bluuebunny/crossref_metadata_2025 huggingface dataset:
Flavofun: Exploration of fungal flavoproteomes
Authors: Kerschbaumer Bianca , Bijelic Aleksandar , Macheroux Peter
Published: December 2022

Fungi produce a plethora of natural products exhibiting a fascinating diversity of chemical structures with an enormous potential for medical applications. Despite the importance of understanding the scope of natural products and their biosynthetic pathways, a systematic analysis of the involved enzymes has not been undertaken. In our previous studies, we examined the flavoprotein encoding gene pool in archaea, eubacteria, the yeast Saccharomyces cerevisiae, Arabidopsis thaliana, and Homo sapiens. In the present survey, we have selected the model fungus Neurospora crassa as a starting point to investigate the flavoproteomes in the fungal kingdom. Our analysis showed that N. crassa harbors 201 flavoprotein-encoding genes amounting to 2% of the total protein-encoding genome. The majority of these flavoproteins (133) could be assigned to primary metabolism, termed the “core flavoproteome”, with the remainder of flavoproteins (68) serving in, as yet unidentified, reactions. The latter group of “accessory flavoproteins” is dominated by monooxygenases, berberine bridge enzyme-like enzymes, and glucose-methanol-choline-oxidoreductases. Although the exact biochemical role of most of these enzymes remains undetermined, we propose that they are involved in activities closely associated with fungi, such as the degradation of lignocellulose, the biosynthesis of natural products, and the detoxification of harmful compounds in the environment. Based on this assumption, we have analyzed the accessory flavoproteomes in the fungal kingdom using the MycoCosm database. This revealed large differences among fungal divisions, with Ascomycota, Basidiomycota, and Mucoromycota featuring the highest average number of genes encoding accessory flavoproteins. Moreover, a more detailed analysis showed a massive accumulation of accessory flavoproteins in Sordariomycetes, Agaricomycetes, and Glomeromycotina. In our view, this indicates that these fungal classes are proliferative producers of natural products and also interesting sources for flavoproteins with potentially useful catalytic properties in biocatalytic applications.
Favorable effect of renal denervation on elevated renal vascular resistance in patients with resistant hypertension and type 2 diabetes mellitus
Authors: Manukyan Musheg , Falkovskaya Alla , Mordovin Victor , Pekarskiy Stanislav , Zyubanova Irina , Solonskaya Ekaterina , Ryabova Tamara , Khunkhinova Simzhit , Vtorushina Anastasia , Popov Sergey
Published: December 2022

Objective

To assess the effect of renal denervation (RDN) on renal vascular resistance and renal function in patients with drug-resistant hypertension (HTN) and type 2 diabetes mellitus (T2DM).

Materials and methods

Fifty-nine patients (mean age 60.3 ± 7.9 years, 25 men) with resistant HTN [mean 24-h ambulatory blood pressure (BP) 158.0 ± 16.3/82.5 ± 12.7 mmHg, systolic/diastolic] and T2DM (mean HbA1c 7.5 ± 1.5%) were included in the single-arm prospective study and underwent RDN. Renal resistive index (RRI) derived from ultrasound Doppler; estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration formula), office and 24-h ambulatory BP were measured at baseline, 6, and 12 months after RDN to evaluate the respective changes in renal vascular resistance, renal function, and BP during treatment.

Results

Forty-three patients completed 12 months follow-up. The RRI changed depending on the baseline value. Specifically, the RRI decreased significantly in patients with elevated baseline RRI values ≥ 0.7 {n = 23; −0.024 [95% confidence interval (CI): −0.046, −0.002], p = 0.035} and did not change in those with baseline RRI < 0.7 [n = 36; 0.024 (95% CI: −0.002, 0.050), p = 0.069]. No significant change was observed in eGFR whereas BP was significantly reduced at 12 months after RDN by −10.9 (95% CI: −16.7, −5.0)/−5.5 (95% CI: −8.7, −2.4) mmHg, systolic/diastolic. No relationship was found between the changes in RRI and BP.

Conclusion

Our study shows that RDN can decrease elevated renal vascular resistance (RRI > 0.7) and stabilize kidney function in patients with RHTN and T2DM independently of its BP-lowering effect.
Neoatherosclerosis prediction using plaque markers in intravascular optical coherence tomography images
Authors: Lee Juhwan , Pereira Gabriel T. R. , Motairek Issam , Kim Justin N. , Zimin Vladislav N. , Dallan Luis A. P. , Hoori Ammar , Al-Kindi Sadeer , Guagliumi Giulio , Wilson David L.
Published: December 2022

Introduction

In-stent neoatherosclerosis has emerged as a crucial factor in post-stent complications including late in-stent restenosis and very late stent thrombosis. In this study, we investigated the ability of quantitative plaque characteristics from intravascular optical coherence tomography (IVOCT) images taken just prior to stent implantation to predict neoatherosclerosis after implantation.

Methods

This was a sub-study of the TRiple Assessment of Neointima Stent FOrmation to Reabsorbable polyMer with Optical Coherence Tomography (TRANSFORM-OCT) trial. Images were obtained before and 18 months after stent implantation. Final analysis included images of 180 lesions from 90 patients; each patient had images of two lesions in different coronary arteries. A total of 17 IVOCT plaque features, including lesion length, lumen (e.g., area and diameter); calcium (e.g., angle and thickness); and fibrous cap (FC) features (e.g., thickness, surface area, and burden), were automatically extracted from the baseline IVOCT images before stenting using dedicated software developed by our group (OCTOPUS). The predictive value of baseline IVOCT plaque features for neoatherosclerosis development after stent implantation was assessed using univariate/multivariate logistic regression and receiver operating characteristic (ROC) analyses.

