A C-type lectin with dual carbohydrate recognition domains functions in innate immune response in Asian corn borer, Ostrinia furnacalis.

C-type lectins (CTLs) act as pattern recognition receptors (PRRs) to initiate the innate immune response in insects. A CTL with dual carbohydrate recognition domains (CRDs) (named immulectin-4 [IML-4]) was selected from the Ostrinia furnacalis transcriptome dataset for functional studies. We cloned the full-length complementary DNA of O. furnacalis IML-4 (OfIML-4). It encodes a 328-residue protein with a Glu-Pro-Asn (EPN) and Gln-Pro-Asp (QPD) motifs in 2 CRDs, respectively. OfIML-4 messenger RNA levels increased significantly upon the bacterial and fungal infection. Recombinant OfIML-4 (rIML-4) and its individual CRDs (rCRD1 and rCRD2) exhibited the binding ability to various microorganisms including Escherichia coli, Micrococcus luteus, Pichia pastoris, and Beauveria bassiana, and the cell wall components including lipopolysaccharide from E. coli, peptidoglycan from M. luteus or Bacillus subtilis, and curdlan from Alcaligenes faecalis. The binding further induced the agglutination of E. coli, M. luteus, and B. bassiana in the presence of calcium, the phagocytosis of Staphylococcus aureus by the hemocytes, in vitro encapsulation and melanization of nickel-nitrilotriacetic acid beads, and a significant increase in phenoloxidase activity of plasma. In addition, rIML-4 significantly enhanced the phagocytosis, nodulation, and resistance of O. furnacalis to B. bassiana. Taken together, our results suggest that OfIML-4 potentially works as a PRR to recognize the invading microorganisms, and functions in the innate immune response in O. furnacalis.

Association between two novel anthropometric measures and type 2 diabetes in a Chinese population.

AIMS: To investigate the associations of conicity index (C-index) and relative fat mass (RFM) with incident type 2 diabetes mellitus (T2DM) among adults in China. MATERIALS AND METHODS: A total of 10 813 participants aged over 18 years in Shenzhen Longhua district were enrolled in a follow-up study conducted from 2018 to 2022. The participants were categorized based on quartiles (Q) of C-index and RFM. The Cox proportional hazards model was performed to examine the relationships between C-index, RFM and the risk of T2DM. RESULTS: After adjusting for potential confounding factors, including age, sex, occupation, marital status, education level, smoking status, alcohol consumption, physical exercise, hypertension status, fasting blood glucose (FBG) and total cholesterol (TC), both C-index and RFM showed positive and independent associations with risk of T2DM. The multivariable-adjusted hazard ratios (95% confidence intervals) for T2DM risk in participants in C-index Q3 and Q4 compared with those in C-index Q1 were 1.50 (1.12, 2.02) and 1.73 (1.29, 2.30), and 1.94 (1.44, 2.63), 3.18 (1.79, 5.64), 4.91 (2.68, 9.00) for participants in RFM Q2, Q3 and Q4 compared with RFM Q1. These differences were statistically significant (all p < 0.05). CONCLUSION: C-index and RFM are strongly associated with new-onset T2DM and could be used to identify the risk of diabetes in large-scale epidemiological studies.

METTL14 regulates CD8+T-cell activation and immune responses to anti-PD-1 therapy in lung cancer.

