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Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant diseases affecting the pig industry worldwide and is caused by the PRRS virus (PRRSV), which has complex genetic variation due to frequent mutations, indels, and recombination. The emergence of PRRSV L1C.5 in 2020 in the United States has raised worldwide concerns about PRRSV with the RFLP 1-4-4 pattern and lineage 1C. However, studies on the pathogenic characteristics, epidemiological distribution, and effectiveness of vaccines against PRRSV with L1C and RFLP1-4-4 pattern in China are still insufficient. In this study, a novel recombinant variant of PRRSV with RFLP 1-4-4 and lineage 1C features, different from L1C.5 in the United States, was isolated in China in 2021. In pathogenicity experiments in specific pathogen-free piglets or farm piglets, 60-100% of artificially infected experimental piglets died with high fever and respiratory symptoms. Inflammatory cytokine and chemokine levels were upregulated in infected piglets. A commercially modified live vaccine against highly pathogenic PRRSV did not provide effective protection when the vaccinated piglets were challenged with the novel L1C-1-4-4 variant. Therefore, this strain merits special attention when devising control and vaccine strategies. These findings suggest that extensive joint surveillance is urgently needed and that vaccine strategies should be updated to prevent the disease from spreading further., (© 2024. The Author(s).)

Automated synthesis planning has recently re-emerged as a research area at the intersection of chemistry and machine learning. Despite the appearance of steady progress, we argue that imperfect benchmarks and inconsistent comparisons mask systematic shortcomings of existing techniques, and unnecessarily hamper progress. To remedy this, we present a synthesis planning library with an extensive benchmarking framework, called SYNTHESEUS, which promotes best practice by default, enabling consistent meaningful evaluation of single-step and multi-step synthesis planning algorithms. We demonstrate the capabilities of SYNTHESEUS by re-evaluating several previous retrosynthesis algorithms, and find that the ranking of state-of-the-art models changes in controlled evaluation experiments. We end with guidance for future works in this area, and call on the community to engage in the discussion on how to improve benchmarks for synthesis planning.

Metal-mediated chemical transformations are promising approaches to manipulate and regulate proteins in fundamental biological research and therapeutic development. Nevertheless, unlike bond-forming reactions, the exploration of selective bond cleavage reactions catalyzed by metals that are fully compatible with proteins and living systems remains relatively limited. Here, it is reported that Copper(II)/tris(3-hydroxypropyltriazolylmethyl)amine (THPTA), commonly used in copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, can be repurposed as a new bioorthogonal catalyst for thiazolidine (Thz) bond cleavage. This process liberates an α-oxo-aldehyde group under physiological conditions, without requiring additional additives. To showcase the utility of this method, this simple catalyst system is coupled with genetic code expansion technology to achieve on-demand activation of genetically encoded Thz-caged α-oxo-aldehydes, enabling further functionalization of proteins. For the first time, this cell-compatible Thz uncaging reaction allows for the site-specific installation of α-oxo-aldehydes at the internal positions of proteins in phage and bacterial surface display systems, expanding the chemical space of proteins. Overall, this study expands the toolkit of bioorthogonal catalysts and paves the way for metal-promoted chemical reactions in living systems, potentially benefiting various applications in the future., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Irisin, a product of the post-translational processing of fibronectin type III domain-containing protein 5 (FNDC5), is a novel myokine which is upregulated during exercise. This hormone not only promotes the transformation of white adipose tissue into a brown-fat-like phenotype but also enhances energy expenditure and mitigates fat accumulation. Its role is crucial in the management of certain metabolic disorders such as diabetes and heart disease. Of note, the type of exercise performed significantly affects blood irisin levels, indicating the critical role of physical activity in regulating this hormone. This article aims to summarize the current scientific understanding of the role of irisin and the mechanisms through which it mediates cardiovascular protection through exercise. Moreover, this article aims to establish irisin as a potential target for preventing and treating cardiovascular diseases., Competing Interests: The authors declare that they have no competing interests., (© 2024 Guo et al.)

Ethnopharmacological Relevance: The traditional Chinese herbal remedy Atractylodes macrocephala Koidz is renowned for its purported gastrointestinal regulatory properties and immune-enhancing capabilities. Atractylenolide III (ATL III), a prominent bioactive compound in Atractylodes macrocephala Koidz, has demonstrated significant pharmacological activities. However, its impact on neuroinflammation, oxidative stress, and therapeutic potential concerning Alzheimer's disease (AD) remain inadequately investigated., Aim of the Study: This study aims to assess the plasma pharmacokinetics of ATL III in Sprague-Dawley (SD) rats and elucidate its neuropharmacological effects on AD via the PI3K/AKT/GSK3β pathway. Through this research, we endeavor to furnish experimental substantiation for the advancement of novel therapeutics centered on ATL III., Materials and Methods: The pharmacokinetic profile of ATL III in SD rat plasma was analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). AD models were induced in SD rats through bilateral intracerebroventricular (ICV) administration of streptozotocin (STZ). ATL III was administered at doses of 0.6 mg/kg, 1.2 mg/kg, and 2.4 mg/kg, while donepezil (1 mg/kg) served as control. Cognitive function assessments were conducted employing behavioral tests including the Morris Water Maze and Novel Object Recognition. Neuronal pathology and histological changes were evaluated through Nissl staining and Hematoxylin-Eosin (HE) staining, respectively. Oxidative stress levels were determined by quantifying malondialdehyde (MDA) content and total superoxide dismutase (T-SOD) activity. Molecular docking analysis was employed to explore the direct binding between ATL III and its relevant targets, followed by validation using Western blot (WB) experiments to assess the expression of p-Tau, PI3K, AKT, GSK3β, and their phosphorylated forms., Results: Within the concentration range of 5-500 ng/mL, ATL III demonstrated exceptional linearity (R 2  = 0.9991), with a quantification limit of 5 ng/mL. In male SD rats, ATL III exhibited a T max of 45 min, a t1/2 of 172.1 min, a C max of 1211 ng/L, and an AUC (0-t) of 156031 ng/L*min. Treatment with ATL III significantly attenuated Tau hyperphosphorylation in intracerebroventricular-streptozotocin (ICV-STZ) rats. Furthermore, ATL III administration mitigated neuroinflammation and oxidative stress, as evidenced by reduced Nissl body loss, alleviated histological alterations, decreased MDA content, and enhanced T-SOD activity. Molecular docking analyses revealed strong binding affinity between ATL III and the target genes PI3K, AKT, and GSK3β. Experimental validation corroborated that ATL III stimulated the phosphorylation of PI3K and AKT while reducing the phosphorylation of GSK3β., Conclusions: Our results indicate that ATL III can mitigate Tau protein phosphorylation through modulation of the PI3K/AKT/GSK3β pathway. This attenuation consequently ameliorates neuroinflammation and oxidative stress, leading to enhanced learning and memory abilities in ICV-STZ rats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: It is still being determined if prophylaxis (PR) has superior cost effectiveness compared with on-demand (OD) treatment for moderate or severe hemophilia A (HA) children in China., Objective/purpose: To evaluate the cost-effectiveness of PR and OD treatment for children with moderate or severe HA without inhibitors in China., Methods: A retrospective cost-effectiveness study was conducted on 640 HA children (373 and 267 children were on the PR and OD treatment, respectively) from January 2021 to November 2022. The Markov model was used to estimate the economic and clinical outcomes and would run for 17 yearly cycles with the initial age at 2 years. The transfer probabilities were extracted from the data of "Hemophilia Home Care Center" and the literature published. All patients' drug costs were collected from the data of "Hemophilia Home Care Center". One-way and probabilistic sensitivity analyses were conducted on the data to evaluate the robustness of the results., Results/findings: PR was consistently associated with higher overall quality-adjusted life years (QALYs) compared with OD treatment (9.59 QALYs vs. 6.85 QALYs). The incremental cost-effectiveness ratio (ICER) of PR compared with the OD treatment was calculated to be approximately US$12,151.35 (RMB¥81,778.55) per QALY gained. This amount was lower than the willingness-to-pay (WTP) threshold of US$38,212.74 (RMB¥257,171.71). One-way sensitivity analysis found that the results were sensitive to the cost of OD and PR treatments., Conclusions/implications: This study indicated that PR is cost-effective compared with OD treatment for children with moderate or severe HA without inhibitors in China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Bilateral duplicated kidney and ureter is a rare condition in urology, and it is even rarer for patients to have multiple stones simultaneously. We delineate the diagnostic and therapeutic trajectory of a patient presenting with bilateral duplex kidneys and ureters, characterized by the presence of multiple stones. Notably, the left kidney is a complete duplication, whereas the right kidney exhibits an incomplete duplication., Case Presentation: A 47-year-old male patient was diagnosed with bilateral duplex kidney and ureter combined with multiple stones. Ureteral flexible lithotripsy and percutaneous nephrolithotomy were performed successively in our hospital. On the postoperative five day, he was discharged from the hospital without apparent discomfort.The double J tube was pulled out one month later, and no stone recurrence was found after 3 months of follow-up., Conclusions: Bilateral duplicated renal ureteral malformations combined with multiple stones are very rare. Stones can be removed by ureteroscopic lithotripsy or percutaneous nephrolithotripsy and sometimes multiple procedures are required, which should be chosen according to the patient's relevant condition., (© 2024. The Author(s).)

