A novel multilevel iterative training strategy for the ResNet50 based mitotic cell classifier.

The number of mitotic cells is an important indicator of grading invasive breast cancer. It is very challenging for pathologists to identify and count mitotic cells in pathological sections with naked eyes under the microscope. Therefore, many computational models for the automatic identification of mitotic cells based on machine learning, especially deep learning, have been proposed. However, converging to the local optimal solution is one of the main problems in model training. In this paper, we proposed a novel multilevel iterative training strategy to address the problem. To evaluate the proposed training strategy, we constructed the mitotic cell classification model with ResNet50 and trained the model with different training strategies. The results showed that the models trained with the proposed training strategy performed better than those trained with the conventional strategy in the independent test set, illustrating the effectiveness of the new training strategy. Furthermore, after training with our proposed strategy, the ResNet50 model with Adam optimizer has achieved 89.26% F1 score on the public MITOSI14 dataset, which is higher than that of the state-of-the-art methods reported in the literature.

A critical review of the bioactive ingredients and biological functions of camellia oleifera oil.

Camellia oleifera oil is a pure and natural high-grade oil prevalent in South China. Camellia oleifera oil is known for its richness in unsaturated fatty acids and high nutritional value. There is increasing evidence indicating that a diet rich in unsaturated fatty acids is beneficial to health. Despite the widespread production of Camellia oleifera oil and its bioactive components, reports on its nutritional components are scarce, especially regarding systematic reviews of extraction methods and biological functions. This review systematically summarized the latest research on the bioactive components and biological functions of Camellia oleifera oil reported over the past decade. In addition to unsaturated fatty acids, Camellia oleifera oil contains six main functional components contributing to its antioxidant, antibacterial, anti-inflammatory, antidiabetic, anticancer, neuroprotective, and cardiovascular protective properties. These functional components are vitamin E, saponins, polyphenols, sterols, squalene, and flavonoids. This paper reviewed the biological activity of Camellia oleifera oil and its extraction methods, laying a foundation for further development of its bioactive components.

Carbon flow, energy metabolic intensity and metagenomic characteristics of a Fe (III)-enhanced anerobic digestion system during treating swine wastewater.

Deep treatment and bioenergy recovery of swine wastewater (SW) are beneficial for constructing a low-carbon footprint and resource-recycling society. In this study, Fe (III) addition from 0 to 600 mg/L significantly increased the methane (CH4) content of the recovered biogas from 61.4 ± 2.0 to 89.3 ± 2.0 % during SW treatment in an anaerobic membrane digestion system. The specific methane yields (SMY) also increased significantly from 0.20 ± 0.05 to 0.29 ± 0.02 L/g COD. Fe (III) and its bio-transformed products which participated in establishing direct interspecific electron transfer (DIET), upregulated the abundance of e-pili and Nicotinamide adenine dinucleotide (NADH), enriched electroactive bacteria. The increase in cellular adenosine triphosphate (cATP) from 6583 to 14,518 ng/gVSS and electron transport system (ETS) from 1468 to 1968 mg/(g·h) promoted the intensity of energy flow and electron flow during anaerobic digestion of SW. Moreover, Fe (III) promoted the hydrolysis and acidification of organic matters, and strengthened the acetoacetic methanogenesis pathway. This study established an approach for harvesting high quality bioenergy from SW and revealed the effects and mechanisms from the view of carbon flow, energy metabolic intensity and metagenomics.

Helicobacter pylori and Gastrointestinal Cancers: Recent Advances and Controversies.

Helicobacter pylori (H pylori), a gastric bacterium, has been extensively studied for its association with gastritis, peptic ulcers, and gastric cancer. However, recent evidence suggests its potential implications beyond the stomach, linking it to other gastrointestinal malignancies, such as esophageal cancer, liver cancer, pancreatic cancer, gallbladder cancer, and colorectal cancer. In light of the expanding research landscape and the increasing interest in exploring H pylori broader role in gastrointestinal tumorigenesis, this comprehensive review aims to elucidate the relationship between H pylori and gastrointestinal tumors. This review encompasses recent epidemiological studies, research progress, and emerging perspectives, providing a comprehensive assessment of the relationship between H pylori and gastrointestinal tumors. The findings highlight the captivating world of H pylori and its intricate involvement in gastrointestinal malignancies.

High expression circRALGPS2 in atretic follicle induces chicken granulosa cell apoptosis and autophagy via encoding a new protein.

