bluuebunny/crossref_metadata_2025 huggingface dataset:
Crosstalk Communications Between Islets Cells and Insulin Target Tissue: The Hidden Face of Iceberg
Authors: Langlois Allan , Dumond Aurore , Vion Julie , Pinget Michel , Bouzakri Karim
Published: February 2022

The regulation of insulin secretion is under control of a complex inter-organ/cells crosstalk involving various metabolites and/or physical connections. In this review, we try to illustrate with current knowledge how β-cells communicate with other cell types and organs in physiological and pathological contexts. Moreover, this review will provide a better understanding of the microenvironment and of the context in which β-cells exist and how this can influence their survival and function. Recent studies showed that β-cell insulin secretion is regulated also by a direct and indirect inter-organ/inter-cellular communication involving various factors, illustrating the idea of “the hidden face of the iceberg”. Moreover, any disruption on the physiological communication between β-cells and other cells or organs can participate on diabetes onset. Therefore, for new anti-diabetic treatments’ development, it is necessary to consider the entire network of cells and organs involved in the regulation of β-cellular function and no longer just β-cell or pancreatic islet alone. In this context, we discuss here the intra-islet communication, the β-cell/skeletal muscle, β-cell/adipose tissue and β-cell/liver cross talk.
Decarbonization, Environmental Regulation, and Economic Boom: An Indicator Assessment Based on the Industrial Waste
Authors: Yang Liu , Ma Zhili , Ma Minda , Xu Yang
Published: February 2022

Energy-based economic development brings about some environmental problems, and as China’s economy shifts from rapid growth to high-quality development, the implementation of environmental regulation is crucial to achieving environmental protection and high-quality economic development. Based on the panel data of 14 prefectures and cities from 2000 to 2018 in Xinjiang, this study explored the impact of environmental regulation on high-quality economic development by constructing a comprehensive evaluation index system and using entropy method and Tobit regression model. The results show that 1) overall, each 1% increase in environmental regulation is associated with a 0.037% rise in high-quality economic development level; 2) regionally, each 1% increase in environmental regulation is associated with a 0.119% rise in high-quality economic development level in northern Xinjiang, but the effect on the southern Xinjiang is not significant; 3) each 1% increase in environmental regulation, the level of high-quality economic development decreased by 0.034% from 2000 to 2010 and increased by 0.061% from 2011 to 2018. In general, this study adds to the theoretical and empirical study on the influence of environmental regulation on high-quality economic development while providing a methodology for other economies to assess the relationship between the two.
Factor Mobility, Industrial Transfer and Industrial Carbon Emission: A Spatial Matching Perspective
Authors: Zheng Xiao , Yu Hong , Yang Lin
Published: February 2022

This paper proposes a dynamic industrial transfer index for the first time to characterize the spatial matchability of factor mobility and industrial transfer, and then explores the correlation between factor mobility, industrial transfer and industrial carbon emission intensity by using panel data from 30 provinces in China during 2004–2019. The results show that China’s ability to reduce carbon emissions is improving, and the intensity of industrial carbon emission has dropped by 44.84%. In addition, there is an obvious spatial mismatch between factor mobility and industrial transfer. Specifically, production factors generally flow from high-carbon emission intensity areas to low-carbon emission intensity areas, while the direction of industrial transfer is generally opposite to that of factor mobility. And the empirical analysis finds that the interaction between factor mobility and industrial transfer will affect the carbon reduction. If the direction of capital mobility is the same as that of capital-intensive industries, it is unfavorable to the carbon emission reduction. While the carbon reduction effect will be enhanced if the directions of labor and technology mobility are consistent with those of labor-intensive and technology-intensive industrial transfer, respectively. Finally, based on the findings, some recommendations are provided for governments to formulate policies.
Chemosensory Receptors in the Larval Maxilla of Papilio hospiton
Authors: Crava Cristina M. , Bobkov Yuriy V. , Sollai Giorgia , Anfora Gianfranco , Crnjar Roberto , Cattaneo Alberto Maria
Published: February 2022

Among the butterflies of the genus Papilio (Lepidoptera: Papilionidae), Papilio hospiton (Géné) has a geographical distribution limited to the Mediterranean islands of Sardinia (Italy) and Corsica (France). This is mainly due to the host range that includes only a few plant species of Apiaceae and Rutaceae growing on these islands. In a previous electrophysiological investigation conducted on the maxillary gustatory system of larvae of P. hospiton and its closely phylogenetically related species Papilio machaon, a significantly higher spike activity was shown for the gustatory neurons of lateral and medial styloconic sensilla in P. hospiton when bitter compounds were tested. This effect was possibly correlated to the limited host choice range for P. hospiton. To shed light on the molecular aspects of this phenomenon, we investigated the expression pattern of sensory-related sequences by conducting a transcriptomic analysis from total RNA isolates of P. hospiton larval maxillae. We identified several transcripts that may be involved in taste (one gustatory receptor, one divergent ionotropic receptor, and several transient receptor potential channels, TRPs) as well as transcripts supporting an olfactory function for this appendage, including odorant receptors (ORs), antennal ionotropic receptors (A-IRs), sensory neuron membrane proteins (SNMPs), and odorant-binding proteins (OBPs). We used Human Embryonic Kidney (HEK293A) cells to heterologously express two of the identified receptors, PhospOR1 and PhospPain, together with their orthologs from P. machaon, for functional characterization. While our data suggest no activation of these two receptors by the ligands known so far to activate the electrophysiological response in larval maxillary neurons of Papilio species, nor temperature activation of both Papilio TRPA-channel Painless, they represent the first attempt in connecting neuronal activity with their molecular bases to unravel diet specialization between closely related Papilio species.
Towards Personalized 3D Augmented Reality Windshield Displays in the Context of Automated Driving
Authors: Riegler Andreas , Riener Andreas , Holzmann Clemens
Published: February 2022

