bluuebunny/crossref_metadata_2025 huggingface dataset:
Granulocyte Macrophage-Colony Stimulating Factor Produces a Splenic Subset of Monocyte-Derived Dendritic Cells That Efficiently Polarize T Helper Type 2 Cells in Response to Blood-Borne Antigen
Authors: Ryu Seul Hye , Shin Hyun Soo , Eum Hye Hyeon , Park Ji Soo , Choi Wanho , Na Hye Young , In Hyunju , Kim Tae-Gyun , Park Sejung , Hwang Soomin , Sohn Moah , Kim Eun-Do , Seo Kyoung Yul , Lee Hae-Ock , Lee Min-Geol , Chu Min Kyung , Park Chae Gyu
Published: January 2022

Dendritic cells (DCs) are key antigen-presenting cells that prime naive T cells and initiate adaptive immunity. Although the genetic deficiency and transgenic overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) signaling were reported to influence the homeostasis of DCs, the in vivo development of DC subsets following injection of GM-CSF has not been analyzed in detail. Among the treatment of mice with different hematopoietic cytokines, only GM-CSF generates a distinct subset of XCR1-33D1- DCs which make up the majority of DCs in the spleen after three daily injections. These GM-CSF-induced DCs (GMiDCs) are distinguished from classical DCs (cDCs) in the spleen by their expression of CD115 and CD301b and by their superior ability to present blood-borne antigen and thus to stimulate CD4+ T cells. Unlike cDCs in the spleen, GMiDCs are exceptionally effective to polarize and expand T helper type 2 (Th2) cells and able to induce allergic sensitization in response to blood-borne antigen. Single-cell RNA sequencing analysis and adoptive cell transfer assay reveal the sequential differentiation of classical monocytes into pre-GMiDCs and GMiDCs. Interestingly, mixed bone marrow chimeric mice of Csf2rb+/+ and Csf2rb-/- demonstrate that the generation of GMiDCs necessitates the cis expression of GM-CSF receptor. Besides the spleen, GMiDCs are generated in the CCR7-independent resident DCs of the LNs and in some peripheral tissues with GM-CSF treatment. Also, small but significant numbers of GMiDCs are generated in the spleen and other tissues during chronic allergic inflammation. Collectively, our present study identifies a splenic subset of CD115hiCD301b+ GMiDCs that possess a strong capacity to promote Th2 polarization and allergic sensitization against blood-borne antigen.
Transcriptomic and Histological Analysis of Exacerbated Immune Response in Multidrug-Resistant Pseudomonas aeruginosa in a Murine Model of Endophthalmitis
Authors: Naik Poonam , Pandey Suchita , Naik Milind N. , Mishra Dilip Kumar , Boyenpally Sreedhar Rao , Joseph Joveeta
Published: January 2022

Multidrug-resistant (MDR) endophthalmitis is a serious threat to the whole spectrum of therapeutic procedures associated with the risk of managing and preventing vision loss. We have earlier shown the interplay of immune mediators in patients with MDR Pseudomonas aeruginosa (PA) endophthalmitis leading to worse outcome. Expanding on these findings, a murine model of endophthalmitis was developed to explore the effects of drug resistance on the pathogenesis by analyzing the temporal changes in retinal morphology along with its transcriptomic signatures. Clinical isolates of susceptible (S-PA) and multidrug-resistant PA (MDR-PA) were injected intravitreally in C57BL/6 mice followed by enucleation at 6 and 24 h time points postinfection. Disease progression and retinal changes were monitored by clinical and histological assessment and transcriptome analysis in a pair-wise manner. Histological assessment of MDR-PA eyeball revealed higher disease severity (p < 0.05), CD45+ cells (p = 0.007), MPO+ cells (p = 0.01), GFAP+ (p = 0.02), along with higher retinal cell death in mice infected with MDR-PA (p = 0.008). Temporal transcriptome analysis revealed differential expression of nearly 923 genes at 6 h p.i. and 2,220 genes at 24 h p.i. (FC ≥2, adjusted p-value <0.05). Pathway enrichment analysis identified differential regulation of chemokine- and cytokine-mediated, MAPK, and NF-кβ signaling pathways. In conclusion, rapid deterioration of retinal architecture and immune exacerbation was significantly associated with the MDR endophthalmitis, suggesting the need for immunomodulatory agents to strengthen host cell functions and support antibiotics to save the retinal structure from inevitable deterioration and restoration of the vision.
Grass Carp (Ctenopharyngodon idella) KAT8 Inhibits IFN 1 Response Through Acetylating IRF3/IRF7
Authors: Li Meifeng , Hu Jihuan , Mao Huiling , Li Dongming , Jiang Zeyin , Sun Zhichao , Yu Tingting , Hu Chengyu , Xu Xiaowen
Published: January 2022