The production of pro-coagulation factors can affect the development and prognosis of acute myocardial infarction (AMI). The clinical value of coagulation-related genes (CRGs) was investigated to discover new targets for diagnosing and treating AMI. We screened 335 differentially expressed genes (DEGs) between AMI and healthy individuals based on the GSE66360 dataset. We took the intersection of the obtained DEGs with 139 CRGs. Finally, 10 differentially expressed CEGs were screened out. The random forest algorithm was constructed to identify 6 signature CRGs (THBS1, SERPINA1, THBD, MMP9, MAFF, and PLAU). Subsequently, the established predictive model was found to have good diagnostic accuracy (AUC = 0.9694 in the training cohort [GSE66360 dataset] and 0.9076 in the external validation cohort [GSE48060 dataset]). Consensus clustering identified the CRG clusters, and the accuracy of the grouping was verified. We found that AMI patients can be divided into two distinct subgroups based on the differentially expressed CRGs. Immune cell infiltration level was consistent with the expression levels of CRGs based on single sample gene set enrichment analysis. These findings reveal the potential role of CRGs in AMI. Characterizing the coagulation features of AMI patients can help in the risk stratification of patients and provide personalized treatment strategies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Recently, synthesized N-linked-disalicylaldehyde H 2 Q JI probes have been used to detect heavy metal ions in the experiment conveniently. Nevertheless, there needs to be a more in-depth examination of the excited state intramolecular proton transfer (ESIPT) mechanism and photophysical properties of the probe. This work remedied it based on quantum chemistry calculations. We contained due hydrogen bond (O1-H2 ⋯ N3 and O4-H5 ⋯ O6) and then analyzed bond parameters, IR vibration spectra, and non-covalent interaction. The bond strength is enhanced under photoexcitation, and the former is significantly stronger. The calculated electron spectra are in agreement with the experimental values. The results of the S 0 and S 1 potential energy curves and IRC calculations also confirm the unique ESIPT behavior, which isan excited stated stepwise double proton transfer. The fluorescence, internal conversion, and intersystem crossing rate of KD molecules (twisted-, double proton transfer) were calculated respectively to reveal the radiative and non-radiative pathways. It proved that the corresponding spectra are not obtained since the electrons are mainly deactivated by the ISC (S 1 ->T 1 ). Furthermore, the interfragment charge transfer (IFCT) approach indicates that the molecule possesses twisted intramolecular charge transfer (TICT) characteristics, which lead to the quenching of fluorescence introduction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This retrospective study at Beijing Children's Hospital (2020-2023) analyzed surgical procedures and complications in 24 pediatric hemophilia patients undergoing Totally Implantable Venous Access Port (TIVAP) insertion, primarily in the right jugular vein (RJV). We detailed the surgical process, including patient demographics and intraoperative imaging use. The choice of the RJV for TIVAP placement was influenced by its larger diameter and superficial anatomical position, potentially reducing risks like thrombosis and infection. Our findings support the RJV as a safer alternative for port placement in pediatric patients, aligning with current literature. Statistical analysis revealed no significant correlation between complications and baseline characteristics like weight and diagnosis type. However, the length of hospital stay and implant brand were significant risk factors for catheter or port displacement and removal. The limited patient number may introduce bias, suggesting a need for further studies with larger samples. Despite a 14.7 %-33 % complication rate and 5 port removals, the advantages of TIVAP, including reliable venous access, reduced discomfort, and treatment convenience, were evident. Most complications improved with symptomatic treatment, and there were no deaths due to port-related complications, underscoring the impact of TIVAP on improving pediatric hemophilia treatment., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Older adults living in elderly caring social organizations (SOs) are prone to suffer from depression. Many studies have found correlations between environmental and quality-of-life factors and depression; however, evidence from elderly caring SOs is rare, particularly in China., Methods: A cross-sectional study was conducted among service recipients in elderly caring SOs in Anhui and Chongqing, China. Data on demographic and health-related characteristics, living environment factors, and service quality satisfaction factors in 2171 older adults were used for analysis. The binary logistic regression model was conducted to estimate the association between living environment and service quality satisfaction factors and depression., Results: Our results indicated that living environment factors in terms of exposure to suitable temperature and humidity (OR = 0.655; 95 % CI: 0.446, 0.963), green coverage >30 % (OR = 0.432; 95 % CI: 0.337, 0.553) were associated with lower odds of developing depression. Also, an opposite relationship was found in the noise factor (OR = 1.985; 95 % CI: 1.395, 2.823). Higher satisfaction with admission and discharge services, dietary services, entertainment services, and psychological support services were also found to be associated with a lower risk of depression., Limitations: A cross-sectional design precluded determining whether living environment, service quality satisfaction, and depression are causally related. Measurement of living environment factors and service quality satisfaction factors needs to be further clarified comprehensively., Conclusions: Enhancing the living environment and the quality of the services provided to seniors in the elderly caring SOs is conducive to the reduction of the likelihood of depression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In the realm of renewable energy, the integration of wind power and hydrogen energy systems represents a promising avenue towards environmental sustainability. However, the development of cost-effective hydrogen energy storage solutions is crucial to fully realize the potential of hydrogen as a renewable energy source. By combining wind power generation with hydrogen storage, a comprehensive hydrogen energy system can be established. This study aims to devise a physiologically inspired optimization approach for designing a standalone wind power producer that incorporates a hydrogen energy system on a global scale. The optimization process considers both total cost and capacity loss to determine the optimal configuration for the system. The optimal setup for an off-grid solution involves the utilization of eight distinct types of compact horizontal-axis wind turbines. Additionally, a sensitivity analysis is conducted by varying component capital costs to assess their impact on overall cost and load loss. Simulation results indicate that at a 15 % loss, the cost of energy (COE) is $1.3772, while at 0 % loss, it stands at $1.6908. Capital expenses associated with wind turbines and hydrogen storage systems significantly contribute to the overall cost. Consequently, the wind turbine-hydrogen storage system emerges as the most cost-effective and reliable option due to its low cost of energy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Hypoxia has been found to cause cellular dysfunction and cell death, which are essential mechanisms in the development of acute myocardial infarction (AMI). However, the impact of hypoxia-related genes (HRGs) on AMI remains uncertain., Methods: The training dataset GSE66360, validation dataset GSE48060, and scRNA dataset GSE163956 were downloaded from the GEO database. We identified hub HRGs in AMI using machine learning methods. A prediction model for AMI occurrence was constructed and validated based on the identified hub HRGs. Correlations between hub HRGs and immune cells were explored using ssGSEA analysis. Unsupervised consensus clustering analysis was used to identify robust molecular clusters associated with hypoxia. Single-cell analysis was used to determine the distribution of hub HRGs in cell populations. RT-qPCR verified the expression levels of hub HRGs in the human cardiomyocyte model of AMI by oxygen-glucose deprivation (OGD) treatment in AC16 cells., Results: Fourteen candidate HRGs were identified by differential analysis, and the RF model and the nomogram based on 8 hub HRGs (IRS2, ZFP36, NFIL3, TNFAIP3, SLC2A3, IER3, MAFF, and PLAUR) were constructed, and the ROC curves verified its good prediction effect in training and validation datasets (AUC = 0.9339 and 0.8141, respectively). In addition, the interaction between hub HRGs and smooth muscle cells, immune cells was elucidated by scRNA analysis. Subsequently, the HRG pattern was constructed by consensus clustering, and the HRG gene pattern verified the accuracy of its grouping. Patients with AMI could be categorized into three HRG subclusters, and cluster A was significantly associated with immune infiltration. The RT-qPCR results showed that the hub HRGs in the OGD group were significantly overexpressed., Conclusion: A predictive model of AMI based on HRGs was developed and strongly associated with immune cell infiltration. Characterizing patients for hypoxia could help identify populations with specific molecular profiles and provide precise treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Liao, Lv, Zhu, Long and Xie.)