As vehicle automation advances, drivers of automated vehicles become more disengaged from the primary driving task. Windshield displays provide a large screen space supporting drivers in non-driving related activities. This article presents user preferences as well as task and safety issues for 3D augmented reality windshield displays in automated driving. Participants of a user study (n = 24) customized two modes of content presentation (multiple content-specific windows vs. one main window), and could freely adjust visual parameters for these content windows using a simulated “ideal” windshield display in a virtual reality driving simulator. We found that user preferences differ with respect to contextual aspects. Additionally, using one main content window resulted in better task performance and lower take-over times, but the subjective user experience was higher for the multi-window user interface. These findings help automotive interface designers to improve experiences in automated vehicles.
Case Report: Twin Pregnancy Gives Birth to a Girl with Partial Trisomy 21 Mosaicism after in vitro Fertilization and Embryo Transfer
Authors: Guo Zhenglong , Kang Bing , Wu Dong , Xiao Hai , Hao Leilei , Hao Bingtao , Liao Shixiu
Published: February 2022

Objective: To report a rare case in which an IVF-ET twin pregnancy gave birth to a partial trisomy 21 chimera girl.

Design: Case report.

Setting: University hospital.

Patient: A girl with partial trisomy 21 mosaicism after in vitro fertilization and embryo transfer.

Interventions:In vitro fertilization (IVF) and embryo transfer (ET).

Main Outcome Measure: Karyotype analysis, Copy Number Variation sequencing (CNV-seq), stLFR-WGS, and Short Tandem Repeat (STR) analysis.

Results: Being assisted with IVF and EF technology, the couple successfully gave birth to twin sisters at 37 weeks of gestational age. The NonInvasive Prenatal Testing (NIPT) and Nuchal Translucency (NT) examination showed no detectable genetic abnormalities during pregnancy. However, the younger infant displayed growth retardation and feeding difficulties after birth, which was not observed in her twin sister. Further genetic counseling and diagnosis suggested that she is a Chimera with complex partial trisomy 21. The stLFR-WGS assay showed multiple CNV variations in Chr21 and STR analysis confirmed the paternal origin of the additional fragments.

Conclusion: It is rare for IVF-ET-assisted twin pregnancy to give birth to a girl with a complex combination of abnormal Chr21, which might result from paternal chromosome rearrangement during meiosis and mitosis.
Expression and Clinical Correlation Analysis Between Repulsive Guidance Molecule a and Neuromyelitis Optica Spectrum Disorders
Authors: Tang Jinhua , Zeng Xiaopeng , Yang Jun , Zhang Lei , Li Hang , Chen Rui , Tang Shi , Luo Yetao , Qin Xinyue , Feng Jinzhou
Published: February 2022

Objectives

This study sought to explore the expression patterns of repulsive guidance molecules a (RGMa) in neuromyelitis optica spectrum disorders (NMOSD) and to explore the correlation between RGMa and the clinical features of NMOSD.

Methods

A total of 83 NMOSD patients and 22 age-matched healthy controls (HCs) were enrolled in the study from October 2017 to November 2021. Clinical parameters, including Expanded Disability Status Scale (EDSS) score, degree of MRI enhancement, and AQP4 titer were collected. The expression of serum RGMa was measured by enzyme-linked immunosorbent assay (ELISA) and compared across the four patient groups. The correlation between serum RGMa levels and different clinical parameters was also assessed.

Results

The average serum expression of RGMa in the NMOSD group was significantly higher than that in the HC group (p < 0.001). Among the patient groups, the acute phase group exhibited significantly higher serum RGMa levels than did the remission group (p < 0.001). A multivariate analysis revealed a significant positive correlation between RGMa expression and EDSS score at admission, degree of MRI enhancement, and segmental length of spinal cord lesions. There was a significant negative correlation between the expression of RGMa in NMOSD and the time from attack to sampling or delta EDSS.

Conclusions

The current study suggests that RGMa may be considered a potential biomarker predicting the severity, disability, and clinical features of NMOSD.
Population-Based Incidence of Guillain-Barré Syndrome During Mass Immunization With Viral Vaccines: A Pooled Analysis
Authors: Wang Fengge , Wang Donglan , Wang Yingjie , Li Cancan , Zheng Yulu , Guo Zheng , Liu Pengcheng , Zhang Yichun , Wang Wei , Wang Youxin , Hou Haifeng
Published: February 2022

