Ecogroups and maternal haplogroups reveal the ancestral origin of native Chinese goat populations based on the variation of mtDNA D-loop sequences.

China is rich in goat breeding resources. Officially recognized local goat breeds are mainly distributed in agro-ecological regions. The population structure and matrilineal origin of native Chinese goats can be used to formulate protection and utilization strategies for these genetic resources. In this study, the genetic structure and maternal origin of native Chinese goats were investigated using mtDNA D-loop sequences. A total of 329 goat samples from 25 Chinese indigenous goat populations and five introduced goat breeds from abroad were collected; these populations were distributed in four ecogroups designated as Southwest, South-central, the North China Plain, and Foreign-ecogroup. A larger average number of nucleotide differences and richer nucleotide diversity were observed in South-central and Foreign-ecogroup, whereas these were lower in Southwest. The 216 haplotypes divided into several haplogroups, of which HapA contained 99 haplotypes distributed in Southwest, the North China Plain, and Foreign-ecogroup with high frequency (0.53-0.77), whereas the frequency of HapA in South-central was <0.09. HapB was mostly found in South-central (0.5538) and was distributed to the North China Plain (0.2667), while it was rare in Southwest (<0.08) and Foreign-ecogroup (<0.07). According to the estimation of kinship and ancestry, HapA had five ancestors (A2, A3, A5, A10, and A12), HapB had a single maternal ancestor (A8), and HapC had two maternal ancestors (A1 and A4). This study showed that native Chinese goat breeds were mainly divided into three haplogroups (HapA, HapB, and HapC) and goat populations have expanded in the ecological regions.

Histogram analysis of ultrasonographic images in the differentiation of benign and malignant parotid gland tumors.

OBJECTIVE: We evaluated the diagnostic value of histogram analysis (HA) using ultrasonographic (US) images for differentiation among pleomorphic adenoma (PA), adenolymphoma (AL), and malignant tumors (MT) of the parotid gland. STUDY DESIGN: Preoperative US images of 48 patients with PA, 39 patients with AL, and 17 patients with MT were retrospectively analyzed for gray-scale histograms. Nine first-order texture features derived from histograms of the tumors were compared. Area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of texture features. The Youden index maximum exponent was used to calculate sensitivity and specificity. RESULTS: Statistically significant differences were discovered in Mean and Skewness HA values between PA and AL (P<0.001), and in Mean values between AL and MT (P<0.001). However, comparison of PA and MT showed no statistically significant differences (P>0.01). Excellent discrimination was detected between PA and AL (AUC=0.802), and between AL and MT (AUC=0.822). The combination of Mean plus Skewness improved discrimination between PA and AL (AUC=0.823) with sensitivity values reaching 1.00. However, Mean plus Skewness applied to differentiate PA from AL and Mean values applied to distinguish AL and MT resulted in low specificity, indicating many false positive interpretations. CONCLUSIONS: Histogram analysis is useful for differentiating PA from AL and AL from MT but not PA from MT.

Activation of Kir2.1 improves myocardial fibrosis by inhibiting Ca 2+ overload and the TGF-ß1/Smad signaling pathway.

The inwardly rectifying potassium channel Kir2.1 is closely associated with many cardiovascular diseases. However, the effect and mechanism of Kir2.1 in diabetic cardiomyopathy remain unclear. In vivo, we use STZ to establish the model, and ventricular structural changes, myocardial inflammatory infiltration, and myocardial fibrosis severity are detected by echocardiography, histological staining, immunohistochemistry, and western blot analysis, respectively. In vitro, a myocardial fibrosis model is established with high glucose. The Kir2.1 current amplitude, intracellular calcium concentration, fibrosis-related proteins, and TGF-ß1/Smad pathway proteins are detected by whole-cell patch clamp, calcium probes, western blot analysis, and immunofluorescence, respectively. The in vivo results show that compared to diabetic cardiomyopathy, zacopride (a Kir2.1 selective agonist) significantly reduces the left ventricular systolic diameter and diastolic diameter, increases the left ventricular ejection fraction and left ventricular short-axis shortening, improves the degree of cell necrosis, and reduces the expression of myocardial interstitial fibrosis protein and collagen fibre deposition area. The in vitro results show that the current amplitude and protein expression of Kir2.1 are both decreased in the high glucose-induced myocardial fibrosis model. Additionally, zacopride significantly upregulates the expression of Kir2.1 and inhibits the expressions of the fibrosis-related proteins α-SMA, collagen I, and collagen III. Activation of Kir2.1 reduces the intracellular calcium concentration and inhibits the protein expressions of TGF-ß1 and p-Smad 2/3. Activation of Kir2.1 can improve myocardial fibrosis induced by diabetic cardiomyopathy, and the possible mechanism may be related to inhibiting Ca 2+ overload and the TGF-ß1/Smad signaling pathway.