Results

Follow-up IVOCT identified stents with (n = 19) and without (n = 161) neoatherosclerosis. Greater lesion length and maximum calcium angle and features related to FC were associated with a higher prevalence of neoatherosclerosis after stent implantation (p < 0.05). Hierarchical clustering identified six clusters with the best prediction p-values. In univariate logistic regression analysis, maximum calcium angle, minimum calcium thickness, maximum FC angle, maximum FC area, FC surface area, and FC burden were significant predictors of neoatherosclerosis. Lesion length and features related to the lumen were not significantly different between the two groups. In multivariate logistic regression analysis, only larger FC surface area was strongly associated with neoatherosclerosis (odds ratio 1.38, 95% confidence interval [CI] 1.05–1.80, p < 0.05). The area under the ROC curve was 0.901 (95% CI 0.859–0.946, p < 0.05) for FC surface area.

Conclusion

Post-stent neoatherosclerosis can be predicted by quantitative IVOCT imaging of plaque characteristics prior to stent implantation. Our findings highlight the additional clinical benefits of utilizing IVOCT imaging in the catheterization laboratory to inform treatment decision-making and improve outcomes.
Paleoseismology of the Marquesado-La Rinconada thrust system, Eastern Precordillera of Argentina
Authors: Rockwell Thomas K. , Costa Carlos H. , Meigs Andrew J. , Ragona Daniel , Owen Lewis A. , Murari Madhav Krishna , Masana Eulalia , Richard Andrés D.
Published: December 2022

Excavated trenches at two sites across the Marquesado–La Rinconada fault system along the eastern Precordilleran front south of San Juan, Argentina, reveal the earthquake history of this rapidly urbanizing region. Interpretation of earthquakes is based on both the generation of colluvial wedges and upward fault terminations, as well as folding events in fine-grained alluvium ponded behind upslope-facing fault scarps. The ages of the past five interpreted earthquakes at the Loma Negra site are E1 at 2.8 ± 2.8 ka, E2 at 7.1 ± 1.5 ka, E3 at 9.6 ± 1.3 ka, E4 at 14.4 ± 2.1 ka, and E5 at 17.2 ± 3.1 ka. At the Jejenes sites, we documented event ages of 2.7 ± 0.1 ka, 3.9 ± 0.6 ka, 5.9 ± 1.3 ka, and 11.4 ± 4 ka. These results indicate that the recurrence interval along the Marquesado–La Rinconada fault zone averages several thousand years. The inferred displacements at the Jejenes site are about 1.1 m for E1, E3, and E4 and 2.1 m for event E2, whereas the displacements at Loma Negra averaged about 1 m, but the most recent event displays less slip. Notably, the older events seem to have been larger and emergent, whereas the youngest event appears to have been smaller and blind in the ponded sediment; this may partially explain the poor expression of classic colluvial wedges associated with some events. Despite the fact that active surface faulting has an uncertain relationship with the primary seismic sources at depth in the crust, past and future events of Mw∼7.5 are consistent with the length scale of active deformation, the ∼1–2 m slip per event scale of these ruptures, and the size of historical earthquakes.
Validation of automated scoring for learning progression-aligned Next Generation Science Standards performance assessments
Authors: Kaldaras Leonora , Haudek Kevin C.
Published: December 2022

Introduction

The Framework for K-12 Science Education promotes supporting the development of knowledge application skills along previously validated learning progressions (LPs). Effective assessment of knowledge application requires LP-aligned constructed-response (CR) assessments. But these assessments are time-consuming and expensive to score and provide feedback for. As part of artificial intelligence, machine learning (ML) presents an invaluable tool for conducting validation studies and providing immediate feedback. To fully evaluate the validity of machine-based scores, it is important to investigate human-machine score consistency beyond observed scores. Importantly, no formal studies have explored the nature of disagreements between human and machine-assigned scores as related to LP levels.

Methods

We used quantitative and qualitative approaches to investigate the nature of disagreements among human and scores generated by two approaches to machine learning using a previously validated assessment instrument aligned to LP for scientific argumentation.

Results

We applied quantitative approaches, including agreement measures, confirmatory factor analysis, and generalizability studies, to identify items that represent threats to validity for different machine scoring approaches. This analysis allowed us to determine specific elements of argumentation practice at each level of the LP that are associated with a higher percentage of misscores by each of the scoring approaches. We further used qualitative analysis of the items identified by quantitative methods to examine the consistency between the misscores, the scoring rubrics, and student responses. We found that rubrics that require interpretation by human coders and items which target more sophisticated argumentation practice present the greatest threats to the validity of machine scores.

Discussion

We use this information to construct a fine-grained validity argument for machine scores, which is an important piece because it provides insights for improving the design of LP-aligned assessments and artificial intelligence-enabled scoring of those assessments.
Development of Type 1 Diabetes may occur through a Type 2 Diabetes mechanism
Authors: Josefsen Knud , Krogvold Lars , Gerling Ivan C. , Pociot Flemming , Dahl-Jørgensen Knut , Buschard Karsten
Published: December 2022

Background

At diagnosis of Type 1 Diabetes (T1D), 30% of the beta cells are dormant, i.e. alive, but inactive. This could reduce beta cell destruction, as cellular stress contributes to beta cell damage. However, the beta cells, that are still active, must produce more insulin and are therefore more vulnerable. The inactive beta cells represent a potential for restoring the insulin secretion.

