bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of YAP1 in survival prediction, immune modulation, and drug response: A pan-cancer perspective
Authors: Hu Xueqing , Zhang Yingru , Yu Hao , Zhao Yiyang , Sun Xiaoting , Li Qi , Wang Yan
Published: November 2022

Introduction

Dysregulation of the Hippo signaling pathway has been implicated in multiple pathologies, including cancer, and YAP1 is the major effector of the pathway. In this study, we assessed the role of YAP1 in prognostic value, immunomodulation, and drug response from a pan-cancer perspective.

Methods

We compared YAP1 expression between normal and cancerous tissues and among different pathologic stages survival analysis and gene set enrichment analysis were performed. Additionally, we performed correlation analyses of YAP1 expression with RNA modification-related gene expression, tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoint regulator expression, and infiltration of immune cells. Correlations between YAP1 expression and IC50s (half-maximal inhibitory concentrations) of drugs in the CellMiner database were calculated.

Results

We found that YAP1 was aberrantly expressed in various cancer types and regulated by its DNA methylation and post-transcriptional modifications, particularly m6A methylation. High expression of YAP1 was associated with poor survival outcomes in ACC, BLCA, LGG, LUAD, and PAAD. YAP1 expression was negatively correlated with the infiltration of CD8+ T lymphocytes, CD4+ Th1 cells, T follicular helper cells, NKT cells, and activated NK cells, and positively correlated with the infiltration of myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) in pan-cancer. Higher YAP1 expression showed upregulation of TGF-β signaling, Hedgehog signaling, and KRAS signaling. IC50s of FDA-approved chemotherapeutic drugs capable of inhibiting DNA synthesis, including teniposide, dacarbazine, and doxorubicin, as well as inhibitors of hypoxia-inducible factor, MCL-1, ribonucleotide reductase, and FASN in clinical trials were negatively correlated with YAP1 expression.

Discussion

In conclusion, YAP1 is aberrantly expressed in various cancer types and regulated by its DNA methylation and post-transcriptional modifications. High expression of YAP1 is associated with poor survival outcomes in certain cancer types. YAP1 may promote tumor progression through immunosuppression, particularly by suppressing the infiltration of CD8+ T lymphocytes, CD4+ Th1 cells, T follicular helper cells, NKT cells, and activated NK cells, as well as recruiting MDSCs and CAFs in pan-cancer. The tumor-promoting activity of YAP1 is attributed to the activation of TGF-β, Hedgehog, and KRAS signaling pathways. AZD2858 and varlitinib might be effective in cancer patients with high YAP1 expression.
Divergent roles of PD-L1 in immune regulation during ischemia–reperfusion injury
Authors: Luo Jianheng , Liu Ke , Wang Yong , Li Hongge
Published: November 2022

Ischemia–reperfusion (I/R) injury is a type of pathological injury that commonly arises in various diseases. Various forms of immune response are involved in the process of I/R injury. As a member of the B7 costimulatory molecule family, programmed death 1-ligand 1 (PD-L1) is an important target for immune regulation. Therefore, PD-L1 may be implicated in the regulation of I/R injury. This review briefly describes the immune response during I/R injury and how PD-L1 is involved in its regulation by focusing on findings from various I/R models. Despite the limited number of studies in this field of research, PD-L1 has shown sufficient potential as a clinical therapeutic target.
Histones: The critical players in innate immunity
Authors: Li Xia , Ye Youyuan , Peng Kailan , Zeng Zhuo , Chen Li , Zeng Yanhua
Published: November 2022

The highly conserved histones in different species seem to represent a very ancient and universal innate host defense system against microorganisms in the biological world. Histones are the essential part of nuclear matter and act as a control switch for DNA transcription. However, histones are also found in the cytoplasm, cell membranes, and extracellular fluid, where they function as host defenses and promote inflammatory responses. In some cases, extracellular histones can act as damage-associated molecular patterns (DAMPs) and bind to pattern recognition receptors (PRRs), thereby triggering innate immune responses and causing initial organ damage. Histones and their fragments serve as antimicrobial peptides (AMPs) to directly eliminate bacteria, viruses, fungi, and parasites in vitro and in vivo. Histones are also involved in phagocytes-related innate immune response as components of neutrophil extracellular traps (NETs), neutrophil activators, and plasminogen receptors. In addition, as a considerable part of epigenetic regulation, histone modifications play a vital role in regulating the innate immune response and expression of corresponding defense genes. Here, we review the regulatory role of histones in innate immune response, which provides a new strategy for the development of antibiotics and the use of histones as therapeutic targets for inflammatory diseases, sepsis, autoimmune diseases, and COVID-19.
SARS-COV-2 infections in inborn errors of immunity: A single center study
Authors: Cousins Kimberley , DeFelice Nicholas , Jeong Stephanie , Feng Jin , Lee Ashley Sang Eun , Rotella Karina , Sanchez David , Jaber Faris , Agarwal Shradha , Ho Hsi-en , Cunningham-Rundles Charlotte
Published: November 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). One of the main topics of conversation in these past months in the world of immunology has been the issue of how patients with immune defects will fare if they contract this infection. To date there has been limited data on larger cohorts of patients with Inborn Errors of Immunity (IEI) diagnosed with COVID-19. Here, we review the data of COVID-19 infections in a single center cohort of 113 patients from the Mount Sinai Immunodeficiency program, who had 132 infections between January 2020 and June 2022. This included 56 males and 57 females, age range 2 - 84 (median 42). The mortality rate was 3%. Comparison between admitted patients revealed a significantly increased risk of hospitalization amongst the unvaccinated patients, 4% vaccinated vs 40% unvaccinated; odds ratio 15.0 (95% CI 4.2 – 53.4; p <0.00001). Additionally, COVID anti-spike antibody levels, determined in 36 of these patients post vaccination and before infection, were highly variable.
Epigenetic-related gene mutations serve as potential biomarkers for immune checkpoint inhibitors in microsatellite-stable colorectal cancer
Authors: Liu Chao , Xiao Huiting , Cui Luying , Fang Lin , Han Shuling , Ruan Yuli , Zhao Wenyuan , Zhang Yanqiao
Published: November 2022

