Environmental colloid behaviors of humic acid - Cadmium nanoparticles in aquatic environments.

Humic acid (HA), a principal constituent of natural organic matter (NOM), manifests ubiquitously across diverse ecosystems and can significantly influence the environmental behaviors of Cd(II) in aquatic systems. Previous studies on NOM-Cd(II) interactions have primarily focused on the immobilization of Cd(II) solids, but little is known about the colloidal stability of organically complexed Cd(II) particles in the environment. In this study, we investigated the formation of HA-Cd(II) colloids and quantified their aggregation, stability, and transport behaviors in a saturated porous media representative of typical subsurface conditions. Results from batch experiments indicated that the relative quantity of HA-Cd(II) colloids increased with increasing C/Cd molar ratio and that the carboxyl functional groups of HA dominated the stability of HA-Cd(II) colloids. The results of correlation analysis between particle size, critical aggregation concentration (CCC), and zeta potential indicated that both Derjaguin-Landau-Verwey-Overbeek (DLVO) and non-DLVO interactions contributed to the enhanced colloidal stability of HA-Cd(II) colloids. Column results further confirmed that the stable HA-Cd(II) colloid can transport fast in a saturated media composed of clean sand. Together, this study provides new knowledge of the colloidal behaviors of NOM-Cd(II) nanoparticles, which is important for better understanding the ultimate cycling of Cd(II) in aquatic systems.

Distinct characteristics and progression patterns of facet joint structural lesions in radiographic axial spondyloarthritis.

Background: Both vertebral bodies and posterior elements of the vertebrae (facet joints, FJ) can engage in bone formation in radiographic axial spondyloarthritis (r-axSpA). However, little is known about the specific structural lesions and progression patterns of FJs in r-axSpA. Objectives: To identify specific lesions related to r-axSpA and to investigate the distinct progression patterns by comparing the FJ changes of r-axSpA with that of diffuse idiopathic skeletal hyperostosis (DISH), osteoarthritis (OA), and control group (CG). Design: Single-center, retrospective study. Longitudinal imaging data were retrieved and collected. Methods: Age- and sex-matched patients with complete thoracic and lumbar spine computed tomography (CT) data were included and their bilateral FJs were assessed. FJ changes were divided into erosions, ankylosis, joint-space narrowing, osteophytes, subchondral sclerosis, subchondral cysts, and vacuum phenomena. Average progressed year was defined as "number of changed vertebrae × interval years"/number of changed vertebrae. Results: In all, 50 patients in each group were included. Subchondral cysts and vacuum phenomena were not observed. Bilateral FJ ankylosis (FJA)/erosions in the thoracic and lumbar spine, and unilateral ankylosis/erosions in T1-4, T9-12 were significantly more common in r-axSpA. Joint-space narrowing/osteophytes/subchondral sclerosis were significantly more common in DISH and OA. FJ lesions progressed in 56.34% of vertebrae of r-axSpA. The most common pattern was "FJ normal advanced to ankylosis" (17.54%) which required 2.63 years. It was followed by "erosions advanced to ankylosis" (12.3%) which took 2.05 years, and by "normal FJ advanced to erosions" (11.04%) which took 2.29 years, respectively. Degenerative changes could also progress to FJ erosions/ankylosis (24.83%). The majority pattern in DISH/OA was "FJ changes advanced to subchondral sclerosis/osteophytes/joint-space narrowing." Conclusion: Bilateral FJA/erosions are r-axSpA-specific lesions. The specific progression pattern for r-axSpA was "FJ changes advanced to ankylosis/erosions." Repeated CT examination in intervals of at least 2 years will be more appropriate for monitoring FJ progression.

APEX1 in intestinal epithelium triggers neutrophil infiltration and intestinal barrier damage in ulcerative colitis.