Methods

We analyzed the expression of selected genes in islets from live, newly diagnosed T1D patients from the DiViD study and organ doners with longer duration of T1D, type 2 diabetes (T2D), or no diabetes from the nPOD study. Additionally, analysis of polymorphisms was performed on all the investigated genes.

Findings

Various possibilities were considered for the inactivity of the beta cells: secretion defect, fetal state, hibernation, and insulin resistance. We analyzed genes related to the ceramide and sphingomyelin synthesis and degradation, secretion, circadian rhythm and insulin action, and found changes in T1D islets that resemble fetal dedifferentiation and asynchrony. Furthermore, we found low levels of insulin receptor mRNA in the islets. No polymorphisms were found.

Interpretation

Our findings suggest a secretion defect, but also fetal dedifferentiation and desynchronization in the inactive beta cells. Together with previous evidence, that predisposing factors for T2D are also present for T1D development, we raise the idea to treat individuals with ongoing T1D development prophylactically with T2D medicine like GLP-1 receptor agonists, metformin, or others, combined with anti-inflammatory compounds, in order to reactivate the dormant beta cells, and to prevent autoimmune destruction. T2D mechanisms during T1D development should be investigated further.
Variation in the hydrological cycle in the Three-River Headwaters Region based on multi-source data
Authors: Yang Yong , Chen Rensheng , Ding Yongjian , Zhao Qiudong , Li Hongyuan , Liu Zhangwen
Published: December 2022

The hydrological processes in the Three-River Headwaters Region (TRHR), which is located in the Qinghai-Tibetan Plateau and includes the Yangtze River Headwater Region (YARHR), the Yellow River Headwater Region (YERHR), and the Lantsang River Headwater Region (LARHR), have changed under climate warming. Based on multi-source data, the spatial and temporal changes in precipitation, evapotranspiration, soil water storage, glacier melt, snowmelt and runoff in the Three-River Headwaters Region from 1982 to 2014 were comprehensively analysed. The annual precipitation data for the Three-River Headwaters Region from ERA5-Land, the Climatic Research Unit, the China Meteorological Forcing Dataset and the Global Land Data Assimilation System (GLDAS) all showed an increasing trend; the annual evapotranspiration data from ERA5-Land, Global Land Data Assimilation System, Global Land Evaporation Amsterdam Model (GLEAM) and Terrestrial Evapotranspiration Dataset across China (TEDC) all showed an increasing trend; and the annual soil water storage data from ERA5-Land, Global Land Data Assimilation System and Global Land Evaporation Amsterdam Model all showed an increasing trend. The annual snowmelt data from ERA5-Land, Global Land Data Assimilation System and SMT-Y datasets all showed a decreasing trend. The annual glacier melt increased in the Yangtze River Headwater Region and Yellow River Headwater Region and decreased in the Lantsang River Headwater Region. The increases in precipitation, evapotranspiration, soil water content and glacial melt, and the decreases in snowfall and snowmelt indicate an accelerated hydrological cycle in the Three-River Headwaters Region over the 1982 to 2014 period. The significant increase in precipitation is the main reason for the significant increase in runoff in the Yangtze River Headwater Region. The increase in precipitation in the Yellow River Headwater Region was less than the sum of the increase in evapotranspiration and soil water storage, resulting in a decreasing trend of runoff in the Yellow River Headwater Region. The increase in precipitation in the Lantsang River Headwater Region was slightly larger than the sum of that in evapotranspiration and soil water storage, and there was an insignificant increase in the runoff in the Lantsang River Headwater Region.
Breaking the cycle of malaria treatment failure
Authors: Boni Maciej F.
Published: December 2022

Treatment of symptomatic malaria became a routine component of the clinical and public health response to malaria after the second world war. However, all antimalarial drugs deployed against malaria eventually generated enough drug resistance that they had to be removed from use. Chloroquine, sulfadoxine-pyrimethamine, and mefloquine are well known examples of antimalarial drugs to which resistance did and still does ready evolve. Artemisinin-based combination therapies (ACTs) are currently facing the same challenge as artemisinin resistance is widespread in Southeast Asia and emerging in Africa. Here, I review some aspects of drug-resistance management in malaria that influence the strength of selective pressure on drug-resistant malaria parasites, as well as an approach we can take in the future to avoid repeating the common mistake of deploying a new drug and waiting for drug resistance and treatment failure to arrive. A desirable goal of drug-resistance management is to reduce selection pressure without reducing the overall percentage of patients that are treated. This can be achieved by distributing multiple first-line therapies (MFT) simultaneously in the population for the treatment of uncomplicated falciparum malaria, thereby keeping treatment levels high but the overall selection pressure exerted by each individual therapy low. I review the primary reasons that make MFT a preferred resistance management option in many malaria-endemic settings, and I describe two exceptions where caution and additional analyses may be warranted before deploying MFT. MFT has shown to be feasible in practice in many endemic settings. The continual improvement and increased coverage of genomic surveillance in malaria may allow countries to implement custom MFT strategies based on their current drug-resistance profiles.
Assessment of immunotherapy response in intracranial malignancy using semi-automatic segmentation on magnetic resonance images
Authors: Tan Jia , Liu Chang , Li Yan , Ma Yiqi , Xie Ruoxi , Li Zheng , Wan Hengjiang , Lui Su , Wu Min
Published: December 2022

Objective

To explore multi-aspect radiologic assessment of immunotherapy response in intracranial malignancies based on a semi-automatic segmentation technique, and to explore volumetric thresholds with good performance according to RECIST 1.1 thresholds.

