bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid Exercise Program for Sarcopenia in Older Adults: The Effectiveness of Explainable Artificial Intelligence-Based Clinical Assistance in Assessing Skeletal Muscle Area
Authors: Wei Meiqi , Meng Deyu , Guo Hongzhi , He Shichun , Tian Zhibo , Wang Ziyi , Yang Guang , Wang Ziheng
Published: August 2022

Background: Sarcopenia is a geriatric syndrome characterized by decreased skeletal muscle mass and function with age. It is well-established that resistance exercise and Yi Jin Jing improve the skeletal muscle mass of older adults with sarcopenia. Accordingly, we designed an exercise program incorporating resistance exercise and Yi Jin Jing to increase skeletal muscle mass and reverse sarcopenia in older adults. Additionally, machine learning simulations were used to predict the sarcopenia status after the intervention. Method: This randomized controlled trial assessed the effects of sarcopenia in older adults. For 24 weeks, 90 older adults with sarcopenia were divided into intervention groups, including the Yi Jin Jing and resistance training group (YR, n = 30), the resistance training group (RT, n = 30), and the control group (CG, n = 30). Computed tomography (CT) scans of the abdomen were used to quantify the skeletal muscle cross-sectional area at the third lumbar vertebra (L3 SMA). Participants’ age, body mass, stature, and BMI characteristics were analyzed by one-way ANOVA and the chi-squared test for categorical data. This study explored the improvement effect of three interventions on participants’ L3 SMA, skeletal muscle density at the third lumbar vertebra (L3 SMD), skeletal muscle interstitial fat area at the third lumbar vertebra region of interest (L3 SMFA), skeletal muscle interstitial fat density at the third lumbar vertebra (L3 SMFD), relative skeletal muscle mass index (RSMI), muscle fat infiltration (MFI), and handgrip strength. Experimental data were analyzed using two-way repeated-measures ANOVA. Eleven machine learning models were trained and tested 100 times to assess the model’s performance in predicting whether sarcopenia could be reversed following the intervention. Results: There was a significant interaction in L3 SMA (p < 0.05), RSMI (p < 0.05), MFI (p < 0.05), and handgrip strength (p < 0.05). After the intervention, participants in the YR and RT groups showed significant improvements in L3 SMA, RSMI, and handgrip strength. Post hoc tests showed that the YR group (p < 0.05) yielded significantly better L3 SMA and RSMI than the RT group (p < 0.05) and CG group (p < 0.05) after the intervention. Compared with other models, the stacking model exhibits the best performance in terms of accuracy (85.7%) and F1 (75.3%). Conclusion: One hybrid exercise program with Yi Jin Jing and resistance exercise training can improve skeletal muscle area among older adults with sarcopenia. Accordingly, it is possible to predict whether sarcopenia can be reversed in older adults based on our stacking model.
Comparative Analysis of the Effects of Retirement on Health Status of Older Adulthood
Authors: Fang Liang , Shi Ruiyao
Published: August 2022

This study examines the causal effect of retirement on the health of middle-aged and older adults in China. We used the mandatory retirement age in China as an instrument variable with a fuzzy discontinuity design. This served to examine the exogenous impact on retirement behavior. Two regression analyses were used, each with the dependent variable as self-assessed health status (SAH) and depression levels, respectively. Changes in an individual’s internal and external environment after retirement were associated with an increase in SAH and a decrease in depression. Highly educated men are 93.5% more likely to improve their health. Women are 0.26% less likely to be depressed. People with higher education tend to reduce their vigorous activities and increase walking for over 10 minutes after retirement. This study may promote research on aging and the health status of the Chinese population. It may provide a scientific basis for formulating, revising, and improving social security policies in China.
Biodegradation of Azo Dye Methyl Red by Pseudomonas aeruginosa: Optimization of Process Conditions
Authors: Ikram Muhammad , Naeem Mohammad , Zahoor Muhammad , Rahim Abdur , Hanafiah Marlia Mohd , Oyekanmi Adeleke Abdulrahman , Shah Abdul Bari , Mahnashi Mater H. , Al Ali Amer , Jalal Naif A. , Bantun Farkad , Sadiq Abdul
Published: August 2022

Water pollution due to textile dyes is a serious threat to every life form. Bacteria can degrade and detoxify toxic dyes present in textile effluents and wastewater. The present study aimed to evaluate the degradation potential of eleven bacterial strains for azo dye methyl red. The optimum degradation efficiency was obtained using P. aeruginosa. It was found from initial screening results that P. aeruginosa is the most potent strain with 81.49% degradation activity and hence it was subsequently used in other degradation experiments. To optimize the degradation conditions, a number of experiments were conducted where only one variable was varied at a time and where maximum degradation was observed at 20 ppm dye concentration, 1666.67 mg/L glucose concentration, 666.66 mg/L sodium chloride concentration, pH 9, temperature 40 °C, 1000 mg/L urea concentration, 3 days incubation period, and 66.66 mg/L hydroquinone (redox mediator). The interactive effect of pH, incubation time, temperature, and dye concentration in a second-order quadratic optimization of process conditions was found to further enhance the biodegradation efficiency of P. aeruginosa by 88.37%. The metabolites of the aliquot mixture of the optimized conditions were analyzed using Fourier transform infrared (FTIR), GC-MS, proton, and carbon 13 Nuclear Magnetic Resonance (NMR) spectroscopic techniques. FTIR results confirmed the reduction of the azo bond of methyl red. The Gas Chromatography–Mass Spectrometry (GC-MS) results revealed that the degraded dye contains benzoic acid and o-xylene as the predominant constituents. Even benzoic acid was isolated from the silica gel column and identified by 1H and 13C NMR spectroscopy. These results indicated that P. aeruginosa can be utilized as an efficient strain for the detoxification and remediation of industrial wastewater containing methyl red and other azo dyes.
Elastic Dynamic Sling on Subluxation of Hemiplegic Shoulder in Patients with Subacute Stroke: A Multicenter Randomized Controlled Trial
Authors: Kim Min Gyun , Lee Seung Ah , Park Eo Jin , Choi Min Kyu , Kim Ji Min , Sohn Min Kyun , Jee Sung Ju , Kim Yeong Wook , Son Jung Eun , Lee Seo Jun , Hwang Keum Sun , Yoo Seung Don
Published: August 2022

