bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial, anticancer, and biofilm inhibition studies of highly reduced graphene oxide (HRG): In vitro and in silico analysis
Authors: Alangari Abdulaziz , Mateen Ayesha , Alqahtani Mohammed S. , Shahid Mudassar , Syed Rabbani , Shaik Mohammed Rafi , Khan Mujeeb , Adil Syed Farooq , Kuniyil Mufsir
Published: March 2023

Background: Bacterial infections and cancers may cause various acute or chronic diseases, which have become serious global health issues. This requires suitable alternatives involving novel and efficient materials to replace ineffective existing therapies. In this regard, graphene composites are being continuously explored for a variety of purposes, including biomedical applications, due to their remarkable properties.

Methods: Herein, we explore, in-vitro, the different biological properties of highly reduced graphene oxide (HRG), including anti-cancer, anti-bacterial, and anti-biofilm properties. Furthermore, to analyze the interactions of graphene with proteins of microbes, in silico docking analysis was also carried out. To do this, HRG was prepared using graphene oxide as a precursor, which was further chemically reduced to obtain the final product. The as-prepared HRG was characterized using different types of microscopic and spectroscopic techniques.

Results: The HRG revealed significant cytotoxic ability, using a dose-dependent anti-cell proliferation approach, which substantially killed human breast cancer cells (MCF-7) with IC50 of 29.51 ± 2.68 μg/mL. The HRG demonstrated efficient biological properties, i.e., even at low concentrations, HRG exhibited efficient anti-microbial properties against a variety of microorganisms. Among the different strains, Gram-positive bacteria, such as B. subtilis, MRSA, and S. aureus are more sensitive to HRG compared to Gram-negative bacteria. The bactericidal properties of HRG are almost similar to a commercially available effective antibiotic (ampicillin). To evaluate the efficacy of HRG against bacterial biofilms, Pseudomonas aeruginosa and MRSA were applied, and the results were compared with gentamycin and ampicillin, which are commonly applied standard antibiotics. Notably, HRG demonstrated high inhibition (94.23%) against P.aeruginosa, with lower MIC (50 μg/mL) and IC50 (26.53 μg/mL) values, whereas ampicillin and gentamicin showed similar inhibition (90.45% and 91.31% respectively) but much higher MIC and IC50 values.

Conclusion: Therefore, these results reveal the excellent biopotential of HRG in different biomedical applications, including cancer therapy; antimicrobial activity, especially anti-biofilm activity; and other biomedicine-based therapies. Based on the molecular docking results of Binding energy, it is predicted that pelB protein and HRG would form the best stable docking complex, and high hydrogen and hydrophobic interactions between the pelB protein and HRG have been revealed. Therefore, we conclude that HRG could be used as an antibiofilm agent against P. aeruginosa infections.
Mesenchymal stem cell-derived secretome enhances nucleus pulposus cell metabolism and modulates extracellular matrix gene expression in vitro
Authors: Tilotta Veronica , Vadalà Gianluca , Ambrosio Luca , Cicione Claudia , Di Giacomo Giuseppina , Russo Fabrizio , Papalia Rocco , Denaro Vincenzo
Published: March 2023

Introduction: Intradiscal mesenchymal stromal cell (MSC) therapies for intervertebral disc degeneration (IDD) have been gaining increasing interest due to their capacity to ameliorate intervertebral disc metabolism and relieve low back pain (LBP). Recently, novel investigations have demonstrated that most of MSC anabolic effects are exerted by secreted growth factors, cytokines, and extracellular vesicles, collectively defined as their secretome. In this study, we aimed to evaluate the effect of bone-marrow-MSCs (BM-MSCs) and adipose-derived stromal cells (ADSCs) secretomes on human nucleus pulposus cells (hNPCs) in vitro.

Methods: BM-MSCs and ADSCs were characterized according to surface marker expression by flow cytometry and multilineage differentiation by Alizarin red, Red Oil O and Alcian blue staining. After isolation, hNPCs were treated with either BM-MSC secretome, ADSC secretome, interleukin (IL)-1β followed by BM-MSC secretome or IL-1β followed by ADSC secretome. Cell metabolic activity (MTT assay), cell viability (LIVE/DEAD assay), cell content, glycosaminoglycan production (1,9-dimethylmethylene blue assay), extracellular matrix and catabolic marker gene expression (qPCR) were assessed.

Results: 20% BM-MSC and ADSC secretomes (diluted to normal media) showed to exert the highest effect towards cell metabolism and were then used in further experiments. Both BM-MSC and ADSC secretomes improved hNPC viability, increased cell content and enhanced glycosaminoglycan production in basal conditions as well as after IL-1β pretreatment. BM-MSC secretome significantly increased ACAN and SOX9 gene expression, while reducing the levels of IL6, MMP13 and ADAMTS5 both in basal conditions and after in vitro inflammation with IL-1β. Interestingly, under IL-1β stimulation, ADSC secretome showed a catabolic effect with decreased extracellular matrix markers and increased levels of pro-inflammatory mediators.

Discussion: Collectively, our results provide new insights on the biological effect of MSC-derived secretomes on hNPCs, with intriguing implications on the development of cell-free approaches to treat IDD.
Targeted microbubbles combined with low-power focused ultrasound promote the thrombolysis of acute deep vein thrombosis
Authors: Chen Jianfu , Yang Yuan , Li Yunyan , Xu Lirong , Zhao Chun , Chen Qi , Lu Yongping
Published: March 2023

Introduction: The side effects of conventional therapy for acute deep vein thrombosis (DVT) are severe, with inflammatory reactions playing a pivotal role. It is particularly important to explore new ways of treatment thrombosis by targeting inflammatory factors.

