bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of newly isolated fungal cultures for the selective delignification of bamboo culms
Authors: Zhao Bo , Liu Rui , Guo Qi , Xu Gang , Zhang Li , Sun Peng , Cao Ying , Hu Shanglian
Published: September 2023

The screening of ligninolytic enzyme-producing fungal species in samples led to the identification of Paracremonium sp. LCB1, Clonostachys compactiuscula LCD1 and C. compactiuscula LCN1. Both these strains produced high levels of hemicellulase and ligninolytic enzyme production over a relatively short fermentation period of 3–5 days while exhibiting very low levels of cellulase activity. The results of the tests indicated that co-culturing LCB1 and LCN1 enhanced the ability to degrade lignin, and the ideal degrading circumstances and internal degrading mechanism of combined fungi were examined. The results showed that under conditions of temperature (30°C), pH (5), culture time (40 d), solid-liquid ratio (1:2.5), the pretreatment of bamboo culms with a co-culture of LCB1 and LCN1 resulted in a pronounced 76.37% drop in lignin weight and a high lignin/cellulose loss ratio (>10). Fourier transform infrared spectroscopy, X-ray diffractometry, and scanning electron microscopy were used to characterize the physicochemical properties of these bio-pretreated bamboo culms, further confirming that LCB1 and LCN1 co-culture represents an effective approach to bamboo delignification.
Coinfection of SARS-CoV-2 and influenza A (H3N2) detected in bronchoalveolar lavage fluid of a patient with long COVID using metagenomic next−generation sequencing: a case report
Authors: Liang Xuefei , Wang Qiushi , Liu Jia , Ma Jing , Zhang Yajuan , Wang Meng , Yu Yang , Wang Linlin
Published: September 2023

The growing number of long COVID cases has drawn clinical attention to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has been spreading worldwide since winter 2019. Its symptoms are not limited to fatigue and shortness of breath but also affect daily life. We report the use of metagenomic next-generation sequencing (mNGS) to detect coinfection with SARS-CoV-2 and influenza A virus in a patient with long COVID. The patient was admitted with fever, expectoration, fatigue, and shortness of breath. The PCR test was negative due to possible clearance of SARS-Cov-2 in the upper respiratory tract of patients with long COVID. Other routine microbiological tests were also negative, making the clinical diagnosis difficult. Bronchoalveolar lavage fluid (BALF) samples were tested using mNGS. The patient was diagnosed and treated promptly, recovered quickly, and continued taking azvudine after discharge; his condition was stable. This study illustrates that mNGS may be valuable for the timely diagnosis of patients with long COVID and their mixed infections.
Detailed characterisation of invasive aspergillosis in a murine model of X-linked chronic granulomatous disease shows new insights in infections caused by Aspergillus fumigatus versus Aspergillus nidulans
Authors: King Jill , Dambuza Ivy M. , Reid Delyth M. , Yuecel Raif , Brown Gordon D. , Warris Adilia
Published: September 2023

Introduction

Invasive aspergillosis (IA) is the most prevalent infectious complication in patients with chronic granulomatous disease (CGD). Yet, understanding of fungal pathogenesis in the CGD host remains limited, particularly with regards to A. nidulans infection.

Methods

We have used a murine model of X-linked CGD to investigate how the pathogenesis of IA varies between A. fumigatus and A. nidulans, comparing infection in both X-linked CGD (gp91-/-) mice and their parent C57BL/6 (WT) mice. A 14-colour flow cytometry panel was used to assess the cell dynamics over the course of infection, with parallel assessment of pulmonary cytokine production and lung histology.

Results

We observed a lack of association between pulmonary pathology and infection outcome in gp91-/- mice, with no significant mortality in A. nidulans infected mice. An overwhelming and persistent neutrophil recruitment and IL-1 release in gp91-/- mice following both A. fumigatus and A. nidulans infection was observed, with divergent macrophage, dendritic cell and eosinophil responses and distinct cytokine profiles between the two infections.

Conclusion

We have provided an in-depth characterisation of the immune response to pulmonary aspergillosis in an X-linked CGD murine model. This provides the first description of distinct pulmonary inflammatory environments in A. fumigatus and A. nidulans infection in X-linked CGD and identifies several new avenues for further research.
Changes in compound flood event frequency in northern and central Europe under climate change
Authors: Heinrich Philipp , Hagemann Stefan , Weisse Ralf , Gaslikova Lidia
Published: September 2023

The simultaneous occurrence of increased river discharge and high coastal water levels may cause compound flooding. Compound flood events can potentially cause greater damage than the separate occurrence of the underlying extreme events, making them essential for risk assessment. Even though a general increase in the frequency and/or severity of compound flood events is assumed due to climate change, there have been very few studies conducted for larger regions of Europe. Our work, therefore, focuses on the high-resolution analysis of changes in extreme events of coastal water levels, river discharge, and their concurrent appearance at the end of this century in northern and central Europe (2070–2099). For this, we analyze downscaled data sets from two global climate models (GCMs) for the two emissions scenarios RCP2.6 and RCP8.5. First, we compare the historical runs of the downscaled GCMs to historical reconstruction data to investigate if they deliver comparable results for northern and central Europe. Then we study changes in the intensity of extreme events, their number, and the duration of extreme event seasons under climate change. Our analysis shows increases in compound flood events over the whole European domain, mostly due to the rising mean sea level. In some areas, the number of compound flood event days increases by a factor of eight at the end of the current century. This increase is concomitant with an increase in the annual compound flood event season duration. Furthermore, the sea level rise associated with a global warming of 2K will result in double the amounts of compound flood event days for nearly every European river estuary considered.
Augmentative and Alternative Communication and digital participation
Authors: Wahl Michael , Weiland Katharina
Published: September 2023