Background: Shoulder subluxation occurs in 17–64% of hemiplegic patients after stroke and develops mostly during the first three weeks of hemiplegia. A range of shoulder orthoses has been used in rehabilitation to prevent subluxation. However, there is little evidence of their efficacy. AIM: This study aimed to investigate whether there is a difference in the subluxation distance, pain, and functional level of the hemiplegic upper extremity among patients with two different shoulder orthoses. Design: This is a prospective, randomized controlled trial with intention-to-treat analysis. SETTING: Multicenter, rehabilitation medicine department of two university hospitals in South Korea. Population: Forty-one patients with subacute stroke with shoulder subluxation with greater than 0.5 finger width within 4 weeks of stroke were recruited between January 2016 and October 2021. Methods: The experimental group used an elastic dynamic sling while sitting and standing to support the affected arm for eight weeks. The control group used a Bobath sling while sitting and standing. The primary outcome was to assess the distance of the shoulder subluxation on radiography. The secondary outcomes were upper-extremity function, muscle power, activities of daily living, pain and spasticity. Result: The horizontal distance showed significant improvement in the elastic dynamic sling group, but there were no significant differences in the vertical distance between the elastic dynamic and Bobath sling groups. Both groups showed improvements in upper-extremity movements and independence in daily living after 4 and 8 weeks of using shoulder orthoses, and the differences within the groups were significant (p < 0.05). However, there were no significant differences in upper-extremity movements and independence in daily living between the two groups. Conclusions: The subluxation distance showed better results in the elastic dynamic sling, which has both proximal and distal parts, than in the Bobath sling, which holds only the proximal part. Both shoulder orthoses showed improvements in the modified Barthel index, upper-extremity function, and manual muscle testing.
Reliability of the Athlete Food Choice Questionnaire in Diverse Settings
Authors: Thurecht Rachael L. , Pelly Fiona E. , Burkhart Sarah
Published: August 2022

Understanding the factors that influence an athletes’ food choice is important to supporting optimal dietary intake. The Athlete Food Choice Questionnaire (AFCQ) is a new validated tool for assisting practitioners and researchers to understand athlete eating behaviours. However, the AFCQ previously has only been applied at international competition events. This observational study explored the online application of the AFCQ outside of the competition environment with detailed examination of factor reliability. The AFCQ factors include ‘nutritional attributes of the food’, ‘emotional influences’, ‘food and health awareness’, ‘influence of others’, ‘usual eating practices’, ‘weight control’, ‘food values and beliefs’, ‘sensory appeal’, and ‘performance’. A total of 131 athletes, representing 19 countries and 36 sports, participated using an online questionnaire. Reliability via Cronbach’s alpha (α) and item correlation scores were compared to those from previous competition events. Acceptable reliability was attained for seven of the nine factors (α ≥ 0.7, range 0.70–0.92). ‘Food values and beliefs’ and ‘usual eating practices’ (α = 0.60, 0.64) were tolerable and consistent against previous major competition samples, indicating that the setting is unlikely responsible for lower reliability scores. Three factors (‘emotional influence’; ‘nutritional attributes of the food’; ‘influence of others’) differed in reliability between the online sample compared to one or both major competition samples. The ‘religious food beliefs’ item within the ‘food values and beliefs’ factor may warrant removal due to recurrent low internal consistency. This study confirms the AFCQ’s reliability regardless of competition phase and supports use of the AFCQ for understanding the eating behaviours of athletes.
Causes of and Alternatives to Medication for Behaviours That Challenge in People with Intellectual Disabilities: Direct Care Providers’ Perspectives
Authors: Deb Shoumitro (Shoumi) , Limbu Bharati , Unwin Gemma L. , Weaver Tim
Published: August 2022

Behaviours that challenge (BtC), such as aggression and self-injury, are manifested by many people with intellectual disabilities (ID). National and international guidelines recommend non-pharmacological psychosocial intervention before considering medication to address BtC. Support staff play a pivotal role in the prescription process. Using coproduction, we developed a training programme for support staff, called SPECTROM, to give them knowledge and empower them to question inappropriate prescriptions and ask for the discontinuation of medication if appropriate and instead look for ways to help people with ID when they are distressed without relying on medication. We have presented data from two focus groups that we conducted during the development of SPECTROM: one that included support staff, and another that had service managers and trainers. In these focus groups, we explored participants’ views on the use of medication to address BtC with a particular emphasis on the causes of and alternatives to medication for BtC. Along with the participants’ views, we have also presented how we have addressed these issues in the SPECTROM resources.
Key Influencing Factors and Optimization Strategy of Epidemic Resilience in Urban Communities—A Case Study of Nanjing, China
Authors: Cui Peng , Liu Yi , Ju Xuan , Gu Tiantian
Published: August 2022

