Yan Zhang’s research while affiliated with Nanyang Technological University and other places

This study aims to explore how different forms and cumulative experiences of childhood maltreatment (CM) relate to cognitive biases. A total of 121 participants diagnosed with major depressive disorder (MDD) and 120 healthy controls (HC) were recruited for this cross-sectional study. CM and cognitive biases were assessed, respectively, utilizing the Childhood Trauma Questionnaire and the Cognitive Bias Questionnaire. The latter evaluates two distinct dimensions of cognitive biases: depression and distortion, according to which cognitive characteristics were categorized into four combinations: depressed-distorted (D-D), depressed-nondistorted (D-ND), nondepressed-distorted (ND-D), and nondepressed-nondistorted (ND-ND). The Childhood Maltreatment Count (CMC) was defined as the cumulative count of distinct CM types. The findings indicate the association between CM and cognitive bias among the participants. In the MDD cohort, a significant association was observed between higher physical neglect scores and diminished ND-ND scores (β = –0.297, p = 0.012). In the HC group, no comparable relationship was identified. Furthermore, CMC was significantly correlated with decreased ND-ND scores both in the MDD group (β = −0.273, p = 0.006) and the HC group (β = −0.234, p = 0.010). This study underscores the significance of investigating the repercussions of physical neglect in MDD patients. Moreover, increased childhood trauma counts may function as a predisposing factor for more pronounced cognitive bias, with potential implications for clinical interventions and future research in diverse cultural contexts.

Background Chemotherapy resistance is a major challenge in the treatment of intermediate and advanced gastric cancer (GC). This study aimed to recognize oxaliplatin resistance-related genes (OXARGs) in GC and to explore their role and mechanism in oxaliplatin resistance of GC. Methods OXARGs with prognostic value in GC were analyzed using GC oxaliplatin resistance data from the GEO and TCGA databases. RT-qPCR and WB assay were applied to verify the expression of MT2A, NOTCH1 and SLC7A5 in oxaliplatin-resistant GC cells (HGC27R and MKN45R). The effect of SLC7A5 on the malignant phenotype of oxaliplatin-resistant GC cells was verified by CCK-8, EDU, TUNEL, colony formation, wound healing, transwell assay, tumor bearing experiments and WB assay. Results Bioinformatics analysis and experimental validation indicate that SLC7A5 was a target for oxaliplatin-resistance in GC. Knockdown of SLC7A5 obviously decreased the viability, migration, and invasion of oxaliplatin-resistant GC cells in vitro and tumor growth in vivo. It also increased the apoptosis levels and BAX expression, and reduced the expression of BCL2, MMP 2 and MMP9. Additionally, the knockdown of SLC7A5 enhanced the sensitivity of oxaliplatin-resistant GC cells to oxaliplatin both in vitro and in vivo. Furthermore, knockdown of SLC7A5 downregulated the expression of HK2, LDHA, Glut1, and PDK1 both in vivo and in vitro, leading to increased extracellular glucose levels and decreased lactate levels. However, glutathione significantly attenuated the regulatory effect of SLC7A5 knockdown on the malignant phenotype of oxaliplatin-resistant GC cells. Trial registration Not Applicable. Conclusion Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in GC by suppressing glycolysis.

Purpose To establish a population pharmacokinetic (PopPK) model of tacrolimus in the early stages after renal transplantation and evaluate the model’s predictive performance with external data. Methods Intravenous and oral tacrolimus were administered to 302 renal transplant recipients in the early posttransplantation stages. Related data were obtained from the electronic medical records. Single nucleotide polymorphisms in genes associated with tacrolimus pharmacokinetics were tested. The data were analyzed by NONMEM. The external data from 153 patients were subsequently used to evaluate model extrapolation. Results A one-compartment model was used to determine tacrolimus pharmacokinetics. The estimated clearance (CL), volume of distribution (V) and bioavailability (F) of tacrolimus were 4.91 L/h, 77 L and 26.5%, respectively. CL and V decreased with increasing hematocrit. CL and F decreased with increasing operation time. Diltiazem and Wuzhi capsule resulted in 28.4% and 43.9% decreases in the CL, respectively. Omeprazole or esomeprazole resulted in a 9% increase in F. The value of F for patients expressing CYP3A5 was 36.6% lower than that for the patients who did not express CYP3A5. The evaluation of external data revealed that the proportion of individual prediction error within 20% of the observed tacrolimus concentration was greater than 77.3%. Conclusions A PopPK model for tacrolimus was established for early renal transplantation. CYP3A5 was a significant covariate for F. Fat-free mass was the best predictor of the influence of body size on CL and V. The model could be extrapolated to stable renal transplant recipients.

