Semaglutide attenuates doxorubicin-induced cardiotoxicity by ameliorating BNIP3-Mediated mitochondrial dysfunction.

AIMS: Doxorubicin is a powerful chemotherapeutic agent for cancer, whose use is limited due to its potential cardiotoxicity. Semaglutide (SEMA), a novel analog of glucagon-like peptide-1 (GLP-1), has received widespread attention for the treatment of diabetes. However, increasing evidence has highlighted its potential therapeutic benefits on cardiac function. Therefore, the objective of this study was to examine the efficacy of semaglutide in ameliorating doxorubicin-induced cardiotoxicity. METHODS AND RESULTS: Doxorubicin-induced cardiotoxicity is an established model to study cardiac function. Cardiac function was studied by transthoracic echocardiography and invasive hemodynamic monitoring. The results showed that semaglutide significantly ameliorated doxorubicin-induced cardiac dysfunction. RNA sequencing suggested that Bnip3 is the candidate gene that impaired the protective effect of semaglutide in doxorubicin-induced cardiotoxicity. To determine the role of BNIP3 on the effect of semaglutide in doxorubicin-induced cardiotoxicity, BNIP3 with adeno-associated virus serotype 9 (AAV9) expressing cardiac troponin T (cTnT) promoter was injected into tail vein of C57/BL6J mice to overexpress BNIP3, specifically in the heart. Overexpression of BNIP3 prevented the improvement in cardiac function caused by semaglutide. In vitro experiments showed that semaglutide, via PI3K/AKT pathway, reduced BNIP3 expression in the mitochondria, improving mitochondrial function. CONCLUSION: Semaglutide ameliorates doxorubicin-induced mitochondrial and cardiac dysfunction via PI3K/AKT pathway, by reducing BNIP3 expression in mitochondria. The improvement in mitochondrial function reduces doxorubicin-mediated cardiac injury and improves cardiac function. Therefore, semaglutide is a potential therapy to reduce doxorubicin-induced acute cardiotoxicity.

Algicidal activity synchronized with nitrogen removal by actinomycetes: Algicidal mechanism, stress response of algal cells, denitrification performance, and indigenous bacterial community co-occurrence.

The harmful algal blooms (HABs) can damage the ecological equilibrium of aquatic ecosystems and threaten human health. The bio-degradation of algal by algicidal bacteria is an environmentally friendly and economical approach to control HABs. This study applied an aerobic denitrification synchronization algicidal strain Streptomyces sp. LJH-12-1 (L1) to control HABs. The cell-free filtrate of the strain L1 showed a great algolytic effect on bloom-forming cyanobacterium, Microcystis aeruginosa (M. aeruginosa). The optimal algicidal property of strain L1 was indirect light-dependent algicidal with an algicidal rate of 85.0%. The functional metabolism, light-trapping, light-transfer efficiency, the content of pigments, and inhibition of photosynthesis of M. aeruginosa decreased after the addition of the supernatant of the strain L1 due to oxidative stress. Moreover, 96.05% nitrate removal rate synchronized with algicidal activity was achieved with the strain L1. The relative abundance of N cycling functional genes significantly increased during the strain L1 effect on M. aeruginosa. The algicidal efficiency of the strain L1 in the raw water was 76.70% with nitrate removal efficiency of 81.4%. Overall, this study provides a novel route to apply bacterial strain with the property of denitrification coupled with algicidal activity in treating micro-polluted water bodies.

Lower Melatonin Indicates Poor Short-term Prognosis in Patients with Acute Ischemic Stroke.