BACKGROUND: N6-methyladenosine (m6A) modification plays an important role in lung cancer. However, methyltransferase-like 14 (METTL14), which serves as the main component of the m6A complex, has been less reported to be involved in the immune microenvironment of lung cancer. This study aimed to analyze the relationship between METTL14 and the immune checkpoint inhibitor programmed death receptor 1 (PD-1) in lung cancer. METHODS: CCK-8, colony formation, transwell, wound healing, and flow cytometry assays were performed to explore the role of METTL14 in lung cancer progression in vitro. Furthermore, syngeneic model mice were treated with sh-METTL14 andan anti-PD-1 antibody to observe the effect of METTL14 on immunotherapy. Flow cytometry and immunohistochemical (IHC) staining were used to detect CD8 expression. RIP and MeRIP were performed to assess the relationship between METTL14 and HSD17B6. LLC cells and activated mouse PBMCs were cocultured in vitro to mimic immune cell infiltration in the tumor microenvironment. ELISA was used to detect IFN-γ and TNF-α levels. RESULTS: The online database GEPIA showed that high METTL14 expression indicated a poor prognosis in patients with lung cancer. In vitro assays suggested that METTL14 knockdown suppressed lung cancer progression. In vivo assays revealed that METTL14 knockdown inhibited tumor growth and enhanced the response to PD-1 immunotherapy. Furthermore, METTL14 knockdown enhanced CD8+T-cell activation and infiltration. More importantly, METTL14 knockdown increased the stability of HSD17B6 mRNA by reducing its m6A methylation. In addition, HSD17B6 overexpression promoted the activation of CD8+ T cells. CONCLUSION: The disruption of METTL14 contributed to CD8+T-cell activation and the immunotherapy response to PD-1 via m6A modification of HSD17B6, thereby suppressing lung cancer progression.

Identification and immunological characteristics of anoikis-associated molecular clusters in lung adenocarcinoma.

Anoikis plays a crucial role in the progression, prognosis, and immune response of lung adenocarcinoma (LUAD). However, its specific impact on LUAD remains unclear. In this study, we investigated the intricate interplay of nesting apoptotic factors in LUAD. By analyzing nine key nesting apoptotic factors, we categorized LUAD patients into two distinct clusters. Further examination of immune cell profiles revealed that Cluster A exhibited greater infiltration of innate immune cells than did Cluster B. Additionally, we identified two genes closely associated with prognosis and developed a predictive model to differentiate patients based on molecular clusters. Our findings suggest that the loss of specific anoikis-related genes could significantly influence the prognosis, tumor microenvironment, and clinical features of LUAD patients. Furthermore, we validated the expression and functional roles of two pivotal prognostic genes, solute carrier family 2 member 1 (SLC2A1) and sphingosine kinase 1 (SPHK1), in regulating tumor cell viability, migration, apoptosis, and anoikis. These results offer valuable insights for future mechanistic investigations. In conclusion, this study provides new avenues for advancing our understanding of LUAD, improving prognostic assessments, and developing more effective immunotherapy strategies.

SPINK5 inhibits esophageal squamous cell carcinoma metastasis via immune activity.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of esophageal cancer with relatively high mortality worldwide. Serine peptidase inhibitor Kazal-type 5 (SPINK5) is reported to be downregulated in ESCC. However, its explicit role in ESCC remains further investigation. METHODS: The tumor tissues and adjacent non-cancerous tissues were obtained from 196 patients with ESCC for the determination of SPINK5 mRNA levels. Additionally, the relationship between SPINK5 mRNA levels and clinicopathological features of ESCC patients was explored. The effects of SPINK5 on the invasion and migration of ESCC cells were assessed using Transwell assays. Furthermore, SPINK5 mRNA and LEKTI protein were measured in ESCC cell lines after treatment with poly (I:C), lipopolysaccharide (LPS) or unmethylated CpG DNA. Moreover, the correlation between expression of SPINK5 and nuclear factor-kappa B (NF-κB) signaling pathway-related genes was analyzed in the TCGA-ESCC cohort, and the effects of SPINK5 on NF-κB transcription was analyzed using a luciferase reporter gene assay. Finally, the correlations between SPINK5 and infiltration of immune cells, immune scores, stromal scores and ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) scores were explored. RESULTS: SPINK5 mRNA levels were downregulated in tumor tissues, which was significantly correlated with higher lymph node metastases. Overexpressed SPINK5 inhibited cell invasion and migration in ESCC cell lines. Mechanistically, LPS-induced activation of Toll-like receptor 4 (TLR4) decreased SPINK5 mRNA and LEKTI in KYSE150 and KYSE70 cells. Spearman correlation analysis revealed that SPINK5 mRNA was significantly negatively correlated with a total of seven NF-κB signaling pathway-related genes in TCGA-ESCC patients. Moreover, downregulation of SPINK5 increased and upregulation of SPINK5 decreased the activity of the NF-κB promoter in HEK293T cells. Finally, immune cells infiltration analysis revealed that SPINK5 was significantly correlated with the infiltration of various immune cells, stromal scores, immune scores and ESTIMATE scores. CONCLUSIONS: SPINK5 plays critical roles in the TLR4/NF-κB pathway and immune cells infiltration, which might contribute to the ESCC metastasis. The findings of the present study may provide a promising biomarker for the diagnosis and treatment of esophageal squamous cell carcinoma.