Methods: A targeted microbubble contrast agent was prepared using the biotin-avidin method. The 40 DVT model rabbits were established and divided into four groups according to different treatment regimens. The four coagulation indexes, TNF-α, and D-dimer content of experimental animals were measured before modeling and before and after treatment, and the thrombolysis was assessed by ultrasound imaging. Finally, the results were verified by pathology.

Results and Discussion: Fluorescence microscopy verified the successful preparation of targeted microbubbles. Among the groups, PT, APTT, and TT in Group II-IV were longer than those in Group I (all p < 0.05). FIB and D-dimer content were lower than those in Group I (all p < 0.05), and TNF-α content in Group IV was lower than that in Group I-III (all p < 0.05). Pairwise comparison before modeling and before treatment and after treatment showed that, after treatment, the PT, APTT, and TT in Group II-IV were longer than those before modeling (all p < 0.05). The contents of FIB and D-dimer were lower than those before modeling and before treatment (all p < 0.05). The content of TNF-α decreased significantly only in Group IV, but increased in the other three groups. Targeted microbubbles combined with Low-power focused ultrasound can reduce inflammation, significantly promote thrombolysis, and provide new ideas and methods for the diagnosis and treatment of acute DVT.
Mutagenic analysis of actin reveals the mechanism of His161 flipping that triggers ATP hydrolysis
Authors: Iwasa Mitsusada , Takeda Shuichi , Narita Akihiro , Maéda Yuichiro , Oda Toshiro
Published: March 2023

The dynamic assembly of actin is controlled by the hydrolysis of ATP, bound to the center of the molecule. Upon polymerization, actin undergoes a conformational change from the monomeric G-form to the fibrous F-form, which is associated with the flipping of the side chain of His161 toward ATP. His161 flipping from the gauche-minus to gauche-plus conformation leads to a rearrangement of the active site water molecules, including ATP attacking water (W1), into an orientation capable of hydrolysis. We previously showed that by using a human cardiac muscle α-actin expression system, mutations in the Pro-rich loop residues (A108G and P109A) and in a residue that was hydrogen-bonded to W1 (Q137A) affect the rate of polymerization and ATP hydrolysis. Here, we report the crystal structures of the three mutant actins bound to AMPPNP or ADP-Pi determined at a resolution of 1.35–1.55 Å, which are stabilized in the F-form conformation with the aid of the fragmin F1 domain. In A108G, His161 remained non-flipped despite the global actin conformation adopting the F-form, demonstrating that the side chain of His161 is flipped to avoid a steric clash with the methyl group of A108. Because of the non-flipped His161, W1 was located away from ATP, similar to G-actin, which was accompanied by incomplete hydrolysis. In P109A, the absence of the bulky proline ring allowed His161 to be positioned near the Pro-rich loop, with a minor influence on ATPase activity. In Q137A, two water molecules replaced the side-chain oxygen and nitrogen of Gln137 almost exactly at their positions; consequently, the active site structure, including the W1 position, is essentially conserved. This seemingly contradictory observation to the reported low ATPase activity of the Q137A filament could be attributed to a high fluctuation of the active site water. Together, our results suggest that the elaborate structural design of the active site residues ensures the precise control of the ATPase activity of actin.
Calaxin is required for asymmetric bend initiation and propagation in sperm flagella
Authors: Shiba Kogiku , Baba Shoji A. , Fujiwara Eiji , Inaba Kazuo
Published: March 2023

Regulation of waveform asymmetry in flagella is critical for changes in direction when sperm are swimming, as seen during the chemotaxis of sperm towards eggs. Ca2+ is an important regulator of asymmetry in flagellar waveforms. A calcium sensor protein, calaxin, is associated with the outer arm dynein and plays a key role in the regulation of flagellar motility in a Ca2+-dependent manner. However, the underlying mechanism of regulating asymmetric waves by means of Ca2+ and calaxin remains unclear. To clarify the calaxin-dependent mechanism for generating Ca2+-dependent asymmetric flagellar waveforms, we analyzed the initial step of flagellar bend formation and propagation in the sperm of the ascidian Ciona intestinalis. Our experiment used demembranated sperm cells, which were then reactivated by UV flash photolysis of caged ATP under both high and low Ca2+ concentrations. Here, we show that initial bends in the flagella are formed at the base of the sperm and propagate towards the tip during waveform generation. However, the direction of the initial bend differed between asymmetric and symmetric waves. When a calaxin inhibitor (repaglinide) was applied, it resulted in the failure of asymmetric wave formation and propagation. This was because repaglinide had no effect on initial bend formation, but it significantly inhibited the generation of the subsequent bend in the reverse direction. Switching of dynein sliding activity by mechanical feedback is crucial for flagellar oscillation. Our results suggest that the Ca2+/calaxin mechanism plays an important role in the switching of dynein activity from microtubule sliding in the principal bend into the suppressed sliding in the reverse bend, thereby allowing the sperm to successfully change direction.
Maternal vaginal fluids play a major role in the colonization of the neonatal intestinal microbiota
Authors: Xie Jingxian , Tang Chen , Hong Shouqiang , Xin Yuntian , Zhang Jie , Lin Yi , Mao Lindong , Xiao Yunshan , Wu Quanfeng , Zhang Xueqin , Shen Heqing
Published: March 2023

Background

Caesarean section (CS) is associated with newborns’ health risks due to the blocking of microbiome transfer. The gut microbiota of CS-born babies was different from those born vaginally, which may be attributed to reduced exposure to maternal vaginal microbes during labour. To understand the microbial transfer and reduce CS disadvantages, the effect of vaginal microbiota exposure on infant gut microbiota composition was evaluated using 16s rDNA sequencing-based techniques.

