bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term cardiovascular outcomes of biodegradable polymer drug eluting stents in patients with diabetes versus non-diabetes mellitus: a meta-analysis
Authors: Wang Hong , Zu Quannan , Tang Hairong , Lu Ming , Chen Rongfa , Yang Zhiren
Published: August 2023

Background

Today, diabetes mellitus (DM) has become a worldwide concern. DM is a major risk factor for the development of cardiovascular diseases (CVD). Eligible patients with CVD are treated invasively by percutaneous coronary intervention (PCI) whereby a stent is implanted inside the coronary vessel with the particular lesion to allow sufficient blood flow. Newer scientific research have shown that even though associated with a lower rate of re-stenosis, first-generation drug eluting stents (DES) were associated with a higher rate of late stent thrombosis. Recently, newer stents, namely biodegradable polymer DES (BP-DES) have been developed to overcome the safety issues of earlier generation DES. In this analysis we aimed to systematically compare the long term (≥ 12 months) adverse cardiovascular outcomes observed in DM versus non-DM patients who were implanted with BP-DES.

Methods

Cochrane central, MEDLINE (Subset PubMed), EMBASE, Web of Science, http://www.ClinicalTrials.gov and Google scholar were searched for relevant publications involving BP-DES in patients with DM versus non-DM and their associated adverse cardiovascular outcomes. The mean follow-up time period ranged from 12 to 120 months. Data analysis was carried out with the latest version of the RevMan software (version 5.4). Based on the Mantel-Haenszel test, risk ratios (RR) with 95% confidence intervals (CI) were calculated and used to represent the results following analysis.

Results

Seven (7) studies with a total number of 10,246 participants were included in this analysis. Stents which were implanted during PCI were BP-DES. Participants were enrolled from the year 2006 to 2013. Our current results showed that in patients who were implanted with BP-DES, the risks of major adverse cardiac events (RR: 1.30, 95% CI: 1.18–1.43; P = 0.00001), myocardial infarction (RR: 1.48, 95% CI: 1.14–1.93; P = 0.003), all-cause mortality (RR: 1.70, 95% CI: 1.29–2.23; P = 0.0002), cardiac death (RR: 1.93, 95% CI: 1.28–2.93; P = 0.002), target vessel revascularization (RR: 1.35, 95% CI: 1.03–1.77; P = 0.03), target lesion revascularization (RR: 1.28, 95% CI: 1.07–1.54; P = 0.007) and target lesion failure (RR: 1.79, 95% CI: 1.52–2.12; P = 0.00001) were significantly higher in the DM group. Definite and probable stent thrombosis (RR: 1.80, 95% CI: 1.28–2.55; P = 0.0009) were also significantly higher in the DM group.

Conclusions

Diabetes mellitus was an independent risk factor associated with long term adverse cardiovascular outcomes following PCI with BP-DES.
Mechanism of microbial production of acetoin and 2,3-butanediol optical isomers and substrate specificity of butanediol dehydrogenase
Authors: Li Yuchen , Zhao Xiangying , Yao Mingjing , Yang Wenli , Han Yanlei , Liu Liping , Zhang Jiaxiang , Liu Jianjun
Published: August 2023

3-Hydroxybutanone (Acetoin, AC) and 2,3-butanediol (BD) are two essential four-carbon platform compounds with numerous pharmaceutical and chemical synthesis applications. AC and BD have two and three stereoisomers, respectively, while the application of the single isomer product in chemical synthesis is superior. AC and BD are glucose overflow metabolites produced by biological fermentation from a variety of microorganisms. However, the AC or BD produced by microorganisms using glucose is typically a mixture of various stereoisomers. This was discovered to be due to the simultaneous presence of multiple butanediol dehydrogenases (BDHs) in microorganisms, and AC and BD can be interconverted under BDH catalysis. In this paper, beginning with the synthesis pathways of microbial AC and BD, we review in detail the studies on the formation mechanisms of different stereoisomers of AC and BD, summarize the properties of different types of BDH that have been tabulated, and analyze the structural characteristics and affinities of different types of BDH by comparing them using literature and biological database data. Using microorganisms, recent research on the production of optically pure AC or BD was also reviewed. Limiting factors and possible solutions for chiral AC and BD production are discussed.
A 4-hydroxybenzoate 3-hydroxylase mutant enables 4-amino-3-hydroxybenzoic acid production from glucose in Corynebacterium glutamicum
Authors: Nonaka Kyoshiro , Osamura Tatsuya , Takahashi Fumikazu
Published: August 2023

Background

Microbial production of aromatic chemicals is an attractive method for obtaining high-performance materials from biomass resources. A non-proteinogenic amino acid, 4-amino-3-hydroxybenzoic acid (4,3-AHBA), is expected to be a precursor of highly functional polybenzoxazole polymers; however, methods for its microbial production have not been reported. In this study, we attempted to produce 4,3-AHBA from glucose by introducing 3-hydroxylation of 4-aminobenzoic acid (4-ABA) into the metabolic pathway of an industrially relevant bacterium, Corynebacterium glutamicum.

