Multi-instance learning based artificial intelligence model to assist vocal fold leukoplakia diagnosis: A multicentre diagnostic study.

OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.

Development and validation of a risk prediction model and prediction tools for post-thrombotic syndrome in patients with lower limb deep vein thrombosis.

PURPOSE: Our research aims to compare the predictive performance of decision tree algorithms (DT) and logistic regression analysis (LR) in constructing models, and develop a Post-Thrombotic Syndrome (PTS) risk stratification tool. METHODS: We retrospectively collected and analyzed relevant case information of 618 patients diagnosed with DVT from January 2012 to December 2021 in three different tertiary hospitals in Jiangxi Province as the modeling group. Additionally, we used the case information of 212 patients diagnosed with DVT from January 2022 to January 2023 in two tertiary hospitals in Hubei Province and Guangdong Province as the validation group. We extracted electronic medical record information including general patient data, medical history, laboratory test indicators, and treatment data for analysis. We established DT and LR models and compared their predictive performance using receiver operating characteristic (ROC) curves and confusion matrices. Internal and external validations were conducted. Additionally, we utilized LR to generate nomogram charts, calibration curves, and decision curves analysis (DCA) to assess its predictive accuracy. RESULTS: Both DT and LR models indicate that Year, Residence, Cancer, Varicose Vein Operation History, DM, and Chronic VTE are risk factors for PTS occurrence. In internal validation, DT outperforms LR (0.962 vs 0.925, z = 3.379, P < 0.001). However, in external validation, there is no significant difference in the area under the ROC curve between the two models (0.963 vs 0.949, z = 0.412, P = 0.680). The validation results of calibration curves and DCA demonstrate that LR exhibits good predictive accuracy and clinical effectiveness. A web-based calculator software of nomogram (https://sunxiaoxuan.shinyapps.io/dynnomapp/) was utilized to visualize the logistic regression model. CONCLUSIONS: The combination of decision tree and logistic regression models, along with the web-based calculator software of nomogram, can assist healthcare professionals in accurately assessing the risk of PTS occurrence in individual patients with lower limb DVT.

Predictive value of TCM tongue characteristics for chemotherapy-induced myelosuppression in patients with lung cancer.

This study aimed to investigate the clinical predictors, including traditional Chinese medicine tongue characteristics and other clinical parameters for chemotherapy-induced myelosuppression (CIM), and then to develop a clinical prediction model and construct a nomogram. A total of 103 patients with lung cancer were prospectively enrolled in this study. All of them were scheduled to receive first-line chemotherapy regimens. Participants were randomly assigned to either the training group (n = 52) or the test group (n = 51). Tongue characteristics and clinical parameters were collected before the start of chemotherapy, and then the incidence of myelosuppression was assessed after treatment. We used univariate logistic regression analysis to identify the risk predictors for assessing the incidence of CIM. Moreover, we developed a predictive model and a nomogram using multivariate logistic regression analysis. Finally, we evaluated the predictive performance of the model by examining the area under the curve value of the receiver operating characteristic, calibration curve, and decision curve analysis. As a result, a total of 3 independent predictors were found to be associated with the CIM in multivariate regression analysis: the fat tongue (OR = 3.67), Karnofsky performance status score (OR = 0.11), and the number of high-toxic drugs in chemotherapy regimens (OR = 4.78). Then a model was constructed using these 3 predictors and it exhibited a robust predictive performance with an area under the curve of 0.82 and the consistent calibration curves. Besides, the decision curve analysis results suggested that applying this predictive model can result in more net clinical benefit for patients. We established a traditional Chinese medicine prediction model based on the tongue characteristics and clinical parameters, which could serve as a useful tool for assessing the risk of CIM.

Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, and its development comprises a multistep process from intraepithelial neoplasia (IN) to carcinoma (CA). However, the critical regulators and underlying molecular mechanisms remain largely unknown. AIM: To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention. METHODS: A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide (4NQO) to C57BL/6 mice. Moreover, we established a control group without 4NQO treatment of mice. Then, transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses, including low-grade IN (LGIN), high-grade IN (HGIN), and CA, and controlled normal tissue (NOR) samples. Differentially expressed genes (DEGs) were identified in the LGIN, HGIN, and CA groups, and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The CIBERSORT algorithm was used to detect the pattern of immune cell infiltration. Immunohistochemistry (IHC) was also conducted to validate our results. Finally, the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice. RESULTS: Compared with those in the NOR group, a total of 681541, and 840 DEGs were obtained in the LGIN, HGIN, and CA groups, respectively. Using the intersection of the three sets of DEGs, we identified 86 genes as key genes involved in the development of ESCC. Enrichment analysis revealed that these genes were enriched mainly in the keratinization, epidermal cell differentiation, and interleukin (IL)-17 signaling pathways. CIBERSORT analysis revealed that, compared with those in the NOR group, M0 and M1 macrophages in the 4NQO group showed stronger infiltration, which was validated by IHC. Serum cytokine analysis revealed that, compared with those in the NOR group, IL-1ß and IL-6 were upregulated, while IL-10 was downregulated in the LGIN, HGIN, and CA groups. Moreover, the expression of the representative key genes, such as S100a8 and Krt6b, was verified in external human samples, and the results of immunohistochemical staining were consistent with the findings in mice. CONCLUSION: We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions. In addition, we found that macrophage infiltration and abnormal alterations in the levels of inflammation-associated cytokines, such as IL-1ß, IL-6, and IL-10, in the peripheral blood may be closely associated with the development of ESCC.

Sex- and Age-Specific Prevalence of Osteopenia and Osteoporosis: Sampling Survey.

BACKGROUND: Osteopenia and osteoporosis are posing a long-term influence on the aging population's health contributing to a higher risk of mortality, loss of autonomy, hospitalization, and huge health system costs and social burden. Therefore, more pertinent data are needed to demonstrate the current state of osteoporosis. OBJECTIVE: This sampling survey seeks to assess the trends in the prevalence of osteopenia and osteoporosis in a Chinese Han population. METHODS: A community-based cross-sectional study involving 16,377 participants used a multistage sampling method. Bone mineral density was measured using the quantitative ultrasonic densitometry. Student t test and Mann-Whitney U test were used to test the difference between normally and nonnormally distributed quantitative variables between male and female participants. A chi-square (χ2) test was used to compare categorized variables. Stratified analysis was conducted to describe the prevalence rates of osteoporosis (T score ≤-2.5) and osteopenia (T score -2.5 to -1.0) across age, sex, calcium intake, and menopause. A direct standardization method was used to calculate the age-standardized prevalence rates of osteoporosis and osteopenia. T-score was further categorized into quartiles (T1-T4) by age- and sex-specified groups. RESULTS: The prevalence rates of osteopenia and osteoporosis were 40.5% (6633/16,377) and 7.93% (1299/16,377), respectively, and the age-standardized prevalence rates were 27.32% (287,877,129.4/1,053,861,940) and 3.51% (36,974,582.3/1,053,861,940), respectively. There was an increase in osteopenia and osteoporosis prevalence from 21.47% (120/559) to 56.23% (754/1341) and 0.89% (5/559) to 17.23% (231/1341), respectively, as age increased from 18 years to 75 years old. The prevalence rates of osteopenia and osteoporosis were significantly higher in female participants (4238/9645, 43.94% and 1130/9645, 11.72%) than in male participants (2395/6732, 35.58% and 169/6732, 2.51%; P<.001), and in postmenopausal female participants (3638/7493, 48.55% and 1053/7493, 14.05%) than in premenopausal female participants (538/2026, 26.55% and 53/2026, 2.62%; P<.001). In addition, female participants with a history of calcium intake had a lower osteoporosis prevalence rate than female participants without any history of calcium intake in all age groups (P=.004). From low quartile to high quartile of T-score, the prevalence of diabetes mellitus (752/4037, 18.63%; 779/4029, 19.33%; 769/3894, 19.75%; and 869/3879, 22.4%) and dyslipidemia (2228/4036, 55.2%; 2304/4027, 57.21%; 2306/3891, 59.26%; and 2379/3878, 61.35%) were linearly increased (P<.001), while the prevalence of cancer (112/4037, 2.77%; 110/4029, 2.73%; 103/3894, 2.65%; and 77/3879, 1.99%) was decreased (P=.03). CONCLUSIONS: Our data imply that as people age, osteopenia and osteoporosis are more common in females than in males, particularly in postmenopausal females than in premenopausal females, and bone mineral density significantly affects the prevalence of chronic diseases. These findings offer information that can be applied to intervention programs meant to prevent or lessen the burden of osteoporosis in China.