Long-term air pollutants exposure and respiratory mortality: A large prospective cohort study.

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05-3.39), 1.62 (1.23-2.12), 2.06 (1.73-2.45), 1.20 (1.16-1.25), and 1.07 (1.05-1.08) per 10 µg/m3 increase in PM2.5, PM2.5-10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33-1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.

Trilobolide-6-O-isobutyrate exerts anti-tumor effects on cholangiocarcinoma cells through inhibiting JAK/STAT3 signaling pathway.

Trilobolide-6-O-isobutyrate exhibits significant antitumor effects on cholangiocarcinoma (CCA) cells by effectively inhibiting the JAK/STAT3 signaling pathway. This study aims to investigate the mechanisms underlying the antitumor properties of trilobolide-6-O-isobutyrate, and to explore its potential as a therapeutic agent for CCA. This study illustrates that trilobolide-6-O-isobutyrate efficiently suppresses CCA cell proliferation in a dose- and time-dependent manner. Furthermore, trilobolide-6-O-isobutyrate stimulates the production of reactive oxygen species, leading to oxidative stress and initiation of apoptosis via the activation of the mitochondrial pathway. Data from xenograft tumor assays in nude mice confirms that TBB inhibits tumor growth, and that there are no obvious toxic effects or side effects in vivo. Mechanistically, trilobolide-6-O-isobutyrate exerts antitumor effects by inhibiting STAT3 transcriptional activation, reducing PCNA and Bcl-2 expression, and increasing P21 expression. These findings emphasizes the potential of trilobolide-6-O-isobutyrate as a promising therapeutic candidate for the treatment of CCA.

Citrate Improves Biomimetic Mineralization Induced by Polyelectrolyte-Cation Complexes Using PAsp-Ca&Mg Complexes.

Magnesium ions are highly enriched in early stage of biological mineralization of hard tissues. Paradoxically, hydroxyapatite (HAp) crystallization is inhibited significantly by high concentration of magnesium ions. The mechanism to regulate magnesium-doped biomimetic mineralization of collagen fibrils has never been fully elucidated. Herein, it is revealed that citrate can bioinspire the magnesium-stabilized mineral precursors to generate magnesium-doped biomimetic mineralization as follows: Citrate can enhance the electronegativity of collagen fibrils by its absorption to fibrils via hydrogen bonds. Afterward, electronegative collagen fibrils can attract highly concentrated electropositive polyaspartic acid-Ca&Mg (PAsp-Ca&Mg) complexes followed by phosphate solution via strong electrostatic attraction. Meanwhile, citrate adsorbed in/on fibrils can eliminate mineralization inhibitory effects of magnesium ions by breaking hydration layer surrounding magnesium ions and thus reduce dehydration energy barrier for rapid fulfillment of biomimetic mineralization. The remineralized demineralized dentin with magnesium-doped HAp possesses antibacterial ability, and the mineralization mediums possess excellent biocompatibility via cytotoxicity and oral mucosa irritation tests. This strategy shall shed light on cationic ions-doped biomimetic mineralization with antibacterial ability via modifying collagen fibrils and eliminating mineralization inhibitory effects of some cationic ions, as well as can excite attention to the neglected multiple regulations of small biomolecules, such as citrate, during biomineralization process.