BACKGROUND: The reproductive performance of chickens mainly depends on the development of follicles. Abnormal follicle development can lead to decreased reproductive performance and even ovarian disease among chickens. Chicken is the only non-human animal with a high incidence of spontaneous ovarian cancer. In recent years, the involvement of circRNAs in follicle development and atresia regulation has been confirmed. RESULTS: In the present study, we used healthy and atretic chicken follicles for circRNA RNC-seq. The results showed differential expression of circRALGPS2. It was then confirmed that circRALGPS2 can translate into a protein, named circRALGPS2-212aa, which has IRES activity. Next, we found that circRALGPS2-212aa promotes apoptosis and autophagy in chicken granulosa cells by forming a complex with PARP1 and HMGB1. CONCLUSIONS: Our results revealed that circRALGPS2 can regulate chicken granulosa cell apoptosis and autophagy through the circRALGPS2-212aa/PARP1/HMGB1 axis.

Morusin Alleviates Aortic Valve Calcification by Inhibiting Valve Interstitial Cell Senescence Through Ccnd1/Trim25/Nrf2 Axis.

The senescence of aortic valve interstitial cells (VICs) plays a critical role in the progression of calcific aortic valve disease (CAVD). However, the precise mechanisms underlying the senescence of VICs remain unclear, demanding the identification of a novel target to mitigate this process. Previous studies have highlighted the anti-aging potential of morusin. Thus, this study aimed to explore the therapeutic potential of morusin in CAVD. Cellular experiments reveal that morusin effectively suppresses cellular senescence and cause a shift toward osteogenic differentiation of VICs in vitro. Mechanistically, morusin activate the Nrf2-mediated antiaging signaling pathway by downregulating CCND1 expression and aiding Keap1 degradation through Trim 25. This activation lead to the upregulated expression of antioxidant genes, thus reducing reactive oxygen species production and thereby preventing VIC osteogenic differentiation. In vivo experiments in ApoE-/- mice on a high-fat Western diet demonstrate the positive effect of morusin in mitigating aortic valve calcification. These findings emphasize the antiaging properties of morusin and its potential as a therapeutic agent for CAVD.

Insights into Zwitterionic Surfactant Interactions at the Oil-Water Interface by Interferometry Experiments and MDS Calculations.

In this work, the interaction performance of zwitterionic surfactant [dodecyl dimethyl sulfopropyl betaine (DSB-12) and hexadecyl dimethyl sulfopropyl betaine (DSB-16)] at the n-octadecane oil surface is investigated from experimental and simulation insights. For a macroscopic experiment, interfacial interferometry technology was developed for real-time monitor interaction performances and to obtain the quantitative interfacial thickness and mass results. The Langmuir model was characterized by thermodynamic analysis, deducing the aggregation spontaneity of DSB-16 > DSB-12 with ΔGagg(DSB-16) = -5.94 kJ mol-1 < ΔGagg(DSB-12) = 24.08 kJ mol-1. A three-step dynamic model (adsorption, arrangement, and aggregation) was characterized by kinetic analysis, indicating arrangement process as slow-limiting step with k2(arr) < k1(ads), k3(agg). For microscopic simulation, and molecular dynamic (MD) method was utilized to theoretically investigate interaction performances and obtain the interfacial configuration and energy results. The interaction stability and interaction strength were indicated to be DSB-16 > DSB-12 with differences of final energy ΔEfin = 48-88 kcal mol-1. The interaction mechanism was explained by proposing the model of "response enhancement" and "deposition activity" for DSB-16 interactions, and "response decrease" and "elution activity" for DSB-12 interactions. The different performances can be attributed to the different interaction forms and forces of surfactants. This work provided a platform for performance and mechanism investigation between the surfactant molecule and oil surface, which is of great significance in reservoir exploitation and enhanced oil recovery (EOR).

NR4A1 depletion inhibits colorectal cancer progression by promoting necroptosis via the RIG-I-like receptor pathway.