Clinical Efficacy of Programmed Cell Death Ligand 1 Antibody in Treatment of Extranodal Natural Killer/T-Cell Lymphoma With Hemophagocytic Lymphohistiocytosis.

Extranodal natural killer/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis (ENKTCL-LAHS) is a rare disease with poor prognosis. Currently, there are no well-established treatments for LAHS. Almost 50% of patients experience relapsed or refractory disease to anti-hemophagocytic lymphohistiocytosis (HLH) treatment, and the regimen for salvage therapy is limited. We report a case of ENKTCL-LAHS that was successfully treated with a programmed cell death ligand 1 (PD-L1) antibody (sugemalimab) alone and provide a literature review on existing ENKTCL-LAHS treatment options. A 31-year-old man with relapsed ENKTCL complicated by HLH was admitted to our hospital. Following the administration of the PD-L1 antibody sugemalimab, fever was resolved, Epstein-Barr virus (EBV) DNA copy number was negative, and HLH-related blood biochemical markers were decreased in the patient. Consequently, the patient achieved complete remission with a progression-free time (PFS) of 44 months. The prognosis of ENKTCL-LAHS is extremely poor, and the clinical treatment of ENKTCL-HLH is challenging. No previous reports exist regarding the use of PD-L1 antibodies in ENKTCL-LAHS treatment. This study is the first to report a patient with ENKTCL-LAHS treated with the PD-L1 antibody alone, who achieved a long PFS of 44 months. Our results suggest the effectiveness and safety of sugemalimab in the treatment of ENKTCL-LAHS; however, more clinical cases are required for validation. The PD-L1 antibody presents a novel treatment option for patients with ENKTCL-LAHS and warrants further clinical promotion.

Circulating plasma cells as a predictive biomarker in Multiple myeloma: an updated systematic review and meta-analysis.

BACKGROUND: Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status. METHODS: The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software. RESULTS: Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81-2.66, p < 0.001) and PFS (HR = 2.45, 95% CI: 1.93-3.12, p < 0.001). Subgroup analyses did not alter the prognostic role of CPCs, regardless of region, sample size, cut-off value, detection time, initial treatment, or data type. Moreover, the increased CPCs were significantly related to advanced tumour stage (ISS III vs. ISS I-II: pooled OR = 2.89, 95% CI: 2.41-3.46, p < 0.001; R-ISS III vs. R-ISS I-II: pooled OR = 3.65, 95% CI: 2.43-5.50, p < 0.001) and high-risk cytogenetics (high-risk vs. standard-risk: OR = 2.22, 95% CI: 1.60-3.08, p < 0.001). CONCLUSION: Our meta-analysis confirmed that the increased number of CPCs had a negative impact on the PFS and OS of MM patients. Therefore, CPCs could be a promising prognostic biomarker that helps with risk stratification and disease monitoring.

There is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.Our meta-analysis revealed that a high CPCs level was significantly associated with worse OS and PFS in MM patients.CPCs could be a promising predictive biomarker that helps with risk stratification and disease monitoring.

First-in-human study of GFH018, a small molecule inhibitor of transforming growth factor-ß receptor I inhibitor, in patients with advanced solid tumors.

