Catalytic Asymmetric Synthesis of Vicinal Quaternary Stereocenters Enabled by Alkylation of α,α-Disubstituted Aldehydes with 3-Bromooxindoles.

An organocatalytic enantioselective alkylation of α,α-disubstituted aldehydes with 3-bromooxindoles is reported. Enantioenriched oxindoles with vicinal quaternary stereocenters are accessed by an asymmetric conjugate addition process of branched aldehydes with o-azaxylylene intermediates (indol-2-ones). Key to the success of highly diastereo- and enantioselective transformations is the combined use of a triphenylsilyl-protected ß-amino alcohol catalyst derived from the spiropyrrolidine scaffold and 3,5-dinitrobenzoic acid. This study also presents a rare example of aldehyde alkylation with the formation of consecutive quaternary stereocenters.

Corrigendum: Exosomes as a delivery tool of exercise-induced beneficial factors for the prevention and treatment of cardiovascular disease: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fphys.2023.1190095.].

Experimental study on the an-isotropic critical current of REBCO tape.

Superconducting magnets are widely used in nuclear fusion reactors, high-energy particle accelerators, steady-state high magnetic fields, etc. Higher magnetic fields and higher operating temperatures are two application trends. High temperature superconducting (HTS) materials are the only choice for high temperature and high field magnets in the future. The first- and second-generation HTS materials have a typical tape structure; their critical performance is magnetic field angle and temperature dependent. A new test facility is developed for an experimental study on the an-isotropic critical current. The field angle can be changed from 0° to 360° with a resolution of 1°. The rotation deviation angle is measured to be 0.2° when the upper part rotates 90°. The temperature can be changed from 4.2 to 80 K. The temperature errors are ±50, ±80, and ±135 mK for 4.2-20, 20-40, and 40-80 K, respectively. The angle dependence of critical current (Ic) of the tested rare-earth barium copper oxide tape within 0°-30° is strong. From 30° to 90°, the sample Ic almost does not change with the magnetic field angle. The implementation of the project will not only promote the structural optimization of HTS tapes but also promote the miniaturization and economical application of HTS magnets.

Oxygen Vacancy Defect Enhanced NIR-II Photothermal Performance of BiOxCl Nanosheets for Combined Phototherapy of Cancer Guided by Multimodal Imaging.

Narrow photo-absorption range and low carrier utilization are significant barriers that restrict the antitumor efficiency of 2D bismuth oxyhalide (BiOX, X = Cl, Br, I) nanosheets (NSs). Introducing oxygen vacancy (OV) defects can expand the absorption range and improve carrier utilization, which are crucial but also challenging. In this study, a series of BiOxCl NSs with different OV defect concentrations (x = 1, 0.7, 0.5) is developed, which shows full spectrum absorption and strong absorption in the second near-infrared region (NIR-II). Density functional theory calculations are utilized to calculate the crystal structure and density states of BiOxCl, which confirm that part of the carriers is separated by OV enhanced internal electric field to improve carrier utilization. The carriers without redox reaction can be trapped in the OV, leading to great majority of photo-generated carriers promoting the photothermal performance. Triggered by single NIR-II (1064 nm), BiOxCl NSs' bidirectional efficient utilization of carriers achieves synchronously combined phototherapy, leading to enhanced tumor ablation and multimodal diagnostic in vitro and vivo. It is thus believed that this work provides an innovative strategy to design and construct nanoplatforms of indirect band gap semiconductors for clinical phototheranostics.

Co-exposure with cadmium elevates the toxicity of microplastics: Trojan horse effect from the perspective of intestinal barrier.

Microplastics (MPs) have been shown to adsorb heavy metals and serve as vehicles for their environmental transport. To date, insufficient studies have focused on enterohepatic injury in mice co-exposed to both MPs and cadmium (Cd). Here, we report that Cd adsorption increased the surface roughness and decreased the monodispersity of PS-MPs. Furthermore, exposure to both PS-MPs and Cd resulted in a more severe toxic effect compared to single exposure, with decreased body weight gain, shortened colon length, and increased colonic and hepatic inflammatory response observed. This can be attributed to an elevated accumulation of Cd resulting from increased gut permeability, coupled with the superimposed effects of oxidative stress. In addition, using 16 S sequencing and fecal microbiota transplantation, it was demonstrated that gut microbiota dysbiosis plays an essential role in the synergistic toxicity induced by PS-MPs and Cd in mice. This study showed that combined exposure to MPs and Cd induced more severe intestinal and liver damage in mice compared to individual exposure, and provided a new perspective for a more systematic risk assessment process related to MPs exposure.