Methods

Patients diagnosed with intracranial malignancies and treated with immunotherapy were included retrospectively. In all MR images, target lesions were measured using a semi-automatic segmentation technique that could intelligently generate visual diagrams including RECIST 1.1, total volume, and max. 3D diameter. The changes in parameters were calculated for each patient after immunotherapy. The ROC curve was used to analyze the sensitivity and specificity of the size change of the legion. This was useful to find new volumetric thresholds with better efficiency in response assessment. The changes in total volume were assessed by conventional volumetric thresholds, while RECIST 1.1 thresholds were for the max. 3D diameter. A chi-square test was used to compare the concordance and diagnostic correlation between the response assessment results of the three criteria.

Results

A total of 20 cases (average age, 58 years; range, 23 to 84 years) and 58 follow-up MR examinations after immunotherapy were included in the analysis. The P-value of the chi-square test between RECIST 1.1 and total volume is 0 (P <0.05), same as that in RECIST 1.1 and max. 3D diameter. The kappa value of the former two was 0.775, and the kappa value for the latter two was 0.742. The above results indicate a significant correlation and good concordance for all three criteria. In addition, we also found that the volumetric assessment had the best sensitivity and specificity for the immunotherapy response in intracranial malignancies, with a PR threshold of −64.9% and a PD threshold of 21.4%.

Conclusions

Radiologic assessment of immunotherapy response in intracranial malignancy can be performed by multiple criteria based on semi-automatic segmentation technique on MR images, such as total volume, max. 3D diameter and RECIST 1.1. In addition, new volumetric thresholds with good sensitivity and specificity were found by volumetric assessment.
The immune landscape of high-grade brain tumor after treatment with immune checkpoint blockade
Authors: Park Jang Hyun , Kang In , Lee Heung Kyu
Published: December 2022

Despite the therapeutic success of immune checkpoint blockade (ICB) therapy against multiple tumors, many patients still do not benefit from ICB. In particular, high-grade brain tumors, such as glioblastoma multiforme (GBM), have a very low response rate to ICB, resulting in several failed clinical trials. This low response rate might be caused by a lack of understanding of the unique characteristics of brain immunity. To overcome this knowledge gap, macroscopic studies of brain immunity are needed. We use single cell RNA sequencing to analyze the immune landscape of the tumor microenvironment (TME) under anti-PD-1 antibody treatment in a murine GBM model. We observe that CD8 T cells show a mixed phenotype overall that includes reinvigoration and re-exhaustion states. Furthermore, we find that CCL5 induced by anti-PD-1 treatment might be related to an increase in the number of anti-inflammatory macrophages in the TME. Therefore, we hypothesize that CCL5-mediated recruitment of anti-inflammatory macrophages may be associated with re-exhaustion of CD8 T cells in the TME. We compare our observations in the murine GBM models with publicly available data from human patients with recurrent GBM. Our study provides critical information for the development of novel immunotherapies to overcome the limitations of anti-PD-1 therapy.
Fatty acid metabolism is related to the immune microenvironment changes of gastric cancer and RGS2 is a new tumor biomarker
Authors: Yang Shifeng , Sun Boshi , Li Wenjing , Yang Hao , Li Nana , Zhang Xinyu
Published: December 2022

Background

Alterations in lipid metabolism promote tumor progression. However, the role of lipid metabolism in the occurrence and development of gastric cancer have not been fully clarified

Method

Here, genes that are related to fatty acid metabolism and differentially-expressed between normal and gastric cancer tissues were identified in the TCGA-STAD cohort. The intersection of identified differentially-expressed genes with Geneset was determined to obtain 78 fatty acid metabolism-related genes. The ConsensusClusterPlus R package was used to perform differentially-expressed genes, which yielded divided two gastric cancer subtypes termed cluster 1 and cluster 2.

Results

Patients in cluster 2 was found to display poorer prognosis than patients in cluster 1. Using machine learning method to select 8 differentially expressed genes among subtypes to construct fatty acid prognostic risk score model (FARS), which was found to display good prognostic efficacy. We also identified that certain anticancer drugs, such as bortezomib, elesclomol, GW843682X, and nilotinib, showed significant sensitivity in the high FARS score group. RGS2 was selected as the core gene upon an analysis of the gastric cancer single-cell, and Western blotting and immunofluorescence staining results revealed high level of expression of this gene in gastric cancer cells. The results of immunohistochemical staining showed that a large amount of RGS2 was deposited in the stroma in gastric cancer. A pan-cancer analysis also revealed a significant association of RGS2 with TMB, TIDE, and CD8+ T-cell infiltration in other cancer types as well. RGS2 may thus be studied further as a new target for immunotherapy in future studies on gastric cancer.