AIMS: We evaluated endogenous melatonin levels in the acute phase of cerebral infarction and explored the impact of possible changes in melatonin levels on the prognosis of patients. METHODS: This study recruited acute ischemic stroke (AIS) patients from the Department of the Second Affiliated Hospital of Soochow University between December 2019 and June 2021, along with healthy control subjects. Salivary melatonin samples were collected from each participant between 7 pm and 10 pm, and fasting plasma was collected the following morning to measure the levels of inflammatory markers. The prognosis was assessed through follow-up three months after discharge. The relationship between melatonin levels and plasma inflammatory markers was assessed, followed by an analysis of the effect of melatonin levels on patient prognosis. RESULTS: The study enrolled a total of 160 participants, including 120 AIS patients aged 50 years or older (61.7% male) and 40 age-matched controls (55.0% male). The AIS group exhibited lower salivary melatonin levels at 19 (P = 0.002), 20 (P < 0.001), 21 (P < 0.001), and 22 (P < 0.001) o'clock, and the average melatonin level was also lower (P < 0.001). Logistic regression analysis models indicated an association between low melatonin levels and poor prognosis. Salivary melatonin levels demonstrated good predictive ability for the prognosis of AIS patients. CONCLUSION: Melatonin levels were lower in AIS patients compared to controls. In addition, lower melatonin levels were associated with a poorer prognosis among AIS patients.

SGLT2i improves kidney senescence by down-regulating the expression of LTBP2 in SAMP8 mice.

Senescent kidney can lead to the maladaptive repairment and predispose age-related kidney diseases. Here, we explore the renal anti-senescence effect of a known kind of drug, sodium-dependent glucose transporters 2 inhibitor (SGLT2i). After 4 months intragastrically administration with dapagliflozin on senescence-accelerated mouse prone 8 (SAMP8) strain mice, the physiologically effects (lowering urine protein, enhancing glomerular blood perfusion, inhibiting expression of senescence-related biomarkers) and structural changes (improving kidney atrophy, alleviating fibrosis, decreasing glomerular mesangial proliferation) indicate the potential value of delaying kidney senescence of SGLT2i. Senescent human proximal tubular epithelial (HK-2) cells induced by H2 O2 also exhibit lower senescent markers after dapagliflozin treatment. Further mechanism exploration suggests LTBP2 have the great possibility to be the target for SGLT2i to exert its renal anti-senescence role. Dapagliflozin down-regulate the LTBP2 expression in kidney tissues and HK-2 cells with senescent phenotypes. Immunofluorescence staining show SGLT2 and LTBP2 exist colocalization, and protein-docking analysis implies there is salt-bridge formation between them; these all indicate the possibility of weak-interaction between the two proteins. Apart from reducing LTBP2 expression in intracellular area induced by H2 O2 , dapagliflozin also decrease the concentration of LTBP2 in cell culture medium. Together, these results reveal dapagliflozin can delay natural kidney senescence in non-diabetes environment; the mechanism may be through regulating the role of LTBP2.

EGFR and ERBB2 Exon 20 Insertion Mutations in Chinese Non-small Cell Lung Cancer Patients: Pathological and Molecular Characterization, and First-Line Systemic Treatment Evaluation.

BACKGROUND: Data from studies looking at both EGFR and ERBB2 exon 20 insertion mutations (-20ins) in the same cohort of patients with non-small cell lung cancer (NSCLC) are limited. OBJECTIVE: The purpose of this study was to analyze EGFR/ERBB2-20ins in all-stage NSCLC patients to reveal their histological and molecular features, and to retrospectively evaluate the results of first-line real-world systemic treatments in patients with advanced-stage disease. PATIENTS AND METHODS: We collected 13,920 formalin-fixed paraffin-embedded NSCLC specimens. Clinicopathological features were recorded and DNA-based next-generation sequencing was performed. First-line systemic treatment data were obtained via chart review. RESULTS: In total, 414 (2.97%) EGFR-20ins cases and 666 (4.78%) ERBB2-20ins cases were identified. Both were more common in women, non-smokers, and patients with adenocarcinoma. The incidence of EGFR/ERBB2-20ins in adenocarcinoma is inversely proportional to the degree of invasion; 77 and 26 variants were detected in EGFR-20ins and ERBB2-20ins cases, respectively. The most common concurrently mutated genes were TP53 and RB1. In invasive adenocarcinoma, lepidic components were more common in EGFR/ERBB2-20ins-alone cases than in those with other concurrent mutated genes. In EGFR-/ERBB2-20ins patients, there was no significant difference in progression-free survival (PFS) or treatment response to first-line systemic treatments in this study. There was no significant difference in PFS or treatment response among patients with different EGFR/ERBB2-20ins variants and those with or without concurrent mutated genes. CONCLUSIONS: EGFR/ERBB2-20ins is more common in early lung adenocarcinoma. EGFR-20ins had more variants. In both cohorts, the results for first-line systemic treatments showed no significant difference.

