bluuebunny/crossref_metadata_2025 huggingface dataset:
Which contributes more to the relict flora distribution pattern in East Asia, geographical processes or climate change? New evidence from the phylogeography of Rehderodendron kwangtungense
Authors: Jin Jiehao , Zhao Wanyi , Chen Sufang , Gu Chao , Chen Zhihui , Liu Zhongcheng , Liao Wenbo , Fan Qiang
Published: May 2024

Background

Relict species are important for enhancing the understanding of modern biogeographic distribution patterns. Although both geological and climatic changes since the Cenozoic have affected the relict flora in East Asia, the contributions of geographical processes remain unclear. In this study, we employed restriction-site associated DNA sequencing (RAD-seq) and shallow genome sequencing data, in conjunction with ecological niche modeling (ENM), to investigate the spatial genetic patterns and population differentiation history of the relict species Rehderodendron kwangtungense Chun.

Results

A total of 138 individuals from 16 populations were collected, largely covering the natural distribution of R. kwangtungense. The genetic diversity within the R. kwangtungense populations was extremely low (HO = 0.048 ± 0.019; HE = 0.033 ± 0.011). Mantel tests revealed isolation-by-distance pattern (R2 = 0.38, P < 0.001), and AMOVA analysis showed that the genetic variation of R. kwangtungense occurs mainly between populations (86.88%, K = 7). Between 23 and 21 Ma, R. kwangtungense underwent a period of rapid differentiation that coincided with the rise of the Himalayas and the establishment of the East Asian monsoon. According to ENM and population demographic history, the suitable area and effective population size of R. kwangtungense decreased sharply during the glacial period and expanded after the last glacial maximum (LGM).

Conclusion

Our study shows that the distribution pattern of southern China mountain relict flora may have developed during the panplain stage between the middle Oligocene and the early Miocene. Then, the flora later fragmented under the force of orogenesis, including intermittent uplift during the Cenozoic Himalayan orogeny and the formation of abundant rainfall associated with the East Asian monsoon. The findings emphasized the predominant role of geographical processes in shaping relict plant distribution patterns.
Inflammatory biomarkers in cardiac syndrome X: a systematic review and meta-analysis
Authors: Zhao Yuexia , Ghaedi Arshin , Azami Pouria , Nabipoorashrafi Seyed Ali , Drissi Hamed Bazrafshan , Dezfouli Maryam Amin , Sarejloo Shirin , Lucke-Wold Brandon , Cerillo John , Khanzadeh Monireh , Jafari Negar , Khanzadeh Shokoufeh
Published: May 2024

Introduction

In the current systematic review and meta-analysis, we aim to analyze the existing literature to evaluate the role of inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) among individuals with cardiac syndrome X (CSX) compared to healthy controls.

Methods

We used PubMed, Web of Science, Scopus, Science Direct, and Embase to systematically search relevant publications published before April 2, 2023. We performed the meta-analysis using Stata 11.2 software (Stata Corp, College Station, TX). So, we used standardized mean difference (SMD) with a 95% confidence interval (CI) to compare the biomarker level between patients and healthy controls. The I2 and Cochran’s Q tests were adopted to determine the heterogeneity of the included studies.

Results

Overall, 29 articles with 3480 participants (1855 with CSX and 1625 healthy controls) were included in the analysis. There was a significantly higher level of NLR (SMD = 0.85, 95%CI = 0.55–1.15, I2 = 89.0 %), CRP (SMD = 0.69, 95%CI = 0.38 to 1.02, p < 0.0001), IL-6 (SMD = 5.70, 95%CI = 1.91 to 9.50, p = 0.003), TNF-a (SMD = 3.78, 95%CI = 0.63 to 6.92, p = 0.019), and PLR (SMD = 1.38, 95%CI = 0.50 to 2.28, p = 0.02) in the CSX group in comparison with healthy controls.

Conclusion

The results of this study showed that CSX leads to a significant increase in inflammatory biomarkers, including NLR, CRP, IL-6, TNF-a, and PLR.
SPAG5 deficiency activates autophagy to reduce atherosclerotic plaque formation in ApoE−/− mice
Authors: Guo Liangyun , Yuan Huijing , Zhu Huayao , Zhou Jie , Wan Zixin , Zhou Yihua
Published: May 2024

Background

Autophagy, as a regulator of cell survival, plays an important role in atherosclerosis (AS). Sperm associated antigen 5 (SPAG5) is closely associated with the classical autophagy pathway, PI3K/Akt/mTOR signaling pathway. This work attempted to investigate whether SPAG5 can affect AS development by regulating autophagy.

Methods

Human umbilical vein endothelial cells (HUVECs) were treated with oxidized-low density lipoprotein (ox-LDL) to induce cell damage. ApoE−/− mice were fed a Western diet to establish an AS mouse model. Haematoxylin and eosin (H&E) staining and Oil Red O staining evaluated the pathological changes and in lipid deposition in aortic tissues. CCK-8 and flow cytometry detected cell proliferation and apoptosis. Immunohistochemistry, Enzyme linked immunosorbent assay, qRT-PCR and western blotting assessed the levels of mRNA and proteins.