In recent years, significant advancements have been made in molecular generation algorithms aimed at facilitating drug development, and molecular diversity holds paramount importance within the realm of molecular generation. Nonetheless, the effective quantification of molecular diversity remains an elusive challenge, as extant metrics exemplified by Richness and Internal Diversity fall short in concurrently encapsulating the two main aspects of such diversity: quantity and dissimilarity. To address this quandary, we propose Hamiltonian diversity, a novel molecular diversity metric predicated upon the shortest Hamiltonian circuit. This metric embodies both aspects of molecular diversity in principle, and we implement its calculation with high efficiency and accuracy. Furthermore, through empirical experiments we demonstrate the high consistency of Hamiltonian diversity with real-world chemical diversity, and substantiate its effects in promoting diversity of molecular generation algorithms. Our implementation of Hamiltonian diversity in Python is available at: https://github.com/HXYfighter/HamDiv .Scientific contributionWe propose a more rational molecular diversity metric for the community of cheminformatics and drug development. This metric can be applied to evaluation of existing molecular generation methods and enhancing drug design algorithms., (© 2024. The Author(s).)

Background: Acute myocardial infarction (AMI) is a global health problem with high mortality. Early diagnosis can prevent the development of AMI and provide valuable information for subsequent treatment. Angiogenesis has been shown to be a critical factor in the development of infarction and targeting this process may be a potential protective strategy for preventing myocardial injury and improving the prognosis of AMI patients. This study aimed to screen and verify diagnostic markers related to angiogenesis in AMI and to investigate the molecular mechanisms of action associated with AMI in terms of immune cell infiltration., Methods: The GSE66360 and the GSE60993 datasets were both downloaded from the GEO database and were used as the training cohort and the external validation cohort, respectively. Angiogenesis-related genes (ARGs) were downloaded from the MSigDB database. The hub ARGs were identified via LASSO, RF, and SVM-RFE algorithms. ROC curves were used to assess the accuracy of the hub ARGs. The potential mechanisms of the hub ARGs were analyzed by GSEA. The ssGSEA algorithm was used to determine differences in immune cell infiltration and immune function. The CIBERSORT algorithm was used for immune cell infiltration analysis. In addition, we constructed a ceRNA network map of differentially expressed ARGs., Results: We identified the thrombomodulin (THBD) gene from ARGs as a potential diagnostic marker for AMI based on the LASSO, SVM-RFE, and RF algorithms. THBD was differentially expressed and had a potential diagnostic value (area under the curve [AUC] = 0.931 and 0.765 in the training and testing datasets, respectively). GSEA showed that the MAPK signaling pathway was more enriched in the high-expression group of THBD (P < 0.05). Immune cell infiltration analysis demonstrated that THBD was mainly positively correlated with monocytes (R = 0.48, P = 0.00055) and neutrophils (R = 0.36, P = 0.013). Finally, in the ceRNA regulatory network, THBD was closely associated with 9 miRNAs and 42 lncRNAs involved in AMI., Conclusion: THBD can be used as a potential diagnostic marker for AMI. This study provides new insights for future AMI diagnosis and molecular mechanism research. Moreover, immune cell infiltration plays an essential role in the occurrence and development of AMI., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Recent regional investigations in the United States have revealed a thought-provoking perspective: household electricity consumption may act as an inferior commodity, displaying a negative correlation with wealth. This finding challenges the outcomes of various other econometric analyses and underscores the importance of scrutinizing power consumption patterns across different regional service areas. While it is commonly believed that home electricity usage decreases as income rises, this may not always hold true universally. This study focuses on power usage in Seattle, Washington households, a prominent urban economy in the Pacific Northwest. Employing dynamic error correction modeling techniques, the research demonstrates statistically significant fluctuations in domestic power usage attributed to variations in actual value, actual revenue, and cold weather. In the immediate future, energy for homes in this urban economy resembles any other commodity. However, investing in electricity for homes in Seattle may not be advisable in the long run. Home power usage in Seattle declines with each percentage point increase in actual per capita income over 1.2 %. This finding highlights the need for careful consideration and strategic planning in energy management policies for urban economies like Seattle., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Aging is a challenge to global development. This challenge is particularly significant for China because it has the largest elderly population worldwide. The proportion of aging population continues to increase, and solely relying on government efforts to meet the needs of the elderly is inadequate. Hence, involvement of social organizations in elderly care services is needed. Their core members exhibit higher sense of responsibility and identification with the organization than regular members, thus profoundly affecting organizational development. Based on the Social Capital Theory, this study employed a multistage stratified random sampling method to examine the social capital stock of elderly social organizations and their core members across six cities in Anhui Province, China. Chi-square tests analyzed the relationship between the core members' demographic factors and individual performance. Independent-sample t-tests assessed the relationship between social capital and individual performance. Finally, binary logistic regression models determined the factors influencing the individual performance of core members. Social networks within core members' social capital and the internal social capital of elderly caring social organizations (ESOs) affect the individual performance of core members. Therefore, organizations should provide more training opportunities for core members to expand their networks. Cultivating a shared language and vision as components of social capital can enhance organizational cohesion and operational stability.

Lithium-sulfur batteries (LSBs) are facing many challenges, such as the inadequate conductivity of sulfur, the shuttle effect caused by lithium polysulfide (LiPSs), lithium dendrites, and the flammability, which have hindered their commercial applications. Herein, a "four-in-one" functionalized coating is fabricated on the surface of polypropylene (PP) separator by using a novel flame-retardant namely InC-HCTB to meet these challenges. InC-HCTB is obtained by cultivating polyphosphazene on the surface of carbon nanotubes with an in situ growth strategy. First, this unique architecture fosters an enhanced conductive network, bolstering the bidirectional enhancement of both ionic and electronic conductivities. Furthermore, InC-HCTB effectively inhibits the shuttle effect of LiPSs. LSBs exhibit a remarkable capacity of 1170.7 mA h g -1 at 0.2 C, and the capacity degradation is a mere 0.0436% over 800 cycles at 1 C. Third, InC-HCTB coating serves as an ion migration network, hindering the growth of lithium dendrites. More importantly, InC-HCTB exhibits notable flame retardancy. The radical trapping action in the gas phase and the protective effect of the shielded char layer in the condensed phase are simulated and verified. This facile in situ growth strategy constructs a "four-in-one" functional separator coating, rendering InC-HCTB a promising additive for the large-scale production of safe and stable LSBs., (© 2024 Wiley‐VCH GmbH.)