Ectopic Expression of TIGIT in Lung Adenocarcinoma and Its Clinical Significance.

This study aimed to investigate the T cell immunoreceptor with ITIM and Ig domains (TIGIT) expression in lung adenocarcinoma (LUAD). TIGIT expression was measured by western blot, reverse transcription quantitative polymerase chain reaction. Seventy-two paired surgical specimens were collected from patients with stage I-IV LUAD. The expression of TIGIT in surgical specimens was determined using immunohistochemistry. TIGIT was overexpressed in LUAD tissues. Moreover, overexpressed TIGIT was significantly associated with advanced clinical staging, lymph node metastasis, distant metastasis, and TP53 mutations in LUAD. Moreover, high expression of TIGIT was negatively correlated with purity of CD4+ T cells. High rations of TIGIT+CD4+ T cells predicted poor overall survival of LUAD patients. Additionally, high ratios of TIGIT+CD4+ T cells is closely related to CD4+ T cell depletion. Taken together, TIGIT was overexpressed in LUAD patients. High levels of TIGIT induced the alteration of CD4+ T cell based immunomodulation and predicted poor prognosis of LUAD patients. Therefore, TIGIT can be potential biomarker for LUAD.

Rational Design of a Potent Antimicrobial Peptide Based on the Active Region of a Gecko Cathelicidin.

The emergence of multidrug-resistant (MDR) bacteria presents a significant challenge to public health, increasing the risk of infections that are resistant to current antibiotic treatment. Antimicrobial peptides (AMPs) offer a promising alternative to conventional antibiotics in the prevention of MDR bacterial infections. In the present study, we identified a novel cathelicidin AMP from Gekko japonicus, which exhibited broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with minimal inhibitory concentrations ranging from 2.34 to 4.69 µg/mL. To improve its potential therapeutic application, a series of peptides was synthesized based on the active region of the gecko-derived cathelicidin. The lead peptide (RH-16) showed an antimicrobial activity comparable to that of the parent peptide. Structural characterization revealed that RH-16 adopted an amphipathic α-helical conformation. Furthermore, RH-16 demonstrated neither hemolytic nor cytotoxic activity but effectively killed a wide range of clinically isolated, drug-resistant bacteria. The antimicrobial activity of RH-16 was attributed to the nonspecific targeting of bacterial membranes, leading to rapid bacterial membrane permeabilization and rupture. RH-16 also retained its antibacterial activity in plasma and exhibited mild toxicity in vivo. Notably, RH-16 offered robust protection against skin infection in a murine model. Therefore, this newly identified cathelicidin AMP may be a strong candidate for future pharmacological development targeting multidrug resistance. The use of a rational design approach for isolating the minimal antimicrobial unit may accelerate the transition of natural AMPs to clinically applicable antibacterial agents.

A high concentrate diet inhibits forkhead box protein A2 expression, and induces oxidative stress, mitochondrial dysfunction and mitochondrial unfolded protein response in the liver of dairy cows.