Misunderstanding temporal coincidence of adverse events during mass vaccination and invalid assessment of possible safety concerns have negative effects on immunization programs, leading to low immunization coverage. We conducted this systematic review and meta-analysis to identify the incidence rates of GBS that are temporally associated with viral vaccine administration but might not be attributable to the vaccines. By literature search in Embase and PubMed, we included 48 publications and 2,110,441,600 participants. The pooled incidence rate of GBS was 3.09 per million persons (95% confidence interval [CI]: 2.67 to 3.51) within six weeks of vaccination, equally 2.47 per 100,000 person-year (95%CI: 2.14 to 2.81). Subgroup analyses illustrated that the pooled rates were 2.77 per million persons (95%CI: 2.47 to 3.07) for individuals who received the influenza vaccine and 2.44 per million persons (95%CI: 0.97 to 3.91) for human papillomavirus (HPV) vaccines, respectively. Our findings evidence the GBS-associated safety of virus vaccines. We present a reference for the evaluation of post-vaccination GBS rates in mass immunization campaigns, including the SARS-CoV-2 vaccine.
Roles of HLA-G/KIR2DL4 in Breast Cancer Immune Microenvironment
Authors: Zheng Guoxu , Jia Lintao , Yang An-Gang
Published: February 2022

Human leukocyte antigen (HLA)-G is a nonclassical MHC Class I molecule, which was initially reported as a mediator of immune tolerance when expressed in extravillous trophoblast cells at the maternal-fetal interface. HLA-G is the only known ligand of killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4), an atypical family molecule that is widely expressed on the surface of NK cells. Unlike other KIR receptors, KIR2DL4 contains both an arginine–tyrosine activation motif in its transmembrane region and an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail, suggesting that KIR2DL4 may function as an activating or inhibitory receptor. The immunosuppressive microenvironment exemplified by a rewired cytokine network and upregulated immune checkpoint proteins is a hallmark of advanced and therapy-refractory tumors. Accumulating evidence has shown that HLA-G is an immune checkpoint molecule with specific relevance in cancer immune escape, although the role of HLA-G/KIR2DL4 in antitumor immunity is still uncharacterized. Our previous study had shown that HLA-G was a pivotal mediator of breast cancer resistance to trastuzumab, and blockade of the HLA-G/KIR2DL4 interaction can resensitize breast cancer to trastuzumab treatment. In this review, we aim to summarize and discuss the role of HLA-G/KIR2DL4 in the immune microenvironment of breast cancer. A better understanding of HLA-G is beneficial to identifying novel biomarker(s) for breast cancer, which is important for precision diagnosis and prognostic assessment. In addition, it is also necessary to unravel the mechanisms underlying HLA-G/KIR2DL4 regulation of the immune microenvironment in breast cancer, hopefully providing a rationale for combined HLA-G and immune checkpoints targeting for the effective treatment of breast cancer.
Extracellular Vesicles in Transplantation
Authors: Sailliet Nicolas , Ullah Matti , Dupuy Amandine , Silva Amanda K. A. , Gazeau Florence , Le Mai Hoa , Brouard Sophie
Published: February 2022

Extracellular vesicles (EVs) have been extensively studied in the last two decades. It is now well documented that they can actively participate in the activation or regulation of immune system functions through different mechanisms, the most studied of which include protein–protein interactions and miRNA transfers. The functional diversity of EV-secreting cells makes EVs potential targets for immunotherapies through immune cell-derived EV functions. They are also a potential source of biomarkers of graft rejection through donor cells or graft environment-derived EV content modification. This review focuses on preclinical studies that describe the role of EVs from different cell types in immune suppression and graft tolerance and on the search for biomarkers of rejection.
Monitoring Pre- and Post-Operative Immune Alterations in Patients With Locoregional Colorectal Cancer Who Underwent Laparoscopy by Single-Cell Mass Cytometry
Authors: Zhou Chuanyong , Wang Zaozao , Jiang Beihai , Di Jiabo , Su Xiangqian
Published: February 2022

Surgical excision is currently the principal therapy for locoregional colorectal cancer (CRC). However, surgical trauma leads to controlled tissue damage, causing profound alterations in host immunity and, in turn, affecting post-operative outcomes. Surgery-induced immune alterations in CRC remain poorly defined. Here, single-cell mass cytometry was applied to serial blood samples collected pre-operatively, and on days 1, 3, and 7 post-operatively from 24 patients who underwent laparoscopic surgical resection of CRC to comprehensively monitor the perioperative phenotypic alterations in immune cells and dynamics of immune response. Characterization of immune cell subsets revealed that the post-operative immune response is broad but predominantly suppressive, supported by the decreases in total frequencies of circulating T cells and natural killer (NK) cells, as well as decreased HLA-DR expression on circulating monocytes. The proportion of T cells significantly decreased on day 1 and recovered to the pre-surgical level on day 3 after surgery. The frequency of monocytes was significantly elevated on day 1 after surgery and declined to baseline level on day 3. NK cells temporarily contracted on post-operative day 3. T cells, monocytes, DCs, NK cells, and B cells were partitioned into phenotypically different single-cell clusters. The dynamics of single-cell clusters were different from those of the bulk lineages. T cell clusters in the same response phase fluctuate inconsistently during the perioperative period. Comparing to the baseline levels, the frequencies of CD11b(+)CD33(+)CD14(+)CD16(−) classical monocytes expanded followed by contraction, whereas CD11b(+)CD33(+)CD14(high)CD16(low) intermediate monocytes remained unchanged; HLA-DR expression in monocytes were significantly reduced; the frequencies of intermediate CD56(bright)CD16(+) NK cell subsets increased; and the percentage of memory B lymphocytes were elevated after surgery. Post-operative pro- and anti-inflammatory cytokines were both altered. Furthermore, perioperative immune perturbations in some of the cell subsets were unrecovered within seven days after surgery. Chronological monitoring major immune lineages provided an overview of surgery-caused alterations, including cell augments and contractions and precisely timed changes in immune cell distribution in both innate and adaptive compartments, providing evidence for the interaction between tumor resection and immune modulation.
The Human Leukocyte Antigen G as an Immune Escape Mechanism and Novel Therapeutic Target in Urological Tumors
Authors: Jasinski-Bergner Simon , Eckstein Markus , Taubert Helge , Wach Sven , Fiebig Christian , Strick Reiner , Hartmann Arndt , Seliger Barbara
Published: February 2022