Results

Ox-LDL treatment elevated SPAG5 expression and the expression of autophagy-related proteins, LC3-I, LC3-II, Beclin-1, and p62, in HUVECs. GFP-LC3 dots were increased in ox-LDL-treated HUVECs and LPS-treated HUVECs. SPAG5 knockdown reversed both ox-LDL and LPS treatment-mediated inhibition of cell proliferation and promotion of apoptosis in HUVECs. SPAG5 silencing further elevated autophagy and repressed the expression of PI3K, p-Akt/Akt, and p-mTOR/mTOR in ox-LDL-treated HUVECs. 3-MA (autophagy inhibitor) treatment reversed SPAG5 silencing-mediated increase of cell proliferation and decrease of apoptosis in ox-LDL-treated HUVECs. In vivo, SPAG5 knockdown reduced atherosclerotic plaques in AS mice through activating autophagy and inhibiting PI3K/Akt/mTOR signaling pathway.

Conclusion

This work demonstrated that SPAG5 knockdown alleviated AS development through activating autophagy. Thus, SPAG5 may be a potential target for AS therapy.
Comparative performance of contact plate metod and swab method for surface microbial contamination on medical fabrics
Authors: Chen Feng , Li Yaru , Wang Wanqiu , Li Juan , Wang Dong , Sun Xiaxia , Peng Yaping , Deng Jianjun
Published: May 2024

Background

The contact plate method is widely accepted and used in various fields where hygiene and contamination levels are crucial. Evidence regarding the applicability of the contact plate method for sampling fabric microbial contamination levels in real medical environments was limited. This study aimed to assess the applicability of the contact plate method for detecting microbial contamination on medical fabrics in a real healthcare environment, thereby providing a benchmark for fabric microbial sampling methods.

Methods

In a level three obstetrics ward of a hospital, twenty-four privacy curtains adjacent to patient beds were selected for this study. The contact plate and swab method were used to collect microbial samples from the privacy curtains on the 1st, 7th, 14th, and 28th days after they were hung. The total colony count on each privacy curtain surface was calculated, and microbial identification was performed.

Results

After excluding the effects of time, room type, and curtain location on the detected microbial load, the linear mixed-effects model analysis showed that contact plate method yielded lower colony counts compared to swab method (P < 0.001). However, the contact plate method isolated more microbial species than swab method (P < 0.001). 291 pathogenic strains were isolated using the contact plate method and 133 pathogenic strains were isolated via the swab method. There was no difference between the two sampling methods in the detection of gram-negative bacteria (P = 0.089). Furthermore, the microbial load on curtains in double-occupancy rooms was lower than those in triple-occupancy rooms (P = 0.021), and the microbial load on curtains near windows was lower than that near doors (P = 0.004).

Conclusion

Contact plate method is superior to swab method in strain isolation. Swab method is more suitable for evaluating the bacterial contamination of fabrics.
Development and validation of a prenatal predictive nomogram for the risk of NICU admission in infants born to Chinese mothers over 35 years of age: a retrospective cohort study
Authors: Wei Yihong , Xu Shuai , Sun Wenjuan , Hong Fanzhen
Published: May 2024

Background

The rising number of women giving birth at advanced maternal age has posed significant challenges in obstetric care in recent years, resulting in increased incidence of neonatal transfer to the Neonatal Intensive Care Unit (NICU). Therefore, identifying fetuses requiring NICU transfer before delivery is essential for guiding targeted preventive measures.

Objective

This study aims to construct and validate a nomogram for predicting the prenatal risk of NICU admission in neonates born to mothers over 35 years of age.

Study design

Clinical data of 4218 mothers aged ≥ 35 years who gave birth at the Department of Obstetrics of the Second Hospital of Shandong University between January 1, 2017 and December 31, 2021 were reviewed. Independent predictors were identified by multivariable logistic regression, and a predictive nomogram was subsequently constructed for the risk of neonatal NICU admission.

Results

Multivariate logistic regression demonstrated that the method of prenatal screening, number of implanted embryos, preterm premature rupture of the membranes, preeclampsia, HELLP syndrome, fetal distress, premature birth, and cause of preterm birth are independent predictors of neonatal NICU admission. Analysis of the nomogram decision curve based on these 8 independent predictors showed that the prediction model has good net benefit and clinical utility.

Conclusion

The nomogram demonstrates favorable performance in predicting the risk of neonatal NICU transfer after delivery by mothers older than 35 years. The model serves as an accurate and effective tool for clinicians to predict NICU admission in a timely manner.
Impact of ophthalmic clinical service use in mitigating myopia onset and progression in preschool children: a retrospective cohort study
Authors: Lyu Pingping , Hu Jingwen , Wang Yujie , Wang Jingjing , He Xiangui , Shi Huijing
Published: May 2024

Background

Although school screenings identify children with vision problems and issue referrals for medical treatment at an ophthalmic hospital, the effectiveness of this approach remains unverified.

Objective

To investigate the impact of ophthalmic clinical services on the onset and progression of myopia in preschool children identified with vision impairment.

