bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new self‐immolative colistin prodrug with dual targeting functionalities and reduced toxicity for the treatment of intracellular bacterial infections
Authors: Liu Gengqi , Lu Di , Zhu Shiyu , Hao Minchao , Yang Xingyue , Wang Xiaojian , Zhang Yumiao 
Published: May 2022

AbstractColistin is a potent antibiotic but its severe side effects including nephrotoxicity and neurotoxicity are the roadblock for their wide use in clinics. To solve this problem, we synthesized a new prodrug, mannose‐maltose‐colistin conjugate, termed MMCC that can reversibly mask the five amines of colistin that are primarily responsible for the toxicity. The deliberated design of disulfide‐based self‐immolative linker warranted the reversibly release of the pristine amines of colistin on demand without sacrificing antimicrobial efficacy. Once MMCC was delivered in cells, reducing agents cleaves the disulfide bond and release the pristine amines. The targeting ligands of maltose and mannose were grafted on colistin conjugate for targeting delivery of colistin to bacteria and macrophages, respectively. Taken together, MMCC as a new class of antimicrobial biomaterials, demonstrates its great potential for the treatment of intracellular bacterial infections.
Calcimimetics Alter Periosteal and Perilacunar Bone Matrix Composition and Material Properties in Early Chronic Kidney Disease
Authors: Damrath John G. , Moe Sharon M. , Wallace Joseph M. 
Published: May 2022

ABSTRACT
Chronic kidney disease (CKD) affects 15% of Americans and greatly increases fracture risk due to elevated parathyroid hormone, cortical porosity, and reduced bone material quality. Calcimimetic drugs are used to lower parathyroid hormone (PTH) in CKD patients, but their impact on bone matrix properties remains unknown. We hypothesized that tissue-level bone quality is altered in early CKD and that calcimimetic treatment will prevent these alterations. To test this hypothesis, we treated Cy/+ rats, a model of spontaneous and progressive CKD-mineral and bone disorder (CKD-MBD), with KP-2326, a preclinical analogue of etelcalcetide, early in the CKD disease course. To measure tissue-level bone matrix composition and material properties, we performed colocalized Raman spectroscopy and nanoindentation on new periosteal bone and perilacunar bone using hydrated femur sections. We found that CKD and KP treatment lowered mineral type B carbonate substitution whereas KP treatment increased mineral crystallinity in new periosteal bone. Reduced elastic modulus was lower in CKD but was not different in KP-treated rats versus CTRL. In perilacunar bone, KP treatment lowered type B carbonate substitution, increased crystallinity, and increased mineral-to-matrix ratio in a spatially dependent manner. KP treatment also increased reduced elastic modulus and hardness in a spatially dependent manner. Taken together, these data suggest that KP treatment improves material properties on the tissue level through a combination of lowering carbonate substitution, increasing mineral crystallinity, and increasing relative mineralization of the bone early in CKD. As a result, the mechanical properties were improved, and in some regions, were the same as control animals. Therefore, calcimimetics may help prevent CKD-induced bone deterioration by improving bone quality in new periosteal bone and in bone tissue near osteocyte lacunae. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Low concentrations of bisphenol A promote the activation of the mitochondrial apoptotic pathway on Beta‐TC‐6 cells via the generation of intracellular reactive oxygen species and mitochondrial superoxide
Authors: Anastasiou Ioanna A. , Eleftheriadou Ioanna , Tentolouris Anastasios , Sarantis Panagiotis , Angelopoulou Andriani , Katsaouni Athanasia , Mourouzis Iordanis , Karamouzis Michalis V. , Gorgoulis Vasilios , Pantos Constantinos , Tentolouris Nikolaos 
Published: May 2022

