2020 to August 2022, a total of 1566 consecutive patients underwent colonoscopy by an endoscopist. Their medical records were reviewed. According to the Boston bowel preparation scale, patients were divided into excellent, good, and poor bowel preparation quality groups. ADR/PDR, diminutive ADR/PDR, small ADR/PDR, intermediate ADR/PDR, large ADR/PDR, and number of adenomas/polyps were compared among them. Logistic regression analyses were performed to identify the factors that were significantly associated with ADR/PDR. Results: Overall, 1232 patients were included, of whom 463, 636, and 133 were assigned to the excellent, good, and poor groups, respectively. The good group had a significantly higher ADR/PDR (63% vs 55%, P = .015) and a larger number of adenomas/polyps (2.5 ± 3.2 vs 2.0 ± 2.8, P = .030) than the poor group. Both ADR/PDR (63% vs 55%, P = .097) and number of adenomas/polyps (2.2 ± 2.8 vs 2.0 ± 2.8, P = .219) were not significantly different between excellent and poor groups. The excellent (9% vs 4%, P = .045) and good (9% vs 4%, P = .040) groups had a significantly higher intermediate ADR/PDR than the poor group. Logistic regression analyses showed that either good (odds ratio [OR] = 1.786, 95% CI = 1.046-3.047, P = .034) or excellent (OR = 2.179, 95% CI = 1.241-3.826, P = .007) bowel preparation quality was independently associated with a higher ADR/PDR compared with poor bowel preparation quality. Excellent (OR = 1.202, 95% CI = 0.848-1.704, P = .302) bowel preparation quality was not independently associated with a higher ADR/PDR compared with good bowel preparation quality. Conclusions: The pursuit of excellence in bowel preparation does not show an association with increased ADR/PDR and number of adenomas/polyps compared with a good level. In addition, our study further contributes to the existing evidence that poor bowel preparation compromises ADR/PDR and number of adenomas/polyps.

Neurodevelopmental impairment following surgical necrotizing enterocolitis with gestational age ≥ 28 weeks: who is at risk?

PURPOSE: Surgical necrotizing enterocolitis (NEC) is a severe medical condition that, even after surgery, a portion of the survival infants may still have neurological sequelae. The objective of this study was to identify the risk factors associated with the development of permanent neurodevelopmental impairment (NDI) in neonates with surgical NEC. METHODS: Between January 2016 and June 2022, a retrospective data collection was conducted on 98 individuals who experienced surgical NEC with gestational age ≥ 28 weeks. Among these patients, 27 patients were diagnosed with NDI, while the remaining 71 patients did not have NDI. Based on this division, the patients were categorized into the NDI group and the Non-NDI group. Demographics, comorbidities, and admission lab results were analyzed using univariate and logistic regression analyses. RESULTS: Of the 98 neonates following surgical NEC, 27(27.6%) developed permanent neurodevelopmental impairment (NDI). Predictors of NDI were identified through the final multivariable logistic regression analysis, which revealed that gestational age ≤ 32 weeks (p = 0.032; odds ratio [OR], 5.673), assisted mechanical ventilation after NEC onset (p = 0.047; OR, 5.299), postoperative acute kidney injury (p = 0.040; OR, 5.106), CRP day 3 after NEC onset (p = 0.049; OR, 1.037), time from presentation to surgery (p = 0.003; OR, 1.047) were significant risk factors. CONCLUSIONS: Our study identified gestational age ≤ 32 weeks, assisted mechanical ventilation after NEC onset, postoperative acute kidney injury, CRP day 3 after NEC onset, and time from presentation to surgery as significant risk factors for NDI in neonates with surgical NEC. These factors would be helpful to refine treatment modalities for better disease outcomes. We also determined the cut-off values of CRP day 3 after NEC onset and time from presentation to surgery, allowing for the individualized evaluation of NDI risk and the implementation of earlier targeted laparotomy.

Detection and identification of oil spill species based on polarization information.