Prognostic significance of integrating total metabolic tumor volume and EGFR mutation status in patients with lung adenocarcinoma.

Background: The objective of this study was to investigate the prognostic significance of total metabolic tumor volume (TMTV) derived from baseline 18F-2-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), in conjunction with epidermal growth factor receptor (EGFR) mutation status, among patients with lung adenocarcinoma (LUAD). Methods: We performed a retrospective analysis on 141 patients with LUAD (74 males, 67 females, median age 67 (range 34-86)) who underwent 18F-FDG PET/CT and had their EGFR mutation status determined. Optimal cutoff points for TMTV were determined using time-dependent receiver operating characteristic curve analysis. The survival difference was compared using Cox regression analysis and Kaplan‒Meier curves. Results: The EGFR mutant patients (n = 79, 56.0%) exhibited significantly higher 2-year progression-free survival (PFS) and overall survival (OS) rates compared to those with EGFR wild-type (n = 62, 44.0%), with rates of 74.2% vs 69.2% (P = 0.029) and 86.1% vs 67.7% (P = 0.009), respectively. The optimal cutoff values of TMTV were 36.42 cm3 for PFS and 37.51 cm3 for OS. Patients with high TMTV exhibited significantly inferior 2-year PFS and OS, with rates of 22.4% and 38.1%, respectively, compared to those with low TMTV, who had rates of 85.8% and 95.0% (both P < 0.001). In both the EGFR mutant and wild-type groups, patients exhibiting high TMTV demonstrated significantly inferior 2-year PFS and OS compared to those with low TMTV. In multivariate analysis, EGFR mutation status (hazard ratio, HR, 0.41, 95% confidence interval, CI [0.18-0.94], P = 0.034) and TMTV (HR 8.08, 95% CI [2.34-28.0], P < 0.001) were independent prognostic factors of OS, whereas TMTV was also an independent prognosticator of PFS (HR 2.59, 95% CI [1.30-5.13], P = 0.007). Conclusion: Our study demonstrates that the integration of TMTV on baseline 18F-FDG PET/CT with EGFR mutation status improves the accuracy of prognostic evaluation for patients with LUAD.

BadLabel: A Robust Perspective on Evaluating and Enhancing Label-Noise Learning.

Label-noise learning (LNL) aims to increase the model's generalization given training data with noisy labels. To facilitate practical LNL algorithms, researchers have proposed different label noise types, ranging from class-conditional to instance-dependent noises. In this paper, we introduce a novel label noise type called BadLabel, which can significantly degrade the performance of existing LNL algorithms by a large margin. BadLabel is crafted based on the label-flipping attack against standard classification, where specific samples are selected and their labels are flipped to other labels so that the loss values of clean and noisy labels become indistinguishable. To address the challenge posed by BadLabel, we further propose a robust LNL method that perturbs the labels in an adversarial manner at each epoch to make the loss values of clean and noisy labels again distinguishable. Once we select a small set of (mostly) clean labeled data, we can apply the techniques of semi-supervised learning to train the model accurately. Empirically, our experimental results demonstrate that existing LNL algorithms are vulnerable to the newly introduced BadLabel noise type, while our proposed robust LNL method can effectively improve the generalization performance of the model under various types of label noise. The new dataset of noisy labels and the source codes of robust LNL algorithms are available at https://github.com/zjfheart/BadLabels.

Metabolic parameters of pretreatment 2-[18F]fluoro-D-glucose positron emission tomography for prognosis in patients with gallbladder adenocarcinoma: a cohort study.

