bluuebunny/crossref_metadata_2025 huggingface dataset:
SLAMF8 Downregulates Mouse Macrophage Microbicidal Mechanisms via PI3K Pathways
Authors: Romero-Pinedo Salvador , Barros Domingo I. Rojas , Ruiz-Magaña María José , Maganto-García Elena , Moreno de Lara Laura , Abadía-Molina Francisco , Terhorst Cox , Abadía-Molina Ana C.
Published: June 2022

Signaling lymphocytic activation molecule family 8 (SLAMF8) is involved in the negative modulation of NADPH oxidase activation. However, the impact of SLAMF8 downregulation on macrophage functionality and the microbicide mechanism remains elusive. To study this in depth, we first analyzed NADPH oxidase activation pathways in wild-type and SLAMF8-deficient macrophages upon different stimulus. Herein, we describe increased phosphorylation of the Erk1/2 and p38 MAP kinases, as well as increased phosphorylation of NADPH oxidase subunits in SLAMF8-deficient macrophages. Furthermore, using specific inhibitors, we observed that specific PI3K inhibition decreased the differences observed between wild-type and SLAMF8-deficient macrophages, stimulated with either PMA, LPS, orSalmonella typhimuriuminfection. Consequently, SLAMF8-deficient macrophages also showed increased recruitment of small GTPases such as Rab5 and Rab7, and the p47phoxsubunit to cytoplasmicSalmonella, suggesting an impairment ofSalmonella-containing vacuole (SCV) progression in SLAMF8-deficient macrophages. Enhanced iNOS activation, NO production, and IL-6 expression were also observed in the absence of SLAMF8 uponSalmonellainfection, eitherin vivoorin vitro, while overexpression of SLAMF8 in RAW264.7 macrophages showed the opposite phenotype. In addition, SLAMF8-deficient macrophages showed increased activation of Src kinases and reduced SHP-1 phosphate levels upon IFNγ andSalmonellastimuli in comparison to wild-type macrophages. In agreement within vitroresults,Salmonellaclearance was augmented in SLAMF8-deficient mice compared to that in wild-type mice. Therefore, in conclusion, SLAMF8 intervention upon bacterial infection downregulates mouse macrophage activation, and confirmed that SLAMF8 receptor could be a potential therapeutic target for the treatment of severe or unresolved inflammatory conditions.
Host and Microbiome Interplay Shapes the Vaginal Microenvironment
Authors: Kwon Myoung Seung , Lee Heung Kyu
Published: June 2022

The female reproductive tract harbors a unique microbiome, especially the vagina. The human vaginal microbiome exhibits a low diversity and is dominated by Lactobacillus species, compared to the microbiome of other organs. The host and vaginal microbiome mutually coexist in the vaginal microenvironment. Host cells provide Lactobacillus glycogen as an energy source, and Lactobacillus produce lactic acid, which lowers vaginal pH thereby preventing growth of other bacteria. Bacterial vaginosis can modulate host immune systems, and is frequently associated with various aspects of disease, including sexually transmitted infection, gynecologic cancer, and poor pregnancy outcomes. Because of this, numerous studies focused on the impact of the vaginal microbiome on women`s health and disease. Furthermore, numerous epidemiologic studies also have demonstrated various host factors regulate the vaginal microbiome. The female reproductive tract undergoes constant fluctuations due to hormonal cycle, pregnancy, and other extrinsic factors. Depending on these fluctuations, the vaginal microbiome composition can shift temporally and dynamically. In this review, we highlight the current knowledge of how host factors modulate vaginal microbiome composition and how the vaginal microbiome contributes to maintaining homeostasis or inducing pathogenesis. A better understanding of relationship between host and vaginal microbiome could identify novel targets for diagnosis, prognosis, or treatment of microbiome-related diseases.
Breeding Technology as a Tool for Sustainable Aquaculture Production and Ecosystem Services
Authors: Azra Mohamad Nor , Okomoda Victor Tosin , Ikhwanuddin Mhd
Published: June 2022

Aquaculture is the aquatic equivalent of agriculture. While agriculture is predominantly based on the use of freshwater to grow crops, aquaculture utilizes freshwater (i.e. inland waters) and brackish water/seawater (i.e. coastal waters) to culture fish, plants, shellfish (bivalve, abalone, sea urchins and sea cucumbers), macro and microalgae. The increasing scarcity of captive aquatic fisheries resources has led to the regenerative farming practices of aquaculture. Aquaculture is the fastest-growing food sector in the world and about the most important means of providing sustainable food production currently. Among the several aquaculture techniques used, breeding technology has been exploited to improve food production. Beyond captive production, breeding technology has also been exploited for restocking programs of many aquatic ecosystems (i.e. rivers, lakes, sea, estuaries, etc.), hence, contributing positively to their management and ecosystem services. This comment, therefore, highlights some breeding technology as regards to their ability to improve sustainable captive production and aquatic ecosystem services.
Marine Microeukaryote Metatranscriptomics: Sample Processing and Bioinformatic Workflow Recommendations for Ecological Applications
Authors: Cohen Natalie R. , Alexander Harriet , Krinos Arianna I. , Hu Sarah K. , Lampe Robert H.
Published: June 2022

