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Abstract This study investigated the possible mechanisms of microRNA-124a on the differentiation of bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanism. β-Thiol ethanol induced Notch1 mRNA expression, microRNA-124a inhibitor reduced the effects of β-thiol ethanol on Notch1 mRNA expression in BMSCs. Baicalin induced Hes1 mRNA expression, and microRNA-124a inhibitor reduced the effects of baicalin on Hes1 mRNA expression in BMSCs. Si-Notch1 suppressed Hes1 mRNA expression in BMSCs. Baicalin increased the effects of Notch1 on Hes1 mRNA expression in BMSCs. Si-Notch1 increased cell growth of BMSCs. Baicalin reduced the effects of si-Notch1 on cell growth and the differentiation of BMSCs. We demonstrated that microRNA-124a promoted the differentiation of BMSCs into neurons through Notch/Hes1 signal pathway.

Abstract Background Elevated blood glucose at hospital admission is frequently observed and has been associated with adverse outcomes in various patient populations. This meta-analysis sought to consolidate existing evidence to assess the association between elevated blood glucose at admission and clinical outcomes amongst pneumonia patients. Methods We searched PubMed, Medline, Cochrane library, Web of Science (WoS), and Scopus databases for studies, published up to 31 August 2023, and reporting on the clinical outcomes and the blood glucose levels at admission. Data were extracted by two independent reviewers. Random-effects meta-analyses were used to pool odds ratios (ORs) with 95% confidence intervals (CI) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes. Results A total of 23 studies with 34,000 participants were included. Elevated blood glucose at admission was significantly associated with increased short-term (pooled OR: 2.67; 95%CI: 1.73–4.12) and long-term mortality (pooled OR: 1.70; 95%CI: 1.20–2.42). Patients with raised glucose levels were more likely to require ICU admission (pooled OR: 1.86; 95%CI: 1.31–2.64). Trends also suggested increased risks for hospital readmission and mechanical ventilation, though these were not statistically significant. Elevated blood glucose was linked with approximately 0.72 days longer duration of hospital stay. Conclusion Elevated blood glucose level at the time of hospital admission is associated with several adverse clinical outcomes, especially mortality, in patients with pneumonia. These findings underscore the importance of recognizing hyperglycemia as significant prognostic marker in pneumonia patients. Further research is needed to determine whether targeted interventions to control glucose levels can improve these outcomes.

Abstract Irradiation (IR) induces immunogenic cell death (ICD) in tumors, but it rarely leads to the abscopal effect (AE); even combining IR with immune checkpoint inhibitors has shown only anecdotal success in inducing AEs. In this study, we aimed to enhance the IR-induced immune response and generate reproducible AEs using the anti-alcoholism drug, disulfiram (DSF), complexed with copper (DSF/Cu) to induce tumor ICD. We measured ICD in vitro and in vivo. In mouse tumor models, DSF/Cu was injected intratumorally followed by localized tumor IR, creating an in situ cancer vaccine. We determined the anticancer response by primary tumor rejection and assessed systemic immune responses by tumor rechallenge and the occurrence of AEs relative to spontaneous lung metastasis. In addition, we analyzed immune cell subsets and quantified proinflammatory and immunosuppressive chemokines/cytokines in the tumor microenvironment (TME) and blood of the vaccinated mice. Immune cell depletion was investigated for its effects on the vaccine-induced anticancer response. The results showed that DSF/Cu and IR induced more potent ICD under hypoxia than normoxia in vitro. Low-dose intratumoral (i.t.) injection of DSF/Cu and IR(12Gy) demonstrated strong anti-primary and -rechallenged tumor effects and robust AEs in mouse models. These vaccinations also increased CD8+ and CD4+ cell numbers while decreasing Tregs and myeloid-derived suppressor cells in the 4T1 model, and increased CD8+, dendritic cells (DC), and decreased Treg cell numbers in the MCa-M3C model. Depleting both CD8+ and CD4+ cells abolished the vaccine’s anticancer response. Moreover, vaccinated tumor-bearing mice exhibited increased TNFα levels and reduced levels of immunosuppressive chemokines/cytokines. In conclusion, our novel approach generated an anticancer immune response that results in a lack of or low tumor incidence post-rechallenge and robust AEs, i.e., absence of or decreased spontaneous lung metastasis in tumor-bearing mice. This approach is readily translatable to clinical settings and may increase IR-induced AEs in cancer patients.