BACKGROUND: Transforming growth factor-ß (TGF-ß) is a cytokine with multiple functions, including cell growth regulation, extracellular matrix production, angiogenesis homeostasis adjustment and et al. TGF-ß pathway activation promotes tumor metastasis/progression and mediates epithelial-mesenchymal transmission suppressing immunosurveillance in advanced tumors. GFH018, a small molecule inhibitor blocking TGF-ß signal transduction, inhibits the progression and/or metastasis of advanced cancers. This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of GFH018 monotherapy in patients with advanced solid tumors. METHODS: This phase I, open-label, multicenter study used a modified 3+3 dose escalation and expansion design. Adult patients with advanced solid tumors failing the standard of care were enrolled. Starting at 5 mg, eight dose levels up to 85 mg were evaluated. Patients received GFH018 BID (14d-on/14d-off) starting on the 4th day after a single dose on cycle 1, day 1. Subsequent cycles were defined as 28 days. The study also explored the safety of 85 mg BID 7d-on/7d-off. Adverse events were graded using NCI criteria for adverse events (NCI-CTCAE v5.0). PK was analyzed using a noncompartmental method. Efficacy was evaluated using RECIST 1.1. Blood samples were collected for biomarker analysis. RESULTS: Fifty patients were enrolled and received at least one dose of GFH018. No dose-limiting toxicity occurred, and the maximum tolerated dose was not reached. Forty-three patients (86.0%) had at least one treatment-related adverse event (TRAE), and three patients (6.0%) had ≥ G3 TRAEs. The most common TRAEs (any grade/grade ≥3) were AST increased (18%/0%), proteinuria (14%/2%), anemia (14%/2%), and ALT increased (12%/0%). No significant cardiotoxicity or bleeding was observed. GFH018 PK was linear and dose-independent, with a mean half-life of 2.25-8.60 h from 5 - 85 mg. Nine patients (18.0%) achieved stable disease, and one patient with thymic carcinoma achieved tumor shrinkage, with the maximum target lesion decreased by 18.4%. Serum TGF-ß1 levels were not associated with clinical responses. The comprehensive recommended dose for Phase II was defined as 85 mg BID 14d-on/14d-off. CONCLUSIONS: GFH018 monotherapy presented a favorable safety profile without cardiac toxicity or bleeding. Modest efficacy warrants further studies, including combination strategies. TRIAL REGISTRATION: ClinicalTrial. gov ( https://www. CLINICALTRIALS: gov/ ), NCT05051241. Registered on 2021-09-02.

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer.

Natural killer (NK) cells play essential roles in the tumor development, diagnosis, and prognosis of tumors. In this study, we aimed to establish a reliable signature based on marker genes in NK cells, thus providing a new perspective for assessing immunotherapy and the prognosis of patients with gastric cancer (GC). We analyzed a total of 1560 samples retrieved from the public database. We performed a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of gastric cancer and identified 377 marker genes for NK cells. By performing Cox regression analysis, we established a 12-gene NK cell-associated signature (NKCAS) for the Cancer Genome Atlas (TCGA) cohort, that assigned GC patients into a low-risk group (LRG) or a high-risk group (HRG). In the TCGA cohort, the areas under curve (AUC) value were 0.73, 0.81, and 0.80 at 1, 3, and 5 years. External validation of the predictive ability for the signature was then validated in the Gene Expression Omnibus (GEO) cohorts (GSE84437). The expression levels of signature genes were measured and validated in GC cell lines by real-time PCR. Moreover, NKCAS was identified as an independent prognostic factor by multivariate analysis. We combined this with a variety of clinicopathological characteristics (age, M stage, and tumor grade) to construct a nomogram to predict the survival outcomes of patients. Moreover, the LRG showed higher immune cell infiltration, especially CD8+ T cells and NK cells. The risk score was negatively associated with inflammatory activities. Importantly, analysis of the independent immunotherapy cohort showed that the LRG had a better prognosis and immunotherapy response when compared with the HRG. The identification of NK cell marker genes in this study suggests potential therapeutic targets. Additionally, the developed predictive signatures and nomograms may aid in the clinical management of GC.

Targeting high circDNA2v levels in colorectal cancer induces cellular senescence and elicits an anti-tumor secretome.

The efficacy of immunotherapy against colorectal cancer (CRC) is impaired by insufficient immune cell recruitment into the tumor microenvironment. Our study shows that targeting circDNA2v, a circular RNA commonly overexpressed in CRC, can be exploited to elicit cytotoxic T cell recruitment. circDNA2v functions through binding to IGF2BP3, preventing its ubiquitination, and prolonging the IGF2BP3 half-life, which in turn sustains mRNA levels of the protooncogene c-Myc. Targeting circDNA2v by gene silencing downregulates c-Myc to concordantly induce tumor cell senescence and the release of proinflammatory mediators. Production of CXCL10 and interleukin-9 by CRC cells is elicited through JAK-STAT1 signaling, in turn promoting the chemotactic and cytolytic activities of CD8+ T cells. Clinical evidence associates increased circDNA2v expression in CRC tissues with reductions in CD8+ T cell infiltration and worse outcomes. The regulatory relationship between circDNA2v, cellular senescence, and tumor-infiltrating lymphocytes thus provides a rational approach for improving immunotherapy in CRC.