Background: The incidence of gallbladder adenocarcinoma (GBA) is relatively low, yet it exhibits a high degree of malignancy and a significantly low 5-year survival rate. The aim of this study was to investigate the prognostic value of pretreatment 2-[18F]fluoro-D-glucose positron emission tomography {2-[18F]FDG PET} parameters in predicting outcomes for patients with GBA. Methods: In total, 67 patients with GBA who underwent 2-[18F]FDG PET/computed tomography (CT) before treatment were retrospectively analyzed at Chinese PLA General Hospital from January 2012 to June 2022. All patients were diagnosed by pathology, and their baseline characteristics and clinical data were collected. The metabolic PET parameters of the primary and metastatic lesions were measured, including the maximum and average standardized uptake values (SUVs), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The prognostic significance of metabolic parameters and other clinical variables was assessed using Cox proportional hazards regression models. Differences in progression-free survival (PFS) and overall survival (OS) in relation to metabolic parameters were examined using the Kaplan-Meier method. Results: During a median follow-up period of 14.2 months, 43 patients (64.2%) experienced tumor recurrence or progression, and 38 patients (56.7%) died of cancer. In the univariate Cox regression analysis, liver parenchymal invasion (P=0.001), lymph node metastasis (P=0.007), distant metastases (P=0.049), tumor differentiation (P=0.028), surgery (P=0.014), carcinoembryonic antigen (CEA) level (P=0.030), carbohydrate antigen 19-9 (CA19-9) level (P=0.003), TLG (P=0.005), MTV (P<0.001), sum of the TLGs of the primary and metastatic lesions (total TLG, tTLG) (P=0.001), and sum of the MTVs of the primary and metastatic lesions (total MTV, tMTV) (P<0.001) were significant predictors of PFS. In multivariate analysis, MTV was an independent predictor of PFS [hazard ratio (HR) =2.785; 95% confidence interval (CI): 1.204-6.441; P=0.017]. In the univariate Cox regression analysis, liver parenchymal invasion (P=0.001), lymph node metastasis (P=0.027), distant metastases (P=0.036), tumor differentiation (P=0.047), surgery (P=0.002), neutrophil-to-lymphocyte ratio (NLR) (P=0.011), CEA level (P=0.036), CA19-9 level (P<0.001), TLG (P=0.007), MTV (P<0.001), tTLG (P=0.003), and tMTV (P<0.001) were significant predictors of OS. In the multivariate analysis, higher CA19-9 levels >37 U/mL and a greater tMTV (HR =2.961; 95% CI: 1.092-8.024; P=0.033) were predictive of OS. Conclusions: Our study results suggest that pretreatment 2-[18F]FDG PET parameters can not only assist in the diagnosis of patients with GBA but may also serve as predictive factors for the prognosis of these patients and should thus be applied in their treatment.

Learning a robust foundation model against clean-label data poisoning attacks at downstream tasks.

In the transfer learning paradigm, models that are pre-trained on large datasets are used as the foundation models for various downstream tasks. However, this paradigm exposes downstream practitioners to data poisoning threats, as attackers can inject malicious samples into the re-training datasets to manipulate the behavior of models in downstream tasks. In this work, we propose a defense strategy that significantly reduces the success rate of various data poisoning attacks in downstream tasks. Our defense aims to pre-train a robust foundation model by reducing adversarial feature distance and increasing inter-class feature distance. Experiments demonstrate the excellent defense performance of the proposed strategy towards state-of-the-art clean-label poisoning attacks in the transfer learning scenario.

The moderating role of resilience in the association between workload and depressive symptoms among radiology residents in China: results from a nationwide cross-sectional study.

