bluuebunny/crossref_metadata_2025 huggingface dataset:
A Study of Short Term Outcomes among Covid-19 Patients Discharged without Follow up In the New York Metropolitan Area
Authors: Christine Louise Molmenti , Neil Mitra , Abhinit Shah , Anne Flynn , Zenobia Brown , Kathryn Baxter , Vesna Cekic , Hallie Bleau , Jacqueline Picone , Christina Olivieri , Debbie Allis , Patricia Perlas , Pashmena Ahmadi , Victoria Dicanio , Giovanna Smeragliuolo , Shelby Bossie , Bossie Mammen , Richard Larry Whelan
Published: November 2021

Background: A shortage of beds, high case volume, decreased availability of outpatient medical doctors, and limited disease knowledge resulted in the premature discharge and poor follow up of COVID-19 patients in the New York Metropolitan Area.
Objective: The primary objective of this retrospective study and phone survey was to characterize the demographics and clinical outcomes (e.g., readmission rates, comorbidities, mortality, and functional status) of COVID-19 patients discharged without follow-up. The secondary objective was to assess the impact of race and comorbidities on readmission rates and the extent to which patients were escalated to another care provider.
Methods: Electronic medical records were reviewed for COVID-19 patients discharged from 3 NYMA hospitals in March 2020. Follow up data regarding medical status, ability to perform activities of daily living and functional status was also obtained from patients via phone call. The Chi-square, Fishers exact test and t-tests were used to analyze the data.
Results: 349 patients were included in the analysis. The hospital readmission rate was 10.6% (58.8% for pulmonary reasons) and did not differ by race. 74.3% of readmissions were <14 days after release. The post-discharge mortality rate was 2.6%. Hypertension was the most common comorbidity (43%). There was a statistically significant association between mortality and number of comorbidities (p=<0.0001). 82% of patients were contacted by phone. 66.6% of patients returned to pre-COVID baseline function in ≥1 month. As a result of information obtained on the follow up phone call, 4.2% of patients required “escalation” to another provider.
Conclusion: Discharging COVID-19 patients without prearranged follow up was associated with high readmission and mortality rates. While the majority of patients recovered, prolonged weakness, lengthy recovery, and the need for additional medical intervention was noted. Further work to assess the effectiveness COVID-19 post-discharge programs is warranted.
PERAN DAN MANFAAT KOMUNIKASI PEMBANGUNAN PADA APLIKASI PELACAK COVID-19 SEBAGAI MEDIA KOMUNIKASI KESEHATAN
Authors: KENCANA WORO HARKANDI
Published: November 2021

Covid-19 telah ditetapkan oleh WHO sebagai pandemi. Penyebaran virus yang sangat cepat di hampir semua negara dunia memberikan perubahan besar pada kehidupan masyarakat. Pemerintah negara khususnya Indonesia membuat berbagai kebijakan untuk mencegah penyebaran virus yang begitu masif ini. Komunikasi kesehatan dilakukan oleh pemerintah melalui berbagi media dalam menyampaikan pesan terkait Covid-19 kepada masyarakat. Salah satu media yang digunakan adalah aplikasi pelacak Covid-19 yang bernama PeduliLindungi.penelitian ini ingin mengetahui bagaimana aplikasi PeduliLindungi ini dalam era digital menjadi media komunikasi kesehatan antara pemerintah dengan masyarakat. Penelitian ini menggunakan pendekatan komunikasi kesehatan dan teori second media age. Metodologi yang digunakan adalah kualitatti deskriptif dengan teknik pengumpulan data berupa wawancara kepada pengguna aplikasi dan observasi terhadap aplikasi PeduliLindungi. Hasil penelitian ini aplikasi PeduliLindungi, merupakan media komunikasi kesehatan mengenai Covid 19 dimana Aplikasi ini mengandalkan partisipasi masyarakat untuk saling membagikan data lokasinya saat bepergian agar penelusuran riwayat kontak dengan penderita COVID-19 dapat dilakukan.aplikasi ini memberikan informasi kesehatan dan protokoler menghadapi pandemi Covid-19. Dengan mengaktifkan aplikasi merupakan gerakan sosial dalam  membangun kesadaran dan advokasi penggunaan Internet sebagai sumber berita sebagai kontrol informasi.
De Novo Production of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide in Saccharomyces cerevisiae
Authors: Huang Ying , Jiang Dan , Ren Guangxi , Yin Yan , Sun Yifan , Liu Tengfei , Liu Chunsheng
Published: November 2021

Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) is a rare compound in licorice and its short supply limits the wide applications in the pharmaceutical, cosmetic, and food industries. In this study, de novo biosynthesis of GAMG was achieved in engineered Saccharomyces cerevisiae strains based on the CRISPR/Cas9 genome editing technology. The introduction of GAMG biosynthetic pathway resulted in the construction of a GAMG-producing yeast strain for the first time. Through optimizing the biosynthetic pathway, improving the folding and catalysis microenvironment for cytochrome P450 enzymes (CYPs), enhancing the supply of UDP-glucuronic acid (UDP-GlcA), preventing product degradation, and optimizing the fermentation conditions, the production of GAMG was increased from 0.02 μg/L to 92.00 μg/L in shake flasks (4,200-fold), and the conversion rate of glycyrrhetic acid (GA) to GAMG was higher than 56%. The engineered yeast strains provide an alternative approach for the production of glycosylated triterpenoids.
In Sickness and in Health: The Oxygen Reactive Species and the Bone
Authors: Reis Joana , Ramos António
Published: November 2021

