The relationship between diabetes and the dementia risk: a meta-analysis.

BACKGROUND: The link between diabetes and dementia risk is not well understood. This study evaluates the factors linking diabetes to dementia onset, providing guidance for preventing dementia in diabetic patients. METHODS: This analysis utilized databases such as PubMed, Embase, Web of Science, and the Cochrane Library to review literature from January 31, 2012, to March 5, 2023. Articles were rigorously assessed using specific inclusion and exclusion criteria. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies. Data analysis was performed with STATA 15.0. RESULTS: The study analyzed 15 articles, covering 10,103,868 patients, with 8,821,516 diagnosed with diabetes. The meta-analysis reveals a substantial association between diabetes and an increased risk of dementia [RR: 1.59, 95%CI (1.40-1.80), P < 0.01, I²=96.4%]. A diabetes duration of less than five years is linked to a higher dementia risk [RR: 1.29, 95%CI (1.20-1.39), P < 0.01, I²=92.6%]. Additionally, hypoglycemia significantly raises dementia risk [RR: 1.56, 95%CI (1.13-2.16), P < 0.01, I²=51.5%]. Analyses of blood sugar control, glycated hemoglobin, and fasting blood sugar indicated no significant effects on the onset of dementia. CONCLUSION: Diabetes notably increases dementia risk, particularly where diabetes duration is under five years or hypoglycemia is present. REGISTRATION: The research protocol was registered with PROSPERO and assigned the registration number CRD42023394942.

Emerging Chemodynamic Nanotherapeutics for Cancer Treatment.

Chemodynamic therapy (CDT) has emerged as a transformative paradigm in the realm of reactive oxygen species -mediated cancer therapies, exhibiting its potential as a sophisticated strategy for precise and effective tumor treatment. CDT primarily relies on metal ions and hydrogen peroxide to initiate Fenton or Fenton-like reactions, generating cytotoxic hydroxyl radicals. Its notable advantages in cancer treatment are demonstrated, including tumor specificity, autonomy from external triggers, and a favorable side-effect profile. Recent advancements in nanomedicine are devoted to enhancing CDT, promising a comprehensive optimization of CDT efficacy. This review systematically elucidates cutting-edge achievements in chemodynamic nanotherapeutics, exploring strategies for enhanced Fenton or Fenton-like reactions, improved tumor microenvironment modulation, and precise regulation in energy metabolism. Moreover, a detailed analysis of diverse CDT-mediated combination therapies is provided. Finally, the review concludes with a comprehensive discussion of the prospects and intrinsic challenges to the application of chemodynamic nanotherapeutics in the domain of cancer treatment.

A new substrate equalization method for optimizing the influent conditions and fluid flow patterns of a multifed upflow anaerobic sludge blanket reactor with mature anammox granules.

To improve nitrogen removal efficiency (NRE) and achieve homogenous distribution of anammox sludge and substrate, a new substrate equalization theory and a cumulative overload index was proposed for multifed upflow anaerobic sludge bed (MUASB) reactors with mature anammox granules. The performance and flow patterns of MUASB reactors were investigated under various influent conditions. The results showed that the nitrogen removal performance and stability of MUASB reactors could be optimized by minimizing the cumulative load. The NRE gradually increased from 83.3 ± 2.2 %, 86.8 ± 4.2 % to 89.3 ± 4.1 % and 89.7 ± 1.6 % in feeding flow tests and feeding port tests, respectively. Furthermore, the flow patterns were compared based on residence time distribution and computational fluid dynamics, indicating that a better equilibrium distribution of microorganisms and substrates could be achieved in the MUASB reactors under the lowest cumulative load. Therefore, substrate equalization theory can be used to optimize the nitrogen removal performance of MUASB reactors with low-carbon footprints.

Prediction of intraoperative red blood cell transfusion in valve replacement surgery: machine learning algorithm development based on non-anemic cohort.