Results

Six different 4-hydroxybenzoate 3-hydroxylases (PHBHs) were heterologously expressed in C. glutamicum strains, which were then screened for the production of 4,3-AHBA by culturing with glucose as a carbon source. The highest concentration of 4,3-AHBA was detected in the strain expressing PHBH from Caulobacter vibrioides (CvPHBH). A combination of site-directed mutagenesis in the active site and random mutagenesis via laccase-mediated colorimetric assay allowed us to obtain CvPHBH mutants that enhanced 4,3-AHBA productivity under deep-well plate culture conditions. The recombinant C. glutamicum strain expressing CvPHBHM106A/T294S and having an enhanced 4-ABA biosynthetic pathway produced 13.5 g/L (88 mM) 4,3-AHBA and 0.059 g/L (0.43 mM) precursor 4-ABA in fed-batch culture using a nutrient-rich medium. The culture of this strain in the chemically defined CGXII medium yielded 9.8 C-mol% of 4,3-AHBA from glucose, corresponding to 12.8% of the theoretical maximum yield (76.8 C-mol%) calculated using a genome-scale metabolic model of C. glutamicum.

Conclusions

Identification of PHBH mutants that could efficiently catalyze the 3-hydroxylation of 4-ABA in C. glutamicum allowed us to construct an artificial biosynthetic pathway capable of producing 4,3-AHBA on a gram-scale using glucose as the carbon source. These findings will contribute to a better understanding of enzyme-catalyzed regioselective hydroxylation of aromatic chemicals and to the diversification of biomass-derived precursors for high-performance materials.
Effect of cardiopulmonary bypass on plasma and erythrocytes oxylipins
Authors: Liu Tong , Dogan Inci , Rothe Michael , Potapov Evgenij , Schoenrath Felix , Gollasch Maik , Luft Friedrich C. , Gollasch Benjamin
Published: August 2023

Background

Oxylipins, the oxidative metabolites of polyunsaturated fatty acids (PUFAs), serve as key mediators of oxidative stress, inflammatory responses, and vasoactive reactions in vivo. Our previous work has established that hemodialysis affects both long chain fatty acids (LCFAs) and oxylipins in plasma and erythrocytes to varying degrees, which may be responsible for excess cardiovascular complications in end-stage renal disease. In this study, we aimed to determine changes in blood oxylipins during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery to identify novel biomarkers and potential metabolites of CPB-related complications. We tested the hypothesis that CPB would differentially affect plasma oxylipins and erythrocytes oxylipins.

Methods

We conducted a prospective observational study of 12 patients undergoing elective cardiac surgery with expected CPB procedure. We collected venous and arterial blood samples before CPB, 15 and 45 min after the start of CPB, and 60 min after the end of CPB, respectively. Oxylipins profiling in plasma and erythrocytes was achieved using targeted HPLC‐MS mass spectrometry.

Results

Our results revealed that most venous plasma diols and hydroxy- oxylipins decreased after CPB initiation, with a continuous decline until the termination of CPB. Nevertheless, no statistically significant alterations were detected in erythrocytes oxylipins at all time points.

Conclusions

CPB decreases numerous diols and hydroxy oxylipins in blood plasma, whereas no changes in erythrocytes oxylipins are observed during this procedure in patients undergoing cardiac surgery. As lipid mediators primarily responsive to CPB, plasma diols and hydroxy oxylipins may serve as potential key biomarkers for CPB-related complications.
Nanoparticles systemically biodistribute to regenerating skeletal muscle in DMD
Authors: Hicks Michael R. , Liu Xiangsheng , Young Courtney S. , Saleh Kholoud , Ji Ying , Jiang Jinhong , Emami Michael R. , Mokhonova Ekaterina , Spencer Melissa J. , Meng Huan , Pyle April D.
Published: August 2023

Skeletal muscle disease severity can often progress asymmetrically across muscle groups and heterogeneously within tissues. An example is Duchenne Muscular Dystrophy (DMD) in which lack of dystrophin results in devastating skeletal muscle wasting in some muscles whereas others are spared or undergo hypertrophy. An efficient, non-invasive approach to identify sites of asymmetry and degenerative lesions could enable better patient monitoring and therapeutic targeting of disease. In this study, we utilized a versatile intravenously injectable mesoporous silica nanoparticle (MSNP) based nanocarrier system to explore mechanisms of biodistribution in skeletal muscle of mdx mouse models of DMD including wildtype, dystrophic, and severely dystrophic mice. Moreover, MSNPs could be imaged in live mice and whole muscle tissues enabling investigation of how biodistribution is altered by different types of muscle pathology such as inflammation or fibrosis. We found MSNPs were tenfold more likely to aggregate within select mdx muscles relative to wild type, such as gastrocnemius and quadriceps. This was accompanied by decreased biodistribution in off-target organs. We found the greatest factor affecting preferential delivery was the regenerative state of the dystrophic skeletal muscle with the highest MSNP abundance coinciding with the regions showing the highest level of embryonic myosin staining and intramuscular macrophage uptake. To demonstrate, muscle regeneration regulated MSNP distribution, we experimentally induced regeneration using barium chloride which resulted in a threefold increase of intravenously injected MSNPs to sites of regeneration 7 days after injury. These discoveries provide the first evidence that nanoparticles have selective biodistribution to skeletal muscle in DMD to areas of active regeneration and that nanoparticles could enable diagnostic and selective drug delivery in DMD skeletal muscle.
P65 mediated UBR4 in exosomes derived from menstrual blood stromal cells to reduce endometrial fibrosis by regulating YAP Ubiquitination
Authors: Qi Jiarui , Zhang Xudong , Zhang Siwen , Wu Shanshan , Lu Yimeng , Li Shuyu , Li Pingping , Tan Jichun
Published: August 2023

Background

Intrauterine adhesion (IUA) is a recurrent and refractory reproductive dysfunction disorder for which menstrual blood-derived stromal cells (MenSCs) might be a promising intervention. We reported that administration of MenSCs-derived exosomes (MenSCs-EXO) could achieve similar therapeutic effects to MenSCs transplantation, including alleviating endometrial fibrosis and improving fertility in IUA rats. The mass spectrometry sequencing result suggested that UBR4, a member of the proteasome family, was abundantly enriched in MenSCs-EXO. This study aimed to investigate the key role of UBR4 in MenSCs-EXO for the treatment of IUA and the specific molecular mechanism.