The effect of a disability-targeted cash transfer program on universal health coverage and universal access to education: a nationwide cohort study of Chinese children and adolescents with disabilities.

Background: To achieve improved outcomes for children and adolescents with disabilities, it is central to have universal health coverage (UHC) and universal access to education. This study investigates whether a disability-targeted cash transfer (CT) program is associated with improved access to healthcare and education for children and adolescents with disabilities. Methods: We used nationwide survey data of two million children and adolescents living with disabilities, who aged 8-15 years when entering the cohort between January 1, 2015, and December 31, 2019. With a quasi-experimental study design, we compared the outcomes between CT beneficiaries who newly received CT benefits during the study period and non-beneficiaries who were disabled but never received CT using logistic regressions after propensity score matching with a 1:1 ratio. Outcomes of interest were utilization of rehabilitation services in the past year, medical treatment if the individual had illness in the past two weeks, school attendance if not in school at the start of the study, and reported financial hardship to access these services. Findings: Of the total cohort, 368,595 children and adolescents fit the inclusion criteria, including 157,707 new CT beneficiaries and 210,888 non-beneficiaries. After matching, CT beneficiaries showed 2.27 (95% confidence interval [CI]: 2.23, 2.31) higher odds of utilizing rehabilitation services and 1.34 (95% CI: 1.23, 1.46) higher odds of getting medical treatment compared to non-beneficiaries. CT benefits were also significantly associated with less report of financial barrier to access rehabilitation services (odds ratio [OR]: 0.63, 95% CI: 0.60, 0.66) and medical treatment (OR: 0.66, 95% CI: 0.57, 0.78). Moreover, CT program was associated with higher odds of school attendance (OR: 1.99, 95% CI: 1.85, 2.15) and lower odds of reporting financial difficult to access education (OR: 0.41, 95% CI: 0.36, 0.47). Interpretation: Our results suggest that the receipt of CT was associated with improved access to health and educational resources. This finding provides supporting evidence for the identification of efficient and feasible interventions to move toward UHC and universal education under the Sustainable Development Goals. Funding: This research was supported by Sanming Project of Medicine in Shenzhen (NO.SZSM202111001), China National Natural Science Foundation (Grant/Award Number: 72274104, 71904099) and Tsinghua University Spring Breeze Fund (20213080028).

Transcriptome analysis reveals critical factors for survival after adenovirus serotype 4 infection.

Fowl adenovirus serotype-4 (FAdV-4) is highly lethal to poultry, making it one of the leading causes of economic losses in the poultry industry. However, a small proportion of poultry can survive after FAdV-4 infection. It is unclear whether there are genetic factors that protect chickens from FAdV-4 infection. Therefore, the livers from chickens uninfected with FAdV-4 (Normal), dead after FAdV-4 infection (Dead) or surviving after FAdV-4 infection (Survivor) were collected for RNA-seq, and 2,649 differentially expressed genes (DEGs) were identified. Among these, many immune-related cytokines and chemokines were significantly upregulated in the Dead group compared with the Survivor group, which might indicate that death is related to an excessive inflammatory immune response (cytokine storm). Subsequently, the KEGG results for DEGs specifically expressed in each comparison group indicated that cell cycle and apoptosis-related DEGs were upregulated and metabolism-related DEGs were downregulated in the Dead group, which also validated the reliability of the samples. Furthermore, GO and KEGG results showed DEGs expressed in all three groups were mainly associated with cell cycle. Among them, BRCA1, CDK1, ODC1, and MCM3 were screened as factors that might influence FAdV-4 infection. The qPCR results demonstrated that these 4 factors were not only upregulated in the Dead group but also significantly upregulated in the LMH cells after 24 h infection by FAdV-4. Moreover, interfering with BRCA1, CDK1, ODC1, and MCM3 significantly attenuated viral replication of FAdV-4. And interfering of BRCA1, CDK1, and MCM3 had more substantial hindering effects. These results provided novel insights into the molecular changes following FAdV-4 infection but also shed light on potential factors driving the survival of FAdV-4 infection in chickens.

Three-dimensional speckle tracking echocardiography to evaluate left ventricular function in patients with acute ST-segment elevation myocardial infarction after percutaneous coronary intervention following Tongxinluo treatment.