Ulcerative colitis (UC) can lead to the generation of large amounts of reactive oxygen species and DNA damage. DNA repair caused by base excision repair (BER) enzymes is an important mechanism for maintaining genomic integrity. However, the specific relationship between the function of BER enzymes and UC remains unclear. To address this, we conducted a study on non-cancerous colon tissue from patients with UC, focusing on the role of apurinic/apyrimidinic endonuclease 1 (APEX1) in BER to explore its significance in the progression of UC. Our research found that the expression of APEX1 in epithelium cells was significantly correlated to the severity of inflammatory bowel disease (IBD) and the infiltration and function of neutrophils in human UC and mouse models, particularly in relation to neutrophil extracellular traps (NETs) and the degranulation processes. APEX1 deficiency resulted in decreased production of the chemokines CXCL1 by the NF-κB pathway in epithelium cells, leading to reduced accumulation and activation of neutrophils associated with colitis in colon tissue, as well as decreased levels of IL-1ß. Furthermore, APEX1 deficiency reduced symptoms of colitis by decreasing epithelial cell apoptosis and altering the gut microbiome. Studies related to the redox activity of APEX1 have shown that the combination of the redox inhibitor E3330 with 5-aminosalicylic acid (5-ASA) can effectively alleviate colitis, indicating that APEX1 has promising prospects for clinical treatment of IBD. APEX1 is required for interactions between neutrophil and intestinal epithelial cells. This study provided a mechanism demonstrating that APEX1 protein triggered the risk of UC by promoting neutrophil infiltration and compromising intestinal epithelial barrier function.

Evaluating the predictive efficacy of real-time 3D echocardiography in cardiac resynchronization therapy.

BACKGROUND: The aim of this study is to assess the predictive efficacy of real-time three-dimensional echocardiography (RT-3DE) and QRS wave duration in determining the response to cardiac resynchronization therapy (CRT) and assessing left ventricular systolic function pre- and post-CRT device implantation. METHOD: A total of 51 patients with heart failure undergoing CRT at the Second Affiliated Hospital of Nantong University between January 1, 2013, and October 31, 2020, were enrolled in this study. Traditional two-dimensional echocardiography and RT-3DE were performed pre and post-CRT, with QRS wave width data from electrocardiograms and additional clinical information collected. Patients were categorized into CRT responder (n = 36) and CRT non-responder (n = 15) groups based on their response to CRT device implantation. Comparative analyses were conducted on the general characteristics of both groups, as well as the predictive efficacy of RT-3DE and QRS wave width for CRT responsiveness and left ventricular systolic function. Data on the standard deviation (Tmsv16-SD, Tmsv12-SD, Tmsv6-SD) and maximum difference (Tmsv16-Dif, Tmsv12-Dif, Tmsv6-Dif) of left ventricular end-systolic volume (LVESV) at segments 16, 12, and 6, as well as QRS wave width, were collected and analyzed. RESULTS: The indicators Tmsv6-Dif, Tmsv12-Dif, Tmsv16-Dif, Tmsv6-SD, Tmsv12-SD, Tmsv16-SD, and QRS wave width exhibited significantly higher values in the CRT responder group when compared to the CRT non-responder group (P < 0.05). Among these, Tmsv16-SD demonstrated superior predictive performance for post-CRT response, with a sensitivity of 88.9%, specificity of 80.0%, and a diagnostic cut-off value of 6.19%. This predictive capability exceeded that of the conventional indicator, QRS wave width. CONCLUSION: RT-3DE enables accurate prediction of post-CRT patient response and significantly facilitates quantitative assessment of CRT therapy efficacy.

Stabilization of sulfidated nano zerovalent iron with biochar: Enhanced transport and application for hexavalent chromium removal from water.

Nano zerovalent iron (nZVI) has been broadly used in the treatment of chromium (Cr) pollution. However, conventional nZVI particles are prone to surface oxidation and particle agglomeration, limiting their effectiveness in contaminant removal. To address these issues, sulfidated nZVI (S-nZVI) was synthesized on the corn stover biochar (BC) surface for rapid removal of Cr(VI) from water. Sedimentation and column transport experiments demonstrated that S-nZVI@BC exhibits excellent dispersion and transport properties, efficiently removing Cr(VI) in the pH range of 2.5-5.0 and showing minimal impact from dissolved oxygen. The Fe0, Fe(Ⅱ), and S2- components of the material, along with the leached Fe2+ ions, contributed to the Cr(VI) removal. A portion of the removed Cr(VI) was reduced to Cr(III) in solution, while another portion was adsorbed on the material's surface through precipitation, with 42.0% of Cr being adsorbed within 30 min. Cycling and water matrix interference experiments further demonstrated the material's excellent reusability and resistance to interference. Notably, the continuous Cr(VI) removal capability in column experiments and the reactivation potential of S-nZVI@BC highlight its promise for practical applications. Future studies are suggested to explore the ecotoxicological effects of the S-nZVI@BC and its capacity for the simultaneous removal of multiple contaminants.