COVID-19 has posed a significantly severe impact on both people’s lives and the global economic development. Increasing the community epidemic resilience will considerably improve the national public health emergency response capacity from bottom to top. This study identifies the influencing factors of community epidemic resilience through systematic literature review under the 4R framework, then obtains the relationships of influencing factors through Interpretive structural model, and finally assesses the performance of epidemic resilience using PROMETHEE II method through empirical cases in Nanjing, China. The results show that: (1) Eight factors influencing the epidemic resilience of community are identified, and the economic level plays the root role; (2) Community epidemic resilience can be improved from robustness, rapidity, redundancy and resourcefulness aspects; (3) Through the empirical analysis, the epidemic resilience ranking of community can be displayed (Community D > T > S > F); (4) Additionally, the performance and sensitivity analysis of influencing factors in each community can be demonstrated. (5) Finally, four implications are proposed, namely, allocating public resources rationally, significantly increasing the economic level, ensuring the accuracy of information delivery and conducting disaster learning.
12/15-Lipoxygenase Regulation of Diabetic Cognitive Dysfunction Is Determined by Interfering with Inflammation and Cell Apoptosis
Authors: Chen Qi , Zheng Qixue , Yang Yang , Luo Ying , Wang Hong , Li Huan , Yang Lu , Hu Congli , Zhang Jiahua , Li Yuke , Xia Hui , Chen Zhihao , Ma Jie , Tian Xiaoyan , Yang Junqing
Published: August 2022

This study aimed to discuss the role of 12/15-lipoxygenase (12/15-LOX) regulation involved in diabetes cognitive dysfunction. First, Mini Mental State Examination (MMSE) test was used to evaluate cognitive ability in diabetic patients and normal controls. The plasma test showed that the plasma level of 12/15-LOX in patients with MMSE scores below 27 was significantly increased compared with that of the normal group. Second, 12/15-LOX inhibitor was administered to diabetic rats. Behavioral tests, biochemistry, enzyme-linked immunosorbent assays, and Western blotting were used in this study. We found that the levels of fasting and random blood glucose increased rapidly in diabetic rats, the levels of triglycerides and total cholesterol in the diabetic group increased, and insulin levels decreased significantly. In the Morris water maze test, the escape latency was prolonged, and the crossing times decreased in the diabetic group. Under the microscope, the apoptosis of hippocampal neurons in diabetic rats increased significantly. The levels of TNF-α, IL-6 and 12-hydroxyindoleic acid (12(S)-HETE) significantly increased, and the protein expression of 12/15-LOX, p38 MAPK, Aβ1-42, caspase-3, caspase-9 and cPLA2 increased, while that of Bcl-2 decreased. However, the use of 12/15-LOX inhibitor reversed these results. Third, 12/15-LOX shRNA and p38MAPK inhibitor were administered to HT22 cells in high-glucose medium. The results of the cell experiment were consistent with those of the animal experiment. Our results indicated that the 12/15-LOX pathway participates in diabetic brain damage by activating p38MAPK to promote inflammation and neuronal apoptosis, and intervention 12/15-LOX can improve diabetic cognitive dysfunction.
Microbe Related Chemical Signalling and Its Application in Agriculture
Authors: Abdul Hamid Nur Wahida , Nadarajah Kalaivani
Published: August 2022

The agriculture sector has been put under tremendous strain by the world’s growing population. The use of fertilizers and pesticides in conventional farming has had a negative impact on the environment and human health. Sustainable agriculture attempts to maintain productivity, while protecting the environment and feeding the global population. The importance of soil-dwelling microbial populations in overcoming these issues cannot be overstated. Various processes such as rhizospheric competence, antibiosis, release of enzymes, and induction of systemic resistance in host plants are all used by microbes to influence plant-microbe interactions. These processes are largely founded on chemical signalling. Producing, releasing, detecting, and responding to chemicals are all part of chemical signalling. Different microbes released distinct sorts of chemical signal molecules which interacts with the environment and hosts. Microbial chemicals affect symbiosis, virulence, competence, conjugation, antibiotic production, motility, sporulation, and biofilm growth, to name a few. We present an in-depth overview of chemical signalling between bacteria-bacteria, bacteria-fungi, and plant-microbe and the diverse roles played by these compounds in plant microbe interactions. These compounds’ current and potential uses and significance in agriculture have been highlighted.
Microfluidic Approaches for Affinity-Based Exosome Separation
Authors: Theel Eike K. , Schwaminger Sebastian P.
Published: August 2022