Results

Pregnant women were recruited in the Women and Children’s Hospital, School of Medicine, Xiamen University from June 1st to August 15th, 2017. Maternal faeces (n = 26), maternal vaginal fluids (n = 26), and neonatal transitional stools (n = 26) were collected, while the participants underwent natural delivery (ND) (n = 6), CS (n = 4) and CS with the intervention of vaginal seedings (I) (n = 16). 26 mothers with the median age 26.50 (25.00-27.25) years showed no substantial clinical differences. The newborns’ gut microbiota altered among ND, CS and I, and clustered into two groups (PERMANOVA P = 0.001). Microbial composition of ND babies shared more features with maternal vaginal samples (PERMANOVA P = 0.065), while the microbiota structure of ND babies was obviously different from that of sample of maternal faeces. The genus Bacteroides in CS-born babies with intervention approached to vaginal-born neonates, compared with CS-born neonates without intervention.

Conclusions

Neonatal gut microbiota was dependent on the delivery mode. And the gut microbiota CS newborns with vaginal seeding shared more features with those of ND babies, which hinted the aberrant gut microbiota composition initiated by CS might be partly mitigated by maternal vaginal microbiota exposure.
Molecular mechanisms of Huanglian Jiedu decoction in treating Alzheimer’s disease by regulating microbiome via network pharmacology and molecular docking analysis
Authors: Zheng Renyuan , Shi Shenggan , Zhang Qin , Yuan Shuqin , Guo Tong , Guo Jinlin , Jiang Peidu
Published: March 2023

Background

Huanglian Jiedu decoction (HLJDD) is a famous traditional Chinese medicine prescription, which is widely used in the treatment of Alzheimer’s disease (AD). However, the interaction between bioactive substances in HLJDD and AD-related targets has not been well elucidated.

Aim

A network pharmacology-based approach combined with molecular docking was performed to determine the bioactives, key targets, and potential pharmacological mechanism of HLJDD against AD, through the regulation of microbial flora.

Materials and methods

Bioactives and potential targets of HLJDD, as well as AD-related targets, were retrieved from Traditional Chinese Medicine Systems Pharmacology Analysis Database (TCMSP). Key bioactive components, potential targets, and signaling pathways were obtained through bioinformatics analysis, including protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was performed to predict the binding of active compounds with core targets.

Results

102 bioactive ingredients of HLJDD and 76 HLJDD-AD-related targets were screened. Bioinformatics analysis revealed that kaempferol, wogonin, beta-sitosterol, baicalein, acacetin, isocorypalmine, (S)-canadine, (R)-canadine may be potential candidate agents. AKT1, TNF, TP53, VEGFA, FOS, PTGS2, MMP9 and CASP3 could become potential therapeutic targets. 15 important signaling pathways including the cancer pathway, VEGF signaling pathway, and NF-κB signaling pathway might play an important role in HLJDD against AD. Moreover, molecular docking analysis suggested that kaempferol, wogonin, beta-sitosterol, baicalein, acacetin, isocorypalmine, (S)-canadine, and (R)-canadine combined well with AKT1, TNF, TP53, VEGFA, FOS, PTGS2, MMP9, CASP3, respectively.

Conclusion

Our results comprehensively illustrated the bioactives, potential targets, and possible molecular mechanisms of HLJDD against AD. HLJDD may regulate the microbiota flora homeostasis to treat AD through multiple targets and multiple pathways. It also provided a promising strategy for the use of traditional Chinese medicine in treating human diseases.
Association between human papillomavirus infection and common sexually transmitted infections, and the clinical significance of different Mycoplasma subtypes
Authors: A Disi , Bi Hui , Zhang Dai , Xiao Bingbing
Published: March 2023

Introduction

Human papillomavirus (HPV) infection, especially persistent high-risk HPV, is associated with cervical cancer. Female reproductive tract microecological disorders and lower genital tract infections have been increasingly correlated with HPV infection and cervical lesions. Due to their common risk factors and transmission routes, coinfection with other sexually transmitted infections (STIs) has become a concern. Additionally, the clinical significance of Mycoplasma subtypes appear to vary. This study aimed to assess the correlations between common STIs and HPV infection, and to investigate the clinical significance of Mycoplasma subtypes.

Methods

We recruited 1,175 patients undergoing cervical cancer screening at the Peking University First Hospital gynecological clinic from March 2021 to February 2022 for vaginitis and cervicitis tests. They all received HPV genotyping and detection of STIs, and 749 of them underwent colposcopy and cervical biopsy.