Methods

Using data from the Shanghai Child and Adolescent Large-scale Eye Study (SCALE), this retrospective cohort study evaluated the visual development of children from three districts—Jing’an, Minhang, and Pudong—which are representative of geographic diversity and economic disparity in Shanghai’s 17 districts. Initially, in 2015, the study encompassed 14,572 children aged 4–6 years, of whom 5,917 needed a referral. Our cohort consisted of 5,511 children who had two or more vision screenings and complete personal information over the follow-up period from January 2015 to December 2020. We divided these children into two groups based on their initial spherical equivalent (SE): a High-risk group (SE > -0.5 D) and a Myopia group (SE ≤ -0.5 D). Within each of these groups, we further categorized children into Never, Tardily, and Timely groups based on their referral compliance to compare the differences in the occurrence and progression of myopia. Cox proportional models were applied to estimate hazard ratios (HRs) for myopia incidence per person-years of follow-up in High-risk group. Generalized additive models(GAM) was used to calculating the progression for annual spherical equivalent changes in all children.

Results

Of the 5,511 preschool children (mean age, 5.25 years; 52.24% male) who received a referral recommendation, 1,327 (24.08%) sought clinical services at an ophthalmic hospital. After six years of follow-up, 65.53% of children developed myopia. The six-year cumulative incidence of myopia in the Never, Tardily, and Timely groups was 64.76%, 69.31%, and 57.14%, respectively. These percentages corresponded to hazard ratios (HRs) of 1.31 (95% CI, 1.10–1.55) for the Tardily group and 0.55 (95% CI, 0.33–0.93) for the Timely group, compared with the Never group. The HRs were adjusted for age, sex, and SE at study entry. Interestingly, the Timely group showed significantly less SE progression than the other groups (P < 0.001), and SE progression was higher in the High-risk group (-0.33 ± 0.37D/year) than in children with myopia (-0.08 ± 0.55D/year).

Conclusion

Timely utilization of ophthalmic clinical services among children aged 4 to 6 years who fail school vision screenings can significantly reduce the incidence of myopia and slow SE progression.
Association of parental depression with adolescent children’s psychological well-being and health behaviors
Authors: Kim Sung-In , Kim Sung Min , Park Sun Jae , Song Jihun , Lee Jaewon , Kim Kyae Hyung , Park Sang Min
Published: May 2024

Background

Parental depression is a significant problem that negatively affects parents’ welfare and influences family dynamics, children’s academic and health behaviors, and mental health. However, there is limited evidence regarding the impact of the parental depression into the children’s’ psychological and physical wellbeing on Asian cultures. This study examined the psychological burdens and health behaviors of adolescent children with parents with depression in the Republic of Korea.

Methods

We conducted a cross-sectional study using data from the Korean National Health and Nutrition Examination Survey (KNHANES) spanning 2013 to 2021 to compare health behaviors and mental health outcomes between 203 adolescent children with parents diagnosed with depression and 3,856 control adolescents aged 12–19 years.

Results

Following multivariate adjustments, the risk of depressive mood for more than two weeks was significantly increased in boys with parental depression (adjusted Odds Ratio [aOR] = 2.05, 95% Confidence Interval [CI] = 1.91–3.52) and adolescents with parents with moderate-to-severe depression (aOR = 2.60, 95% CI = 1.17–5.77). Adolescents with parental depression reported significantly worse subjective health status (aOR = 1.88, 95% CI = 1.05–3.36) and higher stress levels (aOR = 1.91, 95% CI = 1.33–2.76). Additionally, when parental depression was present and the time since depression diagnosis was more than five years, adolescents with parental depression exhibited even poorer subjective health status and higher stress levels.

Conclusions

The study found that adolescents whose parents experienced depression had poorer mental health than those whose parents did not have mental health issues. These findings emphasize the importance of providing support for the mental health of adolescents in families affected by parental depression.
Socioeconomic inequalities in pandemic-induced psychosocial stress in different life domains among the working-age population
Authors: Beese Florian , Wachtler Benjamin , Grabka Markus M. , Blume Miriam , Kersjes Christina , Gutu Robert , Mauz Elvira , Hoebel Jens
Published: May 2024

Background

Psychosocial stress is considered a risk factor for physical and mental ill-health. Evidence on socioeconomic inequalities with regard to the psychosocial consequences of the COVID-19 pandemic in Germany is still limited. We aimed to investigate how pandemic-induced psychosocial stress (PIPS) in different life domains differed between socioeconomic groups.

Methods

Data came from the German Corona-Monitoring nationwide study – wave 2 (RKI-SOEP-2, November 2021–February 2022). PIPS was assessed using 4-point Likert scales with reference to the following life domains: family, partnership, own financial situation, psychological well-being, leisure activity, social life and work/school situation. Responses were dichotomised into “not stressed/slightly stressed/rather stressed” (0) versus “highly stressed” (1). The sample was restricted to the working-age population in Germany (age = 18–67 years, n = 8,402). Prevalence estimates of high PIPS were calculated by sex, age, education and income. Adjusted prevalence ratios (PRs) were estimated using Poisson regression to investigate the association between education/income and PIPS; high education and income were the reference groups.