Metal element-based adsorbents for phosphorus capture: Chaperone effect, performance and mechanism.

Excessive phosphorus (P) enters the water bodies via wastewater discharges or agricultural runoff, triggering serious environmental problems such as eutrophication. In contrast, P as an irreplaceable key resource, presents notable supply-demand contradictions due to ineffective recovery mechanisms. Hence, constructing a system that simultaneously reduce P contaminants and effective recycling has profound theoretical and practical implications. Metal element-based adsorbents, including metal (hydro) oxides, layered double hydroxides (LDHs) and metal-organic frameworks (MOFs), exhibit a significant chaperone effect stemming from strong orbital hybridization between their intrinsic Lewis acid sites and P (Lewis base). This review aims to parse the structure-effect relationship between metal element-based adsorbents and P, and explores how to optimize the P removal properties. Special emphasis is given to the formation of the metal-P chemical bond, which not only depends on the type of metal in the adsorbent but also closely relates to its surface activity and pore structure. Then, we delve into the intrinsic mechanisms behind these adsorbents' remarkable adsorption capacity and precise targeting. Finally, we offer an insightful discussion of the prospects and challenges of metal element-based adsorbents in terms of precise material control, large-scale production, P-directed adsorption and effective utilization.

The Causal Association Between Blood Lead and Sleep Disorders: Evidence from National Health and Nutrition Examination Survey and Mendelian Randomization Analysis.

BACKGROUND: Poor sleep quality is a global public health concern. This study aimed to identify the risk factors for sleep disorders and clarify their causal effects. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) and Mendelian randomization (MR)-Base databases. Baseline characteristics of individuals with and without sleep disorders were compared. A multivariate logistic regression analysis was performed to calculate the effects of each variable on sleep disorders. Causal effects of blood lead levels and hypertension on sleep disorders were assessed using MR analysis. RESULTS: In total, 3660 individuals were enrolled in the study. The prevalence of self-reported sleep disorders was 26.21%. Serum lead level, serum mercury level, serum retinol level, prevalence of hypertension, and daily vigorous work duration were significantly higher for those in the sleep disorders group than the control group. After adjusting for various covariates, the effects of serum lead and hypertension on sleep disorders were stable from logistic regression models 1-4. MR analysis showed that blood lead levels were causally related to the risk of sleep disorders (odds ratio (OR) = 1.09, 95% confidence interval (CI) 1.01-1.17, P = 0.030). There was no causal link between elevated blood pressure and sleep disorders (OR = 0.99, 95% CI 0.94-1.04, P = 0.757). Goodness-of-fit tests and sensitivity analyses were used to verify the reliability of the results. CONCLUSIONS: Blood lead is positively and causally associated with an increased risk of sleep disorders. These findings provide a novel perspective regarding sleep protection. Taking effective measures to reduce lead exposure may significantly improve sleep health.

Climate match is key to predict range expansion of the world's worst invasive terrestrial vertebrates.

