bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Extracellular pH on Apoptotic and Non-Apoptotic TRAIL-Induced Signaling in Pancreatic Ductal Adenocarcinoma Cells
Authors: Hagelund Sofie , Trauzold Anna
Published: February 2022

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an important mediator of tumor immune surveillance. In addition, its potential to kill cancer cells without harming healthy cells led to the development of TRAIL receptor agonists, which however did not show the desired effects in clinical trials. This is caused mainly by apoptosis resistance mechanisms operating in primary cancer cells. Meanwhile, it has been realized that in addition to cell death, TRAIL also induces non-apoptotic pro-inflammatory pathways that may enhance tumor malignancy. Due to its late detection and resistance to current therapeutic options, pancreatic ductal adenocarcinoma (PDAC) is still one of the deadliest types of cancer worldwide. A dysregulated pH microenvironment contributes to PDAC development, in which the cancer cells become highly dependent on to maintain their metabolism. The impact of extracellular pH (pHe) on TRAIL-induced signaling in PDAC cells is poorly understood so far. To close this gap, we analyzed the effects of acidic and alkaline pHe, both in short-term and long-term settings, on apoptotic and non-apoptotic TRAIL-induced signaling. We found that acidic and alkaline pHe differentially impact TRAIL-induced responses, and in addition, the duration of the pHe exposition also represents an important parameter. Thus, adaptation to acidic pHe increases TRAIL sensitivity in two different PDAC cell lines, Colo357 and Panc1, one already TRAIL-sensitive and the other TRAIL-resistant, respectively. However, the latter became highly TRAIL-sensitive only by concomitant inhibition of Bcl-xL. None of these effects was observed under other pHe conditions studied. Both TRAIL-induced non-apoptotic signaling pathways, as well as constitutively expressed anti-apoptotic proteins, were regulated by acidic pHe. Whereas the non-apoptotic pathways were differently affected in Colo357 than in Panc1 cells, the impact on the anti-apoptotic protein levels was similar in both cell lines. In Panc1 cells, adaptation to either acidic or alkaline pHe blocked the activation of the most of TRAIL-induced non-apoptotic pathways. Interestingly, under these conditions, significant downregulation of the plasma membrane levels of TRAIL-R1 and TRAIL-R2 was observed. Summing up, extracellular pH influences PDAC cells’ response to TRAIL with acidic pHe adaptation, showing the ability to strongly increase TRAIL sensitivity and in addition to inhibit TRAIL-induced pro-inflammatory signaling.
Higher Expression of DNA (de)methylation-Related Genes Reduces Adipogenicity in Dental Pulp Stem Cells
Authors: Argaez-Sosa Adaylu A. , Rodas-Junco Beatriz A. , Carrillo-Cocom Leydi M. , Rojas-Herrera Rafael A. , Coral-Sosa Abel , Aguilar-Ayala Fernando J. , Aguilar-Pérez David , Nic-Can Geovanny I.
Published: February 2022

Obesity is a significant health concern that has reached alarming proportions worldwide. The overconsumption of high-energy foods may cause metabolic dysfunction and promote the generation of new adipocytes by contributing to several obesity-related diseases. Such concerns demand a deeper understanding of the origin of adipocytes if we want to develop new therapeutic approaches. Recent findings indicate that adipocyte development is facilitated by tight epigenetic reprogramming, which is required to activate the gene program to change the fate of mesenchymal stem cells (MSCs) into mature adipocytes. Like adipose tissue, different tissues are also potential sources of adipocyte-generating MSCs, so it is interesting to explore whether the epigenetic mechanisms of adipogenic differentiation vary from one depot to another. To investigate how DNA methylation (an epigenetic mark that plays an essential role in controlling transcription and cellular differentiation) contributes to adipogenic potential, dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PLSCs) were analyzed during adipogenic differentiation in vitro. Here, we show that the capacity to differentiate from DPSCs or PLSCs to adipocytes may be associated with the expression pattern of DNA methylation-related genes acquired during the induction of the adipogenic program. Our study provides insights into the details of DNA methylation during the adipogenic determination of dental stem cells, which can be a starting point to identify the factors that affect the differentiation of these cells and provide new strategies to regulate differentiation and adipocyte expansion.
Perinatal Combinational Exposure to Bisphenol A and a High-Fat Diet Contributes to Transgenerational Dysregulation of Cardiovascular and Metabolic Systems in Mice
Authors: Liu Juncheng , Liao Maolin , Huang Rongfeng , You Yuehua , Lin Xiaojing , Yang Hong , Fan Lei , Zhong Ying , Li Xinyu , Li Jibin , Xiao Xiaoqiu
Published: February 2022