Communication is a basic need for all people to fully participate in life. Persons with disabilities may face particular challenges in developing their communication skills and using them appropriately in different situations. Augmentative and Alternative Communication (AAC) tools and methods can assist individuals in this process. Increasing digitization has changed the way everyone communicates, and this offers opportunities for persons using AAC. This paper briefly outlines what has been achieved in terms of digitalization in AAC. The need for full, adapted access to technology is highlighted and research desiderata are identified.
B-type natriuretic peptide and N-terminal Pro-B-type natriuretic peptide in severe aortic stenosis: a comprehensive literature review
Authors: Cavalcante Pâmela Nogueira , Kanhouche Gabriel , Rosa Vitor Emer Egypto , Campos Carlos M. , Lopes Mariana Pezzute , Lopes Maria Antonieta Albanez A. de M. , Sampaio Roney Orismar , Brito Júnior Fábio Sândoli de , Tarasoutchi Flavio , Abizaid Alexandre Antonio Cunha
Published: September 2023

B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro BNP) are cardiac biomarkers that are released in response to increased ventricular and atrial wall stress. Aortic stenosis (AS) leads to hemodynamic changes and left ventricular hypertrophy and may be associated with natriuretic peptide levels. Several studies have shown that increased natriuretic peptide levels are correlated with AS severity and can predict the need for intervention. It can be useful in risk stratification, monitoring follow-up, and predicting cardiovascular outcomes of patients with severe AS. This paper aims to summarize the evidence of the role of BNP and NT-pro BNP in AS, before and after intervention.
Left atrial appendage sizing for percutaneous closure in virtual reality—a feasibility study
Authors: Heidari Houtan , Kanschik Dominika , Erkens Ralf , Maier Oliver , Wolff Georg , Bruno Raphael Romano , Werner Nikos , Daniel Reinartz Sebastian , Antoch Gerald , Kelm Malte , Zeus Tobias , Jung Christian , Afzal Shazia
Published: September 2023

Background and aims

The complex and highly variable three-dimensional anatomy of the left atrial appendage (LAA) makes planning and device sizing for interventional occlusion procedures (LAAC) challenging. Several imaging modalities [e.g. echocardiography, multi-slice computed tomography (MSCT)] are used for this purpose. Virtual reality (VR) is an emerging imaging technique to immerse into a three-dimensional left atrium and appendage, offering unprecedented options of visualization and measurement. This study aimed to investigate the feasibility, accuracy and reproducibility of visualizing the LAA in VR for preprocedural planning of LAAC.

Methods and results

Twenty-one patients (79 ± 7 years, 62% male) who underwent LAAC at University Hospital Düsseldorf were included in our study. A dedicated software generated three-dimensional VR models from preprocedural MSCT imaging data. Conventional measurements of LAA dimensions (ostium, landing zone and depth) using a commercially available software were compared to measurements in VR: MSCT and VR ostium min. (r = 0.93), max. (r = 0.80) and mean (r = 0.88, all p < 0.001) diameters as well as landing zone (LZ) min. (r = 0.84), max. (r = 0.86) and mean diameters (r = 0.90, all p < 0.001) showed strong correlations. Three-dimensional orientation was judged superior by physicians in VR compared to MSCT (p < 0.05).

Conclusion

Virtual reality visualization of the left atrium and appendage based on MSCT data is feasible and allows precise and reproducible measurements in planning of LAA occlusion procedures with enhanced 3D orientation. Further studies need to explore additional benefits of three-dimensional visualization for operators in preprocedural planning.
The association between early menarche and higher-risk cardiometabolic profile: a dose–response analysis of the Tabari cohort at enrollment phase
Authors: Kheradmand Motahareh , Hamzehgardeshi Zeinab , Shahhosseini Zohreh , Mirjalili Razie , Moosazadeh Mahmood
Published: September 2023

Objectives

The association between age at menarche and higher-risk cardiometabolic factors is controversial and more strands of evidence are required. Therefore, in this study, we aimed to investigate the effect of early menarche on cardiometabolic profile in a large-scale cohort population.

Study design

Data collected in the enrollment phase of the Tabari cohort study were utilized for the present study. We analyzed data from 6,103 women aged 35–70 years. Logistic regression and dose–response (trend) analyses were used to investigate the effect of early menarche on prevalence of diabetes, dyslipidemia, obesity, high waist circumference (WC), high waist-to-hip ratio (WHR), and high waist-to-height ratio (WHtR).