Results

Aerobic vaginitis/desquamative inflammatory vaginitis and STIs (mainly single STIs) were found significantly more often in the HPV-positive group than in the HPV-negative group. Among patients with a single STI, rates of infection with herpes simplex virus type 2 or UP6 in the HPV-positive group were significantly higher than in the HPV-negative group (ORadj: 1.810, 95%CI: 1.211–2.705, P=0.004; ORadj: 11.032, 95%CI: 1.465–83.056, P=0.020, respectively).

Discussion

Through detailed Mycoplasma typing, a correlation was found between different Mycoplasma subtypes and HPV infection. These findings suggest that greater attention should be paid to detecting vaginal microecological disorders in those who are HPV-positive. Further, lower genital tract infections, including both vaginal infections and cervical STIs, are significantly more common among women who are HPV-positive and who thus require more thorough testing. Detailed typing and targeted treatment of Mycoplasma should become more routine in clinical practice.
Development and validation of nomogram for unplanned ICU admission in patients with dilated cardiomyopathy
Authors: Li Xiao-Lei , Adi Dilare , Zhao Qian , Aizezi Aibibanmu , Keremu Munawaer , Li Yan-Peng , Liu Fen , Ma Xiang , Li Xiao-Mei , Azhati Adila , Ma Yi-Tong
Published: March 2023

Objective

Unplanned admission to the intensive care unit (ICU) is the major in-hospital adverse event for patients with dilated cardiomyopathy (DCM). We aimed to establish a nomogram of individualized risk prediction for unplanned ICU admission in DCM patients.

Methods

A total of 2,214 patients diagnosed with DCM from the First Affiliated Hospital of Xinjiang Medical University from January 01, 2010, to December 31, 2020, were retrospectively analyzed. Patients were randomly divided into training and validation groups at a 7:3 ratio. The least absolute shrinkage and selection operator and multivariable logistic regression analysis were used for nomogram model development. The area under the receiver operating characteristic curve, calibration curves, and decision curve analysis (DCA) were used to evaluate the model. The primary outcome was defined as unplanned ICU admission.

Results

A total of 209 (9.44%) patients experienced unplanned ICU admission. The variables in our final nomogram included emergency admission, previous stroke, New York Heart Association Class, heart rate, neutrophil count, and levels of N-terminal pro b-type natriuretic peptide. In the training group, the nomogram showed good calibration (Hosmer–Lemeshow χ2 = 14.40, P = 0.07) and good discrimination, with an optimal-corrected C-index of 0.76 (95% confidence interval: 0.72–0.80). DCA confirmed the clinical net benefit of the nomogram model, and the nomogram maintained excellent performances in the validation group.

Conclusion

This is the first risk prediction model for predicting unplanned ICU admission in patients with DCM by simply collecting clinical information. This model may assist physicians in identifying individuals at a high risk of unplanned ICU admission for DCM inpatients.
Pattern and effect of economic agglomeration in the Yangtze River Delta region based on population-land allometric growth
Authors: Zhu Yiheng , Yang Shan , Lin Jinping , Cai Anning
Published: March 2023

The speed of urban growth affects urban development’s momentum and urban agglomeration’s spatial state. The influence of the asymmetric flow of population and land factors on the economic agglomeration effect is an essential issue in the coordinated development of urbanization. To study its impact on the orderly development of China’s urban economy, this paper selects 41 cities in the Yangtze River Delta (YRD) region, measuring the spatial and temporal evolution of the allometric growth relationship between population and land, explores the mechanism of the effect of allometric relationships on the economic agglomeration effect. The results show that: 1) Population-land allometric growth is characterized by a transition from population to land expansion. The transition phase is divided into six stages, from positive to negative allometric growth. In terms of scaling coefficients, the period from 2000 to 2011 is characterized by negative allometric growth, and the period from 2012 to 2019 is characterized by positive allometric growth. Spatially, the Shanghai metropolitan area evolves into a positive allometric primary stage, while the core and central areas evolve into a positive allometric secondary stage, with the latter’s development transition lagging behind the former by about 10 years. 2) The spatial dependence of economic agglomeration in the Yangtze River Delta is strong, showing a spatial distribution trend of “high in the middle, low in the north and south, high in the east and low in the west,” the agglomeration gap is gradually reduced, forming a “continuous area of high-value economic agglomeration” with the core area as the center and spreading outward, reflecting the efficacy of the Yangtze River Delta integrated development strategy. 3) The economic agglomeration effect of allometric growth is classified into four types: positive-allometric positive-effect, positive-allometric negative-effect, negative-allometric positive-effect, and negative-allometric negative-effect. In the Yangtze River Delta region, 70.7% of the cities have positive effects, of which 93.1% are positive-positive. 4) The allometric growth has an important impact on the reconfiguration of economic agglomeration pattern, 78% of the cities in the study period produced leapfrog movements in different quadrants, and the incongruity between population growth and land expansion should be actively regulated in the future to promote the evolution of cities towards an intensive type of population-land coordination to lead the high-quality development of the regional economy.
Geology and geochemistry of Zn-Pb(-Ge-Ag) deposits in the Sichuan-Yunnan-Guizhou Triangle area, China: A review and a new type
Authors: Runsheng Han , Yan Zhang , Wenlong Qiu , Tianzhu Ding , Mingzhi Wang , Feng Wang
Published: March 2023