As a subspecies of extracellular vesicles (EVs), exosomes have provided promising results in diagnostic and theranostic applications in recent years. The nanometer-sized exosomes can be extracted by liquid biopsy from almost all body fluids, making them especially suitable for mainly non-invasive point-of-care (POC) applications. To achieve this, exosomes must first be separated from the respective biofluid. Impurities with similar properties, heterogeneity of exosome characteristics, and time-related biofouling complicate the separation. This practical review presents the state-of-the-art methods available for the separation of exosomes. Furthermore, it is shown how new separation methods can be developed. A particular focus lies on the fabrication and design of microfluidic devices using highly selective affinity separation. Due to their compactness, quick analysis time and portable form factor, these microfluidic devices are particularly suitable to deliver fast and reliable results for POC applications. For these devices, new manufacturing methods (e.g., laminating, replica molding and 3D printing) that use low-cost materials and do not require clean rooms are presented. Additionally, special flow routes and patterns that increase contact surfaces, as well as residence time, and thus improve affinity purification are displayed. Finally, various analyses are shown that can be used to evaluate the separation results of a newly developed device. Overall, this review paper provides a toolbox for developing new microfluidic affinity devices for exosome separation.
Characterization of Adherent-Invasive Escherichia coli (AIEC) Outer Membrane Proteins Provides Potential Molecular Markers to Screen Putative AIEC Strains
Authors: Saitz Waleska , Montero David , Pardo Mirka , Araya Daniela , De la Fuente Marjorie , Hermoso Marcela , Farfán Mauricio , Ginard Daniel , Rosselló-Móra Ramon , Rasko Dave , Del Canto Felipe , Vidal Roberto
Published: August 2022

Adherent-invasive E. coli (AIEC) is a pathotype associated with the etiopathogenesis of Crohn’s disease (CD), albeit with an as-yet unclear role. The main pathogenic mechanisms described for AIEC are adherence to epithelial cells, invasion of epithelial cells, and survival and replication within macrophages. A few virulence factors have been described as participating directly in these phenotypes, most of which have been evaluated only in AIEC reference strains. To date, no molecular markers have been identified that can differentiate AIEC from other E. coli pathotypes, so these strains are currently identified based on the phenotypic characterization of their pathogenic mechanisms. The identification of putative AIEC molecular markers could be beneficial not only from the diagnostic point of view but could also help in better understanding the determinants of AIEC pathogenicity. The objective of this study was to identify molecular markers that contribute to the screening of AIEC strains. For this, we characterized outer membrane protein (OMP) profiles in a group of AIEC strains and compared them with the commensal E. coli HS strain. Notably, we found a set of OMPs that were present in the AIEC strains but absent in the HS strain. Moreover, we developed a PCR assay and performed phylogenomic analyses to determine the frequency and distribution of the genes coding for these OMPs in a larger collection of AIEC and other E. coli strains. As result, it was found that three genes (chuA, eefC, and fitA) are widely distributed and significantly correlated with AIEC strains, whereas they are infrequent in commensal and diarrheagenic E. coli strains (DEC). Additional studies are needed to validate these markers in diverse strain collections from different geographical regions, as well as investigate their possible role in AIEC pathogenicity.
Making the Rounds: Exploring the Role of Circulating Tumor DNA (ctDNA) in Non-Small Cell Lung Cancer
Authors: Shields Misty Dawn , Chen Kevin , Dutcher Giselle , Patel Ishika , Pellini Bruna
Published: August 2022

Advancements in the clinical practice of non-small cell lung cancer (NSCLC) are shifting treatment paradigms towards increasingly personalized approaches. Liquid biopsies using various circulating analytes provide minimally invasive methods of sampling the molecular content within tumor cells. Plasma-derived circulating tumor DNA (ctDNA), the tumor-derived component of cell-free DNA (cfDNA), is the most extensively studied analyte and has a growing list of applications in the clinical management of NSCLC. As an alternative to tumor genotyping, the assessment of oncogenic driver alterations by ctDNA has become an accepted companion diagnostic via both single-gene polymerase chain reactions (PCR) and next-generation sequencing (NGS) for advanced NSCLC. ctDNA technologies have also shown the ability to detect the emerging mechanisms of acquired resistance that evolve after targeted therapy. Furthermore, the detection of minimal residual disease (MRD) by ctDNA for patients with NSCLC after curative-intent treatment may serve as a prognostic and potentially predictive biomarker for recurrence and response to therapy, respectively. Finally, ctDNA analysis via mutational, methylation, and/or fragmentation multi-omic profiling offers the potential for improving early lung cancer detection. In this review, we discuss the role of ctDNA in each of these capacities, namely, for molecular profiling, treatment response monitoring, MRD detection, and early cancer detection of NSCLC.
Inhibition of Vps34 and p110δ PI3K Impairs Migration, Invasion and Three-Dimensional Spheroid Growth in Breast Cancer Cells
Authors: Di Donato Marzia , Giovannelli Pia , Migliaccio Antimo , Bilancio Antonio
Published: August 2022

Breast cancer is a heterogeneous disease that represents the most common cancer around the world; it comprises 12% of new cases according to the World Health Organization. Despite new approaches in early diagnosis and current treatment, breast cancer is still the leading cause of death for cancer mortality. New targeted therapies against key signalling transduction molecules are required. Phosphoinositide 3-kinase (PI3K) regulates multiple biological functions such as proliferation, survival, migration, and growth. It is well established that PI3K isoform-selective inhibitors show fewer toxic side effects compared to broad spectrum inhibition of PI3K (pan-PI3K inhibitors). Therefore, we tested the PI3K p110δ-selective inhibitor, IC87114, and Vps34-selective inhibitor, Vps34-IN1, on the breast cancer cell lines MCF-7 and MDA-MB-231, representing hormone-responsive and triple-negative breast cancer cells, respectively. Our data show that both inhibitors decreased migration of MCF-7 and MDA-MB-231 cells, and Vps34 also significantly impacted MCF-7 cell proliferation. Three-dimensional (3D) in vitro culture models show that IC87114 and Vps34-IN1 treatment reduced the growth of MCF-7 and MDA-MB-231 cells in 3D tumour spheroid cultures. This study identifies IC87114 and Vps34-IN1 as potential therapeutic approaches in breast cancer.
Global Identification of White Lupin lncRNAs Reveals Their Role in Cluster Roots under Phosphorus Deficiency
Authors: Aslam Mehtab Muhammad , Waseem Muhammad , Xu Weifeng , Ying Li , Zhang Jianhua , Yuan Wei
Published: August 2022