Conclusion

In summary, the FARS model developed here enhances our understanding of lipid metabolism in the TME in gastric cancer, and provides a theoretical basis for predicting tumor prognosis and clinical treatment.
3D tumor explant as a novel platform to investigate therapeutic pathways and predictive biomarkers in cancer patients
Authors: Rodolfo Monica , Huber Veronica , Cossa Mara , Gallino Gianfrancesco , Leone Biagio E. , Vallacchi Viviana , Rivoltini Licia , Vergani Elisabetta
Published: December 2022

Immunotherapy with immune checkpoint inhibitors can induce durable clinical responses in different human malignancies but the number of responding patients remains globally modest. The limited therapeutic efficacy of ICI depends on multiple factors, among which the immune suppressive features of the tumor microenvironment play a key role. For this reason, experimental models that enable dissection of the immune-hostile tumor milieu components are required to unravel how to overcome resistance and obtain full-fledged anti-tumor immunity. Recent evidence supports the usefulness of 3D ex vivo systems in retaining features of tumor microenvironment to elucidate molecular and immunologic mechanisms of response and resistance to immune checkpoint blockade. In this perspective article we discuss the recent advances in patient-derived 3D tumor models and their potential in support of treatment decision making in clinical setting. We will also share our experience with dynamic bioreactor tumor explant culture of samples from melanoma and sarcoma patients as a reliable and promising platform to unravel immune responses to immune checkpoint inhibitors.
Case report: JAKi and TNFi dual therapy is a potential treatment strategy for difficult-to-treat rheumatoid arthritis
Authors: Chen Jing-Wen , Zhang Wen-Shuang , Lin Chang-Song , Xu Qiang
Published: December 2022

Rheumatoid arthritis (RA) is a heterogeneous chronic disease. RA patients should start disease modifying anti-rheumatic drugs (DMARDs) therapy immediately after diagnosis. If first-line treatment with conventional synthetic DMARDs does not relieve the disease, biology and targeted synthetic DMARDs are options for patients. Patients can switch to different types of biological and targeted synthetic DMARDs if remission is not achieved. However, for patients with difficult-to-treat RA, achieving disease stabilization after the failure of multiple biological and targeted synthetic DMARDs is a clinical challenge that needs to be addressed. As distinct cytokine pathways, the benefits and challenges of dual therapy are worth discussing. As the most extensively used biologic DMARDs, adalimumab is an anti-tumor necrosis factor monoclonal antibody used to treat RA. Tofacitinib, as a Janus Kinase inhibitor, is an orally administered targeted synthetic DMARDs that involved in the regulation of immune responses by directly or indirectly inhibiting cytokine pathways. This report describes a successful case of a 48-year-old woman with difficult-to-treat RA who treated with Tofacitinib combined with adalimumab. She had been on glucocorticosteroid for a long time, but had persistent joint pain and fatigue. At more than one year of follow-up, her Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-ESR) remained in complete remission, and she discontinued her glucocorticosteroid medications. Also, she did not develop a mycobacterial tuberculosis infection, herpes zoster, and new-onset cardiovascular events.
Species-specific and seasonal differences in the resistance of salt-marsh vegetation to wave impact
Authors: Reents Svenja , Möller Iris , Evans Ben R. , Schoutens Ken , Jensen Kai , Paul Maike , Bouma Tjeerd J. , Temmerman Stijn , Lustig Jennifer , Kudella Matthias , Nolte Stefanie
Published: December 2022

The coastal protection function provided by the vegetation of tidal wetlands (e.g. salt marshes) will play an important role in defending coastlines against storm surges in the future and depend on how these systems respond to such forcing. Extreme wave events may induce vegetation failure and thereby risking loss of functionality in coastal protection. However, crucial knowledge on how hydrodynamic forces affect salt-marsh vegetation and whether plant properties might influence plant resistance is missing. In a true-to-scale flume experiment, we exposed two salt-marsh species to extreme hydrodynamic conditions and quantified wave-induced changes in plant frontal area, which was used to estimate plant damage. Moreover, half of the plants were artificially weakened to induce senescence, thus allowing us to examine potential seasonal effects on plant resistance. Morphological, biomechanical as well as biochemical plant properties were assessed to better explain potential differences in wave-induced plant damage. Our results indicate that the plants were more robust than expected, with pioneer species Spartina anglica showing a higher resistance than the high-marsh species Elymus athericus. Furthermore, wave-induced plant damage mostly occurred in the upper part of the vegetation canopy and thus higher canopies (i.e. Elymus athericus) were more vulnerable to damage. Besides a taller canopy, Elymus athericus had weaker stems than Spartina anglica, suggesting that biomechanical properties (flexural stiffness) also played a role in defining plant resistance. Under the highest wave conditions, we also found seasonal differences in the vulnerability to plant damage but only for Elymus athericus. Although we found higher concentrations of a strengthening compound (biogenic silica) in the plant material of the weakened plants, the flexibility of the plant material was not affected indicating that the treatment might not has been applied long enough. Nevertheless, this study yields important implications since we demonstrate a high robustness of the salt-marsh vegetation as well as species-specific and seasonal differences in the vulnerability to plant damage.
Degradable composite aerogel with excellent water-absorption for trace water removal in oil and oil-in-water emulsion filtration
Authors: Lu Hong , Jiang Xueliang , Wang Jintao , Hu Ruofei
Published: December 2022