Results

The highest stress levels were reported in the domains social life and leisure activity. Women and younger participants reported high stress levels more frequently. The highest inequalities were found regarding people’s own financial situation, and PIPS was higher in low vs. high income groups (PR 5.54, 95% CI 3.61–8.52). Inequalities were also found regarding partnerships with higher PIPS in low vs. high education groups (PR 1.68, 95% CI 1.13–2.49) – and psychological well-being with higher PIPS in low vs. high income groups (PR 1.52, 95% CI 1.14–2.04).

Conclusion

Socioeconomic inequalities in PIPS were found for different life domains. Generally, psychosocial support and preventive interventions to help people cope with stress in a pandemic context should be target-group-specific, addressing the particular needs and circumstances of certain socioeconomic groups.
Association of Life's Essential 8 with all-cause mortality and risk of cancer: a prospective cohort study
Authors: Jiang Jinguo , Ning Ning , Liu Yang , Cai Zhiwei , Zhao Maoxiang , Peng Xinyi , Li Liuxin , Chen Shuohua , Wang Jing , Wang Feng , Qin Xueying , Ma Yanan , Wu Shouling
Published: May 2024

Background

No study has concentrated on the association of LE8 with cancer risk and death. We aim to examine the association of LE8 with death and cancer.

Methods

A total of 94733 adults aged 51.42 ± 12.46 years and 77551 participants aged 54.09±12.06 years were enrolled in longitudinal and trajectory analysis respectively. Baseline LE8 was divided into three groups based on the American Heart Association criteria and three trajectory patterns by latent mixture models. We reviewed medical records and clinical examinations to confirm incident cancer during the period from 2006 to 2020. Death information was collected from provincial vital statistics offices. Cox models were used.

Results

12807 all-cause deaths and 5060 cancers were documented during a 14-year follow-up. Relative to participants with high LE8 at baseline, participants with lower levels of LE8 have a significantly increased risk of mortality and incident cancer. All these risks have an increasing trend with LE8 level decreasing. Meanwhile, the trajectory analysis recorded 7483 all-cause deaths and 3037 incident cancers after approximately 10 years. The associations of LE8 with death and cancer were identical to the longitudinal study. In the subtype cancer analysis, LE8 has a strong effect on colorectal cancer risk. Moreover, the cut point is 56.67 in the association between LE8 and death, while the cut point altered to 64.79 in the association between LE8 and incident cancers. These associations were enhanced among younger adults.

Conclusions

There was a significant association of LE8 with death and cancer risk, especially for the young population.
Comparison of the vitality test with sensitivity tests in mature and immature teeth: clinical trial
Authors: Çağırır Dindaroğlu Funda , Özay Güngör Narin
Published: May 2024

Background

One of the most important steps in deciding on the treatment of a tooth is to determine the vitality and health status of the pulp. Since immature teeth innervation is not completed, the response to sensitivity tests may not yield definite results. Pulse oximetry (PO) which is considered as a vitality test, measures the arterial oxygen saturation (SpO2). This study aims to compare PO, electric pulp test (EPT) and cold test in mature and immature permanent teeth.

Methods

20 immature and 20 mature permanent incisors of 6-12-year-old ASA1 children who did not use any analgesics, were included in the study. Pulp vitality of the teeth was determined by EPT, cold test and PO. An infant probe of PO device (CMS60D, Contec Medical Systems Co. Ltd, China) was used to determine the SpO2 of the teeth. The SpO2 level is controlled on the patient’s finger by a children’s probe and an infant probe of PO. Shapiro-Wilk, Spearman rank correlation test and Kruskal-Wallis test/Dunn post-hoc analysis were used for statistical comparisons.

Results

There was no significant correlation between finger SpO2 and the mature/immature teeth SpO2 (r=-0.026, r = 0.253). Arterial oxygen saturation values in the immature teeth were significantly higher than in the mature teeth (p = 0.002). There was a high correlation between the vitality response of the EPT, cold test and PO.

Conclusions

Pulse oximetry can be used as an effective vitality test compared to sensitivity tests in both immature and mature permanent incisors.
Comparative effects of 17% ethylenediaminetetraacetic acid and 9% etidronic acid applied with different irrigant activation techniques on the release of growth factors from dentin: in vitro study
Authors: Mumcu Arzu Kaya , Kurnaz Safa , Kiraz Gülsen , Gündüz Meliha Koldemir
Published: May 2024

Background

Growth factors embedded in the extracellular matrix of the dentin play an important role in the migration, proliferation, and differentiation of dental pulp stem cells in regenerative endodontics. In regenerative endodontic treatments, the type of irrigation solution used is crucial for the release of growth factors (GFs) from the dentin matrix. This study evaluated the effectiveness of different irrigant activation techniques (IAT) using two different chelating agents, 17% ethylenediaminetetraacetic acid (EDTA) and 9% etidronic acid (HEDP), in terms of their GF release.

Methods

Seventy-two mandibular premolar teeth were prepared to simulate an open apex. The root fragments were irrigated with 20 ml of 1.5% sodium hypochlorite and 20 ml of saline solution. Eight root fragments were randomly separated for the control group, and the remaining 64 fragments were randomly separated into eight groups based on two different chelating agents (17% EDTA and 9% HEDP) and four different IAT ((conventional needle irrigation (CNI), passive ultrasonic irrigation (PUI), sonic activation with EDDY, and XP-endo Finisher (XPF)). TGF-β1, VEGF-A, BMP-7 and IGF-1 release levels were determined using an ELISA, and statistical analysis was performed using the Kolmogorov–Smirnov test, ANOVA, and the Tukey test (p < .05).