The non-classical human leukocyte antigen G (HLA-G) is a potent regulatory protein involved in the induction of immunological tolerance. This is based on the binding of membrane-bound as well as soluble HLA-G to inhibitory receptors expressed on various immune effector cells, in particular NK cells and T cells, leading to their attenuated functions. Despite its restricted expression on immune-privileged tissues under physiological conditions, HLA-G expression has been frequently detected in solid and hematopoietic malignancies including urological cancers, such as renal cell and urothelial bladder carcinoma and has been associated with progression of urological cancers and poor outcome of patients: HLA-G expression protects tumor cells from anti-tumor immunity upon interaction with its inhibitory receptors by modulating both the phenotype and function of immune cells leading to immune evasion. This review will discuss the expression, regulation, functional and clinical relevance of HLA-G expression in urological tumors as well as its use as a putative biomarker and/or potential therapeutic target for the treatment of renal cell carcinoma as well as urothelial bladder cancer.
Platelets as Key Factors in Inflammation: Focus on CD40L/CD40
Authors: Cognasse Fabrice , Duchez Anne Claire , Audoux Estelle , Ebermeyer Theo , Arthaud Charles Antoine , Prier Amelie , Eyraud Marie Ange , Mismetti Patrick , Garraud Olivier , Bertoletti Laurent , Hamzeh-Cognasse Hind
Published: February 2022

Platelets are anucleate cytoplasmic fragments derived from the fragmentation of medullary megakaryocytes. Activated platelets adhere to the damaged endothelium by means of glycoproteins on their surface, forming the platelet plug. Activated platelets can also secrete the contents of their granules, notably the growth factors contained in the α-granules, which are involved in platelet aggregation and maintain endothelial activation, but also contribute to vascular repair and angiogenesis. Platelets also have a major inflammatory and immune function in antibacterial defence, essentially through their Toll-like Receptors (TLRs) and Sialic acid-binding immunoglobulin-type lectin (SIGLEC). Platelet activation also contributes to the extensive release of anti- or pro-inflammatory mediators such as IL-1β, RANTES (Regulated on Activation, Normal T Expressed and Secreted) or CD154, also known as the CD40-ligand. Platelets are involved in the direct activation of immune cells, polynuclear neutrophils (PNNs) and dendritic cells via the CD40L/CD40 complex. As a general rule, all of the studies presented in this review show that platelets are capable of covering most of the stages of inflammation, primarily through the CD40L/CD40 interaction, thus confirming their own role in this pathophysiological condition.
Single-Cell Sequencing Facilitates Elucidation of HIV Immunopathogenesis: A Review of Current Literature
Authors: Zaongo Silvere D. , Harypursat Vijay , Chen Yaokai
Published: February 2022

Knowledge gaps remain in the understanding of HIV disease establishment and progression. Scientists continue to strive in their endeavor to elucidate the precise underlying immunopathogenic mechanisms of HIV-related disease, in order to identify possible preventive and therapeutic targets. A useful tool in the quest to reveal some of the enigmas related to HIV infection and disease is the single-cell sequencing (scRNA-seq) technique. With its proven capacity to elucidate critical processes in cell formation and differentiation, to decipher critical hematopoietic pathways, and to understand the regulatory gene networks that predict immune function, scRNA-seq is further considered to be a potentially useful tool to explore HIV immunopathogenesis. In this article, we provide an overview of single-cell sequencing platforms, before delving into research findings gleaned from the use of single cell sequencing in HIV research, as published in recent literature. Finally, we describe two important avenues of research that we believe should be further investigated using the single-cell sequencing technique.
The Emerging Role of Bile Acids in the Pathogenesis of Inflammatory Bowel Disease
Authors: Thomas John P. , Modos Dezso , Rushbrook Simon M. , Powell Nick , Korcsmaros Tamas
Published: February 2022

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory disorder of the gastrointestinal tract that arises due to complex interactions between host genetic risk factors, environmental factors, and a dysbiotic gut microbiota. Although metagenomic approaches have attempted to characterise the dysbiosis occurring in IBD, the precise mechanistic pathways interlinking the gut microbiota and the intestinal mucosa are still yet to be unravelled. To deconvolute these complex interactions, a more reductionist approach involving microbial metabolites has been suggested. Bile acids have emerged as a key class of microbiota-associated metabolites that are perturbed in IBD patients. In recent years, metabolomics studies have revealed a consistent defect in bile acid metabolism with an increase in primary bile acids and a reduction in secondary bile acids in IBD patients. This review explores the evolving evidence that specific bile acid metabolites interact with intestinal epithelial and immune cells to contribute to the inflammatory milieu seen in IBD. Furthermore, we summarise evidence linking bile acids with intracellular pathways that are known to be relevant in IBD including autophagy, apoptosis, and the inflammasome pathway. Finally, we discuss how novel experimental and bioinformatics approaches could further advance our understanding of the role of bile acids and inform novel therapeutic strategies in IBD.
Diatoms Versus Copepods: Could Frustule Traits Have a Role in Avoiding Predation?
Authors: Petrucciani Alessandra , Chaerle Peter , Norici Alessandra
Published: February 2022