OBJECTIVE: Bying comparing the correlation between three-dimensional speckle tracking echocardiography (3D-STE) and troponin I (cTn I), three-dimensional left ventricular ejection fraction (3D-LVEF), to explore the 3D-STE to evaluate the left ventricle of patients with acute ST-segment elevation myocardial infarction (AMI) after percutaneous coronary intervention (PCI) following routine treatment with Tongxinluo drugs. METHODS: Altogether, 61 patients with AMI and 30 healthy adults were selected, and the patients were divided into the routine group and the Tongxinluo group. The serum creatine kinase isoenzyme (CK-MB) and troponin I (cTn I) levels were detected in all patients after admission. All patients underwent PCI, and routine echocardiography and 3D-STE assessments were performed for each group 72 h after PCI and 12 months after PCI to obtain the following left ventricular-related functional parameters: left ventricular end-diastolic diameter (LVEDD), end-ventricular septal end-diastolic thickness (IVSD), left ventricular posterior wall end-diastolic thickness (LVPWD), left ventricular short axis shortening fraction (LVFS), Simpson's left ventricular ejection fraction (Simpson's LVEF), three-dimensional left ventricular ejection fraction (3D-LVEF), global longitudinal strain (GLS), global circumferential strain (GCS), left ventricular twist angle (LVtw), Torsion (Tor), peak strain dispersion (PSD), and myocardial comprehensive index (MCI). The same parameters were collected in the control group, the results were compared. The correlation analysis between 3D-STE parameters and 3D-LVE, cTn I was performed. A total of 10 individuals were selected for repeatability testing. RESULTS: Compared with the control group, the LVFS, LVEF (Simpson), 3D-LVEF, GLS, GCS, LVtw, Tor, and MCI significantly decreased in patients with STEMI after PCI, while the PSD significantly increased (p < 0.05). Compared with the values 72 h after PCI, the LVEDD, LVFS, LVEF (Simpson), 3D-LVEF, GLS, GCS, LVtw, Tor, and MCI significantly increased at 12 m after PCI, while PSD significantly decreased (p < 0.05). No significant difference was observed between the two groups at 72 h after PCI (p > 0.05). At 12 months after PCI, the LVEF, GLS, GCS, LVtw, Tor, and MCI of the Tongxinluo group were higher than those of the routine group. The PSD was significantly lower in the Tongxinluo group (p < 0.05). MCI and 3D-LVEF, cTn I have the strongest correlation and the highest consistency, which can best reflect the changes in the left ventricular function in patients with AMI after PCI. CONCLUSION: 3D-STE can be used to evaluate the protective effect of Tongxinluo on the left ventricular function in patients with AMI after PCI.

Inhibition of KIR2.1 decreases pulmonary artery smooth muscle cell proliferation and migration.

The investigation of effective therapeutic drugs for pulmonary hypertension (PH) is critical. KIR2.1 plays crucial roles in regulating cell proliferation and migration, and vascular remodeling. However, researchers have not yet clearly determined whether KIR2.1 participates in the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and its role in pulmonary vascular remodeling (PVR) also remains elusive. The present study aimed to examine whether KIR2.1 alters PASMC proliferation and migration, and participates in PVR, as well as to explore its mechanisms of action. For the in vivo experiment, a PH model was established by intraperitoneally injecting Sprague­Dawley rats monocrotaline (MCT). Hematoxylin and eosin staining revealed evidence of PVR in the rats with PH. Immunofluorescence staining and western blot analysis revealed increased levels of the KIR2.1, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) proteins in pulmonary blood vessels and lung tissues following exposure to MCT, and the TGF­ß1/SMAD2/3 signaling pathway was activated. For the in vitro experiments, the KIR2.1 inhibitor, ML133, or the TGF­ß1/SMAD2/3 signaling pathway blocker, SB431542, were used to pre­treat human PASMCs (HPASMCs) for 24 h, and the cells were then treated with platelet­derived growth factor (PDGF)­BB for 24 h. Scratch and Transwell assays revealed that PDGF­BB promoted cell proliferation and migration. Immunofluorescence staining and western blot analysis demonstrated that PDGF­BB upregulated OPN and PCNA expression, and activated the TGF­ß1/SMAD2/3 signaling pathway. ML133 reversed the proliferation and migration induced by PDGF­BB, inhibited the expression of OPN and PCNA, inhibited the TGF­ß1/SMAD2/3 signaling pathway, and reduced the proliferation and migration of HPASMCs. SB431542 pre­treatment also reduced cell proliferation and migration; however, it did not affect KIR2.1 expression. On the whole, the results of the present study demonstrate that KIR2.1 regulates the TGF­ß1/SMAD2/3 signaling pathway and the expression of OPN and PCNA proteins, thereby regulating the proliferation and migration of PASMCs and participating in PVR.