Results

Compared to the control group, the experimental groups showed significantly higher GF release when using EDTA or HEDP. Among the activation groups, the EDDY group triggered the highest GF release, and the CNI group triggered the lowest.

Conclusions

IAT with EDTA and HEDP can increase GF release, with EDDY being the most effective IAT method. Using chelating agents with IAT may be beneficial in regenerative endodontic treatments.
The experiences of patients with COVID-19 and their relatives from receiving professional home care nursing: a qualitative content analysis
Authors: Shayestefar Mina , Raiesdana Nayyereh , Nobahar Monir
Published: May 2024

Background

To overcome of patients with COVID-19 over the capacity of hospitals and mild to moderate severity of the disease in most cases, the World Health Organization and the Centers for Disease Control and Prevention in the United States, recommend home care for these patients. Receiving care at home will face challenges that can be context-based, especially in crises like the Coronavirus pandemic. The present study aimed to describe the experiences of patients with COVID-19 and their relatives from receiving professional home care nursing.

Methods

This study was conducted using a qualitative content analysis method. Nine participants with COVID-19 who were receiving home care nursing in Semnan participated in this study. The purposive sampling method was used. Sampling continued until no new categories appeared, meaning the category’s theoretical saturation. Deep and semi-structured interviews were used to collect data based on the research question. Data was analyzed using the conventional content analysis method using Graneheim and Lundman’s approach.

Results

After analyzing the interviews and comparing codes based on similarities and differences, three main themes, 11 categories, and 30 subcategories were identified. The main themes included “The value of home care” (personalization of care, being economical, providing intellectual security, and reducing the concern of family), “Comprehensive care” (professional commitment, empathy, mastery in care, and patronage), and “Care challenges” (cultural barriers, inadequate services, and lack of information about costs and conditions).

Conclusion

The patients with COVID-19 who received professional nursing care at home mentioned some challenges, such as the caregiver not being of the same sex as the patient, delay in receiving the service, the inadequacy of the centers, the limitation of the right to choose the care provider, and insufficient information about the cost of services received before receiving each care.
Nurses, non-nurse healthcare providers, and clients’ perspectives, encounters, and choices of nursing gender in Tanzania: a qualitative descriptive study
Authors: Masibo Racheal Mukoya , Kibusi Stephen M. , Masika Golden M.
Published: May 2024

Background

A growing share of male nurses in the nursing profession in Tanzania has changed the trend of diversity of nursing gender. This might have created a divergent perspective within the communities. Therefore, the current study aimed to explore the perspective, encounters, and choices of nursing gender among licensed nurses, non-nurse healthcare providers, and clients in Tanzania.

Methods

The study employed a qualitative descriptive design. The data were collected between August 2022 to January 2023 by the principal investigator and one research assistant. Twelve Focus Group Discussions (FGDs) were carried out in four different hospitals in Dar es Salaam comprised of total participants (n = 59). The participants were nurses, clients, and non-nurse healthcare providers. The data was collected through an interview guide developed by the principal investigator and validated by nurse experts. The data was analyzed using qualitative content analysis to generate themes and subthemes.

Results

Eight themes and twenty-seven subthemes emerged from the study. The following are themes; ① Variations of male and female nurses in communication ② Differences of male and female nurses in carrying out leadership roles ③ Divergent clinical qualities and outcomes across nursing gender ④ Positive value of male nurses in clinical facilities from colleagues and patients ⑤ Different cooperation of male and female nurses at the clinical settings ⑥ Mixed perspective towards clinical competencies across nursing gender ⑦ Perspective towards gender diversity in nursing ⑧ Preferences of nurse’s gender, reasons, and opinion towards gender preferences.

Conclusion

Male nurses and female nurses differ in how they communicate, execute leadership roles, and clinical qualities. However, their variations don’t mean one gender is underrated than the other, but every gender has unique communication styles, leadership styles, and clinical qualities that both lead to effective outcomes. Diversity in nursing gender is very important and should be strategized. Since preferences of nursing gender seems to enhance somebody’s freedom and creates an environment where a person can discuss sensitive issues, nursing bodies and healthcare stakeholders might initiate a discussion about approaches to promote the implementation of nursing preference and perform the feasibility studies.
Diabetes and further risk of cancer: a nationwide population-based study
Authors: Chang Wei-Chuan , Hsieh Tsung-Cheng , Hsu Wen-Lin , Chang Fang-Ling , Tsai Hou-Ren , He Ming-Shan
Published: May 2024

Background

Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood.

Methods

This was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period.

Results

We observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001).

Conclusions

This study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops.
A comparative study of the biosynthesis of CuNPs by Niallia circulans G9 and Paenibacillus sp. S4c strains: characterization and application as antimicrobial agents
Authors: Aziz Nahla M. Abdel , Goda Doaa A. , Abdel-Meguid Dina I. , EL-Sharouny Ebaa E. , Soliman Nadia A.
Published: May 2024

Background

Biosynthesis of metallic nanoparticles using microorganisms are a fabulous and emerging eco-friendly science with well-defined sizes, shapes and controlled monodispersity. Copper nanoparticles, among other metal particles, have sparked increased attention due to their applications in electronics, optics, catalysis, and antimicrobial agents.