Mitochondrial dysfunction has been known to contribute to the worsening of acute myocardial infarction (AMI). We screened differentially expressed genes (DEGs) between AMI and healthy individuals based on the GSE66360 dataset. We took the intersection of the obtained DEGs with 1,136 mitochondria-related genes. Finally, we screened out mitochondria-related DEGs (MitoDEGs). Eight MitoDEGs were identified as hub genes based on the random forest algorithm. Two mitochondria-related robust molecular clusters were identified by consensus clustering. Immune infiltration analysis showed that immune cell infiltration was significantly increased in the high-expression group of MitoDEGs. We obtained the potential drugs targeted at ALDH2 , PMAIP1 , and BCL2A1 , such as disulfiram, obatoclax mesylate, and bortezomib. Quantitative reverse-transcription polymerase chain reaction further validated the expression of the MitoDEGs in the cell model of AMI. These findings reveal the potential role of MitoDEGs in AMI and provide new insights into risk stratification and individualized treatment of AMI patients., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: Angiogenesis has been discovered to be a critical factor in developing tumors and ischemic diseases. However, the role of angiogenesis-related genes (ARGs) in acute myocardial infarction (AMI) remains unclear., Methods: The GSE66360 dataset was used as the training cohort, and the GSE48060 dataset was used as the external validation cohort. The random forest (RF) algorithm was used to identify the signature genes. Consensus clustering analysis was used to identify robust molecular clusters associated with angiogenesis. The ssGSEA was used to analyze the correlation between ARGs and immune cell infiltration. In addition, we constructed miRNA-gene, transcription factor network, and targeted drug network of signature genes. RT-qPCR was used to verify the expression levels of signature genes., Results: Seven signature ARGs were identified based on the RF algorithm. Receiver operating characteristic curves confirmed the classification accuracy of the risk predictive model based on signature ARGs (area under the curve [AUC] = 0.9596 in the training cohort and AUC = 0.7773 in the external validation cohort). Subsequently, the ARG clusters were identified by consensus clustering. Cluster B had a more generalized high expression of ARGs and was significantly associated with immune infiltration. The miRNA and transcription factor network provided new ideas for finding potential upstream targets and biomarkers. Finally, the results of RT-qPCR were consistent with the bioinformatics analysis, further validating our results., Conclusions: Angiogenesis is closely related to AMI, and characterizing the angiogenic features of patients with AMI can help to risk-stratify patients and provide personalized treatment.

Importance: It remained unclear that the efficacy comparison between low-dose immune tolerance induction (LD-ITI) incorporating immunosuppressants (IS) when severe hemophilia A (SHA) patients had inhibitor-titer ≥200 Bethesda Units (BU)/mL (LD-ITI-IS 200 regimen) and LD-ITI combining with IS when SHA patients had inhibitor-titer ≥40 BU/mL (LD-ITI-IS 40 regimen)., Objective: To compare the efficacy of the LD-ITI-IS 200 regimen with that of the LD-ITI-IS 40 regimen for SHA patients with high-titer inhibitors., Methods: A prospective cohort study on patients receiving LD-ITI-IS 200 compared to those receiving LD-ITI-IS 40 from January 2021 to December 2023. Both received LD-ITI [FVIII 50 IU/kg every other day]. IS (rituximab + prednisone) was added when peak inhibitor tier ≥200 BU/mL in the LD-ITI-IS 200 regimen and ≥40 BU/mL in the LD-ITI-IS 40 regimen. Success is defined as a negative inhibitor plus FVIII recovery ≥66% of the expected., Results: We enrolled 30 patients on LD-ITI-IS 200 and 64 patients on LD-ITI-IS 40 , with similar baseline clinical characteristics. A lower IS-use rate was discovered in the LD-ITI-IS 200 regimen compared to the LD-ITI-IS 40 regimen (30.0% vs. 62.5%). The two regimens (LD-ITI-IS 200 vs. LD-ITI-IS 40 ) had similar success rate (70.0% vs. 79.7%), median time to success (9.4 vs. 10.6 months), and annualized bleeding rate during ITI (3.7 vs. 2.8). The cost to success was lower for LD-ITI-IS 200 than for LD-ITI-IS 40 (2107 vs. 3256 US Dollar/kg). Among patients with peak inhibitor-titer 40-199 BU/mL, 10 non-IS-using (on LD-ITI-IS 200 regimen) and 28 IS-using (on LD-ITI-IS 40 regimen) had similar success rates (70.0% vs. 78.6%) and time to success (9.0 vs. 8.8 months)., Interpretation: In LD-ITI, IS are not necessary for inhibitor titer <200 BU/mL., Competing Interests: Man‐Chiu Poon declares no conflict of interest for this work. However, he has otherwise received an honorarium for events sponsored by Takeda and for attending advisory Board meetings for KVR Pharm, Novo Nordisk, Octapharma, and Sobi. The other authors declare no conflict of interest., (© 2024 Chinese Medical Association. Pediatric Investigation published by John Wiley & Sons Australia, Ltd on behalf of Futang Research Center of Pediatric Development.)

Aiming to address the vibration noise problems on ships, we constructed a piezoelectric phononic crystal (PC) plate structure model, solved the governing equations of the structure using the partial differential equations module (PDE) in the finite element softwareCOMSOL6.1, and obtained the corresponding energy band structure, transmission curves, and vibration modal diagrams. The application of this method to probe the structural properties of two-dimensional piezoelectric PCs is described in detail. The calculation results obtained using this method were compared with the structures obtained using the traditional plane wave expansion method (PWE) and the finite element method (FE). The results were found to be in perfect agreement, which verified the feasibility of this method. To safely and effectively adjust the bandgap within a reasonable voltage range, this paper explored the order of magnitude of the plate thickness, the influence of the voltage on the bandgap, and the dependence between them. It was found that the smaller the order of magnitude of the plate thickness, the smaller the order of magnitude of the band in which the bandgap was located. The magnitude of the driving voltage that made the bandgap change became smaller accordingly. The new idea of attaching the PC plate to the conventional plate structure to achieve a vibration damping effect is also briefly introduced. Finally, the effects of lattice constant, plate width, and thickness on the bandgap were investigated.

Large-scale genomic variations are fundamental resources for crop genetics and breeding. Here we sequenced 1,904 genomes of broomcorn millet to an average of 40× sequencing depth and constructed a comprehensive variation map of weedy and cultivated accessions. Being one of the oldest cultivated crops, broomcorn millet has extremely low nucleotide diversity and remarkably rapid decay of linkage disequilibrium. Genome-wide association studies identified 186 loci for 12 agronomic traits. Many causative candidate genes, such as PmGW8 for grain size and PmLG1 for panicle shape, showed strong selection signatures during domestication. Weedy accessions contained many beneficial variations for the grain traits that are largely lost in cultivated accessions. Weedy and cultivated broomcorn millet have adopted different loci controlling flowering time for regional adaptation in parallel. Our study uncovers the unique population genomic features of broomcorn millet and provides an agronomically important resource for cereal crops., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Stover and manure are the main solid waste in agricultural industry. The generation of stover and manure could lead to serious environmental pollution if not handled properly. Composting is the potential greener solution to remediate and reduce agricultural solid waste, through which stover and manure could be remediated and converted into organic fertilizer, but the long composting period and low efficiency of humic substance production are the key constraints in such remediation approach. In this study, we explore the effect of lignocellulose selective removal on composting by performing chemical pretreatment on agricultural waste followed by utilization of biochar to assist in the remediation by co-composting treatment and reveal the impacts of different lignocellulose component on organic fertilizer production. Aiming to discover the key factors that influence humification during composting process and improve the composting quality as well as comprehensive utilization of agricultural solid waste. The results demonstrated that the removal of selective lignin or hemicellulose led to the shift of abundances lignocellulose-degrading bacteria, which in turn accelerated the degradation of lignocellulose by almost 51.2%. The process also facilitated the remediation of organic waste via humification and increased the humic acid level and HA/FA ratio in just 22 days. The richness of media relies on their lignocellulose content, which is negatively correlated with total nitrogen content, humic acid (HA) content, germination index (GI), and pH, but positively correlated with fulvic acid (FA) and total organic carbon (TOC). The work provides a potential cost effective and efficient framework for agricultural solid waste remediation and reduction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Polycarboxylate superplasticizers (PCEs) are indispensable functional ingredients in modern construction, and their usage is extensive. Herein, a polyether macromonomer (VPEG) with high reactivity was used to prepare VAPCEs with different interfacial adsorption properties (acid-ether ratio) at low temperatures and reacted in 30 min. The effects of various VAPCEs on the fluidity, rheology, and strength of cement were investigated with a w/c (water/cement) ratio of 0.35. Results showed that VAPCE-3 (acid-ether ratio is 3) exhibited the best dispersion, and the fluidity of cement slurry with VAPCE-3 (280 mm) is 278.38% higher than that of the control sample (74 mm). The reason is summarized as VAPCE-3 having good adsorption performance on the surface of cement particles and having a large steric hindrance between particles. The compressive strength of cement with VAPCE-3 was enhanced by 8.29% compared with pure cement in 3 days of curing age due to its densification on microstructure and lowest R orientation index of calcium hydroxide. With the amount of acrylic acid in VAPCE increasing, the flexural strength enhanced because a more cross-linking network was formed with Ca 2+ in cement with the increase of COO - content in VAPCEs.