Post-translational modifications (PTMs), such as phosphorylation and ubiquitination, etc., have been reported to modulate the activities of IRF3 and IRF7. In this study, we found an acetyltransferase KAT8 in grass carp (CiKAT8, MW286472) that acetylated IRF3/IRF7 and then resulted in inhibition of IFN 1 response. CiKAT8 expression was up-regulated in the cells under poly I:C, B-DNA or Z-DNA stimulation as well as GCRV(strain 873) or SVCV infection. The acetyltransferase domain (MYST domain) of KAT8 promoted the acetylation of IRF3 and IRF7 through the direct interaction with them. So, the domain is essential for KAT8 function. Expectedly, KAT8 without MYST domain (KAT8-△264-487) was granularly aggregated in the nucleus and failed to down-regulate IFN 1 expression. Subcellular localization analysis showed that KAT8 protein was evenly distributed in the nucleus. In addition, we found that KAT8 inhibited the recruitment of IRF3 and IRF7 to ISRE response element. Taken together, our findings revealed that grass carp KAT8 blocked the activities of IRF3 and IRF7 by acetylating them, resulting in a low affinity interaction of ISRE response element with IRF3 and IRF7, and then inhibiting nucleic acids-induced innate immune response.
Co-Expression of miR155 or LSD1 shRNA Increases the Anti-Tumor Functions of CD19 CAR-T Cells
Authors: Zhang Jing , Zhu Jingjing , Zheng Genhui , Wang Qianyu , Li Xiaorui , Feng Yaru , Shang Fengqin , He Siqi , Jiang Qiyao , Shi Bingjie , Wang Dong , Cao Zhiwei , Wang Jianxun
Published: January 2022

Chimeric antigen receptor (CAR) T cells targeting CD19 antigen have produced remarkable clinical outcomes for cancer patients. However, identifying measures to enhance effector function remains one of the most challenging issues in CD19-targeted immunotherapy. Here, we report a novel approach in which a microRNA (miRNA) or short-hairpin RNA (shRNA) cassette was integrated into CAR-expressing retroviral vectors. Using this system, we generated anti-CD19 CAR-T cells co-expressing miR155 or LSD1 shRNA and found that anti-CD19 CAR-T cells with miR155 upregulation or LSD1 downregulation exhibited increased anti-tumor functions in vitro and in vivo. Transcriptional profiling analysis by RNA sequencing revealed the targets of miR155 and LSD1 in anti-CD19 CAR-T cells. Our experiments indicated that introduction of miRNA or shRNA expression into anti-CD19 CAR T-cells might be an effective strategy to improve the anti-tumor effects of CAR-T cell therapy.
Structural Basis of Antibody Conformation and Stability Modulation by Framework Somatic Hypermutation
Authors: Sheng Zizhang , Bimela Jude S. , Katsamba Phinikoula S. , Patel Saurabh D. , Guo Yicheng , Zhao Haiqing , Guo Youzhong , Kwong Peter D. , Shapiro Lawrence
Published: January 2022

Accumulation of somatic hypermutation (SHM) is the primary mechanism to enhance the binding affinity of antibodies to antigens in vivo. However, the structural basis of the effects of many SHMs remains elusive. Here, we integrated atomistic molecular dynamics (MD) simulation and data mining to build a high-throughput structural bioinformatics pipeline to study the effects of individual and combination SHMs on antibody conformation, flexibility, stability, and affinity. By applying this pipeline, we characterized a common mechanism of modulation of heavy-light pairing orientation by frequent SHMs at framework positions 39H, 91H, 38L, and 87L through disruption of a conserved hydrogen-bond network. Q39LH alone and in combination with light chain framework 4 (FWR4L) insertions further modulated the elbow angle between variable and constant domains of many antibodies, resulting in improved binding affinity for a subset of anti-HIV-1 antibodies. Q39LH also alleviated aggregation induced by FWR4L insertion, suggesting remote epistasis between these SHMs. Altogether, this study provides tools and insights for understanding antibody affinity maturation and for engineering functionally improved antibodies.
Year-Round Dive Characteristics of Male Beluga Whales From the Eastern Beaufort Sea Population Indicate Seasonal Shifts in Foraging Strategies
Authors: Storrie Luke , Hussey Nigel E. , MacPhee Shannon A. , O’Corry-Crowe Greg , Iacozza John , Barber David G. , Nunes Alex , Loseto Lisa L.
Published: January 2022