Both bisphenol A (BPA) and high-fat diet (HFD) exert unfavorable effects on animals and humans; moreover, they could affect the health of their offspring. BPA and HFD often coexist in modern lifestyles; however, the long-term effects of simultaneous exposure of mothers to BPA and HFD during the perinatal period on the cardiovascular and metabolic systems of the offspring remain unclear. This study aimed to examine the effect of simultaneous exposure of mothers to BPA and HFD on the risk of metabolic and cardiovascular abnormalities in offspring. Institute of Cancer Research female mice (F0) were exposed to BPA and fed with HFD before and during gestation until the end of lactation. F0 mice were mated with untreated males to produce the first generation (F1); subsequently, adult F1 males/females were mated with normal females/males to produce the second generation (F2). Combined maternal exposure to BPA and HFD caused myocardial hypertrophy and aortic tunica media thickening as well as increased the cross-sectional area of cardiomyocytes and blood pressure in the matrilineal F2 generation. These cardiovascular changes might be associated with reduced endothelial nitric oxide synthase (eNOS) levels. The patrilineal female F2 was more likely to be obese than the patrilineal male F2. Re-feeding with a HFD showed a more significant weight gain and reduced energy expenditure. However, the aforementioned effects were not observed with exposure to HFD or BPA alone during the perinatal period. Our findings suggest that perinatal combinational exposure to BPA and HFD could cause metabolic and cardiovascular disorders in the offspring, Further, our findings demonstrate that the synergistic effects of HFD and BPA could be transmitted to future generations in a sex-dependent manner.
Skin Immunosenescence and Type 2 Inflammation: A Mini-Review With an Inflammaging Perspective
Authors: Chen Bangtao , Yang Jing , Song Yao , Zhang Daojun , Hao Fei
Published: February 2022

Skin-resident stromal cells, including keratinocytes, fibroblasts, adipocytes, and immune cells including Langerhans cells, dendritic cells, T cells, and innate lymphoid cells, and their functional products work in concert to ensure the realization of skin barrier immunity. However, aging-induced immunosenescence predisposes the elderly to pruritic dermatoses, including type 2 inflammation-mediated. Inflammaging, characterized by chronic low level of pro-inflammatory cytokines released from senescent cells with the senescence-associated secretory phenotype (SASP), may drive immunosenescence and tangle with type 2 inflammatory dermatoses. The present mini-review summarizes current evidence on immunosenescence and type 2 inflammation in the skin and further focuses on future needs from an inflammaging perspective to clarify their complexity.
Multiscale Approach to Dairy Products Design
Authors: Díaz-Bustamante Martha L. , Fernández-Niño Miguel , Reyes Luis H. , Alvarez Solano Oscar Alberto
Published: February 2022

Dairy products are among the most popular nutritious foods in the world. Understanding the relationship between the composition, process, and structural properties at different scales (molecular, microscopic, and macroscopic) is fundamental to designing dairy products. This review highlights the need to analyze this relationship from different scales as an essential step during product design through a multiscale approach.
Comparative N-Glycoproteomics Analysis of Clinical Samples Via Different Mass Spectrometry Dissociation Methods
Authors: Zeng Wenjuan , Zheng Shanshan , Su Tao , Cheng Jiahan , Mao Yonghong , Zhong Yi , Liu Yueqiu , Chen Jianhai , Zhao Wanjun , Lin Tianhai , Liu Fang , Li Guisen , Yang Hao , Zhang Yong
Published: February 2022

Site-specific N-glycosylation characterization requires intact N-glycopeptide analysis based on suitable tandem mass spectrometry (MS/MS) method. Electron-transfer/higher-energy collisional dissociation (EThcD), stepped collision energy/higher-energy collisional dissociation (sceHCD), higher-energy collisional dissociation-product-dependent electron-transfer dissociation (HCD-pd-ETD), and a hybrid mass spectrometry fragmentation method EThcD-sceHCD have emerged as valuable approaches for glycoprotein analysis. However, each of them incurs some compromise, necessitating the systematic performance comparisons when applied to the analysis of complex clinical samples (e.g., plasma, urine, cells, and tissues). Herein, we compared the performance of EThcD-sceHCD with those previous approaches (EThcD, sceHCD, HCD-pd-ETD, and sceHCD-pd-ETD) in the intact N-glycopeptide analysis, and determined its applicability for clinical N-glycoproteomic study. The intact N-glycopeptides of distinct samples, namely, plasma from prostate cancer (PCa) patients, urine from immunoglobulin A nephropathy (IgAN) patients, human hepatocarcinoma cell line (HepG2), and thyroid tissues from thyroid cancer (TC) patients were analyzed by these methods. We found that EThcD-sceHCD outperformed other methods in the balance of depth and accuracy of intact N-glycopeptide identification, and sceHCD and EThcD-sceHCD have good complementarity. EThcD-sceHCD holds great potential for biomarker discovery from clinical samples.
Recent Progress of Exosome Isolation and Peptide Recognition-Guided Strategies for Exosome Research
Authors: Xu Kun , Jin Yulong , Li Yongming , Huang Yanyan , Zhao Rui
Published: February 2022

Exosomes are membrane extracellular vesicles secreted by almost all kinds of cells, which are rich in proteins, lipids, and nucleic acids. As a medium of intercellular communication, exosomes play important roles in biological processes and are closely related to the occurrence, and development of many diseases. The isolation of exosomes and downstream analyses can provide important information to the accurate diagnosis and treatment of diseases. However, exosomes are various in a size range from 30 to 200 nm and exist in complex bio-systems, which provide significant challenges for the isolation and enrichment of exosomes. Different methods have been developed to isolate exosomes, such as the “gold-standard” ultracentrifugation, size-exclusion chromatography, and polymer precipitation. In order to improve the selectivity of isolation, affinity capture strategies based on molecular recognition are becoming attractive. In this review, we introduced the main strategies for exosome isolation and enrichment, and compared their strengths and limitations. Furthermore, combined with the excellent performance of targeted peptides, we summarized the application of peptide recognition in exosome isolation and engineering modification.
Streptococcus agalactiae Infects Glial Cells and Invades the Central Nervous System via the Olfactory and Trigeminal Nerves
Authors: Chacko Anu , Delbaz Ali , Choudhury Indra N. , Eindorf Tanja , Shah Megha , Godfrey Christopher , Sullivan Matthew J. , St John James A. , Ulett Glen C. , Ekberg Jenny A. K.
Published: February 2022

