Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model.

Although hypervalent iodine(III) reagents have become staples in organic chemistry, the exploration of their isoelectronic counterparts, namely hypervalent bromine(III) and chlorine(III) reagents, has been relatively limited, partly due to challenges in synthesizing and stabilizing these compounds. In this study, we conduct a thorough examination of both homolytic and heterolytic bond dissociation energies (BDEs) critical for assessing the chemical stability and functional group transfer capability of cyclic hypervalent halogen compounds using density functional theory (DFT) analysis. A moderate linear correlation was observed between the homolytic BDEs across different halogen centers, while a strong linear correlation was noted among the heterolytic BDEs across these centers. Furthermore, we developed a predictive model for both homolytic and heterolytic BDEs of cyclic hypervalent halogen compounds using machine learning algorithms. The results of this study could aid in estimating the chemical stability and functional group transfer capabilities of hypervalent bromine(III) and chlorine(III) reagents, thereby facilitating their development.

X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway.

BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

Associations between serum uric acid and breast cancer incidence: A systematic review and meta-analysis.

BACKGROUND: Serum uric acid (SUA) may be involved in the development of cancer by inhibiting oxidative stress, but its relationship with breast cancer remains unclear. METHODS: The PubMed, Embase, and Web of Science databases were searched systematically for studies on SUA levels in women with breast cancer and the effect of SUA levels on the risk of breast cancer. The Newcastle‒Ottawa Quality Assessment Scale (NOS) was used to assess the quality of all relevant studies included. RESULTS: A total of 19 studies were included, including 75,827 women with breast cancer and 508,528 healthy controls. A meta-analysis found that SUA levels were negatively correlated with breast cancer risk in women (HR = 0.94, 95% CI: 0.89 - 0.99, p = 0.003). SUA levels in female breast cancer patients were not significantly different from those in healthy controls (SMD = 0.49, 95% CI = -0.09 - 1.08, p = 0.10), while SUA levels were increased in female breast cancer patients in articles published after 2010, SUA concentration detected by spectrophotometry, and non-Asian populations, regardless of menopausal state and treatment state. CONCLUSION: High levels of SUA may reduce the risk of breast cancer in women, suggesting that SUA was a protective factor in women.

Research Progress of Vagal Nerve Regulation Mechanism in Acupuncture Treatment of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.

Causal Relationships of Ligamentous Injuries in the Knee on Corticospinal Tract Structure: A Mendelian Randomization Analysis.

BACKGROUND: The association between ligamentous knee injuries and corticospinal tract (CST) structure has attracted attention; however, any causal relationship remains uncertain. We performed Mendelian randomization (MR) analysis to identify the causal effects of ligamentous knee injuries on the CST. HYPOTHESIS: Ligamentous knee injuries impair CST microstructure (ie, by reducing fractional anisotropy [FA] and increasing mean diffusivity [MD]). STUDY DESIGN: MR analysis. LEVEL OF EVIDENCE: Level 2. METHODS: MR uses genetic variants as instrumental variables to infer causal relationships between exposures and outcomes. Summary data for ligamentous injuries in knee and CST structure were obtained from genome-wide association study datasets. Significant and independent (5 × 10-6; r2 < 0.001; 10,000 kb) single-nucleotide polymorphisms were extracted for MR analysis. Three methods for MR analysis were used (hypothesis-driven 1-tailed inverse variance weighted, MR-Egger, and weighted median), and sensitivity analyses were conducted to test reliability and stability. RESULTS: Results from 3 MR methods consistently demonstrated that ligamentous knee injuries increased MD of the right CST (ß, 0.063; 90% CI, 0.003-0.123; P = 0.04), and weak statistical significance suggested increased MD of the left CST (ß, 0.060; 90% CI, -0.002 to -0.121; P = 0.05). However, no significant causal relationships were observed in CST FA, and no significant pleiotropy or heterogeneity was observed. Sensitivity analysis utilizing 2-tailed tests had no significant associations between ligamentous knee injuries and changes in CST structure. CONCLUSION: There is statistically weak genetic evidence that corticospinal pathway abnormalities may evolve after ligamentous knee injuries, which manifests as abnormally organized neurites. CLINICAL RELEVANCE: Ligamentous knee injuries require attention not only to damage to the structure of the knee joint itself but also to the process of maladaptive neuroplasticity that leads to structural and functional changes of the CST; novel interventions that target the corticospinal pathway may provide subsequent treatment of ligamentous knee injuries.