OBJECTIVES: The current study aimed to explore the moderating role of psychological resilience in the association between workload and depressive symptoms among radiology residents during standardized residency training (SRT) in China. METHODS: A nationwide cross-sectional online survey was conducted among radiology residents in China. Workload was measured by working hours per week and the frequency of frontline nightwork in the last month. Resilience was assessed by the 2-item Connor-Davidson Resilience Scale. Depressive symptoms were measured by the Depression Anxiety Stress Scales. The hierarchical regression and simple slope analyses were performed to examine the moderating effect of resilience. RESULTS: Among 3666 radiology residents, the mean age was 27.3 years (SD = 2.6) and 58% were female. About 24.4% of the participants reported medium to severe depressive symptoms. The hierarchical regression showed that working hours (ba = 0.11, 95%CI: 0.08, 0.14) and having frontline nightwork more than once (ba = 1.22, 95%CI: 0.67, 1.78) were positively associated with depressive symptoms; the moderating effect of resilience was significant in the association of depressive symptoms with working hours (ba = - 0.02, 95%CI: - 0.03, - 0.01) and having frontline nightwork more than once (ba = - 0.28, 95%CI: - 0.49, - 0.07). The simple slope test showed the association between workload-related variables and depressive symptoms was only significant in those with a relatively lower level of resilience. CONCLUSIONS: The study found that resilience was an important modifier buffering the positive association between workload and depressive symptoms among radiology residents in China. Future medical training programs are suggested to include effective intervention components to increase personal resilience. CLINICAL RELEVANCE STATEMENT: Heavy workload in clinical setting may pose adverse effect on mental health and job performance of radiology residents. The study investigated whether psychological resilience would mitigate the association between workload and depressive symptoms among Chinese radiology residents. KEY POINTS: • Radiology residents with a heavier workload presented a higher level of depressive symptoms in China. • Psychological resilience mitigated the positive association between workload and depressive symptoms. • The association between workload and depressive symptoms was only statistically significant in radiology residents with a relatively lower level of resilience.

Association between cigarette smoking history, metabolic phenotypes, and EGFR mutation status in patients with non-small cell lung cancer.

Background: Cigarette smoking exerts a significant impact on metabolic phenotypes and epidermal growth factor receptor (EGFR) mutation status; however, their correlation remains insufficiently established. Therefore, the aim of this study was to investigate the association between cigarette smoking history, metabolic phenotypes, and EGFR mutation status in patients with non-small cell lung cancer (NSCLC). Methods: We retrospectively analyzed 198 consecutive patients with NSCLC who underwent 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) before treatment and were tested for EGFR mutation status between September 2019 and March 2022. Metabolic phenotypes, including the maximum standardized uptake value (SUVmax) of the primary tumors (pSUVmax), metastatic lymph nodes (nSUVmax), and distant metastases (mSUVmax) were assessed. Patients were classified into never-smokers and smokers based on detailed smoking history. The correlations between smoking status, metabolic parameters, and EGFR mutation status were evaluated in patients with NSCLC. Results: We observed EGFR mutations in 73 (60.3%) of 121 never-smokers and 18 (23.4%) of 77 smokers (P<0.001). EGFR-mutant NSCLC had a lower pSUVmax than that of EGFR wild-type (WT; 8.9±4.5 vs. 12.7±6.9, P<0.001). Smokers had a higher pSUVmax than never-smokers (12.5±6.4 vs. 9.9±5.9, P=0.004). With the increase of cumulative smoking dose, the pSUVmax increased significantly (r=0.198, P=0.005). There was no significant difference between nSUVmax and mSUVmax in patients with or without EGFR mutation and smoking history. Cumulative smoking dose, pSUVmax, and their combination predicted EGFR mutation status with areas under the receiver operating characteristic (ROC) curves (AUCs) 0.688, 0.673, and 0.753, respectively. Conclusions: Our findings indicate that cigarette smoking may be one of the triggers for increased pSUVmax and decreased EGFR mutations, further suggesting that EGFR mutations are associated with low pSUVmax, which may guide clinicians in risk stratification and treatment strategy selection for patients with NSCLC.

The utility of quantitative computed tomography in cohort studies of chronic obstructive pulmonary disease: a narrative review.

Background and Objective: Chronic obstructive pulmonary disease (COPD) is a significant contributor to global morbidity and mortality. Quantitative computed tomography (QCT), a non-invasive imaging modality, offers the potential to assess lung structure and function in COPD patients. Amidst the coronavirus disease 2019 (COVID-19) pandemic, chest computed tomography (CT) scans have emerged as a viable alternative for assessing pulmonary function (e.g., spirometry), minimizing the risk of aerosolized virus transmission. However, the clinical application of QCT measurements is not yet widespread enough, necessitating broader validation to determine its usefulness in COPD management. Methods: We conducted a search in the PubMed database in English from January 1, 2013 to April 20, 2023, using keywords and controlled vocabulary related to QCT, COPD, and cohort studies. Key Content and Findings: Existing studies have demonstrated the potential of QCT in providing valuable information on lung volume, airway geometry, airway wall thickness, emphysema, and lung tissue density in COPD patients. Moreover, QCT values have shown robust correlations with pulmonary function tests, and can predict exacerbation risk and mortality in patients with COPD. QCT can even discern COPD subtypes based on phenotypic characteristics such as emphysema predominance, supporting targeted management and interventions. Conclusions: QCT has shown promise in cohort studies related to COPD, since it can provide critical insights into the pathogenesis and progression of the disease. Further research is necessary to determine the clinical significance of QCT measurements for COPD management.