Background: Our study aimed to develop machine learning algorithms capable of predicting red blood cell (RBC) transfusion during valve replacement surgery based on a preoperative dataset of the non-anemic cohort. Methods: A total of 423 patients who underwent valvular replacement surgery from January 2015 to December 2020 were enrolled. A comprehensive database that incorporated demographic characteristics, clinical conditions, and results of preoperative biochemistry tests was used for establishing the models. A range of machine learning algorithms were employed, including decision tree, random forest, extreme gradient boosting (XGBoost), categorical boosting (CatBoost), support vector classifier and logistic regression (LR). Subsequently, the area under the receiver operating characteristic curve (AUC), accuracy, recall, precision, and F1 score were used to determine the predictive capability of the algorithms. Furthermore, we utilized SHapley Additive exPlanation (SHAP) values to explain the optimal prediction model. Results: The enrolled patients were randomly divided into training set and testing set according to the 8:2 ratio. There were 16 important features identified by Sequential Backward Selection for model establishment. The top 5 most influential features in the RF importance matrix plot were hematocrit, hemoglobin, ALT, fibrinogen, and ferritin. The optimal prediction model was CatBoost algorithm, exhibiting the highest AUC (0.752, 95% CI: 0.662-0.780), which also got relatively high F1 score (0.695). The CatBoost algorithm also showed superior performance over the LR model with the AUC (0.666, 95% CI: 0.534-0.697). The SHAP summary plot and the SHAP dependence plot were used to visually illustrate the positive or negative effects of the selected features attributed to the CatBoost model. Conclusions: This study established a series of prediction models to enhance risk assessment of intraoperative RBC transfusion during valve replacement in no-anemic patients. The identified important predictors may provide effective preoperative interventions.

Successful surgical treatment of impending paradoxical embolism with pulmonary embolism and myocardial infarction.

BACKGROUND: Paradoxical embolism is a rare cause of acute arterial occlusion. This phenomenon arises when embolic material travels from the venous system crosses an abnormal shunt such as patent foramen ovale, atrial septal defects, ventricular septal defects, or pulmonary arteriovenous malformations, into the arterial system. Impending paradoxical embolism refers to the presence of an entrapped thrombus in the patent foramen ovale. CASE PRESENTATION: We report a case of a 68-year-old female patient who presented with an impending paradoxical embolism, alongside both concomitant pulmonary embolism and myocardial infarction with ST-segment elevation. Swiftly addressed through emergency cardiac surgery and systemic anticoagulation, the patient's condition was effectively treated. CONCLUSIONS: While the ideal treatment strategy for impending paradoxical embolism remains a topic of debate due to limited and inconclusive evidence, emergent open surgery should be contemplated in patients as it signifies a critical clinical emergency.

Spatial accessibility and equity of residential care facilities in Beijing from 2010 to 2020.

In recent years, the aging population in Beijing has rapidly increased and the demand for residential care facilities (RCFs) has also risen. As RCFs have quickly developed, the question of whether residential care resources dynamically match the changes in the demand of the elderly population is an urgent issue that must be addressed. This study analyzes the spatiotemporal variation in the supply and demand of RCFs, applies a Gaussian two-step floating catchment area method with a multi-level search radius to measure the spatial accessibility of RCFs in Beijing in 2010 and 2020, and evaluates the equity of spatial accessibility. The results show that the elderly population was decentralized from the central urban area to New Urban Development Area. However, the distribution of RCF beds shows further agglomeration towards the central urban area. The accessibility of residential care resources in the central urban area and New Urban Development Area has increased, while accessibility in Ecological Protection Area has decreased. The spatial disparities in accessibility have been reduced and the spatial equity in accessibility has been improved over the past decade. The findings provide policy recommendations for the future allocation of RCFs by considering the spatiotemporal changes in the distribution of the supply and demand of residential care resources.

Prenatal hormone stress triggers embryonic cardiac hypertrophy outcome by ubiquitin-dependent degradation of mitochondrial mitofusin 2.