A fluorescent probe based on cyclochalcone for detecting peroxynitrite.

A novel cyclic chalcone fluorescent probe C-PN was synthesized to detect ONOO-. After reaction with peroxynitrite, the double bond of C-PN in the cyclic chalcone structure was disconnected, which caused the change of intramolecular charge transfer (ICT) effect, emitting blue fluorescence and quenching orange red fluorescence. Visible to the naked eye, the color of the probe solution changed. The probe showed low sensitivity (detection limit = 20.2 nm), short response time (less than 60 s) at low concentration of ONOO-, good visibility, and good selectivity and stability for ONOO-.

Production of constrained L-cyclo-tetrapeptides by epimerization-resistant direct aminolysis.

The synthesis of constrained 12-membered rings is notably difficult. The main challenges result from constraints during the linear peptide cyclization. Attempts to overcome constraints through excessive activation frequently cause peptidyl epimerization, while insufficient activation of the C-terminus hampers cyclization and promotes intermolecular oligomer formation. We present a ß-thiolactone framework that enables the synthesis of cyclo-tetrapeptides via direct aminolysis. This tactic utilizes a mechanism that restricts C-terminal carbonyl rotation while maintaining high reactivity, thereby enabling efficient head-to-tail amidation, reducing oligomerization, and preventing epimerization. A broad range of challenging cyclo-tetrapeptides ( > 20 examples) are synthesized in buffer and exhibits excellent tolerance toward nearly all proteinogenic amino acids. Previously unattainable macrocycles, such as cyclo-L-(Pro-Tyr-Pro-Val), have been produced and identified as µ-opioid receptor (MOR) agonists, with an EC50 value of 2.5 nM. Non-epimerizable direct aminolysis offers a practical solution for constrained peptide cyclization, and the discovery of MOR agonist activity highlights the importance of overcoming synthetic challenges for therapeutic development.

Capsular Repair Versus No Repair After Hip Arthroscopy in Patients Without Dysplasia or Generalized Ligamentous Laxity: A Systematic Review and Meta-analysis.

Background: Many recent studies have shown that patients who undergo capsular repair after hip arthroscopy achieve superior clinical outcomes compared with those who do not. However, patients with dysplasia or generalized ligamentous laxity (GLL) were not excluded from most of these studies, which may have affected the outcomes. Purpose: To determine whether capsular repair influences the outcomes of hip arthroscopy for patients without dysplasia or GLL. Study Design: Systematic review; Level of evidence, 1. Methods: Under the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, randomized controlled trials comparing the outcomes of capsulotomy with versus without repair were included, but studies that included patients with dysplasia or GLL were excluded. The study outcomes were patient-reported outcome measures (PROMs) at 6 months and 2 years postoperatively-including the modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), and Hip Outcome Score-Sport-Specific Subscale (HOS-SSS)- and were compared between the repair and no-repair groups. A narrative analysis and meta-analysis were performed to integrate and compare the results of the 2 groups. In the meta-analysis of the outcome measures, studies with significant differences in the preoperative scores between the repair and no-repair groups were excluded because previous studies have shown that these can affect the outcomes. Results: A total of 761 studies were initially identified, of which 3 were included. Of the 322 included patients, 136 underwent capsular repair, and 186 underwent capsulotomy with no repair. The meta-analysis showed that capsular repair was associated with significantly higher postoperative PROMs: the mHHS at 2 years (P = .03), the HOS-ADL at 6 months (P = .02) and 2 years (P < .0001), and the HOS-SSS at 6 months (P = .02) and 2 years (P = .001). Conclusion: Capsular repair after hip arthroscopy was associated with superior clinical outcomes when compared with no capsular repair in patients without dysplasia or GLL.