Mississippi Valley Type (MVT)1 deposits represent the majority of carbonate-hosted Zn–Pb deposits globally. They typically form in an extensional tectonic setting along passive margins. However, studies on carbonate-hosted Zn–Pb deposits in the Sichuan–Yunnan–Guizhou Triangle area (SYGT) reveal differences in terms of the essential features of typical MVT deposits. We discuss the main features of these deposits, controlled by folds and faults, high-grade Zn–Pb ores and symbiotic or associated elements (i.e., abundant Ag and dispersed amounts of Ge, Ga, and Cd) of significant economic value. Based on a comparison of Pb-Zn deposits in SYGT and classical MVT deposits formed in an extensional tectonic setting, as well as a subsequent discussion on deposit classification, we propose that the Huize-style Zn–Pb deposits are a new deposit style, whose basic features can guide future ore exploration. We define the Huize-style deposits based on four factors: i) Hierarchical ore-controlling system of strike-slip fault-fold structures, ii) litho-facies associated with typical alternation and mineralisation, iii) ore-forming geochemical features revealed by typical mineral assemblages, mineralisation alteration zoning, fluid-inclusion, isotope geochemistry and metallogenic acid–alkali geochemical barriers, and iv) different prospecting methods to those typically used for MVT deposits. The Huize-style and typical MVT deposits constitute the carbonate-hosted non-magmatic epigenetic hydrothermal-type (CNHT) Zn–Pb deposits.
Shear wave velocity structure in the middle segment of the Xiaojiang fault zone using ambient noise tomography
Authors: Liang Yao , Xie Tongtong , Lu Zhanwu , Li Qiusheng , Zhang Xinyan , Wang Guangwen , Wang Guan , Chen Si , Chang Chang
Published: March 2023

The middle segment of the Xiaojiang fault zone consists of strike-slip faults with frequent strong and medium–strong earthquakes under the joint influence of NE-trending faults and deep structural characteristics. The distribution characteristics of the deep subfaults of each branch need to be revealed. Two short-period dense array survey lines are deployed in the area. Shear wave velocity structures are obtained using ambient noise tomography. The results reveal that the faults in each branch dip nearly eastward, with strike-slip characteristics in the north‒south direction. Strong velocity lateral variation infer imply that the deformation characteristics of the upper crust may be brittle. NE faults are observed, which are characterized by typical compression. The high-velocity zone in the Songming Basin may be related to the deeper upwelling of high-velocity strata in the upper crustal flow.
Research on the influence of stress on the penetration behavior of hydraulic fracture: Perspective from failure type of beddings
Authors: Bai Yuesong , Hu Yaoqing , Liao Xingchuan , Tan Jin , Zheng Yongxiang , Wang Wei
Published: March 2023

The failure types of bedding determine the penetration behavior of hydraulic fracture. A stratum model containing bedding was established based on the 3D block distinct element method to explore the penetration behavior of hydraulic fractures with different types of bedding. The mechanics of hydraulic fractures penetrating the shear- failure bedding plane and tensile-failure bedding plane were analyzed. The results showed that the shear-failure bedding plane was more difficult to expand than the tensile-failure bedding plane after the hydraulic fracture turns to bedding plane. The initial stress magnitude controls the expansion difficulty of hydraulic fractures, and the high stress magnitude attenuated penetration behavior. The vertical stress affected the shear failure by increasing the shear strength of the bedding plane. It affected the tensile failure by increasing the initiation stress of the bedding plane. The effect of horizontal stress on the penetration behavior included the influence on the initiation stress of vertical joints and the enhancement of the interference stress on the horizontal bedding plane. The conclusions can provide the guidance for hydraulic fracturing in reservoir with bedding planes.
Fostering students’ willingness to act pro-environmentally through an identity-oriented socio-scientific exhibition on the energy transition
Authors: Kellberg Sarah , Nordine Jeffrey , Keller Melanie , Lewalter Doris
Published: March 2023

Successfully communicating the importance of a global energy transition toward carbon-free energy sources and increasing participation in it depends on society as a whole, including the socio-cultural identities and personal values of all involved. Since a person’s willingness to engage in the energy transition is strongly influenced by their social environmental identity, we argue that interventions offering students opportunities to develop this part of themselves should foster their overall willingness to do so. We argue that modern museum exhibitions on socio-scientific issues addressing visitors as individual, social or political actors, represent particularly suitable sites for such an approach. We investigated the extent to which students’ overall willingness to act pro-environmentally changed after visiting a socio-scientific exhibition on the energy transition and the extent to which students’ subsequent overall willingness to act was influenced by their prior conceptual knowledge about energy and topic-related interest. Data for the study was collected in a pre-post design, with students (N = 185) visiting the exhibition for 90 min in between. We found that students’ overall willingness to act changed significantly from prior to after their exhibition visit, and we found that students’ prior energy knowledge but not their interest impacted their willingness to act after the visit to the exhibition. Based on these findings, we discuss that providing a broad range of opportunities for identity work to students outside of the school context fosters their willingness to act on a global scale – and that modern socio-scientific museum exhibitions are thus a useful way to complement formal education.
Specifics of the students’ critical thinking formation within active learning space
Authors: Solovyeva Nataliya , Tapalova Olga , Smirnov Sergei
Published: March 2023