Oxidative stress plays a central role in physiological and pathological bone conditions. Its role in signalment and control of bone cell population differentiation, activity, and fate is increasingly recognized. The possibilities of its use and manipulation with therapeutic goals are virtually unending. However, how redox balance interplays with the response to mechanical stimuli is yet to be fully understood. The present work summarizes current knowledge on these aspects, in an integrative and broad introductory perspective.
Improved the Activity of Phosphite Dehydrogenase and its Application in Plant Biotechnology
Authors: Liu Tongtong , Yuan Lili , Deng Suren , Zhang Xiangxian , Cai Hongmei , Ding Guangda , Xu Fangsen , Shi Lei , Wu Gaobing , Wang Chuang
Published: November 2021

Phosphorus (P) is a nonrenewable resource, which is one of the major challenges for sustainable agriculture. Although phosphite (Phi) can be absorbed by the plant cells through the Pi transporters, it cannot be metabolized by plant and unable to use as P fertilizers for crops. However, transgenic plants that overexpressed phosphite dehydrogenase (PtxD) from bacteria can utilize phosphite as the sole P source. In this study, we aimed to improve the catalytic efficiency of PtxD from Ralstonia sp.4506 (PtxDR4506), by directed evolution. Five mutations were generated by saturation mutagenesis at the 139th site of PtxD R4506 and showed higher catalytic efficiency than native PtxDR4506. The PtxDQ showed the highest catalytic efficiency (5.83-fold as compared to PtxDR4506) contributed by the 41.1% decrease in the Km and 2.5-fold increase in the kcat values. Overexpression of PtxDQ in Arabidopsis and rice showed increased efficiency of phosphite utilization and excellent development when phosphite was used as the primary source of P. High-efficiency PtxD transgenic plant is an essential prerequisite for future agricultural production using phosphite as P fertilizers.
3D Bioprinting Strategies, Challenges, and Opportunities to Model the Lung Tissue Microenvironment and Its Function
Authors: Barreiro Carpio Mabel , Dabaghi Mohammadhossein , Ungureanu Julia , Kolb Martin R. , Hirota Jeremy A. , Moran-Mirabal Jose Manuel
Published: November 2021

Human lungs are organs with an intricate hierarchical structure and complex composition; lungs also present heterogeneous mechanical properties that impose dynamic stress on different tissue components during the process of breathing. These physiological characteristics combined create a system that is challenging to model in vitro. Many efforts have been dedicated to develop reliable models that afford a better understanding of the structure of the lung and to study cell dynamics, disease evolution, and drug pharmacodynamics and pharmacokinetics in the lung. This review presents methodologies used to develop lung tissue models, highlighting their advantages and current limitations, focusing on 3D bioprinting as a promising set of technologies that can address current challenges. 3D bioprinting can be used to create 3D structures that are key to bridging the gap between current cell culture methods and living tissues. Thus, 3D bioprinting can produce lung tissue biomimetics that can be used to develop in vitro models and could eventually produce functional tissue for transplantation. Yet, printing functional synthetic tissues that recreate lung structure and function is still beyond the current capabilities of 3D bioprinting technology. Here, the current state of 3D bioprinting is described with a focus on key strategies that can be used to exploit the potential that this technology has to offer. Despite today’s limitations, results show that 3D bioprinting has unexplored potential that may be accessible by optimizing bioink composition and looking at the printing process through a holistic and creative lens.
Magnetic Microdimer as Mobile Meter for Measuring Plasma Glucose and Lipids
Authors: Yu Shimin , Sun Zhongqi , Zhang Zhanxiang , Sun Haoran , Liu Lina , Wang Wuyi , Li Mu , Zhao Qingsong , Li Tianlong
Published: December 2021

With the development of designed materials and structures, a wide array of micro/nanomachines with versatile functionalities are employed for specific sensing applications. Here, we demonstrated a magnetic propelled microdimer-based point-of-care testing system, which can be used to provide the real-time data of plasma glucose and lipids relying on the motion feedback of mechanical properties. On-demand and programmable speed and direction of the microdimers can be achieved with the judicious adjustment of the external magnetic field, while their velocity and instantaneous postures provide estimation of glucose, cholesterol, and triglycerides concentrations with high temporal accuracy. Numerical simulations reveal the relationship between motility performance and surrounding liquid properties. Such technology presents a point-of-care testing (POCT) approach to adapt to biofluid measurement, which advances the development of microrobotic system in biomedical fields.
Metagenomic Analysis Reveals the Heterogeneity of Conjunctival Microbiota Dysbiosis in Dry Eye Disease
Authors: Liang Qiaoxing , Li Jing , Zou Yanli , Hu Xiao , Deng Xiuli , Zou Bin , Liu Yu , Wei Lai , Liang Lingyi , Wen Xiaofeng
Published: December 2021

Background: Dry eye disease (DED) is a multifactorial inflammatory disease of the ocular surface. It is hypothesized that dysbiosis of the conjunctival microbiota contributes to the development of DED. However, species-level compositions of the conjunctival microbiota in DED and the potential dysbiosis involving microorganisms other than bacteria remain largely uncharacterized.

Methods: We collected conjunctival impression samples from a cohort of 95 individuals, including 47 patients with DED and 48 healthy subjects. We examined the conjunctival microbiota of these samples using shotgun metagenomic sequencing and analyzed microbial dysbiosis in DED at the species level.