A longer Achilles tendon moment arm length is not associated with superior hopping performance.

Variability in musculoskeletal and lower leg structure has the potential to influence hopping height. Achilles tendon moment arm length and plantarflexor muscle strength can influence ankle joint torque development and, consequently, hopping performance. While most studies have examined the connection of the Achilles tendon moment arm with hopping performance including the resting length, in this study we attempted to explore how the changes in Achilles tendon moment arm are related to hopping performance. Therefore, the purpose of this study was to test for correlations between foot and lower leg muscle structure parameters (i.e., muscle mass, volume, cross-sectional area and Achilles tendon moment arm length) and hopping height performance in relation to changes in Achilles tendon moment arm length. Eighteen participants (10 males 8 female) performed repetitive bilateral hopping on a force platform while sagittal plane kinematics of the lower leg were recorded. Additionally, maximal isometric plantarflexion was measured. To obtain structural parameters of the lower leg, the right lower leg of each participant was scanned with magnetic resonance imaging. The cross-sectional areas of the Achilles tendon, soleus, lateral and medial gastrocnemius were measured, while muscle volumes, muscle mass, and Achilles tendon moment arm length were calculated. Contrary to our initial assumption, longer Achilles tendon moment arm did not result in superior hopping performance. Interestingly, neither maximal isometric plantarflexion force nor muscle size correlated with repetitive bilateral hopping performance. We can assume that the mechanical characteristics of the tendon and the effective utilization of the stored strain energy in the tendon may play a more important role in repetitive hopping than the structural parameters of the lower leg.

Nanotechnology-Based Drug Delivery Systems to Control Bacterial-Biofilm-Associated Lung Infections.

Airway mucus dysfunction and impaired immunological defenses are hallmarks of several lung diseases, including asthma, cystic fibrosis, and chronic obstructive pulmonary diseases, and are mostly causative factors in bacterial-biofilm-associated respiratory tract infections. Bacteria residing within the biofilm architecture pose a complex challenge in clinical settings due to their increased tolerance to currently available antibiotics and host immune responses, resulting in chronic infections with high recalcitrance and high rates of morbidity and mortality. To address these unmet clinical needs, potential anti-biofilm therapeutic strategies are being developed to effectively control bacterial biofilm. This review focuses on recent advances in the development and application of nanoparticulate drug delivery systems for the treatment of biofilm-associated respiratory tract infections, especially addressing the respiratory barriers of concern for biofilm accessibility and the various types of nanoparticles used to combat biofilms. Understanding the obstacles facing pulmonary drug delivery to bacterial biofilms and nanoparticle-based approaches to combatting biofilm may encourage researchers to explore promising treatment modalities for bacterial-biofilm-associated chronic lung infections.

Natural course of perianal abscess in infants: a real-world study.

Natural course of perianal abscess (PA) in infancy remains obscure. This study aimed to investigate the natural course of infants with PA after conservative treatment. A retrospective cohort study was conducted in infants with PA who were treated conservatively (due to the parents' refusal of surgery), for more than 2 months between 2014 and 2020 at a single tertiary center. 153 patients (149 boys and 4 girls) were identified. The median follow-up was 5.3 years (range 3-8.2 years). Initially, 119 patients (77.8%) were completely cured by conservative treatment, and 34 (22.2%) failed. Among the 34 patients, 23 continued conservative treatment (20 cure, 3 fistula formation) and 11 underwent surgery. After conservative treatment, the rate of fistula formation, abscess recurrence, and new-onset abscess were 15.0%, 4.6%, and 6.5%, respectively. Overall, 139 patients (90.8%) were cured conservatively without surgery, and 11 (7.2%) underwent surgical management. In addition, 3 (2.0%) patients developed fistula-in-ano (under observation). PA in infants may be a time-limited and self-limited condition. Conservative management should be the first choice of treatment in most cases. Longer periods of conservative treatment may achieve better clinical outcomes in selected cases. There will be a percentage of patients (about 10%) that would require surgical treatment.