Background

Combination therapy with immune checkpoint inhibitors (ICIs) may benefit approximately 10-20% of microsatellite-stable colorectal cancer (MSS-CRC) patients. However, there is a lack of optimal biomarkers. This study aims to understand the predictive value of epigenetic-related gene mutations in ICIs therapy in MSS-CRC patients.

Methods

We analyzed DNA sequences and gene expression profiles from The Cancer Genome Atlas (TCGA) to examine their immunological features. The Harbin Medical University Cancer Hospital (HMUCH) clinical cohort of MSS-CRC patients was used to validate the efficacy of ICIs in patients with epigenetic-related gene mutations (Epigenetic_Mut).

Results

In TCGA, 18.35% of MSS-CRC patients (78/425) had epigenetic-related gene mutations. The Epigenetic_Mut group had a higher tumor mutation burden (TMB) and frameshift mutation (FS_mut) rates. In all MSS-CRC samples, Epigenetic_Mut was elevated in the immune subtype (CMS1) and had a strong correlation with immunological features. Epigenetic_Mut was also associated with favorable clinical outcomes in MSS-CRC patients receiving anti-PD-1-based therapy from the HMUCH cohort. Using immunohistochemistry and flow cytometry, we demonstrated that Epigenetic_Mut samples were associated with increased anti-tumor immune cells both in tumor tissues and peripheral blood.

Conclusion

MSS-CRC patients with epigenetic regulation impairment exhibit an immunologically active environment and may be more susceptible to treatment strategies based on ICIs.
Ferroptosis increases obesity: Crosstalk between adipocytes and the neuroimmune system
Authors: Zhang Sen , Sun Zhiyuan , Jiang Xing , Lu Zhimin , Ding Ling , Li Chengzhi , Tian Xuewen , Wang Qinglu
Published: November 2022

Ferroptosis requires not only the accumulation of iron ions, but also changes in many ferroptosis-related regulators, including a decrease in GPX4 and inhibition of SLC7A11 for classical ferroptosis, a deletion of FSP1 or GCH1. Surprisingly, adipose tissue (AT) in the obesity conditions is also accompanied by iron buildup, decreased GSH, and increased ROS. On the neurological side, the pro-inflammatory factor released by AT may have first caused ferroptosis in the vagus nerve by inhibiting of the NRF2-GPX4 pathway, resulting in disorders of the autonomic nervous system. On the immune side, obesity may cause M2 macrophages ferroptosis due to damage to iron-rich ATMs (MFehi) and antioxidant ATMs (Mox), and lead to Treg cells ferroptosis through reductions in NRF2, GPX4, and GCH1 levels. At the same time, the reduction in GPX4 may also trigger the ferroptosis of B1 cells. In addition, some studies have also found the role of GPX4 in neutrophil autophagy, which is also worth pondering whether there is a connection with ferroptosis. In conclusion, this review summarizes the associations between neuroimmune regulation associated with obesity and ferroptosis, and on the basis of this, highlights their potential molecular mechanisms, proposing that ferroptosis in one or more cells in a multicellular tissue changes the fate of that tissue.
Preparing for the next pandemic: Simulation-based deep reinforcement learning to discover and test multimodal control of systemic inflammation using repurposed immunomodulatory agents
Authors: Cockrell Chase , Larie Dale , An Gary
Published: November 2022

Background

Preparation to address the critical gap in a future pandemic between non-pharmacological measures and the deployment of new drugs/vaccines requires addressing two factors: 1) finding virus/pathogen-agnostic pathophysiological targets to mitigate disease severity and 2) finding a more rational approach to repurposing existing drugs. It is increasingly recognized that acute viral disease severity is heavily driven by the immune response to the infection (“cytokine storm” or “cytokine release syndrome”). There exist numerous clinically available biologics that suppress various pro-inflammatory cytokines/mediators, but it is extremely difficult to identify clinically effective treatment regimens with these agents. We propose that this is a complex control problem that resists standard methods of developing treatment regimens and accomplishing this goal requires the application of simulation-based, model-free deep reinforcement learning (DRL) in a fashion akin to training successful game-playing artificial intelligences (AIs). This proof-of-concept study determines if simulated sepsis (e.g. infection-driven cytokine storm) can be controlled in the absence of effective antimicrobial agents by targeting cytokines for which FDA-approved biologics currently exist.