Results: The conjunctival microbiota in DED exhibited a decreased α-diversity and an increased inter-individual variation. The α-diversity of female patients with DED was higher than that of male patients. Despite a decreased prevalence in DED, 23 microbial species were identified to show abnormally high abundance in DED samples positive for the species. Among these species, a fungal species Malassezia globosa was enriched female patients. In addition, distinct patterns of associations with disease status were observed for different species of the same genus. For DED subtypes, Staphylococcus aureus and S. capitis were associated with meibomian gland dysfunction (MGD), whereas S. hominis was enriched in patients solely with aqueous tear deficiency (ATD). The microbiota of patients with a mixed type of diagnosis was more similar to MGD patients than ATD patients.

Conclusion: We demonstrated that the conjunctival microbiota dysbiosis in DED is characterized by significant heterogeneity. Microbial signatures may offer novel insights into the complicated etiology of DED and potentially promote the development of personalized treatment for DED in the future.
The Role of Sphingolipid Metabolism in Bone Remodeling
Authors: Qi Tang , Li Liao , Weidong Tian
Published: December 2021

Emerging studies of bioactive lipids have made many exciting discoveries in recent years. Sphingolipids and their metabolites perform a wide variety of cellular functions beyond energy metabolism. Emerging evidence based on genetically manipulated mouse models and molecular biology allows us to obtain new insights into the role sphingolipid played on skeletal remodeling. This review summarizes studies or understandings of the crosstalk between sphingomyelin, ceramide, and sphingosine-1-phosphate (S1P) of sphingolipids family and the cells, especially osteoblasts and osteoclasts of the bone through which bone is remodeled during life constantly. This review also shows agonists and antagonists of S1P as possible therapeutic options and opportunities on bone diseases.
PPARβ/δ Agonist Alleviates Diabetic Osteoporosis via Regulating M1/M2 Macrophage Polarization
Authors: Chen Miao , Lin Weimin , Ye Rui , Yi Jianru , Zhao Zhihe
Published: December 2021

Diabetic osteoporosis is a common complication in diabetic patients, leading to increased fracture risk and impaired bone healing. As a member of the peroxisome proliferator-activated receptor (PPAR) family, PPARβ/δ agonist is suggested as a therapeutic target for the treatment of metabolic syndrome, and has been reported to positively regulate bone turnover by improving osteogenesis. However, its regulatory role in diabetic osteoporosis has not been reported yet. Here, we explored the therapeutic effects and potential mechanisms of PPARβ/δ agonist to the osteoporotic phenotypes of diabetic mice. Our results indicated that the osteoporotic phenotypes could be significantly ameliorated in diabetic mice by the administration of PPARβ/δ agonists. In vitro experiments suggested that PPARβ/δ agonist treatment could alleviate the abnormal increase of osteoclast activity in diabetic mice by rectifying high glucose-mediated macrophage dysfunction instead of directly inhibiting osteoclast differentiation. Mechanistically, Angptl4 may act as a downstream target of PPARβ/δ to regulate macrophage polarization. In conclusion, our study demonstrates the potential of PPARβ/δ agonist as a therapeutic target for the treatment of osteoporosis and immune homeostasis disorder in diabetic patients.
Deregulation of Transcription Factor Networks Driving Cell Plasticity and Metastasis in Pancreatic Cancer
Authors: van Roey Ruthger , Brabletz Thomas , Stemmler Marc P. , Armstark Isabell
Published: November 2021

Pancreatic cancer is a very aggressive disease with 5-year survival rates of less than 10%. The constantly increasing incidence and stagnant patient outcomes despite changes in treatment regimens emphasize the requirement of a better understanding of the disease mechanisms. Challenges in treating pancreatic cancer include diagnosis at already progressed disease states due to the lack of early detection methods, rapid acquisition of therapy resistance, and high metastatic competence. Pancreatic ductal adenocarcinoma, the most prevalent type of pancreatic cancer, frequently shows dominant-active mutations in KRAS and TP53 as well as inactivation of genes involved in differentiation and cell-cycle regulation (e.g. SMAD4 and CDKN2A). Besides somatic mutations, deregulated transcription factor activities strongly contribute to disease progression. Specifically, transcriptional regulatory networks essential for proper lineage specification and differentiation during pancreas development are reactivated or become deregulated in the context of cancer and exacerbate progression towards an aggressive phenotype. This review summarizes the recent literature on transcription factor networks and epigenetic gene regulation that play a crucial role during tumorigenesis.
Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways
Authors: Li Hefei , Zhang Yushan , Lan Xiaomei , Yu Jianhua , Yang Changshuang , Sun Zhijian , Kang Ping , Han Yi , Yu Daping
Published: November 2021

Lung cancer is the leading cause of cancer death worldwide. Cisplatin is the major DNA-damaging anticancer drug that cross-links the DNA in cancer cells, but many patients inevitably develop resistance with treatment. Identification of a cisplatin sensitizer might postpone or even reverse the development of cisplatin resistance. Halofuginone (HF), a natural small molecule isolated from Dichroa febrifuga, has been found to play an antitumor role. In this study, we found that HF inhibited the proliferation, induced G0/G1 phase arrest, and promoted apoptosis in lung cancer cells in a dose-dependent manner. To explore the underlying mechanism of this antitumor effect of halofuginone, we performed RNA sequencing to profile transcriptomes of NSCLC cells treated with or without halofuginone. Gene expression profiling and KEGG analysis indicated that PI3K/AKT and MAPK signaling pathways were top-ranked pathways affected by halofuginone. Moreover, combination of cisplatin and HF revealed that HF could sensitize the cisplatin-resistant patient-derived lung cancer organoids and lung cancer cells to cisplatin treatment. Taken together, this study identified HF as a cisplatin sensitizer and a dual pathway inhibitor, which might provide a new strategy to improve prognosis of patients with cisplatin-resistant lung cancer.
The Basally Expressed p53-Mediated Homeostatic Function
Authors: Nagpal Isha , Yuan Zhi-Min
Published: November 2021