High-concentrate diet induce subacute ruminal acidosis (SARA) and cause liver damage in ruminants. It has been reported that forkhead box protein A2 (FOXA2) can enhance mitochondrial membrane potential but its function in mitochondrial dysfunction induced by high concentrate diets is still unknown. Therefore, the aim of this study was to elucidate the effect of high-concentrate (HC) diet on hepatic FOXA2 expression, mitochondrial unfolded protein response (UPRmt), mitochondrial dysfunction and oxidative stress. A total of 12 healthy mid-lactation Holstein cows were selected and randomized into 2 groups: the low concentrate (LC) diet group (concentrate:forage = 4:6) and HC diet group (concentrate:forage = 6:4). The trial lasted 21 d. The rumen fluid, blood and liver tissue were collected at the end of the experiment. The results showed that the rumen fluid pH level was reduced in the HC group and the pH was lower than 5.6 for more than 4 h/d, indicating that feeding HC diets successfully induced SARA in dairy cows. Both FOXA2 mRNA and protein abundance were significantly reduced in the liver of the HC group compared with the LC group. The activity of antioxidant enzymes (CAT, G6PDH, T-SOD, Cu/Zn SOD, Mn SOD) and mtDNA copy number in the liver tissue of the HC group decreased, while the level of H2O2 significantly increased, this increase was accompanied by a decrease in oxidative phosphorylation (OXPHOS). The balance of mitochondrial division and fusion was disrupted in the HC group, as evidenced by the decreased mRNA level of OPA1, MFN1, and MFN2 and increased mRNA level of Drp1, Fis1, and MFF. At the same time, HC diet downregulated the expression level of SIRT1, SIRT3, PGC-1α, TFAM, and Nrf 1 to inhibit mitochondrial biogenesis. The HC group induced UPRmt in liver tissue by upregulating the mRNA and protein levels of CLPP, LONP1, CHOP, Hsp10, and Hsp60. In addition, HC diet could increase the protein abundance of Bax, CytoC, Caspase 3 and Cleaved-Caspase 3, while decrease the protein abundance of Bcl-2 and the Bcl-2/Bax ratio. Overall, our study suggests that the decreased expression of FOXA2 may be related to UPRmt, mitochondrial dysfunction, oxidative stress, and apoptosis in the liver of dairy cows fed a high concentrate diet.

Iterative learning control for differential inclusion systems with random fading channels by varying average technique.

The aim of this paper is to study iterative learning control for differential inclusion systems with random fading channels between the plant and the controller. In reality, the phenomenon of fading will inevitably occur in network transmission, which will greatly affect the tracking ability of output trajectory. This study discusses the impact of fading channel on tracking performance at the input and output sides, respectively. First, a set-valued mapping in a differential inclusion system with uncertainty is converted into a single-valued mapping by means of a Steiner-type selector. Then, to offset the effect of the fading channel and improve the tracking ability, a variable local average operator is constructed. The convergence of the learning control algorithm designed by the average operator is proved. The results show that the parameters in the varying local average operator can be adjusted to trade-off between the learning rate and the fading offset rate. Finally, the theoretical results are verified by numerical simulation of the switched reluctance motors.

Distributed Learning Control for High-Speed Trains Subject to Operation Safety Constraints.

Trajectory tracking problems related to high-speed trains (HSTs) are fundamental issues that affect the operation safety and ride comfort. This study proposes a distributed learning control scheme based on a multiagent system framework for trajectory tracking of HSTs subject to operation safety constraints. Two different connection modes are considered between the carriages: 1) a soft connection achieved via information exchange and 2) a hard connection enforced via couplers. Both relative displacement and speed constraints are carefully analyzed in the tracking control process. By constructing an appropriate barrier composite energy function, the convergence of the tracking error and satisfaction of the operation safety constraints are rigorously proven for the proposed scheme. The theoretical results are verified using numerical simulations.

The E3 ubiquitin ligase RNF135 modulates chemotherapy resistance to oxaliplatin for colorectal cancer by modulating autophagy.

BACKGROUND: RING finger protein 135 plays an important role in tumorigenesis and is associated with drug resistance. METHODS: Bioinformatics analysis showed that RNF135 was significantly differentially expressed in colorectal cancer. RT-qPCR and western blot were used to detect the expression of RNF135. Immunohistochemical analysis were used to measure the expression of RNF135 and Ki-67. RESULTS: The expression of RNF135 was up-regulated in human tissue samples and colorectal cancer and was positively correlated with Ki-67. Compared with oxaliplatin sensitive patients, RNF135 expression levels were higher in the tissue of resistant patients. The regulatory effect of RNF135 on colorectal cancer cells was further investigated in vitro. Therefore, inhibition of autophagy by down-regulating RNF135 can partially increase its susceptibility to oxaliplatin.

