Research Foundation Research Articles

One-year outcomes of traumatic injuries among survivors in Ethiopia: a cross-sectional study on the employment outcomes and functioning state

BackgroundTraumatic injury is one of the top public health challenges globally. Injury survivors often experience poor health and functioning and restricted participation in employment. In Ethiopia, there is a paucity...

Genome-wide identification of polyamine metabolism and ethylene synthesis genes in Chenopodium quinoa Willd. and their responses to low-temperature stress

Abstract Background Quinoa (Chenopodium quinoa Willd.) is valued for its nutritional richness. However, pre-harvest sprouting poses a significant threat to yield and grain quality. This study aims to enhance our understanding of pre-harvest sprouting mitigation strategies, specifically through delayed sowing and avoiding rainy seasons during quinoa maturation. The overarching goal is to identify cold-resistant varieties and unravel the molecular mechanisms behind the low-temperature response of quinoa. We employed bioinformatics and genomics tools for a comprehensive genome-wide analysis of polyamines (PAs) and ethylene synthesis gene families in quinoa under low-temperature stress. Results This involved the identification of 37 PA biosynthesis and 30 PA catabolism genes, alongside 227 ethylene synthesis. Structural and phylogenetic analyses showcased conserved patterns, and subcellular localization predictions indicated diverse cellular distributions. The results indicate that the PA metabolism of quinoa is closely linked to ethylene synthesis, with multiple genes showing an upregulation in response to cold stress. However, differential expression within gene families suggests a nuanced regulatory network. Conclusions Overall, this study contributes valuable insights for the functional characterization of the PA metabolism and ethylene synthesis of quinoa, which emphasize their roles in plant low-temperature tolerance and providing a foundation for future research in this domain.

Corruption Disclosure and Electoral Accountability System: Reducing Political Corruption

This literature review explores how corruption exposure affects voter behavior, political dynamics, and the fate of current political parties and politicians. This demonstrates the importance of strengthening electoral accountability in maintaining democracy, combating corruption, and improving political systems. Research has found that the disclosure of corrupt practices significantly impacts voter behavior, as it may lead to a decrease in support for current political parties and politicians affected by corruption. In addition, exposing dereliction of duty is an important tool in combating political corruption, making the election process more transparent and accountable. Therefore, this review emphasizes the crucial role of exposing corrupt behavior in shaping voter behavior, holding politicians accountable, and maintaining the integrity of democratic systems under electoral accountability systems. This proves that strengthening electoral accountability plays an important role in maintaining democratic integrity and promoting responsive political models and provides an important foundation for future research in this field. Promote transparency in the election process and strengthen the implementation of accountability policies.

Novel results for separate families of fuzzy-dominated mappings satisfying advanced locally contractions in b-multiplicative metric spaces with applications

AbstractThe objective of this research is to present new fixed point theorems for two separate families of fuzzy-dominated mappings. These mappings must satisfy a unique locally contraction in a complete b-multiplicative metric space. Also, we have obtained novel results for families of fuzzy-dominated mappings on a closed ball that meet the requirements of a generalized locally contraction. This research introduces new and challenging fixed-point problems for families of ordered fuzzy-dominated mappings in ordered complete b-multiplicative metric spaces. Moreover, we demonstrate a new concept for families of fuzzy graph-dominated mappings on a closed ball in these spaces. Additionally, we present novel findings for graphic contraction endowed with graphic structure. These findings are groundbreaking and provide a strong foundation for future research in this field. To demonstrate the uniqueness of our novel findings, we provide evidence of their applicability in obtaining the common solution of integral and fractional differential equations. Our findings have resulted in modifications to several contemporary and classical results in the research literature. This provides further evidence of the originality and impact of our work.