In this study, using chitosan (CS) and carboxymethyl cellulose (CMC) as backbone and introducing citric acid (CA)to enhance the electrostatic interaction of the system, citric acid/chitosan/carboxymethyl cellulose (CA/CS/CMC) aerogel is obtained by simple freeze-drying. CA/CS/CMC composite aerogel exhibits light weight, low density, high porosity, outstanding hydrophilic and water retention properties, and satisfactory underwater oleophobicity. The water adsorption capacity of the obtained aerogels can reach 43.87–80.28 g/g, which are far more than that of carboxymethyl cellulose and chitosan aerogels (14.27–20.08 g/g). In addition, with strong hydrophilicity, underwater oleophobicity and water retention endowed by the rough internal microstructure and the rich hydroxyl, amino, and carboxyl groups, the fabricated aerogel can also be used as a filter to achieve effective separation of oil-in-water emulsions and oil/water mixtures. The separation efficiency of aerogel for oil/water mixtures are higher than 90.7%. Because the developed preparation method is green, simple and mild and the raw materials are readily available and environmentally friendly, the obtained CA/CS/CMC aerogel with strong water absorption capacity and good separation efficiency displays a promising application in water-oil separation.
Bacteriophage: A new therapeutic player to combat neutrophilic inflammation in chronic airway diseases
Authors: Laucirica Daniel R. , Stick Stephen M. , Garratt Luke W. , Kicic Anthony
Published: December 2022

Persistent respiratory bacterial infections are a clinical burden in several chronic inflammatory airway diseases and are often associated with neutrophil infiltration into the lungs. Following recruitment, dysregulated neutrophil effector functions such as increased granule release and formation of neutrophil extracellular traps (NETs) result in damage to airway tissue, contributing to the progression of lung disease. Bacterial pathogens are a major driver of airway neutrophilic inflammation, but traditional management of infections with antibiotic therapy is becoming less effective as rates of antimicrobial resistance rise. Bacteriophages (phages) are now frequently identified as antimicrobial alternatives for antimicrobial resistant (AMR) airway infections. Despite growing recognition of their bactericidal function, less is known about how phages influence activity of neutrophils recruited to sites of bacterial infection in the lungs. In this review, we summarize currentin vitroandin vivofindings on the effects of phage therapy on neutrophils and their inflammatory mediators, as well as mechanisms of phage-neutrophil interactions. Understanding these effects provides further validation of their safe use in humans, but also identifies phages as a targeted neutrophil-modulating therapeutic for inflammatory airway conditions.
Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9
Authors: Shi Shang , Liu Yang , Wang Zhiyue , Jin Xiangren , Yan Wei , Guo Xiao , Lin Baiqiang , Wang Haoran , Li Bowen , Zheng Jianjun , Wei Yunwei
Published: December 2022

Background

Despite advances in anastomotic techniques and perioperative care, the incidence of anastomotic leak (AL) has not substantially decreased over time. Although it is known that AL etiology is multifactorial and the mechanisms involved remain unclear, there is accumulating evidence pointing at AL related to gut microbiota.

Method

We firstly performed a clinical study to analyze the gut microbiota between colorectal cancer patients who developed AL and those who did not (nAL) using 16S-rRNA sequencing and quantitative real-time PCR to identify AL risk bacterial taxa. Then we built a rat anastomosis model and performed a bacteria transplantation to ensure the cause-effect relationship. The anastomotic healing score was used to evaluate the healing of anastomosis. In addition, we assessed the adhesion ability of bacteria by staining with fluorescein isothiocyanate and attachment assay. The expression of matrix metalloproteinase 9 (MMP9) was detected by western blot, and the activity was detected by gelatin zymography.

Results

We found that the abundance and positive rate of Fusobacterium nucleatum (Fn) were higher in the AL patients. Exposure of the rat’s colon anastomosis to Fn contributes to the loss of submucosa collagen I and III, leading to AL’s pathogenesis. Fn can attach to the gut epithelial cells and stimulate intestinal MMP9 expression in vitro and in vivo. We further confirmed that these effects of Fn depended on the E-cadherin/β-catenin signaling pathway.

Conclusion

This work demonstrates that Fn attaches and then stimulates the expression of epithelial cells MMP9 by the E-cadherin/β-catenin signaling pathway. These effects contribute to collagen break down in the intestinal tissue, finally leading to AL.
A new dawn for monoclonal antibodies against antimicrobial resistant bacteria
Authors: Troisi Marco , Marini Eleonora , Abbiento Valentina , Stazzoni Samuele , Andreano Emanuele , Rappuoli Rino
Published: December 2022

Antimicrobial resistance (AMR) is a quickly advancing threat for human health worldwide and almost 5 million deaths are already attributable to this phenomenon every year. Since antibiotics are failing to treat AMR-bacteria, new tools are needed, and human monoclonal antibodies (mAbs) can fill this role. In almost 50 years since the introduction of the first technology that led to mAb discovery, enormous leaps forward have been made to identify and develop extremely potent human mAbs. While their usefulness has been extensively proved against viral pathogens, human mAbs have yet to find their space in treating and preventing infections from AMR-bacteria and fully conquer the field of infectious diseases. The novel and most innovative technologies herein reviewed can support this goal and add powerful tools in the arsenal of weapons against AMR.
Endogenous tagging of Unc-13 reveals nanoscale reorganization at active zones during presynaptic homeostatic potentiation
Authors: Dannhäuser Sven , Mrestani Achmed , Gundelach Florian , Pauli Martin , Komma Fabian , Kollmannsberger Philip , Sauer Markus , Heckmann Manfred , Paul Mila M.
Published: December 2022

Introduction

Neurotransmitter release at presynaptic active zones (AZs) requires concerted protein interactions within a dense 3D nano-hemisphere. Among the complex protein meshwork the (M)unc-13 family member Unc-13 of Drosophila melanogaster is essential for docking of synaptic vesicles and transmitter release.