Aiming at the problem of poor oil identification accuracy in existing oil spill detection technologies, the polarization degree model of oil spill on rough sea surface under different azimuths and zenith angles was established based on Fresnel theory. The analytical expressions of visible light polarization degree in calm and fluctuating water surface were derived respectively, and the polarization degree model of oil spill in reflection space was constructed. The effectiveness of the method and its influence on the polarization distribution of oil spill were analyzed by simulation. A portable turntable was designed to test the polarization characteristics of the experiment, and the visible light polarization detection experiment was carried out. The visible light polarization images of five typical oil spills at different observation azimuth and zenth angles were obtained. The differences in the polarization degrees of different oil species were analyzed, and the correctness of the theoretical model was proved by experiments. The polarization detection experiment of visible light pBRDF was completed, which more intuitively showed the variation law of the polarization characteristics of light reflected by different oil spills in different spatial positions. Using polarization information to distinguish oil species is a useful supplement to the traditional oil spill detection method and has important significance to improve the marine pollution control ability.

Severity assessment to guide empiric antibiotic therapy for cholangitis in children after Kasai portoenterostomy: a multicenter prospective randomized control trial in China.

BACKGROUND: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM. RESULTS: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P >0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00-48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up. CONCLUSIONS: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.

Improvement of coated aluminum sheet pBRDF model based on scattering and phase function optimization.

The pBRDF model is able to relate the properties of target materials to the polarization information of incident and reflected light, and is an important basis for obtaining polarization information of targets in space. It is an important basis for obtaining target polarization information and polarization detection of space targets. P-G model is the first strictly pBRDF model officially released, but there are still deficiencies. In this paper, we first analyze the assumption framework of the P-G model, derive the imperfections in the framework through the analysis of the assumption framework, and add scattering and phase function to enhance the existing model. On the basis of the existing P-G model and parameter inversion, the output results of the model are compared with the experimental data through simulation, and the results show that the relative error of the target's linear polarizability is reduced under the improved model, which proves the accuracy and precision of the improved model.

Eicosapentaenoic Acid-Enriched Phospholipids Alleviate Skeletal Muscle Atrophy in Lewis Lung Carcinoma Mouse Model.

SCOPE: Skeletal muscle atrophy is a critical feature of cancer-associated cachexia (CAC) and it is responsible for poor quality of life and high mortality in cancer patients. The previous study demonstrates that eicosapentaenoic acid-enriched phospholipids (EPA-PL) prevent body weight loss in a mouse model of CAC. However, the role of EPA-PL on cancer-induced skeletal muscle atrophy remains unclear. METHODS AND RESULTS: In the present study, a Lewis lung carcinoma (LLC) mouse model is established, then the effect and underlying mechanism of EPA-PL on skeletal muscle atrophy in LLC-bearing mice are investigated. The results reveal that EPA-PL treatment significantly attenuates skeletal muscle atrophy in LLC-bearing mice, as evidenced by suppressing the reductions of skeletal muscle mass, myofiber cross-sectional area, and grip strength. Besides, the study finds that EPA-PL alleviated cancer-induced skeletal muscle atrophy via balancing muscle protein degradation and synthesis, inhibiting type I oxidative muscle fibers atrophy, and promoting mitochondrial function. Furthermore, the results also indicate that EPA-PL may counteract skeletal muscle atrophy in LLC mouse model via a sirtuin 1-dependent mechanism. CONCLUSION: These findings provide evidence that EPA-PL may be beneficial as a nutritional supplement for prevention and treatment of cancer-induced skeletal muscle atrophy.

Factors of easy and difficult cecal intubation during unsedated colonoscopy.