Microeukaryotes (protists) serve fundamental roles in the marine environment as contributors to biogeochemical nutrient cycling and ecosystem function. Their activities can be inferred through metatranscriptomic investigations, which provide a detailed view into cellular processes, chemical-biological interactions in the environment, and ecological relationships among taxonomic groups. Established workflows have been individually put forth describing biomass collection at sea, laboratory RNA extraction protocols, and bioinformatic processing and computational approaches. Here, we present a compilation of current practices and lessons learned in carrying out metatranscriptomics of marine pelagic protistan communities, highlighting effective strategies and tools used by practitioners over the past decade. We anticipate that these guidelines will serve as a roadmap for new marine scientists beginning in the realms of molecular biology and/or bioinformatics, and will equip readers with foundational principles needed to delve into protistan metatranscriptomics.
The Fourth-Order Nonlinear Schrödinger Equation and Stability Analysis for Stokes Waves on Slowly Varying Topography
Authors: Zhang Xufeng , Zhang Yifeng , Li Ruijie
Published: June 2022

The surface gravity wave equation is expanded to the fourth-order wave steepness on slowly varying topography, obtaining a topographic modified nonlinear Schrödinger (TMNLS) equation. When the time scale is longer than ε-3 times of the dominant wave period or the space scale is larger than ε-3 times the dominant wavelength, the second water depth derivative and the square of the first water depth derivative affect the first-order wave amplitude. The instability area for a uniform Stokes wave train by small perturbations is the entire wavenumber space, except for a specific stability curve on infinite and slowly varying depth. The depth variation terms affect the growth rate of uniform Stokes wave train on the order of 0.01. The stability curve shows more sensitive to the depth variation in x direction than that in y direction. The increment of the value for depth variation in x direction contributes the stable wave number of perturbation to approach or parallel to y axis. The increment of the value for depth variation in y direction helps the stable wave number of perturbation to approach or parallel to x axis.
Effect of Transport Density on Greater Amberjack (Seriola dumerili) Stress, Metabolism, Antioxidant Capacity and Immunity
Authors: Liu Hongyan , Fu Zhengyi , Yu Gang , Ma Zhenhua , Fu Zhilu
Published: June 2022

This study sought to characterize the effect of density stress on greater amberjack (Seriola dumerili) survival to determine an optimal transport density. To achieve this, this experiment simulated the transport conditions of fish (body length: 4.09 ± 1.00 cm; weight: 0.9 ± 0.05 g) using closed oxygen transport at 5 different densities (D1 = 1.125 kg/m3, D2 = 2.25 kg/m3, D3 = 3.375 kg/m3, D4 = 4.5 kg/m3, and D5 = 6.75 kg/m3) for 8 hours, after which biochemical indicators, stress, metabolism, and antioxidant capacity were evaluated. After 8h, only the D1 and D3 groups exhibited survival rates above 90%. The pH of the water decreased with density, whereas the ammonia nitrogen and nitrite increased with density. Cortisol (COR) levels were not significantly different among all the groups, but tended to increase with increasing density. In this study, COR is a relatively stable index with the increase in density, but in D3 group, the change of COR will not cause the change of immune-related genes, so COR can inhibit the expression of immune genes within a certain density. The D3 density group exhibited the highest catalase (CAT) and glutathione peroxidase glutathione peroxidase (GSH‐PX) levels. In addition, the expression levels of immune related factor interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), major histocompatibility complex (MHC-1) and nuclear factor kappa-B (NF-KB1) were the lowest in D3 density group. The density of fish during transportation significantly affects water quality, metabolism, and immunity. During transportation, assuming that the plastic bags are airtight to ensure aerobic conditions and that the transportation time is within 8 h, transport density should be maintained at approximately 3.375 kg/m3.
Arrangement and Decomposition of Grain Boundary Dislocations: Two-Mode Phase-Field Crystal Simulation
Authors: Li Huanqing , Wang Xiaona , Zhang Haibin , Tian Xiaolin , Hou Hua , Zhao Yuhong
Published: June 2022

The grain-boundary dislocation arrangement and decomposition during constant-volume deformation of a nanoscale bi-crystal system in fcc-structured materials were studied by using the two-mode phase-field crystal (2PFC) method. The effects of different grain boundary misorientations (GBMs) and tensile deformation directions on the dislocation arrangement and decomposition are analyzed. In three different symmetrical tilt grain boundaries evaluated by PFC, the atomic density profile of grain boundaries changed periodically at equilibrium. The initial grain boundary dislocation arrangement of the three samples is almost the same when tensile deformation is applied to the samples in the x- or y- direction, and all are symmetrically arranged in a “bowknot ”structure. The stress at the grain boundary is concentrated with the increase of strain, and dislocation decomposition can effectively reduce the stress concentration. The time steps of dislocation decomposition at grain boundaries decreases with increasing strain rate. This work facilitates the application of PFC in the analysis of grain-boundary mechanics in an extended range of materials.
Solvent-Directed Morphological Transformation in Covalent Organic Polymers
Authors: Cao Xuan Thang , Kumar Subodh , Nemec Ivan , Kopp Josef , Varma Rajender S.
Published: June 2022

Synthesis of bi-functional covalent organic polymers in two distinctive morphologies has been accomplished by simply switching the solvent from DMF to DMSO when 1,3,5-tribenzenecarboxyldehyde and 2,5-diaminobenzene sulfonic acid were reacted via Schiff base condensation reaction to afford covalent organic polymers (COPs) encompassing flower (F-COPDMF)- and circular (C-COPDMSO)-type morphologies. Chemical and morphological natures of the synthesized COPs were compared by characterization using TEM, SEM, XRD, FT-IR, and XPS analysis techniques. Besides diverse morphology, both the polymeric materials were found to comprise similar chemical natures bearing protonic acid–SO3H and Lewis base–C=N functionalities. Subsequently, both the COPs were evaluated for the synthesis of hydroxymethylfurfural (HMF) by the dehydration of fructose to investigate their morphology-dependent catalytic activity.
The Ethical and Societal Considerations for the Rise of Artificial Intelligence and Big Data in Ophthalmology
Authors: Liu T. Y. Alvin , Wu Jo-Hsuan
Published: June 2022