The cabbage whitefly (A. proletella) (Hemiptera: Aleyrodidae) is a major agricultural pest that primarily targets cruciferous crops, such as cabbage, broccoli, and kale, causing extensive damage through feeding and honeydew. However, its associated virome has received limited research attention. In this study, we collected cabbage whiteflies in Xinjiang Agricultural University (43.80833 N, 87.56778 E, 882.3 m), systematically identified the RNA virome of the A. proletella and successfully identified three novel iflaviruses (Aleyrodes proletella iflavirus 1 (APIV1), Aleyrodes proletella iflavirus 2 (APIV2) and Aleyrodes proletella iflavirus 3 (APIV3)). APIV1–3 all have a 5′ structural protein region and a 3’ non-structural protein region. Phylogenetic and sequence identity analyses suggest that APIV1–3 are novel members of the family Iflaviridae. Structural modeling using AlphaFold3 revealed a conserved protein core region and a variable outer loop region. This study provides valuable insights into the virome diversity of A. proletella, establishing a foundation for future research on virus–host interactions and the potential for biocontrol applications in sustainable agriculture.

Purpose This study aimed to construct and validate a novel nomogram for prediction of lymph node metastasis in HER2-positive breast cancer based on the optimal number of examined lymph nodes (ELNs) for accurate nodal staging. Methods We included 4,040 patients diagnosed with HER2-positive breast cancer from the SEER database, randomly allocating them into training and validation cohorts in a 7:3 ratio. The optimal number of ELNs was identified via piecewise linear regression. The association of ELNs count with nodal migration was evaluated through Logistic Regression (LR) analysis and Random Forest (RF). The nomogram was constructed, and its’ performance was evaluated by the receiver operating characteristic curves, calibration curve and Decision curve analysis curves. Results The optimal number of ELNs was 13. LR and RF identified the optimal number of ELNs, radiotherapy status, chemotherapy status, T stage, and grade as independent predictive variables for node metastasis, which were used in the nomogram’s construction. And the area under the curve values for the nomogram were 0.829 (95% confidence interval (CI): 0.813–0.845) and 0.833 (95% CI:0.808–0.858) in the training and test split respectively, surpassing those of the optimal number of ELNs (0.649, 95% CI: 0.631–0.667 and 0.676, 95% CI:0.648–0.704). Calibration plots exhibited low Brier scores (0.150 for training split, 0.145 for test split). Conclusion This study developed a novel nomogram that integrates the optimal number of ELNs with other independent risk factors, facilitating individualized prediction of lymph node metastasis in patients with HER2-positive breast cancer.

The immunomodulatory effects of seminal plasma (SP) on the maternal immune system play an important role in the implantation and development of the embryo. Decidual macrophages (dMΦs) are one of the major immune cells in the maternal–fetal immune microenvironment, and their M2-type polarization facilitates the establishment and maintenance of pregnancy. However, the role of SP on the polarization of dMΦs is unknown. In this study, we investigated the role and mechanism of SP on the polarization of dMΦs by gene chip sequencing as well as in vitro and in vivo experiments. The results revealed that SP promoted dMΦs M2-type polarization. Gene chip sequencing revealed that miR-26-5p was highly expressed in seminal exosomes (SEs) which could act on PTEN/PI3K/AKT signaling pathway and significantly promote MΦs M2 polarization. Moreover, SEs supplementation significantly reduced embryo resorption in spontaneously aborted mice. In conclusion, our study demonstrated that the SEs derived miR-26-5p in SP promoted the M2 polarization of dMΦs by targeting PTEN/PI3K/AKT signaling pathway, which created an immune-tolerant environment conducive to embryo implantation and development. This study provided new ideas for clinical SP-assisted therapy to improve pregnancy outcomes.