Abstract Background S. pyogenes, is a primary pathogen that leads to pharyngitis and can also trigger severe conditions like necrotizing fasciitis and streptococcal toxic shock syndrome (STSS), often resulting in high mortality rates. Therefore, prompt identification and appropriate treatment of S. pyogenes infections are crucial in preventing the worsening of symptoms and alleviating the disease's impact. Results In this study, a newly developed technique called multiple cross displacement amplification (MCDA) was employed to detect S. pyogenes,specifically targeting the speB gene, at a temperature of 63°C within 30 min. Then, an easily portable and user-friendly nanoparticles-based lateral flow biosensor (LFB) assay was introduced for the rapid analysis of MCDA products in just 2 min. The results indicated that the LFB offers greater objectivity compared to Malachite Green and is simpler than electrophoresis. The MCDA-LFB assay boasts a low detection limit of 200 fg and exhibits no cross-reaction with non-S. pyogenes strains. Among 230 clinical swab throat samples, the MCDA-LFB method identified 27 specimens as positive, demonstrating higher sensitivity compared to 23 samples detected positive by qPCR assay and 18 samples by culture. The only equipment needed for this assay is a portable dry block heater. Moreover, each MCDA-LFB test is cost-effective, priced at approximately $US 5.5. Conclusion The MCDA-LFB assay emerges as a straightforward, specific, sensitive, portable, and user-friendly method for the rapid diagnosis of S. pyogenes in clinical samples.

Stroke is a devastating disease with high morbidity, disability, and mortality, among which ischemic stroke is more common. However, there is still a lack of effective methods to improve the prognosis and reduce the incidence of its complications. At present, there is evidence that peripheral organs are involved in the inflammatory response after stroke. Moreover, the interaction between central and peripheral inflammation includes the activation of resident and peripheral immune cells, as well as the activation of inflammation-related signaling pathways, which all play an important role in the pathophysiology of stroke. In this review, we discuss the mechanisms of inflammatory response after ischemic stroke, as well as the interactions through circulatory pathways between peripheral organs (such as the gut, heart, lung and spleen) and the brain to mediate and regulate inflammation after ischemic stroke. We also propose the potential role of meningeal lymphatic vessels (MLVs)-cervical lymph nodes (CLNs) as a brain-peripheral crosstalk lymphatic pathway in ischemic stroke. In addition, we also summarize the mechanisms of anti-inflammatory drugs in the treatment of ischemic stroke.

Understanding the dynamics of ecosystem services (ESs) in arid landscapes and socio-ecological systems is crucial for sustainable development and human well-being. This study uses the Invest model to quantify the spatio-temporal changes in four key ecosystems services in Altay from 1990 to 2020: water yield (water yield), carbon stock (carbon stock), soil retention (soil retention), and habitat quality (habitat quality). The trade-offs/synergies between different ESs were investigated via Spearman’s correlation analysis. Ecosystem service bundles (ESBs) were mapped using self-organizing mapping (SOM), and the key drivers of ES relationships and the spatio-temporal dynamics of ESBs were revealed through redundancy analysis. The results showed that water yield increased by 33.7% and soil retention increased by 1.2%, while carbon stock and habitat quality decreased by 3.5% and 1.24%, respectively. The spatial distribution pattern had a clear zonal pattern, with the northern mountainous areas higher than the southern desert areas. The six pairs of ESs, in general, showed mainly low trade-off and high synergistic relationships, with trade-offs between water yield and carbon stock, soil retention and habitat quality, and a decreasing trend of trade-offs over time. Four types of ESBs were distinguished, and the compositional differences and spatial distribution within each ESB were determined by interactions between ESs and landscape types. There are complex non-linear relationships between the drivers and the four ESBs in different years. Before 2010, ecological factors were the key drivers influencing the spatio-temporal changes in ESBs, whereas social and environmental factors combined to drive changes in ESB allocations after 2010. Additionally, this study found that the implementation of conservation measures, such as reforestation and sustainable land management practices, positively influenced the provision of ecosystem services in the Altay region. These findings underscore the importance of integrating conservation efforts into land use planning and decision-making processes to ensure the sustainable delivery of ecosystem services in arid landscapes.