Necroptosis is a regulated necrotic cell death mechanism and plays a crucial role in the progression of cancers. However, the potential role and mechanism of necroptosis in colorectal cancer (CRC) has not been fully elucidated. In this study, we found that nuclear receptor subfamily 4 group A member 1 (NR4A1) was highly expressed in CRC cells treated with TNF-α, Smac mimetic, and z-VAD-FMK (TSZ). The depletion of NR4A1 significantly enhanced the sensitivity of CRC cells to TSZ-induced necroptosis, while NR4A1 overexpression suppressed these effects, as evidenced by the LDH assay, flow cytometry analysis of cell death, PI staining, and expression analysis of necrosome complexes (RIPK1, RIPK3, and MLKL). Moreover, NR4A1 deficiency made HT29 xenograft tumors sensitive to necroptotic cell death in vivo. Mechanistically, NR4A1 depletion promoted necroptosis activation in CRC through the RIG-I-like receptor pathway by interacting with DDX3. Importantly, the RIG-I pathway agonist poly(I:C) or inhibitor cFP abolished the effects of NR4A1 overexpression or suppression on necroptosis in CRC cells. Moreover, we observed that NR4A1 was highly expressed in CRC tissues and was associated with a poor prognosis. In conclusion, our results suggest that NR4A1 plays a critical role in modulating necroptosis in CRC cells and provide a new therapeutic target for CRC.

CRDet: A circle representation detector for lung granulomas based on multi-scale attention features with center point calibration.

Lung granuloma is a very common lung disease, and its specific diagnosis is important for determining the exact cause of the disease as well as the prognosis of the patient. And, an effective lung granuloma detection model based on computer-aided diagnostics (CAD) can help pathologists to localize granulomas, thereby improving the efficiency of the specific diagnosis. However, for lung granuloma detection models based on CAD, the significant size differences between granulomas and how to better utilize the morphological features of granulomas are both critical challenges to be addressed. In this paper, we propose an automatic method CRDet to localize granulomas in histopathological images and deal with these challenges. We first introduce the multi-scale feature extraction network with self-attention to extract features at different scales at the same time. Then, the features will be converted to circle representations of granulomas by circle representation detection heads to achieve the alignment of features and ground truth. In this way, we can also more effectively use the circular morphological features of granulomas. Finally, we propose a center point calibration method at the inference stage to further optimize the circle representation. For model evaluation, we built a lung granuloma circle representation dataset named LGCR, including 288 images from 50 subjects. Our method yielded 0.316 mAP and 0.571 mAR, outperforming the state-of-the-art object detection methods on our proposed LGCR.

Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia.

Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3+ T-cells to engage and lyse CD19+ target cells. Here we demonstrate that subcutaneous (SC) blinatumomab can provide high efficacy and greater convenience of administration. In the expansion phase of a multi-institutional phase 1b trial (ClinicalTrials.gov, NCT04521231), heavily pretreated adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) received SC blinatumomab at two doses: (1) 250 µg once daily (QD) for week 1 and 500 µg three times weekly (TIW) thereafter (250 µg/500 µg) or (2) 500 µg QD for week 1 and 1000 µg TIW thereafter (500 µg/1000 µg). The primary endpoint was complete remission/complete remission with partial hematologic recovery (CR/CRh) within two cycles. At the data cutoff of September 15, 2023, 29 patients were treated: 14 at the 250 µg/500 µg dose and 13 at 500 µg/1000 µg dose. Data from two ineligible patients were excluded. At the end of two cycles, 12 of 14 patients (85.7%) from the 250 µg/500 µg dose achieved CR/CRh of which nine patients (75.0%) were negative for measurable residual disease (MRD; <10-4 leukemic blasts). At the 500 µg/1000 µg dose, 12 of 13 patients (92.3%) achieved CR/CRh; all 12 patients (100.0%) were MRD-negative. No treatment-related grade 4 cytokine release syndrome (CRS) or neurologic events (NEs) were reported. SC injections were well tolerated and all treatment-related grade 3 CRS and NEs responded to standard-of-care management, interruption, or discontinuation. Treatment with SC blinatumomab resulted in high efficacy, with high MRD-negativity rates and acceptable safety profile in heavily pretreated adults with R/R B-ALL.

Calculation of Charge Transport Phenomena and Mobility Analysis in the Insulating Oil Using First Principle and Marcus Theory.