Radical-Mediated α-tert-Alkylation of Aldehydes by Consecutive 1,4- and 1,3-(Benzo)thiazolyl Migrations.

The direct alkylation of the α-position of aldehydes is an effective method for accessing a wide range of structurally diverse aldehydes, yet tert-alkylation has proven to be a challenging task. In this study, we present a novel radical-mediated tert-alkylation approach targeting the α-position of aldehydes, enabling the synthesis of complex aliphatic aldehydes. The transformation is initiated by the interaction between an in situ generated enamine intermediate and α-bromo sulfone, forming an electron donor-acceptor (EDA) complex, followed by consecutive 1,4- and 1,3-functional group migrations. This protocol operates under metal-free and mild photochemical conditions, delivering a broad scope of products and providing new mechanistic insights into radical rearrangement reactions.

Copper Difluorocarbene Enables Catalytic Difluoromethylation.

Despite the synthetic versatility of difluorocarbene, its high reactivity severely regulates widespread applications of difluorocarbene in organic synthesis. Here, we report a copper difluorocarbene-involved catalytic coupling, representing a new mode of the difluoromethylation reaction. This method allows difluoromethylation of a wide range of readily available allyl/propargyl electrophiles with NaBH3CN and low-cost difluorocarbene precursor BrCF2CO2K, featuring high cost-efficiency, high stereo- and regioselectivities, and high functional group tolerance, even with complex drug-like molecules. Applying the method led to the efficient synthesis of deuterated difluoromethylated compounds of medicinal interest. The resulting difluoromethylated allyl and allenyl products can serve as versatile synthons for diverse transformations, rendering the approach attractive for synthesizing complex fluorinated structures. Experimental mechanistic studies and computational calculations reveal that the formation of a difluoromethylcopper(I) intermediate through the nucleophilic attack of boron hydride on the copper(I) difluorocarbene is the key step in the reaction.

Carbene-Assisted Arene Ring-Opening.

Despite the significant achievements in dearomatization and C-H functionalization of arenes, the arene ring-opening remains a largely unmet challenge and is underdeveloped due to the high bond dissociation energy and strong resonance stabilization energy inherent in aromatic compounds. Herein, we demonstrate a novel carbene assisted strategy for arene ring-opening. The understanding of the mechanism by our DFT calculations will stimulate wide application of bulk arene chemicals for the synthesis of value-added polyconjugated chain molecules. Various aryl azide derivatives now can be directly converted into valuable polyconjugated enynes, avoiding traditional synthesis including multistep unsaturated precursors, poor selectivity control, and subsequent transition-metal catalyzed cross-coupling reactions. The simple conditions required were demonstrated in the late-stage modification of complex molecules and fused ring compounds. This chemistry expands the horizons of carbene chemistry and provides a novel pathway for arene ring-opening.

Metformin induction of heat shock factor 1 activation and the mitochondrial unfolded protein response alleviate cardiac remodeling in spontaneously hypertensive rats.