Methods

We employ minos-mediated integration cassette (MiMIC)-based gene editing using GFSTF (EGFP-FlAsH-StrepII-TEV-3xFlag) to endogenously tag all annotated Drosophila Unc-13 isoforms enabling visualization of endogenous Unc-13 expression within the central and peripheral nervous system.

Results and discussion

Electrophysiological characterization using two-electrode voltage clamp (TEVC) reveals that evoked and spontaneous synaptic transmission remain unaffected in unc-13GFSTF 3rd instar larvae and acute presynaptic homeostatic potentiation (PHP) can be induced at control levels. Furthermore, multi-color structured-illumination shows precise co-localization of Unc-13GFSTF, Bruchpilot, and GluRIIA-receptor subunits within the synaptic mesoscale. Localization microscopy in combination with HDBSCAN algorithms detect Unc-13GFSTF subclusters that move toward the AZ center during PHP with unaltered Unc-13GFSTF protein levels.
Case report: MELAS and concomitant presumed antiphospholipid antibody syndrome in an adult woman
Authors: Nouduri Sirisha , Padmanabhan Rajiv , Hicks Richard , Abbott Mary-Alice , O'Brien Dennis , Schlaug Gottfried
Published: December 2022

Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes, and other features (short stature, headaches, seizures, and sensorineural hearing loss) constitute characteristics of MELAS syndrome. MELAS is a rare condition due to mutations in maternally inherited mitochondrial DNA with levels of heteroplasmy possibly related to late adulthood presentation. A previously reported MELAS case coexisted with presumed Antiphospholipid Antibody Syndrome (APLAS), but the connection between MELAS and a potential APLAS is unclear. A 29-year-old woman presented with mild right-sided sensorimotor symptoms and mixed aphasia in November 2021. She presented again in May 2022 for unrelenting headaches and was found to have a new right hemisphere syndrome with mild left-sided sensorimotor symptoms, hemineglect, and anosognosia. Characteristic lab and imaging studies were obtained. During the first presentation (October 2021), the discovery of anticardiolipin IgM antibodies (aCL) (and their replication 3 months later) led to a diagnosis of APLAS, and Warfarin was initiated. During the second admission (May 2022), a new stroke-like lesion on the right hemisphere with characteristic features not suggestive of ischemia was detected, which led to a diagnosis of MELAS (m3243A > G mutation). Although MELAS and APLAS could co-exist, alternatively, it is possible that antiphospholipid antibodies might be generated when the strongly anionic Cardiolipin-Hydroperoxide from the inner mitochondrial membrane is exposed to immune component cells upon cell lysis. Thus, the presence of aCL in patients with stroke-like lesions might masquerade as an APLAS, but should probably be questioned if only aCL are repeatedly found and imaging findings are not characteristic for ischemic lesions.
Mushroom polysaccharides with potential in anti-diabetes: Biological mechanisms, extraction, and future perspectives: A review
Authors: Liu Xiaofei , Luo Donghui , Guan Jingjing , Chen Jin , Xu Xiaofei
Published: December 2022

Diabetes mellitus (DM) is a global health threat. Searching for anti-diabetic components from natural resources is of intense interest to scientists. Mushroom polysaccharides have received growing attention in anti-diabetes fields due to their advantages in broad resources, structure diversity, and multiple bioactivities, which are considered an unlimited source of healthy active components potentially applied in functional foods and nutraceuticals. In this review, the current knowledge about the roles of oxidative stress in the pathogenesis of DM, the extraction method of mushroom polysaccharides, and their potential biological mechanisms associated with anti-diabetes, including antioxidant, hypolipidemic, anti-inflammatory, and gut microbiota modulatory actions, were summarized based on a variety of in vitro and in vivo studies, with aiming at better understanding the roles of mushroom polysaccharides in the prevention and management of DM and its complications. Finally, future perspectives including bridging the gap between the intervention of mushroom polysaccharides and the modulation of insulin signaling pathway, revealing structure-bioactivity of mushroom polysaccharides, developing synergistic foods, conducting well-controlled clinical trials that may be very helpful in discovering valuable mushroom polysaccharides and better applications of mushroom polysaccharides in diabetic control were proposed.
Valorization of whey proteins and beetroot peels to develop a functional beverage high in proteins and antioxidants
Authors: Abdo Eman M. , Allam Marwa G. , Gomaa Mohamed A. E. , Shaltout Omayma E. , Mansour Hanem M. M.
Published: December 2022

Introduction

Adequate protein and antioxidant intake are crucial for everyone, particularly athletes, to promote muscle performance and prevent muscle damage. Whey proteins are high-quality proteins with high digestibility and bioavailability; beetroot peels are an abundant antioxidant source.

Methods

The present study was designated to develop a functional beverage based on mixing whey protein isolate (5%) with different concentrations of beetroot peel water extract (1, 2.5, and 5%) and flavored with strawberries puree (5%). In addition, we examined the stability of the physicochemical parameters and the bioactive components of the beverages during cold storage (4°C) for 14 days.