Methods

We use a previously validated agent-based model, the Innate Immune Response Agent-based Model (IIRABM), for control discovery using DRL. DRL training used a Deep Deterministic Policy Gradient (DDPG) approach with a clinically plausible control interval of 6 hours with manipulation of six cytokines for which there are existing drugs: Tumor Necrosis Factor (TNF), Interleukin-1 (IL-1), Interleukin-4 (IL-4), Interleukin-8 (IL-8), Interleukin-12 (IL-12) and Interferon-γ(IFNg).

Results

DRL trained an AI policy that could improve outcomes from a baseline Recovered Rate of 61% to one with a Recovered Rate of 90% over ~21 days simulated time. This DRL policy was then tested on four different parameterizations not seen in training representing a range of host and microbe characteristics, demonstrating a range of improvement in Recovered Rate by +33% to +56%

Discussion

The current proof-of-concept study demonstrates that significant disease severity mitigation can potentially be accomplished with existing anti-mediator drugs, but only through a multi-modal, adaptive treatment policy requiring implementation with an AI. While the actual clinical implementation of this approach is a projection for the future, the current goal of this work is to inspire the development of a research ecosystem that marries what is needed to improve the simulation models with the development of the sensing/assay technologies to collect the data needed to iteratively refine those models.
Seasonal dynamics of major phytoplankton functional types in the coastal waters of the west coast of Canada derived from OLCI Sentinel 3A
Authors: Vishnu Perumthuruthil Suseelan , Xi Hongyan , Belluz Justin Del Bel , Hussain Midhun Shah , Bracher Astrid , Costa Maycira
Published: November 2022

Monitoring the spatial distribution and seasonal dynamics of phytoplankton functional types (PFTs) in coastal oceans is essential for understanding fisheries production, changes in water quality, and carbon export to the deep ocean. The launch of new generation ocean color sensors such as OLCI (Ocean Land Color Instrument) onboard Sentinel 3A provides an unprecedented opportunity to study the surface dynamics of PFTs at high spatial (300 m) and temporal (daily) resolution. Here we characterize the seasonal dynamics of the major PFTs over the surface waters of the west coast of Canada using OLCI imagery and Chemical Taxonomy (CHEMTAX, v1.95) software. The satellite-based approach was adapted from a previously proven Empirical Orthogonal Function (EOF)-based algorithm by using a local matchup dataset comprising CHEMTAX model output and EOF scores derived from OLCI remote sensing reflectance. The algorithm was developed for the following PFTs: diatoms, dinoflagellates, dictyochophytes, haptophytes, green algae, cryptophytes, cyanobacteria, raphidophytes, and total chlorophyll-a (TChla) concentration. Of these PFTs, first level evaluation of the OLCI-derived retrievals showed reliable performance for diatoms and raphidophytes. The second level of validation showed that TChla had the best performance, and green algae, cryptophytes, and diatoms followed seasonal trends of a high temporal resolution in situ CHEMTAX time-series. Somewhat reduced correspondence was observed for raphidophytes. Due to their low contribution to the phytoplankton community (26%) and low range of variation, weak performance was noted for haptophytes, dictyochophytes, cyanobacteria, and dinoflagellates. The EOF-based PFT maps from daily OLCI imagery showed seasonal spring and fall diatom blooms with succession from spring blooms to high diversity flagellate dominated summer conditions. Furthermore, strong localized summer raphidophyte blooms (Heterosigma akashiwo) were observed, which are a regionally important harmful species. Overall, this study demonstrates the potential of the OLCI in deriving the surface dynamics of major PFTs of the Strait of Georgia (SoG), a critical habitat for the juvenile Pacific Salmon.
Seasonal gain in body condition of foraging humpback whales along the Western Antarctic Peninsula
Authors: Bierlich K. C. , Hewitt Joshua , Schick Robert S. , Pallin Logan , Dale Julian , Friedlaender Ari S. , Christiansen Fredrik , Sprogis Kate R. , Dawn Allison H. , Bird Clara N. , Larsen Gregory D. , Nichols Ross , Shero Michelle R. , Goldbogen Jeremy , Read Andrew J. , Johnston David W.
Published: November 2022

Most baleen whales are capital breeders that use stored energy acquired on foraging grounds to finance the costs of migration and reproduction on breeding grounds. Body condition reflects past foraging success and can act as a proxy for individual fitness. Hence, monitoring the seasonal gain in body condition of baleen whales while on the foraging grounds can inform how marine mammals support the costs of migration, growth, and reproduction, as well as the nutritional health of the overall population. Here, we use photogrammetry from drone-based imagery to examine how the body condition of humpback whales (Megaptera novaeangliae) changed over the foraging season (November to June) along the Western Antarctic Peninsula (WAP) from 2017 to 2019. This population (IWC stock G) is recovering from past whaling and is growing rapidly, providing an opportunity to study how whales store energy in a prey-rich environment. We used a body area index (BAI) to estimate changes in body condition and applied a Bayesian approach to incorporate measurement uncertainty associated with different drone types used for data collection. We used biopsy samples to determine sex and pregnancy status, and a length-based maturity classification to assign reproductive classes (n = 228; calves = 31, juveniles = 82, lactating females = 31, mature males = 12, mature unknown sex = 56, non-pregnant females = 12, pregnant females = 3, pregnant & lactating females = 1). Average BAI increased linearly over the feeding season for each reproductive class. Lactating females had lower BAI compared to other mature whales late in the season, reflecting the high energetic costs of nursing a calf. Mature males and non-pregnant females had the highest BAI values. Calves and juvenile whales exhibited an increase in BAI but not structural size (body length) over the feeding season. The body length of lactating mothers was positively correlated with the body length of their calves, but no relationship was observed between the BAI of mothers and their calves. Our study establishes a baseline for seasonal changes in the body condition for this humpback whale population, which can help monitor future impacts of disturbance and climate change.
Marine turtle hotspots in the Gulf of Mexico and Mesoamerican Reef: Strengthening management and preparedness
Authors: Cuevas Eduardo , Liceaga-Correa María de los Angeles , Uribe-Martínez Abigail , Gallegos-Fernández Sandra A. , Moncada-Gavilán Félix , González-Díaz-Mirón Raúl J. , López-Castro Melania C. , Guzmán-Hernández Vicente , López Martha
Published: November 2022