Medical specialties with access to a large amount of imaging data, such as ophthalmology, have been at the forefront of the artificial intelligence (AI) revolution in medicine, driven by deep learning (DL) and big data. With the rise of AI and big data, there has also been increasing concern on the issues of bias and privacy, which can be partially addressed by low-shot learning, generative DL, federated learning and a “model-to-data” approach, as demonstrated by various groups of investigators in ophthalmology. However, to adequately tackle the ethical and societal challenges associated with the rise of AI in ophthalmology, a more comprehensive approach is preferable. Specifically, AI should be viewed as sociotechnical, meaning this technology shapes, and is shaped by social phenomena.
Predicting Axial Length From Choroidal Thickness on Optical Coherence Tomography Images With Machine Learning Based Algorithms
Authors: Lu Hao-Chun , Chen Hsin-Yi , Huang Chien-Jung , Chu Pao-Hsien , Wu Lung-Sheng , Tsai Chia-Ying
Published: June 2022

Purpose

We formulated and tested ensemble learning models to classify axial length (AXL) from choroidal thickness (CT) as indicated on fovea-centered, 2D single optical coherence tomography (OCT) images.

Design

Retrospective cross-sectional study.

Participants

We analyzed 710 OCT images from 355 eyes of 188 patients. Each eye had 2 OCT images.

Methods

The CT was estimated from 3 points of each image. We used five machine-learning base algorithms to construct the classifiers. This study trained and validated the models to classify the AXLs eyes based on binary (AXL < or > 26 mm) and multiclass (AXL < 22 mm, between 22 and 26 mm, and > 26 mm) classifications.

Results

No features were redundant or duplicated after an analysis using Pearson’s correlation coefficient, LASSO-Pattern search algorithm, and variance inflation factors. Among the positions, CT at the nasal side had the highest correlation with AXL followed by the central area. In binary classification, our classifiers obtained high accuracy, as indicated by accuracy, recall, positive predictive value (PPV), negative predictive value (NPV), F1 score, and area under ROC curve (AUC) values of 94.37, 100, 90.91, 100, 86.67, and 95.61%, respectively. In multiclass classification, our classifiers were also highly accurate, as indicated by accuracy, weighted recall, weighted PPV, weighted NPV, weighted F1 score, and macro AUC of 88.73, 88.73, 91.21, 85.83, 87.42, and 93.42%, respectively.

Conclusions

Our binary and multiclass classifiers classify AXL well from CT, as indicated on OCT images. We demonstrated the effectiveness of the proposed classifiers and provided an assistance tool for physicians.
Associations Between Sarcopenia, Heart Failure and Myocardial Infarction in Patients With Systemic Lupus Erythematosus and Rheumatoid Arthritis
Authors: Chang Ching-Mao , Lin Jr-Rung , Fu Tieh-Cheng
Published: June 2022

Objectives

To evaluate associations between sarcopenia, type of autoimmune disease and risk of heart failure (HF) and myocardial infarction (MI) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods

In this population-based, cross-sectional study, discharge data from the 2005–2014 US Nationwide Inpatient Sample (NIS) of hospitalized patients with SLE or RA were extracted and analyzed. Univariate and multivariable regression analyses were conducted to determine associations between sarcopenia, type of autoimmune disease and risk of HF/MI.

Results

After exclusions, 781,199 hospitalized patients diagnosed with SLE or RA were included. Among the study cohort, 127,812 (16.4%) were hospitalized with HF, and 12,781 (1.6%) were hospitalized with MI. Sarcopenia was found in only 0.1% of HF/MI patients. Logistic regression analyses revealed that sarcopenia was not significantly associated with presence of either HF or MI. Patients with RA had significantly lower odds of HF than SLE patients (aOR = 0.77, 95%CI: 0.76, 0.79) or MI (aOR = 0.86, 95%CI: 0.82, 0.91).

Conclusion

In the US, among hospitalized adults diagnosed with SLE or RA, patients with RA are significantly less likely to have HF or MI than those with SLE. Whether sarcopenia leads to increased HF or MI remains inconclusive. Further studies are warranted to investigate the pathophysiology underlying discrepancies between RA and SLE regarding risk for MI or HF.
Akt-Dependent Glycolysis-Driven Lipogenesis Supports Proliferation and Survival of Human Pulmonary Arterial Smooth Muscle Cells in Pulmonary Hypertension
Authors: Jiang Lifeng , Goncharov Dmitry A. , Shen Yuanjun , Lin Derek , Chang Baojun , Pena Andressa , DeLisser Horace , Goncharova Elena A. , Kudryashova Tatiana V.
Published: June 2022