Streptococcus agalactiae causes neonatal meningitis and can also infect the adult central nervous system (CNS). S. agalactiae can cross the blood-brain barrier but may also reach the CNS via other paths. Several species of bacteria can directly invade the CNS via the olfactory and trigeminal nerves, which extend between the nasal cavity and brain and injury to the nasal epithelium can increase the risk/severity of infection. Preterm birth is associated with increased risk of S. agalactiae infection and with nasogastric tube feeding. The tubes, also used in adults, can cause nasal injuries and may be contaminated with bacteria, including S. agalactiae. We here investigated whether S. agalactiae could invade the CNS after intranasal inoculation in mice. S. agalactiae rapidly infected the olfactory nerve and brain. Methimazole-mediated model of nasal epithelial injury led to increased bacterial load in these tissues, as well as trigeminal nerve infection. S. agalactiae infected and survived intracellularly in cultured olfactory/trigeminal nerve- and brain-derived glia, resulting in cytokine production, with some differences between glial types. Furthermore, a non-capsulated S. agalactiae was used to understand the role of capsule on glial cells interaction. Interestingly, we found that the S. agalactiae capsule significantly altered cytokine and chemokine responses and affected intracellular survival in trigeminal glia. In summary, this study shows that S. agalactiae can infect the CNS via the nose-to-brain path with increased load after epithelial injury, and that the bacteria can survive in glia.
Alterations of Gut Mycobiota Profiles in Adenoma and Colorectal Cancer
Authors: Gao Renyuan , Xia Kai , Wu Minkang , Zhong Hui , Sun Jing , Zhu Yin , Huang Linsheng , Wu Xiaocai , Yin Lu , Yang Rong , Chen Chunqiu , Qin Huanlong
Published: February 2022

Accumulating evidence indicates that gut microbiota dysbiosis contributes to colorectal cancer and adenoma. However, a few studies revealed the altered gut mycobiota architecture in colorectal cancer. The present study characterized the gut mycobiota profiles in adenoma and colorectal cancer patients by metagenomic sequencing. Malassezia restricta increased, while Leucoagaricus_sp_SymCcos and fungal_sp_ARF18 significantly decreased in adenoma. Phanerochaete_chrysosporium, Lachancea_waltii, and Aspergillus_rambellii were the top 3 fungi that were significantly enriched in colorectal cancer, while Candida_versatilis, Pseudocercospora_pini_densiflorae, and Candida_sp_JCM_15000 were dominant in the healthy controls. Thirteen fungi, ranked as critical biomarkers in diagnosing colorectal cancer, showed positive associations among all samples. Lachancea_waltii and Phanerochaete_chrysosporium showed the most significant association within CRC. The values of area under the receiver-operating characteristics curve (AUROC) of selected 13 mycobiota were 0.926 in the training model and 0.757 in the 10-fold validation model. Our study provided a reliable investigation of the alterations of gut mycobiota in the development of colorectal cancer and established a convincing diagnostic model for colorectal cancer, which might improve the treatment strategy for colorectal cancer in the future.
Pericardial Involvement in ST-Segment Elevation Myocardial Infarction as Detected by Cardiac MRI
Authors: Massalha Eias , Brodov Yafim , Oren Daniel , Fardman Alex , Natanzon Sharon Shalom , Mazin Israel , Beinart Roy , Goldkorn Ronen , Konen Eli , Segni Elio Di , Segev Amit , Beigel Roy , Matetzky Shlomi , Goitein Orly
Published: February 2022

Background

Post myocardial infarction pericarditis is considered relatively rare in the current reperfusion era. The true incidence of pericardial involvement may be underestimated since the diagnosis is usually based on clinical and echocardiographic parameters.

Objectives

This study aims to document the incidence, extent, and prognostic implication of pericardial involvement in ST-segment elevation myocardial infarction (PISTEMI) using cardiac MRI (CMR).

Methods

One hundred and eighty-seven consecutive ST-segment elevation myocardial infarction patients underwent CMR on day 5 ± 1 following admission, including steady-state free precession (SSFP) and late Gadolinium enhancement (LGE) sequences. Late Gadolinium enhancement and microvascular obstruction (MVO) were quantified as a percentage of left ventricular (LV) mass. Late Gadolinium enhancement was graded for transmurality according to the 17 AHA left ventricle (LV) segment model (LGE score). Late pericardial enhancement (LPE), the CMR evidence of pericardial involvement, was defined as enhanced pericardium in the LGE series and was retrospectively recorded as present or absent according to the 17 AHA segments. Late pericardial enhancement was evaluated adjacent to the LV, the right ventricle, and both atria. Clinical, laboratory, angiographic, and echocardiographic data were collected. Clinical follow-up for major adverse cardiac events (MACE) was documented and correlated with CMR indices, including LGE, MVO, and LPE.

Results

Late pericardial enhancement (LPE+) was documented in 77.5% of the study cohort. A strong association was found between LPE and the degree and extent of myocardial injury (LGE, MVO). Both LGE and MVO were significantly correlated with increased MACE on follow-up. On the contrary, LPE presence, either adjacent to the LV or the other cardiac chambers, was associated with a lower MACE rate in a median of 3 years of follow-up HR 0.39, 95% CI (0.21–0.7), p = 0.002, and HR 0.48, 95% CI (0.26–0.9), p = 0.02, respectively.