Predation is one of the strongest selection pressures phytoplankton has evolved strategies to cope with. Concurrently, phytoplankton growth must deal with resource acquisition. Experiments on mono- and mixed cultures of morphologically different diatoms exposed to copepods were performed to assess if size and shape were primary drivers in avoiding predation. Additionally, frustule silicification was investigated as a potential factor affecting prey selection by copepods. Thalassiosira pseudonana, Conticribra weissflogii, Cylindrotheca closterium, and Phaeodactylum tricornutum were exposed to the presence of Temora longicornis, a calanoid copepod. The physiological response in terms of growth, elemental composition and morphology was determined. The power of Image Flow Cytometry allowed functional single-cell analyses of mixed cultures in the presence and absence of copepods. Results highlighted that T. pseudonana although the most eaten by copepods in monospecific cultures, was not the preferred prey when the bigger C. weissflogii was added to the culture. When pennates were co-cultured with centric diatoms, their growth was unaffected by predators. Our data suggested that the frustule morphology contributes to long-term prey-predator interaction since the elongated thinner frustule, which evolved more recently, benefited cells in escaping from predators also when facing competition for resources.
Emergence of Large-Scale Hydrodynamic Structures Due to Atmospheric Offshore Wind Farm Wakes
Authors: Christiansen Nils , Daewel Ute , Djath Bughsin , Schrum Corinna
Published: February 2022

The potential impact of offshore wind farms through decreasing sea surface wind speed on the shear forcing and its consequences for the ocean dynamics are investigated. Based on the unstructured-grid model SCHISM, we present a new cross-scale hydrodynamic model setup for the southern North Sea, which enables high-resolution analysis of offshore wind farms in the marine environment. We introduce an observational-based empirical approach to parameterize the atmospheric wakes in a hydrodynamic model and simulate the seasonal cycle of the summer stratification in consideration of the recent state of wind farm development in the southern North Sea. The simulations show the emergence of large-scale attenuation in the wind forcing and associated alterations in the local hydro- and thermodynamics. The wake effects lead to unanticipated spatial variability in the mean horizontal currents and to the formation of large-scale dipoles in the sea surface elevation. Induced changes in the vertical and lateral flow are sufficiently strong to influence the residual currents and entail alterations of the temperature and salinity distribution in areas of wind farm operation. Ultimately, the dipole-related processes affect the stratification development in the southern North Sea and indicate potential impact on marine ecosystem processes. In the German Bight, in particular, we observe large-scale structural change in stratification strength, which eventually enhances the stratification during the decline of the summer stratification toward autumn.
Efficacy of Quadratus Lumborum Block for Pain Control in Patients Undergoing Hip Surgeries: A Systematic Review and Meta-Analysis
Authors: Li Jinfeng , Wei Chenpu , Huang Jiangfa , Li Yuguo , Liu Hongliang , Liu Jun , Jin Chunhua
Published: February 2022

Background

Several studies have reported the use of anterior, posterior and lateral quadratus lumborum block (QLB) for pain control in hip surgeries. However, high-quality evidence is lacking. The current review aimed to summarize data on the efficacy of QLB for pain control in patients undergoing hip surgeries.

Methods

PubMed, Embase, and Google Scholar databases were searched up to August 5, 2021 for randomized controlled trials (RCTs) or non-RCTs assessing the efficacy of QLB for any type of hip surgery.

Results

Thirteen studies were included (nine RCTs and four non-RCTs). On pooled analysis, there was a statistically significant reduction of 24-h total opioid consumption in patients receiving QLB as compared to the control group (MD: −9.92, 95% CI: −16.35, −3.48 I2 = 99% p = 0.003). We noted a statistically significant reduction of pain scores in the QLB group as compared to control group at 2–4 h (MD: −0.57, 95% CI: −0.98, −0.17 I2 = 61% p = 0.005), 6–8 h (MD: −1.45, 95% CI: −2.09, −0.81 I2 = 86% p < 0.00001), 12 h (MD: −1.12, 95% CI: −1.89, −0.34 I2 = 93% p = 0.005), 24 h (MD: −0.71, 95% CI: −1.27, −0.15 I2 = 89% p = 0.01) and 48 h (MD: −0.76, 95% CI: −1.37, −0.16 I2 = 85% p = 0.01) after the procedure. There was a statistically significant reduction in the risk of nausea/vomiting (RR: 0.40, 95% CI: 0.18, 0.88 I2 = 62% p = 0.02) in patients receiving QLB but no difference in the risk of pruritis (RR: 0.46, 95% CI: 0.17, 1.24 I2 = 16% p = 0.13) and urinary retention (RR: 0.44, 95% CI: 0.19, 1.02 I2 = 0% p = 0.06).