Results

The results of the adjusted logistic regression analysis showed that women who experienced early menarche had significantly higher odds of obesity (odds ratio: 1.64, 95% CI: 1.36–1.99, P for trend <0.001), high WC (odds ratio: 1.34, 95% CI: 1.07–1.67, P for trend = 0.035), high WHR (odds ratio: 1.32, 95% CI: 1.05–1.66, P for trend = 0.057), and high WHtR (odds ratio: 1.83, 95% CI: 1.22–2.74, P for trend = 0.006) compared to those aged ≥14 at menarche. The prevalence of dyslipidemia was also higher among women who experienced early menarche than in women aged ≥14 at menarche (79.9% vs. 76.6%), but the difference was not statistically significant (P = 0.098). Additionally, each year of earlier menarche was significantly associated with an increase in the chance of diabetes (by 5%), obesity (10%), high WC (5%), and high WHtR (13%).

Conclusion

The present study showed that early menarche is a strong predictor for later development of obesity and diabetes, and for high WC, WHR, and WHtR. Among all factors examined, age at menarche had the greatest predictive power for WHtR. As an age-dependent anthropometric index for central obesity, WHtR is more suitable as an index for identification of individuals with increased cardiometabolic risk.
Prediction of postoperative health-related quality of life among patients with metastatic spinal cord compression secondary to lung cancer
Authors: Fu Yufang , Shi Weiqing , Zhao Jing , Cao Xuyong , Cao Yuncen , Lei Mingxing , Su Xiuyun , Cui Qiu , Liu Yaosheng
Published: September 2023

Background

Health-related quality of life (HRQoL) is a critical aspect of overall well-being for patients with lung cancer, particularly those with metastatic spinal cord compression (MSCC). However, there is currently a lack of universal evaluation of HRQoL in this specific patient population. The aim of this study was to develop a nomogram that can accurately predict HRQoL outcomes in patients with lung cancer-related MSCC.

Methods

A total of 119 patients diagnosed with MSCC secondary to lung cancer were prospectively collected for analysis in the study. The least absolute shrinkage and selection operator (LASSO) regression analysis, along with 10-fold cross-validation, was employed to select the most significant variables for inclusion in the nomogram. Discriminative and calibration abilities were assessed using the concordance index (C-index), discrimination slope, calibration plots, and goodness-of-fit tests. Net reclassification index (NRI) and integrated discrimination improvement (IDI) analyses were conducted to compare the nomogram’s performance with and without the consideration of comorbidities.

Results

Four variables were selected to construct the final nomogram, including the Eastern Cooperative Oncology Group (ECOG) score, targeted therapy, anxiety scale, and number of comorbidities. The C-index was 0.87, with a discrimination slope of 0.47, indicating a favorable discriminative ability. Calibration plots and goodness-of-fit tests revealed a high level of consistency between the predicted and observed probabilities of poor HRQoL. The NRI (0.404, 95% CI: 0.074–0.734, p = 0.016) and the IDI (0.035, 95% CI: 0.004–0.066, p = 0.027) confirmed the superior performance of the nomogram with the consideration of comorbidities.

Conclusions

This study develops a prediction nomogram that can assist clinicians in evaluating postoperative HRQoL in patients with lung cancer-related MSCC. This nomogram provides a valuable tool for risk stratification and personalized treatment planning in this specific patient population.
Extraction of farmland shelterbelts from remote sensing imagery based on a belt-oriented method
Authors: Deng Rongxin , Guo Qunzuo , Jia Menghao , Wu Yuzong , Zhou Qiwen , Xu Zhengran
Published: September 2023

Introduction

Farmland shelterbelts play a positive role in ensuring food security and ecological safety. The absence or degradation of shelterbelt structures can lead to fragmentation of the remotely extracted results. Conversely, shelterbelt maintenance and management system considers these shelterbelts as entire units, even if they are divided into several parts by the gaps in them. It is essential to propose a remote extraction method to fill in fragmented results and accurately represent the distribution of farmland shelterbelts.

Methods

In this study, random forest algorithm was employed to classify land cover from ZY-3 (ZiYuan-3 satellite from China) imagery. Then, a thinning algorithm of mathematical morphology was applied to extract farmland shelterbelts, and the straight-line connection algorithm was used to connect central lines belonging to the same belt. Finally, the result was validated using nine uniformly distributed training sample areas across the entire region.

Results and discussion

This method achieved a correct identification rate of 94.9% within the training areas. Among the different regions, the highest identification accuracy recorded was 98.4% and the lowest was 87.7%. In conjunction with cropland information and the shape index of forest patches, it was possible to remove information for non-farmland shelterbelts without introducing external information. This approach achieved a more refined extraction of forestland information. The combination of the thinning algorithm and straight-line connection algorithm addressed the issue of fragmented results in farmland shelterbelt extraction, compensating for the limitations of relying solely on mathematical morphology for belt connectivity. The research method can provide technical support for the monitoring and management of farmland shelterbelts.
Association of serum vitamin D concentration with the final course of hospitalization in patients with COVID-19
Authors: Konikowska Klaudia , Kiliś-Pstrusińska Katarzyna , Matera-Witkiewicz Agnieszka , Kujawa Krzysztof , Adamik Barbara , Doroszko Adrian , Kaliszewski Krzysztof , Pomorski Michał , Protasiewicz Marcin , Sokołowski Janusz , Madziarska Katarzyna , Jankowska Ewa Anita
Published: September 2023

Background

Vitamin D deficiency is a substantial public health problem. The present study evaluated the association between vitamin D concentration and hospitalization and mortality risk in patients with coronavirus disease 19 (COVID-19).