Understanding the determinants of the range expansion of invasive alien species is crucial for developing effective prevention and control strategies. Nevertheless, we still lack a global picture of the potential factors influencing the invaded range expansion across taxonomic groups, especially for the world's worst invaders with high ecological and economic impacts. Here, by extensively collecting data on 363 distributional ranges of 19 of world's worst invasive terrestrial vertebrates across 135 invaded administrative jurisdictions, we observed remarkable variations in the range expansion across species and taxonomic groups. After controlling for taxonomic and geographic pseudoreplicates, model averaging analyses based on generalized additive mixed-effect models showed that species in invaded regions having climates more similar to those of their native ranges tended to undergo a larger range expansion. In addition, as proxies of propagule pressure and human-assisted transportation, the number of introduction events and the road network density were also important predictors facilitating the range expansion. Further variance partitioning analyses validated the predominant role of climate match in explaining the range expansion. Our study demonstrated that regions with similar climates to their native ranges could still be prioritized to prevent the spread of invasive species under the sustained global change.

Investigation and Application of Perforation Optimization Method on Shale Gas Horizontal Well with Numerical Simulation of Multicluster Fracturing under Dense-Segment Pattern.

Multicluster fracturing of horizontal wells has evolved into a mature and widely adopted technique for exploiting unconventional oil and gas fields. A well-designed multicluster completion strategy can yield an ideal fracturing outcome, significantly enhancing production rates and potentially delivering substantial economic benefits. Nevertheless, empirical evidence suggests that fractured horizontal wells frequently exhibit pronounced nonuniform production profiles, a prevalent issue stemming from the irregular geometry of propagated fractures. This issue critically constrains production rates. To mitigate the adverse effects of low-uniformity fracture propagation, it is imperative to elucidate the factors influencing uniformity levels and their corresponding patterns. Despite extensive discussions on hydraulic fracture propagation mechanisms and optional factors in hydraulic fracturing engineering, there exists a notable oversight regarding the optimization of perforation parameters to achieve improved fracturing uniformity during well completion procedures. This paper introduces an optimization method for perforation parameters based on a fully coupled pseudo-3D numerical model of multicluster fracturing. The impact patterns of cluster spacing, perforation number, and initial perforation diameter on multifracture propagation results and uniformity levels are thoroughly examined. The multicluster fracturing model, developed using the displacement discontinuous method (DDM), is coupled with material balance, pressure transmission, hole erosion computation, and initiation asynchrony estimation. To quantify the uniformity level of the fracturing result, the modified propagation uniformity index (Ufm) is employed. Simulation results from 20 cases are categorized into six groups based on varied changing patterns of perforation parameters, leading to the identification of five recommendations for optimizing perforation parameters. By implementation of the discussed optimized perforation parameters, successful fracturing outcomes were realized.

Correlation of Circadian Rhythms and Improvement of Depressive Symptoms in Acute Ischemic Stroke Patients.

OBJECTIVES: To investigate the correlation between evening melatonin timing secretion, dim light melatonin onset (DLMO), and post-stroke depression (PSD) in acute ischemic stroke (AIS) patients and their influence on the improvement of depressive symptoms. MATERIALS AND METHODS: 120 patients with a recent magnetic resonance imaging confirmed stroke were included. Salivary melatonin samples were collected at 5 time points within 1 week after hospitalization (7 p.m.-11 p.m., 1 sample per hour). The circadian phase was defined by calculating DLMO secretion. Post-stroke depressive symptoms were evaluated by the 17-item Hamilton Rating Scale for Depression (HRSD) both on day 7 of hospitalization and 3 months after stroke. Patients were divided into PSD and non-PSD groups based on whether the acute phase HRSD score was ≥8. Similarly, patients were divided into the improved depressive symptoms (IDS) and no improvement in depressive symptoms (non-IDS) groups based on whether the HRSD score at 3 months was lower than at baseline. Neurological recovery at 3 months was assessed using the modified Rankin Scale (mRS). RESULTS: The difference in DLMO between PSD and non-PSD patients was not statistically significant (p =0.173). In the non-IDS group, there was a significant decrease in melatonin secretion at 10 p.m. (p =0.012), and DLMO was significantly later than in the IDS group (p =0.017). Logistic regression analysis showed that DLMO (OR 1.91, 95%CI:1.13-3.23, p = 0.016) was an independent risk factor for persistent no improvement in depressive symptoms, which was associated with a markedly worse prognosis (p <0.001). CONCLUSION: Our findings suggest possible interventions for the very early identification of non- IDS patients.