Conclusions

Prognostic implication of pericardial involvement in ST-segment elevation myocardial infarction was documented by CMR in 77.5% of our STEMI cohort. Late pericardial enhancement presence correlated significantly with the extent and severity of the myocardial damage. Unexpectedly, it was associated with a considerably lower MACE rate in the follow-up period.
Seismic Event Identification Based on a Generative Adversarial Network and Support Vector Machine
Authors: Liu Heyi , Song Jindong , Li Shanyou
Published: February 2022

Identifying appropriate seismic events is the primary precondition for conducting meaningful analysis in seismological research. The successful creation of a method to automatically identify earthquakes from large amounts of data has become increasingly vital, especially with the construction of seismic stations, the collection of extensive seismic data, and the development of earthquake early warning (EEW) systems. To accurately identify seismic events, a combined model based on a generative adversarial network (GAN) and a support vector machine (SVM) is proposed to distinguish between earthquakes and microtremors. We first use 52,537 strong ground motion records from Japan to train a GAN and extract the characteristics of P waves and then use an SVM to discriminate seismic events in the testing set, thereby transforming the complex seismic event identification into a simpler binary classification of earthquakes and microtremors. The results illustrate that the combined model can achieve accuracies of 99.74% for P waves and 99.93% for microtremors, which represents an increase in accuracy of 14.13% compared with the traditional short-term averaging/long-term averaging (STA/LTA) method. Additionally, 98% of the local seismic events in the Great East Japan earthquake were identified. Therefore, the combined model has a wide range of applications in EEW and earthquake monitoring.
Hydrate Attenuation Characteristics Based on the Patchy-Saturation Model
Authors: Liu Pengqi , Huang Handong , Hu Liguo , Mao Shuang , Tian Zhongbin , Shen Youyi
Published: February 2022

At present, attenuation characteristics of hydrate applicable to the seismic frequency band are still controversial. In this study, the dispersion and attenuation characteristics of hydrate in different occurrence modes were defined from the mesoscale perspective, and the saturation of hydrate in the study area is estimated. Based on effective medium theory and cementation theory, the skeleton elastic modulus of the sedimentary layer was obtained in the present study. The variation of P-wave attenuation with hydrate saturation was obtained by the patchy-saturation theory. P-wave attenuation increased with saturation when hydrate occurred in the suspension mode. P-wave attenuation decreased with saturation when hydrate occurred in the particle-contact or cementation mode. The particle-contact mode and cementation mode hydrate made the P-wave attenuation peak shift to the right. The influence of the cementation mode on attenuation was greater than that of the particle-contact mode. The conclusions of this study are applicable to the frequency range of seismic exploration, thus solving the problems of hydrate saturation prediction and resource quantity calculation assessment in the study area.
Blood Bacterial 16S rRNA Gene Alterations in Women With Polycystic Ovary Syndrome
Authors: Wang Qing , Wang Qi , Zhao Lanbo , Bin Yadi , Wang Li , Wang Lei , Zhang Kailu , Li Qiling
Published: February 2022

Background

Evidence proved the association between gut microbiome dysbiosis and polycystic ovary syndrome (PCOS) in metabolic disorder, decreased fertility, and hyperandrogenism. However, alterations in blood microbiome of PCOS remained unknown.

Objective

This study aims to measure the blood microbiome profile of PCOS patients compared with healthy controls by 16S rRNA sequencing and to investigate its association with PCOS.

Methods

In this case–control study, bacterial DNA in blood of 24 PCOS patients and 24 healthy controls was investigated by 16S rRNA gene sequencing using the MiSeq technology. Alpha and beta diversity were used to analyze within-sample biodiversity and similarity of one group to another, respectively. Linear discriminant analysis effect size (LEfSe) was calculated to determine biomarkers between groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional prediction was performed at genera level.

Result

Alpha diversity of blood microbiome decreased significantly in women with PCOS, and beta diversity analysis demonstrated a major separation between the two groups. In the PCOS group, the relative abundance of Proteobacteria, Firmicutes, and Bacteroidetes decreased significantly, while Actinobacteria increased significantly. Cladogram demonstrated the microbiome differences between the two groups at various phylogenic levels. Meanwhile, linear discriminant analysis (LDA) presented significant decreases in Burkholderiaceae, Lachnospiraceae, Bacteroidaceae, Ruminococcaceae, and S24-7 and significant increases in Nocardioidaceae and Oxalobacteraceae of the PCOS group. KEGG pathway analysis at genera level suggested that 14 pathways had significant differences between the two groups.

Conclusion

Our findings demonstrated that blood microbiome had a significantly lower alpha diversity, different beta diversity, and significant taxonomic variations in PCOS patients compared with healthy controls.
Triglyceride to High-Density Lipoprotein Cholesterol (TG/HDL-C) Ratio, a Simple but Effective Indicator in Predicting Type 2 Diabetes Mellitus in Older Adults
Authors: Liu Hongzhou , Liu Jing , Liu Jixiang , Xin Shuanli , Lyu Zhaohui , Fu Xiaomin
Published: February 2022

Background

A simple and readily available biomarker can provide an effective approach for the surveillance of type 2 diabetes mellitus (T2DM) in the elderly. In this research, we aim to evaluate the role of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as an indicator for new-onset T2DM in an elderly Chinese population aged over 75 years.