AbstractΤhe natural history of type 2 diabetes mellitus is characterized by a progressive loss of pancreatic beta cell function and insulin resistance. Bisphenol A (BPA) is an endocrine‐disrupting chemical that is used widely in industry; people are exposed to BPA and its products daily. Studies have delineated that BPA alters the function of pancreatic beta cells. Herein, we examined the effect of low doses of BPA on pancreatic beta cell viability and apoptosis and we tried to elucidate the mechanisms involved in these processes. Beta‐TC‐6 (ATCC® CRL‐11506™) cells were cultured with a medium containing the following dilutions of BPA: 0.002, 0.02, 0.1, 0.2, 2 μΜ up to 72 h. We examined the viability and adenosine triphosphate (ATP) levels of cells. Then, we measured apoptosis, cell cycle, and insulin levels. We quantified the levels of proteins implicated in the mitochondrial pathway of apoptosis; and finally, we quantified the intracellular reactive oxygen species and mitochondrial superoxide. We found that the exposure of Beta‐TC‐6 cells to BPA results in a decrease in cell viability, ATP levels, and an increase in insulin levels. We found an increase in apoptosis levels and a decrease in cell cycle levels. In addition, we provide evidence of the levels of apoptotic proteins. Finally, we found an increase in the cellular reactive oxygen species and mitochondrial superoxide production. Exposure to low concentrations of BPA triggers the mitochondrial pathway of apoptosis via the generation of intracellular reactive oxygen species and mitochondrial superoxide on Beta‐TC‐6 cells in a dose‐dependent way.
The physical nature of the ultrashort spike–ring interaction in iron maiden molecules
Authors: Jabłoński Mirosław 
Published: May 2022

AbstractThe so‐called ‘iron maiden’ molecules belong to one of the most interesting subgroups of cyclophanes due to the presence of the ultrashort interaction between the CX apical bond and the benzene ring. This article presents an in‐depth theoretical study of 16 ‘iron maiden’ molecules, in which X = H, F, Cl or Br and the side chains are of various lengths and types: CSC, CSCC, CCC, and CCCC. It is shown that the H → F → Cl → Br substitution leads to a significant expansion of the ‘iron maiden’ molecule. Shorter chains lead to more pronounced effects, while insertion of sulfur atoms into the side chains lowers them. Structural changes are associated with an increase in energetic destabilization of X. Moreover, unlike for H, in the case of X = halogen, theout → inisomerization is energetically disadvantageous. The ‘iron maiden’ molecules are characterized by the presence of only three X⋯CArbond paths. Particularly noteworthy are unusually large (even up to 32) values of the X⋯CArbond ellipticity, which results from flat electron density distribution. The X⋯πinteraction in each of the investigated ‘iron maiden’ molecule turned out to be multi‐center, stabilizing and almost purely covalent in nature as indicated by the definitely dominant percentage (94.8%–101.6%) of the exchange‐correlation energy. The spatial hindrance within the ‘iron maiden’ molecules appears to be not so much due to the X⋯πrepulsion, but due to unfavorable steric interactions between X and the CC side bonds. It is also confirmed that some CH⋯HC interactions in aliphatic chains can be very weakly stabilizing.
Ambra1 deficiency impairs mitophagy in skeletal muscle
Authors: Gambarotto Lisa , Metti Samuele , Chrisam Martina , Cerqua Cristina , Sabatelli Patrizia , Armani Andrea , Zanon Carlo , Spizzotin Marianna , Castagnaro Silvia , Strappazzon Flavie , Grumati Paolo , Cescon Matilde , Braghetta Paola , Trevisson Eva , Cecconi Francesco , Bonaldo Paolo 
Published: May 2022

AbstractBackgroundMaintaining healthy mitochondria is mandatory for muscle viability and function. An essential surveillance mechanism targeting defective and harmful mitochondria to degradation is the selective form of autophagy called mitophagy. Ambra1 is a multifaceted protein with well‐known autophagic and mitophagic functions. However, the study of its role in adult tissues has been extremely limited due to the embryonic lethality caused by full‐body Ambra1 deficiency.MethodsTo establish the role of Ambra1 as a positive regulator of mitophagy, we exploited in vivo overexpression of a mitochondria‐targeted form of Ambra1 in skeletal muscle. To dissect the consequence of Ambra1 inactivation in skeletal muscle, we generated muscle‐specific Ambra1 knockout (Ambra1fl/fl:Mlc1f‐Cre) mice. Mitochondria‐enriched fractions were obtained from muscles of fed and starved animals to investigate the dynamics of the mitophagic flux.ResultsOur data show that Ambra1 has a critical role in the mitophagic flux of adult murine skeletal muscle and that its genetic inactivation leads to mitochondria alterations and myofibre remodelling. Ambra1 overexpression in wild‐type muscles is sufficient to enhance mitochondria clearance through the autophagy‐lysosome system. Consistently with this, Ambra1‐deficient muscles display an abnormal accumulation of the mitochondrial marker TOMM20 by +76% (n = 6–7; P < 0.05), a higher presence of myofibres with swollen mitochondria by +173% (n = 4; P < 0.05), and an alteration in the maintenance of the mitochondrial membrane potential and a 34% reduction in the mitochondrial respiratory complex I activity (n = 4; P < 0.05). Lack of Ambra1 in skeletal muscle leads to impaired mitophagic flux, without affecting the bulk autophagic process. This is due to a significantly decreased recruitment of DRP1 (n = 6–7 mice; P < 0.01) and Parkin (n = 6–7 mice; P < 0.05) to the mitochondrial compartment, when compared with controls. Ambra1‐deficient muscles also show a marked dysregulation of the endolysosome compartment, as the incidence of myofibres with lysosomal accumulation is 20 times higher than wild‐type muscles (n = 4; P < 0.05). Histologically, Ambra1‐deficient muscles of both 3‐ and 6‐month‐old animals display a significant decrease of myofibre cross‐sectional area and a 52% reduction in oxidative fibres (n = 6–7; P < 0.05), thus highlighting a role for Ambra1 in the proper structure and activity of skeletal muscle.ConclusionsOur study indicates that Ambra1 is critical for skeletal muscle mitophagy and for the proper maintenance of functional mitochondria.
Comparative study on the effect of poly (vinylpyrrolidone) and polyethylene glycol as additives on polysulfone synthesized ultrafiltration membranes
Authors: Rhimi Asma , Zlaoui Khira , Van der Bruggen Bart , Horchani‐Naifer Karima , Ennigrou Dorra Jellouli 
Published: May 2022