Analysis of the importance of business model and business plan in the process of entrepreneurship: Taking college students entrepreneurship as an example

This article explores in depth entrepreneurship focusing on business models and business plans. Taking the difficulties and challenges faced by college students as an example, it analyzes the importance of business model innovation to entrepreneurial enterprises and its key role in market competition. The article first summarizes the concept of entrepreneurship and the problems it faces, and second introduces the business model and its application in entrepreneurship, the definition and components of the business plan, and how to make an effective business plan according to the market demand, technology trends and competitive environment. This paper points out that a successful business model needs to be closely combined with market positioning, product strategy, marketing means, profit model and other elements, and the formulation of a business plan requires rigorous steps. The study has concluded that: the business model is the core of the business plan, and the plan is the specific implementation of the model. The two need to adjust each other and jointly determine the success of the enterprise. The future development trend of business model and business plan is the trend of digitalization and intelligence, personalization and customization, flexibility and adaptability. This paper puts forward suggestions for entrepreneurs represented by college students: in-depth understanding of market and customer needs, the need to maintain innovative thinking, the feasibility of socialist plan, etc. Thus improving the success rate of entrepreneurship. This paper enriches the relevant theories of entrepreneurship, lays the foundation for in-depth research, and has certain theoretical significance.

Two missense STK11 gene variations impaired LKB1/adenosine monophosphate-activated protein kinase signaling in Peutz-Jeghers syndrome

BACKGROUND Peutz-Jeghers syndrome (PJS) is a rare hereditary neoplastic disorder mainly associated with serine/threonine kinase 11 (STK11 /LKB1 ) gene mutations. Preimplantation genetic testing can protect a patient’s offspring from mutated genes; however, some variations in this gene have been interpreted as variants of uncertain significance (VUS), which complicate reproductive decision-making in genetic counseling. AIM To identify the pathogenicity of two missense variants and provide clinical guidance. METHODS Whole exome gene sequencing and Sanger sequencing were performed on the peripheral blood of patients with PJS treated at the Reproductive and Genetic Hospital of Citic-Xiangya. Software was employed to predict the protein structure, conservation, and pathogenicity of the two missense variation sites in patients with PJS. Additionally, plasmids were constructed and transfected into HeLa cells to observe cell growth. The differences in signal pathway expression between the variant group and the wild-type group were compared using western blot and immunohistochemistry. Statistical analysis was performed using one-way analysis of variance. P < 0.05 was considered statistically significant. RESULTS We identified two missense STK11 gene VUS [c.889A>G (p.Arg297Gly) and c.733C>T (p.Leu245Phe)] in 9 unrelated PJS families who were seeking reproductive assistance. The two missense VUS were located in the catalytic domain of serine/threonine kinase, which is a key structure of the liver kinase B1 (LKB1) protein. In vitro experiments showed that the phosphorylation levels of adenosine monophosphate-activated protein kinase (AMPK) at Thr172 and LKB1 at Ser428 were significantly higher in transfected variation-type cells than in wild-type cells. In addition, the two missense STK11 variants promoted the proliferation of HeLa cells. Subsequent immunohistochemical analysis showed that phosphorylated-AMPK (Thr172) expression was significantly lower in gastric, colonic, and uterine polyps from PJS patients with missense variations than in non-PJS patients. Our findings indicate that these two missense STK11 variants are likely pathogenic and inactivate the STK11 gene, causing it to lose its function of regulating downstream phosphorylated-AMPK (Thr172), which may lead to the development of PJS. The identification of the pathogenic mutations in these two clinically characterized PJS patients has been helpful in guiding them toward the most appropriate mode of pregnancy assistance. CONCLUSION These two missense variants can be interpreted as likely pathogenic variants that mediated the onset of PJS in the two patients. These findings not only offer insights for clinical decision-making, but also serve as a foundation for further research and reanalysis of missense VUS in rare diseases.

The Characterization of G-Quadruplexes in Tobacco Genome and Their Function under Abiotic Stress

Tobacco is an ideal model plant in scientific research. G-quadruplex is a guanine-rich DNA structure, which regulates transcription and translation. In this study, the prevalence and potential function of G-quadruplexes in tobacco were systematically analyzed. In tobacco genomes, there were 2,924,271,002 G-quadruplexes in the nuclear genome, 430,597 in the mitochondrial genome, and 155,943 in the chloroplast genome. The density of the G-quadruplex in the organelle genome was higher than that in the nuclear genome. G-quadruplexes were abundant in the transcription regulatory region of the genome, and a difference in G-quadruplex density in two DNA strands was also observed. The promoter of 60.4% genes contained at least one G-quadruplex. Compared with up-regulated differentially expressed genes (DEGs), the G-quadruplex density in down-regulated DEGs was generally higher under drought stress and salt stress. The G-quadruplex formed by simple sequence repeat (SSR) and its flanking sequence in the promoter region of the NtBBX (Nitab4.5_0002943g0010) gene might enhance the drought tolerance of tobacco. This study lays a solid foundation for further research on G-quadruplex function in tobacco and other plants.

