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Abstract. Background:. Studies that comprehensively address the characteristics of centenarian deaths are rare. The present study aimed to depict the characteristics of centenarian deaths in China and their changing trends. Methods:. Data on centenarian deaths between 2013 and 2020 were obtained from the national mortality surveillance system of China, including date, place of death (PoD), and underlying cause of death (CoD). Descriptive analyses were performed to understand the epidemiological characteristics, and a joinpoint regression model was adopted to examine the changing trends in the proportions of different PoDs, CoDs among centenarians, and centenarian deaths accounting for all deaths and deaths among people aged 65 years and older. Results:. There were 46,938 registered centenarian deaths between 2013 and 2020 that included 34,311 females (73.10%) and 12,627 males (26.90%). January (12.05%), February (9.99%), and December (9.74%) were the top three months with the highest number of deaths. The proportions of deaths that occurred in homes, hospitals, and nursing homes were 81.71%, 13.63%, and 2.68%, respectively. The proportion of deaths in nursing homes increased by 9.60% (95% confidence intervals [CIs], 6.4–12.9%) from 2014 to 2020. Heart disease (35.72%) was the leading cause of death, followed by respiratory diseases (17.63%), cerebrovascular disease (15.60%), and old age (11.22%). The proportion of respiratory diseases decreased by 4.8% (95% CI, –8.8 to –0.7%), and the proportion of deaths from old age decreased by 2.3% (95% CI, –4.4 to –0.1%) per year. Shanghai had the highest proportions of deaths in hospitals (39.38%) and nursing homes (14.68%). Sichuan had the highest proportion of deaths attributed to respiratory diseases (32.30%), while Jiangsu (26.58%) and Zhejiang (23.61%) had the highest proportions of deaths from old age. Conclusion:. Unlike other countries, centenarian deaths in China are characterized by a higher proportion of home and heart disease deaths, and this death pattern differs across provinces.

Abstract Objective This retrospective study aimed to investigate the factors influencing the occurrence of neutropenia in patients with endometrial cancer (EC) following adjuvant chemoradiotherapy (CRT). Methods Retrospective analysis of EC patients who underwent adjuvant CRT from January 2012 to June 2023 in the Department of Gynecology and Oncology of the First Affiliated Hospital of Shandong First Medical University. Neutropenia was defined as an Absolute Neutrophil Count (ANC) of peripheral blood neutrophils below 2 × 109/L. Factors affecting neutropenia in EC patients treated with CRT using Generalized Estimating Equation (GEE), and Logistic regression was used to further analyze the effect of adding radiotherapy to different chemotherapy cycles on neutropenia, so that patients receive optimal adjuvant CRT while the risk of neutropenia is appropriately controlled. Results A total of 144 patients met the inclusion criteria. They underwent 330 cycles of adjuvant chemotherapy, of whom 96 (66.7%) developed neutropenia, which occurred 140 times. The results of one-way GEE analysis showed that before CRT, White Blood Cell (WBC) (OR = 0.827; 95%CI, 0.701–0.976), ANC (OR = 0.749; 95%CI, 0.586–0.957), Absolute Monocyte Count (AMC) (OR = 0.047; 95%CI, 0.008–0.283), Blood Urea Nitrogen (BUN) (OR = 0.857; 95%CI, 0.741–0.991), platinum and docetaxel (platinum/docetaxel) dosing regimen (OR = 2.284; 95%CI, 1.130–4.618) were associated with neutropenia with adjuvant CRT for EC (p

Abstract Designing conservation interventions for rare species can be hindered by a lack of relevant data. Local ecological knowledge (LEK) has potential to provide rapidly collected, cost‐effective data across large spatio‐temporal scales, but has rarely been used as a source of conservation‐relevant information for the Asian Songbird Crisis. The Blue‐crowned Laughingthrush (Pterorhinus courtoisi; BCLT) is a Critically Endangered passerine found only in southeastern China. It is unclear why the species' breeding range and global population are extremely small, as it occurs in human‐occupied forest‐agricultural landscapes similar to surrounding environments across southern China. We conducted systematic range‐wide interviews on BCLT (n = 519) to collect novel information on the species' temporal and spatial distribution, and on potential human activities and landscape changes associated with its presence or absence. Recognition of BCLT was moderate (45.0% of respondents reported sightings), with sightings within the previous 18 months across the study area, within and beyond their known distribution. Over half of known breeding villages were confirmed by LEK data, and nesting was reported from two villages with no previous breeding records. BCLT trapping was reported across the study landscape, mostly from the last decade and associated with trappers from urban centres. BCLT trapping and lack of fengshui forest were associated with sites where BCLTs did not breed. Breeding sites were associated with increases in vegetable gardens over respondents' lifetimes, and other sites within the species' range were associated with decreases in bush/scrub. We demonstrate that LEK can identify potential threats, new breeding sites and landscape changes correlated with species presence or absence for threatened birds affected by the Asian songbird crisis. This study provides the first evidence of ongoing trapping as a threat to BCLT, and remedial measures are urgently required across the region. Read the free Plain Language Summary for this article on the Journal blog.

To address the demand for multilevel package, a low-melting-point high entropy alloy (HEA) solder was developed. It consists of 43In28Sn14Bi9Zn6Ag micro- and nano-particles with a melting point of about 62.80 °C. We obtained 43In28Sn14Bi9Zn6Ag nanoparticles by combining ultrasonic heating interaction with a ''hot shock'' process. Upon reflowing at 115 °C for 5 min, a Cu/Zn/Ag ternary intermetallic compound (IMC) formed at the interface between the solder and the copper substrate, leading to a shear strength of 40 MPa. The microstructure of this joint exhibits a complex composition with at least three phases, including Bi3In5 phase, Ag5Zn8 phase, and In0.2Sn0.8 solid solution. The stable Ag5Zn8 phase not only enhances the overall strength of the alloy matrix but also impedes the diffusion of In and Bi atoms, thereby preventing the segregation of the Bi3In5 phase. The high mixing entropy and pronounced lattice distortion in this high entropy alloy hinder the diffusion of elements within the solder matrix, mitigating the issue of excessive interfacial IMC growth. Consequently, the solder joints exhibit little degradation even after a high-temperature aging test. This high-entropy alloy solder has promising potential for multi-level chip stacking in 3D packaging.

Abstract Polyps are abnormal tissue clumps growing primarily on the inner linings of the gastrointestinal tract. While such clumps are generally harmless, they can potentially evolve into pathological tumors, and thus require long-term observation and monitoring. Polyp segmentation in gastrointestinal endoscopy images is an important stage for polyp monitoring and subsequent treatment. However, this segmentation task faces multiple challenges: the low contrast of the polyp boundaries, the varied polyp appearance, and the co-occurrence of multiple polyps. So, in this paper, an implicit edge-guided cross-layer fusion network (IECFNet) is proposed for polyp segmentation. The codec pair is used to generate an initial saliency map, the implicit edge-enhanced context attention module aggregates the feature graph output from the encoding and decoding to generate the rough prediction, and the multi-scale feature reasoning module is used to generate final predictions. Polyp segmentation experiments have been conducted on five popular polyp image datasets (Kvasir, CVC-ClinicDB, ETIS, CVC-ColonDB, and CVC-300), and the experimental results show that the proposed method significantly outperforms a conventional method, especially with an accuracy margin of 7.9% on the ETIS dataset.