AbstractBACKGROUNDPolysulfone ultrafiltration membranes were prepared by phase inversion technique with 1‐methyl‐2‐pyrrolidinone as solvent, and with poly (vinyl pyrrolidone) (2 wt% and 3 wt%) and polyethylene glycol (6 wt%) as additives.Water contact angle measurements, scanning electron microscopy, and Fourier transform infrared spectroscopy were used to characterize the synthesized membranes. The membrane permeation has been evaluated in terms of ultrapure water, bovine serum albumin, cobalt, and copper retention.This study compared the effects of the amount and nature of additives on the performance and structure of synthesized membranes to enhance the hydrophilicity of polysulfone membranes.RESULTSIt was found that 2 wt% poly (vinyl pyrrolidone) gives the optimal values on retention and flux permeation. When applied to ultrafiltration, the membrane exhibited high retention of bovine serum albumin, cobalt, and copper (99.1%, 28.9%, and 46.7%, respectively). The retention values of cobalt and copper are not high.CONCLUSIONIn the polyelectrolyte enhanced ultrafiltration process, the addition of a complexing agent, such as sodium alginate, enhances the retention of cobalt and copper to 94% and 97%, respectively. The optimal performances have been obtained at 2 bar and pH 4 for copper and cobalt retention., © 2022 Society of Chemical Industry (SCI).
Stress, coping, and the Strong Black Woman: An empirical analysis
Authors: Graham Jasmine , Welfare Laura E. , Day‐Vines Norma L. , Ghoston Michelle 
Published: May 2022

AbstractThe Strong Black Woman icon presents an image of Black women as infrangible, able to endure hardships unscathed, and in possession of indomitable strength. In this quantitative study of 100 Black women, statistically significant relationships were found between Strong Black Woman attitudes and stress. Implications for Strong Black Women clientele in a professional counseling context are provided.
Respiratory viruses among pediatric inpatients with acute lower respiratory tract infections in Jinan, China, 2016–2019
Authors: Chu Fu‐Lu , Li Chen , Chen Li , Dong Bo , Qiu Yang , Liu Yiqing 
Published: May 2022

AbstractThe viral etiologies responsible for acute lower respiratory tract infections (ALRI) are a major cause of pediatric hospitalization, and some develop severe diseases requiring pediatric intensive care unit (PICU) admission. The aim of this study is to determine the prevalence of viruses and risk factors associated with PICU admission among patients hospitalized for ALRI. Nasopharyngeal swabs were collected to detect human rhinovirus (HRV), influenza A and B viruses (IAV and IBV), parainfluenza viruses (PIV), and respiratory syncytial virus (RSV) by reverse transcription‐polymerase chain reaction (PCR) and adenovirus (ADV) by PCR. Of the 5590 pediatric inpatients enrolled, respiratory viral infection occurred in 2102 (37.60%) patients, including 1846 (33.02%) single and 256 (4.58%) mixed viral infections. Among the nasopharyngeal swabs from pediatric inpatients, HRV accounted for the highest detection rate (16.48%), followed by PIV (8.35%), RSV (7.41%), ADV (4.63%), IAV (3.51%), and IBV (2.08%). The positive rate of viral tests decreased with increasing age and was higher in males (39.29%) than females (34.67%). The prevalence of viral infection was the highest in winter (41.57%) and lowest in autumn (31.78%). Each virus had a seasonal pattern, with peaks occurring in months of their epidemic seasons. RSV infection and the presence of comorbidities including congenital tracheal stenosis, congenital heart disease, metabolic disorder, immunodeficiency, renal disease, gastrointestinal disease, and neurological disorder might be associated with the need for PICU admission. Therefore, this study provides useful information for the prevention and control of virus‐related respiratory diseases and the early identification of and intervention in severe cases.
NURR1‐deficient mice have age‐ and sex‐specific behavioral phenotypes
Authors: Montarolo Francesca , Martire Serena , Chiara Francesco , Allegra Sarah , De Francia Silvia , Hoxha Eriola , Tempia Filippo , Capobianco Marco Alfonso , Bertolotto Antonio 
Published: May 2022