Renewable Energy Consumption in the Context of Economic Development, CO2 Emissions and Implications for Public Administration: The Case of Visegrad Group Countries

Renewable energy consumption has gained growing importance in the world energy consumption portfolio over recent years. One of the reasons is the increasingly negative development of climate change. The research carried out in this paper aims to discern whether the examined economic indicator (GDP per capita) and the environmental indicator (CO2 emissions per capita) affect the renewable energy consumption in the region of the Visegrad Group (V4 – Czech Republic, Hungary, Poland, and Slovak Republic) countries, and to draw implications for public administration in the given issue. The fixed effects panel regression model was used to verify the mentioned relationships between variables from 1990-2020. The results show that the level of the share of renewable energy consumption on the total energy consumption in the region of the V4 countries can be affected by the GDP per capita (positive relationship validated) and the CO2 emissions per capita (negative relationship validated). These results are mostly in line with the findings of other researchers conducted on different samples of countries, although some differences can be noted, especially regarding the direction of the relationship. The implications of the research results are presented on three levels: practical implications for the business sector, emphasis placed on political implications for public administration, and theoretical implications that lay the foundation for further research. The main limitation of the research results comes from the sample used in V4 countries and, thus, from the limited possibilities of generalizing the results. The direction of further research in the addressed issue will include a larger number of countries in the research and the use of various quantitative and qualitative research methods.

Optimization of extracting technology of iridoid glycosides and phenylethanoid glycosides from Pedicularis decora Franch. by G1-entropy-coupled response surface methodology and rapid identification by UPLC-Q/TOF-MS

Quality control and clarifying ingredients are the foundation of pharmacodynamic material basis research. Pedicularis decora Franch. (P. decora) is clinically used to treat Alzheimer’s disease and exerts significant antioxidative, anti-inflammatory and neuroprotective effects. However, there is little systematic research on the extraction and composition and the current research on P. decora focused on the quality control and extraction with aucubin as only quality marker. It reported that Iridoid glycosides (IGs) and phenylpropanoid glycosides (PeGs), which are characteristic components of the Pedicularis species, have been reported to have various anti-Alzheimer’s activity. This study focused on the extraction and rapid qualitative analysis of IGs and PeGs in P. decora. First, HPLC-UV method was established to detect five IGs and PeGs analytes simultaneously and assess the effect of the extraction technology. Then, the G1-entropy method with the Box-Behnken response surface design methodology was used to optimized extraction technology. The optimum conditions were determined to be reflux with 55% methanol aqueous solutions, at 75 °C for 50 min. Finally, by establishing UPLC-Q/TOF-MS, 15 IGs and 15 PeGs in P. decora were rapidly identified and characterized for the first time. The results will provide a reverence of a higher quality standard and the pharmacodynamic material basis research.

Chromosome-level genome assembly of Hippophae tibetana provides insights into high-altitude adaptation and flavonoid biosynthesis

BackgroundAs an endemic shrub of the Qinghai-Tibetan Plateau (QTP), the distribution of Hippophae tibetana Schlecht. ranges between 2800 and 5200 m above sea level. As the most basal branch of the Hippophae genus, H. tibetana has an extensive evolutionary history. The H. tibetana is a valuable tree for studying the ecological evolution of species under extreme conditions.ResultsHere, we generated a high-quality chromosome-level genome of H. tibetana. The total size of the assembly genome is 917 Mb. The phylogenomic analysis of 1064 single-copy genes showed a divergence between 3.4 and 12.8 Mya for H. tibetana. Multiple gene families associated with DNA repair and disease resistance were significantly expanded in H. tibetana. We also identified many genes related to DNA repair with signs of positive selection. These results showed expansion and positive selection likely play important roles in H. tibetana’s adaptation to comprehensive extreme environments in the QTP. A comprehensive genomic and transcriptomic analysis identified 49 genes involved in the flavonoid biosynthesis pathway in H. tibetana. We generated transgenic sea buckthorn hairy root producing high levels of flavonoid.ConclusionsTaken together, this H. tibetana high-quality genome provides insights into the plant adaptation mechanisms of plant under extreme environments and lay foundation for the functional genomic research and molecular breeding of H. tibetana.