Phosphorus (P) deficiency heterogeneously affected plant nutritional status and physiological performance, ultimately leading to a severe yield reduction. A few putative long non-coding RNAs (lncRNAs) responding to P-starvation in the model crops Arabidopsis thaliana and Oryza sativa have been characterized. White lupin (Lupinus albus) is of prime importance, and is a legume with increasing agronomic value as a protein crop as it exhibits extreme tolerance to nutrient deficiency, particularly P deficiency. Despite its adapted nature to P deficiency, nothing is known about low P-induced lncRNAs in white lupin roots. To address this issue, we identified 39,840 mRNA and 2028 lncRNAs in the eight developmental stages of white lupin root (S0–S7 and lateral root, LR) grown under P deficiency. From these 2028 lncRNAs, 1564 were intergenic and 464 natural antisense intergenic transcript (NAT) lncRNAs. We further predicted six potential targets of miRNAs with twelve lncRNAs, which may regulate P-deficiency-related processes. Moreover, the weighted gene co-expression network analysis (WGCNA) revealed seven modules that were correlated with the expression pattern of lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed 606 GO terms and 27 different pathways including signal transduction, energy synthesis, detoxification, and Pi transport. In addition, we screened 13 putative lncRNAs that showed a distinct expression pattern in each root, indicating their role in the P deficiency regulatory network. Therefore, white lupin may be a reference legume to characterize P-deficiency-responsive novel lncRNAs, which would highlight the role of lncRNAs in the regulation of plant responses to P deficiency.
A2B Adenosine Receptor Enhances Chemoresistance of Glioblastoma Stem-Like Cells under Hypoxia: New Insights into MRP3 Transporter Function
Authors: Rocha José-Dellis , Uribe Daniel , Delgado Javiera , Niechi Ignacio , Alarcón Sebastián , Erices José Ignacio , Melo Rómulo , Fernández-Gajardo Rodrigo , Salazar-Onfray Flavio , San Martín Rody , Quezada Monrás Claudia
Published: August 2022

Glioblastoma is the most common and aggressive primary brain tumor, characterized by its high chemoresistance and the presence of a cell subpopulation that persists under hypoxic niches, called glioblastoma stem-like cells (GSCs). The chemoresistance of GSCs is mediated in part by adenosine signaling and ABC transporters, which extrude drugs outside the cell, such as the multidrug resistance-associated proteins (MRPs) subfamily. Adenosine promotes MRP1-dependent chemoresistance under normoxia. However, adenosine/MRPs-dependent chemoresistance under hypoxia has not been studied until now. Transcript and protein levels were determined by RT-qPCR and Western blot, respectively. MRP extrusion capacity was determined by intracellular 5 (6)-Carboxyfluorescein diacetate (CFDA) accumulation. Cell viability was measured by MTS assays. Cell cycle and apoptosis were determined by flow cytometry. Here, we show for the first time that MRP3 expression is induced under hypoxia through the A2B adenosine receptor. Hypoxia enhances MRP-dependent extrusion capacity and the chemoresistance of GSCs. Meanwhile, MRP3 knockdown decreases GSC viability under hypoxia. Downregulation of the A2B receptor decreases MRP3 expression and chemosensibilizes GSCs treated with teniposide under hypoxia. These data suggest that hypoxia-dependent activation of A2B adenosine receptor promotes survival of GSCs through MRP3 induction.
Dynamic Changes in Colonic Structure and Protein Expression Suggest Regulatory Mechanisms of Colonic Barrier Function in Torpor–Arousal Cycles of the Daurian Ground Squirrel
Authors: Miao Weilan , Han Yuting , Yang Yingyu , Hao Ziwei , An Ning , Chen Jiayu , Zhang Ziwen , Gao Xuli , Storey Kenneth B. , Chang Hui , Wang Shiwei
Published: August 2022

Background: Both pathological conditions and hibernation can affect the barrier function of small intestine mucosa. However, the effect of hibernation on the barrier function of colonic mucosa remains unclear. Methods: We investigated morphological changes in colonic mucosa, the concentrations of specific proteins and molecules, and the enzymatic activity of diamine oxidase (DAO), in serum and colonic tissue; the expression of tight junction proteins and mucin, and the changes in inflammatory, farnesoid X receptor (FXR)–small heterodimer partner (SHP), and apoptosis-related molecules that could play a role in gut permeability changes in Daurian ground squirrels in summer active (SA), late torpor (LT), and interbout arousal (IBA) periods. Results: The results show that hibernation reduced the thickness of the colonic mucosa and the depth of the crypt, decreased the number of goblet cells (GCs), and damaged the structure of some microvilli. The concentrations of proteins and molecules, and the enzymatic activity of DAO, were all increased in the serum and colon, and the localization of tight junction proteins and mucin in the colonic mucosa were altered (compensatory response). Although the ground squirrels ate during the interbout arousal period, the changes remained similar to the response to torpor. Inflammation, apoptosis–anti-apoptosis, and FXR–SHP signaling may be involved in the possible changes in intestinal gut permeability during the torpor–arousal cycle in Daurian ground squirrels. In addition, periodic interbout arousal may play an inflammation-correcting role during the long hibernation season of Daurian ground squirrels.
Metabolomics of Human Semen: A Review of Different Analytical Methods to Unravel Biomarkers for Male Fertility Disorders
Authors: Blaurock Janet , Baumann Sven , Grunewald Sonja , Schiller Jürgen , Engel Kathrin M.
Published: August 2022