Marine turtles are of the highest ecological concern in terms of conservation and restoration programs and marine territorial ordering. Marine resource-extracting industries have severe negative impacts on their populations and their habitats. Thus, private industries and decision makers require the best and most robust spatially explicit scientific knowledge for a sustainable and responsible operation and government administration. Therefore, the identification of marine turtle hotspots is a strategic milestone for ecosystem management and an integral ecological knowledge about any region. We identified and delimited marine turtle hotspots in the Gulf of Mexico and Mesoamerican Reef. We analyzed satellite-tracked data of 178 individuals belonging to four marine turtle species. We used Brownian bridge movement models to estimate space use surfaces and map algebra to weight and merge layers of multiple species, life stages, and movement phases. The Yucatan Peninsula and central Veracruz in Mexico, along with the Florida Keys and Louisiana coast in the US, harbor the primary hotspots where marine turtles aggregate. We defined four primary hotspots used for migration in the western Gulf of Mexico, around the Yucatan Peninsula, a northern route following the Loop Current, and a southern one towards Gorda Bank, Central America. This study is the largest assessment of marine turtle hotspots in Mexico and Cuba and supports strategies for reinforcing regional management actions for their conservation, as well as a stronger response and preparedness for tackling anthropic threats to these species. This milestone contributes to extending the knowledge frontiers about these species to a new level.
An improved algae-YOLO model based on deep learning for object detection of ocean microalgae considering aquacultural lightweight deployment
Authors: Liu Dan , Wang Pengqi , Cheng Yuan , Bi Hai
Published: November 2022

Algae are widely distributed and have a considerable impact on water quality. Harmful algae can degrade water quality and be detrimental to aquaculture, while beneficial algae are widely used. The accuracy and speed of existing intelligent algae detection methods are available, but the size of parameters of models is large, the equipment requirements are high, the deployment costs are high, and there is still little research on lightweight detection methods in the area of algae detection. In this paper, we propose an improved Algae-YOLO object detection approach, which is based on ShuffleNetV2 as the YOLO backbone network to reduce the parameter space, adapting the ECA attention mechanism to improve detection accuracy, and redesigning the neck structure replacing the neck structure with ghost convolution module for reducing the size of parameters, finally the method achieved the comparable accuracy. Experiments showed that the Algal-YOLO approach in this paper reduces the size of parameters by 82.3%, and the computation (FLOPs) is decreased from 16G to 2.9G with less loss of accuracy, and mAP by only 0.007 when compared to the original YOLOv5s. With high accuracy, the smaller model size are achieved, which reduces the equipment cost during actual deployment and helps to promote the practical application of algae detection.
Measurement principle and technology of miniaturized strapdown inertial wave sensor
Authors: Zhou Fenghua , Zhang Rongwang , Zhang Shaowei
Published: November 2022

This paper presents the design and implementation of a low-cost directional inertial wave sensor, DWS19-2, which is suitable for installation on ocean air-sea coupling buoys, offshore environmental monitoring buoys and surface drifting buoys. DWS19-2 integrates an STM32F446 embedded controller with a 9-axis MEMS inertial module QZ901 to measure buoy pitch, roll, heading and accelerations. These parameters are further used to calculate wave parameters and estimate directional and non-directional wave spectra. These wave parameters and spectral information are then reported to the buoy data logger for real-time transmission to shore-based data centers. Details of the electrical design and onboard wave processing algorithm (coordinate projection, numerical integration in the frequency domain, time-based wave parameters, frequency-based wave parameters, directional wave spectrum), in addition to turntable tests, filed marine comparison with DWR-MKIII wave buoy and related ocean observation applications enabled by this device, are described in this paper.
Potential application of a newly isolated phage BUCT609 infecting Stenotrophomonas maltophilia
Authors: Han Ke , Dong Yuqi , An Xiaoping , Song Lihua , Li Mengzhe , Fan Huahao , Tong Yigang
Published: November 2022