[Dose-response relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children]. / 幼儿园儿童年龄与肺炎链球菌疫苗覆盖率间的剂量-ååº”å ³ç³».

OBJECTIVES: To investigate the potential relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children, and to provide a basis for guiding vaccination and developing new protein vaccines. METHODS: The stratified cluster random sampling method was used to select 1 830 healthy children from six kindergartens in Shunde District, Foshan City, China, and nasopharyngeal swabs were collected for the isolation and identification of Streptococcus pneumoniae. The logistic regression model based on restricted cubic spline was used to analyze the dose-response relationship between age and Streptococcus pneumoniae vaccination coverage. RESULTS: The rate of nasal Streptococcus pneumoniae carriage was 22.46% (411/1 830) among the kindergarten children, with the predominant serotypes of 6B, 19F, 15A, 23A, 34, and 23F. The coverage rates of 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) were 53.0% and 57.9%, respectively, and there was a significant non-linear dose-response relationship between age and the coverage rates of PCV10 and PCV13 (P<0.05), with a higher coverage rate of PCV10 (88.0%) and PCV13 (91.1%) in the children aged 2 years. There was a significant non-linear dose-response relationship between age and the coverage rates of pilus islet 1 (PI-1) and pilus islet 2 (PI-2) (P<0.05), with a lower vaccination coverage rate for PI-1 (37.7%) and PI-2 (16.1%). The coverage rates of PI-1 (13.0%-58.5%) and PI-2 (6.0%-29.4%) were lower in all age groups. The virulence genes lytA (99.5%) and ply (99.0%) associated with candidate protein vaccines showed higher vaccination coverage rates. CONCLUSIONS: There is a significant non-linear dose-response relationship between the age of kindergarten children and the coverage rates of PCV10 and PCV13 serotypes, and kindergarten children aged 2 years have a relatively high coverage rate of PCV. The high prevalence of the virulence genes lytA and ply shows that they are expected to become candidate virulence factors for the development of a new generation of recombinant protein vaccines.

Radiology Residents' Perceptions of Artificial Intelligence: Nationwide Cross-Sectional Survey Study.

BACKGROUND: Artificial intelligence (AI) is transforming various fields, with health care, especially diagnostic specialties such as radiology, being a key but controversial battleground. However, there is limited research systematically examining the response of "human intelligence" to AI. OBJECTIVE: This study aims to comprehend radiologists' perceptions regarding AI, including their views on its potential to replace them, its usefulness, and their willingness to accept it. We examine the influence of various factors, encompassing demographic characteristics, working status, psychosocial aspects, personal experience, and contextual factors. METHODS: Between December 1, 2020, and April 30, 2021, a cross-sectional survey was completed by 3666 radiology residents in China. We used multivariable logistic regression models to examine factors and associations, reporting odds ratios (ORs) and 95% CIs. RESULTS: In summary, radiology residents generally hold a positive attitude toward AI, with 29.90% (1096/3666) agreeing that AI may reduce the demand for radiologists, 72.80% (2669/3666) believing AI improves disease diagnosis, and 78.18% (2866/3666) feeling that radiologists should embrace AI. Several associated factors, including age, gender, education, region, eye strain, working hours, time spent on medical images, resilience, burnout, AI experience, and perceptions of residency support and stress, significantly influence AI attitudes. For instance, burnout symptoms were associated with greater concerns about AI replacement (OR 1.89; P<.001), less favorable views on AI usefulness (OR 0.77; P=.005), and reduced willingness to use AI (OR 0.71; P<.001). Moreover, after adjusting for all other factors, perceived AI replacement (OR 0.81; P<.001) and AI usefulness (OR 5.97; P<.001) were shown to significantly impact the intention to use AI. CONCLUSIONS: This study profiles radiology residents who are accepting of AI. Our comprehensive findings provide insights for a multidimensional approach to help physicians adapt to AI. Targeted policies, such as digital health care initiatives and medical education, can be developed accordingly.

Exosomes as a delivery tool of exercise-induced beneficial factors for the prevention and treatment of cardiovascular disease: a systematic review and meta-analysis.