Blinking is a behavior unique to animal taxa with motile eyelids, such as most amphibians and reptiles as well as all birds and mammals 1 . Eyelid movement has physiological functions, such as lubricating the cornea and washing away dust, but its potential signaling functions are not well understood 1 , 2 . The use of eyeblinks as a social signal is currently thought to be restricted to some primates, especially humans and their companion animals, but has not been verified in other taxa 1 , 3 , 4 . Here, through field observation and experiments, we demonstrate that female concave-eared torrent frogs (Odorrana tormota), which inhabit noisy streams, use eyeblinks to communicate with males to urge them to initiate amplexus for mating. Our findings reveal that eyeblinks may serve as a social signal in non-primate species., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Key Message: A genetic linkage map representing proso millet genome was constructed with SSR markers, and a major QTL corresponding to plant height was mapped on chromosome 14 of this map. Proso millet (Panicum miliaceum L.) has the lowest water requirements of all cultivated cereal crops. However, the lack of a genetic map and the paucity of genomic resources for this species have limited the utility of proso millet for detailed genetic studies and hampered genetic improvement programs. In this study, 97,317 simple sequence repeat (SSR) markers were developed based on the genome sequence of the proso millet landrace Longmi 4. Using some of these markers in conjunction with previously identified SSRs, an SSR-based linkage map for proso millet was successfully constructed using a large mapping population (316 F 2 offspring). In total, 186 SSR markers were assigned to 18 linkage groups corresponding to the haploid chromosomes. The constructed map had a total length of 3033.42 centimorgan (cM) covering 78.17% of the assembled reference genome. The length of the 18 linkage groups ranged from 88.89 cM (Chr. 15) to 274.82 cM (Chr. 16), with an average size of 168.17 cM. To our knowledge, this is the first genetic linkage map for proso millet based on SSR markers. Plant height is one of the most important traits in crop improvement. A major QTL was repeatedly detected in different environments, explaining 8.70-24.50% of the plant height variations. A candidate gene affecting auxin biosynthesis and transport, and ROS homeostasis regulation was predicted. Thus, the linkage map and QTL analysis provided herein will promote the development of gene mining and molecular breeding in proso millet., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To investigate any potential bidirectional causal relationships between stroke and venous leg ulcers (VLUs), Mendelian randomization (MR) analyses were carried out in this study. The exposure factor was stroke, the outcome factor was VLUs. The two-sample MR study was carried out based on the online analysis platform (http://app.mrbase.org/). The association of stroke and VLUs was analysed via methods of Inverse Variance Weighted (IVW), Weighted Median, MR-Egger and weighted mode. IVW method suggested no association between stroke and VLUs ((β 1.06; SE 9.321; p = 0.9095)). Weighted median estimator (β 5.906; SE 11.99, p = 0.6223), MR-Egger (β -0.8677; SE 21.89; p = 0.9691) and weighted mode (β 9.336; SE 17.77; p = 0.6089) showed consistent results. Conversely, evidence indicating that the presence of VLUs increased the risk of stroke was lacking. According to this MR study, there is no causal connection between stroke and VLUs, which suggests that therapies targeting stroke may not be effective against VLUs., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Cardiovascular diseases have become the leading cause of death in urban and rural areas. Myocardial fibrosis is a common pathological manifestation at the adaptive and repair stage of cardiovascular diseases, easily predisposing to cardiac death. Non-coding RNAs (ncRNAs), RNA molecules with no coding potential, can regulate gene expression in the occurrence and development of myocardial fibrosis. Recent studies have suggested that Chinese herbal medicine can relieve myocardial fibrosis through targeting various ncRNAs, mainly including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Thus, ncRNAs are novel drug targets for Chinese herbal medicine. Herein, we summarized the current understanding of ncRNAs in the pathogenesis of myocardial fibrosis, and highlighted the contribution of ncRNAs to the therapeutic effect of Chinese herbal medicine on myocardial fibrosis. Further, we discussed the future directions regarding the potential applications of ncRNA-based drug screening platform to screen drugs for myocardial fibrosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Yan, Tan, Zhao, Liu, Zhang, Zhang, Gao and Qin.)

Tuberous sclerosis complex 1 (TSC1) plays important roles in regulating innate immunity. However, the precise role of TSC1 in macrophages in the regulation of oxidative stress response and hepatic inflammation in liver ischemia/reperfusion injury (I/R) remains unknown. In a mouse model of liver I/R injury, deletion of myeloid-specific TSC1 inhibited AKT and MST1 phosphorylation, and decreased NRF2 accumulation, whereas activated TLR4/NF-κB pathway, leading to increased hepatic inflammation. Adoptive transfer of AKT- or MST1-overexpressing macrophages, or Keap1 disruption in myeloid-specific TSC1-knockout mice promoted NRF2 activation but reduced TLR4 activity and mitigated I/R-induced liver inflammation. Mechanistically, TSC1 in macrophages promoted AKT and MST1 phosphorylation, and protected NRF2 from Keap1-mediated ubiquitination. Furthermore, overexpression AKT or MST1 in TSC1-knockout macrophages upregulated NRF2 expression, downregulated TLR4/NF-κB, resulting in reduced inflammatory factors, ROS and inflammatory cytokine-mediated hepatocyte apoptosis. Strikingly, TSC1 induction in NRF2-deficient macrophages failed to reverse the TLR4/NF-κB activity and production of pro-inflammatory factors. Conclusions: Macrophage TSC1 promoted the activation of the AKT/MST1 signaling pathway, increased NRF2 levels via reducing Keap1-mediated ubiquitination, and modulated oxidative stress-driven inflammatory responses in liver I/R injury. Our findings underscore the critical role of macrophage TSC1 as a novel regulator of innate immunity and imply the therapeutic potential for the treatment of sterile liver inflammation in transplant recipients. Schematic illustration of macrophage TSC1-mediated AKT/MST1/NRF2 signaling pathway in I/R-triggered liver inflammation. Macrophage TSC1 can be activated in I/R-stressed livers. TSC1 activation promotes phosphorylation of AKT and MST1, which in turn increases NRF2 expression and inhibits ROS production and TLR4/NF-κB activation, resulting in reduced hepatocellular apoptosis in I/R-triggered liver injury., (© 2024. The Author(s).)