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) can differentiate into Schwann cells (SCs) during peripheral nerve injury; in our previous research, we showed that SC-derived exosomes (SC-exos) played a direct induction role while fibroblast-derived exosomes (Fb-exos) had no obvious induction role. The induction role of neural stem cell (NSC)-derived exosomes (NSC-exos) has also been widely confirmed. However, no studies have compared the induction effects of these three types of cells at the same time. Therefore, by investigating the effect of these three cell-derived exosomes upon the induction of BMSCs to differentiate into SCs, this study explored the role of different exosomes in promoting the differentiation of stem cells into SCs cells, and conducted a comparison between the two groups by RNA sequencing to further narrow the range of target genes and related gene pathways in order to study their related mechanisms. Materials and methods We extracted exosomes from SCs, fibroblasts (Fb) and neural stem cells (NSC) and then investigated the ability of these exosomes to induce differentiation into BMSCs under different culture conditions. The expression levels of key proteins and gene markers were detected in induced cells by fluorescence immunoassays, western blotting and polymerase chain reaction (PCR); then, we statistically compared the relative induction effects under different conditions. Finally, we analyzed the three types of exosomes by RNA-seq to predict target genes and related gene pathways. Results BMSCs were cultured by three media: conventional (no induction), pre-induction or pre-induction + original induction medium (ODM) with exosomes of the same cell origin under different culture conditions. When adding the three different types of exosomes separately, the overall induction of BMSCs to differentiate into SCs was significantly increased (P pre-induction + exosome group > non-induction + exosome group. Using exosomes from different cell sources under the same culture conditions, we observed the following trends under the three culture conditions: RSC96-exos group ≥ NSC-exos group > Fb-exos group. The overall ability to induce BMSCs into SCs was significantly greater in the RSC96-exos group and the NSC-exos group. Although there was no significant difference in induction efficiency when comparing these two groups, the overall induction ability of the RSC96-exos group was slightly higher than that of the NSC-exos group. By combining the differentiation induction results with the RNA-seq data, the three types of exosomes were divided into three comparative groups: RSC vs. NSC, RSC vs. Fb and NSC vs. Fb. We identified 203 differentially expressed mRNA target genes in these three groups. Two differentially expressed genes were upregulated simultaneously, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). We did not identify any co-upregulated target genes for the miRNAs, but did identify one target gene of the lncRNAs, namely ENSRNOG00000065005. Analysis identified 90 GO terms related to nerves and axons in the mRNAs; in addition, KEGG enrichment and GASA analysis identified 13 common differential expression pathways in the three groups. Conclusions Our analysis found that pre-induction + ODM + RSC96/NSC-exos culture conditions were most conducive with regards to induction and differentiation. RSC96-exos and NSC-exos exhibited significantly greater differentiation efficiency of BMSCs into SCs. Although there was no statistical difference, the data indicated a trend for RSC96-exos to be advantageous We identified 203 differentially expressed mRNAs between the three groups and two differentially expressed target mRNAs were upregulated, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). 90 GO terms were related to nerves and axons. Finally, we identified 13 common differentially expressed pathways across our three types of exosomes. It is hoped that the efficiency of BMSCs induction differentiation into SCs can be improved, bringing hope to patients and more options for clinical treatment.

Sliding bearings are crucial rotating mechanical components in nuclear power plants, and their failures can result in severe economic losses and human casualties. Deep learning provides a new approach to bearing fault diagnosis, but there is currently a lack of a universal fault diagnosis model for studying bearing-rotor systems under various operating conditions, speeds and faults. Research on bearing-rotor systems supported by sliding bearings is limited, leading to insufficient fault data. To address these issues, this paper proposes a fault diagnosis model framework for bearing-rotor systems based on a deep convolutional generative adversarial network (TF-DLGAN). This model not only exhibits outstanding fault diagnosis performance but also addresses the issue of insufficient fault data. An experimental platform is constructed to conduct fault experiments under various operating conditions, speeds and faults, establishing a dataset for sliding bearing-rotor system faults. Finally, the model's effectiveness is validated using this dataset.

Abstract Background Public health emergencies are characterized by uncertainty, rapid transmission, a large number of cases, a high rate of critical illness, and a high case fatality rate. The intensive care unit (ICU) is the “last line of defense” for saving lives. And ICU resources play a critical role in the treatment of critical illness and combating public health emergencies. Objective This study estimates the demand for ICU healthcare resources based on an accurate prediction of the surge in the number of critically ill patients in the short term. The aim is to provide hospitals with a basis for scientific decision-making, to improve rescue efficiency, and to avoid excessive costs due to overly large resource reserves. Methods A demand forecasting method for ICU healthcare resources is proposed based on the number of current confirmed cases. The number of current confirmed cases is estimated using a bilateral long-short-term memory and genetic algorithm support vector regression (BILSTM-GASVR) combined prediction model. Based on this, this paper constructs demand forecasting models for ICU healthcare workers and healthcare material resources to more accurately understand the patterns of changes in the demand for ICU healthcare resources and more precisely meet the treatment needs of critically ill patients. Results Data on the number of COVID-19-infected cases in Shanghai between January 20, 2020, and September 24, 2022, is used to perform a numerical example analysis. Compared to individual prediction models (GASVR, LSTM, BILSTM and Informer), the combined prediction model BILSTM-GASVR produced results that are closer to the real values. The demand forecasting results for ICU healthcare resources showed that the first (ICU human resources) and third (medical equipment resources) categories did not require replenishment during the early stages but experienced a lag in replenishment when shortages occurred during the peak period. The second category (drug resources) is consumed rapidly in the early stages and required earlier replenishment, but replenishment is timelier compared to the first and third categories. However, replenishment is needed throughout the course of the epidemic. Conclusion The first category of resources (human resources) requires long-term planning and the deployment of emergency expansion measures. The second category of resources (drugs) is suitable for the combination of dynamic physical reserves in healthcare institutions with the production capacity reserves of corporations. The third category of resources (medical equipment) is more dependent on the physical reserves in healthcare institutions, but care must be taken to strike a balance between normalcy and emergencies.

Abstract This paper presents a novel distributed assembly permutation flowshop scheduling problem (DAPFSP) based on practical problems in automobile production. Different from the existing research on DAPFSP, this study considers that each component of the final product is composed of more than one part. Components are processed in a set of identical components manufacturing factories and are assembled into products in the assembly factory. The integration of manufacturing processes is an important objective of Industry 4.0. For solving this problem with the minimum makespan criterion, we introduce a three-level representation and a novel initialization method. To enhance the search ability of the proposed algorithms, we design three local search methods and two restart procedures according to characteristics of the problem. Then, by incorporating the problem specific knowledge with the social spider optimization algorithm (SSO), we propose three SSO variants: the SSO with hybrid local search strategies (HSSO), the HSSO with restart procedures (HSSOR), and the HSSOR with self-adaptive selection probability (HSSORP). Finally, 810 extended instances based on the famous instances are used to test the proposed algorithms. In most cases, HSSOR performs the best, with an average comparison metric value of 0.158% across three termination conditions, while the average comparison metric value for the best comparison method is 2.446%, which is 15.481 times that of HSSOR. Numerical results demonstrate that the proposed algorithms can solve the problem efficiently.

Abstract Background Compared with aerial plant tissues (such as leaf, stem, and flower), root-associated microbiomes play an indisputable role in promoting plant health and productivity. We thus explored the similarities and differences between rhizosphere and root endosphere bacterial community in the grafted apple system. Results Using pot experiments, three microhabitats (bulk soil, rhizosphere and root endosphere) samples were obtained from two-year-old apple trees grafted on the four different rootstocks. We then investigated the bacterial community composition, diversity, and co-occurrence network in three microhabitats using the Illumina sequencing methods. Only 63 amplicon sequence variants (ASVs) out of a total of 24,485 were shared in the rhizosphere and root endosphere of apple grafted on the four different rootstocks (M9T337, Malus hupehensis Rehd., Malus robusta Rehd., and Malus baccata Borkh.). The core microbiome contained 8 phyla and 25 families. From the bulk soil to the rhizosphere to the root endosphere, the members of the phylum and class levels demonstrated a significant enrichment and depletion pattern. Co-occurrence network analysis showed the network complexity of the rhizosphere was higher than the root endosphere. Most of the keystone nodes in both networks were classified as Proteobacteria, Actinobacteriota and Bacteroidetes and were low abundance species. Conclusion The hierarchical filtration pattern existed not only in the assembly of root endosphere bacteria, but also in the core microbiome. Moreover, most of the core ASVs were high-abundance species, while the keystone ASVs of the network were low-abundance species.