Identification of hub genes in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is a heart valve disorder characterized primarily by calcification of the aortic valve, resulting in stiffness and dysfunction of the valve. CAVD is prevalent among aging populations and is linked to factors such as hypertension, dyslipidemia, tobacco use, and genetic predisposition, and can result in becoming a growing economic and health burden. Once aortic valve calcification occurs, it will inevitably progress to aortic stenosis. At present, there are no medications available that have demonstrated effectiveness in managing or delaying the progression of the disease. In this study, we mined four publicly available microarray datasets (GSE12644 GSE51472, GSE77287, GSE233819) associated with CAVD from the GEO database with the aim of identifying hub genes associated with the occurrence of CAVD and searching for possible biological targets for the early prevention and diagnosis of CAVD. This study provides preliminary evidence for therapeutic and preventive targets for CAVD and may provide a solid foundation for subsequent biological studies.

Effects of nonpharmacological interventions on symptom clusters in breast cancer survivors: A systematic review of randomized controlled trials.

Objective: To summarize nonpharmacological interventions and assess their effects on symptom clusters and quality of life (QoL) in breast cancer (BC) survivors. Methods: Seven English and three Chinese electronic databases and three clinical trial registries were searched from January 2001 to August 2023. A narrative approach was applied to summarize the data. The primary outcome was symptom clusters measured by any patient-reported questionnaires, and the secondary outcomes were QoL and intervention-related adverse events. Results: Six published articles, one thesis, and one ongoing trial involving 625 BC survivors were included. The fatigue-sleep disturbance-depression symptom cluster was the most frequently reported symptom cluster among BC survivors. The nonpharmacological interventions were potentially positive on symptom clusters and QoL among the BC survivors. However, some of the included studies exhibited methodological concerns (e.g., inadequate blinding and allocation concealment). The intervention protocols in only two studies were developed following a solid evidence-based approach. Adverse events related to the targeted interventions were reported in six included studies, with none performing a causality analysis. Conclusions: The nonpharmacological interventions could be promising strategies for alleviating symptom clusters in BC survivors. Future studies should adopt rigorously designed, randomized controlled trials to generate robust evidence. Systematic review registration: INPLASY202380028.

Determining priority control toxic metal for different protection targets based on source-oriented ecological and human health risk assessment around gold smelting area.

Determining the priority control source and pollutant is the key for the eco-health protection and risk management around gold smelting area. To this end, a case study was conducted to explore the pollution characteristics, source apportionment, ecological risk and human health risk of toxic metals (TMs) in agricultural soils surrounding a gold smelting enterprise. Three effective receptor models, including positive matrix factorization model (PMF), ecological risk assessment (ERA), and probabilistic risk assessment (PRA) have been combined to apportion eco-human risks for different targets. More than 95.0% of samples had a Nemerow pollution index (NPI) > 2 (NPImean=4.27), indicating moderately or highly soil TMs contamination. Four pollution sources including gold smelting activity, mining source, agricultural activity and atmosphere deposition were identified as the major sources, with the contribution rate of 17.52%, 44.16%, 13.91%, and 24.41%, respectively. For ecological risk, atmosphere deposition accounting for 30.8% was the greatest contributor, which was mainly loaded on Hg of 51.35%. The probabilistic health risk assessment revealed that Carcinogenic risks and Non-carcinogenic risks of all population were unacceptable, and children suffered from a greater health risk than adults. Gold smelting activity (69.2%) and mining source (42.0%) were the largest contributors to Carcinogenic risks and Non-carcinogenic risks, respectively, corresponding to As and Cr as the target pollutants. The priority pollution sources and target pollutants were different for the eco-health protection. This work put forward a new perspective for soil risk control and management, which is very beneficial for appropriate soil remediation under limited resources and costs.

Ultrathin LayCoOx Nanosheets with High Porosity Featuring Boosted Catalytic Oxidation of Benzene: Mechanism Elucidation via an Experiment-Theory Combined Paradigm.