Critical thinking skills are important for personal development and self-realization in professional activity. Thus, this research was aimed at obtaining data about the formation of students’ critical thinking and the professional competencies of the future specialist within hybrid learning. The developed elective course for psychologists and linguists was introduced into the educational system of a higher educational institution. To measure the level of forced critical thinking, the authors used the California Critical Thinking Disposition Inventory (CCTDI), which is specifically designed for undergraduate and graduate students or comparable groups. The findings describe the specifics of the students’ critical thinking formation within hybrid learning. The statistical data analysis showed positive dynamics and a significant increase in the experimental group. The practical testing and experimental validity of the developed course effectiveness gives prospects for further studies of this phenomenon and the practical implementation of innovative technologies aimed at the students’ critical thinking formation within a blended learning model in higher education institutions. The developed optional course within the blended learning model allows creating and practically implementing new educational programs for university students. The research findings also foresee the need for further study of training competent pedagogical staff for the implementation of blended learning.
Function and mechanism of mesenchymal stem cells in the healing of diabetic foot wounds
Authors: Yu Xiaoping , Liu Pan , Li Zheng , Zhang Zhengdong
Published: March 2023

Diabetes has become a global public health problem. Diabetic foot is one of the most severe complications of diabetes, which often places a heavy economic burden on patients and seriously affects their quality of life. The current conventional treatment for the diabetic foot can only relieve the symptoms or delay the progression of the disease but cannot repair damaged blood vessels and nerves. An increasing number of studies have shown that mesenchymal stem cells (MSCs) can promote angiogenesis and re-epithelialization, participate in immune regulation, reduce inflammation, and finally repair diabetic foot ulcer (DFU), rendering it an effective means of treating diabetic foot disease. Currently, stem cells used in the treatment of diabetic foot are divided into two categories: autologous and allogeneic. They are mainly derived from the bone marrow, umbilical cord, adipose tissue, and placenta. MSCs from different sources have similar characteristics and subtle differences. Mastering their features to better select and use MSCs is the premise of improving the therapeutic effect of DFU. This article reviews the types and characteristics of MSCs and their molecular mechanisms and functions in treating DFU to provide innovative ideas for using MSCs to treat diabetic foot and promote wound healing.
The association between neutrophil counts and neutrophil-to-lymphocyte ratio and stress hyperglycemia in patients with acute ischemic stroke according to stroke etiology
Authors: Feng Xianjing , Yu Fang , Wei Minping , Luo Yunfang , Zhao Tingting , Liu Zeyu , Huang Qin , Tu Ruxin , Li Jiaxin , Zhang Boxin , Cheng Liuyang , Xia Jian
Published: March 2023

Background and purpose

Stress hyperglycemia ratio (SHR), which is used to assess stress hyperglycemia, is associated with the functional outcome of ischemic stroke (IS). IS can induce the inflammatory response. Neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) as good and easily available inflammatory biomarkers, the relationship between neutrophil counts and NLR and SHR were poorly explored in IS. We aimed to systemically and comprehensively explore the correlation between various blood inflammation markers (mainly neutrophil counts and NLR) and SHR.

Methods

Data from 487 patients with acute IS(AIS) in Xiangya Hospital were retrospectively reviewed. High/low SHR groups according to the median of SHR (≤1.02 versus >1.02). Binary logistic regression analysis was used to evaluate the correlation between neutrophil counts and NLR and high SHR group. Subgroup analyses were performed in the TOAST classification and functional prognosis.

Results

The neutrophil counts and NLR were all clearly associated with SHR levels in different logistic analysis models. In the subgroup analysis of TOAST classification, the higher neutrophil counts and NLR were the independent risk factors for high SHR patients with large-artery atherosclerosis (LAA) (neutrophil: adjusted OR:2.047, 95% CI: 1.355-3.093, P=0.001; NLR: adjusted OR:1.315, 95% CI: 1.129-1.530, P<0.001). The higher neutrophil counts were the independent risk factor for high SHR patients with cardioembolism (CE) (adjusted OR:2.413, 95% CI: 1.081-5.383, P=0.031). ROC analysis showed that neutrophil counts was helpful for differentiating high SHR group with CE and low SHR group with CE (neutrophil: AUC =0.776, P=0.002). However, there were no difference in levels of neutrophil counts and NLR between patients with SVO and without SVO. The higher neutrophil counts and NLR independently associated with high SHR patients with mRS ≤2 at 90 days from symptom onset, (neutrophil: adjusted OR:2.284, 95% CI: 1.525-3.420, P<0.001; NLR: adjusted OR:1.377, 95% CI: 1.164-1.629, P<0.001), but not in patients with mRS >2.

Conclusions

This study found that the neutrophil counts and NLR are positively associated with SHR levels in AIS patients. In addition, the correlation between neutrophil counts and NLR and different SHR levels are diverse according to TOAST classification and functional prognosis.
Distribution characteristics of oral microbiota and its relationship with intestinal microbiota in patients with type 2 diabetes mellitus
Authors: Guo Xiao-jing , Dai Shi-xuan , Lou Jin-di , Ma Xu-xiang , Hu Xiao-juan , Tu Li-ping , Cui Ji , Lu Hao , Jiang Tao , Xu Jia-tuo
Published: March 2023

Introduction

Type 2 diabetes mellitus (T2DM) has a high incidence rate globally, increasing the burden of death, disability, and the economy worldwide. Previous studies have found that the compositions of oral and intestinal microbiota changed respectively in T2DM; whether the changes were associated or interacted between the two sites and whether there were some associations between T2DM and the ectopic colonization of oral microbiota in the gut still need to be identified.