Single substrate-functionalized molybdenum oxide nanozyme for specific colorimetric monitoring of xanthine oxidase activity.

Xanthine-functionalized molybdenum oxide nanodots (X-MoO3-x NDs) with peroxidase (POD)-like activity were developed for selective, sensitive, and facile colorimetric quantification of xanthine oxidase (XO). Xanthine functionalization can not only be favorable for the successful nanozyme preparation, but also for the specific recognition of XO as well as the simultaneous generation of hydrogen peroxide, which was subsequently transformed into hydroxyl radical to oxidize the chromogenic reagent based on the POD-like catalysis. Under the optimized conditions, the colorimetric biosensing platform was established for XO assay without addition of further substrates, showing good linearity relationship between absorbance difference (ΔA) and XO concentrations in the range 0.05-0.5 U/mL (R2 = 0.998) with a limit of detection (LOD) of 0.019 U/mL. The quantification of XO occurs in 25 min, which is superior to the previously reported and commercial XO assays. The proposed method has been successfully used in the assay of human serum samples, showing its high potential in the field of clinical monitoring.

Ecological evolution of algae in connected reservoirs under the influence of water transfer: Algal density, community structure, and assembly processes.

Reservoir connectivity provides a solution for regional water shortages. Understanding the water quality of reservoirs and the response of algal communities to water transfer could provide the basis for a long-term evolutionary model of reservoirs. In this study, a water-algal community model was established to study the effects of water transfer on water quality and algal communities in reservoirs. The results showed that water transfer significantly decreased total nitrogen and nitrate concentrations. However, the water transfer resulted in an increase in the CODMn concentration and conductivity in the receiving reservoir. Additionally, the algal density and chlorophyll-a (chl-a) concentration showed an increase with water transfer. Bacillariophyta, Cyanophyta, and Chlorophyta were the dominant algal phyllum in all three reservoirs. Water transfer induced the evolution of the algal community by driving changes in the chemical parameters of the receiving reservoir and led to more complex relationships within the algal community. The effects of stochastic processes on algal communities were also enhanced in the receiving reservoirs. These results provide specific information for water quality safety management and eutrophication prevention in connected reservoirs.

Social media unveils the hidden but high magnitude of human-mediated biological invasions in China.

Humans are responsible for the release of many non-native animals into the wild. However, these releases occur randomly and are difficult to monitor. Here, using two of the worst invasive herpetofauna as model taxa, we applied an iEcology approach and found a high magnitude of human-mediated releases in China, suggesting this approach can be used to monitor introductions and advise management bodies in a timely manner.

Chemical-free vacuum ultraviolet irradiation as ultrafiltration membrane pretreatment technique: Performance, mechanisms and DBPs formation.