Differential diagnostic value of tumor morphology, long/short diameter ratio, and ultrasound gray-scale ratio for 3 parotid neoplasms.

OBJECTIVE: The objective of this study was to evaluate the value of tumor morphology, long-to-short diameter ratio (L/S), and ultrasound gray-scale ratio (UGSR) in the differential diagnosis of 3 parotid neoplasms. STUDY DESIGN: Preoperative ultrasound images of 17 patients with a malignant tumor (MT), 48 patients with pleomorphic adenoma (PA), and 39 patients with adenolymphoma (AL) were analyzed for imaging features and gray-scale histograms. Tumor morphology, L/S, and UGSR of MT, PA, and AL were compared. Receiver operating characteristic analysis of area under the curve (AUC), sensitivity, and specificity were used to measure the differential diagnostic efficacy of L/S, UGSR, and both combined with tumor morphology. RESULTS: Morphologic features, L/S, and UGSR differed significantly in various pairwise comparisons of the 3 tumor types. Acceptable discrimination was detected between MT and AL with UGSR alone (AUC = 0.771) and between PA and AL with L/S and UGSR combined (AUC = 0.741). The combination of tumor boundary with UGSR yielded excellent discrimination between MT and PA (AUC = 0.853) and between MT and AL (AUC = 0.885), with sensitivity and specificity values greater than 0.800. CONCLUSIONS: These ultrasound parameters, alone or in combination, can provide a method for accurate presurgical differential diagnosis of parotid tumors.

Diagnostic Performance of Atherosclerotic Carotid Plaque Neovascularization with Contrast-Enhanced Ultrasound: A Meta-Analysis.

Objectives: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) for atherosclerotic carotid plaque neovascularization. Methods: The electronic databases like PubMed, Embase, OVID, and Web of Science were used to search for the relevant studies, which are involved in the evaluation of the diagnostic parameters of QUS for atherosclerotic carotid plaque neovascularization. Review Manager 5.4 and Stata 14.0 were used to estimate the pooled diagnostic value of CEUS. Forest plots, sensitivity analysis, and Deeks' funnel plots were performed on the included studies. Results: Ten studies eventually met the final inclusion criteria. For diagnostic performance, CUES showed that the pooled values of sensitivity, specificity, positive likelihood odds ratios, negative likelihood odds ratios, and diagnostic odds ratios were 0.83 (95% CI 0.78-0.86), 0.77 (95% CI 0.68-0.84), 3.61 (95% CI 2.59-5.03), 0.23 (95% CI 0.18-0.28), and 16.02 (95% CI 10.02-25.60), respectively. The estimate of the area under curve (AUC) was 0.85 (95% CI 0.82-0.88). Conclusion: Our research supported that CEUS had high sensitivity and specificity in the diagnosis of atherosclerotic carotid plaque neovascularization. More high-quality prospective multicenter studies focusing on the accuracy of CEUS for carotid atherosclerotic plaque should be performed to verify our conclusions.

Period 2 Suppresses the Malignant Cellular Behaviors of Colorectal Cancer Through the Epithelial-Mesenchymal Transformation Process.

INTRODUCTION: The PER2 (Period circadian regulator 2) gene is related to the circadian clock, and it has been deemed as a suppressor gene in osteosarcoma and lung carcinoma. However, the part of PER2 in CRC (colorectal cancer) needs to be further determined. METHODS: First, we collected clinical samples to detect PER2 expression in CRC. Then, we used cell transfection to knock down PER2 expression in CRC cell lines and performed a series of functional experiments to elucidate the effects of PER2 on CRC cells. We next verified whether PER2 affects the epithelial-mesenchymal transformation (EMT) process in CRC by conducting quantitative real-time PCR and western blotting. RESULTS: In the research, we revealed that the expression of PER2 decreased in CRC clinical samples. In addition, knocking down PER2 expression caused CRC cells to acquire malignant biological features. Finally, we found that PER2 knockdown may activate the Snail/Slug axis through inhibiting p53, therefore promote the activation of the EMT pathway. CONCLUSION: In conclusion, low PER2 expression reinforces migration and activates EMT in CRC, suggesting that PER2 is closely related to CRC development and could be used as a potential treatment site in the clinic.