Apart from mutations in the p53 gene, p53 functions can be alternatively compromised by a decrease in nuclear p53 protein levels or activities. In accordance, enhanced p53 protein turnover due to elevated expression of the critical p53 E3 ligase MDM2 or MDM2/MDMX is found in many human cancers. Likewise, the HPV viral E6 protein-mediated p53 degradation critically contributes to the tumorigenesis of cervical cancer. In addition, growth-promoting signaling-induced cell proliferation is accompanied by p53 downregulation. Animal studies have also shown that loss of p53 is essential for oncogenes to drive malignant transformation. The close association between p53 downregulation and carcinogenesis implicates a critical role of basally expressed p53. In accordance, available evidence indicates that a reduced level of basal p53 is usually associated with disruption of homeostasis, suggesting a homeostatic function mediated by basal p53. However, basally expressed p53 under non-stress conditions is maintained at a relatively low abundance with little transcriptional activity, raising the question of how basal p53 could protect homeostasis. In this review, we summarize the findings pertinent to basal p53-mediated activities in the hope of developing a model in which basally expressed p53 functions as a barrier to anabolic metabolism to preserve homeostasis. Future investigation is necessary to characterize basal p53 functionally and to obtain an improved understanding of p53 homeostatic function, which would offer novel insight into the role of p53 in tumor suppression.
Endocrine Regulation of Extra-skeletal Organs by Bone-derived Secreted Protein and the effect of Mechanical Stimulation
Authors: Du Yuxiang , Zhang Lingli , Wang Zhikun , Zhao Xuan , Zou Jun
Published: November 2021

Bone serves as the support for body and provide attachment points for the muscles. The musculoskeletal system is the basis for the human body to complete exercise. Studies believe that bone is not only the basis for constructing structures, but also participates in the regulation of organs outside bone. The realization of this function is closely related to the protein secreted by bone. Whether bone can realize their positions in the human body is also related to their secretion. Bone-derived proteins provide a medium for the targeted regulation of bones on organs, making the role of bone in human body more profound and concrete. Mechanical stimulation effects the extra-skeletal organs by causing quantitative changes in bone-derived factors. When bone receives mechanical stimulation, the nichle of bone responds, and the secretion of various factors changes. However, whether the proteins secreted by bone can interfere with disease requires more research. In this review article, we will first introduce the important reasons and significance of the in-depth study on bone-derived secretory proteins, and summarize the locations, structures and functions of these proteins. These functions will not only focus on the bone metabolism process, but also be reflected in the cross-organ regulation. We specifically explain the role of typical bone-derived secretory factors such as osteocalcin (OCN), osteopontin (OPN), sclerostin (SOST) and fibroblast growth factor 23 (FGF23) in different organs and metabolic processes, then establishing the relationship between them and diseases. Finally, we will discuss whether exercise or mechanical stimulation can have a definite effect on bone-derived secretory factors. Understanding their important role in cross-organ regulation is of great significance for the treatment of diseases, especially for the elderly people with more than one basic disease.
DNA Methylation Signature in Monozygotic Twins Discordant for Psoriatic Disease
Authors: Vecellio Matteo , Paraboschi Elvezia Maria , Ceribelli Angela , Isailovic Natasa , Motta Francesca , Cardamone Giulia , Robusto Michela , Asselta Rosanna , Brescianini Sonia , Sacrini Francesco , Costanzo Antonio , De Santis Maria , Stazi Maria Antonietta , Duga Stefano , Selmi Carlo
Published: November 2021

Background: Psoriatic disease is a multifactorial inflammatory condition spanning from skin and nail psoriasis (Pso) to spine and joint involvement characterizing psoriatic arthritis (PsA). Monozygotic twins provide a model to investigate genetic, early life environmental exposure and stochastic influences to complex diseases, mainly mediated by epigenetics.

Methods: We performed a genome-wide DNA methylation study on whole blood of monozygotic twins from 7 pairs discordant for Pso/PsA using the Infinium Methylation EPIC array (Illumina). MeDiP—qPCR was used to confirm specific signals. Data were replicated in an independent cohort of seven patients with Pso/PsA and 3 healthy controls. Transcriptomic profiling was performed by RNAsequence on the same 7 monozygotic twin pairs.

Results: We identified 2,564 differentially methylated positions between psoriatic disease and controls, corresponding to 1,703 genes, 59% within gene bodies. There were 19 regions with at least two DMPs within 1 kb of distance and significant within-pair Δβ-values (p < 0.005), among them SNX25, BRG1 and SMAD3 genes, all involved in TGF-β signaling pathway, were identified. Co-expression analyses on transcriptome data identified IL-6/JAK/STAT3 and TNF-α pathways as important signaling axes involved in the disease, and they also suggested an altered glucose metabolism in patients’ immune cells, characteristic of pro-inflammatory T lymphocytes.