Glioblastoma is a highly malignant tumor of the central nervous system with a high mortality rate. The mechanisms driving glioblastoma onset and progression are complex, posing substantial challenges for developing precise therapeutic interventions to improve patient survival. Over a century ago, the discovery of the Warburg effect underscored the importance of abnormal glycolysis in tumors, marking a pivotal moment in cancer research. Subsequent studies have identified mitochondrial energy conversion as a fundamental driver of tumor growth. Recently, lipid metabolism has emerged as a critical factor in cancer cell survival, providing an alternative energy source. Research has shown that lipid metabolism is reprogrammed in glioblastoma, playing a vital role in shaping the biological behavior of tumor cells. In this review, we aim to elucidate the impact of lipid metabolism on glioblastoma tumorigenesis and explore potential therapeutic targets. Additionally, we provide insights into the regulatory mechanisms that govern lipid metabolism, emphasizing the critical roles of key genes and regulators involved in this essential metabolic process.

Background Gastric cancer is one of the most prevalent malignant tumors within the digestive system, and ferroptosis playing a crucial role in its progression. Glutathione peroxidase 4 (GPX4), a key negative regulator of ferroptosis, is highly expressed in gastric cancer and contributes to tumor growth. Targeting the regulation of GPX4 has emerged as a promising approach to induce ferroptosis and develop effective therapy for gastric cancer. Methods To confirm that OTUD5 is a deubiquitinase of GPX4 and regulates ferroptosis, we performed Western blotting, Co‐IP, immunofluorescence, quantitative real‐time PCR, Ub assay and flow cytometry experiments. To explore the physiological function of OUTD5, we knocked out the Otud5 gene in the mouse gastric cancer cell line (MFC) using CRISPR‐Cas9 and eatablished the subcutaneous tumour model. Immunohistochemistry (IHC) analysis was used to inveatigate the pathological correlation in human gastric cancer. Results We report that ovarian tumor domain‐containing 5 (OTUD5) interacts with, deubiquitylates and stabilizes GPX4. OTUD5 depletion destabilizes GPX4, promotes lipid peroxidation and sensitizes gastric cancer cells to ferroptosis. Moreover, the p53 activator nutlin‐3a suppresses OTUD5 transcription, leading to GPX4 degradation and ferroptosis of gastric cancer cells. Notably, only wild‐type p53 has the capacity to inhibit OTUD5 transcription, while p53 mutations or deficiencies correlate with increased OTUD5 expression, promoting gastric cancer progression. Additionally, OTUD5 silencing and nutlin‐3a‐induced GPX4 degradation enhances the sensitivity of gastric cancer cells to ferroptosis in vivo. Subsequently, the p53/OTUD5/GPX4 axis is confirmed in clinical gastric cancer samples. Conclusion Collectively, these findings elucidate a mechanism whereby p53 inactivation upregulates OTUD5 transcription to deubiquitylate and stablize GPX4, resulting in ferroptosis inhibition and gastric cancer progression. This discovery highlights the potential therapeutic value of targeting OTUD5 to promote ferroptosis in p53‐inactivated gastric cancer. Key points OTUD5 mediates GPX4 deubiquitination to regulate its stability. Deletion of OTUD5 promotes ferroptosis and inhibits tumor growth. Wild type p53 inhibits OTUD5 transcription, thereby promoting GPX4 degradation and inhibiting the development of gastric cancer. OTUD5, GPX4 expression and p53 activity are highly correlated and correlates with clinical progression in STAD.