ABSTRACT Current microbiome signatures for chronic diseases such as diabetic kidney disease (DKD) are mainly based on low-resolution taxa such as genus or phyla and are often inconsistent among studies. In microbial ecosystems, bacterial functions are strain specific, and taxonomically different bacteria tend to form co-abundance functional groups called guilds. Here, we identified guild-level signatures for DKD by performing in-depth metagenomic sequencing and conducting genome-centric and guild-based analysis on fecal samples from 116 DKD patients and 91 healthy subjects. Redundancy analysis on 1,543 high-quality metagenome-assembled genomes (HQMAGs) identified 54 HQMAGs that were differentially distributed among the young healthy control group, elderly healthy control group, early-stage DKD patients (EDG), and late-stage DKD patients (LDG). Co-abundance network analysis classified the 54 HQMAGs into two guilds. Compared to guild 2, guild 1 contained more short-chain fatty acid biosynthesis genes and fewer genes encoding uremic toxin indole biosynthesis, antibiotic resistance, and virulence factors. Guild indices, derived from the total abundance of guild members and their diversity, delineated DKD patients from healthy subjects and between different severities of DKD. Age-adjusted partial Spearman correlation analysis showed that the guild indices were correlated with DKD disease progression and with risk indicators of poor prognosis. We further validated that the random forest classification model established with the 54 HQMAGs was also applicable for classifying patients with end-stage renal disease and healthy subjects in an independent data set. Therefore, this genome-level, guild-based microbial analysis strategy may identify DKD patients with different severity at an earlier stage to guide clinical interventions.IMPORTANCETraditionally, microbiome research has been constrained by the reliance on taxonomic classifications that may not reflect the functional dynamics or the ecological interactions within microbial communities. By transcending these limitations with a genome-centric and guild-based analysis, our study sheds light on the intricate and specific interactions between microbial strains and diabetic kidney disease (DKD). We have unveiled two distinct microbial guilds with opposite influences on host health, which may redefine our understanding of microbial contributions to disease progression. The implications of our findings extend beyond mere association, providing potential pathways for intervention and opening new avenues for patient stratification in clinical settings. This work paves the way for a paradigm shift in microbiome research in DKD and potentially other chronic kidney diseases, from a focus on taxonomy to a more nuanced view of microbial ecology and function that is more closely aligned with clinical outcomes.

ObjectiveTo explore the application effect of the online and offline mixed teaching mode in nursing practice teaching based on the Source Message Channel Receiver (SMCR) communication model.MethodsBy using the convenience sampling method, 15 nursing students who practiced their internship in the Department of Critical Care Medicine at Beijing Friendship Hospital affiliated to Capital Medical University for 4 weeks, from 1 April 2022 to 31 December 2023, were selected as the experimental group. A total of 16 nursing students who practiced in the same hospital in 2021 were selected as the control group. The control group used traditional teaching mode for teaching, and the experimental group used the online and offline teaching mode for teaching. The theoretical and practical achievements, competency, and teaching satisfaction of the two groups of nursing students were compared and analyzed after the internship.ResultsThe theoretical knowledge, operational performance, competence of the nurses, and satisfaction with the teaching in the experimental group were higher than those of the control group (P < 0.05).ConclusionBased on the SMCR communication model, exploring the online and offline mixed teaching mode plays an important role in the teaching process of nursing practice, which can not only effectively improve the comprehensive performance of nursing students but also help to improve their satisfaction with teaching and has a positive impact on the cultivation of high-quality nursing talents.

Hospital-acquired pressure ulcers (HAPUs) are still an important worldwide issue related to the safety and quality of patient care, which are among the top five adverse events reported. Patients who develop HAPUs have longer stays in the hospital than necessary, are at a greater risk of infections, and are more likely to die. Surgical patients are prone to developing PUs because they often remain immobile for extended periods of time, and their surgical procedures may limit the flow of blood oxygen and nutrition and lead to a decrease in muscle tone. Mesenchymal stem cells (MSCs) represent an attractive stem cell source for tissue regeneration in clinical applications, which have been demonstrated to improve wound healing through re-epithelialization, increased angiogenesis, and granulation tissue formation. Here, we present the case of an emergency surgical patient who developed an ulcer on the right heel during hospitalization. The human umbilical cord Wharton’s jelly-derived MSCs (WJ-MSCs) re-suspended in platelet-rich plasma (PRP) were injected into ulcer margins. Four days after the WJ-MSC application, the patient showed progressive healing of the PU. From days 4 to 33, granulation tissue formation and re-epithelialization were clearly observed. The ulcer was almost healed completely on day 47, and the pain in the patient’s wound area also decreased. Thus, intradermal transplantation of WJ-MSCs and PRP was safe and effective for treatment in patients with pressure ulcers. WJ-MSCs, together with PRP, may offer a promising treatment option for wound healing.

The balance in bacterial community is very important for the maintenance of the health status in the hosts. During the occurrence of a pervasive skin ulcer disease in Sepia pharaonis, bacterial isolate H1 and its antagonist bacterial isolate H2 were simultaneously isolated from the healthy cuttlefish, but only bacterial isolate H1 was isolated from the diseased cuttlefish. In the present study, the genetic and biochemical analysis showed that isolate H1 was identified as Vibrio alginolyticus, and isolate H2 was identified as Pseudoalteromonas piscicida, respectively. The antibiotic susceptibility test using CLSI M45–2015 method showed that the antibiotic resistance of V. alginolyticus H1 and P. piscicida H2 was different, and V. alginolyticus H1 showed strongly resistance to ampicillin. LD50 was calculated based the infection using immerse infection experiment. The result showed that the LD50 for 7 d of V. alginolyticus H1 was 1.58 × 106 CFU/mL, while the no death was observed during the infection of P. piscicida H2. Since the virulence related factors were significantly influenced by host immunity, the virulence factors of pathogen V. alginolyticus H1 was assessed under the stressors of H2O2 and 2,2′-dipyridyl. The results showed that the pathogenicity of V. alginolyticus H1 was associated with the haemolytic activity and bacterial motility. Different components of the P. piscicida H2 were collected and were tested for the antagonistic activity. It was unexpected that no antagonistic substance was detected, while V. alginolyticus H1 showed obvious phobotaxis to P. piscicida H2. It could be concluded that V. alginolyticus H1 was a pathogen of S. pharaonis, and P. piscicida H2 was a potential antagonistic bacteria to inhibit V. alginolyticus H1 via chemotaxis instead of producing antagonistic substance.

In rural areas, land use decisions are not only shaped by economic considerations but also deeply influenced by cultural and social factors. The objective of this research is to examine the complex and diverse aspects of making decisions about how land is used in rural communities, specifically by investigating the influence of cultural and social elements. Using empirical data and rigorous analysis, this research examine how traditional practices, social norms, and community dynamics influence land use patterns. The research topic focuses on the need to have a thorough understanding of the fundamental elements that affect land use choices in rural regions, going beyond only economic incentives. This research objective is to address a significant vacuum in the current literature by examining the cultural and social aspects of land usage. This research provides vital insights for policymakers and stakeholders engaged in land management and rural development projects. This research utilizes a mixed-methods approach, using qualitative interviews, participatory observations, and quantitative surveys to collect comprehensive data on the cultural and socioeconomic elements that impact land use choices. The research sample includes a wide range of rural areas, guaranteeing a thorough representation of various cultural settings and socioeconomic backgrounds. Our study reveals that cultural traditions, social networks, and power structures have a substantial impact on land use practices in rural regions. Traditional land tenure systems, community ownership arrangements, and customary land-use practices play a vital role in influencing land-use choices and resource distribution within communities. The significance of these results is substantial for policymakers, land managers, and rural development practitioners. Policymakers may create land use policies and actions that are more appropriate to the specific cultural and socioeconomic environment by understanding the complex relationship between these aspects. Furthermore, promoting community involvement and allowing local actors to participate in decision-making may result in land management results that are both more sustainable and fair.

The latest progress in the one-dimensional chain SSH model provide the basic understanding of non-Hermitian topological phases. By periodically introducing the gains and losses of imaginary potential ig,-ig,-ig,ig with anti-PT symmetry, we have investigated the topological property of non-Hermitian SSH model with long-range hopping terms. We find that the gains and losses of imaginary potential causes the model to exhibit non-Hermiticity, and the non-Hermiticity induces system to undergo topological phase transitions from topologically trivial phase with non-Hermitian winding number 0 to topologically nontrivial phase with non-Hermitian winding number 1 and −1. The introduction of gains and losses greatly broadens the topological non-trivial region and play a non-trivial role in the model. We fully characterize the topological phase transitions by the band gap closing-reopening, the non-Hermitian winding numbers v and the hidden Chern number C.