Exercise-derived exosomes have been identified as novel players in mediating cell-to-cell communication in the beneficial effects of improving cardiovascular disease (CVD). This review aimed to systematically investigate exosomes as delivery tools for the benefits of exercise in the prevention and treatment of CVD and summarize these outcomes with an overview of their therapeutic implications. Among the 1417 articles obtained in nine database searches (PubMed, EBSCO, Embase, Web of Science, CENTRAL, Ovid, Science Direct, Scopus, and Wiley), 12 articles were included based on eligibility criteria. The results indicate that exercise increases the release of exosomes, increasing exosomal markers (TSG101, CD63, and CD81) and exosome-carried miRNAs (miR-125b-5p, miR-122-5p, miR-342-5p, miR-126, miR-130a, miR-138-5p, and miR-455). These miRNAs mainly regulate the expression of MAPK, NF-kB, VEGF, and Caspase to protect the cardiovascular system. Moreover, the outcome indicators of myocardial apoptosis and myocardial infarction volume are significantly reduced following exercise-induced exosome release, and angiogenesis, microvessel density and left ventricular ejection fraction are significantly increased, as well as alleviating myocardial fibrosis following exercise-induced exosome release. Collectively, these results further confirm that exercise-derived exosomes have a beneficial role in potentially preventing and treating CVD and support the use of exercise-derived exosomes in clinical settings.

An Acute Transition from Rearfoot to Forefoot Strike does not Induce Major Changes in Plantarflexor Muscles Activation for Habitual Rearfoot Strike Runners.

Footstrike pattern has received increased attention within the running community because there is a common belief that forefoot strike running (FFS) is more advantageous (i.e., improve performance and reduce running injuries) than rearfoot strike running (RFS) in distance running. Literature reports suggest greater knee joint flexion magnitude and initial knee angle during stance in FFS compared with RFS running We examined the EMG activation of the triceps surae muscles during an acute transition from RFS to FFS strike. We tested the hypothesis that due to larger knee flexion in FFS the gastrocnemius muscles possibly decrease their EMG activity because muscle fascicles operate under unfavorable conditions. Fourteen competitive healthy middle- and long-distance runners who were habitual RFS runners ran on a treadmill at three speeds: 12, 14, and 16 km·h-1. Each running speed was performed with both FFS and RFS patterns. Lower limb kinematics in the sagittal plane and normalized electromyography (EMG) activity of medial gastrocnemius proximal, middle and distal regions, lateral gastrocnemius and soleus muscles were compared between footstrike patterns and running speeds across the stride cycle. Contrary to our expectations, the knee joint range of motion was similar in FFS and RFS running. However, the sagittal plane ankle joint motion was greater (p < 0.01) while running with FFS, resulting in a significantly greater muscle-tendon unit lengthening (p < 0.01) in FFS compared with RFS running. In addition, medial and lateral gastrocnemius showed higher EMG activity in FFS compared with RFS running in the late swing and early stance but only for a small percentage of the stride cycle. However, strike patterns and running speed failed to induce region-specific activation differences within the medial gastrocnemius muscle. Overall, well-trained RFS runners are able to change to FFS running by altering only the ankle joint kinematics without remarkably changing the EMG activity pattern.

Free Radical and Viral Infection: A Review from the Perspective of Ferroptosis.

Free radicals, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), play critical roles in various physiological activities such as cell differentiation, apoptosis, and vascular tension when existing in cells at low levels. However, excessive amounts of free radicals are harmful, causing DNA damage, lipid peroxidation, protein degeneration, and abnormal cell death. Certain viral infections induce cells to produce excessive free radicals, which in multiple ways help the virus to replicate, mature, and exit. Iron is a necessary element for many intracellular enzymes, involved in both cellular activities and viral replication. Ferroptosis, a programmed cell death mode distinct from apoptosis, necrosis, and pyroptosis, is characterized by lipid peroxide accumulation and damage to the antioxidant system, affecting many cellular processes. Viral infection commonly manifests as decreased glutathione (GSH) content and down-regulated glutathione peroxidase 4 (GPX4) activity, similar to ferroptosis. Recent studies have suggested a possible relationship among free radicals, viral infections and ferroptosis. This review aims to elucidate the molecular mechanism linking free radicals and ferroptosis during viral infections and provide a new theoretical basis for studying viral pathogenesis and control.