Designing transition-metal oxides for catalytically removing the highly toxic benzene holds significance in addressing indoor/outdoor environmental pollution issues. Herein, we successfully synthesized ultrathin LayCoOx nanosheets (thickness of ∼1.8 nm) with high porosity, using a straightforward coprecipitation method. Comprehensive characterization techniques were employed to analyze the synthesized LayCoOx catalysts, revealing their low crystallinity, high surface area, and abundant porosity. Catalytic benzene oxidation tests demonstrated that the La0.029CoOx-300 nanosheet exhibited the most optimal performance. This catalyst enabled complete benzene degradation at a relatively low temperature of 220 °C, even under a high space velocity (SV) of 20,000 h-1, and displayed remarkable durability throughout various catalytic assessments, including SV variations, exposure to water vapor, recycling, and long time-on-stream tests. Characterization analyses confirmed the enhanced interactions between Co and doped La, the presence of abundant adsorbed oxygen, and the extensive exposure of Co3+ species in La0.029CoOx-300 nanosheets. Theoretical calculations further revealed that La doping was beneficial for the formation of oxygen vacancies and the adsorption of more hydroxyl groups. These features strongly promoted the adsorption and activation of oxygen, thereby accelerating the benzene oxidation processes. This work underscores the advantages of doping rare-earth elements into transition-metal oxides as a cost-effective yet efficient strategy for purifying industrial exhausts.

Reciprocal regulation of lncRNA MEF and c-Myc drives colorectal cancer tumorigenesis.

More than half of all cancers demonstrate aberrant c-Myc expression, making this arguably the most important human oncogene. Deregulated long non-coding RNAs (lncRNAs) are also commonly implicated in tumorigenesis, and some limited examples have been established where lncRNAs act as biological tuners of c-Myc expression and activity. Here, we demonstrate that the lncRNA denoted c-Myc Enhancing Factor (MEF) enjoys a cooperative relationship with c-Myc, both as a transcriptional target and driver of c-Myc expression. Mechanistically, MEF functions by binding to and stabilizing the expression of hnRNPK in colorectal cancer cells. The MEF-hnRNPK interaction serves to disrupt binding between hnRNPK and the E3 ubiquitin ligase TRIM25, which attenuates TRIM25-dependent hnRNPK ubiquitination and proteasomal destruction. In turn, the stabilization of hnRNPK through MEF enhances c-Myc expression by augmenting the translation c-Myc. Moreover, modulating the expression of MEF in shRNA-mediated knockdown and overexpression studies revealed that MEF expression is essential for colorectal cancer cell proliferation and survival, both in vitro and in vivo. From the clinical perspective, we show that MEF expression is differentially increased in colorectal cancer tissues compared to normal adjacent tissues. Further, correlations exist between MEF, c-Myc, and hnRNPK suggesting the MEF-c-Myc positive feedback loop is active in patients. Together these data demonstrate that MEF is a pivotal partner of the c-Myc network and propose MEF as a valuable therapeutic target for colorectal cancer.

Female tilapia, Oreochromis sp. mobilised energy differently for growth and reproduction according to living environment.

This study was conducted to investigate the energy mobilisation preference and ionoregulation pattern of female tilapia, Oreochromis sp. living in different environments. Three different treatments of tilapia as physiology compromising model were compared; tilapia cultured in recirculating aquaculture system (RAS as Treatment I-RAS), tilapia cultured in open water cage (Treatment II-Cage) and tilapia transferred from cage and cultured in RAS (Treatment III-Compensation). Results revealed that tilapia from Treatment I and III mobilised lipid to support gonadogenesis, whilst Treatment II tilapia mobilised glycogen as primary energy for daily exercise activity and reserved protein for growth. The gills and kidney Na+/K+ ATPase (NKA) activities remained relatively stable to maintain homeostasis with a stable Na+ and K+ levels. As a remark, this study revealed that tilapia strategized their energy mobilisation preference in accessing glycogen as an easy energy to support exercise metabolism and protein somatogenesis in cage culture condition, while tilapia cultured in RAS mobilised lipid for gonadagenesis purposes.