BackgroundMesenchymal stem cells (MSCs) have important research value and broad application prospects in cardiovascular diseases (CVDs). However, few bibliometric analyses on MSCs in cardiovascular diseases are available. This study aims to provide a thorough review of the cooperation and influence of countries, institutions, authors, and journals in the field of MSCs in cardiovascular diseases, with the provision of discoveries in the latest progress, evolution paths, frontier research hotspots, and future research trends in the regarding field.MethodsThe articles related to MSCs in cardiovascular diseases were retrieved from the Web of Science. The bibliometric study was performed by CiteSpace and VOSviewer, and the knowledge map was generated based on data obtained from retrieved articles.ResultsIn our study, a total of 4,852 publications launched before August 31, 2023 were accessed through the Web of Science Core Collection (WoSCC) database via our searching strategy. Significant fluctuations in global publications were observed in the field of MSCs in CVDs. China emerged as the nation with the largest number of publications, yet a shortage of high-quality articles was noted. The interplay among countries, institutions, journals and authors is visually represented in the enclosed figures. Importantly, current research trends and hotspots are elucidated. Cluster analysis on references has highlighted the considerable interest in exosomes, extracellular vesicles, and microvesicles. Besides, keywords analysis revealed a strong emphasis on myocardial infarction, therapy, and transplantation. Treatment methods-related keywords were prominent, while keywords associated with extracellular vesicles gathered significant attention from the long-term perspective.ConclusionMSCs in CVDs have become a topic of active research interest, showcasing its latent value and potential. By summarizing the latest progress, identifying the research hotspots, and discussing the future trends in the advancement of MSCs in CVDs, we aim to offer valuable insights for considering research prospects.

Objective: Oxidative stress-induced retinal neurodegenerative changes are among the pathological alterations observed in diabetic retinopathy. Resveratrol (RSV), a polyphenolic compound with diverse pharmacological effects, has shown preventive qualities in several neurodegenerative illnesses, including anti-inflammatory, anti-aging, and antioxidant benefits. However, its therapeutic efficacy in diabetic retinal neurodegeneration has not yet been thoroughly elucidated. Our study aimed to explore the protective mechanisms and therapeutic benefits of RSV on diabetic retinal neurodegeneration alterations. Materials and methods: Using streptozotocin, we created a diabetic mouse model and conducted visual electrophysiological examinations on mice from the normal group, diabetic group, and diabetic group treated with RSV. Retinas were harvested for histological staining. Additionally, primary retinal ganglion cells cultured in high glucose conditions were used to assess malondialdehyde (MDA) levels and superoxide dismutase (SOD) levels upon siRNA-mediated nuclear factor erythroid 2-related factor 2 (Nrf2) interference. Protein levels of Nrf-2, heme oxygenase-1 (HO-1), and transcriptional levels of them were also measured. Results: We demonstrated that RSV significantly improved the retinal morphology and function in the diabetic retinopathy model mice. The treated mice exhibited notable improvements in visual electrophysiology, with a significant reduction in retinal ganglion cell apoptosis. Following RSV treatment, the high glucose-cultured ganglion cells demonstrated a considerable rise in SOD levels and a substantial drop in MOD. Moreover, the protein expression of solute carrier family 7 member 11 (SLC7A11) and Nrf2 significantly increased. RT-PCR and Western blot results indicated a significant attenuation of RSV's therapeutic effects upon Nrf2 inhibition. Conclusion: Our findings suggest that RSV may reduce oxidative stress levels in the retina and inhibit retinal ganglion cell apoptosis via reducing the Nrf2/HO-1 pathway, which lessens the harm that excessive glucose causes to the retina.

Objective: In most cases, patients with hepatocellular carcinoma (HCC) develop advanced disease when diagnosed. Finding new molecules to combine with traditional biomarkers is crucial for HCC early diagnosis. In cancer development, tRNA-derived small RNAs (tsRNA) play a crucial role. Here, we aimed to identify a novel biomarker among tsRNAs that can facilitate HCC diagnosis and monitor its prognosis. Methods: We screened candidate tsRNAs in 3 pairs of HCC and adjacent tissues through high-throughput sequencing. tRF-33-RZYQQ9M739P0J was screened in tissues, sera, and cells through quantitative real-time polymerase chain reaction (qRT-PCR) for further analysis. tRF-33-RZYQHQ9M739P0J was characterized using agarose gel electrophoresis, Sanger sequencing, and nuclear and cytoplasmic RNA isolation. Experiments at room temperature and repeated freeze-thaw cycles were conducted to evaluate the detection performance of tRF-33-RZYQHQ9M739P0J. We measured the levels of differential expression of tRF-33-RZYQHQ9M739P0J in sera using qRT-PCR. We applied the chi-square test to evaluate the correlation between tRF-33-RZYQHQ9M739P0J expression levels and clinicopathological features, and assessed its prognostic value by plotting Kaplan-Meier curves. The diagnostic efficacy of tRF-33-RZYQHQ9M739P0J was evaluated using the receiver operating characteristic (ROC) curve. Finally, the downstream genes related to tRF-33-RZYQHQ9M739P0J were explored through bioinformatics prediction. Results: tRF-33-RZYQHQ9M739P0J was highly expressed in HCC tissues and sera, and its expression was correlated with metastasis, TNM stage, BCLC stage, and vein invasion. Expression of tRF-33-RZYQHQ9M739P0J were decreased after surgery in patients with HCC. High serum tRF-33-RZYQHQ9M739P0J levels are associated with low survival rates, and they can predict survival times in patients with HCC according to the Kaplan-Meier analysis. Combining tRF-33-RZYQHQ9M739P0J with serum alpha-fetoprotein and prothrombin induced by vitamin K absence II can improve the diagnostic efficiency of HCC, suggesting its potential as a biomarker for HCC. Conclusion: tRF-33-RZYQHQ9M739P0J may not only be a promising non-invasive marker for early diagnosis, but also a predictor of liver cancer progression.

In this paper, the finite-time projective synchronization (FTPS) problem of fractionalorder quaternion-valued fuzzy memristor neural networks (FOQVFMNNs) is studied. Through establishing a feedback controller with signed functions and an adaptive controller, sufficient conditions for FTPS for FOQVFMNNs are obtained. Furthermore, the synchronization establishment time is calculated. Finally, the practicability of the conclusions is verified by numerical simulations.

Abstract Primary subarachnoid hemorrhage (SAH) is a type of acute stroke, accounting for approximately 10% of cases, with high disability and mortality rate. Early brain injury (EBI) is a critical factor in determining SAH mortality; however, there are no effective treatment interventions for EBI. Based on our results, the transmission of cyclic GMP-AMP (cGAMP) from neurons to microglia is a key molecular event that triggers type I interferon response, amplifies neuroinflammation, and leads to neuronal apoptosis. Abnormal intracytoplasmic mitochondrial DNA (mtDNA) is the initiating factor of the cGAS-cGAMP-STING signaling axis. Overall, the cGAS-cGAMP-STING signaling axis is closely associated with neuroinflammation after subarachnoid hemorrhage. Targeting cGAS triggered by cytoplasmic mtDNA may be useful for comprehensive clinical treatment of patients after SAH. Further studies targeting cGAS-specific antagonists for treating SAH are warranted. Video Abstract

Multiple sclerosis is an inflammatory disorder characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Although current first-line therapies can help manage symptoms and slow down disease progression, there is no cure for multiple sclerosis. The gut-brain axis refers to complex communications between the gut flora and the immune, nervous, and endocrine systems, which bridges the functions of the gut and the brain. Disruptions in the gut flora, termed dysbiosis, can lead to systemic inflammation, leaky gut syndrome, and increased susceptibility to infections. The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors, and gut flora may play a pivotal role in regulating immune responses related to multiple sclerosis. To develop more effective therapies for multiple sclerosis, we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis. This review provides an overview of the role of the gut flora in multiple sclerosis.

Abstract Epinephelus awoara, as known as yellow grouper, is a significant economic marine fish that has been bred artificially in China. However, the genetic structure and evolutionary history of yellow grouper remains largely unknown. Here, this work presents the high-quality chromosome-level genome assembly of yellow grouper using PacBio single molecule sequencing technique (SMRT) and High-through chromosome conformation capture (Hi-C) technologies. The 984.48 Mb chromosome-level genome of yellow grouper was assembled, with a contig N50 length of 39.77 Mb and scaffold N50 length of 41.39 Mb. Approximately 99.76% of assembled sequences were anchored into 24 pseudo-chromosomes with the assistance of Hi-C reads. Furthermore, approximately 41.17% of the genome was composed of repetitive elements. In total, 24,541 protein-coding genes were predicted, of which 22,509 (91.72%) genes were functionally annotated. The highly accurate, chromosome-level reference genome assembly and annotation are crucial to the understanding of population genetic structure, adaptive evolution and speciation of the yellow grouper.