Conclusion

QLB as a part of a multimodal analgesic regimen reduces opioid consumption and pain scores in patients undergoing hip surgeries. The certainty of evidence based on GRADE was moderate. Despite the statistically significant results, the clinical relevance of the analgesic efficacy of QLB is debatable due to the small effect size.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42021267861.
JMJD1A/NR4A1 Signaling Regulates the Procession of Renal Tubular Epithelial Interstitial Fibrosis Induced by AGEs in HK-2
Authors: Wang Shaoting , Zuo Anna , Jiang Weiqiang , Xie Jiarun , Lin Haoyu , Sun Wei , Zhao Min , Xia Jinjin , Shao Junqiao , Zhao Xiaoshan , Liang Donghui , Yang Aicheng , Sun Jia , Wang Ming
Published: February 2022

Diabetic kidney disease (DKD) is one of the most serious complications of diabetic patients. Advanced glycation end products (AGEs) induce epithelial-mesenchymal transformation (EMT) of renal tubular epithelial cells (HK-2), resulting in renal tubulointerstitial fibrosis. However, the underlying epigenetic mechanisms remain to be further investigated. In this work, we investigated the functional role of JMJD1A involved in DKD progression. The molecular mechanism study was performed in AGEs-induced HK-2 cells by gene expression analysis, RNA sequencing (RNA-seq), and JMJD1A lentiviral knockdown and overexpression particle transfection. The results showed that AGEs could upregulate JMJD1A, and the expressions of related fibrotic factor were also increased. At the same time, in the DKD animal model induced by unilateral nephrectomy plus streptozotocin (STZ), IHC immunohistochemical staining showed that compared with the control group, the expressions of JMJD1A, FN, and COL1 in the model group were all increased, masson staining results also show that the model group has typical fibrotic changes. This is consistent with the results of our in vitro experiments. In order to determine the downstream pathway, we screened out JMJD1A downstream transcription factors by RNA-seq. Further analysis showed that JMJD1A overexpression could accelerate the progression of AGEs-induced renal fibrosis by reducing the expression of NR4A1 in HK-2 cells. Meanwhile, NR4A1 inhibitor can promote the expression of fibrosis-related factors such as VIM, a-SMA in HK-2 cells, and aggravate the process of fibrosis. Taken together, JMJD1A/NR4A1 signaling can regulate the procession of renal tubular epithelial interstitial fibrosis induced by AGEs in HK-2.
HTLV-1 and Co-infections
Authors: Rosadas Carolina , Taylor Graham P.
Published: February 2022

Human T lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes lifelong T-cell infection in humans, impacting the host immune response. This virus causes a range of clinical manifestations, from inflammatory conditions, including neuronal damage (HTLV-1 associated myelopathy, HAM) to life-threatening leukemia (adult T-cell leukemia, ATL). Human T lymphotropic virus type 1 is also associated with increased risk of all-cause mortality, but the mechanisms remain unclear. As a blood-borne and sexually transmitted infection (STI), HTLV-1 shares transmission routes to many other pathogens and although it has worldwide distribution, it affects mainly those in low- and middle-income tropical areas, where the prevalence of other infectious agents is high. These factors contribute to a high incidence of co-infections in people living with HTLV-1 (PLHTLV). This comprehensive review addresses the impact of HTLV-1 on several co-infections and vice-versa. There is evidence of higher rates of HTLV-1 infection in association with other blood borne (HCV, HBV) and sexually transmitted (Syphilis, Chlamydia, HPV, HSV) infections but whether this represents increased susceptibility or opportunity is unclear. Higher frequency of Mycobacterium tuberculosis (MTb) and Mycobacterium leprae (M. leprae) is observed in PLHTLV. Reports of opportunistic infections and high frequency of crusted scabies in patients with HTLV-1 points to immune impairment in those individuals. Human T lymphotropic virus type 1 may influence the persistence of pathogens, exemplified by the higher rates of Schistosoma mansoni and Strongyloides stercoralis (St. stercoralis) treatment failure observed in PLHTLV. This retrovirus is also associated with increased tuberculosis (TB) severity with some evidence pointing to a deleterious impact on leprosy outcome as well. These findings are supported by immune alterations observed in those co-infected individuals. Although the role of HTLV-1 in HCV outcome is debatable, most data indicate that HTLV may negatively impact the clinical course of hepatitis C. Co-infections may also influence the risk of developing HTLV-1 associated disease, but data are still limited. The impact of HTLV-1 on the response to more common infections, might contribute to the increased mortality rate of HTLV-1. Large scale prospective controlled studies on the prevalence and impact of HTLV-1 in co-infections and vice-versa are needed. Human T lymphotropic virus type 1 impact in public health is broad. Measures to increase awareness and to prevent new infections are needed.
Eradication of Resistant and Susceptible Aerobic Gram-Negative Bacteria From the Digestive Tract in Critically Ill Patients; an Observational Cohort Study
Authors: Buitinck Sophie H. , Jansen Rogier , Bosman Rob J. , van der Meer Nardo J. M. , van der Voort Peter H. J.
Published: February 2022

Background

Selective Decontamination of the Digestive tract (SDD) aims to prevent nosocomial infections, by eradication of potentially pathogenic micro-organisms from the digestive tract.

Objectives

To estimate the rate of and the time to eradication of resistant vs. susceptible facultative aerobic gram-negative bacteria (AGNB) in patients treated with SDD.

Methods

This observational and retrospective study included patients admitted to the ICU between January 2001 and August 2017. Patients were included when treated with SDD (tobramycin, polymyxin B, and amphotericin B) and colonized in the upper or lower gastro-intestinal (GI) tract with at least one AGNB present on admission. Decontamination was determined after the first negative set of cultures (rectal and throat). An additional analysis was performed of two consecutive negative cultures.