To achieve a highly realistic robot, closely mimicking human skin in terms of materials and functionality is essential. This paper presents an all-protein silk fibroin bionic skin (SFBS) that emulates both fast-adapting (FA) and slow-adapting (SA) receptors. The mechanically different silk film and hydrogel, which exhibited skin-like properties, such as stretchability (>140%), elasticity, low modulus (<10 kPa), biocompatibility, and degradability, were prepared through mesoscopic reconstruction engineering to mimic the epidermis and dermis. Our SFBS, incorporating SA and FA sensors, demonstrated a highly sensitive (1.083 kPa -1 ) static pressure sensing performance ( in vitro and in vivo ), showed the ability to sense high-frequency vibrations (50-400 Hz), could discriminate materials and sliding, and could even identify the fine morphological differences between objects. As proof of concept, an SFBS-integrated rehabilitation glove was synthesized, which could help stroke patients regain sensory feedback. In conclusion, this work provides a practical approach for developing skin equivalents, prostheses, and smart robots.

In recent years, the diagnosis and treatment of hemophilic children in China has significantly improved. However, oral health conditions, which affect quality of life, haven't received attention in this population. To explore the oral health status and oral hygiene of children and adolescents with hemophilia in the Children's Hemophilia Comprehensive Care Center of China. Dental and oral hygiene examinations were performed in children and adolescents with hemophilia who visited Beijing Children's Hospital. DMFT/dmft (decayed, missing, filled teeth in permanent and primary teeth) was assessed according to World Health Organization (WHO) criteria. The simplified oral hygiene index (OHI-S) was used to evaluate the oral hygiene condition of the subjects. Questionnaires were completed by their parents. SPSS 21.0 was used for statistical analysis. A total of 114 children and adolescents were enrolled. The caries prevalence was 57.4%, 72.2% and 41.2% in primary, mixed and permanent dentitions respectively. The filling rates were 14.4%, 13.9%, and 11.4%, respectively, and the OHI-S scores of the three dentition groups were 1.49 ± 0.46, 1.57 ± 0.43, and 1.76 ± 0.46, respectively. A total of 103 valid questionnaires were collected. Sixty-nine children (67%) didn't brushed their teeth 2 times a day. Nearly half of the parents knew little about fluoride toothpaste. Multiple linear regression analysis revealed that brushing teeth with the help of parents had a significant positive impact on OHI-S.  Conclusion: Dental health was unsatisfactory among hemophilic children and adolescents. The caries filling rates were low. Patients and their parents did not give much attention to oral health. What is Known: • Caries and gingivitis are the two main oral diseases that affect children with hemophilia. • However, the oral health conditions of children and adolescents with hemophilia have not received much attention in China. What is New: • This is the first study concentrating on the dental health of children with hemophilia in China. • Dental health was unsatisfactory among children and adolescents with hemophilia in China., (© 2023. The Author(s).)

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disorder on a global scale. Atherosclerosis (AS), a leading cause of cardiovascular diseases, stands as the primary contributor to mortality among patients diagnosed with NAFLD. However, the precise etiology by which NAFLD causes AS remains unclear. Exosomes are nanoscale extracellular vesicles secreted by cells, and are considered to participate in complex biological processes by promoting cell-to-cell and organ-to-organ communications. As vesicles containing protein, mRNA, non-coding RNA and other bioactive molecules, exosomes can participate in the development of NAFLD and AS respectively. Recently, studies have shown that NAFLD can also promote the development of AS via secreting exosomes. Herein, we summarized the recent advantages of exosomes in the pathogenesis of NAFLD and AS, and highlighted the role of exosomes in mediating the information exchange between NAFLD and AS. Further, we discussed how exosomes play a prominent role in enabling information exchange among diverse organs, delving into a novel avenue for investigating the link between diseases and their associated complications. The future directions and emerging challenges are also listed regarding the exosome-based therapeutic strategies for AS under NAFLD conditions., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Irrational nitrogen (N) fertilizer management and application practices have led to a range of ecological and environmental problems that seriously threaten food security. In this study, an effective N fertilizer management strategy was established for improving N fertilizer utilization efficiency (NUE). Biochar, N 2 -fixing bacteria (Enterobacter cloacae), and a nitrification inhibitor (dicyandiamide, DCD) were simultaneously added to the soil during maize cultivation. The goal was to increase soil ammonium nitrogen content and NUE by regulating the relative abundance, enzyme activity, and functional gene expression of N conversion-related soil microbes. Biochar combined with E. cloacae and DCD significantly increased soil N content, and the NUE reached 46.69 %. The relative abundance of Burkholderia and Bradyrhizobium and the activity of nitrogenase increased significantly during biological N 2 fixation. Further, the abundance of the nifH gene was significantly up-regulated. The relative abundance of Sphingomonas, Pseudomonas, Nitrospira, and Castellaniella and the activities of ammonia monooxygenase and nitrate reductase decreased significantly during nitrification and denitrification. Moreover, the abundance of the genes amoA and narG was significantly down-regulated. Correlation analyses showed that the increase in soil N 2 fixation and the suppression of nitrification and denitrification reactions were the key contributors to the increase in soil N content and NUE. Biochar combined with E. cloacae and DCD synergistically enabled the supplementation, slow release, and retention of N, thus providing adequate N for maize growth. Thus, the combination of biochar, E. cloacae, and DCD is effective for mitigating the irrational application of N fertilizers and reducing N pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In the 21st century, cardiovascular disease (CVD) has become one of the leading causes of death worldwide. The prevention and treatment of CVD remain pressing scientific issues. Several recent studies have suggested that ferroptosis may play a key role in CVD. Most studies conducted thus far on ferroptosis and CVD have supported the link. Ferroptosis mediated by different signaling and metabolic pathways can lead to ischemic heart disease, myocarditis, heart failure, ischemia-reperfusion injury, and cardiomyopathy. Still, the specific mechanism of ferroptosis in CVD, the particular organ areas affected, and the stage of disease involved need to be further studied. Therefore, understanding the mechanisms regulating ferroptosis in CVD may improve disease management. Throughout this review, we summarized the mechanism of ferroptosis and its effect on the pathogenesis of CVD. We also predicted and discussed future research directions, aiming to provide new ideas and strategies for preventing and treating CVD., Competing Interests: Declaration of Competing Interest All authors disclosed no relevant relationships., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Mesenchymal stem cells (MSCs), extensively utilized in contemporary stem cell research, hold significant potential in the treatment of neoplastic diseases. This study aims to investigate the influences of umbilical cord mesenchymal stem cells (UMSCs) and their exosomes (UMSCs-exos) on tumor cell phenotypes. UMSCs and UMSCs-exos, isolated from human umbilical cord tissue, were validated for isolation efficiency and differentiation capacity using flow cytometry, electron microscopy, and cell staining. MDA-MB-231, BGC-823, A549, and LN-229, which are human breast (BC), gastric (GC), lung carcinoma (LC) cells and glioma cells, respectively, were treated with UMSCs and UMSCs-exos. Cell counting kit-8 (CCK-8), cell scratch-wound, and Transwell assays were performed on treated cultures to observe the phenotypic changes induced by UMSCs- and UMSCs-exos-treated cancer cells. The results demonstrated that UMSCs highly express PE-labeled positive surface antigens and exhibit low expression of FITC-labeled negative surface antigens, alongside possessing osteogenic and adipogenic differentiation potentials. Electron microscopy revealed UMSCs-exos to be approximately 30-150 nm in diameter, averaging 126.62±1.64 nm, and displaying increased Tsg101, CD9, and CD63 protein expression. Moreover, MDA-MB-231 and BGC-823 cells exhibited enhanced proliferation, invasion, and migration upon UMSCs and UMSCs-exos treatment. In contrast, A549 cells showed minimal alteration to invasiveness but a marked increase in proliferation and migration capabilities, while LN-229 cells displayed a phenotype indicative of suppressed activity. In conclusion, UMSCs and UMSCs-exos effectively promote the growth of BC and LC cells and inhibit the activity of GC and glioma cells, presenting promising avenues for future neoplastic disease treatments., Competing Interests: None., (AJCR Copyright © 2023.)