Methods

This study used the COronavirus in LOwer Silesia (COLOS) dataset collected between February 2020 and June 2021. The medical records of 474 patients with confirmed severe acute respiratory syndrome 2 (SARS-CoV-2) infection, and whose vitamin D concentration was measured, were analyzed.

Results

We determined a significant difference in vitamin D concentration between discharged patients and those who died during hospitalization (p = 0.0096). We also found an effect of vitamin D concentration on the risk of death in patients hospitalized due to COVID-19. As vitamin D concentration increased, the odds ratio (OR) for death slightly decreased (OR = 0.978; 95% confidence interval [CI] = 0.540-0.669). The vitamin D concentration cutoff point was 15.40 ng/ml. In addition, patients with COVID-19 and serum 25-hydroxyvitamin D (25(OH)D) concentrations < 30 ng/ml had a lower survival rate than those with serum 25(OH)D ≥ 30 ng/ml (log-rank test p = 0.0018). Moreover, a Cox regression model showed that patients with an estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 and higher vitamin D concentrations had a 2.8% reduced risk of mortality (hazard ratio HR = 0.972; CI = 0.95-0,99; p = 0.0097).

Conclusions

The results indicate an association between 25(OH)D levels in patients with COVID-19 and the final course of hospitalization and risk of death.
The two-step approach to allogeneic hematopoietic stem cell transplantation
Authors: Ibikunle Sikemi , Grosso Dolores , Gergis Usama
Published: September 2023

Allogeneic hematopoietic stem cell transplantation (HSCT) provides the only potentially curative option for multiple hematological conditions. However, allogeneic HSCT outcomes rely on an optimal balance of effective immune recovery, minimal graft-versus-host disease (GVHD), and lasting control of disease. The quest to attain this balance has proven challenging over the past few decades. The two-step approach to HSCT was conceptualized and pioneered at Thomas Jefferson University in 2005 and remains the main platform for allografting at our institution. Following administration of the transplant conditioning regimen, patients receive a fixed dose of donor CD3+ cells (HSCT step one-DLI) as the lymphoid portion of the graft on day -6 with the aim of optimizing and controlling T cell dosing. Cyclophosphamide (CY) is administered after the DLI (days -3 and -2) to induce donor-recipient bidirectional tolerance. On day 0, a CD34-selected stem cell graft is given as the myeloid portion of the graft (step two). In this two-step approach, the stem cell graft is infused after CY tolerization, which avoids exposure of the stem cells to an alkylating agent, allowing rapid count recovery. Here, the two-step platform is described with a focus on key results from studies over the past two decades. Finally, this review details lessons learned and current strategies to optimize the graft-versus-tumor effect and limit transplant-related toxicities.
The role of tumor immune microenvironment in chordoma: promising immunotherapy strategies
Authors: Xu Jiuhui , Shi Qianyu , Wang Boyang , Ji Tao , Guo Wei , Ren Tingting , Tang Xiaodong
Published: September 2023

Chordoma is a rare malignant bone tumor with limited therapeutic options, which is resistant to conventional chemotherapy and radiotherapy, and targeted therapy is also shown with little efficacy. The long-standing delay in researching its mechanisms of occurrence and development has resulted in the dilemma of no effective treatment targets and no available drugs in clinical practice. In recent years, the role of the tumor immune microenvironment in driving tumor growth has become a hot and challenging topic in the field of cancer research. Immunotherapy has shown promising results in the treatment of various tumors. However, the study of the immune microenvironment of chordoma is still in its infancy. In this review, we aim to present a comprehensive reveal of previous exploration on the chordoma immune microenvironment and propose promising immunotherapy strategies for chordoma based on these characteristics.
Influenza virus decreases albumin uptake and megalin expression in alveolar epithelial cells
Authors: Alberro-Brage Andrés , Kryvenko Vitalii , Malainou Christina , Günther Stefan , Morty Rory E. , Seeger Werner , Herold Susanne , Samakovlis Christos , Vadász István
Published: September 2023

Introduction

Acute respiratory distress syndrome (ARDS) is a common complication of influenza virus (IV) infection. During ARDS, alveolar protein concentrations often reach 40-90% of plasma levels, causing severe impairment of gas exchange and promoting deleterious alveolar remodeling. Protein clearance from the alveolar space is at least in part facilitated by the multi-ligand receptor megalin through clathrin-mediated endocytosis.

Methods

To investigate whether IV infection impairs alveolar protein clearance, we examined albumin uptake and megalin expression in MLE-12 cells and alveolar epithelial cells (AEC) from murine precision-cut lung slices (PCLS) and in vivo, under IV infection conditions by flow cytometry and western blot. Transcriptional levels from AEC and broncho-alveolar lavage (BAL) cells were analyzed in an in-vivo mouse model by RNAseq.

Results

IV significantly downregulated albumin uptake, independently of activation of the TGF-β1/GSK3β axis that has been previously implicated in the regulation of megalin function. Decreased plasma membrane abundance, total protein levels, and mRNA expression of megalin were associated with this phenotype. In IV-infected mice, we identified a significant upregulation of matrix metalloproteinase (MMP)-14 in BAL fluid cells. Furthermore, the inhibition of this protease partially recovered total megalin levels and albumin uptake.