Results

UBR4 was lowly expressed in the endometrial stromal cells (EndoSCs) of IUA patients. MenSCs-EXO treatment could restore the morphology of IUA endometrium, reduce the extent of fibrosis, and promote endometrial and vascular proliferation. Knockdown of UBR4 in MenSCs did not affect the characteristics of exosomes but attenuated the therapeutic effect of exosomes. UBR4 in MenSCs-EXO could alleviate endometrial fibrosis by boosting YAP ubiquitination degradation and promoting YAP nuclear-cytoplasmic translocation. Moreover, P65 could bind to the UBR4 promoter region to transcriptionally promote the expression level of UBR4 in MenSCs.

Conclusion

Our study clarified that MenSCs-EXO ameliorated endometrial fibrosis in IUA primarily by affecting YAP activity mediated through UBR4, while inflammatory signaling P65 may affect UBR4 expression in MenSCs to enhance MenSCs-EXO therapeutic effects. This revealed a novel mechanism for the treatment of IUA with MenSCs-EXO, proposing a potential option for the clinical treatment of endometrial injury.
Oncological effectiveness of bladder-preserving trimodal therapy versus radical cystectomy for the treatment of muscle-invasive bladder cancer: a system review and meta-analysis
Authors: Su Xiaozhe , Dong Caitao , Liao Wenbiao , Liu Wentao
Published: August 2023

Objective

Radical cystectomy (RC) is the gold standard treatment for muscle-invasive bladder cancer (MIBC). As a bladder-preservation option recommended in guidelines, trimodal therapy (TMT) has become increasingly popular in recent years. However, it is still uncertain whether TMT can provide comparable oncologic outcomes to RC. Therefore, it is imperative to evaluate whether TMT yields comparable outcomes to RC.

Methods

We conducted a systematic search of Web of Science, MEDLINE, the Cochrane Library, and EMBASE databases up to June 2023 to identify studies that met our inclusion criteria. The primary outcome measures evaluated in this study were overall survival (OS) and cancer-specific survival (CSS). The study quality was evaluated independently by two authors, and data were extracted accordingly.

Results

After excluding duplicates and ineligible articles, our meta-analysis included seven studies involving 3,489 and 13,877 patients in the TMT and RC groups, respectively. Short-term overall survival rates were comparable between the groups, but beyond 5 and > 10-years, the RC group had significantly higher overall survival rates compared to the TMT group. In terms of cancer-specific survival, there was no significant difference between the groups at 1-year follow-up, but from the second year onwards, including the 5-year and > 10-year nodes, the RC group had significantly better outcomes compared to the TMT group.

Conclusion

The treatment effect of RC is better than that of TMT. Unless the patient can’t tolerate RC or has a strong desire to preserve the bladder, RC should be chosen over TMT in treatment, and patients undergoing TMT should be closely followed up.
The long-term effects of reproductive health education among primary and secondary school students: a longitudinal quasi-experimental study in rural Tanzania
Authors: Shimpuku Yoko , Hirose Naoki , Chen Sanmei , Mwakawanga Dorkasi L. , Madeni Niko , Madeni Frida , Komada Mariko , Teshima Ayaka , Morishima Mayu , Ando Yasunobu , Takahama Koji , Nishida Atsushi
Published: August 2023

Background

Adolescent pregnancy remains a major global health issue, increasing the risk of complications during pregnancy and childbirth in mothers and babies. In Tanzania, adolescent pregnancy threatens girls’ education and makes it difficult for them to obtain a proper job; hence, the majority fall into poverty. Previous studies have developed and conducted reproductive health education for adolescent students; however, they evaluated only the effect immediately after education. Therefore, this study investigated the effects of reproductive health education on attitudes and behaviors toward reproductive health among adolescent girls and boys one year after the intervention in rural Tanzania.

Methods

A longitudinal quasi-experimental study was conducted with 3295 primary and secondary students (2123 in the intervention group, 1172 in the control group) from three purposefully selected wards in Korogwe District. In the intervention group, the students received reproductive health education. We used paper-based questionnaires to evaluate the effect of the adolescent education program on attitudes and behaviors toward reproductive health education. To analyze the association between the intervention and each outcome, mixed-effect multiple regression analyses was conducted.

Results

The mean age, primary school proportion, and female proportion of the intervention and the control group was 13.05 (standard deviation (SD) 1.59), 14.14 (SD 1.7), 77.9% and 34.3%, and 54.2% and 52.6%, respectively. There was no statistically significant effect of reproductive health education on adolescent health attitudes and behaviors in the multiple regression analyses (coefficient: − 0.24 (95% confidence interval (CI): − 0.98 to 0.50), coefficient: 0.01 (95%CI: − 0.42 to 0.43)).

Conclusion

A statistically significant effect of reproductive health education on adolescent health attitudes and behaviors was not found. An effective reproductive health education intervention to improve the attitude and behaviors of reproductive health among Tanzania adolescents in the long term remain to be determined, particularly in real-world settings.

Trial registration The National Institute for Medical Research, Tanzania (NIMR/HQ/R.8a/Vol. IX988).
The effect of conjugated linoleic acids on inflammation, oxidative stress, body composition and physical performance: a comprehensive review of putative molecular mechanisms
Authors: Putera Husna Dharma , Doewes Rumi Iqbal , Shalaby Mohammed Nader , Ramírez-Coronel Andrés Alexis , Clayton Zachary S. , Abdelbasset Walid Kamal , Murtazaev Saidmurodkhon S. , Jalil Abduladheem Turki , Rahimi Pegah , Nattagh-Eshtivani Elyas , Malekahmadi Mahsa , Pahlavani Naseh
Published: August 2023

Conjugated linoleic acids (CLAs) are polyunsaturated fatty acids primarily found in dairy products and ruminant animal products such as beef, lamb, and butter. Supplementation of CLAs has recently become popular among athletes due to the variety of health-promoting effects, including improvements in physical performance. Preclinical and some clinical studies have shown that CLAs can reduce inflammation and oxidative stress and favorably modulate body composition and physical performance; however, the results of previously published clinical trials are mixed. Here, we performed a comprehensive review of previously published clinical trials that assessed the role of CLAs in modulating inflammation, oxidative stress, body composition, and select indices of physical performance, emphasizing the molecular mechanisms governing these changes. The findings of our review demonstrate that the effect of supplementation with CLAs on inflammation and oxidative stress is controversial, but this supplement can decrease body fat mass and increase physical performance. Future well-designed randomized clinical trials are warranted to determine the effectiveness of (1) specific doses of CLAs; (2) different dosing durations of CLAs; (3) various CLA isomers, and the exact molecular mechanisms by which CLAs positively influence oxidative stress, inflammation, body composition, and physical performance.
Human umbilical cord mesenchymal stem cells promoting knee joint chondrogenesis for the treatment of knee osteoarthritis: a systematic review
Authors: Zhang Pengwei , Dong Bo , Yuan Puwei , Li Xun
Published: August 2023

Purpose

The onset of OA is affected by a variety of factors, which eventually lead to the loss of cartilage in the joints, the formation of osteophytes, the loss of normal knee mobility, and pain and discomfort, which seriously affects the quality of life. HUC-MSCs can promote cartilage production and have been widely used in research in the past decade. This article systematically summarizes that it is well used in basic research and clinical studies to promote inflammatory chondrogenesis in the treatment of OA. Provide a theoretical basis for clinical treatment.

Patients and methods

This study collected CNKI, Wanfang, PubMed, and articles related to the treatment of OA with HUC-MSCs since their publication, excluding non-basic and clinical studies such as reviews and meta-analysis. A total of 31 basic experimental studies and 12 clinical studies were included. Systematically analyze the effects of HUC-MSCs on inhibiting inflammatory factors, promoting chondrocyte production, and current clinical treatment.

Results

HUC-MSCs can reduce inflammatory factors such as MMP-13, ADAMTS-5, IL-1β, IL-1, IL-6, TNF-α, induced conversion from M1 to M2 in OA to protect cartilage damage and reduce OA inflammation. Synthesize ColII, SOX9, and aggrecan at the same time to promote cartilage synthesis.

Conclusion

HUC-MSCs not only have typical stem cell biological characteristics, but also have rich sources and convenient material extraction. Compared with stem cells from other sources, HUC-MSCs have stronger proliferation, differentiation, and immune regulation abilities. Furthermore, there are no ethical issues associated with their use. Safety: Primarily attributed to pain, the majority of individuals experience recovery within 24 h following injection. HUC-MSCs possess the ability to alleviate pain, enhance knee joint function, and potentially postpone the need for surgical intervention in both non-surgical and other cases, making them highly deserving of clinical promotion and application.
The safety of telemedicine clinics as an alternative to in-person preoperative assessment for elective laparoscopic cholecystectomy in patients with benign gallbladder disease: a retrospective cohort study
Authors: Urbonas Tomas , Lakha Adil Siraj , King Emily , Pepes Sophia , Ceresa Carlo , Udupa Venkatesha , Soonawalla Zahir , Silva Michael A , Gordon-Weeks Alex , Reddy Srikanth
Published: August 2023

Background

The telemedicine clinic for follow up after minor surgical procedures in general surgery is now ubiquitously considered a standard of care. However, this method of consultation is not the mainstay for preoperative assessment and counselling of patients for common surgical procedures such as laparoscopic cholecystectomy. The aim of this study was to evaluate the safety of assessing and counselling patients in the telemedicine clinic without a physical encounter for laparoscopic cholecystectomy.

Methods

We conducted a retrospective analysis of patients who were booked for laparoscopic cholecystectomy for benign gallbladder disease via general surgery telemedicine clinics from March 2020 to November 2021. The primary outcome was the cancellation rate on the day of surgery. The secondary outcomes were complication and readmission rates, with Clavein-Dindo grade III or greater deemed clinically significant. We performed a subgroup analysis on the cases cancelled on the day of surgery in an attempt to identify key reasons for cancellation following virtual clinic assessment.

Results

We identified 206 cases booked for laparoscopic cholecystectomy from telemedicine clinics. 7% of patients had a cancellation on the day of surgery. Only one such cancellation was deemed avoidable as it may have been prevented by a face-to-face assessment. Severe postoperative adverse events (equal to or greater than Clavien-Dindo grade III) were observed in 1% of patients, and required re-intervention. 30-day readmission rate was 11%.

Conclusions

Our series showed that it is safe and feasible to assess and counsel patients for laparoscopic cholecystectomy remotely with a minimal cancellation rate on the day of operation. Further work is needed to understand the effect of remote consultations on patient satisfaction, its environmental impact, and possible benefits to healthcare economics to support its routine use in general surgery.
Clinical indicators that influence a clinician’s decision to start L-thyroxine treatment in prematurity with transient hypothyroxinemia
Authors: Yilmaz Aslan , Ozer Yavuz , Kaya Nesrin , Cakir Aydilek Dagdeviren , Culpan Hazal Cansu , Perk Yildiz , Vural Mehmet , Evliyaoglu Olcay
Published: August 2023

Background

Transient hypothyroxinemia of prematurity (THOP) is defined as a low level of circulating thyroxine (T4), despite low or normal thyroid-stimulating hormone (TSH) levels. Aims: We aimed to evaluate the incidence of THOP, the clinical and laboratory findings of preterm infants with this condition and the levothyroxine (L-T4) treatment.

Methods

Preterm infants (n = 181) delivered at 24–34 weeks of gestation were evaluated by their thyroid function tests that were performed between the 10th and 20th days of postnatal life and interpreted according to the gestational age (GA) references. Clinical and laboratory characteristics of the patients with THOP and normal thyroid function tests were compared. Patients with THOP and treated with L-T4 were compared with the ones who were not regarding laboratory, and clinical characteristics.

Results

Incidence of hypothyroxinemia of prematurity was 45.8% (n = 83). Euthyroidism, primary hypothyroidism, and subclinical hypothyroidism were diagnosed in 47.5% (n = 86), 5% (n = 9) and 1.7% (n = 3) of the patients, respectively. Mean birth weight (BW) and GA were significantly lower in the hypothyroxinemia group than in the euthyroid group (p < 0.001). L-T4 was started in 43% (n = 36) of the patients with THOP. Treatment initiation rate was 44.4% (n = 16) in 24–27 wk, 41.6% (n = 15) in 28–30 wk, and 13.8% (n = 5) in 31–34 wk. As the GA increased, the incidence of THOP and the rate of treatment initiation decreased (p < 0.001). The lowest free thyroxine (FT4) cut-off value was 0.72 ng/dl in the treated group. In addition, incidences of vancomycin + amikacin, caffeine, dopamine treatments, RDS, IVH, BPD, central catheter, FFP transfusion, and ventilator support were higher in the treated group (P < 0.05).

Conclusion

This study revealed that prevalence of THOP increased as the GA and BW decreased. As the GA decreased, THOP patients requiring L-T4 treatment increased. Additionally, association with comorbid diseases increased the requirement of treatment.
Single-cell RNA reveals a tumorigenic microenvironment in the interface zone of human breast tumors
Authors: Yang Wei , Xu Meiyu , Xu Shuoqi , Guan Qingxian , Geng Shuaiming , Wang Juanhong , Wei Wei , Xu Hongwei , Liu Ying , Meng Yong , Gao Ming-Qing
Published: August 2023

Background

The interface zone, area around invasive carcinoma, can be thought of as the actual tissue of the tumor microenvironment with precedent alterations for tumor invasion. However, the heterogeneity and characteristics of the microenvironment in the interface area have not yet been thoroughly explored.

Methods

For in vitro studies, single-cell RNA sequencing (scRNA-seq) was used to characterize the cells from the tumor zone, the normal zone and the interface zone with 5-mm-wide belts between the tumor invasion front and the normal zone. Through scRNA-seq data analysis, we compared the cell types and their transcriptional characteristics in the different zones. Pseudotime, cell–cell communication and pathway analysis were performed to characterize the zone-specific microenvironment. Cell proliferation, wound healing and clone formation experiments explored the function of differentially expressed gene BMPR1B, which were confirmed by tumor models in vivo.

Results

After screening, 88,548 high-quality cells were obtained and identified. Regulatory T cells, M2 macrophages, angiogenesis-related mast cells, stem cells with weak DNA repair ability, endothelial cells with angiogenic activity, fibroblasts with collagen synthesis and epithelial cells with proliferative activity form a unique tumorigenic microenvironment in the interface zone. Cell–cell communication analysis revealed that there are special ligand–receptor pairs between different cell types in the interface zone, which protects endothelial cell apoptosis and promotes epithelial cell proliferation and migration, compared to the normal zone. Compared with the normal zone, the highly expressed BMPR1B gene promotes the tumorigenic ability of cancer cells in the interface zone.

Conclusions

Our work identified a unique tumorigenic microenvironment of the interface zone and allowed for deeper insights into the tumor microenvironment of breast cancer that will serve as a helpful resource for advancing breast cancer diagnosis and therapy.
High-intensity walking in midlife is associated with improved memory in physically capable older adults
Authors: Choe Young Min , Suh Guk-Hee , Lee Boung Chul , Choi Ihn-Geun , Kim Hyun Soo , Kim Jong Wan , Hwang Jaeuk , Yi Dahyun , Kim Jee Wook
Published: August 2023

Background

Little is known about the associations of midlife- and late life-initiated walking with Alzheimer’s disease (AD)-related cognitive decline in humans. We aimed to investigate whether high-intensity, prolonged, midlife-initiated walking is associated with changes in AD-related cognitive decline in physically capable older adults.

Methods

We studied 188 physically capable participants aged 65–90 years without dementia who underwent comprehensive clinical assessment, including of their walking modality (i.e., intensity, duration, midlife- or late life-onset), memory- or non-memory and total cognitive performance, and blood or nutritional biomarkers.

Results

The walking group showed better episodic memory (B = 2.852, SE = 1.214, β = 0.144, p = 0.020), but not non-memory cognition, than the non-walking group. High-intensity walking starting in midlife was significantly associated with better episodic memory (B = 9.360, SE = 3.314, β = 0.446, p = 0.005) compared to the non-walking group. In contrast, there were no differences in cognition according to walking duration, regardless of the onset time. The walking group also showed a similar association with overall cognition.

Conclusions

Among physically capable older adults without dementia, walking, particularly at high intensity and starting in midlife, is associated with improved episodic memory, an AD-related cognitive domain. Further attention should be paid to the role of walking in terms of AD prevention.
EspE3 plays a role in the pathogenicity of avian pathogenic Escherichia coli
Authors: Li Qianwen , Qi Zhao , Fu Dandan , Tang Bo , Song Xiangjun , Shao Ying , Tu Jian , Qi Kezong
Published: August 2023

APEC encodes multiple virulence factors that have complex pathogenic mechanisms. In this study, we report a virulence factor named EspE3, which can be secreted from APEC. This protein was predicted to have a leucine-rich repeat domain (LRR) and may have a similar function to IpaH class effectors of the type III secretion system (T3SS). For further exploration, the regulatory correlation between the espE3 and ETT2 genes in APEC was analysed. We then assessed the pathogenicity of EspE3, detected it in APEC secretion proteins and screened the proteins of EspE3 that interact with chicken trachea epithelial cells. This study provides data on a new virulence factor for further exploring the pathogenic mechanism of APEC.
Determinants for participation in a prevention and early detection programme for children and adolescents in Germany: does social background play a role?
Authors: Krüger Kathrin , Lapstich Anne-Marie , Reber Katrin Christiane , Sehlen Stephanie , Liersch Sebastian , Krauth Christian
Published: August 2023

Early detection examinations and prevention are particularly important in childhood and adolescence, as certain diseases are already developing and health-related attitudes and behaviour patterns are formed and implemented. Despite the importance of screening and prevention, not all families use the available services and programmes. The aim of this study is to identify factors associated with participation in an early detection and prevention programme for children and adolescents, as well as factors associated with actual uptake of an examination. The analyses are based on questionnaire data of an online survey of participants and non-participants. Descriptive analyses and logistic regression models are conducted on a defined sample (n = 1,289). The results show that both groups differ with regard to several factors: age, chronic diseases, federal state, living space, number of siblings, country of birth, migration background, language spoken at home, mother’s occupational status, household income, treatment duration, and trust in treating physician. Regression I shows that participation in the programme is significantly associated with higher age, language spoken at home, mother’s occupational status and greater trust in the treating physician. The latter demonstrates the highest predictive power. Regression II indicates that the actual uptake of an examination among participants is significantly affected by age, federal state and father’s occupational status. Overall, the results of this study show that social background partly plays a role in participation, but that factors such as trust in the treating physician also have a significant impact. For the future, further research on the factors influencing participation in screening and prevention services or programmes for children and adolescents is important in order to develop strategies to overcome existing barriers and thus reach groups that have not been reached yet. In this context, trust in the treating physician and his or her influence on decision-making should in particular be considered.
The role of cortisol in immunosuppression in subarachnoid haemorrhage
Authors: Hoadley Margaret E. , Galea James , Singh Navneet , Hulme Sharon , Ajao David O. , Rothwell Nancy , King Andrew , Tyrrell Pippa , Hopkins Stephen J.
Published: August 2023

Background

We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral cytokine production following subarachnoid haemorrhage (SAH).

Methods

Whole blood from healthy controls, patients with SAH and healthy volunteers was stimulated with lipopolysaccharide (LPS), to stimulate innate immunity, or phytohaemagglutinin (PHA), to stimulate T cell-mediated immunity. Varying concentrations of cortisol were included, with or without the cortisol antagonist RU486. Concentration of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-alpha) TNFα were determined as a measure of innate immunity. IL-6, IL-17 (interferon gamma) IFNƔ and IL-17 were determined as an indicator of T cell-mediated immunity.

Results

Suppression of innate responses to LPS was apparent in whole blood from SAH patients, relative to healthy controls, and TNFα production was inversely correlated with plasma cortisol concentration. Cytokine production in whole blood from healthy volunteers was inhibited by cortisol concentrations from 0.33 µM, or 1 µM and above, and these responses were effectively reversed by the cortisol antagonist RU-486. In SAH patients, RU-486 reversed suppression of innate TNF-α and IL-6 responses, but not IL-1ß or T cell-mediated responses.

Conclusion

These data suggest that cortisol may play a role in reducing innate, but not T cell-mediated immune responses in patients with injuries such as SAH and that cortisol antagonists could be effective in boosting early innate responses.
Effects of melatonin on rumen microorganisms and methane production in dairy cow: results from in vitro and in vivo studies
Authors: Fu Yao , Yao Songyang , Wang Tiankun , Lu Yongqiang , Han Huigang , Liu Xuening , Lv Dongying , Ma Xiao , Guan Shengyu , Yao Yujun , Liu Yunjie , Yu Haiying , Li Shengli , Yang Ning , Liu Guoshi
Published: August 2023

Background

Methane (CH4) is a major greenhouse gas, and ruminants are one of the sources of CH4 which is produced by the rumen microbiota. Modification of the rumen microbiota compositions will impact the CH4 production. In this study, the effects of melatonin on methane production in cows were investigated both in the in vitro and in vivo studies.

Results

Melatonin treatment significantly reduced methane production in both studies. The cows treated with melatonin reduced methane emission from their respiration by approximately 50%. The potential mechanisms are multiple. First, melatonin lowers the volatile fatty acids (VFAs) production in rumen and reduces the raw material for CH4 synthesis. Second, melatonin not only reduces the abundance of Methanobacterium which are responsible for generating methane but also inhibits the populations of protozoa to break the symbiotic relationship between Methanobacterium and protozoa in rumen to further lowers the CH4 production. The reduced VFA production is not associated with food intake, and it seems also not to jeopardize the nutritional status of the cows. This was reflected by the increased milk lipid and protein contents in melatonin treated compared to the control cows. It is likely that the energy used to synthesize methane is saved to compensate the reduced VFA production.

Conclusion

This study enlightens the potential mechanisms by which melatonin reduces rumen methane production in dairy cows. Considering the greenhouse effects of methane on global warming, these findings provide valuable information using different approaches to achieve low carbon dairy farming to reduce the methane emission.
Predicted results of weak and strong ground motions at the target site of the blind prediction exercise as steps-2 and -3, Report for the experiments for the 6th international symposium on effects of surface geology on seismic motion
Authors: Tsuno Seiji , Nagashima Fumiaki , Kawase Hiroshi , Yamanaka Hiroaki , Matsushima Shinichi
Published: August 2023

In this study, we compared observations and predictions submitted by participants for blind prediction experiments for ground motions using aftershocks, foreshock, and mainshock of the 2016 Kumamoto earthquake sequence, Japan, to improve our understanding of the quality of state-of-the-art methods on the reproducibility of the effects of surface geology on seismic motions. In the blind predictions, 1D, 2D, and 3D methods, Green’s function methods, spectral ratio approaches, and other approaches were applied. As for PGA/PGV, acceleration/velocity duration, Fourier spectrum, pseudo-velocity response spectrum, and site amplification factors, the observed values are mostly within the range of average ± σ of all the predictions in the case of weak and strong ground motions. The results of the mean absolute percentage errors for these indices show that the applied methods can predict weak and strong ground motions for the three components in the range of one-half to twice the observations. The average goodness-of-fit (GOF) scores for weak and strong ground motions indicate either a very good fit (6.5–8) or a good fit (4.5–6.5) for the three components. Finally, examples of the categorized methods are quite limited; however, results indicate that the predictions by all the categorized methods can adequately reproduce weak and strong ground motions within either a very good or good fit. Although we could not find a significant difference in the results from the categorized methods, scores by the 2D and 3D methods in the frequency range of 0.5–1 and 1–2 Hz for all the blind predictions are higher than the scores by the other methods. The GOF score for the part after the S-wave by the 2D and 3D methods is higher than that by the 1D method. This supports that the predictions by the 2D and 3D methods due to the accounting of the proper geometry could reproduce the basin-induced and/or basin-transduced surface waves excited by the basin-edge effect more than the 1D method using the earthquake record observed at the reference site.

Graphical Abstract
A study on the chemical stability of cholesterol-lowering drugs in concomitant simple suspensions with magnesium oxide
Authors: Kato Ginjiro , Mitome Hidemichi , Miyauchi Yusura , Takeda Syu , Toyota Yoshito , Hidaka Noriaki , Tanaka Mamoru , Akira Kazuki
Published: August 2023

Background

Difficulty in taking solid medicines is a common issue particularly for the elderly because of a decline in swallowing function, also known as dysphagia. For patients with such a dysfunction, a simple suspension method, in which solid medicines are disintegrated and suspended using warm water, has been developed and widely used in Japanese clinical settings. However, there is little information on drug stability in the simple co-suspension of multiple formulations especially including acidic or alkaline ones. In this study, the chemical stability of typical cholesterol-lowering drugs was investigated in a simple co-suspension with alkaline magnesium oxide (MgO) which is frequently used as a laxative or antacid in Japan.

Methods

A cholesterol-lowering drug (one tablet) was soaked with or without MgO in warm water (55°C), and the vessel was left at room temperature for 10 min or 5 h. The suspensions prepared were then analyzed by high-performance liquid chromatography. Degradation products were analyzed by nuclear magnetic resonance spectroscopy and mass spectrometry for the structural elucidation.

Results

In the simple co-suspension with MgO, no significant degradation was observed for atorvastatin or pravastatin, while a significant decrease of the recovery from the co-suspension was observed for rosuvastatin after 5 h. On the other hand, simvastatin and ezetimibe co-suspended with MgO were partially degraded to simvastatin acid and a pyran compound, respectively.

Conclusions

A simple co-suspension with MgO is feasible for atorvastatin, pravastatin, and rosuvastatin, although the rosuvastatin tablet should not be left soaking for a long time. Further it is inadvisable to suspend simvastatin or ezetimibe together with MgO because of their partial degradation.
Retinal artery occlusion does not act as an independent marker of upcoming dementia: results from a Danish 20-year cohort study
Authors: Clausen Anna Rebien , Stokholm Lonny , Blaabjerg Morten , Frederiksen Katrine Hartmund , Pedersen Frederik Nørregaard , Grauslund Jakob
Published: August 2023

Purpose

Retinal artery occlusion (RAO) is a vision threatening disease associated with cerebral vascular dysfunction, which may reflect initial signs of cerebral pathology. Early detection of patients in risk of dementia could allow for preventative treatment. Hence, this study aimed to investigate RAO as an independent biomarker of incident dementia.

Methods

This study was a nationwide, 20-year longitudinal cohort study in Denmark with inclusion from 1998 to 2020 and follow up until the end of 2022. We identified 2 205 159 individuals aged 65 or older through the Danish national health registers and monitored RAO (exposure) and dementia (outcome) status. We calculated incidence rate and performed a Cox regression analysis with hazard ratio (HR) and 95% confidence interval (CI) for RAO as a marker of dementia in a crude, a semi-adjusted (age and sex), and a fully adjusted model (furthermore adjusted for marital status and systemic comorbidity.)

Results

We identified 8 863 individuals with RAO. Incidence rates were higher among exposed compared to unexposed individuals (12.28 and 8.18 per 1000 person-years at risk, respectively). Individuals with RAO were more likely to be male and older at inclusion, to have hypertension, dyslipidaemia, cardiovascular disease, chronic kidney disease, and diabetes (p < 0.001). RAO was not associated with all-cause dementia in the crude analysis (HR 1.07 CI [1.00-1.17]) or in the fully adjusted analysis (HR 0.98 CI [0.91–1.06].

Conclusion

Although individuals with RAO had a higher incidence of dementia compared to unexposed individuals, these associations were lost when confounders were taken into account.
Mass production of entomopathogenic fungi Purpureocillium lilacinum PL1 as a biopesticide for the management of Amrasca devastans (Hemiptera: Cicadellidae) in okra plantation
Authors: Nguyen Thi Hai , Nguyen Quynh Nhu , Dang Thi Nhu Quynh , Nguyen Ngoc Lam , Do Anh Duy
Published: August 2023

Background

Effective management strategies are crucial in minimizing the adverse consequences associated with the leafhopper, Amrasca devastans (Dist.) (Hemiptera: Cicadellidae). Economic limitations to entomopathogenic fungi production present a substantial challenge, particularly in developing countries. This study aimed to investigate a cost-effective solid-state fermentation (SSF) for large-scale production of Purpureocillium lilacinum PL1 conidia to manage A. devastans infestations in okra cultivation.

Results

Rice and maize were demonstrated as highly suitable substrates for producing conidia densities of over 2 × 1010 conidia g−1. Furthermore, the influence of agricultural phytosanitary agents on the growth rates of P. lilacinum PL1 was evaluated. Certain pesticides were ineffective on the expansion of P. lilacinum PL1 colonies, while fungicides exhibited complete inhibition. The laboratory investigation revealed that 1 × 107 conidia ml−1 of P. lilacinum PL1 exhibited a success rate of 88.66% in decreasing the population of A. devastans nymphs in vitro. Furthermore, field investigations carried out in okra plantations demonstrated that the utilization of P. lilacinum PL1 at the concentration of 1 × 107 conidia ml−1 of resulted in a significant reduction of the pest nymph population by 72.87% subsequent to the 2 applications.

Conclusion

In conclusion, the cost-effective mass production of P. lilacinum PL1 conidia through SSF presents a promising solution for managing A. devastans infestations in okra farming, particularly in economically challenged regions.
Effect of body mass index on N-terminal pro-brain natriuretic peptide values in patients with heart failure
Authors: Ha Manh Tuan , Do Anh Duong , Le Viet Tung
Published: August 2023

Background

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker used for the diagnosis of heart failure. There is a relationship between NT-proBNP levels and body mass index (BMI). The study aimed to explore the impact of BMI on NT-proBNP concentrations and to examine whether other factors independent of or combined with BMI affect NT-proBNP values in patients with heart failure.

Results

A total of 293 participants were recruited. The mean age was 68.9 ± 13.2 years, males accounted for 46.4% of the total cohort, the mean BMI was 23.1 ± 4.0 kg/m2, and the median NT-proBNP level was 3776 (1672–8806) pg/ml. There was an inverse relationship between BMI and log NT-proBNP (r = − 0.29; p < 0.001, Spearman correlation). Each standard deviation increase in BMI (4 kg/m2) was associated with a 7% decrease in NT-proBNP values in the total cohort. The independent inverse determinants of NT-proBNP other than BMI were male gender and eGFR, while the variables directly correlated to NT-proBNP were LVEF ≤ 40% and NYHA class III–IV heart failure.

Conclusions

There is an inverse association between BMI and NT-proBNP levels. However, the correlation is weak, and there are other variables that have a significant impact on the NT-proBNP values as well. The NT-proBNP levels are still valuable in the diagnosis of heart failure regardless of BMI status.