Methods

This longitudinal retrospective cohort study was conducted using a free database from a health check screening project in China. Participants with baseline TG and HDL measurements were enrolled, and the data of T2DM development were collected. The cumulative incident T2DM rates in different quintile groups of TG/HDL-C ratio (Q1 to Q5) were calculated and plotted. The independent effect of baseline TG/HDL-C ratio on T2DM risk during the follow-up period was tested by the Cox proportional hazard model. Subgroup analysis was also conducted to clarify the role of TG/HDL-C ratio in specific populations.

Results

A total of 231 individuals developed T2DM among 2,571 subjects aged over 75 years during follow-up. Regardless of adjustment for potential confounding variables, elevated TG/HDL-C ratio independently indicated a higher risk of incident T2DM [hazard ratio (HR) = 1.29; 95% confidence interval (CI), 1.14–1.47; P < 0.01. As compared with the lowest quintile (Q1), elevated TG/HDL-C ratio quintiles (Q2 to Q5) were associated with larger HR estimates of incident T2DM [HR (95% CI), 1.35 (0.85–2.17), 1.31 (0.83–2.06), 1.85 (1.20–2.85), and 2.10 (1.38–3.20), respectively]. In addition, a non-linear correlation was found between TG/HDL-C ratio and the risk of T2DM, and the slope of the curve decreased after the cutoff point of 2.54. Subgroup analysis revealed a stronger positive correlation among male individuals and those with body mass index <24 kg/m2.

Conclusions

Increased TG/HDL-C ratio indicates a greater risk of new-onset T2DM regardless of confounding variables. TG/HDL-C ratio is a simple but effective indicator in predicting T2DM in older adults. More future investigations are warranted to further promote the clinical application of TG/HDL-C ratio.
Maximum Power Point Tracking in Power System Control Using Reservoir Computing
Authors: Seddoh Matthew Akatey , Sackey David Mensah , Acakpovi Amevi , Owusu-Manu De-Graft , Sowah Robert A.
Published: February 2022

This article deals with an innovative approach to maximum power point tracking (MPPT) in power systems using the reservoir computing (RC) technique. Even though extensive studies have been conducted on MPPT to improve solar PV systems efficiency, there is still considerable room for improvement. The methodology consisted in modeling and programming with MATLAB software, the reservoir computing paradigm, which is a form of recurrent neural network. The performances of the RC algorithm were compared to two well-known methods of maximum power point tracking: perturbed and observed (P&O) and artificial neural networks (ANN). Power, voltage, current, and temperature characteristics were assessed, plotted, and compared. It was established that the RC-MPPT provided better performances than P&O-MPPT and ANN-MPPT from the perspective of training and testing MSE, rapid convergence, and accuracy of tracking. These findings suggest the need for rapid implementation of the proposed RC-MPPT algorithm on microcontroller chips for the widespread use and adoption globally.
Validation of Computationally Efficient Simulations of Douglas Fir Pyrolysis and Combustion Using Time-Resolved Frequency Comb Laser Measurements
Authors: Glusman Jeffrey F. , Lapointe Caelan B. , Makowiecki Amanda S. , Simons-Wellin Sam , Rieker Gregory B. , Daily John W. , Hamlington Peter E.
Published: February 2022

Computational simulations have the potential to provide low-cost, low-risk insights into wildland fire structure and dynamics. Simulation accuracy is limited, however, by the difficulty of modeling physical processes that span a wide range of spatial scales. These processes include heat transfer via radiation and turbulent advection, as well as both solid- and gas-phase chemistry. In the present study, we perform large eddy simulation (LES) with adaptive mesh refinement to model the multi-phase pyrolysis and combustion of dry Douglas fir, where temperature-based lookup tables corresponding to a multi-step pyrolysis mechanism are used to represent the composition of gas-phase pyrolysis products. Gas-phase and surface temperatures, mass loss, and water vapor mole fraction from the LES are shown to compare favorably with experimental measurements of a radiatively heated Douglas fir fuel sample undergoing pyrolysis and combustion beneath a cone calorimeter. Using frequency comb laser diagnostics, optical and infrared cameras, and a load cell, the experiments provide simultaneous in situ, time-resolved measurements of chemical composition, temperature, and mass loss. The present study thus combines cutting edge computational and experimental techniques with multi-step chemical pyrolysis modeling to provide a validated computational tool for the prediction of solid fuel pyrolysis and combustion relevant to wildland fires.
A Heterochromatic Knob Reducing the Flowering Time in Maize
Authors: Carvalho Renata Flávia , Aguiar-Perecin Margarida Lopes Rodrigues , Clarindo Wellington Ronildo , Fristche-Neto Roberto , Mondin Mateus
Published: February 2022

Maize flowering time is an important agronomic trait, which has been associated with variations in the genome size and heterochromatic knobs content. We integrated three steps to show this association. Firstly, we selected inbred lines varying for heterochromatic knob composition at specific sites in the homozygous state. Then, we produced homozygous and heterozygous hybrids for knobs. Second, we measured the genome size and flowering time for all materials. Knob composition did not affect the genome size and flowering time. Finally, we developed an association study and identified a knob marker on chromosome 9 showing the strongest association with flowering time. Indeed, modelling allele substitution and dominance effects could offer only one heterochromatic knob locus that could affect flowering time, making it earlier rather than the knob composition.
Complex Chromosomal Rearrangement Causes Male Azoospermia: A Case Report and Literature Review
Authors: Liang Yi , Xie Yingjun , Kong Shu , Pan Qianying , Qiu Wenjun , Wang Ding , Li Mengting , Lin Sisi , Liu Zihang , Sun Xiaofang
Published: February 2022

Background: Male carriers of complex chromosomal rearrangements (CCRs) may have decreased fertility and usually present with azoospermia, oligospermia or teratospermia.