Predictive factors for intrathoracic anastomotic leakage and postoperative mortality after esophageal cancer resection.

BACKGROUND: Esophageal cancer is currently one of the high-risk malignant tumors worldwide, posing a serious threat to human health. This study aimed to analyse the causes of postoperative mortality and intrathoracic anastomotic leakage(IAL) after esophagectomy. METHODS: A retrospective analysis was conducted on 172 patients with esophageal cancer resection and focused on the preoperative and postoperative indicators. Cox regression analysis was performed to identify factors affected IAL and evaluated the potential factors on postoperative mortality. The Kaplan-Meier curve was applied to evaluate the effect of leakage on postoperative mortality after propensity score matching. RESULTS: Univariable and multivariable Cox regression analysis showed that infection and high BMI were significant risk factors for IAL, patients with BMI over 24 kg/m2 in IAL group was two times higher than that of the group without IAL (95% CI = 1.01-6.38; P = 0.048). When patients were infected, the hazard ratios(HRs) of anastomotic leakage was twice that of patients without infection (95% CI = 1.22-4.70; P = 0.011). On the other hand, IAL was a significant cause of postoperative mortality, the 40-day postoperative mortality rate in the leakage group was significantly higher than the non leakage group (28.95% in leakage group vs. 7.46% in non leakage group, P<0.01). After propensity score matching, IAL still significantly affected postoperative mortality. The total length of hospital stay of the leakage group was inevitably longer than that of the non leakage group (22.19 ± 10.79 vs. 15.27 ± 8.59). CONCLUSION: IAL was a significant cause of death in patients underwent esophageal cancer resection. Patients with high BMI over 24 kg/m2 and infection may be more prone to developing IAL after esophagectomy. IAL inevitably prolonged the length of hospital stay and increased postoperative mortality.

Development and application of an artificial intelligence-assisted endoscopy system for diagnosis of Helicobacter pylori infection: a multicenter randomized controlled study.

BACKGROUND: The early diagnosis and treatment of Heliobacter pylori (H.pylori) gastrointestinal infection provide significant benefits to patients. We constructed a convolutional neural network (CNN) model based on an endoscopic system to diagnose H. pylori infection, and then examined the potential benefit of this model to endoscopists in their diagnosis of H. pylori infection. MATERIALS AND METHODS: A CNN neural network system for endoscopic diagnosis of H.pylori infection was established by collecting 7377 endoscopic images from 639 patients. The accuracy, sensitivity, and specificity were determined. Then, a randomized controlled study was used to compare the accuracy of diagnosis of H. pylori infection by endoscopists who were assisted or unassisted by this CNN model. RESULTS: The deep CNN model for diagnosis of H. pylori infection had an accuracy of 89.6%, a sensitivity of 90.9%, and a specificity of 88.9%. Relative to the group of endoscopists unassisted by AI, the AI-assisted group had better accuracy (92.8% [194/209; 95%CI: 89.3%, 96.4%] vs. 75.6% [158/209; 95%CI: 69.7%, 81.5%]), sensitivity (91.8% [67/73; 95%CI: 85.3%, 98.2%] vs. 78.6% [44/56; 95%CI: 67.5%, 89.7%]), and specificity (93.4% [127/136; 95%CI: 89.2%, 97.6%] vs. 74.5% [114/153; 95%CI: 67.5%, 81.5%]). All of these differences were statistically significant (P < 0.05). CONCLUSION: Our AI-assisted system for diagnosis of H. pylori infection has significant ability for diagnostic, and can improve the accuracy of endoscopists in gastroscopic diagnosis. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Daping Hospital (10/07/2020) (No.89,2020) and was registered with the Chinese Clinical Trial Registration Center (02/09/2020)   ( www.chictr.org.cn ; registration number: ChiCTR2000037801).

Proton therapy for breast cancer: Reducing toxicity.