Prenatal stress has been extensively documented as a contributing factor to adverse cardiac development and function in fetuses and infants. The release of glucocorticoids (GCs), identified as a significant stressor, may be a potential factor inducing cardiac hypertrophy. However, the underlying mechanism remains largely unknown. Herein, we discovered that corticosterone (CORT) overload induced cardiac hypertrophy in embryonic chicks and fetal mice in vivo, as well as enlarged cardiomyocytes in vitro. The impaired mitochondria dynamics were observed in CORT-exposed cardiomyocytes, accompanied by dysfunction in oxidative phosphorylation and ATP production. This phenomenon was found to be linked to decreased mitochondrial fusion protein mitofusin 2 (MFN2). Subsequently, we found that CORT facilitated the ubiquitin-proteasome-system-dependent degradation of MFN2 with an enhanced binding of appoptosin to MFN2, serving as the underlying cause. Collectively, our findings provide a comprehensive understanding of the mechanisms by which exposure to stress hormones induces cardiac hypertrophy in fetuses.

Exploring the significance of tumor volume in endometrial cancer: Clinical pathological features, prognosis, and adjuvant therapies.

To assist clinicians in formulating treatment strategies for endometrial cancer (EC), this retrospective study explores the relationship between tumor volume and clinical pathological features, as well as prognosis, in patients undergoing staging surgery. Preoperative pelvic MRI examinations were conducted on 234 histologically confirmed EC patients. The ITK-SNAP software was employed to manually delineate the region of interest in the MRI images and calculate the tumor volume (MRI-TV). The analysis focused on investigating the relationship between MRI-TV and the clinical pathological features and prognosis of EC patients. Larger MRI-TV was found to be associated with various adverse prognostic factors (G3, deep myometrial invasion, cervical stromal invasion, lymphovascular space invasion, lymph node metastasis, advanced international federation of gynecology and obstetrics staging, and receipt of adjuvant therapy). The receiver operating characteristic curve indicated that MRI-TV ≥ 8 cm3 predicted deep myometrial invasion, and MRI-TV ≥ 12 cm3 predicted lymph node metastasis. Penalized spline (P-spline) regression analysis identified 14 cm3 of MRI-TV as the optimal prognostic cutoff value. MRI-TV ≥ 14 cm3 was an independent prognostic factor for overall survival and disease-free survival. For patients with MRI-TV ≥ 14 cm3, the disease-free survival rate with adjuvant therapy was superior to that of the sole staging surgery group. This study demonstrates a significant correlation between MRI-TV and clinical pathological features and prognosis in EC. For patients with MRI-TV ≥ 14 cm3, staging surgery followed by adjuvant therapy was superior to sole staging surgery.

Real-Time Optimal States Estimation with Inertial and Delayed Visual Measurements for Unmanned Aerial Vehicles.

Motion estimation is a major issue in applications of Unmanned Aerial Vehicles (UAVs). This paper proposes an entire solution to solve this issue using information from an Inertial Measurement Unit (IMU) and a monocular camera. The solution includes two steps: visual location and multisensory data fusion. In this paper, attitude information provided by the IMU is used as parameters in Kalman equations, which are different from pure visual location methods. Then, the location of the system is obtained, and it will be utilized as the observation in data fusion. Considering the multiple updating frequencies of sensors and the delay of visual observation, a multi-rate delay-compensated optimal estimator based on the Kalman filter is presented, which could fuse the information and obtain the estimation of 3D positions as well as translational speed. Additionally, the estimator was modified to minimize the computational burden, so that it could run onboard in real time. The performance of the overall solution was assessed using field experiments on a quadrotor system, compared with the estimation results of some other methods as well as the ground truth data. The results illustrate the effectiveness of the proposed method.

COVID-stasis of Pregnancy: An Increased Prevalence of COVID-19 in Patients with Cholestasis.