Abstract Intracranial mesenchymal tumor (IMT), FET::CREB fusion-positive is a provisional tumor type in the 2021 WHO classification of central nervous system tumors with limited information available. Herein, we describe five new IMT cases from four females and one male with three harboring an EWSR1::CREM fusion and two featuring an EWSR1::ATF1 fusion. Uniform manifold approximation and projection of DNA methylation array data placed two cases to the methylation class “IMT, subclass B”, one to “meningioma-benign” and one to “meningioma-intermediate”. A literature review identified 74 cases of IMTs (current five cases included) with a median age of 23 years (range 4–79 years) and a slight female predominance (female/male ratio = 1.55). Among the confirmed fusions, 25 (33.8%) featured an EWSR1::ATF1 fusion, 24 (32.4%) EWSR1::CREB1, 23 (31.1%) EWSR1::CREM, one (1.4%) FUS::CREM, and one (1.4%) EWSR1::CREB3L3. Among 66 patients with follow-up information available (median: 17 months; range: 1–158 months), 26 (39.4%) experienced progression/recurrences (median 10.5 months; range 0–120 months). Ultimately, three patients died of disease, all of whom underwent a subtotal resection for an EWSR1::ATF1 fusion-positive tumor. Outcome analysis revealed subtotal resection as an independent factor associated with a significantly shorter progression free survival (PFS; median: 12 months) compared with gross total resection (median: 60 months; p

Converting solar energy to electricity efficiently requires an accurate model with well-estimated parameters in a photovoltaic (PV) system. However, identifying parameters for the PV model remains challenging attributed to the nonlinearity and multimodality inherent in diode circuit models. In this paper, we propose a dual-feedback adaptive clone selection algorithm with a golden sine search. The clonal selection algorithm (CSA), known for its inherent diversity maintenance ability, offers an advantage in handling multimodal optimization problems. The critical factor is the cloning operator, particularly the determination of clone size, crucial for balancing exploration and exploitation. To address the conflict between clone size and convergence speed, we introduce a dual feedback adaptive cloning strategy. This strategy considers both the fitness difference between the hypermutated population and the original population and the harmonic mean distance of the population. Additionally, to improve accuracy, we introduce an elite learning strategy based on the golden sine mechanism. The proposed algorithm’s effectiveness is assessed through comprehensive experiments on PV cells and three PV modules, considering both single diode and double diode models, respectively. The experimental results demonstrate that the accuracy of parameter identification achieved by the proposed algorithm exceeds 99.9% for all three types of PV modules. Moreover, we validate the algorithm’s performance using manufacturer’s datasheets with varying irradiations and temperatures. All experiments consistently indicate the stability and effectiveness of the proposed method in accurately identifying the parameters of PV models.

Improving light-harvesting efficiency and suppressing interfacial charge recombination are of paramount importance to the development of Cu (II/I) redox shuttle-based dye-sensitized solar cells (DSSCs). Here, we present a rational molecular engineering on D-A-π-A organic sensitizers featuring with fluorenyl-substituted bulky donor (HY57, HY60, and HY61) for Cu (II/I) mediated DSSCs. By gradually enhancing conjugation and rigidity of the π-spacer and auxiliary acceptor moieties, the light-harvesting and electron-injection efficiencies can be simultaneously improved. The large size of fluorenyl-substituted arylamine donor together with abundant alkyl chains decorated on the molecular structures assist dense assembly of dye monolayer at surface of nanocrystalline TiO2, which largely suppress interfacial charge recombination losses. When applied in Cu (II/I) mediated DSSCs, the combination of an auxiliary acceptor of phenanthrene-fused-quinoxaline (PFQ) and a π-spacer of cyclopentadithiophene (CPDT) in dye HY61 results in a simultaneous enhancement in short-circuit current (JSC) and open-circuit voltage (VOC), thus improving the power conversion efficiency (PCE) from 7.3% for reference dye HY59 to 10.3% for HY61. This study demonstrates that rigid and fused building block is promising towards constructing highly efficient organic sensitizers.

Abstract Carotenoids, as natural tetraterpenes, play a pivotal role in the yellow coloration of peaches and contribute to human dietary health. Despite a relatively clear understanding of the carotenoid biosynthesis pathway, the regulatory mechanism of miRNAs involved in carotenoid synthesis in yellow peaches remain poorly elucidated. This study investigated a total of 14 carotenoids and 40 xanthophyll lipids, including six differentially accumulated carotenoids: violaxanthin, neoxanthin, lutein, zeaxanthin, cryptoxanthin, and (E/Z)-phytoene. An integrated analysis of RNA-seq, miRNA-seq and degradome sequencing revealed that miRNAs could modulate structural genes such as PSY2, CRTISO, ZDS1, CHYB, VDE, ZEP, NCED1, NCED3 and the transcription factors NAC, ARF, WRKY, MYB, and bZIP, thereby participating in carotenoid biosynthesis and metabolism. The authenticity of miRNAs and target gene was corroborated through quantitative real-time PCR. Moreover, through weighted gene coexpression network analysis and a phylogenetic evolutionary study, coexpressed genes and MYB transcription factors potentially implicated in carotenoid synthesis were identified. The results of transient expression experiments indicated that mdm-miR858 inhibited the expression of PpMYB9 through targeted cleavage. Building upon these findings, a regulatory network governing miRNA-mediated carotenoid synthesis was proposed. In summary, this study comprehensively identified miRNAs engaged in carotenoid biosynthesis and their putative target genes, thus enhancing the understanding of carotenoid accumulation and regulatory mechanism in yellow peach peel and expanding the gene regulatory network of carotenoid synthesis. Graphical Abstract

Abstract Neuroendocrine prostate cancer is a rapidly progressive and lethal disease characterized by early visceral metastasis, poor prognosis, and limited treatment options. Uncovering the oncogenic mechanisms could lead to the discovery of potential therapeutic avenues. Here, we demonstrate that the RNA-binding protein ELAVL3 is specifically upregulated in neuroendocrine prostate cancer and that overexpression of ELAVL3 alone is sufficient to induce the neuroendocrine phenotype in prostate adenocarcinoma. Mechanistically, ELAVL3 is transcriptionally regulated by MYCN and subsequently binds to and stabilizes MYCN and RICTOR mRNA. Moreover, ELAVL3 is shown to be released in extracellular vesicles and induce neuroendocrine differentiation of adenocarcinoma cells via an intercellular mechanism. Pharmacological inhibition of ELAVL3 with pyrvinium pamoate, an FDA-approved drug, effectively suppresses tumor growth, reduces metastatic risk, and improves survival in neuroendocrine prostate cancer mouse models. Our results identify ELAVL3 as a critical regulator of neuroendocrine differentiation in prostate cancer and propose a drug repurposing strategy for targeted therapies.

Abstract Background ETS transcription factors, known as the E26 transformation-specific factors, assume a critical role in the regulation of various vital biological processes in animals, including cell differentiation, the cell cycle, and cell apoptosis. However, their characterization in mollusks is currently lacking. Results The current study focused on a comprehensive analysis of the ETS genes in blood clam Tegillarca granosa and other mollusk genomes. Our phylogenetic analysis revealed the absence of the SPI and ETV subfamilies in mollusks compared to humans. Additionally, several ETS genes in mollusks were found to lack the PNT domain, potentially resulting in a diminished ability of ETS proteins to bind target genes. Interestingly, the bivalve ETS1 genes exhibited significantly high expression levels during the multicellular proliferation stage and in gill tissues. Furthermore, qRT-PCR results showed that Tg-ETS-14 (ETS1) is upregulated in the high total hemocyte counts (THC) population of T. granosa, suggesting it plays a significant role in stimulating hemocyte proliferation. Conclusion Our study significantly contributes to the comprehension of the evolutionary aspects concerning the ETS gene family, while also providing valuable insights into its role in fostering hemocyte proliferation across mollusks.