Conclusion: The study suggests the presence of an epigenetic signature in affected individuals, pointing to genes involved in immunological and inflammatory responses. This result is also supported by transcriptome data, that altogether suggest a higher activation state of the immune system, that could promote the disease status.
Mitochondria in Early Forebrain Development: From Neurulation to Mid-Corticogenesis
Authors: Fame Ryann M. , Lehtinen Maria K.
Published: November 2021

Function of the mature central nervous system (CNS) requires a substantial proportion of the body’s energy consumption. During development, the CNS anlage must maintain its structure and perform stage-specific functions as it proceeds through discrete developmental stages. While key extrinsic signals and internal transcriptional controls over these processes are well appreciated, metabolic and mitochondrial states are also critical to appropriate forebrain development. Specifically, metabolic state, mitochondrial function, and mitochondrial dynamics/localization play critical roles in neurulation and CNS progenitor specification, progenitor proliferation and survival, neurogenesis, neural migration, and neurite outgrowth and synaptogenesis. With the goal of integrating neurodevelopmental biologists and mitochondrial specialists, this review synthesizes data from disparate models and processes to compile and highlight key roles of mitochondria in the early development of the CNS with specific focus on forebrain development and corticogenesis.
Systemic Supplementation of Collagen VI by Neonatal Transplantation of iPSC-Derived MSCs Improves Histological Phenotype and Function of Col6-Deficient Model Mice
Authors: Harada Aya , Goto Megumi , Kato Atsuya , Takenaka-Ninagawa Nana , Tanaka Akito , Noguchi Satoru , Ikeya Makoto , Sakurai Hidetoshi
Published: November 2021

Collagen VI is distributed in the interstitium and is secreted mainly by mesenchymal stromal cells (MSCs) in skeletal muscle. Mutations in COL6A1-3 genes cause a spectrum of COL6-related myopathies. In this study, we performed a systemic transplantation study of human-induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) into neonatal immunodeficient COL6-related myopathy model (Col6a1KO/NSG) mice to validate the therapeutic potential. Engraftment of the donor cells and the resulting rescued collagen VI were observed at the quadriceps and diaphragm after intraperitoneal iMSC transplantation. Transplanted mice showed improvement in pathophysiological characteristics compared with untreated Col6a1KO/NSG mice. In detail, higher muscle regeneration in the transplanted mice resulted in increased muscle weight and enlarged myofibers. Eight-week-old mice showed increased muscle force and performed better in the grip and rotarod tests. Overall, these findings support the concept that systemic iMSC transplantation can be a therapeutic option for COL6-related myopathies.
Performances of Homogeneous and Heterogenized Methylene Blue on Silica Under Red Light in Batch and Continuous Flow Photochemical Reactors
Authors: Lancel Maxime , Gomez Catherine , Port Marc , Amara Zacharias
Published: November 2021

Methylene blue was efficiently immobilized on silica micro- and nanoparticles by electrostatic interactions and the performances of the heterogenized photocatalysts were compared against the homogeneous conditions using the photooxidation of citronellol as a model reaction under red light, in a batch and a continuous flow photochemical reactor. In batch, the heterogeneous photocatalyst outperforms the homogeneous one, presumably due to kinetic and stability effects. The two catalytic systems are also compared in a flow reactor displaying improved mass transfer properties. We demonstrate that this results in a dramatic enhancement in photocatalyst stability, reactivity and productivity. This study highlights the importance of photocatalyst stability under homogeneous versus heterogenized conditions and in batch versus flow photochemistry.
The GW/BSE Method in Magnetic Fields
Authors: Holzer Christof , Pausch Ansgar , Klopper Wim
Published: November 2021

The GW approximation and the Bethe–Salpeter equation have been implemented into the Turbomole program package for computations of molecular systems in a strong, finite magnetic field. Complex-valued London orbitals are used as basis functions to ensure gauge-invariant computational results. The implementation has been benchmarked against triplet excitation energies of 36 small to medium-sized molecules against reference values obtained at the approximate coupled-cluster level (CC2 approximation). Finally, a spectacular change of colour from orange to green of the tetracene molecule is induced by applying magnetic fields between 0 and 9,000 T perpendicular to the molecular plane.
Antibacterial Properties and Mechanism of Lysozyme-Modified ZnO Nanoparticles
Authors: Yuan Kangrui , Liu Xiaoliu , Shi Jianxin , Liu Wei , Liu Kun , Lu Hongmei , Wu Dudu , Chen Zhi , Lu Chengyu
Published: December 2021

The lysozyme-modified nanoparticles (LY@ZnO NPs) were synthesized by the reduction–oxidation method, and the morphology and structure of LY@ZnO were analyzed by Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), scanning electron microsclope (SEM), and particle size analysis. The antibacterial effects of LY@ZnO against Escherichia coli (E. coli, Gram-negative bacteria) and Staphylococcus aureus (S. aureus, Gram-positive bacteria) were discussed by measuring the zone of inhibition (ZOI) and growth inhibition. The antimicrobial experiments showed that the LY@ZnO NPs possessed better antibacterial activity than ZnO. Besides, the antibacterial mechanism of LY@ZnO was also investigated, which was attributed to the generation of reactive oxygen species (ROS). Furthermore, the toxicities of LY@ZnO in vivo and in vitro were discussed by the cell counting kit-8 method and animal experiments, showing that LY@ZnO possessed excellent biocompatibility. Finally, the therapeutic effect of LY@ZnO on a rat skin infection model caused by methicillin-resistant Staphylococcus aureus (MRSA) was also studied, which exhibited good anti-infective activity. Our findings showed that LY@ZnO possessed remarkable antibacterial ability due to its excellent membrane permeability and small particle size. Besides, LY@ZnO also exhibited certain stability and great safety, which showed tremendous prospects for microbial infection in patients. It would also be helpful for a better understanding of the enzyme-modified nanomaterials against bacteria.
A Novel Conductive Antibacterial Nanocomposite Hydrogel Dressing for Healing of Severely Infected Wounds
Authors: Xiao Lizhi , Hui Fang , Tian Tenghui , Yan Ruyue , Xin Jingwei , Zhao Xinyu , Jiang Yingnan , Zhang Zhe , Kuang Yulan , Li Na , Zhao Yu , Lin Quan
Published: November 2021