A comprehensive exploration of twist1 to identify a biomarker for tumor immunity and prognosis in pan-cancer.

Twist1 has been identified as a critical gene in tumor, but current study of this gene remains limitative. This study aims to investigate its roles and potential mechanisms across pan-cancer. The study used various databases and computational techniques to analyze twist's RNA expression, clinical data, gene mutations, tumor stemness, tumor microenvironment, immune regulation. Furthermore, the experimental method of fluorescence staining was carried out to identify twist1 expression in various tumor masses. After analyzing the protein-protein interaction of TWIST, enrichment analysis and predictive potential drugs were performed, and molecular docking was conducted to validate. We found that twist1 expression was significantly higher in various types of cancer and associated with tumor stage, grade, and poor prognosis in multiple cancers. Differential expression of twist1 was linked to gene mutation, RNA modifications, and tumor stemness. Additionally, twist1 expression was positively associated with tumor immunoregulation and immune checkpoint. Salinomycin, klugline, isocephaelince, manassantin B, and pimonidazole are predictive potential drugs targeting TWIST1. This study revealed that twist1 plays an important role in tumor, and might be a curial marker in tumor diagnose and prognosis. The study also highlighted twist1 as a promising therapeutic target for cancer treatment and provided a foundation for future research.

The role of transcription factor FOXA1/C2/M1/O3/P1/Q1 in breast cancer.

Breast cancer is a common malignancy with the highest mortality rate among women worldwide. Its incidence is on the rise year after year, accounting for more than one-tenth of new cancers worldwide. Increasing evidence suggests that forkhead box (FOX) transcription factors play an important role in the occurrence and development of breast cancer. However, little is known about the relationship between the expression, prognostic value, function, and immune infiltration of FOX transcription factors in tumor microenvironment. We used bioinformatics to investigate expression and function of FOX factor in breast cancer. Our results revealed the expression levels of FOXA1 and FOXM1 were significantly higher in breast cancer tissues than in normal tissues. The high expression of mRNA in FOXA1 (P < .05), FOXM1 (P < .01), and FOXP1 (P < .05) groups was related to tumor stage. Survival analysis results showed that increased FOXP1 mRNA levels were significantly associated with overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) in all patients with breast cancer (P < .05). Patients with the FOXA1 high-expression group had better RFS and DMFS than the low-expression group (P < .05), while patients with FOXM1 high-expression group had worse RFS, OS, and DMFS than the low-expression group (P < .05). Meanwhile, mutation analysis showed that genetic alterations in FOX transcription factors were significantly associated with shorter OS and progression-free survival (P < .05), but not with disease-free survival (P = .710) in patients with breast cancer. FOXP1, FOXA1, and FOXM1 may be used as potential biomarkers to predict the prognosis of patients with breast cancer. Functional enrichment indicated that FOX was mainly involved in cell division, cell senescence, cell cycle, and prolactin signaling pathway. In patients with breast cancer, FOXC2 expression was negatively correlated with the infiltration of B cells and positively correlated with the infiltration of neutrophils and dendritic cells. However, FOXM1 was negatively correlated with the infiltration of CD8 + T cells and macrophages and positively correlated with the infiltration of neutrophils and dendritic cells. These findings provided novel insights into the screening of prognostic biomarkers of the FOX family in breast cancer and laid a foundation for further research on the immune infiltration of the FOX transcription factor family members in tumors.

Transcriptome and small RNA analysis unveils novel insights into the C4 gene regulation in sugarcane.