Dive behavior represents multiple ecological functions for marine mammals, but our understanding of dive characteristics is typically limited by the resolution or longevity of tagging studies. Knowledge on the time-depth structures of dives can provide insight into the behaviors represented by vertical movements; furthering our understanding of the ecological importance of habitats occupied, seasonal shifts in activity, and the energetic consequences of targeting prey at a given depth. Given our incomplete understanding of Eastern Beaufort Sea (EBS) beluga whale behavior over an annual cycle, we aimed to characterize dives made by belugas, with a focus on analyzing shifts in foraging strategies. Objectives were to (i) characterize and classify the range of beluga-specific dive types over an annual cycle, (ii) propose dive functions based on optimal foraging theory, physiology, and association with environmental variables, and (iii) identify whether belugas undergo seasonal shifts in the frequency of dives associated with variable foraging strategies. Satellite-linked time-depth-recorders (TDRs) were attached to 13 male belugas from the EBS population in 2018 and 2019, and depth data were collected in time series at a 75 s sampling interval. Tags collected data for between 13 and 357 days, including three tags which collected data across all months. A total of 90,211 dives were identified and characterized by twelve time and depth metrics and classified into eight dive types using a Gaussian mixed modeling and hierarchical clustering analysis approach. Dive structures identify various seasonal behaviors and indicate year-round foraging. Shallower and more frequent diving during winter in the Bering Sea indicate foraging may be energetically cheaper, but less rewarding than deeper diving during summer in the Beaufort Sea and Arctic Archipelago, which frequently exceeded the aerobic dive limit previously calculated for this population. Structure, frequency and association with environmental variables supports the use of other dives in recovery, transiting, and navigating through sea ice. The current study provides the first comprehensive description of the year-round dive structures of any beluga population, providing baseline information to allow improved characterization and to monitor how this population may respond to environmental change and increasing anthropogenic stressors.
Metagenomic Analysis of Bacterial Communities and Antibiotic Resistance Genes in Penaeus monodon Biofloc-Based Aquaculture Environments
Authors: Chen Xieyan , He Zihao , Zhao Jichen , Liao Minze , Xue Yuan , Zhou Jianing , Hoare Rowena , Monaghan Sean J. , Wang Na , Pang Huanying , Sun Chengbo
Published: January 2022

Biofloc technology (BFT) is one of the most promising technologies in global aquaculture for the purpose of improving water quality, waste treatment, and disease prevention in intensive aquaculture systems. However, characterization of the microbial species and antibiotic resistance potentially present in biofloc-based aquaculture environments is needed. In this study, we used high-throughput sequencing technology to comprehensively compare the bacterial communities in mariculture ponds of Penaeus monodon (P. monodon), by testing of water, biofloc, and intestine of P. monodon. Operational taxonomic units (OTUs) cluster analysis showed that the nine samples tested divided into 45 phyla and 457 genera. Proteobacteria was the dominant bacteria in water, biofloc and prawn intestine. In biofloc and intestine, the Ruegeria (2.23–6.31%) genus represented the largest proportion of bacteria, with Marivita (14.01–20.94%) the largest group in water. Microbial functional annotation revealed that in all the samples, genes encoding metabolism were predominant. The antibiotic resistance gene annotation showed the highest absolute abundance of patB, adeF, OXA-243, and Brucella_suis_mprF from Proteobacteria. PatB (11.33–15.01%), adeF (15.79–18.16%), OXA-243 (35.65%), and Brucella_suis_mprF (10.03%) showed the highest absolute abundance of antibiotic resistance genes in water, biofloc, and intestines, respectively. These findings may greatly increase our understanding of the characteristics of the microbiota of shrimp biofloc-based aquaculture systems and the complex interactions among shrimp, ambient microflora, and environmental variables. It provides a reference basis for policy on breeding, environmental safety, and maintaining food safety in the production of P. monodon.
The Rapid Population Collapse of a Key Marine Predator in the Northern Antarctic Peninsula Endangers Genetic Diversity and Resilience to Climate Change
Authors: Krause Douglas J. , Bonin Carolina A. , Goebel Michael E. , Reiss Christian S. , Watters George M.
Published: January 2022

Antarctic fur seals (AFS) are an ecologically important predator and a focal indicator species for ecosystem-based Antarctic fisheries management. This species suffered intensive anthropogenic exploitation until the early 1900s, but recolonized most of its former distribution, including the southern-most colony at Cape Shirreff, South Shetland Islands (SSI). The IUCN describes a single, global AFS population of least concern; however, extensive genetic analyses clearly identify four distinct breeding stocks, including one in the SSI. To update the population status of SSI AFS, we analyzed 20 years of field-based data including population counts, body size and condition, natality, recruitment, foraging behaviors, return rates, and pup mortality at the largest SSI colony. Our findings show a precipitous decline in AFS abundance (86% decrease since 2007), likely driven by leopard seal predation (increasing since 2001, p << 0.001) and potentially worsening summer foraging conditions. We estimated that leopard seals consumed an average of 69.3% (range: 50.3–80.9%) of all AFS pups born each year since 2010. AFS foraging-trip durations, an index of their foraging habitat quality, were consistent with decreasing krill and fish availability. Significant improvement in the age-specific over-winter body condition of AFS indicates that observed population declines are driven by processes local to the northern Antarctic Peninsula. The loss of SSI AFS would substantially reduce the genetic diversity of the species, and decrease its resilience to climate change. There is an urgent need to reevaluate the conservation status of Antarctic fur seals, particularly for the rapidly declining SSI population.
Impact of Thermal Boundary Resistance on Thermoelectric Effects of the Blade-Type Phase-Change Random Access Memory Device
Authors: Lian Xiaojuan , Fu Jinke , Gao Zhixuan , Ren Wang , Wan Xiang , Ren Qingying , Wen Jing , Yang Cihui , Liu Xiaoyan , Wang Lei
Published: January 2022