Background: Human life without sperm is not possible. Therefore, it is alarming that the fertilizing ability of human spermatozoa is continuously decreasing. The reasons for that are widely unknown, but there is hope that metabolomics-based investigations may be able to contribute to overcoming this problem. This review summarizes the attempts made so far. Methods: We will discuss liquid chromatography–mass spectrometry (LC-MS), gas chromatography (GC), infrared (IR) and Raman as well as nuclear magnetic resonance (NMR) spectroscopy. Almost all available studies apply one of these methods. Results: Depending on the methodology used, different compounds can be detected, which is (in combination with sophisticated methods of bioinformatics) helpful to estimate the state of the sperm. Often, but not in all cases, there is a correlation with clinical parameters such as the sperm mobility. Conclusions: LC-MS detects the highest number of metabolites and can be considered as the method of choice. Unfortunately, the reproducibility of some studies is poor, and, thus, further improvements of the study designs are needed to overcome this problem. Additionally, a stronger focus on the biochemical consequences of the altered metabolite concentrations is also required.
Depolarizing Effects in Hydrogen Bond Energy in 310-Helices Revealed by Quantum Chemical Analysis
Authors: Kondo Hiroko X. , Nakamura Haruki , Takano Yu
Published: August 2022

Hydrogen-bond (H-bond) energies in 310-helices of short alanine peptides were systematically examined by precise DFT calculations with the negative fragmentation approach (NFA), a modified method based on the molecular tailoring approach. The contribution of each H-bond was evaluated in detail from the 310-helical conformation of total energies (whole helical model, WH3-10 model), and the results were compared with the property of H-bond in α-helix from our previous study. The H-bond energies of the WH3-10 model exhibited tendencies different from those exhibited by the α-helix in that they depended on the helical position of the relevant H-bond pair. H-bond pairs adjacent to the terminal H-bond pairs were observed to be strongly destabilized. The analysis of electronic structures indicated that structural characteristics cause the destabilization of the H-bond in 310-helices. We also found that the longer the helix length, the more stable the H-bond in the terminal pairs of the WH3-10 model, suggesting the action of H-bond cooperativity.
Phytotherapeuthics Affecting the IL-1/IL-17/G-CSF Axis: A Complementary Treatment Option for Hidradenitis Suppurativa?
Authors: Witte Katrin , Sabat Robert , Witte-Händel Ellen , Ghoreschi Kamran , Wolk Kerstin
Published: August 2022

Hidradenitis suppurativa (HS; also designated as acne inversa) is a chronic inflammatory disease characterized by painful skin lesions that occur in the axillary, inguinal, gluteal and perianal areas of the body. These lesions contain recurring deep-seated, inflamed nodules and pus-discharging abscesses and fistulas. Affecting about 1% of the population, this common disease has gained appropriate clinical attention in the last years. Associated with numerous comorbidities including metabolic syndrome, HS is considered a systemic disease that severely impairs the quality of life and shortens life expectancy. Therapeutic options for HS are limited, comprising long-term antibiotic treatment, the surgical removal of affected skin areas, and neutralization of TNF-α, the only approved systemic treatment. Novel treatment options are needed to close the therapeutic gap. HS pathogenesis is increasingly better understood. In fact, neutrophilic granulocytes (neutrophils) seem to be decisive for the development of the purulent destructive skin inflammation in HS. Recent findings suggest a key role of the immune mediators IL-1β, IL-17A and G-CSF in the migration into and activation of neutrophils in the skin. Although phytomedical drugs display potent immunoregulatory properties and have been suggested as complementary therapy in several chronic disorders, their application in HS has not been considered so far. In this review, we describe the IL-1/IL-17/G-CSF axis and evaluate it as potential target for an integrated phytomedical treatment of HS.
How Hydroxyurea Alters the Gut Microbiome: A Longitudinal Study Involving Angolan Children with Sickle Cell Anemia
Authors: Delgadinho Mariana , Ginete Catarina , Santos Brígida , Fernandes Carolina , Silva Carina , Miranda Armandina , Vasconcelos Jocelyne Neto de , Brito Miguel
Published: August 2022

Sickle cell anemia (SCA) is an inherited hematological disorder and a serious global health problem, especially in Sub-Saharan Africa. Although hydroxyurea (HU) is the leading treatment for patients with SCA, its effects on the gut microbiome have not yet been explored. In this context, the aim of this study was to investigate this association by characterizing the gut microbiome of an Angolan SCA pediatric population before and after 6 months of HU treatment. A total of 66 stool samples were obtained and sequenced for the 16S rRNA gene (V3-V4 regions). Significant associations were observed in alpha and beta-diversity, with higher values of species richness for the children naïve for HU. We also noticed that children after HU had higher proportions of several beneficial bacteria, mostly short-chain fatty acids (SCFAs) producing species, such as Blautia luti, Roseburia inulinivorans, Eubacterium halli, Faecalibacterium, Ruminococcus, Lactobacillus rogosae, among others. In addition, before HU there was a higher abundance of Clostridium_g24, which includes C. bolteae and C. clostridioforme, both considered pathogenic. This study provides the first evidence of the HU effect on the gut microbiome and unravels several microorganisms that could be considered candidate biomarkers for disease severity and HU efficacy.
A Dioscorea opposita Thunb Polysaccharide-Based Dual-Responsive Hydrogel for Insulin Controlled Release
Authors: Liu Wei , Wang Xiaoge , Zhou Danyang , Fan Xiangze , Zhu Jinhua , Liu Xiuhua
Published: August 2022