Oil-paper insulation is widely used as a reliable composite insulation system in power transformers. The dielectric property of oil insulation plays an important role in the reliable operation of power equipment. To recognize the charge transfer process in composite insulation, the mobility of the charge in aged insulating oil is studied. However, few studies have been conducted on the microscopic mechanism of charge transport phenomena at the molecular level. In this research, we have studied the molecular electronic structure and the distribution of holes and electrons in the insulating oil by first-principles calculation. By combining with Marcus theory, the corresponding electron coupling energy, reorganization energy, and free energy are obtained. The corresponding charge hopping model is chosen by the parameter relation, and the hopping rate is calculated. At last, the mobility of holes and electrons in insulating oil within the insulation is simulated by the Monte Carlo method. Other possible charge migration methods are also studied and discussed for the comparison. It is observed that the transfer integral of electrons is 2 orders of magnitude larger than that of holes, which is mostly due to the localization of lowest unoccupied molecular orbitals (LUMO). The hole and charge transfers accord with Marcus hopping, the adiabatic charge transfer model, and the charge hopping rate is obtained. The actual free energy action under an external electric field is obtained by calculating polarizability and permittivity. Monte Carlo simulation is used to obtain the charge transfer image and mobility under an actual electric field. Possible types of traps and mobility of ions and clusters in the insulating oil are also studied.

Recent Progress in Photoelectrochemical Sensing of Pesticides in Food and Environmental Samples: Photoactive Materials and Signaling Mechanisms.

Pesticides have become an integral part of modern agricultural practices, but their widespread use poses a significant threat to human health. As such, there is a pressing need to develop effective methods for detecting pesticides in food and environmental samples. Traditional chromatography methods and common rapid detection methods cannot satisfy accuracy, portability, long storage time, and solution stability at the same time. In recent years, photoelectrochemical (PEC) sensing technology has gained attention as a promising approach for detecting various pesticides due to its salient advantages, including high sensitivity, low cost, simple operation, fast response, and easy miniaturization, thus becoming a competitive candidate for real-time and on-site monitoring of pesticide levels. This review provides an overview of the recent advancements in PEC methods for pesticide detection and their applications in ensuring food and environmental safety, with a focus on the categories of photoactive materials, from single semiconductor to semiconductor-semiconductor heterojunction, and signaling mechanisms of PEC sensing platforms, including oxidation of pesticides, steric hindrance, generation/decrease in sacrificial agents, and introduction/release of photoactive materials. Additionally, this review will offer insights into future prospects and confrontations, thereby contributing novel perspectives to this evolving domain.

Comparison of the EPDS and PHQ-9 in the assessment of depression among pregnant women: Similarities and differences.

BACKGROUND: Perinatal depression has attracted increasing attention. However, a detailed investigation of the network structure of depression is still lacking. We aim to examine the similarities and differences between the Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire (PHQ-9) from a network perspective. METHODS: A cross-sectional study was conducted from August 2020 to March 2022. We followed the STROBE checklist to report our research. Pregnant women (n = 2484) were recruited. All participants completed the EPDS and PHQ-9. We mainly used network analyses for statistical analysis and constructed two network models: the EPDS and PHQ-9 models. RESULTS: The detection rates of prenatal depression measured by the EPDS and PHQ-9 were 30.2 % and 28.2 %, respectively. In the EPDS network, the EPDS8 'sad or miserable' node (strength = 1.2161) was the most central node, and the EPDS10 'self-harming' node (strength = 0.4360) was the least central node. In the PHQ-9 network, the PHQ4 'fatigue' node (strength = 0.9815) was the most central node, and PHQ9 'suicide' was the least central symptom (strength = 0.5667). For both models, 'sad' acted as an important central symptom. CONCLUSIONS: Psychological symptoms may be more important in assessing depression using the EPDS, while physical symptoms may be more influential in assessing depression using the PHQ-9. For both the EPDS and PHQ-9, "sad" was an important central symptom, suggesting that it may be the most important target for further maternal depression interventions in the future.

HOOK3 suppresses proliferation and metastasis in gastric cancer via the SP1/VEGFA axis.

HOOK3, a member of the human hook microtubule-tethering protein family, has been implicated in the progression of cancer. However, the role of HOOK3 in the pathogenesis of gastric cancer (GC) remains incompletely understood. In this study, we investigated the expression of HOOK3 protein in GC tissues using immunohistochemistry (IHC). The findings of our study indicate that the expression levels of HOOK3 in GC tissues were relatively low. Furthermore, a significant negative association was seen between HOOK3 expression and the prognosis of patients with GC. The suppression of HOOK3 resulted in a notable increase in the proliferation, migration, invasion, and survival of GC cells. Conversely, the overexpression of HOOK3 had the opposite impact, reducing these cellular processes. Moreover, in vivo tests have shown evidence that the overexpression of HOOK3 significantly inhibited the formation of tumors and the spread of GC cells to the lungs. In a mechanistic manner, the analysis of RNA-seq data demonstrated that the knockdown of HOOK3 resulted in a notable increase in the expression of vascular endothelial growth factor A (VEGFA) in GC cells. Furthermore, the upregulation of VEGFA counteracted the impacts of HOOK3 upregulation on the proliferation, migration, invasion, and survival of GC cells. Furthermore, it was revealed that specificity protein 1 (SP1) exhibited the ability to bind to the promoter region of VEGFA. Moreover, the overexpression of SP1 successfully counteracted the inhibitory impact of HOOK3 overexpression on the expression of VEGFA in GC cells. In summary, the results of our study indicate that HOOK3 has a role in inhibiting the growth, migration, invasion, and survival of GC cells by modulating the SP1/VEGFA pathway. These findings contribute significant knowledge to our understanding of the underlying mechanisms involved in the development of GC.