BACKGROUND AND AIMS: difficulty of cecal intubation should be a main indicator for the need of sedated colonoscopy and skilled endoscopists. The present study aimed to explore the factors associated with easy and difficult cecal intubation in unsedated colonoscopy. METHODS: all consecutive patients who underwent unsedated colonoscopy at our department by the same endoscopist from December 3, 2020 to August 30, 2022 were retrospectively collected. Age, gender, body mass index (BMI), reasons for colonoscopy, position change, Boston Bowel Preparation Scale score, cecal intubation time (CIT) and major colonoscopic findings were analyzed. CIT < 5 min, CIT 5-10 min and CIT > 10 min or failed cecal intubation were defined as easy, moderate and difficult cecal intubation, respectively. Logistic regression analyses were performed to identify independent factors associated with easy and difficult cecal intubation. RESULTS: overall, 1,281 patients were included. The proportions of easy and difficult cecal intubation were 29.2 % (374/1,281) and 27.2 % (349/1,281), respectively. Multivariate logistic regression analysis found that age ≤ 50 years, male, BMI > 23.0 kg/m2 and the absence of position change were independently associated with easy cecal intubation, and that age > 50 years, female, BMI ≤ 23.0 kg/m2, position change, and insufficient bowel preparation were independently associated with difficult cecal intubation. CONCLUSIONS: some convenient factors independently associated with easy and difficult cecal intubation have been identified, which will be potentially helpful to determine whether a colonoscopy should be sedated and a skilled endoscopist should be selected. The current findings should be further validated in large-scale prospective studies.

Design and experimental study of a polarization imaging optical system for oil spills on sea surfaces.

The marine environment is complex and changeable. To meet the urgent needs of accurate detection and identification of oil spills, a visible/infrared dual-band common-aperture polarization imaging optical system based on a defocused plane polarization detector is designed. The optical system is evaluated by ZEMAX simulation software, and we carried out the polarization imaging oil species discrimination experiment based on the split focal plane polarization detector, which proved that for some oil species that cannot be distinguished by intensity information, the polarization information can be distinguished. It verifies the feasibility of polarization detection in the discrimination of marine oil spills, which is of great practical significance in the field of marine oil spill detection.

miR-200a-3p- and miR-181-5p-Mediated HOXB5 Upregulation Promotes HCC Progression by Transcriptional Activation of EGFR.

Background: Hepatocellular carcinoma (HCC) remains a worldwide burden. However, the mechanisms behind the malignant biological behavior of HCC remain unclear. The homeobox (HOX) family could act as either promoters or suppressors in different kinds of malignancies. Our study discovered the role of HOXB5 in regulating HCC progression. Methods: The HOXB5 expression was assessed by RT-PCR analysis in human HCC samples and cell lines. HOXB5 transcriptional regulation of the EGFR was verified by the luciferase reporter assay and chromatin immunoprecipitation experiment. The oncogenic role of HOXB5 in HCC progression was analyzed by CCK8, colony-forming, and transwell assays. Results: Upregulation of HOXB5 was found in human HCC, and was strongly correlated with HCC tumor size, tumor-nodule metastasis, TNM stage, and relatively unfavorable OS and DFS. Ectopic expression of HOXB5 promoted the capacity of cell growth and clonogenicity, while the inhibition of HOXB5 decreased the proliferation and clonogenicity potential in vitro by CCK8 and colony-forming assays. In addition, HOXB5 also promoted cell migration by transwell experiment. Mechanism studies elucidated that HOXB5 triggers HCC progression via direct transcriptional activation of EGFR. The upregulation of HOXB5 is regulated by miR-200a-3p and miR-181-5p. Transfection of miR-200a-3p and miR-181-5p mimics blocked the cell proliferation and migration regulated by HOXB5, while overexpression of the 3'-UTR mutant HOXB5 abolished the suppressive effect of miR-200a-3p and miR-181-5p, but not the wild-type HOXB5. Conclusion: HOXB5 is a promising prognostic factor in human HCC. Targeting miR-200a-3p and the miR-181-5p/HOXB5/EGFR signaling pathway may provide new options for the treatment strategies of HCC.

Long non-coding RNA taurine up regulated 1 promotes osteosarcoma cell proliferation and invasion through upregulating Ezrin expression as a competing endogenous RNA of micro RNA-377-3p.