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The male and female gametes of higher plants are immobile, but compatible gametes can recognize, attach, and fuse to fulfill fertilization and start embryogenesis after sperm cells are released from the pollen tube. The two fusions of egg and central cells with two sperm cells are controlled by accurate regulation mechanisms that ensure one-to-one gamete fusion. Many of the molecules involved in this process remain unknown, especially the egg cell proteins that are responsible for sperm-egg recognition, attachment, and fusion. The cytoplasm of sperm cells can trigger egg activation without the fusion of male and female gamete nuclei, suggesting that a gene controlling egg division is suppressed in the absence of fertilization. Fertilization in higher plants induces structural, physiological, and molecular biological changes in the fused egg, which are collectively known as egg activation. This review focuses on the early changes that occur in the fused egg of higher plants before fusion of the nuclei of male and female gametes. [ABSTRACT FROM AUTHOR]

The overexpression and misfolding of viral proteins in the endoplasmic reticulum (ER) may cause cellular stress, thereby inducing a cytoprotective, proteostatic host response involving phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (eIF2α). Here, we show that hepatitis A virus, a positive-strand RNA virus responsible for infectious hepatitis, adopts a stress-resistant, eIF2α-independent mechanism of translation to ensure the synthesis of viral proteins within the infected liver. Cap-independent translation directed by the hepatovirus internal ribosome entry site and productive hepatovirus infection of mice both require platelet-derived growth factor subunit A (PDGFA)-associated protein 1 (PDAP1), a small phosphoprotein of unknown function with eIF4E-binding activity. PDAP1 also interacts with eIF1A and is essential for translating stress-resistant host messenger RNAs that evade the proteostatic response to ER stress and that encode proteins promoting the survival of stressed cells. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to establish a predictive model for the risk of post-thoracic endovascular aortic repair (TEVAR) post-implantation syndrome (PIS) in type B aortic dissection (TBAD) patients, assisting clinical physicians in early risk stratification and decision management for high-risk PIS patients. This study retrospectively analyzed the clinical data of 547 consecutive TBAD patients who underwent TEVAR treatment at our hospital. Feature variables were selected through LASSO regression and logistic regression analysis to construct a nomogram predictive model, and the model's performance was evaluated. The optimal cutoff value for the PIS risk nomogram score was calculated through receiver operating characteristic (ROC) curve analysis, further dividing patients into high-risk group (HRG) and low-risk group (LRG), and comparing the short to midterm postoperative outcomes between the two groups. In the end, a total of 158 cases (28.9%) experienced PIS. Through LASSO regression analysis and multivariable logistic regression analysis, variables including age, emergency surgery, operative time, contrast medium volume, and number of main prosthesis stents were selected to construct the nomogram predictive model. The model achieved an area under the curve (AUC) of 0.86 in the training set and 0.82 in the test set. Results from calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) demonstrated that the predictive model exhibited good performance and clinical utility. Furthermore, after comparing the postoperative outcomes of HRG and LRG patients, we found that the incidence of postoperative PIS significantly increased in HRG patients. The duration of ICU stay and mechanical assistance time was prolonged, and the incidence of postoperative type II entry flow and acute kidney injury (AKI) was higher. The risk of aortic-related adverse events (ARAEs) and major adverse events (MAEs) at the first and twelfth months of follow-up also significantly increased. However, there was no significant difference in the mortality rate during hospitalization. This study established a nomogram model for predicting the risk of PIS in patients with TBAD undergoing TEVAR. It serves as a practical tool to assist clinicians in early risk stratification and decision-making management for patients.

The histone acylation reader eleven-nineteen leukemia (ENL) plays a pivotal role in sustaining oncogenesis in acute leukemias, particularly in mixed-lineage leukemia-rearranged (MLL-r) leukemia. ENL relies on its reader domain to recognize histone lysine acylation promoting oncogenic gene expression and leukemia progression. Here, we report the development of MS41, a highly potent and selective von Hippel-Lindau-recruiting ENL degrader that effectively inhibits the growth of ENL-dependent leukemia cells. MS41-induced ENL degradation reduces the chromatin occupancy of ENL-associated transcription elongation machinery, resulting in the suppression of key oncogenic gene expression programs and the activation of differentiation genes. MS41 is well-tolerated in vivo and substantially suppresses leukemia progression in a xenograft mouse model of MLL-r leukemia. Notably, MS41 also induces the degradation of mutant ENL proteins identified in Wilms' tumors. Our findings emphasize the therapeutic potential of pharmacological ENL degradation for treating ENL-dependent cancers, making MS41 not only a valuable chemical probe but also potential anticancer therapeutic for further development. [ABSTRACT FROM AUTHOR]