A defined serum-free culture system for human long-term haematopoietic stem cells.

Long-term repopulating haematopoietic stem cells (LT-HSCs) have the ability to reconstitute the entire haematopoietic system following transplantation permanently. Despite great achievements in HSC transplantation, the limited transplantable HSC number, especially LT-HSCs, remains critical for successful transplantation and broader applications. In this study, we established a defined serum-free culture system for in vitro expansion of LT-HSCs. This culture system (E1) expanded LT-HSCs from umbilical cord blood, human mobilization peripheral blood and bone marrow. These E1-expanded HSCs reconstituted the haematopoietic and immune systems in primary and secondary transplanted mice in a short time. Better haematopoietic reconstitution was observed in secondary xenografted mice. Moreover, we obtained the comprehensive expression profile and cellular components of LT-HSCs from umbilical cord blood. Our study provides a valuable tool for LT-HSC research and may improve clinical applications of HSCs.

Donor/recipient ascending aortic diameter ratio as a novel potential metric for donor selection and improved clinical outcomes in heart transplantation: a propensity score-matched study.

Background: Donor/recipient size matching is paramount in heart transplantation. Body weight, height, body mass index, body surface area, and predicted heart mass (PHM) ratios are generally used in size matching. Precise size matching is important to achieve better clinical outcomes. This study aims to determine the donor/recipient ascending aortic diameter (AAoD) ratio as a metric for donor selection and its effect on postoperative clinical outcomes in heart transplant patients. Methods: We retrospectively reviewed all consecutive patients who underwent heart transplantation from January 2015 to December 2018. A cutoff value of 0.8032 for the donor/recipient AAoD ratio (independent variable for the primary endpoint during unmatched cohort analysis) was determined for predicting in-hospital mortality. The patients were divided into two groups based on the cutoff value. Group A, AAoD < 0.8032 (n = 96), and Group B, AAoD > 0.8032 (n = 265). A propensity score-matched (PSM) study was performed to equalize the two groups comprising 77 patients each in terms of risk. A Cox regression model was developed to identify the independent preoperative variables affecting the primary end-point. The primary endpoint was all-cause in-hospital mortality. Results: A total of 361 patients underwent heart transplantation during the given period. On the multivariate analysis, donor/recipient PHM ratio [HR 16.907, 95% confidence interval (CI) 1.535-186.246, P = 0.021], donor/recipient AAoD ratio < 0.8032 (HR 5.398, 95% CI 1.181-24.681, P = 0.030), and diabetes (HR 3.138, 95% CI 1.017-9.689, P = 0.047) were found to be independent predictors of in-hospital mortality. Group A had higher 3-year mortality than Group B (P = 0.022). The surgery time was longer and postoperative RBC, plasma, and platelets transfusion were higher in Group A (P < 0.05). Although not statistically significant the use of continuous renal replacement therapy (P = 0.054), and extracorporeal membrane oxygenation (P = 0.086), was realatively higher, and ventilation time (P = 0.079) was relatively longer in Group A. Conclusions: The donor/recipient AAoD ratio is a potential metric for patient matching and postoperative outcomes in heart transplantation. A donor/recipient AAoD ratio > 0.8032 could improve post-heart transplantation outcomes and donor heart utilization.

BushenHuoxue formula promotes osteogenic differentiation via affecting Hedgehog signaling pathway in bone marrow stem cells to improve osteoporosis symptoms.