Stenotrophomonas maltophilia (S. maltophilia) is widely distributed in nature and frequently causes nosocomial infections. In this work, the biological characteristics and genome of a new S. maltophilia phage BUCT609 isolated from hospital sewage with S. maltophilia strain No. 3015 as host was analyzed and its therapeutic effect in vivo was explored. It was observed by TEM that phage BUCT609 belongs to the Podoviridae with a 10 nm tail structure and a capsid with a diameter of about 50 nm. It has a short latent period (about 10 min) and its burst size is 382 PFU /cell when multiplicity of infection (MOI) is 0.01. Furthermore, it has a high survival rate in the environment with a pH range from 3 to 10 and temperature range from 4°C to 55°C. The complete genome of phage BUCT609 is linear double-stranded DNA of 43,145 bp in length, and the GC content is 58%. The genome sequence of phage BUCT609 shares <45% homology with other phages. No virulence genes and antibiotic resistance genes were found in bacteriophage BUCT609. In vivo animal experiments showed that the survival rate of mice infected with S. maltophilia was significantly improved after the intranasal injection of phage BUCT609. Therefore, our study supports that phage BUCT609 could be used as a promising antimicrobial candidate for treating S. maltophilia infections.
Metagenomics and metabolomics analysis to investigate the effect of Shugan decoction on intestinal microbiota in irritable bowel syndrome rats
Authors: Hang Lu , Wang Enkang , Feng Ya , Zhou Yan , Meng Yangyang , Jiang Fengru , Yuan Jianye
Published: November 2022

Background

The effect of Shugan Decoction (SGD) on intestinal motility and visceral hypersensitivity in Water avoid stress (WAS)-induced diarrhea predominant irritable bowel syndrome (IBS-D) model rats has been confirmed. However, the mechanisms of its action involved in the treatment of IBS-D need to be further studied. Intestinal microbiota plays an important role in maintaining intestinal homeostasis and normal physiological function. Changes in the intestinal microbiota and its metabolites are thought to participate in the pathophysiological process of IBS.

Aim

This study aimed to analyze the influence of SGD on intestinal microbiota and fecal metabolites in IBS-D rats by multiple omics techniques, including metagenomic sequencing and metabolomics.

Methods

We measured the intestinal motility and visceral sensitivity of three groups of rats by fecal pellets output and colorectal distension (CRD) experiment. In addition, metagenome sequencing analysis was performed to explore the changes in the number and types of intestinal microbiota in IBS-D model rats after SGD treatment. Finally, we also used untargeted metabolomic sequencing to screen the metabolites and metabolic pathways closely related to the therapeutic effect of SGD.

Results

We found that compared with the rats in the control group, the fecal pellets output of the rats in the WAS group increased and the visceral sensitivity threshold was decreased (P < 0.05). Compared with the rats in the WAS group, the fecal pellets output of the SGD group was significantly decreased, and the visceral sensitivity threshold increased (P < 0.05). Besides, compared with the rats in the WAS group, the relative abundance of Bacteroidetes increased in SGD group, while that of Firmicutes decreased at the phylum level, and at the species level, the relative abundance of Bacteroides sp. CAG:714, Lactobacillus reuteri and Bacteroides Barnesiae in SGD group increased, but that of bacterium D42-87 decreased. In addition, compared with the WAS group, several metabolic pathways were significantly changed in SGD group, including Taurine and hypotaurine metabolism, Purine metabolism, Sulfur metabolism, ABC transporters, Arginine and proline metabolism and Bile secretion.

Conclusion

SGD can regulate specific intestinal microbiota and some metabolic pathways, which may explain its effect of alleviating visceral hypersensitivity and abnormal intestinal motility in WAS-induced IBS-D rats.
Manipulation of innate immune signaling pathways by SARS-CoV-2 non-structural proteins
Authors: Lu Yongxu , Michel Hendrik A. , Wang Pei-Hui , Smith Geoffrey L.
Published: November 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic, induces an unbalanced immune response in the host. For instance, the production of type I interferon (IFN) and the response to it, which act as a front-line defense against virus invasion, are inhibited during SARS-CoV-2 infection. In addition, tumor necrosis factor alpha (TNF-α), a proinflammatory cytokine, is upregulated in COVID-19 patients with severe symptoms. Studies on the closely related betacoronavirus, SARS-CoV, showed that viral proteins such as Nsp1, Orf6 and nucleocapsid protein inhibit IFN-β production and responses at multiple steps. Given the conservation of these proteins between SARS-CoV and SARS-CoV-2, it is not surprising that SARS-CoV-2 deploys similar immune evasion strategies. Here, we carried out a screen to examine the role of individual SARS-CoV-2 proteins in regulating innate immune signaling, such as the activation of transcription factors IRF3 and NF-κB and the response to type I and type II IFN. In addition to established roles of SARS-CoV-2 proteins, we report that SARS-CoV-2 proteins Nsp6 and Orf8 inhibit the type I IFN response but at different stages. Orf6 blocks the translocation of STAT1 and STAT2 into the nucleus, whereas ORF8 inhibits the pathway in the nucleus after STAT1/2 translocation. SARS-CoV-2 Orf6 also suppresses IRF3 activation and TNF-α-induced NF-κB activation.
Enhancing erythritol production from crude glycerol in a wild-type Yarrowia lipolytica by metabolic engineering
Authors: Yang Shuling , Pan Xuewei , Wang Qiang , Lv Qinglan , Zhang Xian , Zhang Rongzhen , Rao Zhiming
Published: November 2022

Background: Erythritol is a zero-calorie sweetener that is widely used in the food, pharmaceutical, and medical industries. Crude glycerol is the main by-product of biodiesel, and the effective utilization of crude glycerol will help to improve biodiesel viability. Previous studies on the production of erythritol from Y. lipolytica using crude glycerol as a carbon source have focused on optimizing the fermentation process of the mutant Y. lipolytica Wratislavia K1, while metabolic engineering has not been successfully applied.