Results

This investigation explains the biosynthesis and characterization of copper nanoparticles from soil strains, Niallia circulans G9 and Paenibacillus sp. S4c by an eco-friendly method. The maximum reduction of copper ions and maximum synthesis CuNPs was provided by these strains. Biogenic formation of CuNPs have been characterized by UV–visible absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray analysis and transmission electron microscopy analysis. Using UV-visible spectrum scanning, the synthesised CuNPs’ SPR spectra showed maximum absorption peaks at λ304&308 nm. TEM investigation of the produced CuNPs revealed the development of spherical/hexagonal nanoparticles with a size range of 13–100 nm by the G9 strain and spherical nanoparticles with a size range of 5–40 nm by the S4c strain. Functional groups and chemical composition of CuONPs were also confirmed. The antimicrobial activity of the biosynthesized CuNPs were investigated against some human pathogens. CuNPs produced from the G9 strain had the highest activity against Candida albicans ATCC 10,231 and the lowest against Pseudomonas aeruginosa ATCC 9027. CuNPs from the S4c strain demonstrated the highest activity against Escherichia coli ATCC 10,231 and the lowest activity against Klebsiella pneumonia ATCC 13,883.

Conclusion

The present work focused on increasing the CuNPs production by two isolates, Niallia circulans G9 and Paenibacillus sp. S4c, which were then characterized alongside. The used analytics and chemical composition techniques validated the existence of CuONPs in the G9 and S4c biosynthesized nano cupper. CuNPs of S4c are smaller and have a more varied shape than those of G9 strain, according to TEM images. In terms of antibacterial activity, the biosynthesized CuNPs from G9 and S4c were found to be more effective against Candida albicans ATCC 10,231 and E. coli ATCC 10,231, respectively.
Dynamic monitoring soft tissue healing via visualized Gd-crosslinked double network MRI microspheres
Authors: Chen Tongtong , Cai Zhengwei , Zhao Xinxin , Wei Gang , Wang Hanqi , Bo Tingting , Zhou Yan , Cui Wenguo , Lu Yong
Published: May 2024

By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing for non-invasive, continuous, and dynamic monitoring of the distribution, degradation, and relationship of the HMs with local tissues. However, when these visualization components are physically blended into the HMs, it reduces their relaxation rate and specificity under MRI, weakening the efficacy of real-time dynamic monitoring. To achieve MRI-guided in vivo monitoring of HMs with tissue repair functionality, we utilized airflow control and photo-crosslinking methods to prepare alginate-gelatin-based dual-network hydrogel microspheres (G-AlgMA HMs) using gadolinium ions (Gd (III)), a paramagnetic MRI contrast agent, as the crosslinker. When the network of G-AlgMA HMs degrades, the cleavage of covalent bonds causes the release of Gd (III), continuously altering the arrangement and movement characteristics of surrounding water molecules. This change in local transverse and longitudinal relaxation times results in variations in MRI signal values, thus enabling MRI-guided in vivo monitoring of the HMs. Additionally, in vivo data show that the degradation and release of polypeptide (K2 (SL)6 K2 (KK)) from G-AlgMA HMs promote local vascular regeneration and soft tissue repair. Overall, G-AlgMA HMs enable non-invasive, dynamic in vivo monitoring of biomaterial degradation and tissue regeneration through MRI, which is significant for understanding material degradation mechanisms, evaluating biocompatibility, and optimizing material design.
Anti-ferroptosis exosomes engineered for targeting M2 microglia to improve neurological function in ischemic stroke
Authors: Wang Yong , Liu Zhuohang , Li Luyu , Zhang Zengyu , Zhang Kai , Chu Min , Liu Yang , Mao Xueyu , Wu Di , Xu Dongsheng , Zhao Jing
Published: May 2024

Background

Stroke is a devastating disease affecting populations worldwide and is the primary cause of long-term disability. The inflammatory storm plays a crucial role in the progression of stroke. In the acute phase of ischemic stroke, there is a transient increase in anti-inflammatory M2 microglia followed by a rapid decline. Due to the abundant phospholipid in brain tissue, lipid peroxidation is a notable characteristic of ischemia/reperfusion (I/R), constituting a structural foundation for ferroptosis in M2 microglia. Slowing down the decrease in M2 microglia numbers and controlling the inflammatory microenvironment holds significant potential for enhancing stroke recovery.

Results

We found that the ferroptosis inhibitor can modulate inflammatory response in MCAO mice, characterizing that the level of M2 microglia-related cytokines was increased. We then confirmed that different subtypes of microglia exhibit distinct sensitivities to I/R-induced ferroptosis. Adipose-derived stem cells derived exosome (ADSC-Exo) effectively decreased the susceptibility of M2 microglia to ferroptosis via Fxr2/Atf3/Slc7a11, suppressing the inflammatory microenvironment and promoting neuronal survival. Furthermore, through plasmid engineering, a more efficient M2 microglia-targeted exosome, termed M2pep-ADSC-Exo, was developed. In vivo and in vitro experiments demonstrated that M2pep-ADSC-Exo exhibits significant targeting specificity for M2 microglia, further inhibiting M2 microglia ferroptosis and improving neurological function in ischemic stroke mice.