Heart failure and cardiac remodeling are both characterized by mitochondrial dysfunction. Healthy mitochondria are required for adequate contractile activity and appropriate regulation of cell survival. In the mammalian heart, enhancement of the mitochondrial unfolded protein response (UPRmt) is cardioprotective under pressure overload conditions. We explored the UPRmt and the underlying regulatory mechanism in terms of hypertension-induced cardiac remodeling and the cardioprotective effect of metformin. Male spontaneously hypertensive rats and angiotensin II-treated neonatal rat cardiomyocytes were used to induce cardiac hypertrophy. The results showed that hypertension induced the formation of aberrant mitochondria, characterized by a reduced mtDNA/nDNA ratio and swelling, as well as lower levels of mitochondrial complexes I to V and inhibition of the expression of one protein subunit of each of complexes I to IV. Such changes eventually enlarged cardiomyocytes and increased cardiac fibrosis. Metformin treatment increased the mtDNA/nDNA ratio and regulated the UPRmt, as indicated by increased expression of activating transcription factor 5, Lon protease 1, and heat shock protein 60, and decreased expression of C/EBP homologous protein. Thus, metformin improved mitochondrial ultrastructure and function in spontaneously hypertensive rats. In vitro analyses revealed that metformin reduced the high levels of angiotensin II-induced mitochondrial reactive oxygen species in such animals and stimulated nuclear translocation of heat shock factor 1 (HSF1). Moreover, HSF1 small-interfering RNA reduced the metformin-mediated improvements in mitochondrial morphology and the UPRmt by suppressing hypertrophic signals and cardiomyocyte apoptosis. These results suggest that HSF1/UPRmt signaling contributes to the beneficial effects of metformin. Metformin-mediated targeting of mitochondrial protein homeostasis and modulation of HSF1 levels have potential therapeutic implications in terms of cardiac remodeling.

Predictive Modeling for Functional Outcomes After All-Inside Arthroscopic Anterior Talofibular Ligament Repair of Chronic Ankle Instability.

BACKGROUND: Arthroscopic anterior talofibular ligament repair (AATFLR) is a surgical strategy to treat chronic ankle instability (CAI) patients. This study identified risk factors that influenced the functional outcomes of AATFLR for CAI and developed prognostic nomogram for predicting functional outcomes in future AATFLR cases. METHODS: Patients undergoing AATFLR from January 2016 to June 2022 with at least 10 months of follow-up were included in the study. The Karlsson Ankle Functional Score (KAFS) was evaluated preoperatively and at last follow-up visit. A total of 15 potential predictors including age, sex, body mass index, side affected, time from injury to surgery, sports-related injury, osteophyte, loose bodies, distal tibiofibular syndesmosis, ATFL avulsion fracture, Outerbridge classification of osteochondral lesions, postoperative immobilization method, ambulation time, walking time, and follow-up time, were recorded. We first used univariate binary logistic regression analysis to select the potential significant prognostic features, which were then subjected to the least absolute shrinkage and selection operator (LASSO) regression algorithm for final feature selection. A nomogram based on the regression model was developed to estimate the functional outcomes of patients. Models were validated internally using bootstrapping and externally by calculating their performance on a validation cohort. RESULTS: Overall, 200 ankles fit inclusion criteria. Of these 200, a total of 185 (92.5%) ankles were eligible and divided into development (n = 121) and validation (n = 64) cohorts. Four predictors were ultimately included in the prognostic nomogram model: age, sex, sports-related injury, and postoperative immobilization method. CONCLUSION: We found in our cohort that the significant predictors of poorer functional outcomes of AATFLR were postoperative immobilization with lower-leg cast, female sex, non-sports-related ankle sprain, and increasing age. Prognostic nomograms were created. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Clinical Features Post Anterior Cruciate Ligament Reconstruction Associated with Structural Alterations in Corticospinal Tract.