Phase-change random access memory (PCRAM) is widely regarded as one of the most promising candidates to replace Flash memory as the next generation of non-volatile memories due to its high-speed and low-power consumption characteristics. Recent advent of the blade-type PCRAM with low programming current merit further confirms its prospects. The thermoelectric effects existing inside the PCRAM devices have always been an important factor that determines the phase-transformation kinetics due to a fact that it allows PCRAM to have electric polarity dependent characteristics. However, the potential physics governing the thermoelectric effects for blade-type PCRAM device still remains vague. We establish a three-dimensional (3D) electro-thermal and phase-transformation model to study the influences of thermal boundary resistance (TBR) and device scaling on the thermoelectric effects of the blade-type PCRAM during its “RESET” operation. Our research shows that the presence of TBR significantly improves the electric polarity-dependent characteristics of the blade-type PCRAM, and such polarity-dependent characteristic is found immune to the scaling of the device. It is therefore possible to optimize the thermoelectric effects of the blade-type PCRAM through appropriately tailoring the TBR parameters, thus further lowering resulting power consumption.
Effect of Carbon Content on the Processability of Fe-C Alloys Produced by Laser Based Powder Bed Fusion
Authors: Hearn William , Hryha Eduard
Published: January 2022

The present study examines the processability of Fe-C alloys, with carbon contents up to 1.1 wt%, when using laser based powder bed fusion (LB-PBF). Analysis of specimen cross-sections revealed that lack of fusion porosity was prominent in specimens produced at low volumetric energy density (VED), while keyhole porosity was prominent in specimens produced at high VED. The formation of porosity was also influenced by the carbon content, where increasing the carbon content reduced lack of fusion porosity, while simultaneously increasing the susceptibility to form keyhole porosity. These trends were related to an improved wettability, viscosity, and flow of the melt pool as well an increased melt pool depth as the carbon content increased. Cold cracking defects were also observed in Fe-C alloys that had an as-built hardness ≥425 HV. Reducing the carbon content below 0.75 wt% and increasing the VED, which improved the intrinsic heat treatment during LB-PBF, were found to be effective mitigation strategies to avoid cold cracking defects. Based upon these results, a process window for the Fe-C system was established that produces high density (>99.8%), defect-free specimens via LB-PBF without the requirement of build plate preheating.
Acoustic Slow-Wave Effect Metamaterial Muffler for Noise Control of HVDC Converter Station
Authors: Yang Dingge , Jiang Quanyuan , Wu Jingfeng , Han Yanhua , Ding Bin , Niu Bo , Xie Guolin
Published: January 2022

Aiming at the noise control of the HVDC converter station, a one-dimensional two-port metamaterial muffler based on the acoustic slow-wave effect is designed and manufactured. The metamaterial muffler achieves a broadband quasi-perfect absorption of noise from 600 to 900 Hz while ensuring a certain ventilation capacity. In addition, the internal equivalent sound velocity curve and the sound pressure and velocity field of the muffler are used to reveal the mechanism of its broadband quasi-perfect sound absorption. The performance of the muffler was verified by theoretical, numerical, and experimental models. The work in this paper is of guiding significance for solving the noise problem in HVDC converter stations.
Novel Immune-Related Genetic Expression for Primary Sjögren's Syndrome
Authors: Cui Jiajia , Li Hui , Wang Tianling , Shen Qin , Yang Yuanhao , Yu Xiujuan , Hu Huaixia
Published: January 2022

Objective: To identify novel immune-related genes expressed in primary Sjögren's syndrome (pSS).

Methods: Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were screened. The differences in immune cell proportion between normal and diseased tissues were compared, weighted gene co-expression network analysis was conducted to identify key modules, followed by a protein–protein interaction (PPI) network generation and enrichment analysis. The feature genes were screened and verified using the GEO datasets and quantitative real-time PCR (RT-qPCR).