Conclusion

Collectively, we illustrated a novel potential therapeutic mechanism that Fxr2 in ADSC-Exo could alleviate the M2 microglia ferroptosis via regulating Atf3/Slc7all expression, hence inhibiting the inflammatory microenvironment, improving neurofunction recovery in cerebral I/R injury. We obtained a novel exosome, M2pep-ADSC-Exo, through engineered modification, which exhibits improved targeting capabilities toward M2 microglia. This provides a new avenue for the treatment of stroke.

Graphical Abstract
Megakaryocytic IGF1 coordinates activation and ferroptosis to safeguard hematopoietic stem cell regeneration after radiation injury
Authors: Liao Weinian , Chen Xinliang , Zhang Shuzhen , Chen Jun , Liu Chaonan , Yu Kuan , Zhang Yimin , Chen Mo , Chen Fang , Shen Mingqiang , Lu Binghui , Han Songling , Wang Song , Wang Junping , Du Changhong
Published: May 2024

Background

Hematopoietic stem cell (HSC) regeneration underlies hematopoietic recovery from myelosuppression, which is a life-threatening side effect of cytotoxicity. HSC niche is profoundly disrupted after myelosuppressive injury, while if and how the niche is reshaped and regulates HSC regeneration are poorly understood.

Methods

A mouse model of radiation injury-induced myelosuppression was built by exposing mice to a sublethal dose of ionizing radiation. The dynamic changes in the number, distribution and functionality of HSCs and megakaryocytes were determined by flow cytometry, immunofluorescence, colony assay and bone marrow transplantation, in combination with transcriptomic analysis. The communication between HSCs and megakaryocytes was determined using a coculture system and adoptive transfer. The signaling mechanism was investigated both in vivo and in vitro, and was consolidated using megakaryocyte-specific knockout mice and transgenic mice.

Results

Megakaryocytes become a predominant component of HSC niche and localize closer to HSCs after radiation injury. Meanwhile, transient insulin-like growth factor 1 (IGF1) hypersecretion is predominantly provoked in megakaryocytes after radiation injury, whereas HSCs regenerate paralleling megakaryocytic IGF1 hypersecretion. Mechanistically, HSCs are particularly susceptible to megakaryocytic IGF1 hypersecretion, and mTOR downstream of IGF1 signaling not only promotes activation including proliferation and mitochondrial oxidative metabolism of HSCs, but also inhibits ferritinophagy to restrict HSC ferroptosis. Consequently, the delicate coordination between proliferation, mitochondrial oxidative metabolism and ferroptosis ensures functional HSC expansion after radiation injury. Importantly, punctual IGF1 administration simultaneously promotes HSC regeneration and hematopoietic recovery after radiation injury, representing a superior therapeutic approach for myelosuppression.

Conclusions

Our study identifies megakaryocytes as a last line of defense against myelosuppressive injury and megakaryocytic IGF1 as a novel niche signal safeguarding HSC regeneration.
IL-17 in wound repair: bridging acute and chronic responses
Authors: Mu Xingrui , Gu Rifang , Tang Ming , Wu Xingqian , He Wenjie , Nie Xuqiang
Published: May 2024

Chronic wounds, resulting from persistent inflammation, can trigger a cascade of detrimental effects including exacerbating inflammatory cytokines, compromised blood circulation at the wound site, elevation of white blood cell count, increased reactive oxygen species, and the potential risk of bacterial infection. The interleukin-17 (IL-17) signaling pathway, which plays a crucial role in regulating immune responses, has been identified as a promising target for treating inflammatory skin diseases. This review aims to delve deeper into the potential pathological role and molecular mechanisms of the IL-17 family and its pathways in wound repair. The intricate interactions between IL-17 and other cytokines will be discussed in detail, along with the activation of various signaling pathways, to provide a comprehensive understanding of IL-17’s involvement in chronic wound inflammation and repair.
Omeprazole and risk of osteoarthritis: insights from a mendelian randomization study in the UK Biobank
Authors: Cao Siyang , Wei Yihao , Yue Yaohang , Li Guoqing , Wang Hongli , Lin Jianjing , Wang Qichang , Liu Peng , Yu Fei , Xiong Ao , Zeng Hui
Published: May 2024

Background

A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their causal evidence, however, remains undetermined. The present research endeavors to investigate the underlying causal link between omeprazole and OA through the application of mendelian randomization (MR) analysis.

Methods

The study incorporated the ukb-a-106 and ukb-b-14,486 datasets. The investigation of causal effects employed methodologies such as MR-Egger, Weighted median, Inverse variance weighted (IVW) with multiplicative random effects, and IVW (fixed effects). The IVW approach was predominantly considered for result interpretation. Sensitivity analysis was conducted, encompassing assessments for heterogeneity, horizontal pleiotropy, and the Leave-one-out techniques.