OBJECTIVE: To evaluate the relationship between intrahepatic cholestasis of pregnancy (ICP) and coronavirus disease 2019 (COVID-19). STUDY DESIGN: We performed a retrospective cohort study of pregnant women undergoing induction of labor (IOL) at a single institution between May 2020 to January 2021. Primary exposure was diagnosis of intrahepatic cholestasis of pregnancy (ICP). The primary outcome was the prevalence of COVID-19 as determined by reverse-transcriptase polymerase chain reaction testing on nasopharyngeal swabs for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) on routine admission testing. Secondary outcomes were abnormal laboratory values and adverse fetal outcomes. Logistic regression with log link analysis was performed comparing patients undergoing IOL for ICP compared with IOL for all other indications. The moderating effect of ethnicity was assessed by the interaction between ethnicity and ICP in a logistic regression model. The Wilcoxon rank-sum test and Fisher's exact test were performed for the secondary outcome analyses. RESULTS: Over the course of the study, 596 patients underwent IOL: 24 for ICP and 572 for other indications. The overall prevalence of COVID-19 positivity in the cohort was 5.5% (33 of 596). Those with ICP were more likely to test positive for COVID-19 compared with those with other IOL indications (29.2 vs. 4.5%, RR = 6.4, 95% CI: 2.8-12.5, p < 0.001). All patients with ICP who tested positive for COVID-19 were Hispanic. To analyze the moderating effect of ethnicity, the results of the logistic model found the interaction between ethnicity and ICP to not be significant (p = 0.991). In patients with ICP, the median AST (aspartate aminotransferase) was higher than those with COVID-19 (p = 0.0182). There were no adverse fetal outcomes in the ICP group. CONCLUSION: In this single-site retrospective cohort study, we demonstrated an increased prevalence of COVID-19 in those with ICP in general and among Hispanic patients specifically. Despite this difference, there was no increased risk of adverse fetal outcomes. KEY POINTS: · There is an increased prevalence of COVID-19 among Hispanic patients with ICP.. · The median AST of COVID-19-positive patients was significantly higher than COVID-19-negative patients.. · There was no increased risk of adverse fetal outcomes in with COVID-19 and ICP..

Self-engineered binary nanoassembly enabling closed-loop glutathione depletion-amplified tumor ferroptosis.

Ferroptosis has emerged as a promising target for anticancer treatment, comprising iron-dependent lipid peroxidation and excessive accumulation of reactive oxygen species. Given that glutathione (GSH) overproduced in tumor cells antagonizes the cellular oxidation system, the reduction of GSH production has been extensively explored to induce ferroptosis. However, reducing GSH production alone is insufficient to trigger an intense lipid peroxidation storm. It is highly desirable to achieve systemic GSH depletion through simultaneous production and consumption intervention. Herein, we propose a bidirectional blockage strategy for closed-loop GSH depletion-amplified tumor ferroptosis. Sorafenib (Sor) and gambogic acid (GA) were elaborately fabricated as a self-engineered carrier-free nanoassembly without any nanocarrier materials. The PEGylated dual-drug nanoassembly enables favorable co-delivery and tumor-specific release of Sor and GA. Notably, a closed-loop GSH depletion is observed as a result of a Sor-induced decrease in GSH production and GA-accelerated GSH consumption in vitro and in vivo. As expected, this uniquely engineered dual-drug nanoassembly demonstrates vigorous antitumor activity in 4T1 breast tumor-bearing mice. This study presents a novel nanotherapeutic modality for ferroptosis-driven cancer treatment.

U.S. States' COVID-19 physical distancing policies and working-age adult mental health outcomes.