Results: A total of 345 DEGs were identified, and the proportions of gamma delta T cells, memory B cells, regulatory T cells (Tregs), and activated dendritic cells differed significantly between the control and pSS groups. The turquoise module indicated the highest correlation with pSS, and 252 key genes were identified. The PPI network of key genes showed that RPL9, RBX1, and RPL31 had a relatively higher degree. In addition, the key genes were mainly enriched in coronavirus disease-COVID-2019, hepatitis C, and influenza A. Fourteen feature genes were obtained using the support vector machine model, and two subtypes were identified. The genes in the two subtypes were mainly enriched in the JAK-STAT, p53, and toll-like receptor signaling pathways. The majority of the feature genes were upregulated in the pSS group, verified using the GEO datasets and RT-qPCR analysis.

Conclusions: Memory B cells, gamma delta T cells, Tregs, activated dendritic cells, RPL9, RBX1, RPL31, and the feature genes possible play vital roles in the development of pSS.
Automatic Segmentation of Novel Coronavirus Pneumonia Lesions in CT Images Utilizing Deep-Supervised Ensemble Learning Network
Authors: Peng Yuanyuan , Zhang Zixu , Tu Hongbin , Li Xiong
Published: January 2022

Background: The novel coronavirus disease 2019 (COVID-19) has been spread widely in the world, causing a huge threat to the living environment of people.

Objective: Under CT imaging, the structure features of COVID-19 lesions are complicated and varied greatly in different cases. To accurately locate COVID-19 lesions and assist doctors to make the best diagnosis and treatment plan, a deep-supervised ensemble learning network is presented for COVID-19 lesion segmentation in CT images.

Methods: Since a large number of COVID-19 CT images and the corresponding lesion annotations are difficult to obtain, a transfer learning strategy is employed to make up for the shortcoming and alleviate the overfitting problem. Based on the reality that traditional single deep learning framework is difficult to extract complicated and varied COVID-19 lesion features effectively that may cause some lesions to be undetected. To overcome the problem, a deep-supervised ensemble learning network is presented to combine with local and global features for COVID-19 lesion segmentation.

Results: The performance of the proposed method was validated in experiments with a publicly available dataset. Compared with manual annotations, the proposed method acquired a high intersection over union (IoU) of 0.7279 and a low Hausdorff distance (H) of 92.4604.

Conclusion: A deep-supervised ensemble learning network was presented for coronavirus pneumonia lesion segmentation in CT images. The effectiveness of the proposed method was verified by visual inspection and quantitative evaluation. Experimental results indicated that the proposed method has a good performance in COVID-19 lesion segmentation.
A Bibliometric Analysis of Endoscopic Sedation Research: 2001–2020
Authors: Qin Yi , Chen Sifan , Zhang Yuanyuan , Liu Wanfeng , Lin Yuxuan , Chi Xiaoying , Chen Xuemei , Yu Zhangjie , Su Diansan
Published: January 2022

Background and Aims: To evaluate endoscopic sedation research and predict research hot spots both quantitatively and qualitatively using bibliometric analysis.

Methods: We extracted relevant publications from the Web of Science Core Collection (WoSCC) on 13 December 2020. We examined the retrieved data by bibliometric analysis (e.g., co-cited and cluster analysis, keyword co-occurrence) using the software CiteSpace and VOSviewer and the website of bibliometrics, the Online Analysis Platform of Literature Metrology (http://bibliometric.com/), to analyse and predict the trends and hot spots in this field.

Main Results: We identified 2,879 articles and reviews on endoscopic sedation published between 2001 and 2020. Although the overall trend is increasing, with slight fluctuation in some years, there were significant increases in 2007 and 2012. In respect of the contributions on endoscopic sedation research, the United States (US) had the greatest number of publications, and it was followed by Japan and China. In addition, collaboration network analysis revealed that the most frequent collaboration was between the US and China. Six of the top ten most prolific research institutions were located in the US. The most publications on endoscopic sedation research in the past two decades were found primarily in journals on gastroenterology and hepatology. Keyword co-occurrence and co-citation cluster analysis revealed the most popular terms relating to endoscopic sedation in the manner of cluster labels; these included patient anxiety, tolerance, ketamine, propofol, hypoxia, nursing shortage, endoscopic ultrasonography, colorectal cancer, carbon dioxide insufflation, and water exchange (WE). Keyword burst detection suggested that propofol sedation, adverse event, adenoma detection rate (ADR), hypoxemia, and obesity were newly-emergent research hot spots.