AbstractThe transcription factor NURR1 is essential to the generation and maintenance of midbrain dopaminergic (mDA) neurons and its deregulation is involved in the development of dopamine (DA)‐associated brain disorders, such as Parkinson's disease (PD). The old male NURR1 heterozygous knockout (NURR1‐KO) mouse has been proposed as a model of PD due to its altered motor performance that was, however, not confirmed in a subsequent study. Based on these controversial results, we explored the effects of the NURR1 deficiency on locomotor activity, motor coordination, brain and plasma DA levels, blood pressure and heart rate of old mice, also focusing on the potential effect of sex. As a probable consequence of the role of NURR1 in DA pathway, we observed that the old NURR1‐KO mouse is characterized by motor impairment, and increased brain DA level and heart rate, independently from sex. However, we also observed an alteration in spontaneous locomotor activity that only affects males. In conclusion, NURR1 deficiency triggers sex‐ and age‐specific alterations of behavioral responses, of DA levels and cardiovascular abnormalities. Further studies in simplified systems will be necessary to dissect the mechanism underlying these observations.
Nutrition‐inflammation marker enhances prognostic value to ECOG performance status in overweight or obese patients with cancer
Authors: Zhang Xi , Zhang Qi , Tang Meng , Zhang Kang‐Ping , Zhang Xiao‐Wei , Song Meng‐Meng , Ruan Guo‐Tian , Sun Qiang , Li Wei , Xu Hong‐Xia , Cong Ming‐Hua , Deng Li , Shi Han‐Ping 
Published: May 2022

AbstractBackgroundOverweight or obese cancer patients are more likely to develop a proinflammatory status. The aim of this study was to investigate whether the nutrition‐inflammation marker can provide additional prognostic information on top of well‐established Eastern Cooperative Oncology Group performance status (ECOG‐PS) in overweight or obese patients with cancer.MethodsA total of 1667 overweight or obese cancer patients were enrolled in this study. We assessed the prediction accuracy of 10 nutrition‐inflammation markers by time‐dependent receiver operating characteristic (ROC) and elucidated their association with overall survival by the Kaplan‐Meier method and a Cox model.ResultsIn this analysis, the majority of patients had a good performance status (ECOG‐PS score ≤1; 88.3%). Both the area under ROC curves and the C‐index of the lymphocyte–C‐reactive protein ratio (LCR) demonstrated that LCR was the most significant nutrition‐inflammation marker correlated with survival. In patients with good ECOG‐PS, a low LCR was significantly associated with poorer prognosisand enhanced the predictive ability of one‐year mortality. For specific tumor types, a low LCR was an independent prognostic factor for lung cancer, upper gastrointestinal cancer, and colorectal cancer, and it tended to be a significant predictor for breast cancer. In addition, those patients with a combined low LCR and poorer ECOG‐PS (ECOG‐PS score >1) showed the worst prognosis.ConclusionThe LCR is more strongly associated with overall survival than other nutrition‐inflammation markers, and it is able to further detect patients with worse prognosis on top of ECOG‐PS in overweight or obese patients with cancer.
Raman spectra and structure of hydrogen‐bonded water oligomers in tetrahydrofuran–H2O binary solutions
Authors: Raj Ankit , Chen Yu‐Jou , Wang Chien‐Lung , Hamaguchi Hiro‐o 
Published: May 2022