Discussion

Our results suggest that the previously described MMP-driven shedding mechanisms are potentially involved in downregulation of megalin cell surface abundance and clearance of excess alveolar protein. As lower alveolar edema protein concentrations are associated with better outcomes in respiratory failure, our findings highlight the therapeutic potential of a timely MMP inhibition in the treatment of IV-induced ARDS.
Monocyte chemoattractant protein-1 as a potential marker for patients with sepsis: a systematic review and meta-analysis
Authors: Chen Zhuo , Li Chenwei , Yu Jian
Published: September 2023

Objective

To investigate the diagnostic value of monocyte chemoattractant protein-1 (MCP-1) as a biomarker for adult patients with sepsis.

Methods

Related studies on the diagnostic value of MCP-1 in adult patients with sepsis were searched in PubMed, Cochrane Library, Embase, CNKI, CBM, Web of Science, Scopus, and Wanfang Data databases (published to February 20, 2023) was performed if studies assessed the diagnostic accuracy of MCP-1 in adult patients with sepsis and provided appropriate information sufficient to construct a 2 × 2 linked table, studies were included.

Results

Data from 8 studies with a total of 805 patients were included. The combined sensitivity was 0.84 (95% CI 0.70–0.92), the specificity was 0.82 (95% CI 0.67–0.91), the combined positive likelihood ratio was 3.711 (2.119–6.500), the negative likelihood ratio was 0.287 (0.198–0.415), and the area under the working characteristic curve for combined subjects was 0.88. The diagnostic odds ratio (DOR) was 16.508 (7.632–35.706). Meta-regression analysis showed that the results were not significant. Deeks’ funnel plot showed that there was no publication bias.

Conclusion

According to our meta-analysis, MCP-1 is a valuable biomarker and may provide evidence for the diagnosis of sepsis in adults.
Structural characterization, antioxidant and anti-uropathogenic potential of biogenic silver nanoparticles using brown seaweed Turbinaria ornata
Authors: Raj C. T. Dhanya , Muthukumar Krishnan , Dahms Hans Uwe , James Rathinam Arthur , Kandaswamy Surabhi
Published: September 2023

Alternative treatment strategies for urinary tract infections (UTIs) are becoming more necessary due to increasing drug resistance patterns in uropathogens. Nanoparticle-based therapeutics is emerging as a way to treat UTIs. In the present study, using Turbinaria ornata extract, silver nanoparticles (AgNPs) were synthesized, characterized, and their anti-uropathogenic activity was evaluated. The stability and formation of synthesized To-AgNPs were confirmed by UV-visible spectroscopy, FTIR, XRD, SEM, and DLS. An FTIR spectrum confirmed the presence of seaweed functional groups in To-AgNPs, a XRD analysis confirmed their crystalline nature, and SEM imaging confirmed their spherical nature with an average size of 73.98 nm with diameters ranging from 64.67 to 81.28 nm. This was confirmed by TEM results. DLS determined that the cumulant hydrodynamic diameter of To-AgNPs was 128.3 nm with a PdI of 0.313 and the zeta potential value were found to be –63.3 mV which indicates the To-AgNPs are negatively charged and more stable. DPPH assays were used to assess the antioxidant activity of biosynthesized To-AgNPs, while an agar well diffusion method was used to test the antibacterial activity against uropathogens, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, and Klebsiella pneumoniae. The To-AgNPs showed the highest susceptibility to S. aureus (15.75 ± 0.35 mm) and E. coli (15 ± 0.7 mm) with MIC values of 0.0625 and 0.125 mg/ml, respectively in macro broth dilution method and observed considerable membrane damage under CLSM and SEM. To-AgNPs displayed stronger antioxidant and antimicrobial activity, suggesting they may be developed as a new class of antimicrobial agents for treating UTIs.
Combining docking, molecular dynamics simulations, AD-MET pharmacokinetics properties, and MMGBSA calculations to create specialized protocols for running effective virtual screening campaigns on the autoimmune disorder and SARS-CoV-2 main protease
Authors: Edache Emmanuel Israel , Uzairu Adamu , Mamza Paul Andrew , Shallangwa Gideon Adamu , Yagin Fatma Hilal , Abdel Samee Nagwan , Mahmoud Noha F.
Published: September 2023