Ultraviolet B (UVB) light exposure accelerates skin photoaging. Human adipose-derived stem cell exosomes (hADSC-Exos) and some antioxidants may have anti-photoaging effects. However, it is unknown whether the combination of hADSC-Exos and antioxidants plays a synergistic role in anti-photoaging. In cellular and 3D skin models, we showed that vitamin E (VE) and hADSC-Exos were optimal anti-photoaging combinations. In vivo, VE and hADSC-Exos increased skin tightening and elasticity in UVB-induced photoaging mice Combined treatment with VE and hADSC-Exos inhibited SIRT1/NF-κB pathway. These findings contribute to the understanding of hADSC-Exos in conjunction with other antioxidants, thereby providing valuable insights for the future pharmaceutical and cosmetic industries.

Abstract The present study aims to assess the treatment outcome of patients with diabetes and tuberculosis (TB-DM) at an early stage using machine learning (ML) based on electronic medical records (EMRs). A total of 429 patients were included at Chongqing Public Health Medical Center. The random-forest-based Boruta algorithm was employed to select the essential variables, and four models with a fivefold cross-validation scheme were used for modeling and model evaluation. Furthermore, we adopted SHapley additive explanations to interpret results from the tree-based model. 9 features out of 69 candidate features were chosen as predictors. Among these predictors, the type of resistance was the most important feature, followed by activated partial throm-boplastic time (APTT), thrombin time (TT), platelet distribution width (PDW), and prothrombin time (PT). All the models we established performed above an AUC 0.7 with good predictive performance. XGBoost, the optimal performing model, predicts the risk of treatment failure in the test set with an AUC 0.9281. This study suggests that machine learning approach (XGBoost) presented in this study identifies patients with TB-DM at higher risk of treatment failure at an early stage based on EMRs. The application of a convenient and economy EMRs based on machine learning provides new insight into TB-DM treatment strategies in low and middle-income countries.

Abstract Purpose This study was aimed to investigate the risk factors of necrotizing enterocolitis (NEC) in twin preterm infants. Methods The clinical data of 67 pairs of twin preterm infants admitted to the neonatal department of our hospital from January 2010 to December 2021 were retrospectively collected. One of the twins had NEC (Bell II and above) and the other twin without NEC. They were divided into NEC group and control group according to whether NEC occurred or not. Results Univariate analysis showed that NEC was associated with congenital heart disease, small for gestational age, mild asphyxia at birth and feeding intolerance (P

Abstract Acute type A aortic dissection (AAAD) has a high probability of postoperative adverse outcomes (PAO) after emergency surgery, so exploring the risk factors for PAO during hospitalization is key to reducing postoperative mortality and improving prognosis. An artificial intelligence approach was used to build a predictive model of PAO by clinical data‐driven machine learning to predict the incidence of PAO after total arch repair for AAAD. This study included 380 patients with AAAD. The clinical features that are associated with PAO were selected using the LASSO regression analysis. Six different machine learning algorithms were tried for modeling, and the performance of each model was analyzed comprehensively using receiver operating characteristic curves, calibration curve, precision recall curve, and decision analysis curves. Explain the optimal model through Shapley Additive Explanation (SHAP) and perform an individualized risk assessment. After comprehensive analysis, the authors believe that the extreme gradient boosting (XGBoost) model is the optimal model, with better performance than other models. The authors successfully built a prediction model for PAO in AAAD patients based on the XGBoost algorithm and interpreted the model with the SHAP method, which helps to identify high‐risk AAAD patients at an early stage and to adjust individual patient‐related clinical treatment plans in a timely manner.