Methods: High-resolution karyotype analysis using G-banding on peripheral blood lymphocytes was performed in an azoospermic male. Copy number variations (CNVs) were detected by chromosomal microarray analysis, and genetic variations were determined by long-read nanopore sequencing with Sanger sequencing for breakpoint confirmation.

Results: The karyotype of the patient was 46,XY,t(4;21)(p11;p11),t(5;6;14)(p13q22;p22q22;q22), which did not involve CNVs with clinical significance. Twelve breakpoints in chromosomes 5, 6, and 14 were found by long-read nanopore sequencing. Reports on 17 males carrying CCRs with azoospermia were also reviewed.

Conclusion: The extent of asynaptic regions in synaptonemal complexes during pachytene and the disruption of genes involved in male gametogenesis may cause azoospermia in CCR carriers.
Generation and Analysis of Pyroptosis-Based and Immune-Based Signatures for Kidney Renal Clear Cell Carcinoma Patients, and Cell Experiment
Authors: Lin Gaoteng , Feng Qingfu , Zhan Fangfang , Yang Fan , Niu Yuanjie , Li Gang
Published: February 2022

Background: Pyroptosis is a programmed cell death caused by inflammasomes, which is closely related to immune responses and tumor progression. The present study aimed to construct dual prognostic indices based on pyroptosis-associated and immune-associated genes and to investigate the impact of the biological signatures of these genes on Kidney Renal Clear Cell Carcinoma (KIRC).

Materials and Methods: All the KIRC samples from the Cancer Genome Atlas (TCGA) were randomly and equally divided into the training and testing datasets. Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis were used to screen crucial pyroptosis-associated genes (PAGs), and a pyroptosis-associated genes prognostic index (PAGsPI) was constructed. Immune-associated genes (IAGs) related to PAGs were identified, and then screened through Cox and LASSO regression analyses, and an immune-associated genes prognostic index (IAGsPI) was developed. These two prognostic indices were verified by using the testing and the Gene Expression Omnibus (GEO) datasets and an independent cohort. The patients’ response to immunotherapy was analyzed. A nomogram was constructed and calibrated. qRT-PCR was used to detect the expression of PAGs and IAGs in the tumor tissues and normal tissues. Functional experiment was carried out.

Results: 86 PAGs and 1,774 differentially expressed genes (DEGs) were obtained. After intersecting PAGs with DEGs, 22 differentially expressed PAGs (DEPAGs) were included in Cox and LASSO regression analyses, identifying 5 crucial PAGs. The PAGsPI was generated. Patients in the high-PAGsPI group had a poor prognosis. 82 differentially expressed IAGs (DEIAGs) were highly correlated with DEPAGs. 7 key IAGs were screened out, and an IAGsPI was generated. Patients in the high-IAGsPI group had a poor prognosis. PAGsPI and IAGsPI were verified to be robust and reliable. The results revealed patients in low-PAGsPI group and high-IAGsPI group may be more sensitive to immunotherapy. The calibrated nomogram was proved to be reliable. An independent cohort study also proved that PAGsPI and IAGsPI performed well in prognosis prediction. We found that the expression of AIM2 may affect proliferation of KIRC cells.

Conclusion: PAGsPI and IAGsPI could be regarded as potential biomarkers for predicting the prognosis of patients with KIRC.
Profile of Chromosomal Alterations, Chromosomal Instability and Clonal Heterogeneity in Colombian Farmers Exposed to Pesticides
Authors: Meléndez-Flórez María Paula , Valbuena Duvan Sebastián , Cepeda Sebastián , Rangel Nelson , Forero-Castro Maribel , Martínez-Agüero María , Rondón-Lagos Milena
Published: February 2022

Pesticides are a group of environmental pollutants widely used in agriculture to protect crops, and their indiscriminate use has led to a growing public awareness about the health hazards associated with exposure to these substances. In fact, exposure to pesticides has been associated with an increased risk of developing diseases, including cancer. In a study previously published by us, we observed the induction of specific chromosomal alterations and, in general, the deleterious effect of pesticides on the chromosomes of five individuals exposed to pesticides. Considering the importance of our previous findings and their implications in the identification of cytogenetic biomarkers for the monitoring of exposed populations, we decided to conduct a new study with a greater number of individuals exposed to pesticides. Considering the above, the aim of this study was to evaluate the type and frequency of chromosomal alterations, chromosomal variants, the level of chromosomal instability and the clonal heterogeneity in a group of thirty-four farmers occupationally exposed to pesticides in the town of Simijacá, Colombia, and in a control group of thirty-four unexposed individuals, by using Banding Cytogenetics and Molecular Cytogenetics (Fluorescence in situ hybridization). Our results showed that farmers exposed to pesticides had significantly increased frequencies of chromosomal alterations, chromosomal variants, chromosomal instability and clonal heterogeneity when compared with controls. Our results confirm the results previously reported by us, and indicate that occupational exposure to pesticides induces not only chromosomal instability but also clonal heterogeneity in the somatic cells of people exposed to pesticides. This study constitutes, to our knowledge, the first study that reports clonal heterogeneity associated with occupational exposure to pesticides. Chromosomal instability and clonal heterogeneity, in addition to reflecting the instability of the system, could predispose cells to acquire additional instability and, therefore, to an increased risk of developing diseases.
The Effect of Integration of Family Planning Into HIV Services on Contraceptive Use Among Women Accessing HIV Services in Low and Middle-Income Countries: A Systematic Review
Authors: Grant-Maidment Tallulah , Kranzer Katharina , Ferrand Rashida A.
Published: February 2022