Quantized iterative learning control for impulsive differential inclusion systems with data dropouts.

This paper studies the quantized iterative learning control with encoding-decoding mechanism of a class of impulsive differential inclusion systems with random data dropouts. First, the set-valued mappings in the differential inclusion systems are transformed into single-valued mappings by using the Steiner-type selector. Then, a learning algorithm based on the intermittent update principle is designed to address the data asynchronism problem caused by two-sided data dropouts. If the data are successfully transmitted at the actuator and measurement sides, then the control input is effectively updated. Furthermore, a suitable scaling sequence is introduced to ensure the system output to achieve zero-error tracking performance for a desired trajectory. An upper bound of the quantization level is determined such that the quantization error is always bounded. The results show that the quantization method reduces the burden of network communication at the cost of increasing the amount of computation, and the learning algorithm does not require the data dropouts to satisfy a certain probability distribution. Finally, the effectiveness of the learning algorithm is verified by numerical simulations of the switched reluctance motor system.

Association between regular proton pump inhibitors use and cardiovascular outcomes: A large prospective cohort study.

BACKGROUND: Proton pump inhibitors (PPIs) are widely prescribed for gastroesophageal reflux disease and peptic ulcer disease. However, the association between the regular PPIs use and the risk of cardiovascular disease (CVD) outcomes remains unclear. We aimed to determine whether regular proton pump inhibitors (PPIs) use is associated with an altered incidence of cardiovascular disease (CVD) in the general population. METHODS: This prospective cohort study included 459,207 participants (mean [SD] age, 56.2 [8.1] years) from the UK Biobank study without prevalent CVD who enrolled between 2006 and 2010 and were followed until 2018. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD and its components (coronary heart disease [CHD], stroke, heart failure, atrial fibrillation, and venous thromboembolism) were obtained using Cox proportional hazards models with adjustment for potential confounding factors, including demographic factors, lifestyle behaviors, prevalent comorbidities, and clinical indicators for PPIs use. RESULTS: During the follow-up period, we recorded 26,346 incident CVD events (including 13,749 CHD events, 4144 stroke events, 5812 atrial fibrillation events, 1159 heart failure events, and 4206 venous thromboembolism events). The fully adjusted HRs (and 95% CIs) associated with PPIs users compared to nonusers were 1.44 (95% CI 1.39-1.50) for incident CVD, 1.65 (95% CI 1.57-1.74) for CHD, 1.21 (95% CI 1.09-1.33) for stroke, 1.17 (95% CI 1.08-1.28) for atrial fibrillation, 1.61 (95% CI 1.37-1.89) for heart failure, and 1.36 (95% CI 1.24-1.50) for venous thromboembolism. CONCLUSIONS: Regular PPIs use was associated with higher risk of CVD outcomes. Clinicians should therefore exercise caution when prescribing PPIs.

Endoscopic therapy versus esophagectomy for T1bN0M0 esophageal cancer: A population-based study using propensity score matching.