Conclusions: Our findings showed that hypoxia, adverse event, and ADR, along with conscious sedation and propofol sedation, have been foci of endoscopic sedation research over the past 20 years. The research focus has shifted from sedative drugs to sedative complications and endoscopy quality control, which means that there will be higher requirements and standards for sedative quality and endoscopy quality in the future.
Heterotrophic Bacterioplankton Growth and Physiological Properties in Red Sea Tropical Shallow Ecosystems With Different Dissolved Organic Matter Sources
Authors: Silva Luis , Calleja Maria Ll. , Huete-Stauffer Tamara M. , Ivetic Snjezana , Ansari Mohd I. , Viegas Miguel , Morán Xosé Anxelu G.
Published: January 2022

Despite the key role of heterotrophic bacterioplankton in the biogeochemistry of tropical coastal waters, their dynamics have been poorly investigated in relation to the different dissolved organic matter (DOM) pools usually available. In this study we conducted four seasonal incubations of unfiltered and predator-free seawater (Community and Filtered treatment, respectively) at three Red Sea coastal sites characterized by different dominant DOM sources: Seagrass, Mangrove, and Phytoplankton. Bacterial abundance, growth and physiological status were assessed by flow cytometry and community composition by 16S rRNA gene amplicons. The Seagrass site showed the highest initial abundances (6.93 ± 0.30 × 105 cells mL–1), coincident with maximum DOC concentrations (>100 μmol C L–1), while growth rates peaked at the Mangrove site (1.11 ± 0.09 d–1) and were consistently higher in the Filtered treatment. The ratio between the Filtered and Community maximum bacterial abundance (a proxy for top-down control by protistan grazers) showed minimum values at the Seagrass site (1.05 ± 0.05) and maximum at the Phytoplankton site (1.24 ± 0.30), suggesting protistan grazing was higher in open waters, especially in the first half of the year. Since the Mangrove and Seagrass sites shared a similar bacterial diversity, the unexpected lack of bacterial response to predators removal at the latter site should be explained by differences in DOM characteristics. Nitrogen-rich DOM and fluorescent protein-like components were significantly associated with enhanced specific growth rates along the inshore-offshore gradient. Our study confirms the hypotheses that top–down factors control bacterial standing stocks while specific growth rates are bottom-up controlled in representative Red Sea shallow, oligotrophic ecosystems.
Virus-Like Particles: Revolutionary Platforms for Developing Vaccines Against Emerging Infectious Diseases
Authors: Tariq Hasnat , Batool Sannia , Asif Saaim , Ali Mohammad , Abbasi Bilal Haider
Published: January 2022

Virus-like particles (VLPs) are nanostructures that possess diverse applications in therapeutics, immunization, and diagnostics. With the recent advancements in biomedical engineering technologies, commercially available VLP-based vaccines are being extensively used to combat infectious diseases, whereas many more are in different stages of development in clinical studies. Because of their desired characteristics in terms of efficacy, safety, and diversity, VLP-based approaches might become more recurrent in the years to come. However, some production and fabrication challenges must be addressed before VLP-based approaches can be widely used in therapeutics. This review offers insight into the recent VLP-based vaccines development, with an emphasis on their characteristics, expression systems, and potential applicability as ideal candidates to combat emerging virulent pathogens. Finally, the potential of VLP-based vaccine as viable and efficient immunizing agents to induce immunity against virulent infectious agents, including, SARS-CoV-2 and protein nanoparticle-based vaccines has been elaborated. Thus, VLP vaccines may serve as an effective alternative to conventional vaccine strategies in combating emerging infectious diseases.
The Pyroptosis-Related Gene Signature Predicts the Prognosis of Hepatocellular Carcinoma
Authors: Zhang Shuqiao , Li Xinyu , Zhang Xiang , Zhang Shijun , Tang Chunzhi , Kuang Weihong
Published: January 2022

Objective: Hepatocellular carcinoma (HCC) is a genetically and phenotypically heterogeneous tumor, and the prediction of its prognosis remains a challenge. In the past decade, studies elucidating the mechanisms that induce tumor cell pyroptosis has rapidly increased. The elucidation of their mechanisms is essential for the clinical development optimal application of anti-hepatocellular carcinoma therapeutics.

Methods: Based on the different expression profiles of pyroptosis-related genes in HCC, we constructed a LASSO Cox regression pyroptosis-related genes signature that could more accurately predict the prognosis of HCC patients.

Results: We identified seven pyroptosis-related genes signature (BAK1, CHMP4B, GSDMC, NLRP6, NOD2, PLCG1, SCAF11) in predicting the prognosis of HCC patients. Kaplan Meier survival analysis showed that the pyroptosis-related high-risk gene signature was associated with poor prognosis HCC patients. Moreover, the pyroptosis-related genes signature performed well in the survival analysis and ICGC validation group. The hybrid nomogram and calibration curve further demonstrated their feasibility and accuracy for predicting the prognosis of HCC patients. Meanwhile, the evaluation revealed that our novel signature predicted the prognosis of HCC patients more accurately than traditional clinicopathological features. GSEA analysis further revealed the novel signature associated mechanisms of immunity response in high-risk groups. Moreover, analysis of immune cell subsets with relevant functions revealed significant differences in aDCs, APC co-stimulation, CCR, check-point, iDCs, Macrophages, MHC class-I, Treg, and type II INF response between high- and low-risk groups. Finally, the expression of Immune checkpoints was enhanced in high-risk group, and m6A-related modifications were expressed differently between low- and high-risk groups.