Hyper-proliferation of pulmonary arterial vascular smooth muscle cells (PAVSMC) is an important pathological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Lipogenesis is linked to numerous proliferative diseases, but its role in PAVSMC proliferation in PAH remains to be elucidated. We found that early-passage human PAH PAVSMC had significant up-regulation of key fatty acids synthesis enzymes ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FASN), and increased unstimulated proliferation compared to control human PAVSMC. Treatment with an allosteric ACC inhibitor 5-tetradecyloxy-2-furoic acid (TOFA) significantly decreased proliferation and induced apoptosis of human PAH PAVSMC. Intracellular lipid content and proliferation of PAH PAVSMC were not reduced by incubation in lipid-depleted media but suppressed by a non-metabolizable analog of glucose 2-Deoxy-D-glucose (2-DG) and partially restored by addition of pyruvate. Protein kinase Akt was upregulated in human PAH PAVSMC in a sirtuin 7 (SIRT7)- and c-Jun N-terminal kinase (JNK)-dependent manner. Pharmacological inhibition of Akt down-regulated ACLY and ACC, significantly reduced intracellular lipid content, inhibited proliferation and induced apoptosis of human PAH PAVSMC. Taken together, these data demonstrate that human PAH PAVSMC have up-regulated lipogenesis, which is supported in an Akt- and glycolysis-dependent manner and is required for increased proliferation and survival. Our data suggest that there is a mechanistic link between glycolysis, lipogenesis, and the proliferation of human PAH PAVSMC and call for further studies to determine the potential attractiveness of a SIRT7/JNK-Akt-lipogenesis axis as a target pathway to inhibit PAVSMC hyper-proliferation in PAH.
Longitudinal Photoreceptor Phenotype Observation and Therapeutic Evaluation of a Carbonic Anhydrase Inhibitor in a X-Linked Retinoschisis Mouse Model
Authors: Liu Meng , Liu Jingyang , Wang Weiping , Liu Guangming , Jin Xiuxiu , Lei Bo
Published: June 2022

Purpose

To study the long-term photoreceptor changes and to evaluate the effects of topical application of a carbonic anhydrase inhibitor (CAI) in a mouse model of X-linked retinoschisis (XLRS).

Methods

Conventional electroretinograms (ERGs) and dark-adapted 10-Hz flicker ERGs were recorded in control and Rs1−/Y mice generated with CRISPR/Cas9. ON-pathway blocker 2-amino-4-phosphobutyric acid (APB) was injected intravitreally. Morphology was evaluated with histology and optical coherence tomography (OCT). Mice were treated with a CAI inhibitor brinzolamide eye drops (10 mg/ml) three times a day for 3 months. OCT and ERG findings at 1, 4, and 10 months were analyzed.

Results

Negative ERGs and retinal cavities were evident in Rs1−/Y mice. Both a-wave and b-wave amplitudes decreased with age when compared with age-matched controls. The APB-isolated a-wave (a′) amplitudes of Rs1−/Y mice were reduced in all age groups. In dark-adapted 10-Hz flicker ERG, the amplitude-intensity curve of Rs1−/Y mice shifted down. The thickness of ONL and IS/OS decreased in Rs1−/Y mice. CAI reduced the splitting retinal cavities but didn't affect the ERG.

Conclusions

In addition to post receptoral impairments, photoreceptor cells underwent progressive dysfunction since early age in Rs1−/Y mice. Long-term CAI treatment improved the shrinkage of the splitting retinal cavity, while no functional improvement was observed.
Effect of the Age-Adjusted Charlson Comorbidity Index on All-Cause Mortality and Readmission in Older Surgical Patients: A National Multicenter, Prospective Cohort Study
Authors: Zhang Xiao-Ming , Wu Xin-Juan , Cao Jing , Guo Na , Bo Hai-Xin , Ma Yu-Fen , Jiao Jing , Zhu Chen
Published: June 2022

Background

Identifying a high-risk group of older people before surgical procedures is very important. The study aimed to explore the association between the age-adjusted Charlson comorbidity index (ACCI) and all-cause mortality and readmission among older Chinese surgical patients (age ≥65 years).

Methods

A large-scale cohort study was performed in 25 general public hospitals from six different geographic regions of China. Trained registered nurses gathered data on clinical and sociodemographic characteristics. All-cause mortality was recorded when patients died during hospitalization or during the 90-day follow-up period. Readmission was also tracked from hospital discharge to the 90-day follow-up. The ACCI, in assessing comorbidities, was categorized into two groups (≥5 vs. <5). A multiple regression model was used to examine the association between the ACCI and all-cause mortality and readmission.

Results

There were 3,911 older surgical patients (mean = 72.46, SD = 6.22) in our study, with 1,934 (49.45%) males. The average ACCI score was 4.77 (SD = 1.99), and all-cause mortality was 2.51% (high ACCI = 5.06% vs. low ACCI = 0.66%, P < 0.001). After controlling for all potential confounders, the ACCI score was an independent risk factor for 90-day hospital readmission (OR = 1.18, 95% CI: 1.14, 1.23) and 90-day all-cause mortality (OR = 1.26, 95% CI: 1.16–1.36). Furthermore, older surgical patients with a high ACCI (≥5) had an increased risk of all-cause mortality (OR = 6.13, 95% CI: 3.17, 11.85) and readmission (OR = 2.13, 95% CI: 1.78, 2.56) compared to those with a low ACCI (<5). The discrimination performance of the ACCI was moderate for mortality (AUC:0.758, 95% CI: 0.715–0.80; specificity = 0.591, sensitivity = 0.846) but poor for readmission (AUC: 0.627, 95% CI: 0.605–0.648; specificity = 0.620; sensitivity = 0.590).

Conclusions

The ACCI is an independent risk factor for all-cause mortality and hospital readmission among older Chinese surgical patients and could be a potential risk assessment tool to stratify high-risk older patients for surgical procedures.
What Determines That Older Adults Feel Younger Than They Are? Results From a Nationally Representative Study in Germany
Authors: Heimrich Konstantin G. , Prell Tino , Schönenberg Aline
Published: June 2022

Background

There is increasing evidence that subjective age is an important predictor of beneficial health outcomes besides chronological age. However, little is known about the factors associated with younger subjective age. This study aimed to identify which factors are predictive of feeling younger in old age. In this context, feeling younger was defined as an individual's perception of being younger than their current chronological age.