The development of novel medicines to treat autoimmune diseases and SARS-CoV-2 main protease (Mpro), a virus that can cause both acute and chronic illnesses, is an ongoing necessity for the global community. The primary objective of this research is to use CoMFA methods to evaluate the quantitative structure-activity relationship (QSAR) of a select group of chemicals concerning autoimmune illnesses. By performing a molecular docking analysis, we may verify previously observed tendencies and gain insight into how receptors and ligands interact. The results of the 3D QSAR models are quite satisfactory and give significant statistical results: Q_loo∧2 = 0.5548, Q_lto∧2 = 0.5278, R∧2 = 0.9990, F-test = 3,101.141, SDEC = 0.017 for the CoMFA FFDSEL, and Q_loo∧2 = 0.7033, Q_lto∧2 = 0.6827, Q_lmo∧2 = 0.6305, R∧2 = 0.9984, F-test = 1994.0374, SDEC = 0.0216 for CoMFA UVEPLS. The success of these two models in exceeding the external validation criteria used and adhering to the Tropsha and Glorbaikh criteria’s upper and lower bounds can be noted. We report the docking simulation of the compounds as an inhibitor of the SARS-CoV-2 Mpro and an autoimmune disorder in this context. For a few chosen autoimmune disorder receptors (protein tyrosine phosphatase, nonreceptor type 22 (lymphoid) isoform 1 (PTPN22), type 1 diabetes, rheumatoid arthritis, and SARS-CoV-2 Mpro, the optimal binding characteristics of the compounds were described. According to their potential for effectiveness, the studied compounds were ranked, and those that demonstrated higher molecular docking scores than the reference drugs were suggested as potential new drug candidates for the treatment of autoimmune disease and SARS-CoV-2 Mpro. Additionally, the results of analyses of drug similarity, ADME (Absorption, Distribution, Metabolism, and Excretion), and toxicity were used to screen the best-docked compounds in which compound 4 scaled through. Finally, molecular dynamics (MD) simulation was used to verify compound 4’s stability in the complex with the chosen autoimmune diseases and SARS-CoV-2 Mpro protein. This compound showed a steady trajectory and molecular characteristics with a predictable pattern of interactions. These findings suggest that compound 4 may hold potential as a therapy for autoimmune diseases and SARS-CoV-2 Mpro.
Serum uric acid and prognosis in acute ischemic stroke: a dose–response meta-analysis of cohort studies
Authors: Zhang Wenyuan , Cheng Zicheng , Fu Fangwang , Zhan Zhenxiang
Published: September 2023

Background

There have been contradictory findings regarding the relationship between serum uric acid levels and prognosis in acute ischemic stroke. Whether this association is nonlinear due to uric acid’s paradoxical properties (antioxidant and prooxidant) is unclear.

Methods

We searched PubMed, Web of Science, and Embase databases until December 2022. Cohort studies reporting serum uric acid levels and functional outcome, mortality, or neurological complications in patients with acute ischemic stroke were included. Summary effect estimates were calculated using a random-effect model. Moreover, dose–response relationships were assessed by the generalized least squares trend estimation.

Results

Altogether, 13 cohort studies were identified in this study. Compared to the lowest baseline serum uric acid levels, the highest levels were associated with decreased risk of poor functional outcome (OR = 0.70, 95% CI 0.54–0.91, I2 = 29%), hemorrhagic transformation (OR = 0.15, 95% CI 0.05–0.42, I2 = 79%), and post-stroke depression (OR = 0.04, 95% CI 0.00–0.95, I2 = 89%), but not associated with mortality and symptomatic intracerebral hemorrhage. A nonlinear relationship was observed in poor functional outcome (U-shaped, P for nonlinearity = 0.042), hemorrhagic transformation (inverse, P for nonlinearity = 0.001), and post-stroke depression (inverse, P for nonlinearity = 0.002). In addition, there was a single study reporting a U-shaped association in post-stroke epilepsy (P for nonlinearity <0.001). Furthermore, another study reported a positive curvilinear association in stroke recurrence (P for nonlinearity <0.05). The insufficient number of original articles for some prognostic indicators should be considered when interpreting the results of this meta-analysis.

Conclusion

In patients with acute ischemic stroke, serum uric acid levels are nonlinearly associated with the risk of poor functional outcome (U-shaped). More evidence is needed to confirm the association between serum uric acid levels and neurological complications following acute ischemic stroke.
IRIS: Integrated Retinal Functionality in Image Sensors
Authors: Yin Zihan , Kaiser Md Abdullah-Al , Camara Lamine Ousmane , Camarena Mark , Parsa Maryam , Jacob Ajey , Schwartz Gregory , Jaiswal Akhilesh
Published: September 2023

Neuromorphic image sensors draw inspiration from the biological retina to implement visual computations in electronic hardware. Gain control in phototransduction and temporal differentiation at the first retinal synapse inspired the first generation of neuromorphic sensors, but processing in downstream retinal circuits, much of which has been discovered in the past decade, has not been implemented in image sensor technology. We present a technology-circuit co-design solution that implements two motion computations—object motion sensitivity and looming detection—at the retina's output that could have wide applications for vision-based decision-making in dynamic environments. Our simulations on Globalfoundries 22 nm technology node show that the proposed retina-inspired circuits can be fabricated on image sensing platforms in existing semiconductor foundries by taking advantage of the recent advances in semiconductor chip stacking technology. Integrated Retinal Functionality in Image Sensors (IRIS) technology could drive advances in machine vision applications that demand energy-efficient and low-bandwidth real-time decision-making.
Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders
Authors: Naskar Aditi , Nayak Asima , Salaikumaran Muthu Raj , Vishal Sonali S. , Gopal Pallavi P.
Published: September 2023