Abstract Plating Sn3Ag on copper substrates represents a crucial electronic packaging technique. In this study, we propose a novel composite plating approach, wherein CoSn 3 nanocrystals are deposited within the Sn3Ag coating. The resulting reflowed Sn3Ag joints exhibit a range of distinctive properties. Notably, CoSn 3 nanocrystals dissolve in Sn during the reflow process, thereby lowering the supercooling required for Sn nucleation. Consequently, Sn crystals grow in six-fold cyclic twins. Additionally, the dissolution of Co atoms in Sn leads to a reduced solubility of Cu atoms in Sn, consequently lowering the supercooling required for the nucleation of Cu6Sn5. Simultaneously, this phenomenon promotes the nucleation of Cu6Sn5, resulting in a considerable precipitation of Cu6Sn5 nanoparticles within the joints. Therefore, the mechanical properties of the joints are significantly enhanced, leading to a notable 20% increase in shear strength. Furthermore, the presence and distribution of Co elements within Sn induce changes in the growth pattern of interfacial Cu6Sn5. The growth process of Cu6Sn5 is dominated by the interfacial reaction, leading to its growth in a faceted shape. During the aging process, the dissolution of Co elements in Sn impedes the continuous growth of Cu6Sn5 at the interface, causing Cu6Sn5 to be distributed in the form of islands inside the joint. Remarkably, elemental Co acts as an inhibitor for the development of Cu3Sn and reduces the occurrence of Kirkendall voids.

ABSTRACT: This experiment was conducted to investigate the effects of mulberry leaf extract (MLE) on alleviating fatty liver hemorrhagic syndrome (FLHS) in laying hens. The 576 Jing Fen laying hens of 56 weeks of age with good health and similar weights (1.76 ± 0.17 kg) were randomly divided into 6 groups, with 8 replicates in each group and 12 chickens in each replicate. The experiment lasted 56 d. The control group was fed a corn-soybean meal diet. The FLHS group was fed a high energy-low protein (HELP) diet, and the other four experimental groups were fed HELP diets supplemented with 0.04, 0.40, 0.80, and 1.20% MLE, respectively. The results showed that HELP treatment significantly induced liver injury, which indicated that the FLHS model was successfully established. MLE supplementation could alleviate the FLHS by reducing the liver index, abdominal fat percentage, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) in the serum (P < 0.05), and subsequently increase the egg production rate (P < 0.05). The laying hens fed 0.8% MLE exhibited the greatest production performance (P < 0.05) and could improve serum lipid levels. In addition, the genes associated with fatty acid synthesis (ACC, HMGR and SREBP-1C) were downregulated (P < 0.05), and genes related to fatty acid oxidation (CPT1A, AMPK, and ATGL) were found to be upregulated (P < 0.05). Supplementation with 1.2% MLE significantly reduced the relative abundance of Firmicutes and Desulfurized Bacillus (P < 0.05) and significantly increased the relative abundance of Fecal Bacillus (P < 0.05). In conclusion, MLE may regulate the mRNA expression of lipid metabolism-related genes through the AMPK signaling pathway and improve cecal microbiota balance and serum lipid levels to alleviate FLHS in laying hens and subsequently improve egg production performance.

BackgroundThe status of the sentinel lymph nodes (SLNs) was an important prognostic factor in varies cancers. A one-step nucleic acid amplification (OSNA) assay, a molecular-based whole-node analysis method based on CK19 mRNA copy number, was developed to diagnose lymph node metastases. We aimed to evaluate the value of OSNA for the diagnosis of sentinel lymph node metastasis in CK19 positive cancers. CK19 mRNA and protein expression for pan-caner analysis were obtained from TCGA and the Human protein atlas database.MethodsTwo researchers independently searched the PubMed, Cochrane Library and Web of Science databases for qualified articles published before December 1, 2023. A meta-analysis was performed using MetaDisc and STATA. Risk bias and quality assessments of the included studies were evaluated, and a subgroup analysis was performed. Ten cancer types were found to be CK19 positively expressed and 7 of 10 had been reported to use OSNA for SLN detection.ResultsAfter literature review, there were 61 articles included in the meta-analysis, which consisted of 7115 patients with 18007 sentinel lymph nodes. The pooled sensitivity and specificity of OSNA were 0.87 and 0.95 in overall patients. Moreover, we found the background CK19 expression in normal tissue affected the diagnostic accuracy of OSNA. In breast cancer, we performed subgroup analysis. OSNA exhibited to be a stable method across different population groups and various medical centers. In addition, when 250 copies/μl was chosen as the cutoff point of CK19 mRNA, there were a relatively higher sensitivity and AUC in detecting SLN micro-metastasis than 5000 copies/μl.DiscussionOSNA can predict the occurrence of SLN metastasis accurately in CK19 positive cancers, especially in breast cancer, colorectal cancer, lung cancer, gastric cancer and endometrial cancer. Our study warrants future studies investigating the clinical application of OSNA in pancreatic, ovarian and bladder cancers.

Background: According to statistics, ovarian cancer (OV) is the most prevalent type of gynecologic malignancy and has the highest mortality rate of all gynecologic tumors. Although several studies have shown that oxidative stress (OS) contributes significantly to the onset and progression of cancer, the role of OS in OV needs to be investigated further. Thus, it is critical to comprehend the function of OS-related genes in OV. Methods: In this study, all data related to the transcriptome and clinical status of the patients were retrieved from “The Cancer Genome Atlas” (TCGA) and “Gene Expression Omnibus” (GEO) databases. Using the unsupervised cluster analysis technique, all patients with OV were classified into two different subtypes (categories) based on the OS gene. All hub genes were screened using the weighted gene co-expression network analysis (WGCNA). Since the hub genes and the differentially expressed genes (DEGs) in both categories were found to intersect, the univariate Cox regression analysis was implemented. A multivariate Cox analysis was also performed to construct a novel clinical prognosis model, which was validated using data from the GEO cohort. In addition, the relationship between risk score and immune cell infiltration level was evaluated using CIBERSORT. Finally, qRT-PCR was used to confirm the expression of the genes used to construct the model. Results: Two subtypes of OS were obtained. The findings indicated that OS-C1 had a better survival outcome than OS-C2. The results of WGCNA yielded 112 hub genes. For univariate COX regression analyses, 49 OS-related trait genes were obtained. Finally, a clinical prognostic model containing two genes was constructed. This model could differentiate between patients with OV having varying years of survival in the TCGA and GEO cohorts. The model risk score was verified as an independent prognostic indicator. According to the results of CIBERSORT, many tumor-infiltrating immune cells were found to be significantly related to the risk score. Furthermore, the results revealed that patients with low-risk OV in the CTLA4 treatment group had a high likelihood of benefiting from immunotherapy. qRT-PCR results also showed that the expression of MARVELD1 and VSIG4 was high in the OV samples. Conclusions: Analysis of the results suggested that the newly developed model, which contained two characteristic OS-related genes, could successfully predict the survival outcomes of all patients with OV. The findings of this study could offer valuable information and insights into the refinement of personalized therapy and immunotherapy for OV in the future.

Abstract This study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and food effects (FE) of SC0062, a highly active endothelin‐A (ETA) receptor antagonist, in healthy subjects. The primary objectives of this first‐in‐human phase I study, comprised of single‐ascending‐dose, multiple‐ascending‐dose, and FE parts, were to characterize the safety and tolerability of SC0062, and FE. The secondary objectives were to determine the PK behavior of SC0062 and its major active metabolite M18, whereas exploratory objectives focused on PD effects, principally effects on endothelin‐1 (ET‐1) and total bile acids (TBA). Single doses of 10 to 100 mg and multiple daily doses of 20 and 50 mg for 6 days were well tolerated. SC0062 was rapidly absorbed and plasma exposure of SC0062 and M18 increased disproportionately with dose, achieving steady state by day 3, with accumulation ratios of 1.22 and 1.89 on day 6 for SC0062 and M18, respectively. The geometric mean (geometric standard deviation) terminal elimination half‐life (t1/2) values of SC0062 and M18 were 7.25 (1.70) h and 13.73 (1.32) h, respectively. Plasma ET‐1 concentrations were dose‐proportional, whereas plasma TBA concentrations behaved erratically. Following a single 50 mg dose of SC0062 after a high‐fat meal, Cmax values for SC0062 and M18 increased by 41% and 32%, respectively, and median Tmax values for SC0062 were 3 h longer than fasting values; exposure was unaffected. These favorable safety, PK, and PD results provide a foundation for further studies of SC0062 in pulmonary arterial hypertension, chronic kidney disease, and other relevant indications.