Membrane fouling induced by natural organic matter (NOM) has seriously affected the further extensive application of ultrafiltration (UF). Herein, a simple, green and robust vacuum ultraviolet (VUV) technology was adopted as pretreatment before UF and ultraviolet (UV) technology was used for comparison. The results showed that control effect of VUV pretreatment on membrane fouling was better than that of UV pretreatment, as evidenced by the increase of normalized flux from 0.27 to 0.38 and 0.73 after 30 min UV or VUV pretreatment, respectively. This is related to the fact that VUV pretreatment exhibited stronger NOM degradation ability than UV pretreatment owing to the formation of HO•. The steady-state concentration of HO• was calculated as 3.04 × 10-13 M and the cumulative exposure of HO• reached 5.52 × 10-10 M s after 30 min of VUV irradiation. And the second-order rate constant between NOM and HO• was determined as 1.36 × 104 L mg-1 s-1. Furthermore, fluorescence EEM could be applied to predict membrane fouling induced by humic-enriched water. Standard blocking and cake filtration were major fouling mechanisms. Moreover, extension of UV pretreatment time increased the disinfection by-products (DBPs) formation, the DBPs concentration was enhanced from 322.36 to 1187.80 µg/L after 210 min pretreatment. However, VUV pretreatment for 150 min reduced DBPs content to 282.57 µg/L, and DBPs content continued to decrease with the extension of pretreatment time, revealing that VUV pretreatment achieved effective control of DBPs. The variation trend of cytotoxicity and health risk of DBPs was similar to that of DBPs concentration. In summary, VUV pretreatment exhibited excellent effect on membrane fouling alleviation, NOM degradation and DBPs control under a certain pretreatment time.

Circadian Rhythm Disturbance in Acute Ischemic Stroke Patients and Its Effect on Prognosis.

INTRODUCTION: Poststroke sleep disturbances are common and can affect stroke outcomes, but the clinical studies mainly focus on breathing-related sleep disorders, while the bidirectional impact of circadian rhythm dysfunction in ischemic stroke remains unknown. This study observed the characteristics of melatonin secretion in acute ischemic stroke patients and evaluated whether melatonin rhythm impacts the prognosis after stroke by assessing the neurological function, cognition, emotion, and quality of life 3 months after stroke. METHODS: Acute ischemic stroke patients were selected from the Department of Neurology Inpatients of the Second Hospital affiliated with Soochow University from October 2019 to July 2021. Healthy control subjects were recruited at the same time. Demographic and clinical data were collected, and relevant scale scores (including neurological function, cognition, emotion, and sleep) were assessed within 2 weeks of onset and followed up 3 months later. All participants collected salivary melatonin samples on the 4th day of hospitalization and dim light melatonin onset (DLMO) was calculated according to melatonin concentration. Stroke patients were then divided into three groups based on their DLMO values. RESULTS: A total of 74 stroke patients and 33 control subjects were included in this analysis. Compared with healthy controls, stroke patients exhibited a delayed melatonin rhythm during the acute phase of stroke (21:36 vs. 20:38, p = 0.004). Stroke patients were then divided into three groups, namely normal (n = 36), delayed (n = 28), or advanced DLMO (n = 10), based on their DLMO values. A χ2 test showed that there were significant differences in the rate of poor prognosis (p = 0.011) and depression tendency (p = 0.028) among the three groups. A further pairwise comparison revealed that stroke patients with delayed DLMO were more likely to experience poor short-term outcomes than normal DLMO group (p = 0.003). The average melatonin concentration of stroke patients at 5 time points was significantly lower than that of the control group (3.145 vs. 7.065 pg/mL, p < 0.001). Accordingly, we split stroke patients into three groups, namely low melatonin level (n = 14), normal melatonin level (n = 54), or high melatonin level (n = 6). Unfortunately, there were no great differences in the clinical characteristics, cognition, emotion, sleep quality, and short-term outcome among groups. CONCLUSIONS: This is a preliminary study, and our results indicate that changes in melatonin secretion phase of stroke patients may have effect on their short-term prognosis.

Combined passivators regulate physiological, antioxidant potential and metals accumulation in potato grown in metals contaminated soil.