CONTEXT: Structural evidence for corticospinal tract (CST) abnormality between patients with ACLR and healthy controls, and the relationships between CST structure and clinical features of the patients (e.g., objective sensorimotor outcomes, postoperative duration) are lacking. OBJECTIVES: To investigate whether the structural features of CST 1) differ between patients with ACLR and healthy controls, and 2) were associated with clinical features in patients following ACLR. DESIGN: Cross-sectional study. SETTING: Sports medicine laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-six patients who had undergone ACLR and twenty-six healthy controls were enrolled in this cross-sectional investigation. MAIN OUTCOME MEASURE(S): Using the CST as the region of interest, we performed diffusion tensor imaging to measure the microstructure of white matter tracts. Between-group comparisons and correlation analyses with clinical features in patients with ACLR were performed. RESULTS: The patients with ACLR showed significant, moderate lower fractional anisotropy (FA, Cohen's d = -0.666, 95% CIs -1.221 to -0.104), lower axial diffusivity (AD, Cohen's d = -0.526, 95% CIs -1.077 to 0.030), and higher radial diffusivity (RD, Cohen's d = 0.514, 95% CIs -0.042 to 1.064) when compared to that of healthy controls, with the RD values being significantly correlated with the postoperative duration (r = 0.623, p < 0.001) after controlling the age, sex, and BMI in patients with ACLR. CONCLUSIONS: This study revealed that patients with ACLR have impaired integrity (lower FA values and higher RD values) in the CST contralateral to the ACLR injured limb in comparison with healthy controls. Decreased integrity (higher RD) of the CST in patients was significantly associated with longer postoperative duration, which hinted that impaired structural integrity of the CST may be a maladaptive process of neuroplasticity in ACLR.

Local weak hydrogen bonds induced dipole-dipole interactions in polymer for enhancing photocatalytic oxidation.

Functionalizing organic polymers is an effective strategy for enhancing their photocatalytic performance. However, this approach is currently limited by specific motifs, complex preparation methods, and an unclear electron transfer mechanism. Here, we present a meticulously designed structure of perylene diimide connected with poly (barbituric acid trimer) through self-assembled hydrogen bonding. In particular, the local chemical environment of the two components is adjusted by hydrogen bond-induced dipole-dipole interactions, leading to the emergence of a significant inherent electric field. Additionally, the formation of hydrogen bonds provides electronic pathways that facilitate charge transfer from perylene to adjacent units. Moreover, the distinctive electronic structure enhances polarity transfer and improves activation and adsorption capabilities for reactive molecules. Ultimately, B-PDI exhibits outstanding oxidation rates for benzylamine to N-benzylidene-benzylamine (10.03 mmol g-1h-1) and selectivity (>99.99 %). Our work offers a widely popular approach for enhancing the photocatalytic activity of organic semiconductor materials by constructing hydrogen bonds in heterogeneous molecules.

Caspase-1 deletion reveals pyroptosis participates in neural damage induced by cerebral ischemia/reperfusion in tMCAO model mice.

Pyroptosis, a form of programmed cell death, drives inflammation in the context of cerebral ischemia/reperfusion. The molecular mechanism of pyroptosis underlying ischemia/reperfusion, however, is not fully understood. The transient middle cerebral artery occlusion was applied to wild-type and caspase-1 knockout mice. 2,3,5-Triphenyltetrazolium chloride-staining and immunohistochemistry were used to identify the ischemic region, and western blot and immunofluorescence for the examination of neuronal pyroptosis. The expression of inflammatory factors and the behavioral function assessments were further conducted to examine the effects of caspase-1 knockout on protection against ischemia/reperfusion injury. Ischemia/reperfusion injury increased pyroptosis-related signals represented by the overexpression of pyroptosis-related proteins including caspase-1 and gasdermin D (GSDMD). Meanwhile, the number of GSDMD positive neurons increased in penumbra by immunofluorescence staining. Compared with wild-type mice, those with caspase-1 knockout exhibited decreased levels of pyroptosis-related proteins following ischemia/reperfusion. Furthermore, ischemia/reperfusion attack-induced brain infarction, cerebral edema, inflammatory factors, and neurological outcomes were partially improved in caspase-1 knockout mice. The data indicate that pyroptosis participates in ischemia/reperfusion induced-damage, and the caspase-1 might be involved, it provides some new insights into the molecular mechanism of ischemia.

Reversal of the Regioselectivity of Iron-Promoted Hydrogenation and Hydrohalogenation of gem-Difluoroalkenes.