Abstract Terpenoids are the main active components in the Zanthoxylum armatum leaves, which have extensive medicinal value. The Z. armatum leaf is the main by‐product in the Z. armatum industry. However, the transcription factors involved in the biosynthesis of terpenoids are rarely reported. This study was performed to identify and classify the APETALA2/ethylene‐responsive factor (AP2/ERF) gene family of Z. armatum. The chromosome distribution, gene structure, conserved motifs, and cis‐acting elements of the promoter of the species were also comprehensively analyzed. A total of 214 ZaAP2/ERFs were identified. From the obtained transcriptome and terpenoid content data, four candidate ZaAP2/ERFs involved in the biosynthesis of terpenoids were selected via correlation and weighted gene co‐expression network analysis. A phylogenetic tree was constructed using 13 AP2/ERFs related to the biosynthesis of terpenoids in other plants. ZaERF063 and ZaERF166 showed close evolutionary relationships with the ERFs in other plant species and shared a high AP2‐domain sequence similarity with the two closest AP2/ERF proteins, namelySmERF8 from Salvia miltiorrhiza and AaERF4 from Artemisia annua. Further investigation into the effects of methyl jasmonate (MeJA) treatment on the content of terpenoids in Z. armatum leaves revealed that MeJA significantly induced the upregulation of ZaERF166 and led to a significant increase in the terpenoids content in Z. armatum leaves, indicating that ZaERF166 might be involved in the accumulation of terpenoids of Z. armatum. Results will be beneficial for the functional characterization of AP2/ERFs in Z. armatum and establishment of the theoretical foundation to increase the production of terpenoids via the manipulation of the regulatory elements and strengthen the development and utilization of Z. armatum leaves.

Background: Liver hepatocellular carcinoma (LIHC) is a solid primary malignancy with poor prognosis. This study discovered key prognostic genes based on T cell exhaustion and used them to develop a prognostic prediction model for LIHC. Methods: SingleR's annotations combined with Seurat was used to automatically annotate the single-cell clustering results of the LIHC dataset GSE166635 downloaded from the Gene Expression Omnibus (GEO) database and to identify clusters related to exhausted T cells. Patients were classified using ConsensusClusterPlus package. Next, weighted gene co-expression network analysis (WGCNA) package was employed to distinguish key gene module, based on which least absolute shrinkage and selection operator (Lasso) and multi/univariate cox analysis were performed to construct a RiskScore system. Kaplan-Meier (KM) analysis and receiver operating characteristic curve (ROC) were employed to evaluate the efficacy of the model. To further optimize the risk model, a nomogram capable of predicting immune infiltration and immunotherapy sensitivity in different risk groups was developed. Expressions of genes were measured by quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence and Cell Counting Kit-8 (CCK-8) were performed for analyzing cell functions. Results: We obtained 18,413 cells and clustered them into 7 immune and non-immune cell subpopulations. Based on highly variable genes among T cell exhaustion clusters, 3 molecular subtypes (C1, C2 and C3) of LIHC were defined, with C3 subtype showing the highest score of exhausted T cells and a poor prognosis. The Lasso and multivariate cox analysis selected 7 risk genes from the green module, which were closely associated with the C3 subtype. All the patients were divided into low- and high-risk groups based on the medium value of RiskScore, and we found that high-risk patients had higher immune infiltration and immune escape and poorer prognosis. The nomogram exhibited a strong performance for predicting long-term LIHC prognosis. In vitro experiments revealed that the 7 risk genes all had a higher expression in HCC cells, and that both liver HCC cell numbers and cell viability were reduced by knocking down MMP-9. Conclusion: We developed a RiskScore model for predicting LIHC prognosis based on the scRNA-seq and RNA-seq data. The RiskScore as an independent prognostic factor could improve the clinical treatment for LIHC patients.

Background: Oxidative stress promotes the development of stomach adenocarcinoma (STAD) and resistance of STAD patients to chemotherapy. This study developed a risk classification and prognostic model for STAD based on genes related to oxidative stress. Methods: Univariate Cox regression and least absolute shrinkage and selection operator (Lasso) regression analysis were performed using transcriptome data of STAD from The Cancer Genome Atlas (TCGA) and reactive oxygen species (ROS)-related genes from Gene Set Enrichment Analysis (GSEA) website to develop a risk model. Genetic landscape, pathway characteristics and immune characteristics between the two risk groups were assessed to evaluate patients’ response to anti-tumor therapy. Further, a nomogram was created to evaluate the clinical outcomes of STAD patients. The mRNA levels of genes were detected by reverse transcription quantitative PCR (RT-qPCR). Results: Two ROS-related molecular subtypes (subtype C1 and C2) were classified, with subtype C2 having unfavorable prognosis, higher immune score, and greater infiltration of macrophages, myeloid-derived suppressor cells (MDSCs), mast cells, regulatory T cells, and C–C chemokine receptor (CCR). Five ROS-related genes (ASCL2, COMP, NOX1, PEG10, and VPREB3) were screened to develop a prognostic model, the robustness of which was validated in TCGA and external cohorts. RT-qPCR analysis showed that ASCL2, COMP, NOX1, and PEG10 were upregulated, while the mRNA level of VPREB3 was downregulated in gastric cancer cells. The risk score showed a negative relation to tumor mutation burden (TMB). Low-risk patients exhibited higher mutation frequencies of TTN, SYNE1, and ARID1A, higher response rate to immunotherapy and were more sensitive to 32 traditional chemotherapeutic drugs, while high-risk patients were sensitive to 13 drugs. Calibration curve and DCA confirmed the accuracy and reliability of the nomogram. Conclusion: These findings provided novel understanding on the mechanism of ROS in STAD. The current study developed a ROS-related signature to help predict the prognosis of patients suffering from STAD and to guide personalized treatment.

ObjectiveThis study is aim to discern the Traditional Chinese Medicine (TCM) syndrome classifications relevant to immunotherapy sensitive in non-small cell lung cancer (NSCLC) patients, and to delineate intestinal microbiota biomarkers and impact that wield influence over the efficacy of NSCLC immunotherapy, grounded in the TCM theory of “lung and large intestine stand in exterior-interior relationship.”MethodsThe study cohort consisted of patients with advanced NSCLC who received treatment at the Oncology Department of Chengdu Fifth People’s Hospital. These patients were categorized into distinct TCM syndrome types and subsequently administered immune checkpoint inhibitors (ICIs), specifically PD-1 inhibitors. Stool specimens were collected from patients both prior to and following treatment. To scrutinize the differences in microbial gene sequences and species of the intestinal microbiota, 16S rRNA amplicon sequencing technology was employed. Additionally, peripheral blood samples were collected, and the analysis encompassed the assessment of T lymphocyte subsets and myeloid suppressor cell subsets via flow cytometry. Subsequently, alterations in the immune microenvironment pre- and post-treatment were thoroughly analyzed.ResultsThe predominant clinical manifestations of advanced NSCLC patients encompassed spleen-lung Qi deficiency syndrome and Qi-Yin deficiency syndrome. Notably, the latter exhibited enhanced responsiveness to ICIs with a discernible amelioration of the immune microenvironment. Following ICIs treatment, significant variations in microbial abundance were identified among the three strains: Clostridia, Lachnospiraceae, and Lachnospirales, with a mutual dependency relationship. In the subset of patients manifesting positive PD-L1 expression and enduring therapeutic benefits, the study recorded marked increases in the ratios of CD3+%, CD4+%, and CD4+/CD8+ within the T lymphocyte subsets. Conversely, reductions were observed in the ratios of CD8%, Treg/CD4+, M-MDSC/MDSC, and G-MDSC/MDSC.ConclusionThe strains Clostridia, Lachnospiraceae, and Lachnospirales emerge as potential biomarkers denoting the composition of the intestinal microbiota in the NSCLC therapy. The immunotherapy efficacy of ICIs markedly accentuates in patients displaying durable treatment benefits and those expressing positive PD-L1.