In the early months of the COVID-19 pandemic, states enacted multiple policies to reduce in-person interactions. Scholars have speculated that these policies may have contributed to adverse mental health outcomes. This study examines potential associations between states' COVID-19 physical distancing policies and working-age (18-64) adults' self-reported mental health. Mental health outcomes (depression, anxiety, worsened mental health, and sought treatment for anxiety or depression) are from the National Wellbeing Survey collected from working-age adults in the United States (U.S.) February 1 to March 18, 2021 (N = 3,804). Data on 12 state policies are from the COVID-19 U.S. State Policy Database. Analyses included logistic regression and Bayesian group index modeling, which identified sets, or "bundles," of policies that were associated with each mental health outcome. Multiple policies (both separately and in bundles) were associated with adverse mental health outcomes, with certain policies (closures and curfews on retail and other businesses) being particularly important. A one-month increase in exposure to respective model-derived physical distancing policy bundles was associated with a 36% increase in the odds of reporting that COVID-19 worsened one's mental health (odds ratio [OR] = 1·36; 95% credible interval [CRI] = 1·01 to 1·80), a 6% increase in the odds of meeting the clinical threshold for anxiety (OR = 1·06; CRI = 0·99 to 1·16), and a 15% increase in the odds of seeking treatment for anxiety or depression (OR = 1·15; CRI = 1·02 to 1·49). To accurately understand the role of states' COVID-19 policies on mental health during the pandemic, researchers must consider how collections of policies might influence outcomes.

Honeycomb-like 3D ordered macroporous SiOx/C nanoarchitectures with carbon coating for high-performance lithium storage.

SiOx anodes are garnering significant interest in lithium-ion batteries (LIBs) due to theirs low voltage plateau and high capacity. However, critical drawbacks, including high expansion rate and low electronic conductivity, severely limit their practical applications. While 0D, 1D, and 2D scale nanostructures have been proven to mitigate these issues, these materials tend to accumulate after prolonged cycling, leading to adverse effects on the mass transfer processes within the electrode. Herein, we have developed a honeycomb-like SiOx/C nanoarchitecture with carbon coating based on a 3D ordered macroporous (3DOM) structure. The 3D interconnected pore windows facilitate the diffusion and transport of lithium ions (Li+) in the electrolyte, and the extremely thin walls (<15 nm) provide a shorter transport path for Li+ in the solid. The carbon cladding buffers volume expansion and enhances electronic conductivity. The as-prepared anode demonstrates a high reversible capacity of 1068 mAh/g and an initial coulombic efficiency of 70.7 %. It maintains a capacity of 644 mAh/g (capacity retention of 84.63 %) even at a high current of 1.0 A/g after 700 cycles. The unique honeycomb-like structure offers enormous insights into the study of energy storage in 3D materials.

Effects of N-acetyl-L-cysteine polysulfides on periodontitis in a mouse model.

BACKGROUND: Polysulfides are reported to be involved in various important biological processes. N-acetyl-l-cysteine polysulfide with 2 sulfane sulfur atoms (NAC-S2) regulates diverse toll-like receptor (TLR) signaling pathways. Here, we aimed to determine the role of NAC-S2 in periodontitis and explore the potential mechanism. METHODS: A periodontitis mouse model was established by ligating the subgingival between the first and second molars in wild-type, TLR4-/- , and Myd88-/- mice. RESULTS: NAC-S2 did not affect the proportion of macrophages (CD11b+ F4/80+ ) or neutrophils (CD11b+ GR-1+ ) in the bone marrow. Mechanically, lipopolysaccharides (LPS), Zymosan A, or poly I: C induced tumor necrosis factor (TNF), interleukin (IL)-6, and IL-1ß expression in bone marrow-derived macrophages (BMDMs) could be inhibited by NAC-S2. On the other hand, NAC-S2 suppressed the phosphorylation levels of IκB-α, p65, and IκB kinase (IKK)-ß induced by LPS in BMDMs, while LPS induced phosphorylation of ERK1/2, p38, and transforming growth factor ß-activated kinase 1 (TAK1) could not be affected by NAC-S2. In wild-type periodontitis mice, NAC-S2 administration decreased the cemento-enamel-junction-alveolar bone crest (CEJ-ABC) distance and the relative mRNA expression of TNF, IL-6, and IL-1ß, while such phenomena could not be observed in TLR4 deficiency or Myd88 deficiency mice. CONCLUSIONS: All of these results indicate that NAC-S2 ameliorates TLR4/NF-κB pathway mediated inflammation in mouse periodontitis model.

Genome-Wide Analysis and Expression Profiling of the Glutathione Peroxidase-like Enzyme Gene Family in Solanum tuberosum.