Osteosarcoma (OS) is the most common primary malignant tumor of bone mainly occurring in children and young people, which has a high rate of recurrence and metastasis. Long non-coding RNAs (lncRNAs) have capabilities in regulating target gene expression in various tumors served as competing endogenous RNAs (ceRNAs) to sponge microRNAs (miRNAs). In addition, Ezrin (EZR) is a member of ERM (ezrin/Radixin/moesin) protein family that contributes to the progression of multiple tumors. Previous studies have correlated lncRNA taurine upregulated 1 (TUG1) or Ezrin with OS. However, the correlation between lncRNA TUG1 and Ezrin in OS remains unclear. The expressions of lncRNA TUG1 and Ezrin were upregulated in OS tissues and cells determined by quantitative reverse transcription-PCR (qRT-PCR) and Western blot (WB), respectively. In addition, both lncRNA TUG1 and Ezrin promoted OS cell proliferation identified by Cell Counting Kit-8 (CCK-8) assay and clone formation assay, and enhanced OS cell invasion detected using Transwell assay for cell invasion. Moreover, lncRNA TUG1 upregulated Ezrin expression through sponging miR-377-3p determined by dual-luciferase reporter gene assay and WB. In conclusion, our work revealed that lncRNA TUG1 promoted OS cell proliferation and invasion through upregulating Ezrin expression as a ceRNA of miR-377-3p, which might provide novel therapeutic targets for OS therapy.

Clinical outcomes and functional analysis of third space robotic and endoscopic cooperative surgery versus laparoscopic wedge resection for gastric submucosal tumours: a propensity score-matched study.

Third space robotic and endoscopic cooperative surgery (TS-RECS) is a novel minimally invasive surgery for resecting gastric submucosal tumours (GSMTs), which could accomplish the completely oncological curability and maximal functional preservation. This study investigated the clinical outcomes and gastrointestinal function after TS-RECS versus laparoscopic wedge resection (LWR) for GSMTs. This was a single-centre retrospective study that included 130 patients with GSMTs who underwent LWR or TS-RECS from 2013 to 2019. To overcome selection biases, we performed propensity score matching (1:1) using seven covariates that could impact the group assignment and outcomes. Then, the clinical outcomes and gastrointestinal function in the LWR and TS-RECS groups were compared in a matched cohort. Among the 130 enrolled patients, 96 patients underwent LWR, and 34 underwent TS-RECS and were matched into 30 patients for each group. There was no significant difference in the operation time between the two groups (P = 0.543). However, the TS-RECS group had significantly less blood loss (20,5-100 vs 95,10-310 ml, P < 0.0001) and better postoperative recovery in terms of time to oral intake (2,2-4 vs 3,2-6 days, P < 0.0001) and postoperative hospital stay (5,4-10 vs 8.5,5-16 days, P < 0.0001) than the LWR group. The severity and frequency scores of postoperative gastrointestinal symptoms in the TS-RECS group were significantly lower than those in the LWR group. The median follow-up period was 24 months (10-60 months) in the LWR group and 18 months (10-27 months) in the TS-RECS group, and there was in total a single recurrence in the LWR group. TS-RECS appears to be a technically safe and effective surgery with preservation of gastrointestinal function for resection of GSMT resection.

Mesenchymal stem cell-derived exosomes protect trabecular meshwork from oxidative stress.

This study aims to investigate the beneficial effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on trabecular meshwork cells under oxidative stress and predict candidate genes associated with this process. Trabecular meshwork cells were pretreated with BMSC-derived exosomes for 24 h, and exposed to 0.1 mM H2O2 for 6 h. Survival rate of trabecular meshwork cells was measured with CCK-8 assay. Production of intracellular reactive oxygen species (iROS) was measured using a flow cytometer. RT-PCR and ELISA were used to detect mRNA and protein levels of inflammatory cytokines and matrix metalloproteinases (MMPs). Sequencing of RNA and miRNA for trabecular meshwork cells from Exo and control groups was performed on BGISEQ500 platform. Phenotypically, pretreatment of BMSC-derived exosomes improves survival rate of trabecular meshwork cells exposed to H2O2, reduces production of iROS, and inhibits expression of inflammatory cytokines, whereas increases expression of MMPs. There were 23 miRNAs, 307 lncRNAs, and 367 mRNAs differentially expressed between Exo and control groups. Exosomes derived from BMSCs may protect trabecular meshwork cells from oxidative stress. Candidate genes responsible for beneficial effects, such as DIO2 and HMOX1, were predicted.

Efficient removal of cadmium ions from water by adsorption on a magnetic carbon aerogel.