Liquid–liquid phase separation results in the formation of dynamic biomolecular condensates, also known as membrane-less organelles, that allow for the assembly of functional compartments and higher order structures within cells. Multivalent, reversible interactions between RNA-binding proteins (RBPs), including FUS, TDP-43, and hnRNPA1, and/or RNA (e.g., RBP-RBP, RBP-RNA, RNA-RNA), result in the formation of ribonucleoprotein (RNP) condensates, which are critical for RNA processing, mRNA transport, stability, stress granule assembly, and translation. Stress granules, neuronal transport granules, and processing bodies are examples of cytoplasmic RNP condensates, while the nucleolus and Cajal bodies are representative nuclear RNP condensates. In neurons, RNP condensates promote long-range mRNA transport and local translation in the dendrites and axon, and are essential for spatiotemporal regulation of gene expression, axonal integrity and synaptic function. Mutations of RBPs and/or pathologic mislocalization and aggregation of RBPs are hallmarks of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer’s disease. ALS/FTD-linked mutations of RBPs alter the strength and reversibility of multivalent interactions with other RBPs and RNAs, resulting in aberrant phase transitions. These aberrant RNP condensates have detrimental functional consequences on mRNA stability, localization, and translation, and ultimately lead to compromised axonal integrity and synaptic function in disease. Pathogenic protein aggregation is dependent on various factors, and aberrant dynamically arrested RNP condensates may serve as an initial nucleation step for pathologic aggregate formation. Recent studies have focused on identifying mechanisms by which neurons resolve phase transitioned condensates to prevent the formation of pathogenic inclusions/aggregates. The present review focuses on the phase separation of neurodegenerative disease-linked RBPs, physiological functions of RNP condensates, and the pathologic role of aberrant phase transitions in neurodegenerative disease, particularly ALS/FTD. We also examine cellular mechanisms that contribute to the resolution of aberrant condensates in neurons, and potential therapeutic approaches to resolve aberrantly phase transitioned condensates at a molecular level.
Red and golden tomato administration improves fat diet-induced hepatic steatosis in rats by modulating HNF4α, Lepr, and GK expression
Authors: Pipitone Rosaria Maria , Zito Rossella , Gambino Giuditta , Di Maria Gabriele , Javed Ayesha , Lupo Giulia , Giglia Giuseppe , Sardo Pierangelo , Ferraro Giuseppe , Rappa Francesca , Carlisi Daniela , Di Majo Danila , Grimaudo Stefania
Published: September 2023

Introduction

Nonalcoholic fatty liver disease (NAFLD), characterized by lipid accumulation within hepatocytes exceeding 5% of liver weight, is strongly related to metabolic disorders, obesity, and diabetes and represents a health emergency worldwide. There is no standard therapy available for NAFLD. Lifestyle intervention, including phytonutrient intake, is key in preventing NAFLD development and progression.

Methods

We used a rat model of NAFLD to evaluate the effect of dietary supplementation with red tomato (RT) and golden tomato (GT)—a patented mix of fruit with varying degrees of ripeness and particularly rich in naringenin and chlorogenic acid—after steatosis development. We assessed the effects on body weight, metabolic profile, and hepatic steatosis.

Results and discussion

We found a correlation between the amelioration of all the parameters and the liver gene expression. Our results showed that, together with the reversion of steatosis, the consumption of RT and GT can cause a significant reduction in triglycerides, low-density lipoprotein-cholesterol, fasting glucose, and homeostasis model assessment index. Meanwhile, we observed an increase in high-density lipoprotein-cholesterol according to the amelioration of the general lipidic profile. Regarding hepatic gene expression, we found the upregulation of Gk and Hnf4α involved in metabolic homeostasis, Lepr involved in adipokine signaling, and Il6 and Tnf involved in inflammatory response. Taken together, our results suggest that dietary intake of red and golden tomatoes, as a nutraceutical approach, has potential in preventing and therapeutics of NAFLD.
Case report: Miliary tuberculosis complicated by pediatric acute respiratory distress syndrome in a 12-year-old girl
Authors: Zhu Jiarui , Chen Ning , Shang Yunxiao , Feng Yong
Published: September 2023

Acute respiratory distress syndrome (ARDS) is a rare complication of miliary tuberculosis, particularly in pediatric patients. Comorbidities and delayed diagnosis can worsen the prognosis of patients with miliary tuberculosis. A 12-year-old girl presented with fever for 20 days, and cough and tachypnea for 4 days. She was diagnosed with miliary tuberculosis complicated by pediatric ARDS. She had atypical clinical manifestations and imaging findings, a negative contact history, and negative results of a tuberculin skin test (TST) and T-SPOT.TB. Diagnostic bronchoscopy and bronchoalveolar lavage helped make the diagnosis of tuberculosis. Effective treatment was promptly initiated after confirmation of the diagnosis, and the patient's condition improved. This case illustrates that a negative contact history and laboratory results cannot rule out tuberculosis. False-negative TST and T-SPOT.TB results should be evaluated carefully. Bronchoscopy may be useful for identifying pathogens in patients with pneumonia of unknown etiology, and corticosteroids should be administered with caution.
Novel biomarkers used for early diagnosis and tyrosine kinase inhibitors as targeted therapies in colorectal cancer
Authors: Jiang Huafeng , Zhou Senjun , Li Gang
Published: September 2023