There is substantial unmet need for family planning (FP) among women living with HIV (WLHIV), leading to unintended pregnancies and may contribute indirectly to increasing the risk of transmission of HIV. This review aims to determine whether integration of FP into HIV testing and care results in increased use of contraception, a reduction in unmet need for FP, improved use of safer conception methods and a reduction in unintended pregnancies in low and middle-income countries. A systematic review was undertaken incorporating studies from PubMed, EMBASE, CINAHL, Web of Science and Global Health, the International AIDS Society Abstract Archive, the World STI & HIV Congress Abstract Archive and the Conference on Retroviruses and Opportunistic Infections Abstract Archive published between 2016 and 2021, updating previous systematic reviews. After screening, 13 studies were included, 11 conducted in sub-Saharan Africa and 2 in India. The primary outcome of the review was contraceptive uptake and secondary outcomes included unmet need for FP, safer conception and unintended pregnancy. Integrated FP-HIV facilities were found to increase dual contraceptive use by at least 8% in five studies and modern contraceptive use by at least 8% in four studies. Findings from two studies suggested integration decreased the unmet need for contraception. Limited data prevented a conclusion from being drawn regarding whether integration increases safer conception. There was no evidence of integration reducing unintended pregnancies. The median quality score of studies was 3/9. Overall, integrated facilities have the potential of improving reproductive health of women accessing HIV services in LMICs. FP may be enhanced by including a safer conception component for WLHIV.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021251008, identifier: CRD42021251008.
Multi-Cellular Immunological Interactions Associated With COVID-19 Infections
Authors: Verma Jitender S. , Libertin Claudia R. , Gupta Yash , Khanna Geetika , Kumar Rohit , Arora Balvinder S. , Krishna Loveneesh , Fasina Folorunso O. , Hittner James B. , Antoniades Athos , van Regenmortel Marc H. V. , Durvasula Ravi , Kempaiah Prakasha , Rivas Ariel L.
Published: February 2022

To rapidly prognosticate and generate hypotheses on pathogenesis, leukocyte multi-cellularity was evaluated in SARS-CoV-2 infected patients treated in India or the United States (152 individuals, 384 temporal observations). Within hospital (<90-day) death or discharge were retrospectively predicted based on the admission complete blood cell counts (CBC). Two methods were applied: (i) a “reductionist” one, which analyzes each cell type separately, and (ii) a “non-reductionist” method, which estimates multi-cellularity. The second approach uses a proprietary software package that detects distinct data patterns generated by complex and hypothetical indicators and reveals each data pattern’s immunological content and associated outcome(s). In the Indian population, the analysis of isolated cell types did not separate survivors from non-survivors. In contrast, multi-cellular data patterns differentiated six groups of patients, including, in two groups, 95.5% of all survivors. Some data structures revealed one data point-wide line of observations, which informed at a personalized level and identified 97.8% of all non-survivors. Discovery was also fostered: some non-survivors were characterized by low monocyte/lymphocyte ratio levels. When both populations were analyzed with the non-reductionist method, they displayed results that suggested survivors and non-survivors differed immunologically as early as hospitalization day 1.
Inflammasome Meets Centrosome: Understanding the Emerging Role of Centrosome in Controlling Inflammasome Activation
Authors: Wu Dandan , Zhang Zhenzhen , Jiang Xiaoli , Du Yaning , Zhang Shuangyan , Yang Xiao-Dong
Published: February 2022

Inflammasomes are multi-protein platforms that are assembled in response to microbial and danger signals to activate proinflammatory caspase-1 for production of active form of IL-1β and induction of pyroptotic cell death. Where and how an inflammasome is assembled in cells has remained controversial. While the endoplasmic reticulum, mitochondria and Golgi apparatus have been reported to be associated with inflammasome assembly, none of these sites seems to match the morphology, number and size of activated inflammasomes that are microscopically observable as one single perinuclear micrometer-sized punctum in each cell. Recently, emerging evidence shows that NLRP3 and pyrin inflammasomes are assembled, activated and locally regulated at the centrosome, the major microtubule organizing center in mammalian cells, elegantly accounting for the singularity, size and perinuclear location of activated inflammasomes. These new exciting findings reveal the previously unappreciated importance of the centrosome in controlling inflammasome assembly and activation as well as inflammasome-related diseases.
The Roles of Mesenchymal Stem Cells in Gastrointestinal Cancers
Authors: Xiang Ze , Hua Menglu , Hao Zhou , Biao Huang , Zhu Chaojie , Zhai Guanghua , Wu Jian
Published: February 2022