Abstract Background There is a paucity of Chinese studies evaluating the quality of life (QoL) in young acute type A aortic dissection (AAAD) patients with Marfan syndrome. Methods Young adult AAAD patients (younger than 45 years old) underwent surgical treatment at our institution from January 2017 to December 2020 were consecutive enrolled. The hospital survivors completed 1 year of follow up. Patients were divided into two groups according to the presence or absence of Marfan syndrome (MFS). A 1:1 propensity score matching (PSM) with a caliper 0.2 was conducted to balance potential bias in baseline. The follow-up data were analyzed primarily for change in quality of life and anxiety status. Results After PSM, 32 comparable pairs were matched. The baseline data were comparable and postoperative complications were similar between groups. In terms of SF-36 scale, the role physical, bodily pain, role emotional and mental health subscales were no significantly improved in MFS patients over time. At 1 year after discharged, the subscale of mental health and bodily pain were significantly lower in the MFS group than in the non-MFS group. In terms of HADS assessments, the level of anxiety in MFS patients was significantly higher than in non-MFS patients at 1 year after discharged. Conclusions The QoL in young AAAD patients with MFS is lower than those without MFS after surgery. This may be associated with the uncontrollable persistent chronic pain and the uncertainty and concerns for the disease’s progression.

Abstract Background The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear. Results The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis. Conclusion We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD. Graphical Abstract

The fault detection and diagnosis of a ship’s electric propulsion system is of great significance to the reliability and safety of large modern ships. The traditional fault diagnosis method based on mathematical models and expert knowledge is limited by the difficulty of establishing an accurate model of the complex system, and it is easy to cause false alarms. Data-driven methods, such as deep learning, can automatically learn from the mass of data, extract and analyze fault characteristics, and create a more objective distinction system state. A deep learning fault diagnosis model based on ResNet feature extraction capability and bidirectional long-term memory network timing processing capability is proposed to realize fault diagnosis of high resistance connections in ship electric propulsion systems. The results show that the res-convolutional BiLSTM deep neural network (Res-CBDNN) can fully integrate the advantages of the two networks, efficiently process fault current data, and achieve high-performance fault diagnosis. The accuracy of Res-CBDNN can be kept above 85% in a noisy environment, and it can effectively monitor the high resistance connection fault of ship electric propulsion systems.

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B’s anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.

Background: Digital subtraction angiography (DSA), the gold standard for the diagnosis of intracranial arteriovenous malformations (AVMs), can show clean nidus resection, leading to a perceived cure. Most cases of intracranial AVM recurrence have been reported in pediatric patients. The conventional understanding indicates that AVMs arise when abnormal blood vessels develop between the fourth and eighth weeks of embryonic development, which coincides with the typical period of blood vessel formation in the brain. As such, recurrent ectopic AVM are rare in adults., Case Summary: Herein, we present the case of a 31-year-old adult with a history of an intracranial AVM originally diagnosed with a symptomatic de novo cerebellar AVM formation. Recurrence was observed five years following angiographically-confirmed excision of the initial AVM. DSA performed prior to initial AVM resection indicated no cerebellar abnormalities. Moreover, the recurrent arteries exhibited differences in arteries and draining veins. In addition to reporting this case, we analyzed six previously-reported adult patients with similar ectopic recurrent AVMs. These cases are summarized to review and explore the potential causes of ectopic AVM recurrence in adults, which increase the likelihood of acquired AVM., Conclusion: The clinical course of the reported patients demonstrated the possibility of ectopic AVM recurrence in adults. The median time between the diagnosis of the initial AVM and the occurrence of ectopic recurrent AVM in adults was 11 years (range: 5-20 years). Magnetic resonance imaging follow-up for more than 10 years may be required in adult AVM-treated patients., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The rare co-occurrence of oligodendroglioma and arteriovenous malformation (AVM) in the same intracranial location., Case Summary: In a 61-year-old man presenting with progressive headaches, is described in this case study. Preoperative multimodal imaging techniques (computed tomography, magnetic resonance imaging, magnetic resonance spectroscopy, digital subtraction angiography, and computed tomography angiography) were employed to detect hemorrhage, cystic and solid lesions, and arteriovenous shunting in the right temporal lobe. The patient underwent right temporal craniotomy for lesion removal, and postoperative pathological analysis confirmed the presence of oligodendroglioma (World Health Organization grade II, not otherwise specified) and AVM., Conclusion: The preoperative utilization of multimodal imaging examination can help clinicians reduce the likelihood of misdiagnosis or oversight of these conditions, and provides important information for subsequent treatment. This case supports the feasibility of craniotomy for the removal of glioma with AVM., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest concerning this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)