Radiotherapy is a crucial component in the holistic management of breast cancer, with approximately 60% of individuals diagnosed with breast cancer requiring this treatment. As the survival rate of individuals with breast cancer has significantly increased, there is a growing focus on the long-term well-being of patients. Proton therapy (PT) is a new and rapidly developing radiotherapy method. In comparison with conventional photon therapy, PT offers the benefits of decreased radiation toxicity and increased dosage in the designated region. This can extend patients' lifespan and enhance their overall well-being. The present analysis examines the function of PT in diminishing the harmful effects of radiation in cases of breast cancer, while also providing a brief overview of the future potential and obstacles associated with PT for breast cancer.

AIM2 Deficiency Alleviates Cardiac Inflammation and Hypertrophy in HFD/STZ-Induced Diabetic Mice by Inhibiting the NLRC4/IRF1 Signaling Pathway.

Absent in melanoma 2(AIM2) exacerbates atherosclerosis by inflammasome assembly. However, AIM2-mediated inflammation in diabetic cardiomyopathy remains incompletely understood. Here we investigate the role of AIM2 in high glucose (HG)- and diabetes-induced inflammatory cardiomyopathy. By RNA-seq, we found that AIM2 were significantly upregulated in HG-induced macrophages, upregulation of AIM2 in cardiac infiltrating macrophages was confirmed in a high-fat diet (HFD)/streptozotocin (STZ)-induceddiabetic mouse model . Therefore, AIM2 knockout mice were constructed. Compared to WT mice, HFD/STZ-induced cardiac hypertrophy and dysfunction were significantly improved in AIM2-/- mice, despite no changes in blood glucose and body weight. Further, AIM2 deficiency inhibited cardiac recruitment of M1-macrophages and cytokine production. Mechanistically, AIM2-deficient macrophgaes reduced IL-1ß and TNF-α secretion, which impaired the NLRC4/IRF1 signaling in cardiomyocytes, and reduced further recruitment of macrophages, attenuated cardiac inflammation and hypertrophy, these effects were confirmed by silencing IRF1 in WT mice, and significantly reversed by overexpression of IRF1 in AIM2-/- mice. Taken together, our findings suggest that AIM2 serves as a novel target for the treatment of diabetic cardiomyopathy.

Profound primary prevention of liver cancer following a natural experiment in China: A 50-year perspective and public health implications.

Liver cancer causes upwards of 1 million cancer deaths annually and is projected to rise by at least 55% over the next 15 years. Two of the major risk factors contributing to liver cancer have been well documented by multiple epidemiologic studies and the hepatitis B virus (HBV) and aflatoxin show a synergy that increases by more than 8-fold the risk of liver cancer relative to HBV alone. Using the population-based cancer registry established by the Qidong Liver Cancer Institute in 1972 and aflatoxin-specific biomarkers, we document that reduction of aflatoxin exposure has likely contributed to a nearly 70% decline in age-standardized liver cancer incidence over the past 30 years despite an unchanging prevalence of HBV infection in cases. A natural experiment of economic reform in the 1980s drove a rapid switch from consumption of heavily contaminated corn to minimally, if any, contaminated rice and subsequent dietary diversity. Aflatoxin consumption appears to accelerate the time to liver cancer diagnosis; lowering exposure to this carcinogen adds years of life before a cancer diagnosis. Thus, in 1990 the median age of diagnosis was 48 years, while increasing to 67 years by 2021. These findings have important translational public health implications since up to 5 billion people worldwide might be routinely exposed to dietary aflatoxin, especially in societies using corn as the staple food. Interventions against aflatoxin are an achievable outcome leading to a reduction in liver cancer incidence and years of delay of its nearly always fatal diagnosis.

Efficient mineralization of cadmium and arsenic by poorly crystalline CaFe-layered double hydroxide in soil: Performance and mechanism.