Research design and methods

We performed a cross-sectional observational study; 183 diabetes and 74 controls were enrolled. We used high-throughput sequencing technology to detect the V3-V4 region of 16S rRNA in oral and stool samples. The Source Tracker method was used to identify the proportion of the intestinal microbiota that ectopic colonized from the oral cavity.

Results

The oral marker bacteria of T2DM were found, such as Actinobacteria, Streptococcus, Rothia, and the intestinal marker bacteria were Bifidobacterium, Streptococcus, and Blautia at the genus level. Among them, Actinobacteria and Blautia played a vital role in different symbiotic relationships of oral and intestinal microbiota. The commonly distributed bacteria, such as Firmicutes, Bacteroidetes, and Actinobacteria, were found in both oral and intestine. Moreover, the relative abundance and composition of bacteria were different between the two sites. The glycine betaine degradation I pathway was the significantly up-regulated pathway in the oral and intestinal flora of T2DM. The main serum indexes related to oral and intestinal flora were inflammatory. The relative abundance of Proteobacteria in the intestine and the Spirochete in oral was positively correlated, and the correlation coefficient was the highest, was 0.240 (P<0.01). The proportion of ectopic colonization of oral flora in the gut of T2DM was 2.36%.

Conclusion

The dysbacteriosis exited in the oral and intestine simultaneously, and there were differences and connections in the flora composition at the two sites in T2DM. Ectopic colonization of oral flora in the intestine might relate to T2DM. Further, clarifying the oral-gut-transmitting bacteria can provide an essential reference for diagnosing and treating T2DM in the future.
The length of FOXE1 polyalanine tract in congenital hypothyroidism: Evidence for a pathogenic role from familial, molecular and cohort studies
Authors: Grassi Elisa Stellaria , Rurale Giuditta , de Filippis Tiziana , Gentilini Davide , Carbone Erika , Coscia Francesca , Uraghi Sarah , Bullock Martyn , Clifton-Bligh Roderick J. , Gupta Abhinav K. , Persani Luca
Published: March 2023

Introduction

FOXE1 is required for thyroid function and its homozygous mutations cause a rare syndromic form of congenital hypothyroidism (CH). FOXE1 has a polymorphic polyalanine tract whose involvement in thyroid pathology is controversial. Starting from genetic studies in a CH family, we explored the functional role and involvement of FOXE1 variations in a large CH population.

Methods

We applied NGS screening to a large CH family and a cohort of 1752 individuals and validated these results by in silico modeling and in vitro experiments.

Results

A new heterozygous FOXE1 variant segregated with 14-Alanine tract homozygosity in 5 CH siblings with athyreosis. The p.L107V variant demonstrated to significantly reduce the FOXE1 transcriptional activity. The 14-Alanine-FOXE1 displayed altered subcellular localization and significantly impaired synergy with other transcription factors, when compared with the more common 16-Alanine-FOXE1. The CH group with thyroid dysgenesis was largely and significantly enriched with the 14-Alanine-FOXE1 homozygosity.

Discussion

We provide new evidence that disentangle the pathophysiological role of FOXE1 polyalanine tract, thereby significantly broadening the perspective on the role of FOXE1 in the complex pathogenesis of CH. FOXE1 should be therefore added to the group of polyalanine disease-associated transcription factors.
Effects of hypoxia-inducible factor-prolyl hydroxylase inhibitors vs. erythropoiesis-stimulating agents on iron metabolism in non-dialysis-dependent anemic patients with CKD: A network meta-analysis
Authors: Yang Junlan , Xing Jie , Zhu Xiaodong , Xie Xiaotong , Wang Lina , Zhang Xiaoliang
Published: March 2023

Objective

To compare the effects of five hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs), two erythropoiesis-stimulating agents (ESAs), and placebo on iron metabolism in renal anemia patients with non-dialysis-dependent chronic kidney disease (NDD-CKD).

Method

Five electronic databases were searched for studies. Randomized controlled clinical trials comparing HIF-PHIs, ESAs, and placebo in NDD-CKD patients were selected. The statistical program used for network meta-analysis was Stata/SE 15.1. The main outcomes were the change in hepcidin and hemoglobin (Hb) levels. The merits of intervention measures were predicted by the surface under the cumulative ranking curve method.

Results

Of 1,589 original titles screened, data were extracted from 15 trials (3,228 participants). All HIF-PHIs and ESAs showed greater Hb level–raising ability than placebo. Among them, desidustat demonstrated the highest probability of increasing Hb (95.6%). Hepcidin [mean deviation (MD) = -43.42, 95%CI: -47.08 to -39.76], ferritin (MD= -48.56, 95%CI: -55.21 to -41.96), and transferrin saturation (MD = -4.73, 95%CI: -5.52 to -3.94) were decreased, while transferrin (MD = 0.09, 95%CI: 0.01 to 0.18) and total iron-binding capacity (MD = 6.34, 95%CI: 5.71 to 6.96) was increased in HIF-PHIs versus those in ESAs. In addition, this study observed heterogeneity in the ability of HIF-PHIs to decrease hepcidin. Compared with darbepoetin, only daprodustat (MD = –49.09, 95% CI: –98.13 to –0.05) could significantly reduce hepcidin levels. Meanwhile, daprodustat also showed the highest hepcidin-lowering efficacy (84.0%), while placebo was the lowest (8.2%).