Results: To this end, we engineered the yeast Y. lipolytica to increase the productivity of this strain. Wild strains tolerant to high concentrations of crude glycerol were screened and identified. A series of rational metabolic approaches were employed to improve erythritol production. Among them, the engineered strain Y-04, obtained by tandem overexpression of GUT1 and GUT2, significantly increased glycerol assimilation by 33.3%, which was consistent with the results of RT-qPCR analysis. The effects of tandem overexpression of GUT1, GUT2, TKL1, and TAL1 on erythritol synthesis were also evaluated. The best results were obtained using a mutant that overexpressed GUT1, GUT2, and TKL1 and knocked out EYD1. The final Y-11 strain produced 150 g/l erythritol in a 5-L bioreactor with a yield and productivity of 0.62 g/g and 1.25 g/l/h, respectively. To the best of our knowledge, this is the highest erythritol yield and productivity from crude glycerol ever reported in Y. lipolytica.

Conclusion: This work demonstrated that overexpression of GUT1, GUT2, and TKL1 and knockdown of EYD1 could be used to improve crude glycerol utilization and erythritol synthesis in Y. lipolytica. The process parameters such as erythritol yield and productivity were significantly elevated, which is valuable for industrial applications. Crude glycerol, as a carbon source, could efficiently restrict the synthesis of by-products while enhancing the generation of erythritol, compared to glucose. This indicates considerable potential for synthesizing value-added products from crude glycerol by Y. lipolytica.
Identification of metabolic fingerprints in severe obstructive sleep apnea using gas chromatography–Mass spectrometry
Authors: Mohit  , Tomar Manendra Singh , Araniti Fabrizio , Pateriya Ankit , Singh Kushwaha Ram Awadh , Singh Bhanu Pratap , Jurel Sunit Kumar , Singh Raghuwar Dayal , Shrivastava Ashutosh , Chand Pooran
Published: November 2022

Objective: Obstructive sleep apnea (OSA) is considered a major sleep-related breathing problem with an increasing prevalence rate. Retrospective studies have revealed the risk of various comorbidities associated with increased severity of OSA. This study aims to identify novel metabolic biomarkers associated with severe OSA.

Methods: In total, 50 cases of OSA patients (49.74 ± 11.87 years) and 30 controls (39.20 ± 3.29 years) were included in the study. According to the polysomnography reports and questionnaire-based assessment, only patients with an apnea–hypopnea index (AHI >30 events/hour) exceeding the threshold representing severe OSA patients were considered for metabolite analysis. Plasma metabolites were analyzed using gas chromatography–mass spectrometry (GC-MS).

Results: A total of 92 metabolites were identified in the OSA group compared with the control group after metabolic profiling. Metabolites and their correlated metabolic pathways were significantly altered in OSA patients with respect to controls. The fold-change analysis revealed markers of chronic kidney disease, cardiovascular risk, and oxidative stress-like indoxyl sulfate, 5-hydroxytryptamine, and 5-aminolevulenic acid, respectively, which were significantly upregulated in OSA patients.

Conclusion: Identifying these metabolic signatures paves the way to monitor comorbid disease progression due to OSA. Results of this study suggest that blood plasma-based biomarkers may have the potential for disease management.
Cerebral blood flow regulation is not acutely altered after a typical number of headers in women footballers
Authors: Jack Jacob , Woodgates Alex , Smail Oliver , Brown Felix , Lynam Katie , Lester Alice , Williams Genevieve , Bond Bert
Published: November 2022

Background

The repeated act of heading has been implicated in the link between football participation and risk of neurodegenerative disease, and acutely alters cerebrovascular outcomes in men. This study assessed whether exposure to a realistic number of headers acutely influences indices of cerebral blood flow regulation in female footballers.

Methods

Nineteen female players completed a heading trial and seated control trial on two separate days. The heading trial involved six headers in 1 h (one every 10 min), with the ball traveling at 40 ± 5 km/h. Cerebrovascular reactivity to hypercapnia and hypocapnia was determined using serial breath holding and hyperventilation attempts. Dynamic cerebral autoregulation (dCA) was assessed by scrutinizing the relationship between cerebral blood flow and mean arterial blood pressure during 5 min of squat stand maneuvers at 0.05 Hz. Neurovascular coupling (NVC) was quantified as the posterior cerebral artery blood velocity response to a visual search task. These outcomes were assessed before and 1 h after the heading or control trial.

Results

No significant time by trial interaction was present for the hypercapnic (P = 0.48, ηp2 = 0.05) and hypocapnic (P = 0.47, ηp2 = 0.06) challenge. Similarly, no significant interaction effect was present for any metric of dCA (P > 0.12, ηp2 < 0.16 for all) or NVC (P > 0.14, ηp2 < 0.15 for all).