The co-contamination of arsenic (As) and cadmium (Cd) in the environment is of most concern. In this work, poorly crystalline CaFe-layered double hydroxide (CaFe-LDH) was synthesized with a Ca-to-Fe molar ratio of 4 to ensure effective immobilization of Cd and As in soil. The application of Ca4Fe-LDH in soil remediation demonstrated that the targeted heavy metals gradually mineralized into a relatively stable oxidizable and residual state. At a soil remediation dosage of 1.6%, the availability levels of Cd and As decreased significantly, achieving stabilization efficiencies of 99% and 85.2% respectively. Cd is trapped through isomorphic substitution and dissolution-reprecipitation of calcium (Ca) laminate, resulting in the formation of CdCaFe-LDH mineralization products. As is immobilized through ion exchange with interlayer anions, redox with Fe(III), and Fe-Cd-As complexation. Moreover, the results of the characterization and density functional theoretical (DFT) calculations demonstrate that the CdCaFe-LDH formed by isomeric substitution of Ca for Cd enhanced the adsorption of As on the (110) plane of LDH, indicating that the trap mechanism of Cd and As by Ca4Fe-LDH is synergistically promoted. Overall, the above results prove that mineralization using Ca4Fe-LDH is a promising method to remediate soils combined contaminated by both Cd and As.

ROS-sensitive PD-L1 siRNA cationic selenide nanogels for self-inhibition of autophagy and prevention of immune escape.

In the field of cancer therapy, inhibiting autophagy has emerged as a promising strategy. However, pharmacological disruption of autophagy can lead to the upregulation of programmed death-ligand 1 (PD-L1), enabling tumor immune evasion. To address this issue, we developed innovative ROS-responsive cationic poly(ethylene imine) (PEI) nanogels using selenol chemistry-mediated multicomponent reaction (MCR) technology. This procedure involved simple mixing of low-molecular-weight PEI (LMW PEI), γ-selenobutylacetone (γ-SBL), and poly(ethylene glycol) methacrylate (PEGMA). Through high-throughput screening, we constructed a library of AxSeyOz nanogels and identified the optimized A1.8Se3O0.5/siPD-L1 nanogels, which exhibited a size of approximately 200 nm, excellent colloidal stability, and the most effective PD-L1 silencing efficacy. These nanogels demonstrated enhanced uptake by tumor cells, excellent oxidative degradation ability, and inhibited autophagy by alkalinizing lysosomes. The A1.8Se3O0.5/siPD-L1 nanogels significantly downregulated PD-L1 expression and increased the expression of major histocompatibility complex class I (MHC-I), resulting in robust proliferation of specific CD8+ T cells and a decrease in MC38 tumor growth. As a result, the A1.8Se3O0.5/siPD-L1 nanogels inhibited tumor growth through self-inhibition of autophagy, upregulation of MHC-I, and downregulation of PD-L1. Designed with dynamic diselenide bonds, the A1.8Se3O0.5/siPD-L1 nanogels showed synergistic antitumor efficacy through self-inhibition of autophagy and prevention of immune escape.

lncSNHG16 promotes hepatocellular carcinoma development by inhibiting autophagy.

OBJECTIVE: To investigate the expression of long non-coding RNA lncSNHG16 in hepatocellular carcinoma (HCC), associations between its expression and patient survival, and its potential role in regulating autophagy in the disease. METHODS: Expression of lncSNHG16 was measured using quantitative real-time PCR in HCC cells in culture and HCC tissues from patients. Effects of lncSNHG16 overexpression were examined in HCC cultures using assays of cell proliferation, wound healing, and migration or invasion in Transwell dishes. Effects of lncSNHG16 overexpression were also examined in subcutaneous tumor in mice. Relationships of lncSNHG16 expression to autophagy and apoptosis in HCC cultures were explored using western blotting and flow cytometry. RESULTS: Higher lncSNHG16 expression in HCC tissues was associated with significantly worse overall and recurrence-free survival of patients. Overexpressing lncSNHG16 in HCC cell culture promoted cell proliferation, migration, and invasion while suppressing apoptosis. lncSNHG16 was associated with upregulation of STAT3 as well as inhibition of autophagy and associated apoptosis. Overexpressing lncSNHG16 accelerated tumor growth and weight in mice. CONCLUSION: The non-coding RNA lncSNHG16 suppresses autophagy and associated apoptosis in HCC, making it a potential therapeutic target.

Ultrasonic features of hidradenoma papilliferum: An unexpected mass in the vulvar.

Hidradenoma papilliferum is a rare superficial mass with distinct ultrasonic features. It originates from mammary structures and is commonly observed in the anogenital region of women. We report a hidradenoma papilliferum with clear ultrasound images which have never be described before.