BACKGROUND: The BushenHuoxue formula (BSHX) has been previously demonstrated to ameliorate osteoporosis, but the mechanisms underlying this phenomenon are currently unclear. The present study aims at investigating the mechanisms that BSHX induces osteogenesis. METHODS: We established an osteoporosis model in rats by bilateral ovariectomy and then treated the rats with an osteogenic inducer (dexamethasone, ß-sodium glycerophosphate and Vitamin C) and BSHX. After that, bone marrow density and histopathological bone examination were evaluated by using HE staining and immunohistochemistry, respectively. We also assessed the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts by using immunofluorescence staining. ALP, BMP, and COL1A1 levels were determined by ELISA. We identified genes involved in pathogenesis of osteoporosis through Gene Expression Omnibus (GEO) database and subsequently selected Hedgehog signaling-related genes Shh, Ihh, Gli2, and Runx2 for assessment via qRT-PCR and ELISA, Western blotting. Network pharmacology analysis was performed to identify bioactive metabolites of BSHX. RESULTS: BSHX treatment in osteoporosis model rats promoted tightening of the morphological structure of the trabecular bone and increased the bone mineral density (BMD). BSHX also increased levels of osteoblast makers ALP, BMP, and COL1A1. Additionally, bioinformatics analysis of the GEO dataset showed that Hedgehog signaling pathway was involved in pathogenesis of osteoporosis, especially related genes Shh, Ihh, Gli2, and Runx2. Remarkably, BHSX upregulated these genes indispensably involved in the osteogenesis-related Hedgehog signaling pathway in both bone tissue and BMSCs. Importantly, we identified that quercetin was the active compounds that involved in the mechanism of BSHX-improved OP via affecting Hedgehog-related genes. CONCLUSION: Our results indicate that BSHX promotes osteogenesis by improving BMSC differentiation into osteoblasts via increased expression of Hedgehog signaling-related genes Shh, Ihh, Gli2, and Runx2, and quercetin was the bioactive compound of BSHX.

Probing and Modulation of the Electric Double Layer at the Insulating Oil-Paper Interface.

Charge accumulation in the insulating oil-paper system determines the operating safety of the converter transformers in high-voltage direct current (HVDC) transmissions. However, it has been a long-standing challenge to reveal the charge distribution of the electric double layer (EDL) at the insulating oil-paper interface and relate it to charge transport. In particular, the EDL and charging mechanisms at the oil-paper interface have not been fully understood. We herein demonstrate that the charge distribution of EDL at the oil-paper interface is probed through Kelvin probe force microscopy (KPFM). The origin charge distribution of EDL without any additives shows that the negative charge gathers on the insulating paper surface, while the positive charge diffuses in the insulating oil, which is derived from the electron affinity difference between insulating oil and insulating paper and acts as an additional obstacle to charge transportation at the oil-paper interface. Interestingly, the additive 3-amino-2,4-triazole (ATA) can tune the charge distribution of EDL by bringing extra hole traps, which significantly decreases the interface barrier and reduces the charge accumulation at the oil-paper interface. As well as increasing charge mobility in oil-paper insulation, ATA also ensures stabilization of operation under polarity inversion conditions by accelerating the dissipation rate of accumulated charge.

TRIM69 suppressed the anoikis resistance and metastasis of gastric cancer through ubiquitin‒proteasome-mediated degradation of PRKCD.

The tripartite motif (TRIM) protein family has been investigated in multiple human cancers, including gastric cancer (GC). However, the role of TRIM69 in the anoikis resistance and metastasis of GC cells remains to be elucidated. We identified the differentially expressed genes in anoikis-resistant GC cells using RNA-sequencing analysis. The interaction between TRIM69 and PRKCD was analyzed by coimmunoprecipitation and mass spectrometry. Our results have shown that TRIM69 was significantly downregulated in anoikis-resistant GC cells. TRIM69 overexpression markedly suppressed the anoikis resistance and metastasis of GC cells in vitro and in vivo. TRIM69 knockdown had the opposite effects. Mechanistically, TRIM69 interacted with PRKCD through its B-box domain and catalyzed the K48-linked polyubiquitination of PRKCD. Moreover, TRIM69 inhibited BDNF production in a PRKCD-dependent manner. Importantly, overexpression of PRKCD or BDNF blocked the effects of TRIM69 on the anoikis resistance and metastasis of GC cells. Interestingly, a TRIM69-PRKCD+BDNF+ cell subset was positively associated with metastasis in GC patients. TRIM69-mediated suppression of the anoikis resistance and metastasis of GC cells via modulation of the PRKCD/BDNF axis, with potential implications for novel therapeutic approaches for metastatic GC.