Conclusion

The cerebral blood flow response to changes in carbon dioxide, blood pressure and a visual search task were not altered following six headers in female footballers. Further study is needed to observe whether changes are apparent after more prolonged exposure.
The role of the piriform cortex in temporal lobe epilepsy: A current literature review
Authors: Chee Keanu , Razmara Ashkaun , Geller Aaron S. , Harris William B. , Restrepo Diego , Thompson John A. , Kramer Daniel R.
Published: November 2022

Temporal lobe epilepsy is the most common form of focal epilepsy and can have various detrimental consequences within many neurologic domains. Recent evidence suggests that the piriform cortex may also be implicated in seizure physiology. The piriform cortex is a primary component of the olfactory network and is located at the junction of the frontal and temporal lobes, wrapping around the entorhinal sulcus. Similar to the hippocampus, it is a tri-layered allocortical structure, with connections to many adjacent regions including the orbitofrontal cortex, amygdala, peri- and entorhinal cortices, and insula. Both animal and human studies have implicated the piriform cortex as a critical node in the temporal lobe epilepsy network. It has additionally been shown that resection of greater than half of the piriform cortex may significantly increase the odds of achieving seizure freedom. Laser interstitial thermal therapy has also been shown to be an effective treatment strategy with recent evidence hinting that ablation of the piriform cortex may be important for seizure control as well. We propose that sampling piriform cortex in intracranial stereoelectroencephalography (sEEG) procedures with the use of a temporal pole or amygdalar electrode would be beneficial for further understanding the role of the piriform cortex in temporal lobe epilepsy.
White matter dementia then… and now
Authors: Filley Christopher M.
Published: November 2022

White matter dementia (WMD) is a concept introduced in 1988 to highlight the importance of white matter pathology in producing cognitive dysfunction and dementia. Whereas gray matter, particularly the cerebral cortex, has been primarily investigated in the dementias, subcortical pathology has long been correlated with cognitive loss, and a corticocentric perspective cannot account for the full range of neurobehavioral disorders. Within the subcortical regions, white matter is prominent, accounting for about half the volume of the adult brain, and many white matter diseases, injuries, and intoxications can produce cognitive dysfunction so severe as to justify the term dementia. Recognition of this novel syndrome relied heavily on the introduction of magnetic resonance imaging (MRI) that permitted in vivo visualization of white matter lesions. Neuropsychological studies clarified the clinical presentation of WMD by identifying a profile dominated by cognitive slowing and executive dysfunction, and a precursor syndrome of mild cognitive dysfunction was proposed to identify early cognitive impairment that may later evolve to WMD. As knowledge advanced, the role of white matter in structural connectivity within distributed neural networks was elucidated. In addition, highlighting the frequent commingling of gray and white matter involvement, white matter pathology was associated with neurodegenerative diseases such as Alzheimer's disease and chronic traumatic encephalopathy, with potentially transformative clinical implications. In particular, preventive measures and treatments exploiting white matter restoration and plasticity are gaining much attention. Today, WMD has matured into a concept that not only integrates knowledge from across the spectrum of clinical neuroscience, but also informs new investigations into many perplexing disorders and enables a more complete understanding of brain-behavior relationships.
SF-MVPA: A from raw data to statistical results and surface space-based MVPA toolbox
Authors: Li Qiang , Gong Dinghong , Shen Jie , Rao Chang , Ni Lei , Zhang Hongyi
Published: November 2022

Compared with traditional volume space-based multivariate pattern analysis (MVPA), surface space-based MVPA has many advantages and has received increasing attention. However, surface space-based MVPA requires considerable programming and is therefore difficult for people without a programming foundation. To address this, we developed a MATLAB toolbox based on a graphical interactive interface (GUI) called surface space-based multivariate pattern analysis (SF-MVPA) in this manuscript. Unlike the traditional MVPA toolboxes, which often only include MVPA calculation processes after data preprocessing, SF-MVPA covers the complete pipeline of surface space-based MVPA, including raw data format conversion, surface reconstruction, functional magnetic resonance (fMRI) data preprocessing, comparative analysis, surface space-based MVPA, leave one-run out cross validation, and family-wise error correction. With SF-MVPA, users can complete the complete pipeline of surface space-based MVPA without programming. In addition, SF-MVPA is designed for parallel computing and hence has high computational efficiency. After introducing SF-MVPA, we analyzed a sample dataset of tonal working memory load. By comparison with another surface space-based MVPA toolbox named CoSMoMVPA, we found that the two toolboxes obtained consistent results. We hope that through this toolbox, users can more easily implement surface space-based MVPA.
Polyphenols from foxtail millet bran ameliorate DSS-induced colitis by remodeling gut microbiome
Authors: Yang Ruipeng , Shan Shuhua , An Ning , Liu Fengming , Cui Kaili , Shi Jiangying , Li Hanqing , Li Zhuoyu
Published: November 2022

Introduction

Polyphenols from plants possess the anti-inflammatory and gut microbiota modulated properties. Foxtail millet (Setaria italica L., FM) has potential medical and nutritional functions because of rich phenolic and other phytochemical components.

Methods

Here, the study explored the effects of bound polyphenol of inner shell (BPIS) from FM bran on dextran sodium sulfate (DSS)-induced experimental colitis mice.

Results

Results showed that BPIS administration effectively relieved the weight loss, decreased disease active index (DAI) scores, restrained the secretion of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β, increased anti-inflammatory cytokines IL-10, IL-4, IL-5. BPIS prevented gut barrier damage by enhancing tight junction proteins Claudin1, ZO-1 and Occludin, increasing the number of goblet cells and facilitating the gene expressions of mucin family. In addition, BPIS restored the gut microbiota composition and increased the relative abundance of commensal bacteria such as Lachnospiraceae and Rikenellaceae and restrained the growth of S24-7 and Staphylococcaceae. Concentrations of short-chain-fatty acids (SCFAs) generated by gut microbiota were elevated in BPIS treated colitis mice.