A computer-aided diagnosis system using white-light endoscopy for the prediction of conventional adenoma with high grade dysplasia.

OBJECTIVES: We developed a computer-aided diagnosis system called ECRCCAD using standard white-light endoscopy (WLE) for predicting conventional adenomas with high-grade dysplasia (HGD) to optimise the patients' management decisions during colonoscopy. METHODS: Pretraining model was used to fine-tune the model parameters by transfer learning. 2,397 images of HGD and 2,487 low-grade dysplasia (LGD) images were randomly assigned (8:1:1) to the training, optimising, and internal validation dataset. The prospective validation dataset is the frames accessed from colonoscope videoes. One independent rural hospital provided an external validation dataset. Histopathological diagnosis was used as the standard criterion. The capability of the ECRCCAD to distinguish HGD was assessed and compared with two expert endoscopists. RESULTS: The accuracy, sensitivity and specificity for diagnosis of HGD in the internal validation set were 90.5%, 93.2%, 87.9%, respectively. While 88.2%, 85.4%, 89.8%, respectively, for the external validation set. For the prospective validation set, ECRCCAD achieved an AUC of 93.5% in diagnosing HGD. The performance of ECRCCAD in diagnosing HGD was better than that of the expert endoscopist in the external validation set (88.2% vs. 71.5%, P < 0.0001). CONCLUSION: ECRCCAD had good diagnostic capability for HGD and enabled a more convenient and accurate diagnosis using WLE.

Speckle tracking imaging combined with myocardial comprehensive index to evaluate left ventricular function changes in patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate early changes in left ventricular systolic function in patients with systemic lupus erythematosus (SLE) using three-dimensional speckle tracking imaging (3D-STI). METHODS: A total of 30 SLE patients and 30 healthy people (control group) were selected, the patients were further divided into subgroups according to their Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI) score: ≤ 12: mild-to-moderate group; > 12: severe group. All participants were examined using 3D-STI, the 3D-STI parameters were obtained. Receiver operating curves (ROC) were prepared for above parameters and analyzed to identify correlations among 3D-STI parameters and high sensitivity-TropT (hs-TropT). RESULTS: Compared with the control group, the absolute values of left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), global circumferential strain (GCS), left ventricular twist angle (LVtw), torsion (Tor) and myocardial comprehensive index (MCI) decreased, left ventricular end diastolic mass (LV EDmass), left ventricular end systolic mass (LV ESmass) and peak strain dispersion (PSD) increased in the mild-to-moderate and the severe groups (P2  < 0.05, P3  < 0.05). There was statistically significant difference in terms of 3D-STI parameters between the mild-to-moderate group and the severe group (P1  < 0.05). The highest area under the ROC for MCI was 0.909, the highest sensitivity for MCI was 90.00%, and the highest specificity for Tor was 86.67%. Correlation analysis showed that there was a good correlation between the MCI and hs-TropT (r = - 0.677). CONCLUSION: 3D-STI technology may help detect early changes in left ventricular systolic function in patients with SLE.

Galectin-3 participates in PASMC migration and proliferation by interacting with TGF-ß1.

Pulmonary vascular remodelling is one of the most important factors for pulmonary hypertension (PH). Galectin-3 (Gal-3) is a ß-galactoside-binding lectin. In the latest literature, Gal-3 has been reported to be involved in pulmonary vascular remodelling, and its underlying mechanism is unclear. Our research aims to prove the effect of Gal-3 on the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMC) induced by transforming growth factor ß1 (TGF-ß1) and to study its mechanism. In vivo experiment: In Sprague-Dawley (SD) rats, monocrotaline was injected intraperitoneally to establish a PH model, and the Gal-3 inhibitor (modified citrus pectin, MCP) 28 Ds was administered in the stomach. The results indicate that Gal-3 and TGF-ß1 may be involved in the occurrence and development of PH, which may be related to the Smad2/3 signalling pathway. In vitro experiment: Human pulmonary artery smooth muscle cells were pretreated with the Gal-3 inhibitor (MCP) for 24 h, then TGF-ß1 or Gal-3 was administered to the cells for 24 h. The results show that exogenous TGF-ß1 and Gal-3 can activate the downstream Smad2/3 signalling pathway, and increase the proliferation and migration ability of HPASMC. However, the Gal-3 inhibitor (MCP) inhibited these effects. Further results display that TGF-ß1 and Gal-3 could mutually regulate the protein and mRNA expression levels. In summary, the results of this study indicate that Gal-3 regulates the Smad2/3 signalling pathway through protein interaction with TGF-ß1, in turn regulates the proliferation and migration of HPASMC, thereby regulating the occurrence and development of PH.