Conclusion: The novel pyroptosis-related genes signature can predict the prognosis of patients with HCC and insight into new cell death targeted therapies.
The Biosynthesis and Metabolism of the N-Acylated Aromatic Amino Acids: N-Acylphenylalanine, N-Acyltyrosine, N-Acyltryptophan, and N-Acylhistidine
Authors: Bhandari Suzeeta , Bisht Kirpal S. , Merkler David J.
Published: January 2022

The fatty acid amides are a family of lipids composed of two chemical moieties, a fatty acid and a biogenic amine linked together in an amide bond. This lipid family is structurally related to the endocannabinoid anandamide (N-arachidonoylethanolamine) and, thus, is frequently referred to as a family of endocannabinoid-related lipids. The fatty acid amide family is divided into different classes based on the conjugate amine; anandamide being a member of the N-acylethanolamine class (NAE). Another class within the fatty acid amide family is the N-acyl amino acids (NA-AAs). The focus of this review is a sub-class of the NA-AAs, the N-acyl aromatic amino acids (NA-ArAAs). The NA-ArAAs are not broadly recognized, even by those interested in the endocannabinoids and endocannabinoid-related lipids. Herein, the NA-ArAAs that have been identified from a biological source will be highlighted and pathways for their biosynthesis, degradation, enzymatic modification, and transport will be presented. Also, information about the cellular functions of the NA-ArAAs will be placed in context with the data regarding the identification and metabolism of these N-acylated amino acids. A review of the current state-of-knowledge about the NA-ArAAs is to stimulate future research about this underappreciated sub-class of the fatty acid amide family.
The Oral Complications of COVID-19
Authors: Zhou Xinxuan , Dong Jiajia , Guo Qiang , Li Mingyun , Li Yan , Cheng Lei , Ren Biao
Published: January 2022

Background: COVID-19 is a novel coronavirus infectious disease associated with the severe acute respiratory syndrome. More and more patients are being cured due to the development of clinical guidelines for COVID-19 pneumonia diagnosis, treatment, and vaccines. However, the long-term impact of COVID-19 on patients after recovery is unclear. Currently available reports have shown that patients recovered from COVID-19 continue to experience health problems in respiratory and other organ systems. Oral problem is one of the important complications which has serious impacts on the rehabilitation and future quality of life, such as ageusia and macroglossia, but the oral complication is often being neglected.

Aim of Review: From the perspective of stomatology, we summarized and elaborated in detail the types, pathogenesis of oral complications from COVID-19 patients after rehabilitation, and the reported prevention or treatment recommendations which may improve the COVID-19 patients associated oral diseases.

Key Scientific Concepts of Review: 1) To understand the common oral complications and the mechanisms of the development of oral complications after the COVID-19 recovery; 2) To summary the practical strategies to prevent the oral complications and construct the rehabilitation plans for patients with oral complications.
Longitudinal Prediction of Freezing of Gait in Parkinson's Disease: A Prospective Cohort Study
Authors: Zhao Jiahao , Wan Ying , Song Lu , Wu Na , Zhang Zien , Liu Zhenguo , Gan Jing
Published: January 2022

Objective: Freezing of gait (FOG) is a disabling complication in Parkinson's disease (PD). Yet, studies on a validated model for the onset of FOG based on longitudinal observation are absent. This study aims to develop a risk prediction model to predict the probability of future onset of FOG from a multicenter cohort of Chinese patients with PD.

Methods: A total of 350 patients with PD without FOG were prospectively monitored for ~2 years. Demographic and clinical data were investigated. The multivariable logistic regression analysis was conducted to develop a risk prediction model for FOG.

Results: Overall, FOG was observed in 132 patients (37.70%) during the study period. At baseline, longer disease duration [odds ratio (OR) = 1.214, p = 0.008], higher total levodopa equivalent daily dose (LEDD) (OR = 1.440, p < 0.001), and higher severity of depressive symptoms (OR = 1.907, p = 0.028) were the strongest predictors of future onset of FOG in the final multivariable model. The model performed well in the development dataset (with a C-statistic = 0.820, 95% CI: 0.771–0.865), showed acceptable discrimination and calibration in internal validation, and remained stable in 5-fold cross-validation.