Comparative efficacy and safety of first-line tyrosine kinase inhibitors in chronic myeloid leukemia: a systematic review and network meta-analysis.

Background: Tyrosine kinase inhibitors (TKIs) have become the preferred drugs for the treatment of chronic phase (CP) chronic myeloid leukemia (CML). This study aims to compare the safety and efficacy of different TKIs as first-line treatments for CML using network meta-analysis (NMA), providing a basis for the precise clinical use of TKIs. Methods: A systematic search was conducted on PubMed, Cochrane Library, Embase, China National knowledge Infrastructure (CNKI), Wanfang, Chinese Science and Technology Periodical Databases (VIP), SinoMed and ClinicalTrials.gov to include RCTs that compared the different TKIs as first line treatment for CML. The search timeline was from inception to 21 July 2023. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the frequentist NMA methods, the efficacy and safety of different TKIs were compared, including the rates of major molecular response (MMR), complete cytogenetic response (CCyR), all grade adverse events, grade 3 or higher hematologic adverse events and liver toxicity. Results: A total of 25 RCTs involving 6,823 patients with CML and 6 types of TKIs were included. In terms of efficacy, second-generation TKIs such as dasatinib, nilotinib, and radotinib showed certain advantages in improving patients' MMR and CCyR compared to imatinib. Additionally, imatinib 800 mg provided better MMRs and CCyRs than imatinib 400 mg. As far as safety was concerned, there was no significant difference in the incidence of all grade adverse events among the different TKIs. All TKIs can cause serious grade 3-4 hematologic adverse events, including anemia, thrombocytopenia, and neutropenia. Dasatinib more likely caused anemia, bosutinib thrombocytopenia, and imatinib neutropenia, whereas nilotinib and flumatinib might have better safety profiles in terms of severe hematologic adverse events. For liver toxicity, radotinib 400 mg and imatinib 800 mg, respectively, had the highest likelihood of ranking first in incidence rates of all grade ALT and AST elevation. Conclusions: In CML, second-generation TKIs are more clinically effective than imatinib even if this last drug has a relatively better safety profile. Thus, as each second-generation TKI has a distinct clinical efficacy and safety, and is associated with different economic factors, its choice should be dictated by the specific patient clinical conditions (patient's specific disease characteristics, comorbid conditions, potential drug interactions, as well as their adherence). Nevertheless, due to the limited number of original research, additional high-quality studies are needed to achieve any firm conclusion on which second-generation TKI is the best choice for that peculiar patient.

Regulation of Hippo/YAP axis in colon cancer progression by the deubiquitinase JOSD1.

Colon cancer is a prevalent malignancy, while recent studies revealed the dys-regulation of Hippo signaling as the important driver for colon cancer progression. Several studies have indicated that post-translational modifications on YAP play crucial roles in both Hippo signaling activity and cancer progression. This raises a puzzling question about why YAP/TAZ, an auto-inhibitory pathway, is frequently over-activated in colon cancer, despite the suppressive cascade of Hippo signaling remaining operational. The protein stability of YAP is subject to a tiny balance between ubiquitination and deubiquitination processes. Through correlation analysis of DUBs (deubiquitinases) expression and Hippo target gene signature in colon cancer samples, we found JOSD1 as a critical deubiquitinase for Hippo signaling and colon cancer progression. JOSD1 could facilitate colon cancer progression and in colon cancer, inhibition of JOSD1 via shRNA has been demonstrated to impede tumorigenesis. Furthermore, molecular mechanism studies have elucidated that JOSD1 enhances the formation of the Hippo/YAP transcriptome by impeding K48-linked polyubiquitination on YAP. ChIP assays have shown that YAP binds to JOSD1's promoter region, promoting its gene transcription. These results suggest that JOSD1 is involved in both activating and being targeted by the Hippo signaling pathway in colon cancer. Consequently, a positive regulatory loop between JOSD1 and Hippo signaling has been identified, underscoring their interdependence during colon cancer progression. Thus, targeting JOSD1 may represent a promising therapeutic approach for managing colon cancer.

Unveiling the synergetic benefits of the tunneling technique using stapler tractor in precise resection of lung segments: a retrospective cohort study.