This study reveals miRNA indirect regulation of C4 genes in sugarcane through transcription factors, highlighting potential key regulators like SsHAM3a. C4 photosynthesis is crucial for the high productivity and biomass of sugarcane, however, the miRNA regulation of C4 genes in sugarcane remains elusive. We have identified 384 miRNAs along the leaf gradients, including 293 known miRNAs and 91 novel miRNAs. Among these, 86 unique miRNAs exhibited differential expression patterns, and we identified 3511 potential expressed targets of these differentially expressed miRNAs (DEmiRNAs). Analyses using Pearson correlation coefficient (PCC) and Gene Ontology (GO) enrichment revealed that targets of miRNAs with positive correlations are integral to chlorophyll-related photosynthetic processes. In contrast, negatively correlated pairs are primarily associated with metabolic functions. It is worth noting that no C4 genes were predicted as targets of DEmiRNAs. Our application of weighted gene co-expression network analysis (WGCNA) led to a gene regulatory network (GRN) suggesting miRNAs might indirectly regulate C4 genes via transcription factors (TFs). The GRAS TF SsHAM3a emerged as a potential regulator of C4 genes, targeted by miR171y and miR171am, and exhibiting a negative correlation with miRNA expression along the leaf gradient. This study sheds light on the complex involvement of miRNAs in regulating C4 genes, offering a foundation for future research into enhancing sugarcane's photosynthetic efficiency.

Current global status of male reproductive health

Abstract BACKGROUND The widespread interest in male reproductive health (MRH), fueled by emerging evidence, such as the global decline in sperm counts, has intensified concerns about the status of MRH. Consequently, there is a pressing requirement for a strategic, systematic approach to identify critical questions, collect pertinent information, and utilize this data to develop evidence-based strategies. The methods for addressing these questions and the pathways towards their answers will inevitably vary based on the variations in cultural, geopolitical, and health-related contexts. To address these issues, a conjoint ESHRE and Male Reproductive Health Initiative (MRHI) Campus workshop was convened. OBJECTIVE AND RATIONALE The three objectives were: first, to assess the current state of MRH around the world; second, to identify some of the key gaps in knowledge; and, third, to examine how MRH stakeholders can collaboratively generate intelligent and effective paths forward. SEARCH METHODS Each expert reviewed and summarized the current literature that was subsequently used to provide a comprehensive overview of challenges related to MRH. OUTCOMES This narrative report is an overview of the data, opinions and arguments presented during the workshop. A number of outcomes are presented and can be summarized by the following overarching themes: MRH is a serious global issue and there is a plethora of gaps in our understanding; there is a need for widespread international collaborative networks to undertake multidisciplinary research into fundamental issues, such as lifestyle/environmental exposure studies, and high quality clincial trials; and there is an urgent requirement for effective strategies to educate young people and the general public to safeguard and improve MRH across diverse population demographics and resources. LIMITATIONS, REASONS FOR CAUTION This was a workshop where worldwide leading experts from a wide range of disciplines presented and discussed the evidence regarding challenges related to MRH. Whilst each expert summarised the current literature and placed it in context, the data in a number of areas is limited and/or sparse. Equally, important areas for consideration