Introduction: Angiogenesis plays an important role in the repair of urethral injury, and stem cells and their secretomes can promote angiogenesis. We obtained pediatric urethral mesenchymal stem-like cells (PU-MSLCs) in an earlier study. This project studied the pro-angiogenic effect of PU-MSLC-derived small extracellular vesicles (PUMSLC-sEVs) and the underlying mechanisms., Materials and Methods: PUMSLCs and PUMSLC-sEVs were cultivated and identified. Then, biological methods such as the ethynyl deoxyuridine (EdU) incorporation assay, Cell Counting Kit-8 (CCK-8) assay, scratch wound assay, Transwell assay, and tube formation assay were used to study the effect of PUMSLC-sEVs on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). We explored whether the proangiogenic effect of PUMSLC-sEVs is related to CD73 and whether adenosine (ADO, a CD73 metabolite) promoted angiogenesis. GraphPad Prism 8 software was used for data analysis., Results: We observed that PUMSLC-sEVs significantly promoted the proliferation, migration, and tube-forming abilities of HUVECs. PUMSLC-sEVs delivered CD73 molecules to HUVECs to promote angiogenesis. The angiogenic ability of HUVECs was enhanced after treatment with extracellular ADO produced by CD73, and PUMSLC-sEVs further promoted angiogenesis by activating Adenosine Receptor A2A (A2AR)., Conclusions: These observations suggest that PUMSLC-sEVs promote angiogenesis, possibly through activation of the CD73/ADO/A2AR signaling axis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Broomcorn millet (Panicum miliaceum L.) is an orphan crop with the potential to improve cereal production and quality, and ensure food security. Here we present the genetic variations, population structure and diversity of a diverse worldwide collection of 516 broomcorn millet genomes. Population analysis indicated that the domesticated broomcorn millet originated from its wild progenitor in China. We then constructed a graph-based pangenome of broomcorn millet based on long-read de novo genome assemblies of 32 representative accessions. Our analysis revealed that the structural variations were highly associated with transposable elements, which influenced gene expression when located in the coding or regulatory regions. We also identified 139 loci associated with 31 key domestication and agronomic traits, including candidate genes and superior haplotypes, such as LG1, for panicle architecture. Thus, the study's findings provide foundational resources for developing genomics-assisted breeding programs in broomcorn millet., (© 2023. The Author(s).)

Objective: To explore the feasibility, safety and cost effectiveness of the use of peripherally inserted central catheter (PICC) in children with hemophilia A and inhibitors who underwent ITI treatment., Method: This retrospective cohort study evaluated the effect of PICC placement and ITI on bleeding rates, costs, and parents' satisfaction before and within 6 months after PICC placement in children with hemophilia A and inhibitors., Results: A total of 20 children with hemophilia A and high-titer inhibitors were included, with a success rate for PICC placement of 100%, at a cost of ¥6730.50. Parents' satisfaction with PICC was 100%, and the total length of catheter indwelling was 6055 days. In terms of curative effect, the success rate of ITI treatment was 75%, and the annualized bleeding rate was decreased from 10.90 ± 12.16 times before placement to 2.10 ± 3.32 times ( p  < 0.05). The transportation expense for children and their parents to the clinic decreased from ¥20,920 ± 32,274.57 before catheter placement to ¥2915 ± 2195.99 ( p  < 0.05). Time of children missed school and their parents missed work decreased from 10.85 ± 22.36 days to 1.90 ± 3.58 ( p  < 0.05) days and 40.33 ± 46.11 days to 3.83 ± 7.11 days ( p  < 0.05), respectively., Conclusion: The use of PICC for ITI treatment in children with hemophilia A and accompanying inhibitors in developing countries (e.g. China) can ensure the effect of ITI, reducing expense and improving the quality of life without obvious side effects.

Background: Physical activity is a crucial part of an active lifestyle for haemophiliac children. However, the fear of bleeds has been identified as barriers to participating physical activity for haemophiliac children even with prophylaxis. Lack of evidence and metrics driven by data is key problem., Objectives: We aim to develop machine learning models based on clinical data with multiple potential factors considered to predict risk of physical activity bleeding for haemophilia children with prophylaxis., Methods: From this cohort study, we collected information on 98 haemophiliac children with adequate prophylaxis (trough FVIII:C level > 1 %). The involved potential predictor variables include demographic information, treatment information, physical activity, joint evaluation, and pharmacokinetic parameters, etc. We applied CoxPH, Random Survival Forests (RSF) and DeepSurv to construct prediction models for the risk of bleeding during physical activities. All three survival analysis models were internally and externally validated., Results: A total of 98 patients were enrolled in this study. Their median age was 7.9 (5.5, 10.2) years. The CoxPH, RSF and DeepSurv models' discriminative and calibration abilities were all high, and the RSF model had the best performance (Internal validation: C-index, 0.7648 ± 0.0139; Brier Score, 0.1098 ± 0.0015; External validation: C-index, 0.7260 ± 0.0154; Brier Score, 0.0930 ± 0.0018). The prediction curves demonstrated that the developed RSF model can distinguish the risks well between bleeding and non-bleeding patients, as well as patients with different levels of physical activity. Meanwhile, the feature importance analysis confirmed that physical activity bleeding was deduced by comprehensive effects of various factors, and the importance of different factors on bleeding outcome is discrepant., Conclusions: This study revealed from the mechanism that it is necessary to incorporate multiple factors to accurately predict physical activity related bleeding risk. In clinical practice, the designed machine learning models can provide guidance for children with haemophilia A to positively participate in physical activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Diabetes has become a prominent global public health problem, which is an important cause of death, disease burden, and medical and health economic burden. Previous studies have reported that majority of persons diagnosed with diabetes later presented with psychological and mental health diseases. The study aimed to explore the mediation role of anxiety on social support and depression among diabetic patents in elderly caring social organizations (SOs)., Methods: A multi-stage stratified cluster random sampling method was used in this cross-sectional study, and a questionnaire consisting of demographic questionnaire, MSPSS, GAD-7, and CES-D-10 was utilized to gather data. SPSS 22.0 and MPLUS 7.4 were used for statistical analysis. Spearman correlation analysis was employed to investigate correlations of key variables. A generalized linear model was used to exam factors associated with depression. Finally, the mediation effect among study variables was investigated by structural equation modeling (SEM)., Results: The average scores of social support, anxiety, and depression were 58.41 ± 14.67, 2.95 ± 3.95, and 7.24 ± 5.53, respectively. The factors of gender, social support, and anxiety were identified as significantly influential factors related to depression among diabetic patients in elderly caring SOs. The effect of social support on depression was significantly mediated by anxiety (β = -0.467, 95%CI: -0.813 to -0.251). Furthermore, anxiety partially mediated the relationship between family support and depression (β = -0.112, 95%CI: -0.229 to -0.012), and anxiety functioned as a complete mediator in the effect of significant others' support and depression (β = -0.135, 95%CI: -0.282 to -0.024)., Conclusions: The indirect effect of social support on depression through anxiety among diabetic patients in elderly caring SOs was elucidated. Social support played a key role in maintaining and regulating their mental health, particularly from family and significant others. Social support provided by both family and significant others exerted an important influence on maintaining and regulating their mental health. In light of this pathway, the elderly caring SOs should enhance the magnitude of social support from these two sources, thereby diminishing the likelihood of experiencing anxiety and depression., (© 2023. The Author(s).)

Conventional radiomics analysis requires the manual segmentation of lesions, which is time-consuming and subjective. This study aimed to assess the feasibility of predicting muscle invasion in bladder cancer (BCa) with radiomics using a semi-automatic lesion segmentation method on T2-weighted images. Cases of non-muscle-invasive BCa (NMIBC) and muscle-invasive BCa (MIBC) were pathologically identified in a training cohort and in internal and external validation cohorts. For bladder tumor segmentation, a deep learning-based semi-automatic model was constructed, while manual segmentation was performed by a radiologist. Semi-automatic and manual segmentation results were respectively used in radiomics analyses to distinguish NMIBC from MIBC. An equivalence test was used to compare the models' performance. The mean Dice similarity coefficients of the semi-automatic segmentation method were 0.836 and 0.801 in the internal and external validation cohorts, respectively. The area under the receiver operating characteristic curve (AUC) were 1.00 (0.991) and 0.892 (0.894) for the semi-automated model (manual) on the internal and external validation cohort, respectively (both p < 0.05). The average total processing time for semi-automatic segmentation was significantly shorter than that for manual segmentation (35 s vs. 92 s, p < 0.001). The BCa radiomics model based on semi-automatic segmentation method had a similar diagnostic performance as that of manual segmentation, while being less time-consuming and requiring fewer manual interventions.