Colorectal cancer (CRC) is the third most common and second most lethal type of cancer worldwide, presenting major health risks as well as economic costs to both people and society. CRC survival chances are significantly higher if the cancer is diagnosed and treated early. With the development of molecular biology, numerous initiatives have been undertaken to identify novel biomarkers for the early diagnosis of CRC. Pathological disorders can be diagnosed at a lower cost with the help of biomarkers, which can be detected in stool, blood, and tissue samples. Several lines of evidence suggest that the gut microbiota could be used as a biomarker for CRC screening and treatment. CRC treatment choices include surgical resection, chemotherapy, immunotherapy, gene therapy, and combination therapies. Targeted therapies are a relatively new and promising modality of treatment that has been shown to increase patients’ overall survival (OS) rates and can inhibit cancer cell development. Several small-molecule tyrosine kinase inhibitors (TKIs) are being investigated as potential treatments due to our increasing awareness of CRC’s molecular causes and oncogenic signaling. These compounds may inhibit critical enzymes in controlling signaling pathways, which are crucial for CRC cells’ development, differentiation, proliferation, and survival. On the other hand, only one of the approximately 42 TKIs that demonstrated anti-tumor effects in pre-clinical studies has been licensed for clinical usage in CRC. A significant knowledge gap exists when bringing these tailored medicines into the clinic. As a result, the emphasis of this review is placed on recently discovered biomarkers for early diagnosis as well as tyrosine kinase inhibitors as possible therapy options for CRC.
Targeting gut microbiota and immune crosstalk: potential mechanisms of natural products in the treatment of atherosclerosis
Authors: Jing Jinpeng , Guo Jing , Dai Rui , Zhu Chaojun , Zhang Zhaohui
Published: September 2023

Atherosclerosis (AS) is a chronic inflammatory reaction that primarily affects large and medium-sized arteries. It is a major cause of cardiovascular disease and peripheral arterial occlusive disease. The pathogenesis of AS involves specific structural and functional alterations in various populations of vascular cells at different stages of the disease. The immune response is involved throughout the entire developmental stage of AS, and targeting immune cells presents a promising avenue for its treatment. Over the past 2 decades, studies have shown that gut microbiota (GM) and its metabolites, such as trimethylamine-N-oxide, have a significant impact on the progression of AS. Interestingly, it has also been reported that there are complex mechanisms of action between GM and their metabolites, immune responses, and natural products that can have an impact on AS. GM and its metabolites regulate the functional expression of immune cells and have potential impacts on AS. Natural products have a wide range of health properties, and researchers are increasingly focusing on their role in AS. Now, there is compelling evidence that natural products provide an alternative approach to improving immune function in the AS microenvironment by modulating the GM. Natural product metabolites such as resveratrol, berberine, curcumin, and quercetin may improve the intestinal microenvironment by modulating the relative abundance of GM, which in turn influences the accumulation of GM metabolites. Natural products can delay the progression of AS by regulating the metabolism of GM, inhibiting the migration of monocytes and macrophages, promoting the polarization of the M2 phenotype of macrophages, down-regulating the level of inflammatory factors, regulating the balance of Treg/Th17, and inhibiting the formation of foam cells. Based on the above, we describe recent advances in the use of natural products that target GM and immune cells crosstalk to treat AS, which may bring some insights to guide the treatment of AS.
Identification of novel candidate loci and genes for seed vigor-related traits in upland cotton (Gossypium hirsutum L.) via GWAS
Authors: Li Libei , Hu Yu , Wang Yongbo , Zhao Shuqi , You Yijin , Liu Ruijie , Wang Jiayi , Yan Mengyuan , Zhao Fengli , Huang Juan , Yu Shuxun , Feng Zhen
Published: September 2023

Seed vigor (SV) is a crucial trait determining the quality of crop seeds. Currently, over 80% of China’s cotton-planting area is in Xinjiang Province, where a fully mechanized planting model is adopted, accounting for more than 90% of the total fiber production. Therefore, identifying SV-related loci and genes is crucial for improving cotton yield in Xinjiang. In this study, three seed vigor-related traits, including germination potential, germination rate, and germination index, were investigated across three environments in a panel of 355 diverse accessions based on 2,261,854 high-quality single-nucleotide polymorphisms (SNPs). A total of 26 significant SNPs were detected and divided into six quantitative trait locus regions, including 121 predicted candidate genes. By combining gene expression, gene annotation, and haplotype analysis, two novel candidate genes (Ghir_A09G002730 and Ghir_D03G009280) within qGR-A09-1 and qGI/GP/GR-D03-3 were associated with vigor-related traits, and Ghir_A09G002730 was found to be involved in artificial selection during cotton breeding by population genetic analysis. Thus, understanding the genetic mechanisms underlying seed vigor-related traits in cotton could help increase the efficiency of direct seeding by molecular marker-assisted selection breeding.
Why do academicians share knowledge? A study of higher education institutions in India
Authors: Ahmad Asad , Alam Md Sarwar , Kirmani Mohd Danish , Madsen Dag Øivind
Published: September 2023

Purpose

Indian higher education institutions are diverse in nature; there are institutions with good infrastructure and resources as well as institutes that have little in terms of resources and infrastructure. Keeping in mind the relevance of knowledge sharing in academic institutions, the researchers in the present study have tried to find factors determining the knowledge sharing behavior of the academicians of different institutes in India.

Design

The researchers in the present work have expanded on extant research by demarcating factors that affect the knowledge sharing behavior of academicians. A structured questionnaire was shared through e-mail and social media groups, and a snowball approach was used to reach out to the maximum number of respondents.

Findings

The present study offers an integrated and extended theory of planned behavior (TPB) theoretical model, augmenting it with constructs such as motivation and the opportunity to share knowledge adapted from related studies. The findings of this research provide theoretical as well as practical suggestions in determining and explaining the knowledge sharing behavior of academicians.

Originality

The researchers in the present study have tried to present a shorter and more reliable scale that can be used to assess the behavioral intentions of academicians to share knowledge.