Glutathione peroxidase-like enzyme is an important enzymatic antioxidant in plants. It is involved in scavenging reactive oxygen species, which can effectively prevent oxidative damage and improve resistance. GPXL has been studied in many plants but has not been reported in potatoes, the world's fourth-largest food crop. This study identified eight StGPXL genes in potatoes for the first time through genome-wide bioinformatics analysis and further studied the expression patterns of these genes using qRT-PCR. The results showed that the expression of StGPXL1 was significantly upregulated under high-temperature stress, indicating its involvement in potato defense against high-temperature stress, while the expression levels of StGPXL4 and StGPXL5 were significantly downregulated. The expression of StGPXL1, StGPXL2, StGPXL3, and StGPXL6 was significantly upregulated under drought stress, indicating their involvement in potato defense against drought stress. After MeJA hormone treatment, the expression level of StGPXL6 was significantly upregulated, indicating its involvement in the chemical defense mechanism of potatoes. The expression of all StGPXL genes is inhibited under biotic stress, which indicates that GPXL is a multifunctional gene family, which may endow plants with resistance to various stresses. This study will help deepen the understanding of the function of the potato GPXL gene family, provide comprehensive information for the further analysis of the molecular function of the potato GPXL gene family as well as a theoretical basis for potato molecular breeding.

Growth of preference for solitude in urban and rural Chinese adolescents.

Introduction: As individuals enter adolescence, their preference for solitude (PFS) increases with age, which may be a result of balancing the need for social affiliation and the need for autonomy and independence. These needs are shaped by the social-cultural contexts, and thus the growth rate of PFS may differ across social-cultural contexts.This study examined to what extent the developmental trajectory of PFS differed between urban and rural Chinese adolescents. Methods: Adolescents in urban (n = 326,168 boys, Mage =12.00 years, SD = 0.61) and rural (n = 449, 198 boys, Mage =11.82 years, SD = 0.58) regions in China reported their PFS and shyness each year from Grade 6 to Grade 8. Longitudinal measurement invariance of PFS was established between the urban and rural samples. Location and gender differences in the intercept and the slope of PFS were examined using a latent growth model, while controlling for shyness at each time point. Results: The analyses revealed that adolescents in both urban and rural regions showed an increasing trajectory of PFS. Although urban and rural adolescents did not differ in the initial level of PFS at Grade 6, urban adolescents' PFS increased faster than that of the rural adolescents. The urban-rural difference in the slope of PFS remained significant after controlling for the associations between the intercept and the slope of PFS and shyness at each time point. In addition, in the rural region, boys showed a faster increase of PFS than girls, yet gender differences in the initial level of PFS and the developmental trajectory in the urban region were nonsignificant. Discussion: The findings reveal a normative increasing trend of PFS during early adolescence and faster increase for urban than rural adolescents. To promote adolescents' psychological well-being, parents, teachers and practitioners need to help adolescents establish a good balance between social interaction and solitude. When deciding what is a good balance, it is important to consider the social-cultural context.

Reducing lipid peroxidation attenuates stress-induced susceptibility to herpes simplex virus type 1.

Psychological stress increases the susceptibility to herpes simplex virus type 1 (HSV-1) infection. There is no effective intervention due to the unknown pathogenesis mechanisms. In this study we explored the molecular mechanisms underlying stress-induced HSV-1 susceptibility and the antiviral effect of a natural compound rosmarinic acid (RA) in vivo and in vitro. Mice were administered RA (11.7, 23.4 mg·kg-1·d-1, i.g.) or acyclovir (ACV, 206 mg·kg-1·d-1, i.g.) for 23 days. The mice were subjected to restraint stress for 7 days followed by intranasal infection with HSV-1 on D7. At the end of RA or ACV treatment, mouse plasma samples and brain tissues were collected for analysis. We showed that both RA and ACV treatment significantly decreased stress-augmented mortality and alleviated eye swelling and neurological symptoms in HSV-1-infected mice. In SH-SY5Y cells and PC12 cells exposed to the stress hormone corticosterone (CORT) plus HSV-1, RA (100 µM) significantly increased the cell viability, and inhibited CORT-induced elevation in the expression of viral proteins and genes. We demonstrated that CORT (50 µM) triggered lipoxygenase 15 (ALOX15)-mediated redox imbalance in the neuronal cells, increasing the level of 4-HNE-conjugated STING, which impaired STING translocation from the endoplasmic reticulum to Golgi; the abnormality of STING-mediated innate immunity led to HSV-1 susceptibility. We revealed that RA was an inhibitor of lipid peroxidation by directly targeting ALOX15, thus RA could rescue stress-weakened neuronal innate immune response, thereby reducing HSV-1 susceptibility in vivo and in vitro. This study illustrates the critical role of lipid peroxidation in stress-induced HSV-1 susceptibility and reveals the potential for developing RA as an effective intervention in anti-HSV-1 therapy.