Carbon aerogels are attracting much attention as adsorbents due to their high specific surface and large accessible pores. Herein, we describe a successful synthesis of a magnetic carbon aerogel (MCA) using sodium alginate (SA) as the main carbon source, gelatin (G) as a cross-linking agent and secondary carbon source, and Fe3O4 nanoparticles as the magnetic component. A simple pyrolysis treatment at 550 °C under N2 transformed a Fe3O4/SA/G hydrogel precursor into the MCA. The obtained magnetic carbon aerogel possessed a high specific surface area (145.7 m2/g), a hierarchically porous structure, and an abundance of surface hydroxyl (-OH) and carboxyl (-COOH) groups, resulting in outstanding sorption properties for aqueous Cd(II) (an adsorption capacity of 143.88 mg/Lmg/g). The mechanism of Cd(II) adsorption by the MCA was investigated, with the results obtained suggesting that the MCA removed cadmium ions from water by both electrostatic adsorption and complexation. Since the MCAs contained Fe3O4 nanoparticles, they could easily be separated and recovered from water using a magnet. This study thus identifies a promising and efficient technology for removing Cd(II) ions from aqueous solutions.

HIPK3 Circular RNA Promotes Metastases of HCC Through Sponging miR-338-3p to Induce ZEB2 Expression.

BACKGROUND: Upregulation of circHIPK3 has been observed in several kinds of malignancies. However, the mechanisms of circHIPK3 in HCC metastases remains unclear. We investigated the role and the mechanisms of circHIPK3 in the development of HCC. METHODS: HCC tissues and paired adjacent non-tumor tissues of surgical patients were used to evaluate circHIPK3 expression. A series of biological experiments had been taken to evaluate the pro-metastatic ability of circHIPK3 during HCC development in vitro and in vivo. The potential mechanisms of circHIPK3 in HCC development were identified by RT-qPCR, Western blot, RIP, and luciferase reporter assays. RESULTS: CircHIPK3 expression is significantly upregulated during HCC development. Overexpression of circHIPK3 promotes cell migration, invasion, and metastases in vitro and in vivo. CircHIPK3 promoted HCC metastases by sponging miR-338-3p to regulate EMT-associated proteins E-cadherin, vimentin, and ZEB2 expression. CONCLUSION: CircHIPK3 plays a regulatory role in metastatic HCC by sponging miR-338-3p to induce ZEB2 expression, thus promoting EMT procession.

Porcine Reproductive and Respiratory Syndrome Virus Structural Protein GP3 Regulates Claudin 4 To Facilitate the Early Stages of Infection.

Claudins (CLDN) are a family of proteins that represent the most important components of tight junctions, where they establish the paracellular barrier that controls the flow of molecules in the intercellular space between epithelial cells. Several types of viruses make full use of CLDN to facilitate entry into cells. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry. In this study, we found that CLDN4 functions as an anti-PRRSV factor by blocking its absorption during the early stages of infection. The small extracellular loop (ECL2) of CLDN4 restricted the viral particles outside cells by binding to GP3. A novel function of GP3-mediated regulation of CLDN4 transcription was suggested. CLDN4 can be decreased through downregulating the level of CLDN4 transcription by ubiquitinating the transcription factor, SP1. The mechanism by which highly pathogenic PRRSV infects the epithelium was proposed. Importantly, ECL2 was found to block PRRSV absorption and infection and neutralize the virus. A more in-depth understanding of PRRSV infection is described, and novel therapeutic antiviral strategies are discussed.IMPORTANCE In the present study, the role of CLDN4 in PRRSV infection was studied. The results showed that CLDN4 blocked absorption into cells and restricted extracellular viral particles via the interaction between the CLDN4 small extracellular loop, ECL2, and the viral surface protein GP3. GP3 was found to downregulate CLDN4 through ubiquitination of the transcription factor SP1 to facilitate viral entry. The mechanism by which highly pathogenic PRRSV infects the epithelium is suggested. A novel function of GP3 in regulating gene transcription was discovered. Moreover, ECL2 could block PRRSV absorption and infection, as well as neutralizing the virus in the supernatant, which may lead to the development of novel therapeutic antiviral strategies.