may have been missed. Moreover, there are clear gaps in our knowledge base, which makes some conclusions necessarily speculative and warranting of further study. WIDER IMPLICATIONS Poor MRH is a global issue that suffers from low awareness among the public, patients and heathcare professionals. Addressing this will require a coordinated multidisciplinary approach. Addressing the significant number of knowledge gaps will require policy makers prioritizing MRH and its funding. STUDY FUNDING/COMPETING INTEREST(S) The authors extend their gratitude to ESHRE for financial support of the Budapest Campus Workshop. PB is the Director of the not-for-profit organization Global Action on Men’s Health and receives fees and expenses for his work, (which includes the preparation of this manuscript. Conflicts of interest: CJDJ, CLRB, RAA, PB, MPC, MLE, NG, NJ, CK, AAP, MKO, SR-H, MHV-L: ESHRE Campus Workshop 2022 (Travel support—personal). CJDJ: Cambridge University Press (book royalties—personal). ESHRE Annual Meeting 2022 and Yale University Panel Meeting 2023 (Travel support—personal). CLRB: Ferring and IBSA (Lecture), RBMO editor (Honorarium to support travel etc), ExSeed and ExScentia (University of Dundee), Bill &amp; Melinda Gates Foundation (for research on contraception). MPC: Previously received funding from pharmaceutical companies for health economic research. The funding was not in relation to this work and had no bearing on the contents of this work. No funding from other sources has been provided in relation to this work (Funding was provided to his company Global Market Access Solutions. MLE: Advisor to Ro, Doveras, Next, Hannah, Sandstone CK: European Academy of Andrology (Past president UNPAID), SK: CEO of His Turn, a male fertility Diagnostic and Therapeutic company (No payments or profits to date). RIM: www.healthymale.org.au (Australian Government funded not for profit in men’s health sector (Employed as Medical Director 0.2 FET), Monash IVF Pty Ltd (Equity holder). NJ: Merck (consulting fees), Gedeon Richter (honoraria). SR-H: ESHRE (Travel reimbursements). CN: LLC (Nursing educator); COMMIT (Core Outcomes Measures for Infertility Trials) Advisor, meeting attendee and co-author; COMMA (Core Outcomes in Menopause) Meeting attendee and co-author; International Federation of Gynecology and Obstetrics (FIGO) Delegate Letters and Sciences; ReproNovo, Advisory board; American Board of Urology Examiner; American Urological Association Journal subsection editor, committee member, guidelines co-author Ferring Scientific trial NexHand Chief Technology Officer, stock ownership Posterity Health Board member, stock ownership. AP: Economic and Social Research Council (A collaborator on research grant number ES/W001381/1). Member of an advisory committee for Merck Serono (November 2022), Member of an advisory board for Exceed Health, Speaker fees for educational events organized by Mealis Group; Chairman of the Cryos External Scientific Advisory Committee: All fees associated with this are paid to his former employer The University of Sheffield. Trustee of the Progress Educational Trust (Unpaid). MKO’B: National Health and Medical Research Council and Australian Research Council (Funding for research of the topic of male fertility), Bill and Melinda Gates Foundation (Funding aimed at the development of male gamete-based contraception), Medical Research Future Fund (Funding aimed at defining the long-term consequences of male infertility). MHV-L: Department of Sexual and Reproductive Health and Research (SRH)/Human Reproduction Programme (HRP) Research Project Panel RP2/WHO Review Member; MRHI (Core Group Member), COMMIT (member) EGOI (Member); Human Reproduction (Editor), Fertility and Sterility (Editor), AndroLATAM (Founder and Coordinator).