Methods

Data from 4,665 community-dwelling older people were drawn from wave 7 (2020) of the German Aging Survey (DEAS), a nationally representative study in Germany. Network, mediation, and binomial logistic regression analyses were performed to reveal the associations between feeling younger and biopsychosocial factors.

Results

A total of 4,039 participants reported feeling younger, while 626 did not. Older chronological age, engaging in sports more frequently, a better standard of living, a better state of health, higher satisfaction with life, more positive attitudes toward one's aging, and fewer depressive symptoms are associated with feeling younger in older people.

Conclusion

The present study provides novel and consistent evidence regarding the association between feeling younger and biopsychosocial factors. Further research is needed to confirm these factors and identify how they can be adapted in potential intervention studies to generate the life and health circumstances that allow older people the benefit of feeling younger.
The Association Between METS-IR and Serum Ferritin Level in United States Female: A Cross-Sectional Study Based on NHANES
Authors: Hao Han , Chen Yan , Xiaojuan Ji , Siqi Zhang , Hailiang Chu , Xiaoxing Sun , Qikai Wang , Mingquan Xing , Jiangzhou Feng , Hongfeng Ge
Published: June 2022

Aim

The aim of this study was to investigate the association between the metabolic score for insulin resistance (METS-IR) and serum ferritin in females from the United States.

Methods

We conducted a cross-sectional study with 4,182 participants from the National Health and Nutrition Examination Survey (NHANES). We used METS-IR and serum ferritin as the independent and dependent variables in this study and investigated the relationship by using multiple linear regression and verified the non-linear relationship with a smooth curve fit and threshold effect model.

Results

There was a positive relationship between METS-IR and serum ferritin, with an effect value of (β = 0.29, 95% CI: 0.14–0.44) in a fully adjusted model adjusted for potential confounders. This positive correlation became more significant as METS-IR increased (p for trend < 0.001). Subsequent subgroup analyses showed that sensitive cohorts were those aged ≥40 years, black, and with a body mass index (BMI) < 24.9 kg/m2. In a smoothed curve fit analysis, the correlation between METS-IR and serum ferritin was a straight linear relationship in all participants included in this study, but when stratified by age, race, and BMI, this positive correlation in the participants who were aged ≥40 years old, other race, and had a BMI < 24.9 kg/m2 was non-linear.

Conclusions

There was a positive association between METS-IR and serum ferritin in United States females, and this positive association was more pronounced in participants aged ≥40 years, black race and BMI < 24.9 kg/m2. This positive association was non-linear in the subgroups aged ≥40 years, white race and BMI < 24.9 kg/m2, with inflection points for METS-IR of 69.97, 67.84 and 35.84 in these respective subgroups.
New Screening System Using Forward-Viewing Radial Endoscopic Ultrasound and Magnetic Resonance Imaging for High-Risk Individuals With Familial History of Pancreatic Cancer
Authors: Ashida Reiko , Ioka Tatsuya , Takada Ryoji , Fukutake Nobuyasu , Ikezawa Kenji , Ohkawa Kazuyoshi , Nagata Shigenori , Takahashi Hidenori
Published: June 2022

Background and Aims

Attention is increasingly being paid to family history of pancreatic cancer (PC) as a risk factor for developing PC. It is mandatory to develop a screening system for early detection of PC; however, the relationship between a family history of PC and the incidence of pancreatic abnormalities, such as pancreatic cyst and chronic pancreatitis (CP), in the Japanese population remains unknown.

Patients and Methods

Individuals with a family history of PC were prospectively enrolled in a screening program using forward-viewing radial endoscopic ultrasound (FR-EUS) and magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) as the diagnostic modalities.

Results

In total, forty-three individuals in 37 families were enrolled (mean age, 54 years). All individuals underwent FR-EUS and MRI with no complications. FR-EUS revealed resectable PC (n = 1, 2.3%), pancreatic cysts (n = 24, 55.8%), intraductal papillary mucinous neoplasm (IPMN; n = 13, 30.2%), and early CP-like appearance (n = 15, 34.9%). The detection rate of early CP-like appearance was significantly higher by EUS than by MRI. Pancreatic cysts and IPMN detected by FR-EUS were significantly correlated to age (≥60 years) and less correlated to men (hazard ratio [HR] 22.4; 95% confidence interval [CI], 2.10–236.0; p < 0.01 and HR 0.092; 95% CI, 0.01–0.83; p = 0.033, respectively). Early CP-like appearance detected by FR-EUS was significantly correlated with men and smoking (HR 5.0; 95% CI, 1.3–19.3; p = 0.02 and HR 4.02; 95% CI, 0.991–16.3; p = 0.05, respectively).

Conclusion

A screening system using FR-EUS and MRI/MRCP for individuals with a family history of PC was useful for identifying curable PC and pancreatic abnormalities. The incidence of pancreatic cysts, such as IPMN and early CP-like appearance, was also high in the Japanese cohort.
Trabeculectomy With Antimetabolite Agents for Normal Tension Glaucoma: A Systematic Review and Meta-Analysis
Authors: Lai Chin , Shao Shih-Chieh , Chen Yi-Hung , Kuo Yu-Kai , Lai Chi-Chun , Chuang Lan-Hsin
Published: June 2022

Background

Evidence regarding the impact on visual field (VF), intraocular pressure (IOP), and antiglaucoma medications from trabeculectomy with antimetabolites for normal tension glaucoma (NTG) is conflicting because of insufficient study sample sizes. The aim of this study is to systematically assess VF progression rate, IOP control and antiglaucoma medication use after trabeculectomy with antimetabolites for progressing NTG.