Conclusion

For NDD-CKD patients, HIF-PHIs could ameliorate functional iron deficiency by promoting iron transport and utilization, which may be achieved by decreasing hepcidin levels. Interestingly, HIF-PHIs had heterogeneous effects on iron metabolism.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242777, Identifier CRD42021242777.
Severe ectopic Cushing syndrome in a transgender man with a metastatic gastrinoma and an adrenal tumor—A case report and review of the literature
Authors: Wydra Arnika , Cylke-Falkowska Karolina , Czajka-Oraniec Izabella , Kolasińska-Ćwikła Agnieszka , Ćwikła Jarosław , Zgliczyński Wojciech , Stelmachowska-Banaś Maria
Published: March 2023

A 38-year-old transgender man with advanced metastatic functional pancreatic neuroendocrine neoplasm (PanNEN) gastrinoma was admitted to the Department of Endocrinology due to severe ACTH-dependent hypercortisolemia. An ectopic production of ACTH by PanNEN was suspected. The patient qualified for bilateral adrenalectomy after preoperative treatment with metyrapone. Finally, the patient underwent resection of the left adrenal gland with the tumor only, which surprisingly resulted in a significant decrease in ACTH and cortisol levels, leading to clinical improvement. Pathology report revealed an adenoma of the adrenal cortex with positive ACTH staining. The result of the simultaneous liver lesion biopsy confirmed a metastatic NEN G2 with positive ACTH immunostaining as well. We looked for a correlation between gender-affirming hormone treatment and the onset of the disease and its rapid progression. This may be the first case describing the coexistence of gastrinoma and ectopic Cushing disease in a transsexual patient.
Endometrial stromal cell miR-19b-3p release is reduced during decidualization implying a role in decidual-trophoblast cross-talk
Authors: Menkhorst Ellen , So Teresa , Rainczuk Kate , Barton Siena , Zhou Wei , Edgell Tracey , Dimitriadis Evdokia
Published: March 2023

Introduction

A healthy pregnancy requires successful blastocyst implantation into an adequately prepared or ‘receptive’ endometrium. Decidualization of uterine endometrial stromal fibroblast cells (hESF) is critical for the establishment of a healthy pregnancy. microRNAs (miRs) are critical regulators of cellular function that can be released by a donor cell to influence the physiological state of recipient cells. We aimed to determine how decidualization affects hESF miR release and investigated the function of one decidualization regulated miR, miR-19b-3p, previously shown to be associated with recurrent pregnancy loss.

Method

miR release by hESF was determined by miR microarray on culture media from hESF decidualized in vitro for 3 and 14 days by treatment with oestradiol and medroxyprogesterone acetate. Cellular and whole endometrial/decidual tissue miR expression was quantified by qPCR and localized by in situ hybridization. The function of miR-19b-3p in HTR8/Svneo trophoblast cells was investigated using real time cell analysis (xCELLigence) and gene expression qPCR.

Results

From our miR screen we found that essentially all hESF miR release was reduced following in vitro decidualization, significantly so for miR-17-5p, miR-21-3p, miR-34c-3p, miR-106b-5p, miR-138-5p, miR-296-5p, miR-323a-3p, miR-342-3p, miR-491-5p, miR-503-5p and miR-542-5p. qPCR demonstrated that miR-19b-3p, 181a-2-3p and miR-409-5p likewise showed a significant reduction in culture media following decidualization but no change was found in cellular miR expression following decidualization. In situ hybridization localized miR-19b-3p to epithelial and stromal cells in the endometrium and qPCR identified that miR-19b-3p was significantly elevated in the cycling endometrium of patients with a history of early pregnancy loss compared to normally fertile controls. Functionally, overexpression of miR-19b-3p significantly reduced HTR8/Svneo trophoblast proliferation and increased HOXA9 expression.

Discussion

Our data demonstrates that decidualization represses miR release by hESFs and overexpression of miR-19b-3p was found in endometrial tissue from patients with a history of early pregnancy loss. miR-19b-3p impaired HTR8/Svneo proliferation implying a role in trophoblast function. Overall we speculate that miR release by hESF may regulate other cell types within the decidua and that appropriate release of miRs by decidualized hESF is essential for healthy implantation and placentation.
Statistical analysis and degradation pathway modeling of photovoltaic minimodules with varied packaging strategies
Authors: Nalin Venkat Sameera , Yu Xuanji , Liu Jiqi , Wegmueller Jakob , Jimenez Jayvic Cristian , Barcelos Erika I. , Aung Hein Htet , Li Xinjun , Jaubert Jean-Nicolas , French Roger H. , Bruckman Laura S.
Published: March 2023

Degradation pathway models constructed using network structural equation modeling (netSEM) are used to study degradation modes and pathways active in photovoltaic (PV) system variants in exposure conditions of high humidity and temperature. This data-driven modeling technique enables the exploration of simultaneous pairwise and multiple regression relationships between variables in which several degradation modes are active in specific variants and exposure conditions. Durable and degrading variants are identified from the netSEM degradation mechanisms and pathways, along with potential ways to mitigate these pathways. A combination of domain knowledge and netSEM modeling shows that corrosion is the primary cause of the power loss in these glass/backsheet PV minimodules. We show successful implementation of netSEM to elucidate the relationships between variables in PV systems and predict a specific service lifetime. The results from pairwise relationships and multiple regression show consistency. This work presents a greater opportunity to be expanded to other materials systems.