IntroductionTo evaluate treatment strategies and clinical outcomes following endovascular embolization of tentorial dural arteriovenous fistulas.MethodsWe retrospectively analyzed 19 patients with tentorial dural arteriovenous fistulas admitted to the Department of Neurosurgery at Jiangsu Provincial People’s Hospital between October 2015 and May 2022, all treated with endovascular therapy. To collect and analyze patients’ clinical presentation, imaging data, postoperative complications, and prognosis and to analyze the safety and clinical outcomes of endovascular treatment of tentorial dural arteriovenous fistulas.ResultsImaging cure was achieved in 18 patients, with the arterial route chosen for embolization in 17 patients and the venous route in one patient; one patient received partial embolization. Staged embolization was performed in four patients. At postoperative follow-up of 9–83 months (37.8 ± 21.2), all 19 patients had recovered well (mRS score ≤ 2). Three patients experienced perioperative complications: intraoperative Onyx reflux into the middle cerebral artery in one patient; postoperative permanent limited left visual field loss and deafness in the left ear in one patient; and transient diplopia, vertigo, and decreased pain and temperature sensation of the left limb in one patient, with no abnormalities on post-procedure magnetic resonance examinations. A total of 17 patients completed a postoperative digital subtraction angiography review during follow-up, and one patient had a recurrence of an arteriovenous fistula.ConclusionEndovascular treatment of tentorial dural arteriovenous fistulas is safe and effective. Reduction of the Borden or Cognard classification via eliminating cortical venous reflux through multi-staged embolization or combined open surgery is a reasonable goal of treatment where complete obliteration of the fistula is not achievable.

Our focus of this paper is on global Mittag-Leffler synchronization (GMLS) of the Caputo-type Inertial Cohen-Grossberg Neural Networks (ICGNNs) with discrete and distributed delays. This model takes into account the inertial term as well as the two types of delays, which greatly reduces the conservatism with respect to the model. A change of variables transforms the $ 2\beta $ order inertial frame into $ \beta $ order ordinary frame in order to deal with the effect of the inertial term. In the following steps, two novel types of delay controllers are designed for the purpose of reaching the GMLS. In conjunction with the novel controllers, utilizing differential mean-value theorem and inequality techniques, several criteria are derived to determine the GMLS of ICGNNs within the framework of Caputo-type derivative and calculus properties. At length, the feasibility of the results is further demonstrated by two simulation examples.

The quantitative evaluation of the comprehensive efficiency of the equipment has important significance for making accurate maintenance and other decisions. From the perspective of equipment life cycle cost, this paper constructed the fixed cost function and dynamic cost function of power equipment and obtained the economic life model. The total cost of the whole life cycle of the optimal economic life was obtained by the derivation method. Then, a comprehensive performance evaluation index system including reliability, availability, maintainability and economy had been established. The comprehensive efficiency evaluation model based on economic life and the equipment maintenance optimization model based on comprehensive efficiency evaluation were designed. At last, taking 35 kV circuit breaker as an example, the economic life model and comprehensive efficiency evaluation model were analyzed and calculated. The results proved the correctness of the comprehensive efficiency evaluation model designed in this paper, which could provide technical guidance and support for the selection and maintenance of power equipment.

Abstract Objective This study aims to assess the transformative potential of Virtual Reality (VR) has shown significant potential in transforming nursing education by providing immersive and interactive learning experiences. Our objective is to systematically evaluate and conduct a meta-analysizes on the impact effect of virtual reality technology in teaching nursing students. Methods To achieve this, we conducted comprehensive computer searches on platforms including of PubMed, Web of Science, Wiley Online Library, Zhiwang database, Wanfang database, and China Biomedical Literature Service (SinoMed), were conducted to collect randomized controlled trial studies on the use of virtual reality’s technology for teaching nursing students built up to until March 2023., and the Cochrane Furthermore, the quality of the included literature was assessed evaluated using the quality evaluation criteria specified for randomized controlled trial studies within the Cochrane provided in the evaluation handbook manual. In addition, a meta-analysis was performed using Review Manager 5.3 software. Results The aggregate outcomes from a total of 12 randomized controlled trials, encompassing including 1167 students, indicate were included. Meta-analysis results showed that virtual reality technology significantly enhances could better improve nursing students’’ theoretical knowledge [(SMD = 0.97, 95% CI [0.48, 1.46], p

Abstract Indole alkaloids are one of the largest alkaloid classes, proving valuable structural moiety in pharmaceuticals. Although methods for the synthesis of indole alkaloids are constantly explored, the direct single-step synthesis of these chemical entities with broad structural diversity remains a formidable challenge. Herein, we report a modular assembly of tetrahydrocarboline type of indole alkaloids from simple building blocks in a single step while showing broad compatibility with medicinally relevant functionality. In this protocol, the 2-alkylated or 3-alkylated indoles, formaldehyde, and amine hydrochlorides could undergo a one-pot reaction to deliver γ-tetrahydrocarbolines or β-tetrahydrocarbolines directly. A wide scope of these readily available starting materials is applicable in this process, and numerous structural divergent tetrahydrocarbolines could be achieved rapidly. The control reaction and deuterium-labelling reaction are conducted to probe the mechanism. And mechanistically, this multicomponent reaction relies on a multiple alkylamination cascade wherein an unusual C(sp3)–C(sp3) connection was involved in this process. This method could render rapid access to pharmaceutically interesting compounds, greatly enlarge the indole alkaloid library and accelerate the lead compound optimization thus facilitating drug discovery.

Arbuscular mycorrhizal inoculation can promote plant growth, but specific research on the difference in the symbiosis effect of arbuscular mycorrhizal fungi and plant combination is not yet in-depth. Therefore, this study selected Medicago sativa L., Bromus inermis Leyss, and Festuca arundinacea Schreb., which were commonly used for restoring degraded land in China to inoculate with three AMF separately, to explore the effects of different AMF inoculation on the growth performance and nutrient absorption of different plants and to provide a scientific basis for the research and development of the combination of mycorrhiza and plants. We set up four treatments with inoculation Entrophospora etunicata (EE), Funneliformis mosseae (FM), Rhizophagus intraradices (RI), and non-inoculation. The main research findings are as follows: the three AMF formed a good symbiotic relationship with the three grassland plants, with RI and FM having more significant inoculation effects on plant height, biomass, and tiller number. Compared with C, the aboveground biomass of Medicago sativa L., Bromus inermis Leyss, and Festuca arundinacea Schreb. inoculated with AMF increased by 101.30–174.29%, 51.67–74.14%, and 110.67–174.67%. AMF inoculation enhanced the plant uptake of N, P, and K, and plant P and K contents were significantly correlated with plant biomass. PLS-PM analyses of three plants all showed that AMF inoculation increased plant nutrient uptake and then increased aboveground biomass and underground biomass by increasing plant height and root tillering. This study showed that RI was a more suitable AMF for combination with grassland degradation restoration grass species and proposed the potential mechanism of AMF–plant symbiosis to increase yield.

Background: The objective of this study is to estimate the causal relationship between plasma proteins and myocardial infarction (MI) through Mendelian randomization (MR), predict potential target-mediated side effects associated with protein interventions, and ensure a comprehensive assessment of clinical safety. Methods: From 3 proteome genome-wide association studies (GWASs) involving 9775 European participants, 331 unique blood proteins were screened and chosed. The summary data related to MI were derived from a GWAS meta-analysis, incorporating approximately 61,000 cases and 577,000 controls. The assessment of associations between blood proteins and MI was conducted through MR analyses. A phenome-wide MR (Phe-MR) analysis was subsequently employed to determine the potential on-target side effects of protein interventions. Results: Causal mediators for MI were identified, encompassing cardiotrophin-1 (CT-1) (odds ratio [OR] per SD increase: 1.16; 95% confidence interval [CI]: 1.13–1.18; p = 1.29 × 10-31), Selenoprotein S (SELENOS) (OR: 1.16; 95% CI: 1.13–1.20; p = 4.73 × 10-24), killer cell immunoglobulin-like receptor 2DS2 (KIR2DS2) (OR: 0.93; 95% CI: 0.90–0.96; p = 1.08 × 10-5), vacuolar protein sorting-associated protein 29 (VPS29) (OR: 0.92; 95% CI: 0.90–0.94; p = 8.05 × 10-13), and histo-blood group ABO system transferase (NAGAT) (OR: 1.05; 95% CI: 1.03–1.07; p = 1.41 × 10-5). In the Phe-MR analysis, memory loss risk was mediated by CT-1, VPS29 exhibited favorable effects on the risk of 5 diseases, and KIR2DS2 showed no predicted detrimental side effects. Conclusions: Elevated genetic predictions of KIR2DS2 and VPS29 appear to be linked to a reduced risk of MI, whereas an increased risk is associated with CT-1, SELENOS, and NAGAT. The characterization of side effect profiles aids in the prioritization of drug targets. Notably, KIR2DS2 emerges as a potentially promising target for preventing and treating MI, devoid of predicted detrimental side effects.