A novel hydrogel (DOP/PEI-PBA) based on the “three-component” reaction of 2-formylphenylboric acid (2-FPBA), the primary amine group of polyethyleneimine (PEI) and the cis-o-dihydroxy groups of Dioscorea opposita Thunb polysaccharide (DOP) was designed in this work. The hydrogel can be easily prepared by simply mixing the three reactants at room temperature. The hydrogel had dual responsiveness to glucose and pH, and can realize the controllable release of insulin. Moreover, the hydrogel combining insulin and DOP can inhibit the reactive oxygen species (ROS) level and malondialdehyde (MDA) content, and promote glucose consumption as well as the level of superoxide dismutase (SOD), in high-glucose-induced injury in HL-7702 cells, which reflects the synergistic effect of insulin and DOP to protect hepatocytes from oxidative stress at the same time. Further in vitro cytotoxicity studies showed that the hydrogel had good biocompatibility and no obvious toxicity to cells. These indicate that the prepared hydrogel (DOP/PEI-PBA) can be expected to be applied in the clinical treatment of insulin deficiency in diabetes.
Connective Tissue Disorders and Fragile X Molecular Status in Females: A Case Series and Review
Authors: Butler Merlin G. , Hossain Waheeda A. , Steinle Jacob , Gao Harry , Cox Eleina , Niu Yuxin , Quach May , Veatch Olivia J.
Published: August 2022

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disabilities and the second most common cause after Down syndrome. FXS is an X-linked disorder due to a full mutation of the CGG triplet repeat of the FMR1 gene which codes for a protein that is crucial in synaptogenesis and maintaining functions of extracellular matrix-related proteins, key for the development of normal neuronal and connective tissue including collagen. In addition to neuropsychiatric and behavioral problems, individuals with FXS show physical features suggestive of a connective tissue disorder including loose skin and joint laxity, flat feet, hernias and mitral valve prolapse. Disturbed collagen leads to hypermobility, hyperextensible skin and tissue fragility with musculoskeletal, cardiovascular, immune and other organ involvement as seen in hereditary disorders of connective tissue including Ehlers–Danlos syndrome. Recently, FMR1 premutation repeat expansion or carrier status has been reported in individuals with connective tissue disorder-related symptoms. We examined a cohort of females with features of a connective tissue disorder presenting for genetic services using next-generation sequencing (NGS) of a connective tissue disorder gene panel consisting of approximately 75 genes. In those females with normal NGS testing for connective tissue disorders, the FMR1 gene was then analyzed using CGG repeat expansion studies. Three of thirty-nine females were found to have gray zone or intermediate alleles at a 1:13 ratio which was significantly higher (p < 0.05) when compared with newborn females representing the general population at a 1:66 ratio. This association of connective tissue involvement in females with intermediate or gray zone alleles reported for the first time will require more studies on how the size variation may impact FMR1 gene function and protein directly or in relationship with other susceptibility genes involved in connective tissue disorders.
Graphene Oxide (GO): A Promising Nanomaterial against Infectious Diseases Caused by Multidrug-Resistant Bacteria
Authors: Ng Ida M. J. , Shamsi Suhaili
Published: August 2022

Infectious diseases are major threat due to it being the main cause of enormous morbidity and mortality in the world. Multidrug-resistant (MDR) bacteria put an additional burden of infection leading to inferior treatment by the antibiotics of the latest generations. The emergence and spread of MDR bacteria (so-called “superbugs”), due to mutations in the bacteria and overuse of antibiotics, should be considered a serious concern. Recently, the rapid advancement of nanoscience and nanotechnology has produced several antimicrobial nanoparticles. It has been suggested that nanoparticles rely on very different mechanisms of antibacterial activity when compared to antibiotics. Graphene-based nanomaterials are fast emerging as “two-dimensional wonder materials” due to their unique structure and excellent mechanical, optical and electrical properties and have been exploited in electronics and other fields. Emerging trends show that their exceptional properties can be exploited for biomedical applications, especially in drug delivery and tissue engineering. Moreover, graphene derivatives were found to have in vitro antibacterial properties. In the recent years, there have been many studies demonstrating the antibacterial effects of GO on various types of bacteria. In this review article, we will be focusing on the aforementioned studies, focusing on the mechanisms, difference between the studies, limitations and future directions.
NOS1AP Interacts with α-Synuclein and Aggregates in Yeast and Mammalian Cells
Authors: Matiiv Anton B. , Moskalenko Svetlana E. , Sergeeva Olga S. , Zhouravleva Galina A. , Bondarev Stanislav A.
Published: August 2022