Results

Of the 281 susceptible AGNB in the throat and 1,087 in the rectum on admission, 97.9 and 93.7%, respectively, of these microorganisms were successfully eradicated. In the upper GI-tract no differences in eradication rates were found between susceptible and resistant microorganisms. However, the median duration until eradication was significantly longer for aminoglycosides resistant vs. susceptible microorganisms (5 vs. 4 days, p < 0.01). In the lower GI-tract, differences in eradication rates between susceptible and resistant microorganisms were found for cephalosporins (90.0 vs. 95.6%), aminoglycosides (84.4 vs. 95.5%) and ciprofloxacin (90.0 vs. 95.2%). Differences in median duration until eradication between susceptible and resistant microorganisms were found for aminoglycosides and ciprofloxacin (both 5 days vs. 6 days, p = 0.001). Decontamination defined as two negative cultures was achieved in a lower rate (77–98% for the upper GI tract and 64–77% for the lower GI tract) and a median of 1 day later.

Conclusion

The vast majority of both susceptible and resistant microorganisms are effectively eradicated from the upper and lower GI tract. In the lower GI tract decontamination rates of susceptible microorganisms are significantly higher and achieved in a shorter time period compared to resistant strains.
Analysis of Biosynthetic Gene Clusters, Secretory, and Antimicrobial Peptides Reveals Environmental Suitability of Exiguobacterium profundum PHM11
Authors: Srivastava Alok Kumar , Srivastava Ruchi , Bharati Akhilendra Pratap , Singh Alok Kumar , Sharma Anjney , Das Sudipta , Tiwari Praveen Kumar , Srivastava Anchal Kumar , Chakdar Hillol , Kashyap Prem Lal , Saxena Anil Kumar
Published: February 2022

Halotolerant bacteria produce a wide range of bioactive compounds with important applications in agriculture for abiotic stress amelioration and plant growth promotion. In the present study, 17 biosynthetic gene clusters (BGCs) were identified in Exiguobacterium profundum PHM11 belonging to saccharides, desmotamide, pseudaminic acid, dipeptide aldehydes, and terpene biosynthetic pathways representing approximately one-sixth of genomes. The terpene biosynthetic pathway was conserved in Exiguobacterium spp. while the E. profundum PHM11 genome confirms the presence of the 1-deoxy-d-xylulose 5-phosphate (DXP) pathway for the isopentenyl diphosphate (IPP) synthesis. Further, 2,877 signal peptides (SPs) were identified using the PrediSi server, out of which 592 proteins were prophesied for the secretion having a transmembrane helix (TMH). In addition, antimicrobial peptides (AMPs) were also identified using BAGEL4. The transcriptome analysis of PHM11 under salt stress reveals the differential expression of putative secretion and transporter genes having SPs and TMH. Priming of the rice, wheat and maize seeds with PHM11 under salt stress led to improvement in the root length, root diameters, surface area, number of links and forks, and shoot length. The study shows that the presence of BGCs, SPs, and secretion proteins constituting TMH and AMPs provides superior competitiveness in the environment and make E. profundum PHM11 a suitable candidate for plant growth promotion under salt stress.
Repurposing the Veterinary Antibiotic Apramycin for Antibacterial and Antibiofilm Activity Against Pseudomonas aeruginosa From Cystic Fibrosis Patients
Authors: Di Bonaventura Giovanni , Lupetti Veronica , Verginelli Fabio , Giancristofaro Sara , Barbieri Rosemary , Gherardi Giovanni , Pompilio Arianna
Published: February 2022

Objectives:

To evaluate the in vitro antibacterial, antibiofilm, and antivirulence activities of apramycin, comparatively to tobramycin, against a set of P. aeruginosa from chronically infected cystic fibrosis (CF) patients.

Methods

The activity of antibiotics against planktonic cells was assessed by performing MIC, MBC, and time-kill assays. The activity against mature biofilms was evaluated, in a microtiter plate, both in terms of dispersion (crystal violet assay) and residual viability (viable cell count). The effect of drug exposure on selected P. aeruginosa virulence genes expression was assessed by real-time Reverse Transcription quantitative PCR (RT-qPCR).

Results

Apramycin MIC90 and MBC90 values were found at least fourfold lower than those for tobramycin. A comparable trend was observed for mucoid strains. Only 4 out of 24 strains (16.6%) showed an apramycin MIC higher than the epidemiological cut-off value of 64 mg/L, whereas a higher resistance rate was observed for tobramycin (62.5%; p < 0.01 vs. apramycin). In time-kill analyses, both aminoglycosides were found bactericidal, although apramycin showed a more rapid effect and did not allow for regrowth. Apramycin generally stimulated biofilm biomass formation, whereas tobramycin showed opposite trends depending on the strain tested. Both drugs caused a highly significant, dose-dependent reduction of biofilm viability, regardless of strain and concentration tested. The exposure to apramycin and tobramycin caused increased expression of mexA and mexC (multidrug efflux pumps), whereas tobramycin specifically increased the expression of aprA (alkaline protease) and toxA (exotoxin A). Neither apramycin nor tobramycin showed cytotoxic potential toward IB3-1 bronchial epithelial CF cells.