Wound infections are serious medical complications that can endanger human health. Latest researches show that conductive composite materials may make endogenous/exogenous electrical stimulation more effective, guide/comb cell migration to the wound, and subsequently promote wound healing. To accelerate infected wound healing, a novel medical silver nanoparticle-doped conductive polymer-based hydrogel system (Ag NPs/CPH) dressing with good conductivity, biocompatibility, and mechanical and antibacterial properties was fabricated. For the hydrogel dressing, Ag NPs/CPH, polyvinyl alcohol (PVA), and gelatin were used as the host matrix materials, and phytic acid (PA) was used as the cross-linking agent to introduce conductive polyaniline into the matrix, with antibacterial Ag NPs loaded via impregnation. After a series of analyses, the material containing 5 wt% of PVA by concentration, 1.5 wt% gelatin, 600 μL of AN reactive volume, and 600 μL of PA reactive volume was chosen for Ag NPs/CPH preparation. XPS and FTIR analysis had been further used to characterize the composition of the prepared Ag NPs/CPH. The test on the swelling property showed that the hydrogels had abundant pores with good water absorption (≈140% within 12 h). They can be loaded and continuously release Ag NPs. Thus, the prepared Ag NPs/CPH showed excellent antibacterial property with increasing duration of immersion of Ag NPs. Additionally, to evaluate in vivo safety, CCK-8 experiments of HaCat, LO2 and 293T cells were treated with different concentrations of the Ag NPs/CPH hydrogel soaking solution. The experimental results showed the Ag NPs/CPH had no significant inhibitory effect on any of the cells. Finally, an innovative infection and inflammation model was designed to evaluate the prepared Ag NPs/CPH hydrogel dressing for the treatment of severely infected wounds. The results showed that even when infected with bacteria for long periods of time (more than 20 h), the proposed conductive antibacterial hydrogel could treat severely infected wounds.
A Predictive Model Based on the Gut Microbiota Improves the Diagnostic Effect in Patients With Cholangiocarcinoma
Authors: Zhang Tan , Zhang Sina , Jin Chen , Lin Zixia , Deng Tuo , Xie Xiaozai , Deng Liming , Li Xueyan , Ma Jun , Ding Xiwei , Liu Yaming , Shan Yunfeng , Yu Zhengping , Wang Yi , Chen Gang , Li Jialiang
Published: November 2021

Cholangiocarcinoma (CCA) is a malignant hepatic tumor with a poor prognosis, which needs early diagnosis urgently. The gut microbiota has been shown to play a crucial role in the progression of liver cancer. Here, we explored a gut microbiota model covering genera Burkholderia-Caballeronia-Paraburkholderia, Faecalibacterium, and Ruminococcus_1 (B-F-R) for CCA early diagnosis. A case-control study was conducted to enroll 53 CCA patients, 47 cholelithiasis patients, and 40 healthy controls. The feces samples and clinical information of participants were collected in the same period. The gut microbiota and its diversity of individuals were accessed with 16S rDNA sequencing, and the gut microbiota profile was evaluated according to microbiota diversity. Finally, four enriched genera in the CCA group (genera Bacteroides, Muribaculaceae_unclassified, Muribaculum, and Alistipes) and eight enriched genera in the cholelithiasis group (genera Bifidobacterium, Streptococcus, Agathobacter, Ruminococcus_gnavus_group, Faecalibacterium, Subdoligranulum, Collinsella, Escherichia-Shigella) constitute an overall different microbial community composition (P = 0.001). The B-F-R genera model with better diagnostic value than carbohydrate antigen 19-9 (CA19-9) was identified by random forest and Statistical Analysis of Metagenomic Profiles (STAMP) to distinguish CCA patients from healthy controls [area under the curve (AUC) = 0.973, 95% CI = 0.932–1.0]. Moreover, the correlative analysis found that genera Burkholderia-Caballeronia-Paraburkholderia were positively correlated with body mass index (BMI). The significantly different microbiomes between cholelithiasis and CCA were found via principal coordinates analysis (PCoA) and linear discriminant analysis effect size (LEfSe), and Venn diagram and LEfSe were utilized to identify four genera by comparing microbial compositions among patients with malignant obstructive jaundice (MOJ-Y) or not (MOJ-N). In brief, our findings suggest that gut microbiota vary from benign and malignant hepatobiliary diseases to healthy people and provide evidence supporting gut microbiota to be a non-invasive biomarker for the early diagnosis of CCA.
Roles of Gut Bacteriophages in the Pathogenesis and Treatment of Inflammatory Bowel Disease
Authors: Qv Lingling , Mao Sunbing , Li Yongjun , Zhang Jia , Li Lanjuan
Published: December 2021