The NOS1AP gene encodes a cytosolic protein that binds to the signaling cascade component neuronal nitric oxide synthase (nNOS). It is associated with many different disorders, such as schizophrenia, post-traumatic stress disorder, autism, cardiovascular disorders, and breast cancer. The NOS1AP (also known as CAPON) protein mediates signaling within a complex which includes the NMDA receptor, PSD-95, and nNOS. This adapter protein is involved in neuronal nitric oxide (NO) synthesis regulation via its association with nNOS (NOS1). Our bioinformatics analysis revealed NOS1AP as an aggregation-prone protein, interacting with α-synuclein. Further investigation showed that NOS1AP forms detergent-resistant non-amyloid aggregates when overproduced. Overexpression of NOS1AP was found in rat models for nervous system injury as well as in schizophrenia patients. Thus, we can assume for the first time that the molecular mechanisms underlying these disorders include misfolding and aggregation of NOS1AP. We show that NOS1AP interacts with α-synuclein, allowing us to suggest that this protein may be implicated in the development of synucleinopathies and that its aggregation may explain the relationship between Parkinson’s disease and schizophrenia.
Vitamin D-Related Genetic Variations and Nonalcoholic Fatty Liver Disease: A Systematic Review
Authors: Jaroenlapnopparat Aunchalee , Suppakitjanusant Pichatorn , Ponvilawan Ben , Charoenngam Nipith
Published: August 2022

Background: Studies have demonstrated the link between vitamin-D-related genetic variations and nonskeletal outcomes. We aimed to identify all available data on the association of vitamin-D-related genetic variations with nonalcoholic fatty liver disease (NAFLD). Methods: Potentially eligible studies were identified from Embase and Medline databases from inception to June 2022 using a search strategy that comprised terms for “Vitamin D” and “NAFLD”. Eligible studies must report the association between vitamin D-related genetic variations and presence, severity or response to treatment of NAFLD. Data were extracted from each eligible study. Results: A total of 3495 articles were identified. After a systematic review, twelve studies were included. A total of 26 genetic variations were identified. Presence of NAFLD was associated with variations of GC (rs222054, rs222020, rs10011000, rs7041), VDR (rs2228570, rs11168287, rs10783219, rs4752), CYP24A1 (rs3787557, rs6068816, rs2296241, rs2248359) and CYP27B1 (rs4646536). Severity of NAFLD was associated with variations of GC (rs4588), VDR (rs2228570, rs4334089), CYP2R1 (rs10741657), DHCR7 (rs1544410, rs3829251, rs12785878) and CYP24A1 (rs3787557, rs6068816, rs6097809, rs6127119, rs2248359, rs3787554, rs4809960, rs6022999). Response to calcitriol treatment was associated with variation of VDR (rs10735810). Conclusions: Multiple vitamin D-related genetic variations were associated with NAFLD, indicating the role of vitamin D in the pathogenesis of NAFLD.
Ribosomes: The New Role of Ribosomal Proteins as Natural Antimicrobials
Authors: Hurtado-Rios Jessica J. , Carrasco-Navarro Ulises , Almanza-Pérez Julio Cesar , Ponce-Alquicira Edith
Published: August 2022

Moonlighting proteins are those capable of performing more than one biochemical or biophysical function within the same polypeptide chain. They have been a recent focus of research due to their potential applications in the health, pharmacological, and nutritional sciences. Among them, some ribosomal proteins involved in assembly and protein translation have also shown other functionalities, including inhibiting infectious bacteria, viruses, parasites, fungi, and tumor cells. Therefore, they may be considered antimicrobial peptides (AMPs). However, information regarding the mechanism of action of ribosomal proteins as AMPs is not yet fully understood. Researchers have suggested that the antimicrobial activity of ribosomal proteins may be associated with an increase in intracellular reactive oxidative species (ROS) in target cells, which, in turn, could affect membrane integrity and cause their inactivation and death. Moreover, the global overuse of antibiotics has resulted in an increase in pathogenic bacteria resistant to common antibiotics. Therefore, AMPs such as ribosomal proteins may have potential applications in the pharmaceutical and food industries in the place of antibiotics. This article provides an overview of the potential roles of ribosomes and AMP ribosomal proteins in conjunction with their potential applications.
Profiling of the Candidate Interacting Proteins of SELF-PRUNING 6A (SP6A) in Solanum tuberosum
Authors: Wang Enshuang , Liu Tengfei , Sun Xiaomeng , Jing Shenglin , Zhou Tingting , Liu Tiantian , Song Botao
Published: August 2022

SELF-PRUNING 6A (SP6A), a homolog of FLOWERING LOCUS T (FT), has been identified as tuberigen in potato. StSP6A is a mobile signal synthesized in leaves and transmitted to the stolon through phloem, and plays multiple roles in the growth and development of potato. However, the global StSP6A protein interaction network in potato remains poorly understood. In this study, BK-StSP6A was firstly used as the bait to investigate the StSP6A interaction network by screening the yeast two-hybrid (Y2H) library of potato, resulting in the selection of 200 independent positive clones and identification of 77 interacting proteins. Then, the interaction between StSP6A and its interactors was further confirmed by the Y2H and BiFC assays, and three interactors were selected for further expression analysis. Finally, the expression pattern of Flowering Promoting Factor 1.1 (StFPF1.1), No Flowering in Short Days 1 and 2 (StNFL1 and StNFL2) was studied. The three genes were highly expressed in flowers or flower buds. StFPF1.1 exhibited an expression pattern similar to that of StSP6A at the stolon swelling stages. StPHYF-silenced plants showed up-regulated expression of StFPF1.1 and StSP6A, while expression of StNFL1 and StNFL2 was down-regulated in the stolon. The identification of these interacting proteins lays a solid foundation for further functional studies of StSP6A.