Background: Tunneling technique has shown preliminary promise in lung segmentectomy which requires the use of staplers in specific procedures. However, the obstacle when staples pass is the most obvious factor hindering the implementation and development of this technique. This study investigated whether the obstacle of the technology could be addressed by using an innovative self-designed stapler tractor and analyzed the combined and respective advantages of them. Methods: The clinical data of patients with lung nodules located near anatomical sites with potential tunnel creation treated by segmentectomy were analyzed in this retrospective case-control study. The data were divided into four groups according to four distinct surgical strategies: In Group A, the tunneling technique was performed with a stapler tractor; in Group B, the tunneling technique was performed without a stapler tractor; in Group C, didn't perform the tunneling technique but using stapler tractor in a normal approach; and in Group D, neither performed the technique nor used the stapler tractor. The general linear data, operation times, intraoperative adverse events, postoperative recovery and complications were compared. Results: Compared with other groups, Group A exhibited the best surgical outcomes in comprehensive aspects. Separately, the tunnel groups (Group A&B) had better outcomes in the macro implementation of operation, including resection margin, the number of sampled intrapulmonary lymph nodes and resected subsegments, while the staple tractor groups (Group A&C) performed better on details of the procedure, including operation time, conversion to thoracotomy, and intraoperative bleeding (p < 0.05). Both of them were beneficial for shorter hospital stay, and the tunnel group was more advantageous. Conclusion: The tunneling technique is an advanced and beneficial surgical strategy for performing precise resection of lung segments while a stapler tractor can promote and facilitate it as a supplementary instrument. They show more combined benefits in effectively minimizing the occurrence of erroneous injuries and enhancing the operational efficacy.

[Retracted] MicroRNA­9 inhibits gastric cancer cell proliferation and migration by targeting neuropilin­1.

[This retracts the article DOI: 10.3892/etm.2019.7841.].

USP36 promotes tumorigenesis and tamoxifen resistance in breast cancer by deubiquitinating and stabilizing ERα.

BACKGROUND: Breast cancer is the most prevalent cancer in women globally. Over-activated estrogen receptor (ER) α signaling is considered the main factor in luminal breast cancers, which can be effectively managed with selective estrogen receptor modulators (SERMs) like tamoxifen. However, approximately 30-40% of ER + breast cancer cases are recurrent after tamoxifen therapy. This implies that the treatment of breast cancer is still hindered by resistance to tamoxifen. Recent studies have suggested that post-translational modifications of ERα play a significant role in endocrine resistance. The stability of both ERα protein and its transcriptome is regulated by a balance between E3 ubiquitin ligases and deubiquitinases. According to the current knowledge, approximately 100 deubiquitinases are encoded in the human genome, but it remains unclear which deubiquitinases play a critical role in estrogen signaling and endocrine resistance. Thus, decoding the key deubiquitinases that significantly impact estrogen signaling, including the control of ERα expression and stability, is critical for the improvement of breast cancer therapeutics. METHODS: We used several ER positive breast cancer cell lines, DUB siRNA library screening, xenograft models, endocrine-resistant (ERα-Y537S) model and performed immunoblotting, real time PCR, RNA sequencing, immunofluorescence, and luciferase activity assay to investigate the function of USP36 in breast cancer progression and tamoxifen resistance. RESULTS: In this study, we identify Ubiquitin-specific peptidase 36 (USP36) as a key deubiquitinase involved in ERα signaling and the advancement of breast cancer by deubiquitinases siRNA library screening. In vitro and in vivo studies showed that USP36, but not its catalytically inactive mutant (C131A), could promote breast cancer progression through ERα signaling. Conversely, silencing USP36 inhibited tumorigenesis. In models resistant to endocrine therapy, silencing USP36 destabilized the resistant form of ERα (Y537S) and restored sensitivity to tamoxifen. Molecular studies indicated that USP36 inhibited K48-linked polyubiquitination of ERα and enhanced the ERα transcriptome. It is interesting to note that our results suggest USP36 as a novel biomarker for treatment of breast cancer. CONCLUSION: Our study revealed the possibility that inhibiting USP36 combined with tamoxifen could provide a potential therapy for breast cancer.