Methods

We searched published articles on PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from database inception to March 21, 2022. We selected studies that reported VF data before and after trabeculectomy with antimetabolite agents for NTG. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Data were extracted by 2 independent reviewers, and a random-effects model was employed for the meta-analysis. Study outcomes were VF progression rates measured using the pooled mean deviation (MD) slope, changes in antiglaucoma medications, and IOP. Subgroup analyses of the MD slope according to mean age (over or under 65 years), baseline MD (over or under –12 dB), and baseline IOP (over or under 15 mmHg) were performed to determine the results’ robustness.

Results

We included 7 retrospective observational studies (Japan: 6 studies, United States: 1 study) comprising a total of 166 eyes. Mean preoperative VF MD slopes ranged from –0.52 to –1.05 dB/year. The meta-analysis demonstrated significant MD slope improvement after trabeculectomy (pooled mean difference: 0.54 dB/year, 95% CI: 0.40 to 0.67, I2 = 9%). Mean age, baseline MD, and baseline IOP subgroup analyses revealed MD slope results were consistent with those of the main analyses. The mean IOP (pooled mean difference: –5.54 mmHg, 95% CI: –6.02 to –5.06, I2 = 0%) and mean number of antiglaucoma medications (pooled mean difference: –1.75, 95% CI: –2.97 to –0.53, I2 = 98%) significantly decreased after trabeculectomy. The most frequently reported early complications after trabeculectomy were hypotony, hyphema, and shallow anterior chamber.

Conclusion

This systematic review and meta-analysis indicated that trabeculectomy with antimetabolites is beneficial for progressing NTG; it preserves visual function by alleviating the MD slope and reducing antiglaucoma medication use. However, several post-trabeculectomy complications should be monitored.
Landscape Topography and Regional Drought Alters Dust Microbiomes in the Sierra Nevada of California
Authors: Maltz Mia R. , Carey Chelsea J. , Freund Hannah L. , Botthoff Jon K. , Hart Stephen C. , Stajich Jason E. , Aarons Sarah M. , Aciego Sarah M. , Blakowski Molly , Dove Nicholas C. , Barnes Morgan E. , Pombubpa Nuttapon , Aronson Emma L.
Published: June 2022

Dust provides an ecologically significant input of nutrients, especially in slowly eroding ecosystems where chemical weathering intensity limits nutrient inputs from underlying bedrock. In addition to nutrient inputs, incoming dust is a vector for dispersing dust-associated microorganisms. While little is known about dust-microbial dispersal, dust deposits may have transformative effects on ecosystems far from where the dust was emitted. Using molecular analyses, we examined spatiotemporal variation in incoming dust microbiomes along an elevational gradient within the Sierra Nevada of California. We sampled throughout two dry seasons and found that dust microbiomes differed by elevation across two summer dry seasons (2014 and 2015), which corresponded to competing droughts in dust source areas. Dust microbial taxa richness decreased with elevation and was inversely proportional to dust heterogeneity. Likewise, dust phosphorus content increased with elevation. At lower elevations, early season dust microbiomes were more diverse than those found later in the year. The relative abundances of microbial groups shifted during the summer dry season. Furthermore, mutualistic fungal diversity increased with elevation, which may have corresponded with the biogeography of their plant hosts. Although dust fungal pathogen diversity was equivalent across elevations, elevation and sampling month interactions for the relative abundance, diversity, and richness of fungal pathogens suggest that these pathogens differed temporally across elevations, with potential implications for humans and wildlife. This study shows that landscape topography and droughts in source locations may alter the composition and diversity of ecologically relevant dust-associated microorganisms.
Essential Oils From Citrus unshiu Marc. Effectively Kill Aeromonas hydrophila by Destroying Cell Membrane Integrity, Influencing Cell Potential, and Leaking Intracellular Substances
Authors: Zhong Weiming , Chen Kangyong , Yang Linlin , Tang Tao , Jiang Sifan , Guo Jiajing , Gao Zhipeng
Published: June 2022

Aeromonas hydrophila is one of the important pathogenic bacteria in aquaculture causing serious losses every year. Essential oils are usually used as natural antimicrobial agents to reduce or replace the use of antibiotics. The aim of this study was to evaluate the antibacterial activity and explore the mechanisms of essential oil from satsuma mandarin (Citrus unshiu Marc.) (SMEO) against A. hydrophila. The results of the gas chromatography-mass spectrometer demonstrated that SMEO contains 79 chemical components with the highest proportion of limonene (70.22%). SMEO exhibited strong antibacterial activity against A. hydrophila in vitro, the diameter of the inhibition zone was 31.22 ± 0.46 mm, and the MIC and MBC values were all 1% (v/v). Intracellular material release, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and flow cytometry analysis revealed the dynamic antibacterial process of SMEO, the morphological changes of bacterial cells, and the leakage process of intracellular components. These results demonstrated that SMEO disrupted the extracellular membrane permeability. Our study demonstrated that SEMO has the potential to be used to control and prevent A. hydrophila infections in aquaculture.
Methane Reduction Potential of Brown Seaweeds and Their Influence on Nutrient Degradation and Microbiota Composition in a Rumen Simulation Technique
Authors: Künzel Susanne , Yergaliyev Timur , Wild Katharina J. , Philippi Hanna , Petursdottir Asta H. , Gunnlaugsdottir Helga , Reynolds Chris K. , Humphries David J. , Camarinha-Silva Amélia , Rodehutscord Markus
Published: June 2022