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, are chronic, relapsing intestinal inflammatory disorders. Although the molecular mechanisms governing the pathogenesis of IBD are not completely clear, the main factors are presumed to be a complex interaction between genetic predisposition, host immune response and environmental exposure, especially the intestinal microbiome. Currently, most studies have focused on the role of gut bacteria in the onset and development of IBD, whereas little attention has been paid to the enteroviruses. Among of them, viruses that infect prokaryotes, called bacteriophages (phages) occupy the majority (90%) in population. Moreover, several recent studies have reported the capability of regulating the bacterial population in the gut, and the direct and indirect influence on host immune response. The present review highlights the roles of gut phages in IBD pathogenesis and explores the potentiality of phages as a therapeutic target for IBD treatment.
Virulence Determinants and Plasmid-Mediated Colistin Resistance mcr Genes in Gram-Negative Bacteria Isolated From Bovine Milk
Authors: Tartor Yasmine H. , Gharieb Rasha M. A. , Abd El-Aziz Norhan K. , El Damaty Hend M. , Enany Shymaa , Khalifa Eman , Attia Amira S. A. , Abdellatif Samah S. , Ramadan Hazem
Published: November 2021

A major increase of bacterial resistance to colistin, a last-resort treatment for severe infections, was observed globally. Using colistin in livestock rearing is believed to be the ground of mobilized colistin resistance (mcr) gene circulation and is of crucial concern to public health. This study aimed to determine the frequency and virulence characteristics of colistin-resistant Gram-negative bacteria from the milk of mastitic cows and raw unpasteurized milk in Egypt. One hundred and seventeen strains belonging to Enterobacteriaceae (n = 90), Pseudomonas aeruginosa (n = 10), and Aeromonas hydrophila (n = 17) were screened for colistin resistance by antimicrobial susceptibility testing. The genetic characteristics of colistin-resistant strains were investigated for mcr-1–9 genes, phylogenetic groups, and virulence genes. Moreover, we evaluated four commonly used biocides in dairy farms for teat disinfection toward colistin-resistant strains. Multidrug-resistant (MDR) and extensive drug-resistant (XDR) phenotypes were detected in 82.91% (97/117) and 3.42% (4/117) of the isolates, respectively. Of the 117 tested isolates, 61 (52.14%) were colistin resistant (MIC >2 mg/L), distributed as 24/70 (34.29%) from clinical mastitis, 10/11 (90.91%) from subclinical mastitis, and 27/36 (75%) from raw milk. Of these 61 colistin-resistant isolates, 47 (19 from clinical mastitis, 8 from subclinical mastitis, and 20 from raw milk) harbored plasmid-borne mcr genes. The mcr-1 gene was identified in 31.91%, mcr-2 in 29.79%, mcr-3 in 34.04%, and each of mcr-4 and mcr-7 in 2.13% of the colistin-resistant isolates. Among these isolates, 42.55% (20/47) were E. coli, 21.28% (10/47) A. hydrophila, 19.12% (9/47) K. pneumoniae, and 17.02% (8/47) P. aeruginosa. This is the first report of mcr-3 and mcr-7 in P. aeruginosa. Conjugation experiments using the broth-mating technique showed successful transfer of colistin resistance to E. coli J53-recipient strain. Different combinations of virulence genes were observed among colistin-resistant isolates with almost all isolates harboring genes. Hydrogen peroxide has the best efficiency against all bacterial isolates even at a low concentration (10%). In conclusion, the dissemination of mobile colistin resistance mcr gene and its variants between MDR- and XDR-virulent Gram-negative isolates from dairy cattle confirms the spread of mcr genes at all levels; animals, humans, and environmental, and heralds the penetration of the last-resort antimicrobial against MDR bacteria. Consequently, a decision to ban colistin in food animals is urgently required to fight XDR and MDR bacteria.
Oxidative Stress and Pathogenesis in Malaria
Authors: Vasquez Marilyn , Zuniga Marisol , Rodriguez Ana
Published: December 2021

Malaria is a highly inflammatory and oxidative disease. The production of reactive oxygen species by host phagocytes is an essential component of the host response to Plasmodium infection. Moreover, host oxidative enzymes, such as xanthine oxidase, are upregulated in malaria patients. Although increased production of reactive oxygen species contributes to the clearance of the parasite, excessive amounts of these free radicals can mediate inflammation and cause extensive damage to host cells and tissues, probably contributing to severe pathologies. Plasmodium has a variety of antioxidant enzymes that allow it to survive amidst this oxidative onslaught. However, parasitic degradation of hemoglobin within the infected red blood cell generates free heme, which is released at the end of the replication cycle, further aggravating the oxidative burden on the host and possibly contributing to the severity of life-threatening malarial complications. Additionally, the highly inflammatory response to malaria contributes to exacerbate the oxidative response. In this review, we discuss host and parasite-derived sources of oxidative stress that may promote severe disease in P. falciparum infection. Therapeutics that restore and maintain oxidative balance in malaria patients may be useful in preventing lethal complications of this disease.
Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism
Authors: Sharma Surendra Raj , Crispell Gary , Mohamed Ahmed , Cox Cameron , Lange Joshua , Choudhary Shailesh , Commins Scott P. , Karim Shahid
Published: December 2021