Interferon Regulatory Factor 4 Regulates the Development of Polymorphonuclear Myeloid-Derived Suppressor Cells Through the Transcription of c-Myc in Cancer.

The accumulation of myeloid-derived suppressor cells (MDSCs) is one of the major obstacles to achieve an appropriate anti-tumor immune response and successful tumor immunotherapy. MDSCs in tumor-bearing hosts are primarily polymorphonuclear (PMN-MDSCs). However, the mechanisms regulating the development of MDSCs remain poorly understood. In this report, we showed that interferon regulatory factor 4 (IRF4) plays a key role in the development of PMN-MDSCs, but not monocytic MDSCs. IRF4 deficiency caused a significant elevation of PMN-MDSCs and enhanced the suppressive activity of PMN-MDSCs, increasing tumor growth and metastasis in mice. Mechanistic studies showed that c-Myc was up-regulated by the IRF4 protein. Over-expression of c-Myc almost abrogated the effects of IRF4 deletion on PMN-MDSCs development. Importantly, the IRF4 expression level was negatively correlated with the PMN-MDSCs frequency and tumor development but positively correlated with c-Myc expression in clinical cancer patients. In summary, this study demonstrated that IRF4 represents a novel regulator of PMN-MDSCs development in cancer, which may have predictive value for tumor progression.

Associations of parental depression during adolescence with cognitive development in later life in China: A population-based cohort study.

BACKGROUND: Prior research has underscored negative impacts of perinatal parental depression on offspring cognitive performance in early childhood. However, little is known about the effects of parental depression during adolescence on offspring cognitive development. METHODS AND FINDINGS: This study used longitudinal data from the nationally representative China Family Panel Studies (CFPS). The sample included 2,281 adolescents aged 10-15 years (the median age was 13 years with an interquartile range between 11 and 14 years) in 2012 when their parents were surveyed for depression symptoms with the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). The sample was approximately balanced by sex, with 1,088 females (47.7%). We examined the associations of parental depression in 2012 with offspring cognitive performance (measured by mathematics, vocabulary, immediate word recall, delayed word recall, and number series tests) in subsequent years (i.e., 2014, 2016, and 2018) using linear regression models, adjusting for various offspring (i.e., age, sex, and birth order), parent (i.e., parents' education level, age, whether living with the offspring, and employment status), and household characteristics (i.e., place of residence, household income, and the number of offspring). We found parental depression during adolescence to be significantly associated with worse cognitive performance in subsequent years, in both crude and adjusted models. For example, in the crude models, adolescents whose mothers had depression symptoms in 2012 scored 1.0 point lower (95% confidence interval [CI]: -1.2 to -0.8, p < 0.001) in mathematics in 2014 compared to those whose mothers did not have depression symptoms; after covariate adjustment, this difference marginally reduced to 0.8 points (95% CI: -1.0 to -0.5, p < 0.001); the associations remained robust after further adjusting for offspring earlier cognitive ability in toddlerhood (-1.2, 95% CI: -1.6, -0.9, p < 0.001), offspring cognitive ability in 2012 (-0.6, 95% CI: -0.8, -0.3, p < 0.001), offspring depression status (-0.7, 95% CI: -1.0, -0.5, p < 0.001), and parents' cognitive ability (-0.8, 95% CI: -1.2, -0.3, p < 0.001). In line with the neuroplasticity theory, we observed stronger associations between maternal depression and mathematical/vocabulary scores among the younger adolescents (i.e., 10-11 years) than the older ones (i.e., 12-15 years). For example, the association between maternal depression and 2014 vocabulary scores was estimated to be -2.1 (95% CI: -2.6, -1.6, p < 0.001) in those aged 10-11 years, compared to -1.2 (95% CI: -1.6, -0.8, p < 0.001) in those aged 12-15 years with a difference of 0.9 (95% CI: 0.2, 1.6, p = 0.010). We also observed a stronger association of greater depression severity with worse mathematical scores. The primary limitations of this study were the relatively high attrition rate and residual confounding. CONCLUSIONS: In this study, we observed that parental depression during adolescence was associated with adverse offspring cognitive development assessed up to 6 years later. These findings highlight the intergenerational association between depression in parents and cognitive development across the early life course into adolescence.