Results

The outcomes of the MR analysis indicated a causal relationship between omeprazole and OA, with omeprazole identified as a contributing risk factor for OA development (IVW model: OR = 1.2473, P < 0.01 in ukb-a-106; OR = 1.1288, P < 0.05 in ukb-b-14,486). The sensitivity analysis underscored the robustness and dependability of the above-mentioned analytical findings.

Conclusion

This study, employing MR, reveals that omeprazole, as an exposure factor, elevates the risk of OA. Considering the drug’s efficacy and associated adverse events, clinical practitioners should exercise caution regarding prolonged omeprazole use, particularly in populations with heightened OA risks. Further robust and high-quality research is warranted to validate our findings and guide clinical practice.
Ferredoxin 1: a gatekeeper in halting lung adenocarcinoma progression through activation of the GPRIN2 signaling pathway
Authors: Liu Ming , Wu Shaoxian , Wu Haoyu , Zhou You , Zhang Xinyu , Zhu Dawei , Jiang Jingting
Published: May 2024

Background

Lung adenocarcinoma (LUAD) is a highly lethal form of lung cancer. Despite advancements in treatments, managing LUAD is still challenging due to its aggressive behavior. Recent studies indicate that various molecular pathways, including the dysregulation of ferredoxin 1 (FDX1), play roles in LUAD progression. FDX1, a crucial protein in cellular redox reactions and energy metabolism, has been linked to several cancers. However, its exact role in the development of LUAD is not yet fully understood.

Methods

We investigated the role of ferredoxin 1 (FDX1) in LUAD progression through analysis of its expression in LUAD tissues and its impact on patient survival. Functional assays were performed to assess the effects of FDX1 overexpression on LUAD cell proliferation, migration, and invasion. A xenograft model was employed to evaluate the tumorigenesis potential of LUAD cells with FDX1 overexpression. Mechanistic insights into FDX1 regulation were gained through depletion experiments targeting the G protein-regulated inducer of neurite outgrowth 2 (GPRIN2)/PI3K signaling pathway.

Results

FDX1 expression was down-regulated in LUAD tissues, correlating with shorter patient survival. Overexpression of FDX1 suppressed LUAD cell proliferation, migration, and invasion in vitro, and inhibited tumorigenesis in vivo. Mechanistically, the GPRIN2/PI3K signaling pathway was implicated in FDX1 regulation, as depletion of GPRIN2 reversed the effects of FDX1 overexpression on cellular functions.

Conclusions

Our findings highlight FDX1 as a potential tumor suppressor in LUAD, acting through modulation of the GPRIN2/PI3K signaling pathway. These results suggest FDX1 as a promising therapeutic target for LUAD treatment, warranting further investigation into its clinical relevance.
Neither injury induced macrophages within the nerve, nor the environment created by Wallerian degeneration is necessary for enhanced in vivo axon regeneration after peripheral nerve injury
Authors: Talsma Aaron D. , Niemi Jon P. , Zigmond Richard E.
Published: May 2024

Background

Since the 1990s, evidence has accumulated that macrophages promote peripheral nerve regeneration and are required for enhancing regeneration in the conditioning lesion (CL) response. After a sciatic nerve injury, macrophages accumulate in the injury site, the nerve distal to that site, and the axotomized dorsal root ganglia (DRGs). In the peripheral nervous system, as in other tissues, the macrophage response is derived from both resident macrophages and recruited monocyte-derived macrophages (MDMs). Unresolved questions are: at which sites do macrophages enhance nerve regeneration, and is a particular population needed.

Methods

Ccr2 knock-out (KO) and Ccr2gfp/gfp knock-in/KO mice were used to prevent MDM recruitment. Using these strains in a sciatic CL paradigm, we examined the necessity of MDMs and residents for CL-enhanced regeneration in vivo and characterized injury-induced nerve inflammation. CL paradigm variants, including the addition of pharmacological macrophage depletion methods, tested the role of various macrophage populations in initiating or sustaining the CL response. In vivo regeneration, measured from bilateral proximal test lesions (TLs) after 2 d, and macrophages were quantified by immunofluorescent staining.

Results

Peripheral CL-enhanced regeneration was equivalent between crush and transection CLs and was sustained for 28 days in both Ccr2 KO and WT mice despite MDM depletion. Similarly, the central CL response measured in dorsal roots was unchanged in Ccr2 KO mice. Macrophages at both the TL and CL, but not between them, stained for the pro-regenerative marker, arginase 1. TL macrophages were primarily CCR2-dependent MDMs and nearly absent in Ccr2 KO and Ccr2gfp/gfp KO mice. However, there were only slightly fewer Arg1+ macrophages in CCR2 null CLs than controls due to resident macrophage compensation. Zymosan injection into an intact WT sciatic nerve recruited Arg1+ macrophages but did not enhance regeneration. Finally, clodronate injection into Ccr2gfp KO CLs dramatically reduced CL macrophages. Combined with the Ccr2gfp KO background, depleting MDMs and TL macrophages, and a transection CL, physically removing the distal nerve environment, nearly all macrophages in the nerve were removed, yet CL-enhanced regeneration was not impaired.

Conclusions

Macrophages in the sciatic nerve are neither necessary nor sufficient to produce a CL response.