Design, synthesis, and biological evaluation of naphthoylamide derivatives as inhibitors of STAT3 phosphorylation.

The phosphorylation of STAT3 plays a critical physiological role in the proliferation of rectal cancer. Hence, inhibiting STAT3 phosphorylation is an effective anticancer approach. In this work, we designed a novel 5-R'-1-naphthylmethylamide scaffold as a small molecule inhibitor of STAT3 phosphorylation. The results showed that 3D and 4D have exceptional inhibitory ability against three different colorectal cancer (CRC) cell lines, and can induce apoptosis of CRC cells by inhibiting STAT3 phosphorylation, while having no killing effect on normal human cells. 3D and 4D can inhibit STAT3 phosphorylation in a time- and concentration-dependent manner, and also inhibit the nuclear translocation of interleukin (IL)-6-induced STAT3. In the in vivo tumor model research, 4D significantly reduced the tumor volume of mice and had no drug toxicity on other organ tissues. Furthermore, molecular docking studies revealed that 3D and 4D had greater binding free energy when interacting with the STAT3 SH2 structural domain, and could establish H-π interaction modes. Dynamic simulation studies indicated that both compounds were able to bind tightly to STAT3.

The DDD score outperforms the RENAL score in predicting high-grade renal cell carcinoma.

OBJECTIVES: To explore the relationship between Fuhrman grade of renal cell carcinoma (RCC) and the DDD score. METHODS: We reviewed the records of 527 nonmetastatic RCC patients. Demographic, clinical, and pathologic characteristics were reviewed. Binary logistic regression was used to explore the independent risk factors for high-grade RCC (HGRCC). RESULTS: Sex, BMI (Body Mass Index), RNS, and DDD score were significantly correlated with HGRCC. Based on these independent risk factors, we constructed two predictive models integrating the RNS and DDD scores with sex and BMI to predict tumor grade. The calibration curves of the predictive model showed good agreement between the observations and predictions. The concordance indexes (C-indexes) of the predictive models were 0.768 (95% CI, 0.713-0.824), and 0.809 (95% CI, 0.759-0.859). Receiver operating characteristic (ROC) curves were performed to compare the predictive power of the nomograms, and the prediction model including the DDD score had better prognostic ability (p = 0.01). CONCLUSIONS: This study found that RNS, DDD score, BMI, and sex were independent predictors of HGRCC. We developed effective nomograms integrating the above risk factors to predict HGRCC. Of note, the nomogram including the DDD score achieves better prediction ability for HGRCC.

Endosome associated trafficking regulator 1 promotes tumor growth and invasion of glioblastoma multiforme via inhibiting TNF signaling pathway.

PURPOSE: Endosome associated trafficking regulator 1 (ENTR1) is a novel endosomal protein, which can affect multiple cellular biological behavior by remodeling plasma membrane structures. However, little is known regarding its function and underlying mechanisms in glioblastoma multiforme. METHODS: Expression profile and clinical signature were obtained from The Public Database of human tumor. Immunohistochemical staining and western blotting assays were used to measure ENTR1 expression level. Human primary GBM tumor cells and human GBM cell lines A172, U87 and U251 were used to clarify the precise role of ENTR1. CCK-8 assays, wound healing and transwell invasion assays were designed to investigate cell viability, invasion and migration of GBM cells, respectively. Underlying molecular mechanisms of ENTR1 were determined via RNA-seq analysis. Tumor formation assay was used to validate the influence of ENTR1 in vivo. RESULTS: Compared with normal brain tissues, ENTR1 was highly expressed in gliomas and correlated with malignant grades of gliomas and poor overall survival time. The proliferation and invasion of GBM cells could be weaken and the sensitivity to temozolomide (TMZ) chemotherapy increased after knocking down ENTR1. Overexpression of ENTR1 could reverse this effect. RNA-seq analysis showed that tumor necrosis factor (TNF) signaling pathway might be a putative regulatory target of ENTR1. Tumor formation assay validated that ENTR1 was a significant factor in tumor growth. CONCLUSION: Our results indicated that ENTR1 played an important role in cell proliferation, invasion and chemotherapeutic sensitivity of GBM, suggesting that ENTR1 might be a novel prognostic marker and significant therapeutic target for GBM.