Alpha-Gal Syndrome (AGS) is an IgE-mediated delayed-type hypersensitivity reaction to the oligosaccharide galactose-α-1, 3-galactose (α-gal) injected into humans from the lone-star tick (Amblyomma americanum) bite. Indeed, α-gal is discovered in salivary glands of lone-star tick; however, the tick’s specific intrinsic factors involved in endogenous α-gal production and presentation to host during hematophagy are poorly understood. This study aimed to investigate the functional role of two tick enzymes, α-D-galactosidase (ADGal) and β-1,4 galactosyltransferases (β-1,4GalT), in endogenous α-gal production, carbohydrate metabolism, and N-glycan profile in lone-star tick. The ADGal enzyme cleaves terminal α-galactose moieties from glycoproteins and glycolipids, whereas β-1,4GalT transfers α-galactose to a β1,4 terminal linkage acceptor sugars—GlcNAc, Glc, and Xyl—in various processes of glycoconjugate synthesis. An RNA interference approach was utilized to silence ADGal and β-1,4GalT in Am. americanum to examine their function in α-gal metabolism in tick and AGS onset. Silencing of ADGal led to the significant downregulation of genes involved in galactose metabolism and transport in Am. americanum. Immunoblot and N-glycan analysis of the Am. americanum salivary glands showed a significant reduction in α-gal levels in silenced tissues. However, there was no significant difference in the level of α-gal in β-1,4GalT-silenced tick salivary glands. A basophil-activation test showed a decrease in the frequency of activated basophil by ADGal-silenced salivary glands. These results provide an insight into the roles of ADGal and β-1,4GalT in α-gal production and presentation in ticks and the probable involvement in the onset of AGS.
Assessing African Vultures as Biomonitors and Umbrella Species
Authors: Thompson Lindy J. , Krüger Sonja C. , Coverdale Brent M. , Shaffer L. Jen , Ottinger Mary Ann , Davies John P. , Daboné Clément , Kibuule Micheal , Cherkaoui S. Imad , Garbett Rebecca A. , Phipps W. Louis , Buechley Evan R. , Godino Ruiz Alfonso , Lecoq Miguel , Carneiro Camilo , Harrell Reginal M. , Gore Meredith L. , Bowerman William W.
Published: November 2021

African vulture populations are rapidly declining, yet funding and other resources available for their conservation are limited. Improving our understanding of which African vulture species could best serve as an umbrella species for the entire suite of African vultures could help conservationists save time, money, and resources by focusing their efforts on a single vulture species. Furthermore, improving our understanding of the suitability of African vultures as biomonitors for detecting environmental toxins could help conservation authorities to detect changes in ecosystem health. We used a systematic approach based on criteria selected a priori to objectively evaluate the potential of each of the 10 resident African vulture species as (i) an umbrella species for all of the African vulture species, and (ii) an avian biomonitor. For each criterion, we scored the respective African vulture species and summed the scores to determine which species was best suited as an umbrella species and as an avian biomonitor. Our results showed that, overall, certain aspects of vulture ecology (large population sizes, large body sizes, long lifespans, and their ability to be monitored over numerous seasons) support their suitability as biomonitors, while other ecological traits, including their diets and the public's perceptions of vultures, could diminish their suitability. The White-backed Vulture (Gyps africanus) was the best fit of the 10 vulture species in our assessment as both an avian biomonitor and an umbrella species for all African vulture species. Meanwhile, significant knowledge gaps for other species inhibit their utility as biomonitors. Due to their large home-range sizes, African vultures may only be useful as biomonitors at a regional scale. However, there could be value in using the White-backed Vulture as an umbrella species, as an aid to conserve the entire suite of African vulture species.
Steller Sea Lion (Eumetopias jubatus) Response to Non-lethal Hazing at Bonneville Dam
Authors: Tidwell Kyle S. , Carrothers Brett A. , Blumstein Daniel T. , Schakner Zachary A.
Published: December 2021

Protected Steller sea lions (Eumetopias jubatus) aggregate at Bonneville Dam on the Columbia River and prey upon multiple species of endangered salmon ascending the river. Hazing is a non-lethal activity designed to repel sea lions that includes aversive auditory and physical stimuli to deter animals from an area and has been employed with sea lion—fisheries interactions for more than 40 years but sea lion responses to hazing through time is not well-documented. We observed the behavior of Steller sea lions in periods with and without hazing during two spring Chinook salmon passage seasons to evaluate: (1) what effect hazing had on the number of animals present and their foraging behavior, and (2) whether they habituated to hazing. We found that hazing temporarily reduced the number of Steller sea lions, but only when actively hazed. During hazing, Steller sea lions were more likely to move away from hazers on the dam, decreased their foraging, and increased their time investigating the environment. However, these effects were temporary; their behavior returned to initial observation levels once hazing ceased. Furthermore, their responsiveness to hazing declined throughout the season, indicating habituation and raising concern for the application and long-term efficacy of hazing in managing predation on endangered salmon.
Improving the Stability and Activity of Arginine Decarboxylase at Alkaline pH for the Production of Agmatine
Authors: Hong Eun Young , Lee Sun-Gu , Yun Hyungdon , Kim Byung-Gee
Published: November 2021

Agmatine, involved in various modulatory actions in cellular mechanisms, is produced from arginine (Arg) by decarboxylation reaction using arginine decarboxylase (ADC, EC 4.1.1.19). The major obstacle of using wild-type Escherichia coli ADC (ADCes) in agmatine production is its sharp activity loss and instability at alkaline pH. Here, to overcome this problem, a new disulfide bond was rationally introduced in the decameric interface region of the enzyme. Among the mutants generated, W16C/D43C increased both thermostability and activity. The half-life (T1/2) of W16C/D43C at pH 8.0 and 60°C was 560 min, which was 280-fold longer than that of the wild-type, and the specific activity at pH 8.0 also increased 2.1-fold. Site-saturation mutagenesis was subsequently performed at the active site residues of ADCes using the disulfide-bond mutant (W16C/D43C) as a template. The best variant W16C/D43C/I258A displayed a 4.4-fold increase in the catalytic efficiency when compared with the wild-type. The final mutant (W16C/D43C/I258A) was successfully applied to in vitro synthesis of agmatine with an improved yield and productivity (>89.0% yield based on 100 mM of Arg within 5  h).