Conclusion

These data suggest that BPIS effectively ameliorates DSS-induced colitis by preventing intestinal barrier damage and promoting gut microbiota community.
The role of CXCR3 and its ligands in cancer
Authors: Wang Xiaoming , Zhang Yangyang , Wang Sen , Ni Hongyan , Zhao Peng , Chen Guangyu , Xu Benling , Yuan Long
Published: November 2022

Chemokines are a class of small cytokines or signaling proteins that are secreted by cells. Owing to their ability to induce directional chemotaxis of nearby responding cells, they are called chemotactic cytokines. Chemokines and chemokine receptors have now been shown to influence many cellular functions, including survival, adhesion, invasion, and proliferation, and regulate chemokine levels. Most malignant tumors express one or more chemokine receptors. The CXC subgroup of chemokine receptors, CXCR3, is mainly expressed on the surface of activated T cells, B cells, and natural killer cells, and plays an essential role in infection, autoimmune diseases, and tumor immunity by binding to specific receptors on target cell membranes to induce targeted migration and immune responses. It is vital to treat infections, autoimmune diseases, and tumors. CXCR3 and its ligands, CXCL9, CXCL10, and CXCL11, are closely associated with the development and progression of many tumors. With the elucidation of its mechanism of action, CXCR3 is expected to become a new indicator for evaluating the prognosis of patients with tumors and a new target for clinical tumor immunotherapy. This article reviews the significance and mechanism of action of the chemokine receptor CXCR3 and its specific ligands in tumor development.
Bile-volatile organic compounds in the diagnostics of pancreatic cancer and biliary obstruction: A prospective proof-of-concept study
Authors: Teränen Ville , Nissinen Samuli , Roine Antti , Antila Anne , Siiki Antti , Vaalavuo Yrjö , Kumpulainen Pekka , Oksala Niku , Laukkarinen Johanna
Published: November 2022

Objectives

Detection of volatile organic compounds (VOCs) from bodily fluids with field asymmetric waveform ion mobility spectrometry (FAIMS) and related methods has been studied in various settings. Preliminary results suggest that it is possible to detect prostate, colorectal, ovarian and pancreatic cancer from urine samples. In this study, our primary aim was to differentiate pancreatic cancer from pancreatitis and benign tumours of the pancreas by using bile samples obtained during endoscopic retrograde cholangiopancreatography (ERCP). Secondarily, we aimed to differentiate all pancreatic region malignancies from all other kinds of benign causes of biliary obstruction.

Methods

A bile sample was successfully aspirated from 94 patients during ERCP in Tampere University Hospital. Hospital and patient records were prospectively followed up for at least two years after ERCP. Bile samples were analysed using a Lonestar chemical analyser (Owlstone, UK) using an ATLAS sampling system and a split-flow box. Diagnoses and corresponding data from the analyses were matched and divided into two subcategories for comparison. Statistical analysis was performed using linear discriminant analysis, support vector machines, and 5-fold cross-validation.

Results

Pancreatic cancers (n=8) were differentiated from benign pancreatic lesions (n=9) with a sensitivity of 100%, specificity of 77.8%, and correct rate of 88%. All pancreatic region cancers (n=19) were differentiated from all other kinds of benign causes of biliary obstruction (n=75) with corresponding values of 21.1%, 94.7%, and 80.7%. The sample size was too small to try to differentiate pancreatic cancers from adjacent cancers.

Conclusion

Analysing bile VOCs using FAIMS shows promising capability in detecting pancreatic cancer and other cancers in the pancreatic area.
Comparison of stereotactic body radiation therapy with hepatic resection and radiofrequency ablation as initial treatment in patients with early-stage hepatocellular carcinoma
Authors: Yang Zi-liang , Sun Xu-qi , Tang Yu-hao , Xiong Pei-yao , Xu Li
Published: November 2022

Background

Stereotactic body radiation therapy (SBRT) has emerged as a novel intervention for early-stage hepatocellular carcinoma (HCC). The outcomes of SBRT, liver resection (LR), and radiofrequency ablation (RFA) as the initial treatment for AJCC stage I HCC patients remain unclear.

Methods

Patients with AJCC stage I HCC from the Surveillance, Epidemiology and End Results database were analyzed for survival rates using the Kaplan–Meier method and stratified according to tumor size: S subgroup (≤2 cm), M subgroup (>2–3 cm), and L subgroup (>3 cm). For factors including age, year of diagnosis, sex, race, grade, tumor size, AFP, and fibrosis score, propensity score matching was performed to eliminate the imbalance of baseline features and selection bias during groups.

Results

A total of 4,002 patients were included; the difference in median overall survival (mOS) between the SBRT group and the LR or RFA group in the S subgroup was statistically insignificant (p=0.109 and p=0.744), while that of the RFA group was significantly worse than that of the LR group (p <0.001). In the M and L subgroups, the mOS of the SBRT group was worse than that of the RFA group (p=0.040 and p<0.001, respectively). The mOS of LR was the best when compared with either the SBRT or RFA group regardless of the subgroup M or L (all p<0.001).

Conclusion

For HCC ≤ 2 cm, SBRT can be used as an alternative treatment for RFA. For patients with HCC larger than 2 cm, RFA can provide better long-term survival than SBRT, while LR remains the best choice.