The reaction regioselectivity of gem-difluoroalkenes is dependent on the intrinsic polarity. Thus, the reversal of the regioselectivity of the addition reaction of gem-difluoroalkenes remains a formidable challenge. Herein, we described an unprecedented reversal of regioselectivity of hydrogen atom transfer (HAT) to gem-difluoroalkenes triggered by Fe-H species for the formation of difluoroalkyl radicals. Hydrogenation of the in situ generated radicals gave difluoromethylated products. Mechanism experiments and theoretical studies revealed that the kinetic effect of the irreversible HAT process resulted in the reversal of the regioselectivity of this scenario, leading to the formation of a less stable α-difluoroalkyl radical regioisomer. On basis of this new reaction of gem-difluoroalkene, the iron-promoted hydrohalogenation of gem-difluoroalkenes for the efficient synthesis of aliphatic chlorodifluoromethyl-, bromodifluoromethyl- and iododifluoromethyl-containing compounds was developed. Particularly, this novel hydrohalogenation of gem-difluoroalkenes provided an effect and large-scale access to various iododifluoromethylated compounds of high value for synthetic application.

Uncertainty quantification of the impact of peripheral arterial disease on abdominal aortic aneurysms in blood flow simulations.

Peripheral arterial disease (PAD) and abdominal aortic aneurysms (AAAs) often coexist and pose significant risks of mortality, yet their mutual interactions remain largely unexplored. Here, we introduce a fluid mechanics model designed to simulate the haemodynamic impact of PAD on AAA-associated risk factors. Our focus lies on quantifying the uncertainty inherent in controlling the flow rates within PAD-affected vessels and predicting AAA risk factors derived from wall shear stress. We perform a sensitivity analysis on nine critical model parameters through simulations of three-dimensional blood flow within a comprehensive arterial geometry. Our results show effective control of the flow rates using two-element Windkessel models, although specific outlets need attention. Quantities of interest like endothelial cell activation potential (ECAP) and relative residence time are instructive for identifying high-risk regions, with ECAP showing greater reliability and adaptability. Our analysis reveals that the uncertainty in the quantities of interest is 187% of that of the input parameters. Notably, parameters governing the amplitude and frequency of the inlet velocity exert the strongest influence on the risk factors' variability and warrant precise determination. This study forms the foundation for patient-specific simulations involving PAD and AAAs which should ultimately improve patient outcomes and reduce associated mortality rates.

Photoinduced Remote C(sp3)-H Phosphonylation of Amides.

The present study reports an unprecedented protocol for the phosphonylation of unactivated C(sp3)-H bonds. By utilizing 1 mol % 4DPAIPN (1,2,3,5-tetrakis(diphenylamino)-4,6-dicyanobenzene) as the catalyst, satisfactory yields of γ-phosphonylated amides are obtained through a visible-light-induced reaction between N-((4-cyanobenzoyl)oxy)alkanamides and 9-fluorenyl o-phenylene phosphite at room temperature. This protocol demonstrates broad substrate scope and wide functional group compatibility.

A genome-wide association study of Chinese and English language phenotypes in Hong Kong Chinese children.

Dyslexia and developmental language disorders are important learning difficulties. However, their genetic basis remains poorly understood, and most genetic studies were performed on Europeans. There is a lack of genome-wide association studies (GWAS) on literacy phenotypes of Chinese as a native language and English as a second language (ESL) in a Chinese population. In this study, we conducted GWAS on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; total N = 1046). We performed association tests at the single-variant, gene, and pathway levels. In addition, we tested genetic overlap of these phenotypes with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis. Totally 5 independent loci (LD-clumped at r2 = 0.01; MAF > 0.05) reached genome-wide significance (p < 5e-08; filtered by imputation quality metric Rsq>0.3 and having at least 2 correlated SNPs (r2 > 0.5) with p < 1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with EA and other neuropsychiatric phenotypes, such as MANEA and PLXNC1. In PRS analysis, EA and CP showed the most consistent and significant polygenic overlap with a variety of language traits, especially English literacy skills. To summarize, this study revealed the genetic basis of Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings.