bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of the bone morphogenetic protein pathway suppresses tumor growth through downregulation of epidermal growth factor receptor in MEK/ERK‐dependent colorectal cancer
Authors: Shimizu Shota , Kondo Jumpei , Onuma Kunishige , Coppo Roberto , Ota Kasumi , Kamada Mayumi , Harada Yohei , Tanaka Yoshihisa , Nakazawa Mai Adachi , Tamada Yoshinori , Okuno Yasushi , Kawada Kenji , Obama Kazutaka , Coffey Robert J. , Fujiwara Yoshiyuki , Inoue Masahiro
Published: June 2023

The bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, its role in colorectal cancer (CRC) is controversial, where it can act as context‐dependent tumor promoter or tumor suppressor. Here we have found that CRC cells reside in a BMP‐rich environment based on curation of two publicly available RNA‐sequencing databases. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of select CRC organoids. Colorectal cancer organoids treated with LDN193189 showed a decrease in epidermal growth factor receptor, which was mediated by protein degradation induced by leucine‐rich repeats and immunoglobulin‐like domains protein 1 (LRIG1) expression. Among 18 molecularly characterized CRC organoids, suppression of growth by BMP inhibition correlated with induction of LRIG1 gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth‐suppressive effect of LDN193189. Furthermore, in CRC organoids, which are susceptible to growth suppression by LDN193189, simultaneous treatment with LDN193189 and trametinib, an FDA‐approved MEK inhibitor, resulted in cooperative growth inhibition both in vitro and in vivo. Taken together, the simultaneous inhibition of BMP and MEK could be a novel treatment option in CRC cases, and evaluating in vitro growth suppression and LRIG1 induction by BMP inhibition using patient‐derived organoids could offer functional biomarkers for predicting potential responders to this regimen.
Genetic and nongenetic mechanisms for colorectal cancer evolution
Authors: Kok Sau Yee , Nakayama Mizuho , Morita Atsuya , Oshima Hiroko , Oshima Masanobu
Published: June 2023

The stepwise accumulation of key driver mutations is responsible for the development and malignant progression of colorectal cancer in primary sites. Genetic mouse model studies have revealed combinations of driver gene mutations that induce phenotypic changes in tumors toward malignancy. However, cancer evolution is regulated by not only genetic alterations but also nongenetic mechanisms. For example, certain populations of metastatic cancer cells show a loss of malignant characteristics even after the accumulation of driver mutations, and such cells are eliminated in a negative selection manner. Furthermore, a polyclonal metastasis model has recently been proposed, in which cell clusters consisting of genetically heterogeneous cells break off from the primary site, disseminate to distant organs, and develop into heterogenous metastatic tumors. Such nongenetic mechanisms for malignant progression have been elucidated using genetically engineered mouse models as well as organoid transplantation experiments. In this review article, we discuss the role of genetic alterations in the malignant progression of primary intestinal tumors and nongenetic mechanisms for negative selection and polyclonal metastasis, which we learned from model studies.
Evaluation of aggression level in adolescent girls with classical congenital adrenal hyperplasia
Authors: Isik Recep Oğuzhan , Kizilcan Cetin Sirmen , Cetinkaya Semra , Berberoglu Merih , Siklar Zeynep , Özsu Elif , Aycan Zehra
Published: June 2023

Objective

In patients with classical congenital adrenal hyperplasia (CAH), virilization affects the brain and external genitalia due to antenatal androgen exposure. There are few studies on how the effects of androgens on brain virilization are reflected in behavior. However, there is no study focused on the adolescence period. The aim of this study was to evaluate the level of aggression in adolescent girls with classical CAH (due to 21 hydroxylase and 11β hydroxylase deficiency) and to investigate the disease‐related factors that may affect aggression.

Design

Twenty female and 20 male patients aged 13–20 years, diagnosed with classical CAH, with 21 hydroxylase deficiency and 11β hydroxylase deficiency, and 20 healthy girls and 20 boys from the same age group were included. The Buss‐Perry Aggression Scale (BPAS), which consists of four subgroups measuring physical aggression, verbal aggression, hostility, and angry behaviors, was used.

Results

The ages of the male and female patients with CAH were 16.30 ± 2.65 and 16.60 ± 2.41 years, respectively. Total aggression scale scores were 73.3 ± 14.6 in adolescent girls with CAH, 74.1 ± 11.2 in healthy girls, 71.5 ± 14.8 in boys with CAH, and 75.3 ± 14.5 in healthy boys (p > .05). There was no difference between the subscale scores of patients and healthy adolescents. Aggression scores in adolescents with CAH increased significantly with age.

Conclusions

In this study, we found no difference between the aggression scores of adolescents with classical CAH compared to their healthy peers. The total aggression score and subscale were similar in unaffected female adolescents.
Modulation of gene expression and bone formation by expanded and dense polytetrafluoroethylene membranes during guided bone regeneration: An experimental study
Authors: Turri Alberto , Omar Omar , Trobos Margarita , Thomsen Peter , Dahlin Christer
Published: June 2023

Background

Nonresorbable membranes promote bone formation during guided bone regeneration (GBR), yet the relationships between membrane properties and molecular changes in the surrounding tissue are largely unknown.

Aim

To compare the molecular events in the overlying soft tissue, the membrane, and the underlying bone defect during GBR using dual‐layered expanded membranes versus dense polytetrafluoroethylene (PTFE) membranes.

Materials and Methods

Rat femur defects were treated with either dense PTFE (d‐PTFE) or dual‐layered expanded PTFE (dual e‐PTFE) or left untreated as a sham. Samples were collected after 6 and 28 days for gene expression, histology, and histomorphometry analyses.

Results

The two membranes promoted the overall bone formation compared to sham. Defects treated with dual e‐PTFE exhibited a significantly higher proportion of new bone in the top central region after 28 days. Compared to that in the sham, the soft tissue in the dual e‐PTFE group showed 2‐fold higher expression of genes related to regeneration (FGF‐2 and FOXO1) and vascularization (VEGF). Furthermore, compared to cells in the d‐PTFE group, cells in the dual e‐PTFE showed 2.5‐fold higher expression of genes related to osteogenic differentiation (BMP‐2), regeneration (FGF‐2 and COL1A1), and vascularization (VEGF), in parallel with lower expression of proinflammatory cytokines (IL‐6 and TNF‐α). Multiple correlations were found between the molecular activities in membrane‐adherent cells and those in the soft tissue.

Conclusion

Selective surface modification of the two sides of the e‐PTFE membrane constitutes a novel means of modulating the tissue response and promoting bone regeneration.
Mucosal bleeding correlates with submucosal microbial dysbiosis in peri‐implant mucositis of patients with periodontitis
Authors: Li Siqi , Sun Fei , Wei Yiping , Nie Yong , Wu Xiaolei , Hu Wenjie
Published: June 2023

Objectives

This study aimed to investigate the relationship between microbial communities and the severity of peri‐implant mucosal bleeding in peri‐implant mucositis.

Materials and Methods

Submucosal plaque samples were collected from 54 implants divided into the healthy implant (HI) group, peri‐implant mucositis (PM) group, and peri‐implantitis (PI) group. Sequencing of 16S rRNA was performed using the Illumina MiSeq platform. Alpha diversity (i.e., Shannon and Chao index) and beta diversity were used to measure microbial diversity within and between microbial communities, respectively. Differences in microbial taxa between groups were assessed via linear discriminate analysis effect size. Correlation between the modified sulcus bleeding index (mSBI) and microbial dysbiosis index (MDI) was examined using Spearman correlation analysis and linear models.

Results

The submucosal bacterial richness (Chao index) was positively correlated with the mean mSBI in the PM group. As the mean mSBI increased in the PM group, the beta diversity became closer to that of the PI group. In the PM group, the abundances of 47 genera were significantly correlated with the mean mSBI, and the MDI was positively associated with the mean mSBI. Fourteen of the forty‐seven genera were discriminative taxa between the HI and PI groups, and the abundances of these biomarkers became closer to those in the PI group in the progression of peri‐implant disease.

Conclusions

A higher mSBI value corresponded to a higher risk of microbial dysbiosis in peri‐implant mucositis. The biomarkers identified may be useful for monitoring the progression of peri‐implant disease.
Sustained weight loss with semaglutide once weekly in patients without type 2 diabetes and post‐bariatric treatment failure
Authors: Lautenbach Anne , Kantowski Tobias , Wagner Jonas , Mann Oliver , Stoll Fabian , Aberle Jens
Published: June 2023

About 20%–25% of patients experience weight regain (WR) or insufficient weight loss (IWL) following bariatric surgery (BS). Therefore, we aimed to retrospectively assess the effectiveness of adjunct treatment with semaglutide in patients without type 2 diabetes (T2D) with post‐bariatric treatment failure over a 12 months period. Post‐bariatric patients without T2D with WR or IWL (n = 29) were included in the analysis. The primary endpoint was weight loss 12 months after initiation of adjunct treatment. Secondary endpoints included change in body mass index, HbA1c, lipid profile, high sensitive C‐reactive protein and liver enzymes. Total weight loss during semaglutide treatment added up to 14.7% ± 8.9% (mean ± SD, p < .001) after 12 months. Categorical weight loss was >5% in 89.7% of patients, >10% in 62.1% of patients, >15% in 34.5% of patients, >20% in 24.1% of patients and > 25% in 17.2% of patients. Adjunct treatment with semaglutide resulted in sustained weight loss regardless of sex, WR or IWL and type of surgery. Among patients with prediabetes (n = 6), 12 months treatment led to normoglycemia in all patients (p < .05). Treatment options to manage post‐bariatric treatment failure are scarce. Our results imply a clear benefit of adjunct treatment with semaglutide in post‐bariatric patients over a 12 months follow‐up period.
Macroprudential policy leakage: Evidence from shadow banking activities of Chinese enterprises
Authors: Lin Guiting , Ouyang Alice Y.
Published: June 2023

Using entrusted loan data of Chinese listed enterprises, we study whether the implementation of macroprudential policy leads to enterprise policy arbitrage. Our findings reveal that tightening macroprudential policies significantly contribute to the promotion of shadow banking activities among Chinese enterprises, confirming the existence of policy leakage. When the overall credit is tight, non‐affiliated loans and loans to privately‐owned enterprises increase significantly. Tightening policies also have a more substantial effect on the borrowing cost of non‐affiliated and privately‐owned enterprise borrowers. To enhance the effectiveness of macroprudential policy, our results suggest the necessity of providing appropriate credit supports for small and medium enterprises.
MRLC controls apoptotic cell death and functions to regulate epidermal development during planarian regeneration and homeostasis
Authors: Sun Yujia , Huang Yongding , Hao Zhitai , Zhang Shoutao , Tian Qingnan
Published: June 2023

Adult stem cells (ASCs) are pluripotent cells with the capacity to self‐renew and constantly replace lost cells due to physiological turnover or injury. Understanding the molecular mechanisms of the precise coordination of stem cell proliferation and proper cell fate decision is important to regeneration and organismal homeostasis. The planarian epidermis provides a highly tractable model to study ASC complex dynamic due to the distinct spatiotemporal differentiation stages during lineage development. Here, we identified the myosin regulatory light chain (MRLC) homologue in the Dugesia japonica transcriptome. We found high expression levels of MRLC in wound region during regeneration and also expressed in late epidermal progenitors as an essential regulator of the lineage from neoblasts to mature epidermal cells. We investigated the function of MRLC using in situ hybridization, real‐time polymerase chain reaction and double fluorescent and uncovered the potential mechanism. Knockdown of MRLC leads to a remarkable increase in cell death, causes severe abnormalities during regeneration and homeostasis and eventually leads to animal death. The global decrease in epidermal cell in MRLC RNAi animals induces accelerated epidermal proliferation and differentiation. Additionally, we find that MRLC is co‐expressed with cdc42 and acts cooperatively to control the epidermal lineage development by affecting cell death. Our results uncover an important role of MRLC, as an inhibitor of apoptosis, involves in epidermal development.
Proposed museum service operations framework for addressing overcrowding: A Taipei case study
Authors: Su Yaohua
Published: June 2023

Although the high growth of the tourism market contributes to a record number of visitors to landmark museums, they also encounter the overcrowding problem. This study reviewed the case of National Palace Museum (NPM) in Taipei to discuss the overcrowding problem and provide suggestions to alleviate this problem. This study adopted document analysis to summarize NPM's policies regarding the overcrowding problem that were identified by performing text mining of visitors' reviews for the NPM. And a content analysis involving semantic analysis and coding of negative reviews for NPM retrieved from TripAdvisor was performed for extracting complaint categories regarding the overcrowding problem. On the basis of the results, a service operation management framework in response to museum overcrowding is proposed. This study suggests that a museum can manage the overcrowding problem on the basis of visitor characteristics by adjusting visitor demand, optimizing the service design, diverting visitors' flow, elaborating the floor plan and exhibition design, or forming a decentralized museum hub to move must‐see exhibits for tourists to a stand‐alone pavilion or branch to disperse the crowd.
Bladder prolapse with simultaneous entrapment of a portion of the descending colon through the urethral sphincter secondary to dystocia in a mare
Authors: Sikorra Weronika , Berreta Ana , Voermans Margreet , Robinson Claire
Published: June 2023

Bladder prolapse is rare in mares but may occur as a result of excessive straining during parturition or postpartum. We report a case of dystocia‐associated prolapse and entrapment of the small colon through the external urethral opening into a prolapsed urinary bladder. No previous reports of this condition were found. An 11‐year‐old Thoroughbred mare was presented to The Equine Hospital of the Jockey Club of Saudi Arabia for evaluation and treatment of dystocia. Prolapse of the urinary bladder was concomitantly diagnosed. After initial assessment, replacement of the urinary bladder in the normal position did not appear possible. The mare was immediately prepared for caesarean section. The foal was successfully delivered and resuscitated. Detailed assessment of the bladder during surgery revealed that the small colon had prolapsed through the external urethral opening and was inside the space formed by the everted bladder. The urinary bladder was opened. The small colon was replaced into the abdominal cavity; a surgeon gently replaced the small colon through the external urethral sphincter and a second surgeon retrieved the small colon by gentle traction until normally aligned. The bladder was closed and replaced. The mare recovered uneventfully. The mare and the foal were discharged from the hospital 17 days post‐operatively.
Dupilumab‐associated ocular adverse events are predicted by low tear break‐up time and correlate with high IL‐33 tear concentrations in patients with atopic dermatitis
Authors: Chiricozzi A. , Di Nardo L. , Gori N. , Antonelli F. , Pinto L. , Cuffaro G. , Piro G. , Savino G. , Tortora G. , Peris K.
Published: June 2023

Dupilumab, blocking IL‐4 and IL‐13 signals, improves atopic dermatitis and Quality of Life but might be also associated with the occurrence of ocular adverse events (OAEs). The main objective of our prospective study was to characterize the cytokine and chemokine profile in the tear fluid of dupilumab‐treated patients with moderate‐to‐ severe atopic dermatitis and to identify biomarkers predicting the occurrence of ocular adverse events. Patients with moderate‐to‐severe AD underwent dermatological and ophthalmological evaluation at the baseline (T0) and week 16 or at the time of an eventual ocular adverse events (T1). A multiplex immunoassay measuring multiple cytokines and chemokines in the tear fluid extracted during ocular examination at both T0 and T1 was performed. Thirty‐nine patients with moderate‐to‐severe AD and treated with dupilumab were included in the study. Baseline tear fluid levels revealed a significantly higher concentration of type 2 cytokines and chemokines in AD patients than healthy controls. The occurrence of ocular adverse events during dupilumab therapy was associated with a significant increase of IL‐33 tear fluid levels and a significantly lower tear break‐up time, this latter also identified as predictive factor. Our findings suggest that the ophthalmological examination should be considered a valid support to identify patients at risk of developing OAEs and to provide their appropriate management.
How do I work this? A mixed‐methods evaluation of relationship education for high school youth
Authors: Bradford Kay , Harris Jennifer , Boehme Raquel , Turner Joshua J. , Higginbotham Brian
Published: June 2023

Objective

Guided by social exchange theory, we used mixed methods to examine youth romantic relationship concerns, perceived gains from a relationship education curriculum, and the extent to which the curriculum addressed adolescents' concerns.

Background

Adolescents' relationships influence the health of their future romantic relationships. Relationship education is increasingly offered to youth in the United States, but few studies examine how well these programs address youth concerns.

Methods

Phenomenological content analysis was used to analyze short‐response qualitative data (n = 267) about romantic relationship concerns (pretest) and programmatic gains (posttest). Themes were then compared to examine how well the curriculum addressed youth concerns. Quantitative pretest–posttest outcomes were also examined among a larger sample (n = 9,130). Complementarity was used to consider qualitative and quantitative findings together.

Results

Participants' pretest concerns included relationship knowledge (i.e., how, with whom, and when to have a relationship), and relationship risks (e.g., cheating, coercion). Posttest themes suggested that program content largely addressed participants' concerns (i.e., increased knowledge, ability to discern healthy and unhealthy relationships). Quantitative analyses yielded significant changes in four measures of participant attitudes pretest to posttest, with increased relationship knowledge and healthier attitudes.

Conclusions

Youth perceived that relationship education gave them tools that addressed their stated concerns; quantitative data suggest the program had its intended effect.

Implications

Youth relationship education is a positive preventative intervention.
Using multivariate autoregressive state‐space models to examine stock structure of Greenland halibut in the North Atlantic
Authors: Úbeda J. , Nogueira A. , Tolimieri N. , Vihtakari M. , Elvarsson B. , Treble M. , Boje J.
Published: June 2023

Accurate information on population structure is essential for effective fisheries management. Greenland halibut (Reinhardtius hippoglossoides) in the North Atlantic is managed as four separate offshore stocks. We use Multivariate Autoregressive State‐Space (MARSS) models to assess population structure by means of abundance and biomass trends in four regions (Norwegian Sea, Iceland, Southeast Greenland, and Northwest Atlantic) where three offshore stocks are recognized: (1) Baffin Bay–Davis Strait (Northwest Atlantic stock), (2) Southeast Greenland and Iceland (West Nordic stock (WNS)), and (3) the Barents and Norwegian Seas (Northeast Arctic stock). We formulated model alternatives, using bottom trawl survey data from each region for 1996–2019, to evaluate support for different population structures. Abundance and biomass observations from each region were linked to growth rate parameters in MARSS models and the impact of climate (North Atlantic Oscillation Index) and fishing (commercial catches) on stock dynamics was investigated. Top models identified the Northwest Atlantic as an independent population. Best‐fit models treated Greenland halibut in the WNS as two independent populations (east and west), with potential connections between eastern Iceland and the western Barents Sea. These results suggest a mismatch between current stock perception and management boundaries in the Northeast Atlantic.
Pyrolysis temperature determines the amendment effects of poplar residue‐derived biochars on reducing CO2 emission
Authors: Ding Sihui , Lan Ziyu , Fang Shengzuo
Published: June 2023

Poplars and their hybrids are widely planted in both plantation forestry and agroforestry systems of the world. Along with the utilization and plantation management processes, a large amount of biomass residues are produced, but the relationship between biochar properties and soil CO2 emissions is largely unknown. Here, a laboratory incubation study was conducted to assess the effects of different biochars and their corresponding biomass residues on soil CO2 emissions during the 180 days of incubation. Poplar residue‐derived biochars were larger in the surface area and total pore volume but lower in nutrients and pH values than the rice straw‐derived biochar. Increasing pyrolysis temperature led to a decrease in the total nitrogen (TN) content of poplar leaf‐ and rice straw‐derived biochars, but enhanced the TN in the poplar twig‐ and poplar bark‐derived biochars. After 180‐day incubation, the total cumulative CO2 emission decreased by 33.1%–73.8% in the biochar amendments compared to their corresponding biomass residue addition, whereas the biochars derived from poplar twig and bark residues had more positive effects on reducing soil CO2 emissions, but depended on the pyrolysis temperature. Correlation analysis showed a significant and positive correlation between the CO2 emissions and TN content of bio‐based materials but the negative relationships to total carbon content and C/N ratio. Meanwhile the positive correlations of CO2 emissions to the surface area, t‐plot micropore area, and volume of the biochars were detected. Our results suggest that application of poplar twig‐ and poplar bark‐derived biochars has a great potential for mitigating global warming.
Exploring the molecular characteristics of the malignant potential of gastric adenocarcinoma with enteroblastic differentiation
Authors: Wang Yong , Wei Xiyin , Ke Bin , Liu Jia , Guo Yuhong , Liu Yanxue , Chen Yongzi , Ding Tingting , Wang Yalei , Meng Bin , Sun Baocun , Zang Fenglin
Published: June 2023

Aims

Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare subset of alpha‐fetoprotein (AFP)‐producing carcinomas with poor prognosis. However, the molecular features associated with the malignant potential of GEAD remain partially elucidated.

Methods and results

In this study, the relationship between clinicopathological parameters and aggressive biological behaviour was analysed in 37 patients with GAED. The results showed that GAED tended to infiltrate the deep layer of the gastric wall and possessed more frequent vascular invasion than conventional gastric adenocarcinoma (CGA) (P < 0.001). All distant metastases were observed in the GAED group, not the CGA group (P < 0.001). High HER2 expression was found in nearly 24.32% of the informative cases, and none showed EBV‐encoded RNA positivity or deficient mismatch repair. The most frequently mutated gene in GAED was p53. Programmed cell death‐ligand 1 (PD‐L1) immunostaining revealed 13 patients with a combined positive score (CPS) ≥ 5 (65%, 13 of 20). Thus, based on these molecular markers (immunostaining, in situ hybridisation and mutation analysis), GAED may be classified as a unique subgroup of the chromosomal instability subtype with HER2+/EBV−/MSS/TP53+/PD‐L1+. Next‐generation sequencing analyses showed that mutations in the TOPI, ELOA and NOTCH3 genes were found only in GAED, and abnormally expressed genes in GAED were significantly enriched in hepatocellular carcinoma‐, gland development‐, and gastric cancer‐related pathways.

Conclusion

The HER2+/EBV−/MSS/TP53+/PD‐L1+ profile and hepatocellular carcinoma‐related pathways may be significant in the malignant potential of GAED. In addition to anti‐HER2 therapy, immune check‐point inhibitors may be an effective treatment option for patients with GAED.
The bioceramic sealer iRoot SP promotes osteogenic differentiation of human stem cells from apical papilla via miR‐141‐3p/SPAG9/MAPK signalling pathway
Authors: Xue Kaiyang , Hu Guang , Wu Laidi , Han Hao , Sun Yuhui , Gan Kang , Zhu Juanfang , Du Tianfeng
Published: June 2023

Aim

The premixed bioceramic sealer iRoot SP that is widely used clinically has been reported to kill bacterial biofilms and promote osteogenic differentiation of human stem cells from the apical papilla (hSCAPs). Although miR‐141‐3p has been substantiated to be involved in the osteogenic process, the underlying mechanisms remain unclear. The aim of this study was to investigate the role of miR‐141‐3p in osteogenic differentiation and underlying mechanisms of iRoot SP‐treated hSCAPs.

Methodology

hSCAPs were extracted from tissue blocks with enzyme digestion and identified by using immunofluorescence, flow cytometry and alizarin red staining. The mRNA expression level of miR‐141‐3p in hSCPAs after culture with iRoot SP was examined by quantitative real‐time PCR (qRT‐PCR) assay. SPAG9 was identified as a downstream target gene of miR‐141‐3p by dual‐luciferase report assay. Alkaline phosphatase (ALP) staining and activity detection, alizarin red staining, calcium concentration assay, qRT‐PCR and western blot were used to estimate osteogenic differentiation ability and involved protein expression levels of the osteogenic makers and signalling pathway‐related factors in iRoot SP‐treated hSCAPs. Data were analysed by one‐wayanovaandpost hocTukey's test to determine any statistical differences between the experimental groups and the control group.p < .05 was considered statistically significant.

Results

Expression of miR‐141‐3p was reduced in iRoot SP‐treated hSCAPs with the increased exposure time up to 7 days, and the western blot and qRT‐PCR results revealed that the osteogenic markers osteocalcin (OCN), osterix (OSX), runt‐related transcription factor 2 (RUNX2) and dentin sialophosphoprotein (DSPP) were inversely correlated with miR‐141‐3p. The negative regulatory relationship between miR‐141‐3p and SPAG9/ mitogen‐activated protein kinases (MAPK) signalling axis was validated in thisin vitroexperiments.

Conclusions

The bioceramic sealer iRoot SP promoted osteogenic differentiation of hSCAPs by inhibiting miR‐141‐3p following down‐regulated SPAG9 expression, and activated MAPK pathway. These findings proposed a novel therapeutic impact of bioceramic sealer iRoot SP inducing bone regeneration in refractory periapical periodontitis.
Powder synthesis, densification, microstructure, and mechanical properties of HfB2‐HfC ceramic composites
Authors: Sun Wenzhou , Tian Yu , Xu Shidiao , Liu Limeng , Lu Youjun
Published: June 2023

A new route based on HfO2 + B4C + C → HfB2 + HfC + CO reaction was developed to synthesize HfB2‐HfC hybrid powders. X‐ray diffraction, scanning electron microscopy, energy dispersive spectrometry, and transmission electron microscopy were used to evaluate the powder products. The effects of excess additions of B4C and C on the phase constituents of the powder products were investigated. Thermodynamics of relevant reactions for the synthesis of the hybrid powders were calculated to guide the selection of compositions and processing parameters. The results indicated that HfB2‐HfC hybrid powders were obtained by reaction at 1750°C for 1 h. HfB2:HfC phase content ratios showed a dependence on B4C and C additions. The obtained hybrid powders exhibited good oxidation resistance with an oxidation activation energy of 303 kJ/mol. Good sinterability of the powder products was demonstrated by spark plasma sintering at 2100°C. The consolidated ceramics based on them measured good Vickers’ hardness values (>26.0 ± .5 GPa) and fracture toughness (>3.78 ± .27 MPa·m1/2).
Effect of lactic acid fermentation on the quality and phytochemical constituent in smoothies made from the leaves of different sweet potato (Ipomoea batatas L.) cultivars
Authors: Mashitoa Florence M. , Akinola Stephen A. , Shoko Tinotenda , Seke Faith , Sunette Laurie M. , Sultanbawa Yasmina , Sivakumar Dharini
Published: June 2023

This study investigated the effect of fermentation by Lactiplantibacillus plantarum 75 (L75) on the physicochemical properties, survival of L75, sensory, antioxidants and their activities in leaf smoothies of six sweet potato cultivars [Orange‐fleshed (OFSP): ‘Bophelo’, and ‘Beauregard’; cream‐fleshed (CFSP): ‘Blesbok’ and ‘Ndou’; and purple‐fleshed (PFSP): ‘08.21p’ and ‘Purple‐purple’]. Fermentation significantly affected the physiochemical properties. Fermentation for 24 h improved the carotenoid (TCC), ascorbic acid (AA) (6.8, 6.0 mg 100 g−1) and total phenolic (4435 mg 100 g−1) significantly in, ‘Bophelo’ smoothies. Whilst 48 h fermentation significantly increased the TCC, AA, organic acids, valine and alanine levels in ‘Blesbok’ smoothies'. Principal component analysis separated the unfermented ‘Bophelo’ and Purple‐purple’ leaf smoothies from fermented leaf smoothies of OFSP, CSFP, and PFSP. DPPH scavenging activity and alpha‐carotene were effective markers for separating fermented from unfermented leaf smoothies in the variable importance study. Survival of L75 was influenced by fermentation duration and cultivar type. Fermented and unfermented smoothies were equally acceptable.
Effects of different pH, temperature, and pressurisation time on the stability of chlorophylls treated with Zn2+ and high hydrostatic pressure
Authors: Hu Yuwei , Sun Hongnan , Mu Taihua
Published: June 2023

This study provides an effective method to improve the stability of chlorophylls. The effects of different pH, temperature, and pressurisation time on the colour, antioxidant activity, Zn2+ replacement ratio, structure, and thermal stability of chlorophylls treated with Zn2+ (10 mg 100 mL−1) and high hydrostatic pressure (500 MPa) were investigated. The electronic eye, ultraviolet spectrophotometer, high‐performance liquid chromatography, Fourier transform infrared, and high hydrostatic pressure (HHP) online monitor cooperated with fluorescence spectrophotometer were used to investigate the effects of different pH values, water bath temperatures, and pressurisation time on the colour, antioxidant activity, Zn2+ replacement ratio, and structure of chlorophylls. The highest −a* (6.92), antioxidant activity (ABTS 41.01 g ACE 100 g−1, DPPH 52.86 g ACE 100 g−1, FRAP 35.72 g TE 100 g−1 DW), and Zn2+ replacement ratio (47.32%) were obtained at 50 °C, pH = 7.0, and 20 min. It is hoped that this study will provide a new idea for the protection of natural pigments.
Ethanol/salt aqueous two‐phase systems (ATPS) for enrichment and identification of bioactive constituents escaping during pectin extraction
Authors: Ruan Cheng‐wei , Jiang Wen‐xin , Liao Jin‐song , Liu Zi‐wei , Song Ya‐ting , Qi Jun‐ru
Published: June 2023

The acid heating extraction process is commonly employed to extract pectin from citrus peels, which results in the leaching of bioactive constituents into solvents. However, the discharge of these solvents represents a significant loss of valuable resources. To address this issue, this study aims to identify the composition and concentration of the bioactive constituents that escape into the solvents and propose an extraction process based on an ethanol‐salt aqueous two‐phase system (ATPS). The well‐designed ATPS enables the enrichment and recovery of the bioactive constituents, and the findings demonstrate that the ethanol/sodium citrate‐based ATPS can recover up to 80.61% of limonoids, 84.11% of flavonoids, and 88.09% of polyphenols that escape at an enrichment efficiency of 50.00%. Moreover, HPLC‐DAD and UPLC‐HRMS analysis of the ATPS extracts revealed the presence of nine bioactive constituents, including flavonoids, phenolic acids, and limonoids. Remarkably, in vitro antioxidant capacity studies indicate that the ATPS extracts exhibit superior antioxidant activity compared to the vacuum‐concentrated solution. Thus, these results suggest that the application of ATPS extraction is a feasible and promising strategy for the recovery of bioactive constituents.
Isolation and characterisation of cellulose nanocrystals from kudzu (Pueraria montana var. lobata): a sustainable packaging material
Authors: Punia Bangar Sneh , Love Reid , Whiteside William Scott , Doh Hansol , Darby Duncan O. , Bridges William S.
Published: June 2023

Flexible packaging has become indispensable in the food industry due to its numerous advantages. However, it has certain drawbacks, such as limited recyclability and environmental contamination. While efforts are underway to develop more sustainable and eco‐friendly packaging options, the food industry's reliance on flexible packaging made from unsustainable petro‐based plastics is expected to continue in the foreseeable future. Therefore, more sustainable alternatives that do not sacrifice performance are required. One such option is to use nanocellulose, especially cellulose nanocrystals (CNCs), which can be reinforced into biopolymer to enhance mechanical and barrier properties. The present study aims to isolate kudzu CNCs by depolymerisation, bleaching, acid hydrolysis with 51% sulfuric acid, and mechanical dispersion. Thermogravimetric analysis (TGA) was conducted to assess the thermal stability of kudzu fibres. Further, the FTIR spectra were measured at wave number ranged 4000–500 cm−1, which showed changes in the structure after treatments and confirmed the removal of lignin and hemicellulose from the cellulose. The isolated CNCs were found to have lengths and diameters of 285.01 ± 150.33 nm and 42.78 ± 13.26 nm, respectively, with an aspect ratio of 6.43 ± 1.78. This study showed that kudzu CNCs are a suitable reinforcing material for nanocomposites.
Risk factors and prevalence of cognitive impairment in maintenance haemodialysis patients: A systematic review and meta‐analysis of observational studies
Authors: Cao Ting , An Ran , Wang Ying , Lei Juan , Liang Junqing , Wan Qiaoqin
Published: June 2023

Aims

To systematically identify the risk factors for cognitive impairment in maintenance haemodialysis patients and to assess its prevalence in included studies.

Design

Systematic review and meta‐analysis about observational studies.

Data Sources

Systematic search of seven databases, including PubMed, Web of Science, Scope, Wanfang Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Weipu Chinese Science and Technology Journal Database, from inception until October 2021.

Review Methods

Observational studies reporting the risk factors for cognitive impairment in maintenance haemodialysis patients in English and Chinese language were included. Meta‐analysis was performed to identify risk factors and prevalence of cognitive impairment in maintenance haemodialysis patients with STATA 15.0 software.

Results

Overall, 37 eligible studies encompassing 129,849 cases were included. The risk factors with statistical significance after meta‐analysis were older age, female sex, fewer years of education, hypertension, diabetes, cerebrovascular accident, multiple comorbid conditions, systolic blood pressure variability, arterial stiffness and low haemoglobin and albumin level. The overall prevalence of cognitive impairment in maintenance haemodialysis patients was 49.1%.

Conclusion

The current analysis indicated a high prevalence of cognitive impairment in maintenance haemodialysis patients. Eleven risk factors for cognitive impairment in maintenance haemodialysis patients were identified, among which more attention should be paid to modifiable factors such as cardiovascular disease risk factors and specific kidney and dialysis‐related factors.

Impact

This paper provides an updated estimate of the pooled prevalence of cognitive impairment in maintenance haemodialysis patients. Identification of risk factors associated with cognitive impairment may assist in developing targeted prevention strategies for maintenance haemodialysis patients at high risk.

No Patient or Public Contribution

This study was a systematic review completed by the authors in accordance with relevant guidelines and processes and did not include the participation of patients, service users, caregivers or the general public.
A qualitative study of public health nurses' experiences detecting and preventing child maltreatment in primary care settings
Authors: Midtsund Astrid Durdei , Garnweidner‐Holme Lisa , Valla Lisbeth , Lukasse Mirjam , Henriksen Lena
Published: June 2023

Aim

To explore how public health nurses in child and family health centres experience detecting and preventing child maltreatment.

Design

Qualitative study.

Methods

Fourteen semi‐structured individual interviews with public health nurses who worked in 11 different child and family health centres were conducted. The interviews were analysed using thematic analysis.

Results

Three themes were identified: (i) integrating knowledge to prevent child maltreatment as part of their everyday job, (ii) striving hard to detect child maltreatment and (iii) experiencing the assignment to be complex and demanding.

Conclusion

Despite extensive experience, knowledge and following the guidelines, public health nurses in this study had difficulties finding children exposed to child maltreatment in child and family health centres. Public health nurses called for mutual multidisciplinary cooperation with other services and organizational facilitation, such as enough time and clear guidelines to effectively address this issue.

Implications for Practice

This study provides knowledge about how public health nurses work with child maltreatment at the Child and Family Health Center, which can serve as valuable foundation for further research as well for collaborating services.

Reporting Method

EQUATOR guidelines were followed, using the COREQ checklist.

Patient or Public Contribution

No patient or public contribution.
Single‐cell RNA‐seq reveals actinic keratosis‐specific keratinocyte subgroups and their crosstalk with secretory‐papillary fibroblasts
Authors: Li Jun , Xia Ying , Kong Shumin , Yang Kun , Chen Hui , Zhang Yong , Liu Dongxian , Chen Lan , Sun Xiaoyan
Published: June 2023

Background and Aim

Actinic keratosis (AK) represents an intraepidermal malignant neoplasm with the proliferation of atypical keratinocytes. AK lesions are regarded as early in situ squamous cell carcinomas (SCCs) having the potential to progress into invasive SCC (iSCC) and metastasize, causing death. This study aimed to investigate the heterogeneity of keratinocytes and how this heterogeneity promoted AK development and progression.

Methods

We employed single‐cell RNA sequencing (scRNA‐seq) to examine the heterogeneity of keratinocytes and dermal fibroblast clusters in AKs and adjacent normal skins. Cell clustering, pseudotime trajectory construction, gene ontology enrichment analysis, transcription factor network analysis, and cell–cell communication were used to investigate the heterogeneity of keratinocytes in AK. The cellular identity and function were verified by immunohistochemical and immunofluorescence staining.

Results

Using scRNA‐seq, we revealed 13 keratinocyte subgroups (clusters 0–12) in AK tissues and characterized 2 AK‐specific clusters. Cluster 9 displayed high levels of IL1R2 and WFDC2, and cluster 11 showed high levels of FADS2 and FASN. The percentages of cells in these two clusters significantly increased in AK compared with normal tissues. The existence and spatial localization of AK‐specific IL1R2+WFDC2+ cluster were verified by immunohistochemical and immunofluorescence staining. Functional studies indicated that the genes identified in the IL1R2+WFDC2+ cluster were crucial for epithelial cell proliferation, migration, and angiogenesis. Further immunofluorescent staining revealed the interactions between AK‐specific keratinocytes and secretory‐papillary fibroblasts mainly through ANGPTL4‐ITGA5 signalling pathway rarely seen in normal tissues.

Conclusion

The findings of this study might help better understand AK pathogenesis.
Evolution of posture in amniotes–Diving into the trabecular architecture of the femoral head
Authors: Gônet Jordan , Laurin Michel , Hutchinson John R.
Published: June 2023

Extant amniotes show remarkable postural diversity. Broadly speaking, limbs with erect (strongly adducted, more vertically oriented) posture are found in mammals that are particularly heavy (graviportal) or show good running skills (cursorial), while crouched (highly flexed) limbs are found in taxa with more generalized locomotion. In Reptilia, crocodylians have a “semi-erect” (somewhat adducted) posture, birds have more crouched limbs and lepidosaurs have sprawling (well-abducted) limbs. Both synapsids and reptiles underwent a postural transition from sprawling to more erect limbs during the Mesozoic Era. In Reptilia, this postural change is prominent among archosauriforms in the Triassic Period. However, limb posture in many key Triassic taxa remains poorly known. In Synapsida, the chronology of this transition is less clear, and competing hypotheses exist. On land, the limb bones are subject to various stresses related to body support that partly shape their external and internal morphology. Indeed, bone trabeculae (lattice-like bony struts that form the spongy bone tissue) tend to orient themselves along lines of force. Here, we study the link between femoral posture and the femoral trabecular architecture using phylogenetic generalized least squares. We show that microanatomical parameters measured on bone cubes extracted from the femoral head of a sample of amniote femora depend strongly on body mass, but not on femoral posture or lifestyle. We reconstruct ancestral states of femoral posture and various microanatomical parameters to study the “sprawling-to-erect” transition in reptiles and synapsids, and obtain conflicting results. We tentatively infer femoral posture in several hypothetical ancestors using phylogenetic flexible discriminant analysis from maximum likelihood estimates of the microanatomical parameters. In general, the trabecular network of the femoral head is not a good indicator of femoral posture. However, ancestral state reconstruction methods hold great promise for advancing our understanding of the evolution of posture in amniotes.

Abstract

We use 3D microanatomical parameters measured at the femoral head to study femoral posture in amniotes. We show that these parameters are not good indicators of femoral posture. Methods of ancestral state reconstruction hold great promise for improving our understanding of the evolution of posture in amniotes.
The evolution and ecology of multiple antipredator defences
Authors: Kikuchi David W. , Allen William L. , Arbuckle Kevin , Aubier Thomas G. , Briolat Emmanuelle S. , Burdfield-Steel Emily R. , Cheney Karen L. , Daňková Klára , Elias Marianne , Hämäläinen Liisa , Herberstein Marie E. , Hossie Thomas J. , Joron Mathieu , Kunte Krushnamegh , Leavell Brian C. , Lindstedt Carita , Lorioux-Chevalier Ugo , McClure Melanie , McLellan Callum F. , Medina Iliana , Nawge Viraj , Páez Erika , Pal Arka , Pekár Stano , Penacchio Olivier , Raška Jan , Reader Tom , Rojas Bibiana , Rönkä Katja H. , Rößler Daniela C. , Rowe Candy , Rowland Hannah M. , Roy Arlety , Schaal Kaitlin A. , Sherratt Thomas N. , Skelhorn John , Smart Hannah R. , Stankowich Ted , Stefan Amanda M. , Summers Kyle , Taylor Christopher H. , Thorogood Rose , Umbers Kate , Winters Anne E. , Yeager Justin , Exnerová Alice
Published: June 2023

Prey seldom rely on a single type of antipredator defence, often using multiple defences to avoid predation. In many cases, selection in different contexts may favour the evolution of multiple defences in a prey. However, a prey may use multiple defences to protect itself during a single predator encounter. Such “defence portfolios” that defend prey against a single instance of predation are distributed across and within successive stages of the predation sequence (encounter, detection, identification, approach (attack), subjugation and consumption). We contend that at present, our understanding of defence portfolio evolution is incomplete, and seen from the fragmentary perspective of specific sensory systems (e.g., visual) or specific types of defences (especially aposematism). In this review, we aim to build a comprehensive framework for conceptualizing the evolution of multiple prey defences, beginning with hypotheses for the evolution of multiple defences in general, and defence portfolios in particular. We then examine idealized models of resource trade-offs and functional interactions between traits, along with evidence supporting them. We find that defence portfolios are constrained by resource allocation to other aspects of life history, as well as functional incompatibilities between different defences. We also find that selection is likely to favour combinations of defences that have synergistic effects on predator behaviour and prey survival. Next, we examine specific aspects of prey ecology, genetics and development, and predator cognition that modify the predictions of current hypotheses or introduce competing hypotheses. We outline schema for gathering data on the distribution of prey defences across species and geography, determining how multiple defences are produced, and testing the proximate mechanisms by which multiple prey defences impact predator behaviour. Adopting these approaches will strengthen our understanding of multiple defensive strategies.

Abstract

Evolution of multiple defences as a function of trade-offs & synergies among traits, ecology & evolutionary history, genetics & development, predator cognition.