AbstractRaman spectra of hydrogen‐bonded water oligomers have been resolved from concentration‐dependent Raman spectra of tetrahydrofuran (THF)–water binary solutions with the use of multivariate curve resolution with alternating least‐squares (MCR‐ALS) analysis, assisted by hypothetical addition multivariate analysis with numerical differentiation (HAMAND) procedure. A total of 38 Raman spectra acquired in the broad spectral range of 700–3810 cm−1were analyzed in a multistep procedure to explain the spectral variations in terms of four components: pure THF, Spectra A, Spectra B, and Spectra C. A four‐component MCR‐ALS analysis was performed with initial guesses by HAMAND analysis to refine the spectral components and determine their concentration dependence. Of the MCR‐ALS resolved three spectra, A was identified as THF(H2O), B as THF(H2O)2with two hydrogens attached to THF, and C as THF(H2O)nhaving two or more linearly hydrogen‐bonded oligomers of water (n = 2–4). Observed spectral changes of the OH stretch vibrations of water and those of the C–C/C–O stretches of THF were well reproduced by quantum chemical calculations. Formation of hydrogen‐bonded water oligomers in THF–water complexes has thus been revealed. The present study provides a new insight into the basics of hydrogen bonding formation in aqueous systems. It also provides experimental methodology for extracting concentration‐dependent minor spectral components contained in complex condensed‐phase Raman spectra.
A comparative study based on serum SERS spectra in and on the coffee ring for high precision breast cancer detection
Authors: Lin Xueliang , Jia Xianggang , Lin Jin Yong , Wu Ping Hui , Weng Youliang , Feng Shangyuan 
Published: May 2022

AbstractHuman blood contains a variety of biomolecules that are highly related to the occurrence, progression, and prognosis of diseases, including cancer. The development of rapid and accurate methods for the detection of these biomarkers with extremely low concentration is vital for improving cancer screening. Herein, a label‐free surface‐enhanced Raman scattering (SERS) technology was employed to detect human serum samples from healthy volunteers (n = 51) and breast cancer patients (n = 58) with the aim of exploring the differences in bio‐components between them. Moreover, the influence of measurement location during SERS assay was evaluated due to the occurrence of “coffee‐ring (CR)” effect associated with this work. Results showed that the SERS spectra obtained from the CR area can better reflect the overall biochemical information of serum samples and exhibited excellent diagnostic sensitivity (94.8%) and specificity (98%) for identifying breast cancer from healthy groups using principal component analysis and linear discriminant analysis (PCA‐LDA) algorithm. This work showed a preliminary study of the serum SERS method for breast cancer detection, providing a potential rapid and accurate liquid biopsy strategy for clinical cancer screening.
Morinda officinalis polysaccharide regulates rat bone mesenchymal stem cell osteogenic–adipogenic differentiation in osteoporosis by upregulating miR‐21 and activating the PI3K/AKT pathway
Authors: Wu Pei‐Yu , Chen Wen , Huang He , Tang Wang , Liang Jie 
Published: May 2022

AbstractOsteoporosis (OP) is a prevailing bone metabolic disease. Morinda officinalis polysaccharide (MOP) has biological activities and medicinal potential. This study explored its mechanism in OP. Rat bone mesenchymal stem cells (rBMSCs) were pretreated with low/high concentrations of MOP and subjected to osteogenic differentiation (OD) or adipogenic differentiation (AD) induction. The protein markers of OD (RUNX2 and BMP2) and AD (CEBPα and PPARγ) and miR‐21 expression were detected. miR‐21 was overexpressed to study its effects on rBMSC OD and AD. rBMSCs were transfected with miR‐21 inhibitor and treated with high concentration of MOP for verification. The targeted relationship between miR‐21 and PTEN was verified by bioinformatics and dual‐luciferase assay. The PTEN/PI3K/AKT pathway‐related proteins were detected. Ovariectomy (OVX)‐induced OP rats were treated with MOP. Rat bone mineral density (BMD), serum bone metabolism indexes bone‐derived alkaline phosphatase (BALP), and osteocalcin (BGP) levels were assessed by BMD detectors and ELISA kits. miR‐21 expression in rBMSCs was detected. After treatment with low/high concentrations of MOP, the OD of rBMSCs was increased and AD was inhibited and miR‐21 was upregulated. miR‐21 overexpression enhanced the OD of rBMSCs and inhibited AD. miR‐21 knockdown reversed the effect of high concentration of MOP on rBMSCs. miR‐21 targeted PTEN. After treatment with low/high concentrations of MOP, PI3K, and AKT phosphorylation were increased and the PI3K/AKT pathway was activated. BMD, BALP, BGP, and miR‐21 levels in OVX rats were decreased. MOP partially alleviated OP in OVX rats. Briefly, MOP enhanced rBMSC OD and inhibited AD via the miR‐21/PTEN/PI3K/AKT axis.