Mesenchymal stem cells (MSCs) were reported to have strong immunomodulatory ability, and inhibit the proliferation of T cells and their immune response through cell-to-cell interactions and the generation of cytokines. With high differentiation potential and self-renewal ability, MSCs are considered to function in alleviating inflammatory responses, promoting tissue regeneration and inhibiting tissue fibrosis formation. As the most common malignancies, gastrointestinal (GI) cancers have high incidence and mortality. The accurate diagnosis, exact prognosis and treatment of GI cancers have always been a hot topic. Therefore, the potential applications of MSCs in terms of GI cancers are receiving more and more attention. Recently, there is increasing evidence that MSCs may serve as a key point in the growth, metastasis, inhibition, treatment and prognosis of GI cancers. In this review, we summarized the roles of MSCs in GI cancers, mainly focusing on esophageal cancer (EC), gastric cancer (GC), liver cancer (LC), colorectal cancer (CRC) and pancreatic cancer. Besides, we proposed MSCs as potential targets and treatment strategies for the effective treatment of GI cancers, which may provide better guidance for the clinical treatment of GI cancers.
Aphid Viruses: A Brief View of a Long History
Authors: Guo Ya , Ji Ning , Bai Lisha , Ma Juntian , Li Zhaofei
Published: February 2022

Aphids are common agricultural pests with a wide range of hosts from agriculture to forestry plants. As known, aphids also serve as the major vectors to transmit plant viruses. Although numerous studies have focused on interactions between aphids and plant viruses, little is known about the aphid viruses, i.e., the insect viruses that are infectious to aphids. In the past four decades, several aphid viruses have been identified in diverse aphid species. In this review, we present a brief view of the aphid pathogenic viruses from several aspects, including classification of aphid viruses and characters of the viral genome, integration of viral sequences in host genomes, infection symptoms and influence on aphids, as well as host range and transmission modes. Taken together, these studies have increased our understanding of the rarely known aphid viruses, and will potentially contribute to the development of new strategies for controlling aphid populations.
Barriers to Achieving Conservation Engineering Goals in Commercial Trawl Fisheries
Authors: Murphy Robert , Yochum Noëlle , Wolf Nathan , Kroska Anita C. , Harris Bradley P.
Published: February 2022

The advancement of conservation practices in global trawl fisheries has been impeded in part by a lack of a collective understanding of the most relevant and broad-scale knowledge-needs, along with the identification of potential barriers to addressing these knowledge-needs. Using both an online survey and an in-person workshop, we engaged a diversity of fishing industry stakeholders including scientists, technology companies, trawl net makers, and fishermen working with North Pacific, United States, trawl fisheries to identify and prioritize areas in which further knowledge is required for successful implementation of conservation engineering practices. In addition, we identified barriers to addressing these knowledge-needs. Knowledge-needs related to fishing gear performance were identified among the top priorities, including several areas targeted at improving fishing efficiency that could further advance the sustainability of well-managed trawl fisheries. To better understand the composition and behavior of target versus non-target catch, workshop participants identified the importance of closing data and technology gaps. This highlights areas for potential collaboration between fishermen, researchers, and technology companies to address research prioritized by the end-user. Further, results from the workshop emphasized a need for industry-driven training and workshops focused on elevating fishermen skill for newer entrants through peer-learning and knowledge-sharing to achieve objectives like better non-target avoidance and increased fishing efficiency of the target species. Addressing these prioritized knowledge-needs, by first working toward overcoming the industry-identified barriers, may aid in increasing uptake of conservation practices, thereby contributing to the long-term sustainability of these fisheries and associated social-ecological systems.
Ship Biofouling as a Vector for Non-indigenous Aquatic Species to Canadian Arctic Coastal Ecosystems: A Survey and Modeling-Based Assessment
Authors: Chan Farrah T. , Ogilvie Dawson , Sylvester Francisco , Bailey Sarah A.
Published: February 2022

Ship biofouling is a major vector for the introduction and spread of harmful marine species globally; however, its importance in Arctic coastal ecosystems is understudied. The objective of this study was to provide insight regarding the extent of biofouling (i.e., percent cover, abundance, and species richness) on commercial ships operating in the Canadian Arctic. A questionnaire was used to collect information on travel history, antifouling practices, and self-reported estimates of biofouling extent from ships operating in the region during 2015–2016. Twenty-five percent of ships operating in the region during the study period completed the questionnaire (n = 50). Regression trees were developed to infer the percent cover of biofouling, total abundance of fouling invertebrates, and fouling species richness on respondent ships based on previous underwater wetted surface assessments of commercial ships in Canada. Age of antifouling coating system was the only significant predictor of percent cover and total abundance of biofouling invertebrates, while the number of biogeographic realms previously visited and port residence time were significant predictors for fouling species richness. Comparison of relevant travel history features reported through the questionnaire to the regression tree models revealed that 41.9% of 43 respondent ships had antifouling coating systems older than 630 days and are therefore inferred to have relatively high (> 9.3%) biofouling percent cover. More than half of respondent ships (62.8%) had antifouling coating systems older than 354 days and are therefore inferred to have a relatively high total abundance (over 6,500 individuals) of fouling invertebrates. Nearly half of respondent ships (45.9% of 37 ships) had visited at least three biogeographic realms during their last 10 ports-of-call and are therefore inferred to have relatively high fouling species richness (mean 42 taxa). Self-reported estimates of biofouling cover were unreliable, being much lower than model inferences. Although the regression tree models have relatively low predictive power, explaining only 15–33% of the variance in biofouling extent, this study indicates that commercial ships are an active pathway for the transportation of non-indigenous aquatic species to Canadian Arctic coastal ecosystems via biofouling.