This study aimed to investigate the effects of two brown Icelandic seaweed samples (Ascophyllum nodosumandFucus vesiculosus) onin vitromethane production, nutrient degradation, and microbiota composition. A total mixed ration (TMR) was incubated alone as control or together with each seaweed at two inclusion levels (2.5 and 5.0% on a dry matter basis) in a long-term rumen simulation technique (Rusitec) experiment. The incubation period lasted 14 days, with 7 days of adaptation and sampling. The methane concentration of total gas produced was decreased at the 5% inclusion level ofA. nodosumandF. vesiculosusby 8.9 and 3.6%, respectively (P< 0.001). The total gas production was reduced by all seaweeds, with a greater reduction for the 5% seaweed inclusion level (P< 0.001). Feed nutrient degradation and the production of volatile fatty acids and ammonia in the effluent were also reduced, mostly with a bigger effect for the 5% inclusion level of both seaweeds, indicating a reduced overall fermentation (allP≤ 0.001). Microbiota composition was analyzed by sequencing 16S rRNA amplicons from the rumen content of the donor cows, fermenter liquid and effluent at days 7 and 13, and feed residues at day 13. Relative abundances of the most abundant methanogens varied between the rumen fluid used for the start of incubation and the samples taken at day 7, as well as between days 7 and 13 in both fermenter liquid and effluent (P< 0.05). According to the differential abundance analysis with q2-ALDEx2, in effluent and fermenter liquid samples, archaeal and bacterial amplicon sequence variants were separated into two groups (P< 0.05). One was more abundant in samples taken from the treatment without seaweed supplementation, while the other one prevailed in seaweed supplemented treatments. This group also showed a dose-dependent response to seaweed inclusion, with a greater number of differentially abundant members between a 5% inclusion level and unsupplemented samples than between a 2.5% inclusion level and TMR. Although supplementation of both seaweeds at a 5% inclusion level decreased methane concentration in the total gas due to the high iodine content in the seaweeds tested, the application of practical feeding should be done with caution.
Reverse Vaccinology and Immunoinformatic Assisted Designing of a Multi-Epitopes Based Vaccine Against Nosocomial Burkholderia cepacia
Authors: Alsowayeh Noorah , Albutti Aqel , Al-Shouli Samia T.
Published: June 2022

Burkholderia cepacia is a Gram-negative nosocomial pathogen and is considered as a troublesome bacterium due to its resistance to many common antibiotics. There is no licensed vaccine available to prevent the pathogen infections, thus making the condition more alarming and warrant the search for novel therapeutic and prophylactic approaches. In order to identify protective antigens from pathogen proteome, substantial efforts are put forth to prioritized potential vaccine targets and antigens that can be easily evaluated experimentally. In this vaccine design investigation, it was found that B. cepacia completely sequenced proteomes available in NCBI genome database has a total of 28,966 core proteins. Out of total, 25,282 proteins were found redundant while 3,684 were non-redundant. Subcellular localization revealed that 18 proteins were extracellular, 31 were part of the outer membrane, 75 proteins were localized in the periplasm, and 23 were virulent proteins. Five proteins namely flagellar hook protein (FlgE), fimbria biogenesis outer membrane usher protein, Type IV pilus secretin (PilQ), cytochrome c4, flagellar hook basal body complex protein (FliE) were tested for positive for antigenic, non-toxic, and soluble epitopes during predication of B-cell derived T-cell epitopes. A vaccine peptide of 14 epitopes (joined together via GPGPG linkers) and cholera toxin B subunit (CTBS) adjuvant (joined to epitopes peptide via EAAAK linker) was constructed. Binding interaction of the modeled vaccine with MHC-I, MHC-II, and Toll-like receptor 4 (TLR-4) immune receptors was studied using molecular docking studies and further analyzed in molecular dynamics simulations that affirms strong intermolecular binding and stable dynamics. The maximum root mean square deviation (RMSD) score of complexes in the simulation time touches to 2 Å. Additionally, complexes binding free energies were determined that concluded robust interaction energies dominated by van der Waals. The total energy of each complex is < −190 kcal/mol. In summary, the designed vaccine showed promising protective immunity against B. cepacia and needs to be examined in experiments.
Influence of Androgen Deprivation Therapy on the PD-L1 Expression and Immune Activity in Prostate Cancer Tissue
Authors: Sommer Ulrich , Ebersbach Celina , Beier Alicia-Marie K. , Baretton Gustavo B. , Thomas Christian , Borkowetz Angelika , Erb Holger H. H.
Published: June 2022

Immune checkpoint inhibitors have become a promising new therapy for cancer treatment. However, due to prostate cancer’s high heterogeneity and immune-suppressive tumour microenvironment, clinical trials with immune checkpoint inhibitors for prostate cancer resulted in low or no response. This descriptive and retrospective study investigates the influence of androgen deprivation therapy (ADT) on PD-L1 expression and CD8+ T-cell tumour infiltration and activity in primary prostate cancer tissue. Therefore, immunohistochemistry was used to assess PD-L1, CD8+ T-cell, and the immune activation marker Granzyme B (GrB) in PCa tissue before and under ADT. In line with previous studies, few prostate cancer tissues showed PD-L1 expression and CD8+ T-cell infiltration. However, PD-L1 expression levels on tumour cells or infiltrating immune cells above 5% generated an immune-suppressive tumour microenvironment harbouring hypofunctional CD8+ T-cells. Moreover, analysis of a longitudinal patient cohort before and under ADT revealed that ADT increased hypofunctional CD8+ T cells in the tumour area suggesting a tumour immune milieu optimal for targeting with immunotherapy.
Exploring the Conformational Impact of Glycine Receptor TM1-2 Mutations Through Coarse-Grained Analysis and Atomistic Simulations
Authors: Mhashal Anil Ranu , Yoluk Ozge , Orellana Laura
Published: June 2022