To solve the problem of excessive heavy metals in farmland soil, there is a dire need for research effort to screen for the soil passivator materials. This study aimed to develop a practical novel approach for improving the potato growth and remedial effectiveness of the metals by optimal combination and dosage of various passivators. Experimental treatments were comprised of various levels of passivating agents (sepiolite, quicklime and calcium magnesium phosphate) in individual and combined form. Results showed that application of passivating agents significantly enhanced growth by optimizing photosynthetic attributes, enzymatic antioxidants, and soil health. Balanced application of passivators effectively reduce the bioavailability of metals, curbing their uptake by potato plants. Sole application of all the agents results statistically similar outcomes as compared with combined form. Additionally, passivators indirectly enhance the activity of essential antioxidant enzymes. Synergistic effect of all the agents significantly improved the tuber quality by decreasing the accumulation of proline, malondialdehyde content, and bioaccumulation of Cu, Pb, Cd, and As in potato parts. In crux, combined usage of passivating agents proved to be of better growth, improvement in antioxidative defense system, and better quality of potato. By mitigating heavy metal contamination, passivators not only enhance crop quality and yield but also ensure heavy metal-free potatoes that meet stringent food safety standards.

Aerobic Denitrification Promoting by Actinomycetes Coculture: Investigating Performance, Carbon Source Metabolic Characteristic, and Raw Water Restoration.

The coculture theory that promotes denitrification relies on effectively utilizing the resources of low-efficiency denitrification microbes. Here, the strains Streptomyces sp. PYX97 and Streptomyces sp. TSJ96 were isolated and showed lower denitrification capacity when cultured individually. However, the coculture of strains PYX97 and TSJ96 enhanced nitrogen removal (removed 96.40% of total nitrogen) and organic carbon reduction (removed 92.13% of dissolved organic carbon) under aerobic conditions. Nitrogen balance analysis indicated that coculturing enhanced the efficiency of nitrate converted into gaseous nitrogen reaching 70.42%. Meanwhile, the coculturing promoted the cell metabolism capacity and carbon source metabolic activity. The coculture strains PYX97 and TSJ96 thrived in conditions of C/N = 10, alkalescence, and 150 rpm shaking speed. The coculturing reduced total nitrogen and CODMn in the raw water treatment by 83.32 and 84.21%, respectively. During this treatment, the cell metabolic activity and cell density increased in the coculture strains PYX97 and TSJ96 reactor. Moreover, the coculture strains could utilize aromatic protein and soluble microbial products during aerobic denitrification processes in raw water treatment. This study suggests that coculturing inefficient actinomycete strains could be a promising approach for treating polluted water bodies.

Unraveling genetic causality between type 2 diabetes and pulmonary tuberculosis on the basis of Mendelian randomization.

BACKGROUND: The comorbidity rate between type 2 diabetes mellitus (T2DM) and pulmonary tuberculosis (PTB) is high and imposes enormous strains on healthcare systems. However, whether T2DM is causally associated with PTB is unknown owing to limited evidence from prospective studies. Consequently, the present study aimed to clarify the genetic causality between T2DM and PTB on the basis of Mendelian randomization (MR) analysis. METHODS: Genetic variants for T2DM and PTB were obtained from the IEU OpenGWAS project. The inverse variance weighted method was used as the main statistical analysis method and was supplemented with MR-Egger, weighted median, simple mode, and weighted mode methods. Heterogeneity was analyzed using Cochran's Q statistic. Horizontal pleiotropy was assessed using the MR-PRESSO global test and MR-Egger regression. Robustness of the results was verified using the leave-one-out method. RESULTS: A total of 152 independent single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) to assess the genetic causality between T2DM and PTB. Patients with T2DM had a higher risk of PTB at the genetic level (odds ratio (OR) for MR-Egger was 1.550, OR for weighted median was 1.540, OR for inverse variance weighted was 1.191, OR for simple mode was 1.629, OR for weighted mode was 1.529). There was no horizontal pleiotropy or heterogeneity among IVs. The results were stable when removing the SNPs one by one. CONCLUSIONS: This is the first comprehensive MR analysis that revealed the genetic causality between T2DM and PTB in the East Asian population. The study provides convincing evidence that individuals with T2DM have a higher risk of developing PTB at the genetic level. This offers a significant basis for joint management of concurrent T2DM and PTB in clinical practice.