Atherosclerosis is the leading cause of numerous cardiovascular diseases with a high mortality rate. Non-coding RNAs (ncRNAs), RNA molecules that do not encode proteins in human genome transcripts, are known to play crucial roles in various physiological and pathological processes. Recently, researches on the regulation of atherosclerosis by ncRNAs, mainly including microRNAs, long non-coding RNAs, and circular RNAs, have gradually become a hot topic. Traditional Chinese medicine has been proved to be effective in treating cardiovascular diseases in China for a long time, and its active monomers have been found to target a variety of atherosclerosis-related ncRNAs. These active monomers of traditional Chinese medicine hold great potential as drugs for the treatment of atherosclerosis. Here, we summarized current advancement of the molecular pathways by which ncRNAs regulate atherosclerosis and mainly highlighted the mechanisms of traditional Chinese medicine monomers in regulating atherosclerosis through targeting ncRNAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Tan, Zhao, Wang, Zhang, Zhang, Gao, Liu and Qin.)

Objectives: To assess current treatment-related outcomes for children with severe and moderate haemophilia A (cHA) in China., Methods: This cross-section Patient Report Outcome (PRO) report collected PRO data of severe and moderate cHAs registered in the 'Hemophilia Home Care Center' database (http://web.bjxueyou.cn) between January 2021 and November 2022. Data included records of bleeding, activities, and concentrates consumption. All patients had a confirmed diagnosis of moderate or severe haemophilia A (FVIII: C ≤ 5%) and were < 18 years old., Results: Among 1038 analysable cases, 9.6% of children with inhibitors had a higher rate of intracranial haemorrhage, dropout school rate, and higher FVIII consumption than children without inhibitors. Among 100 children with inhibitors, 36 patients were treated without immune tolerance induction (ITI), 14 patients with irregular treatment and 50 patients received ITI. Children with ITI had a lower ABR (2.4 (0,6.6) vs. 13.4 (9.5, 26.6), p<.001) and AJBR (0 (0, 3.1) vs. 8.9 (1.6, 19.3), p < .001) compared to those without ITI. Among 938 children without inhibitors, 28.5% received on-demand treatment and 71.5% received prophylaxis. Of 528 children with 1343.8 (1050.4, 2922.9)IU/kg/year median FVIII consumption, 43.0% received low-dose, 43.2% received intermediate-dose, and 13.8% received high-dose regimen; these children with prophylaxis had a lower ABR (3.1 (0, 10.7) vs. 12.8 (2.4, 45.5), p < .001), AJBR (0.5 (0, 3.9) vs. 3.0 (0, 12.0), p < .001) and disability rate (9.0% vs.18.5%, p = .032) compared to children who received on-demand treatment., Conclusion: The high rate of drop-out of school and disability still present a huge gap to meet the needs in China. It is necessary to improve the level of medical accessibility and medicine affordability and strengthen the patient/parent's education in China., (© 2023 John Wiley & Sons Ltd.)

Skeletal muscle myoblastic cell lines can provide a valuable new in vitro model for the exploration of the mechanisms that control skeletal muscle development and its associated molecular regulation. In this study, the skeletal muscle tissues of grass carp were digested with trypsin and collagenase I to obtain the primary myoblast cell culture. Myoblast cells were obtained by differential adherence purification and further analyzed by cryopreservation and resuscitation, chromosome analysis, immunohistochemistry, and immunofluorescence. A continuous grass carp myoblast cell line (named CIM) was established from grass carp (Ctenopharyngodon idellus) muscle and has been subcultured > 100 passages in a year and more. The CIM cells revived at 79.78-95.06% viability after 1-6 months of cryopreservation, and shared a population doubling time of 27.24 h. The number of modal chromosomes of CIM cells was 48, and the mitochondrial 12S rRNA sequence of the CIM cell line shared 99% identity with those of grass carp registered in GenBank. No microorganisms (bacteria, fungi, or mycoplasma) were detected during the whole study. The cell type of CIM cells was proven to be myoblast by immunohistochemistry of specific myogenic protein markers, including CD34, desmin, MyoD, and MyHC, as well as relative expression of key genes. And the myogenic rate and fusion index of this cell line after 10 days of induced differentiation were 8.96 ~ 9.42% and 3-24%, respectively. The telomerase activity and transfection efficiency of CIM cell line were 0.027 IU/mgprot and 23 ~ 24%, respectively. These results suggest that a myoblast cell line named CIM with normal biological function has been successfully established, which may provide a valuable tool for related in vitro studies., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Mobile charging devices (MCDs) have been regarded as a promising way to solve the energy shortage of wireless sensor networks. Due to ignoring some important factors, such as redundant sensor nodes, there is still room to improve network lifetimes. We propose a charging strategy for wireless sensor networks with one energy-limited MCD. To give the best support for sensor nodes which need charging the most, an algorithm is proposed to find the minimum sensor nodes which keep the coverage and connectivity of the network and have the least energy requirements. Then, the goal of maximizing network lifetime is changed into how to utilize the limited energy of the MCD to guarantee the minimum sensor nodes work as long as possible. If the MCD has enough energy for all sensor nodes, the charging algorithm is designed to minimize the outage time of the network and maximize charging efficiency. Otherwise, if the energy capacity is larger than the least energy requirement, the charging target minimizes the outage time of the minimum sensor node; otherwise the charging problem becomes maximizing the lifetime of minimum sensor nodes, which has lower complexity. The results of simulation experiments confirm that our scheme prolongs network lifetime and improves charging efficiency.

The sluggish kinetics process and shuttling of soluble intermediates present in complex conversion between sulfur and lithium sulfide severely limit the practical application of lithium-sulfur batteries. Herein, by introducing a designated functional organic molecule to couple with polysulfide intermediators, an endogenous prompting mechanism of sulfur conversions has thus been created leading to an alternative sulfur-electrode process, in another words, to build a fast "internal cycle" of promotors that can promote the slow "external cycle" of sulfur conversions. The coupling-intermediators between the functional organic molecule and polysulfides, organophosphorus polysulfides, to be the "promotors" for sulfur conversions, are not only insoluble in the electrolyte but also with higher redox-activity. So the sulfur-electrode process kinetics is greatly improved and the shuttle effect is eliminated simultaneously by this strategy. Meanwhile, with the endogenous prompting mechanism, the morphology of the final discharge product can be modified into a uniform covering film, which is more conducive to its decomposition when charging. Benefiting from the effective mediation of reaction kinetics and control of intermediates solubility, the lithium-sulfur batteries can act out excellent rate performance and cycling stability., (© 2023 Wiley-VCH GmbH.)

Background: Neurodevelopmental disorder with absent language and variable seizures (NEDALVS, # 618707) are characterized by delayed speech and motor development, ocular abnormalities, and seizures. NEDAVLS is an autosomal dominant disorder caused by de novo mutations in the wasp protein family member 1 (WASF1) gene., Case Presentation: We identified a de novo nonsense variant c.1516 C > T (p.Arg506*) of WASF1 gene (NM&#95;003931.3) in two pediatric female patients with delayed motor and language development., Conclusion: This case demonstrates the effective role of WES in the diagnosis of NEDALVS. To the best of our knowledge, this variant has not been reported in the Chinese population. This contributes to our further understanding of the disease and to research related to the genetic and clinical heterogeneity, the treatment and prognosis of the disease., (© 2023. BioMed Central Ltd., part of Springer Nature.)