Pentameric ligand-gated ion channels (PLGICs) are a family of proteins that convert chemical signals into ion fluxes through cellular membranes. Their structures are highly conserved across all kingdoms from bacteria to eukaryotes. Beyond their classical roles in neurotransmission and neurological disorders, PLGICs have been recently related to cell proliferation and cancer. Here, we focus on the best characterized eukaryotic channel, the glycine receptor (GlyR), to investigate its mutational patterns in genomic-wide tumor screens and compare them with mutations linked to hyperekplexia (HPX), a Mendelian neuromotor disease that disrupts glycinergic currents. Our analysis highlights that cancer mutations significantly accumulate across TM1 and TM2, partially overlapping with HPX changes. Based on 3D-clustering, conservation, and phenotypic data, we select three mutations near the pore, expected to impact GlyR conformation, for further study by molecular dynamics (MD). Using principal components from experimental GlyR ensembles as framework, we explore the motions involved in transitions from the human closed and desensitized structures and how they are perturbed by mutations. Our MD simulations show that WT GlyR spontaneously explores opening and re-sensitization transitions that are significantly impaired by mutations, resulting in receptors with altered permeability and desensitization properties in agreement with HPX functional data.
Photoactivation of a Mechanosensitive Channel
Authors: Crea Fucsia , Vorkas Antreas , Redlich Aoife , Cruz Rubén , Shi Chaowei , Trauner Dirk , Lange Adam , Schlesinger Ramona , Heberle Joachim
Published: June 2022

Optogenetics in the conventional sense, i.e. the use of engineered proteins that gain their light sensitivity from naturally abundant chromophores, represents an exciting means to trigger and control biological activity by light. As an alternate approach, photopharmacology controls biological activity with the help of synthetic photoswitches. Here, we used an azobenzene-derived lipid analogue to optically activate the transmembrane mechanosensitive channel MscL which responds to changes in the lateral pressure of the lipid bilayer. In this work, MscL has been reconstituted in nanodiscs, which provide a native-like environment to the protein and a physical constraint to membrane expansion. We characterized this photomechanical system by FTIR spectroscopy and assigned the vibrational bands of the light-induced FTIR difference spectra of the trans and cis states of the azobenzene photolipid by DFT calculations. Differences in the amide I range indicated reversible conformational changes in MscL as a direct consequence of light switching. With the mediation of nanodiscs, we inserted the transmembrane protein in a free standing photoswitchable lipid bilayer, where electrophysiological recordings confirmed that the ion channel could be set to one of its sub-conducting states upon light illumination. In conclusion, a novel approach is presented to photoactivate and control cellular processes as complex and intricate as gravitropism and turgor sensing in plants, contractility of the heart, as well as sensing pain, hearing, and touch in animals.
Nematode microRNAs can Individually Regulate Interferon Regulatory Factor 4 and mTOR in Differentiating T Helper 2 Lymphocytes and Modulate Cytokine Production in Macrophages
Authors: Soichot Julien , Guttmann Nathalie , Rehrauer Hubert , Joller Nicole , Tritten Lucienne
Published: June 2022

Parasitic nematodes are masterful immunomodulators. This class of pathogens has evolved a spectrum of sophisticated strategies to regulate and evade host immune responses, mediated through the release of various molecules. In this context, the release of microRNAs (miRNAs), short post-transcriptional regulators of gene expression, has been of particular interest in the host-parasite interplay. Evidence that parasite-derived miRNAs modulate host innate and adaptive immune responses has become increasingly compelling. However, since miRNAs are usually contained in extracellular vesicles containing other mediators, it is difficult to assign an observed effect on host cells to miRNAs specifically. Here, the effects of some abundantly secreted miRNAs by nematodes used as models of gastrointestinal infections (Heligmosomoides polygyrus bakeri, Trichuris muris and Ascaris suum) were evaluated, addressing the potential of parasite miRNAs to impair in vitro differentiation of two important types of immune cells in the context of helminth infections, Th2 lymphocytes and macrophages. Mimicking a continuous exposure to low concentrations of nematode miRNAs, the interferon gamma signaling, the IL-2/STAT5 signaling, and the mTOR signaling pathways were identified as downregulated by Hpo-miR-71-5p. Interferon regulatory factor 4 (Irf4) was validated as a target of Hpo-miR-71-5p, while Mtor is targeted by Asu-miR-791-3p, abundant in the T. muris secretions. By trend, Hpo-miR-71-5p impacts mildly but consistently on the amounts of inflammatory cytokines in unpolarized macrophages but leads to slightly increased IL-10 level in alternatively activated cells. In addition, our data suggests that transfected miRNAs remain for days in recipient cells, and that Hpo-miR-71-5p can incorporate into mouse Argonaute protein complexes. Nematode miRNAs can impair both innate and adaptive arms of host immunity. Hpo-miR-71-5p in particular, absent in mammals, interacts with host genes and pathways with crucial involvement in anthelmintic immune responses. This report brings new insights into the dynamics of miRNA-driven immunomodulation and highlights putative targeted pathways. Although the absolute repression is subtle, it is expected that the dozens of different miRNAs released by nematodes may have a synergistic effect on surrounding host cells.