Background: Endoscopic therapy is an optional strategy for the treatment of esophageal cancer (EC) under an early stage, especially stage T1a. However, its efficacy in the treatment of T1b EC has not been thoroughly assessed. We investigated the efficacy of esophagectomy, endoscopic therapy, as well as chemoradiotherapy in patients with T1bN0M0 EC. Methods: The Surveillance, Epidemiology, and End Results database (SEER) was employed to identify patients diagnosed with T1bN0M0 EC. Patient demographics were compared among the endoscopic therapy, esophagectomy, and chemoradiotherapy groups. Our study employed Kaplan-Meier analysis and Cox regression model to evaluate patient outcomes and long-term survival rates. The overall survival (OS) and cancer-specific survival (CSS) rates were compared among patients with EC who underwent endoscopic therapy or esophagectomy, employing propensity score matching (PSM). Results: A total of 820 patients diagnosed with T1bN0M0 EC were identified. The number of patients who received endoscopic therapy, esophagectomy, and chemoradiotherapy was 173, 556, and 91, respectively. Patients subjected to endoscopic therapy and esophagectomy had greatly longer OS and CSS than those who underwent chemoradiotherapy. Patients treated with esophagectomy had longer OS than endoscopic therapy patients, but there were no differences in CSS between the two groups. PSM generated 153 patient pairs among T1bN0M0 patients, demonstrating that both the esophagectomy and endoscopic therapy groups exhibited comparable OS and CSS rates. Conclusion: Endoscopic therapy and esophagectomy were associated with a significant survival advantage compared with chemoradiotherapy in patients with T1bN0M0 EC. In contrast, after PSM, among the EC patients with stage T1bN0M0, OS and CSS did not differ after endoscopic therapy or esophagectomy. These results indicate that endoscopic therapy could be a viable alternative to esophagectomy in patients diagnosed with T1bN0M0 EC.

DPY30 promotes colorectal carcinoma metastasis by upregulating ZEB1 transcriptional expression.

DPY30 belongs to the core subunit of components of the histone lysine methyltransferase complex, which is implicated in tumorigenesis, cell senescence, and other biological events. However, its contribution to colorectal carcinoma (CRC) progression and metastasis has yet to be elucidated. Therefore, this study aimed to investigate the biological function of DPY30 in CRC metastasis both in vitro and in vivo. Herein, our results revealed that DPY30 overexpression is significantly positively correlated with positive lymph nodes, epithelial-mesenchymal transition (EMT), and CRC metastasis. Moreover, DPY30 knockdown in HT29 and SW480 cells markedly decreased EMT progression, as well as the migratory and invasive abilities of CRC cells in vitro and lung tumor metastasis in vivo. Mechanistically, DPY30 increased histone H3K4me3 level and promoted EMT and CRC metastasis by upregulating the transcriptional expression of ZEB1. Taken together, our findings indicate that DPY30 may serve as a therapeutic target and prognostic marker for CRC.

Discrimination of benign and malignant breast lesions on dynamic contrast-enhanced magnetic resonance imaging using deep learning.

PURPOSE: To evaluate the capability of deep transfer learning (DTL) and fine-tuning methods in differentiating malignant from benign lesions in breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: The diagnostic efficiencies of the VGG19, ResNet50, and DenseNet201 models were tested under the same dataset. The model with the highest performance was selected and modified utilizing three fine-tuning strategies (S1-3). Fifty additional lesions were selected to form the validation set to verify the generalization abilities of these models. The accuracy (Ac) of the different models in the training and test sets, as well as the precision (Pr), recall rate (Rc), F1 score (), and area under the receiver operating characteristic curve (AUC), were primary performance indicators. Finally, the kappa test was used to compare the degree of agreement between the DTL models and pathological diagnosis in differentiating malignant from benign breast lesions. RESULTS: The Pr, Rc, f1, and AUC of VGG19 (86.0%, 0.81, 0.81, and 0.81, respectively) were higher than those of DenseNet201 (70.0%, 0.61, 0.63, and 0.61, respectively) and ResNet50 (61.0%, 0.59, 0.59, and 0.59). After fine-tuning, the Pr, Rc, f1, and AUC of S1 (87.0%, 0.86, 0.86, and 0.86, respectively) were higher than those of VGG19. Notably, the degree of agreement between S1 and pathological diagnosis in differentiating malignant from benign breast lesions was 0.720 (κ = 0.720), which was higher than that of DenseNet201 (κ = 0.440), VGG19 (κ = 0.640), and ResNet50 (κ = 0.280). CONCLUSION: The VGG19 model is an effective method for identifying benign and malignant breast lesions on DCE-MRI, and its performance can be further improved via fine-tuning. Overall, our findings insinuate that this technique holds potential clinical application value.