Evaluation of Left Ventricular Systolic Function Using Layer-Specific Strain in Rats Performing Endurance Exercise: A Pilot Study.

OBJECTIVE: The functional characteristics of exercise-induced myocardial hypertrophy were studied in a rat model in conjunction with ultrasound layered strain technique to investigate the hidden changes in the heart brought about by exercise. METHODS: Forty specific pathogen free (SPF) adult Sprague-Dawley rats were selected and randomly divided into two groups of 20 exercise and 20 control rats. The longitudinal and circumferential strain parameters were measured using the ultrasonic stratified strain technique. The differences between the two groups and the predictive effect of stratified strain parameters on left ventricular systolic function were analyzed. RESULTS: The exercise group had significantly higher global endocardial myocardial longitudinal strain (GLSendo), global mid-myocardial global longitudinal strain (GLSmid) and global endocardial myocardial global longitudinal strain (GCSendo) values than the control group (p < 0.05). Even though global mid-myocardial circumferential strain (GCSmid) and global epicardial myocardial circumferential strain (GCSepi) were higher in the exercise group than in the control group, statistical significance was not reached (p > 0.05). Conventional echocardiography parameters were well correlated with GLSendo, GLSmid, and GCSendo (p < 0.05). GLSendo was the best predictor of left ventricular myocardial contractile performance in athletes determined using the receiver operating characteristic curve, with an area under the curve of 0.97, sensitivity of 95% and specificity of 90%. CONCLUSION: Rats performing endurance exercise exhibited subclinical changes in the heart after prolonged high-intensity exercise. A stratified strain parameter, GLSendo, played an important role in the evaluation of LV systolic performance in exercising rats.

Coronavirus RNA-dependent RNA polymerase interacts with the p50 regulatory subunit of host DNA polymerase delta and plays a synergistic role with RNA helicase in the induction of DNA damage response and cell cycle arrest in the S phase.

Disruption of the cell cycle is a common strategy shared by many viruses to create a conducible cellular microenvironment for their efficient replication. We have previously shown that infection of cells with gammacoronavirus infectious bronchitis virus (IBV) activated the theataxia-telangiectasia mutated (ATM) Rad3-related (ATR)/checkpoint kinase 1 (Chk1) pathway and induced cell cycle arrest in S and G2/M phases, partially through the interaction of nonstructural protein 13 (nsp13) with the p125 catalytic subunit of DNA polymerase delta (pol δ). In this study, we show, by GST pulldown, co-immunoprecipitation and immunofluorescent staining, that IBV nsp12 directly interacts with the p50 regulatory subunit of pol δ in vitro and in cells overexpressing the two proteins as well as in cells infected with a recombinant IBV harbouring an HA-tagged nsp12. Furthermore, nsp12 from severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 was also able to interact with p50. These interactions play a synergistic role with nsp13 in the induction of S phase arrest. The fact that subunits of an essential cellular DNA replication machinery physically associate with two core replication enzymes from three different coronaviruses highlights the importance of these associations in coronavirus replication and virus-host interaction, and reveals the potential of targeting these subunits for antiviral intervention.