Phytochemicals derived from Nicotiana tabacum L. plant contribute to pharmaceutical development

The Nicotiana tabacum L. plant, a medicinal resource, holds significant potential for benefiting human health, as evidenced by its use in Native American and ancient Chinese cultures. Modern medical and pharmaceutical studies have investigated that the abundant and distinctive function metabolites in tobacco including nicotine, solanesol, cembranoid diterpenes, essential oil, seed oil and other tobacco extracts, avoiding the toxic components of smoke, mainly have the anti-oxidation, anti-lipid production, pro-lipid oxidation, pro-insulin sensitivity, anti-inflammation, anti-apoptosis and antimicrobial activities. They showed potential pharmaceutical value mainly as supplements or substitutes for treating neurodegenerative diseases including Alzheimer’s and Parkinson’s disease, inflammatory diseases including colitis, arthritis, sepsis, multiple sclerosis, and myocarditis, and metabolic syndrome including Obesity and fatty liver. This review comprehensively presents the research status and the molecular mechanisms of tobacco and its metabolites basing on almost all the English and Chinese literature in recent 20 years in the field of medicine and pharmacology. This review serves as a foundation for future research on the medicinal potential of tobacco plants.

Exploring a multimodal approach for utilizing digital biomarkers for childhood mental health screening

BackgroundDepression and anxiety are prevalent mental health concerns among children and adolescents. The application of conventional assessment methods, such as survey questionnaires to children, may lead to self-reporting issues. Digital biomarkers provide extensive data, reducing bias in mental health self-reporting, and significantly influence patient screening. Our primary objectives were to accurately assess children’s mental health and to investigate the feasibility of using various digital biomarkers.MethodsThis study included a total of 54 boys and girls aged between 7 to 11 years. Each participant’s mental state was assessed using the Depression, Anxiety, and Stress Scale. Subsequently, the subjects participated in digital biomarker collection tasks. Heart rate variability (HRV) data were collected using a camera sensor. Eye-tracking data were collected through tasks displaying emotion-face stimuli. Voice data were obtained by recording the participants’ voices while they engaged in free speech and description tasks.ResultsDepressive symptoms were positively correlated with low frequency (LF, 0.04–0.15 Hz of HRV) in HRV and negatively associated with eye-tracking variables. Anxiety symptoms had a negative correlation with high frequency (HF, 0.15–0.40 Hz of HRV) in HRV and a positive association with LF/HF. Regarding stress, eye-tracking variables indicated a positive correlation, while pNN50, which represents the proportion of NN50 (the number of pairs of successive R-R intervals differing by more than 50 milliseconds) divided by the total number of NN (R-R) intervals, exhibited a negative association. Variables identified for childhood depression included LF and the total time spent looking at a sad face. Those variables recognized for anxiety were LF/HF, heart rate (HR), and pNN50. For childhood stress, HF, LF, and Jitter showed different correlation patterns between the two grade groups.DiscussionWe examined the potential of multimodal biomarkers in children, identifying features linked to childhood depression, particularly LF and the Sad.TF:time. Anxiety was most effectively explained by HRV features. To explore reasons for non-replication of previous studies, we categorized participants by elementary school grades into lower grades (1st, 2nd, 3rd) and upper grades (4th, 5th, 6th).ConclusionThis study confirmed the potential use of multimodal digital biomarkers for children’s mental health screening, serving as foundational research.

Mapping early brain-body interactions: associations of fetal heart rate variation with newborn brainstem, hypothalamic, and dorsal anterior cingulate cortex functional connectivity.

The autonomic nervous system (ANS) regulates the body's physiology, including cardiovascular function. As the ANS develops during the second to third trimester, fetal heart rate variability (HRV) increases while fetal heart rate (HR) decreases. In this way, fetal HR and HRV provide an index of fetal autonomic nervous system development and future neurobehavioral regulation. Fetal HR and HRV have been associated with child language ability and psychomotor development behavior in toddlerhood. However, their associations with post-birth autonomic brain systems, such as the brainstem, hypothalamus, and dorsal anterior cingulate cortex (dACC), have yet to be investigated even though brain pathways involved in autonomic regulation are well established in older individuals. We assessed whether fetal HR and HRV were associated with the brainstem, hypothalamic and dACC functional connectivity in newborns. Data were obtained from 60 pregnant individuals (ages 14-42) at 24-27 and 34-37 weeks gestation using a fetal actocardiograph to generate fetal HR and HRV. During natural sleep, their infants (38 males and 22 females) underwent a fMRI scan between 40-46 weeks of postmenstrual age. Our findings relate fetal heart indices to brainstem, hypothalamic, and dACC connectivity and reveal connections with widespread brain regions that may support behavioral and emotional regulation. We demonstrated the basic physiologic association between fetal HR indices and lower and higher order brain regions involved in regulatory processes. This work provides the foundation for future behavioral or physiological regulation research in fetuses and infants.Significance statement Fetal heart rate indices are quantifiable, developmental markers of the fetal autonomic nervous system. Variations in their trajectories can signal compromised neurodevelopmental outcomes. We assessed associations between fetal heart rate indices and early infant brain development to identify unique or common associations corresponding to autonomic nervous system maturation patterns. We found associations between fetal heart rate indices and infant brainstem, hypothalamic, and dACC connectivity-areas that support autonomic and behavioral regulatory functions. The study demonstrates that these associations between ANS and brain regions involved in autonomic regulation exist early in life. These findings are a first step to understanding how these brain connections form the basis of future regulatory development.

Mesenchymal stem cells derived-exosomes enhanced amniotic membrane extract promotes corneal keratocyte proliferation.