Results and discussion

Whey protein isolates enriched the juices with stable protein content during the storage (4.65–4.69%). Besides, the extract revealed a concentration-dependent effect on the bioactive components, the antioxidant activity, and the microbial load of the juices; it distinguished the fresh juices by high betalains and nitrate content, 87.31–106.44 mg/L and 94.29–112.59 mg/L, respectively. Beverages with 2.5% peel extract (T2) had the preferable sensory attributes compared to control and other treatments. On day 0, phenolics and flavonoids increased in T2 by 44 and 31% compared to the control, which elevated the scavenging activity of the juice (T2) (P < 0.05). At the end of the storage period (14 days), phenolics and flavonoids of T2 recorded their lowest values, 26.23 and 21.75 mg/mL, respectively. However, they stood higher than phenolics (22.21 mg/mL) (p < 0.05) and flavonoids (18.36 mg/mL) (p > 0.05) of control. Similarly, betalains degraded by 45% to reach 47.46 mg/L in T2, which reduced the redness (a*) and increased the yellowness (b*) values.

Conclusion

Consequently, whey/strawberry/beetroot peel (5: 5: 2.5 w/v/w) in d.H2O is a functional beverage that provides the body with a high-quality protein and a considerable amount of antioxidants.
Agrimol B inhibits colon carcinoma progression by blocking mitochondrial function through the PGC-1α/NRF1/TFAM signaling pathway
Authors: Xiang Dongyang , Yang Wenjuan , Fang Zihan , Mao Jialei , Yan Qiuying , Li Liu , Tan Jiani , Yu Chengtao , Qian Jun , Tang Dongxin , Pan Xiaoting , Cheng Haibo , Sun Dongdong
Published: December 2022

Background

The activation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) stimulates the transcription of the downstream target proteins, mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1), which induces mitochondrial biogenesis and promotes colorectal tumorigenesis. Agrimol B (Agr) is a constituent of Agrimonia pilosa Ledeb. that exerts anticancer effects. Herein, we aimed to investigate the antitumor activity of Agr and its mechanism of action.

Methods

The interaction between Agr and PGC-1α was predicted by molecular docking. After the treatment with different concentrations of Agr (0, 144, 288, and 576 nM), the cell viability, migration rate, proliferation rate, and apoptosis rate of human colon cancer HCT116 cells were determined. Mitochondrial activity, cellular reactive oxygen species (ROS), and mitochondrial membrane potential were assessed to measure the regulatory effect of Agr on mitochondrial function. Western blotting (WB) assay was used to examine the expression of PGC-1α, NRF1, and TFAM, as well as of the pro-apoptotic proteins, Bax and Caspase-3, and the antiapoptotic protein (Bcl-2). Finally, subcutaneous tumor xenograft model mice were used to evaluate the effect of Agr on colorectal cancer (CRC) in vivo.

Results

The molecular docking results revealed a high likelihood of Agr interacting with PGC-1α. Agr inhibited the proliferation and migration of HCT116 cells, promoted ROS production and mitochondrial oxidative stress, inhibited mitochondrial activity, and decreased mitochondrial membrane potential. Agr induced cell apoptosis and, in combination with PGC-1α, impaired mitochondrial biogenesis and suppressed the expression of NRF1 and TFAM. Agr also suppressed the expression of Bcl-2 and Cleaved-Caspase-3 and increased the expression of Bax and Caspase-3. In addition, the in vivo antitumor effect and mechanism of Agr were confirmed by using a subcutaneous tumor xenograft mouse model.

Conclusions

Our findings demonstrated that Agr regulates the expression of PGC-1α, thereby inducing mitochondrial dysfunction and promoting tumor cell apoptosis. This work highlights the potential of Agr as a promising therapeutic candidate in CRC.
Clinicopathologic features, treatment, and prognosis of pregnancy-associated breast cancer
Authors: Li Yuechong , Wang Yingjiao , Sun Qiang , Shen Songjie
Published: December 2022

Purpose

To identify the clinicopathological features, treatment, and prognosis of patients with breast cancer, who were diagnosed during and after pregnancy.

Methods

We searched for patients with pregnancy-associated breast cancer (PABC) using the big data query and analysis system of Peking Union Medical College Hospital from between January 1, 2013, and December 31, 2021, and matched each patient with two non-PABC patients by age at diagnosis, year at diagnosis, and tumor stage. The clinicopathologic features, treatment, and outcomes of breast cancer during pregnancy (BC-P) and breast cancer during the first-year post-partum (BC-PP) were examined retrospectively in two case-control studies.

Results

Eighteen BC-P cases, 36 controls for BC-P cases, 62 BC-PP cases, and 124 controls for BC-PP cases were enrolled in our study. The expression of HER-2 and Ki-67 was higher in BC-PP cases than in its controls (P=0.01, 0.018, respectively). Patients with BC-PP were more likely to choose mastectomy than breast-conserving surgery (P=0.001). There were no significant differences in event-free survival (EFS) between patients with BC-P and BC-PP and their controls.

Conclusion

BC-P and BC-PP patients displayed adverse clinicopathological features in our population. However, when matched by age at diagnosis, year of diagnosis, and tumor stage, BC-P and BC-PP patients did not show inferior outcomes to controls, probably due to aggressive multimodality therapy.