Conclusion

Our results warrant future pharmacokinetic and pharmacodynamic studies for supporting the rationale to repurpose apramycin, a veterinary aminoglycoside, for CF lung infections.
Isolation, Characterization and Draft Genome Analysis of Bacteriophages Infecting Acidovorax citrulli
Authors: Gašić Katarina , Obradović Mina , Kuzmanović Nemanja , Zlatković Nevena , Ivanović Milan , Ristić Danijela , Obradović Aleksa
Published: February 2022

Bacterial fruit blotch and seedling blight, caused by Acidovorax citrulli, is one of the most destructive diseases of melon and watermelon in many countries. Pathogen-free seed and cultural practices are major pillars of the disease control. However, use of bacteriophages as natural biocontrol agents might also contribute to the disease management. Therefore, we isolated 12 bacteriophages specific to A. citrulli, from phyllosphere and rhizosphere of diseased watermelon plants. The phage strains were characterized based on their host range, plaque and virion morphology, thermal inactivation point, adsorption rate, one step growth curve, restriction fragment length polymorphism (RFLP), and genomic analysis. Transmission electron microscopy of three phage strains indicated that they belong to the order Caudovirales, family Siphoviridae. All phages lysed 30 out of 32 tested A. citrulli strains isolated in Serbia, and did not lyse other less related bacterial species. They produced clear plaques, 2 mm in diameter, on bacterial lawns of different A. citrulli strains after 24 h of incubation. The thermal inactivation point was 66 or 67°C. They were stable at pH 5–9, but were sensitive to chloroform and inactivated in either 5 or 10 min exposure to ultraviolet (UV) light. RFLP analysis using EcoRI, BsmI and BamHI enzymes did not show genetic differences among the tested phages. Adsorption rate and one step growth curve were determined for the Acidovorax phage ACF1. Draft genome sequence of the ACF1 phage was 59.377 bp in size, with guanine-cytosine (GC) content 64.5%, including 89 open reading frames. This phage shared a very high genomic identity with Acidovorax phage ACPWH, isolated in South Korea. Evaluation of systemic nature of ACF1 strain showed that it can be absorbed by roots and translocated to upper parts of watermelon plants where it survived up to 10 days.
Identification of Antimicrobial Compounds in Two Streptomyces sp. Strains Isolated From Beehives
Authors: Santos-Beneit Fernando , Ceniceros Ana , Nikolaou Athanasios , Salas José A. , Gutierrez-Merino Jorge
Published: February 2022

The World Health Organization warns that the alarming increase in antibiotic resistant bacteria will lead to 2.7 million deaths annually due to the lack of effective antibiotic therapies. Clearly, there is an urgent need for short-term alternatives that help to alleviate these alarming figures. In this respect, the scientific community is exploring neglected ecological niches from which the prototypical antibiotic-producing bacteria Streptomycetes are expected to be present. Recent studies have reported that honeybees and their products carry Streptomyces species that possess strong antibacterial activity. In this study, we have investigated the antibiotic profile of two Streptomycetes strains that were isolated from beehives. One of the isolates is the strain Streptomyces albus AN1, which derives from pollen, and shows potent antimicrobial activity against Candida albicans. The other isolate is the strain Streptomyces griseoaurantiacus AD2, which was isolated from honey, and displays a broad range of antimicrobial activity against different Gram-positive bacteria, including pathogens such as Staphylococcus aureus and Enterococus faecalis. Cultures of S. griseoaurantiacus AD2 have the capacity to produce the antibacterial compounds undecylprodigiosin and manumycin, while those of S. albus AN1 accumulate antifungal compounds such as candicidins and antimycins. Furthermore, genome and dereplication analyses suggest that the number of putative bioactive metabolites produced by AD2 and AN1 is considerably high, including compounds with anti-microbial and anti-cancer properties. Our results postulate that beehives are a promising source for the discovery of novel bioactive compounds that might be of interest to the agri-food sector and healthcare pharmaceuticals.
Analysis of Novel Drug-Resistant Human Cytomegalovirus DNA Polymerase Mutations Reveals the Role of a DNA-Binding Loop in Phosphonoformic Acid Resistance
Authors: Park Kye Ryeong , Kim Young-Eui , Shamim Amen , Gong Shuang , Choi Soo-Han , Kim Kyeong Kyu , Kim Yae-Jean , Ahn Jin-Hyun
Published: February 2022

The appearance of drug-resistant mutations in UL54 DNA polymerase and UL97 kinase genes is problematic for the treatment of human cytomegalovirus (HCMV) diseases. During treatment of HCMV infection in a pediatric hematopoietic cell transplant recipient, H600L and T700A mutations and E576G mutation were independently found in the UL54 gene. Foscarnet (FOS; phosphonoformic acid) resistance by T700A mutation is reported. Here, we investigated the role of novel mutations in drug resistance by producing recombinant viruses and a model polymerase structure. The H600L mutant virus showed an increase in resistance to ganciclovir (GCV) by 11-fold and to FOS and cidofovir (CDV) by 5-fold, compared to the wild type, while the E756G mutant virus showed an increase in resistance to FOS by 9-fold and modestly to CDV by 2-fold. With the FOS-resistant T700A mutation, only H600L produced increased FOS resistance up to 37-fold, indicating an additive effect of these mutations on FOS resistance. To gain insight into drug resistance mechanisms, a model structure for UL54 polymerase was constructed using the yeast DNA polymerase as a template. In this model, HCMV DNA polymerase contains a long palm loop domain of which H600 and T700 are located on each end and T700 interacts with the FOS binding pocket. Our results demonstrate that H600L and E756G mutations in UL54 polymerase are novel drug-resistant mutations and that the acquisition of both H600L and T700A mutations in the DNA-binding loop confers increased resistance to FOS treatment, providing novel insights for the mechanism acquiring foscarnet resistance.