Amniotic membrane extract (AME) and Wharton's jelly mesenchymal stem cells derived-exosomes (WJ-MSC-Exos) are promising therapeutic solutions explored for their potential in tissue engineering and regenerative medicine, particularly in skin and corneal wound healing applications. AME is an extract form of human amniotic membrane and known to contain a plethora of cytokines and growth factors, making it a highly attractive option for topical applications. Similarly, WJ-MSC-Exos have garnered significant interest for their wound healing properties. Although WJ-MSC-Exos and AME have been used separately for wound healing research, their combined synergistic effects have not been studied extensively. In this study, we evaluated the effects of both AME and WJ-MSC-Exos, individually and together, on the proliferation of corneal keratocytes as well as their ability to promote in vitro cell migration, wound healing, and their impact on cellular morphology. Our findings indicated that the presence of both exosomes (3 × 105 Exo/mL) and AME (50 μg/mL) synergistically enhance the proliferation of corneal keratocytes. Combined use of these solutions (3 × 105 Exo/mL + 50 μg/mL) increased cell proliferation compared to only 50 μg/mL AME treatment on day 3 (**** p < 0.0001). This mixture treatment (3 × 105 Exo/mL + 50 μg/mL) increased wound closure rate compared to isolated WJ-MSC-Exo treatment (3 × 105 Exo/mL) (*p < 0.05). Overall, corneal keratocytes treated with AME and WJ-MSC-Exo (3 × 105 Exo/mL + 50 μg/mL) mixture resulted in enhanced proliferation and wound healing tendency. Utilization of combined use of AME and WJ-MSC-Exo can pave the way for a promising foundation for corneal repair research.

TMT-Based Quantitative Proteomic Analysis Reveals the Key Role of Cell Proliferation and Apoptosis in Intestine Regeneration of Apostichopus japonicus

Sea cucumbers are widely known for their powerful regenerative abilities, which allow them to regenerate a complete digestive tract within a relatively short time following injury or autotomy. Recently, even though the histological changes and cellular events in the processes of intestinal regeneration have been extensively studied, the molecular machinery behind this faculty remains unclear. In this study, tandem mass tag (TMT)-based quantitation was utilized to investigate protein abundance changes during the process of intestine regeneration. Approximately 538, 445, 397, 1012, and 966 differential proteins (DEPs) were detected (p &lt; 0.05) between the normal and 2, 7, 12, 20, and 28 dpe stages, respectively. These DEPs also mainly focus on pathways of cell proliferation and apoptosis, which were further validated by 5-Ethynyl-2′-deoxyuridine (EdU) or Tunel-based flow cytometry assay. These findings provide a reference for a comprehensive understanding of the regulatory mechanisms of various stages of intestinal regeneration and provide a foundation for subsequent research on changes in cell fate in echinoderms.

Improving chilling tolerance of peanut seedlings by enhancing antioxidant-modulated ROS scavenging ability, alleviating photosynthetic inhibition, and mobilizing nutrient absorption.

Peanut production is threatened by climate change. Damage to seedlings from low temperatures in early spring can limit yield. Plant adaptations to chilling stress remain unclear in peanut seedlings. It is essential to understand how peanut acquires chilling tolerance. We evaluated effects of chilling stress on growth and recovery of peanut seedlings. We compared and analysed biological characteristics, antioxidants, photosynthesis, biochemical and physiological responses, and nutrient absorption at varying levels of chilling. Compared with chilling-sensitive FH18, the reduced impact of chilling stress on chilling-tolerant NH5 was associated with reduced ROS accumulation, higher ascorbate peroxidase activity and soluble sugar content, lower soluble protein content, and smaller reductions in nutrient content during stress. After removal of chilling stress, FH18 had significant accumulation of O2 •- and H2O2, which decreased photosynthesis, nutrient absorption, and transport. ROS-scavenging reduced damage from chilling stress, allowed remobilization of nutrients, improved chilling tolerance, and restored plant functioning after chilling stress removal. These findings provide a reference for targeted research on peanut seedling tolerance to chilling and lay the foundation for bioinformatics-based research on peanut chilling tolerance mechanisms.