Conclusion: A new prediction model that quantifies the risk of future onset of FOG has been developed. It is based on clinical variables that are readily available in clinical practice and could serve as a small tool for risk counseling.
Brenda Milner: Pioneer of the Study of the Human Frontal Lobes
Authors: Kolb Bryan
Published: January 2022

Although the behavioral effects of damage to the frontal lobes date back to at least the late 19th century even midway through the 20th century very little was known about human frontal lobe function and there was a general consensus that the frontal lobe did not play a key role in cognition. This all changed when Brenda Milner published a chapter in a 1964 volume entitled: The Frontal Granular Cortex and Behavior. Milner’s chapter, “Some effects of frontal lobectomy in man,” was the first systematic study of the effect of frontal lobe excisions on cognition in human patients. Milner had access to a unique population of frontal excision patients at the Montreal Neurological Institute that were being treated by Wilder Penfield and his associates for a wide range of neurological disorders, including intractable epilepsy. Milner and her colleagues engaged in a more than 50-year study that has had a formidable impact on our understanding of frontal lobe function. Paralleling studies of frontal lobe function in non-humans they influence on understanding the evolution and function of the prefrontal cortex of mammals. Thus, although Brenda Milner is best known for her studies of human memory, she has had an equally important contribution to our understanding of the frontal lobes.
Toward a Multimodal Computer-Aided Diagnostic Tool for Alzheimer’s Disease Conversion
Authors: Pena Danilo , Suescun Jessika , Schiess Mya , Ellmore Timothy M. , Giancardo Luca ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2022

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. It is one of the leading sources of morbidity and mortality in the aging population AD cardinal symptoms include memory and executive function impairment that profoundly alters a patient’s ability to perform activities of daily living. People with mild cognitive impairment (MCI) exhibit many of the early clinical symptoms of patients with AD and have a high chance of converting to AD in their lifetime. Diagnostic criteria rely on clinical assessment and brain magnetic resonance imaging (MRI). Many groups are working to help automate this process to improve the clinical workflow. Current computational approaches are focused on predicting whether or not a subject with MCI will convert to AD in the future. To our knowledge, limited attention has been given to the development of automated computer-assisted diagnosis (CAD) systems able to provide an AD conversion diagnosis in MCI patient cohorts followed longitudinally. This is important as these CAD systems could be used by primary care providers to monitor patients with MCI. The method outlined in this paper addresses this gap and presents a computationally efficient pre-processing and prediction pipeline, and is designed for recognizing patterns associated with AD conversion. We propose a new approach that leverages longitudinal data that can be easily acquired in a clinical setting (e.g., T1-weighted magnetic resonance images, cognitive tests, and demographic information) to identify the AD conversion point in MCI subjects with AUC = 84.7. In contrast, cognitive tests and demographics alone achieved AUC = 80.6, a statistically significant difference (n = 669, p < 0.05). We designed a convolutional neural network that is computationally efficient and requires only linear registration between imaging time points. The model architecture combines Attention and Inception architectures while utilizing both cross-sectional and longitudinal imaging and clinical information. Additionally, the top brain regions and clinical features that drove the model’s decision were investigated. These included the thalamus, caudate, planum temporale, and the Rey Auditory Verbal Learning Test. We believe our method could be easily translated into the healthcare setting as an objective AD diagnostic tool for patients with MCI.
High Gamma and Beta Temporal Interference Stimulation in the Human Motor Cortex Improves Motor Functions
Authors: Ma Ru , Xia Xinzhao , Zhang Wei , Lu Zhuo , Wu Qianying , Cui Jiangtian , Song Hongwen , Fan Chuan , Chen Xueli , Zha Rujing , Wei Junjie , Ji Gong-Jun , Wang Xiaoxiao , Qiu Bensheng , Zhang Xiaochu
Published: January 2022

Background: Temporal interference (TI) stimulation is a new technique of non-invasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidated.

Objective: To assess the effectiveness of the envelope-modulated waveform of TI stimulation on the human primary motor cortex (M1).

Methods: Participants attended three sessions of 30-min TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation.

Results: In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential.

Conclusion: These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and paving the way for further explorations.
Early-Life Nutrition Interventions Improved Growth Performance and Intestinal Health via the Gut Microbiota in Piglets
Authors: Luo Chengzeng , Xia Bing , Zhong Ruqing , Shen Dan , Li Jiaheng , Chen Liang , Zhang Hongfu
Published: January 2022

Intestinal infections in piglets are the main causes of morbidity before and after weaning. Studies have not explored approaches for combining pre-weaning and post-weaning nutritional strategies to sustain optimal gut health. The current study thus sought to explore the effects of early-life nutrition interventions through administration of synthetic milk on growth performance and gut health in piglets from 3 to 30 days of age. Twelve sows were randomly allocated to control group (CON) and early-life nutrition interventions group (ENI). Piglets were fed with the same creep diet from 7 days of age ad libitum. Piglets in the ENI group were provided with additional synthetic milk from Day 3 to Day 30. The results showed that early-life nutrition interventions improved growth performance, liver weight, spleen weight, and reduced diarrhea rate of piglets after weaning (P < 0.05). Early-life nutrition interventions significantly upregulated expression of ZO-1, Occludin, Claudin4, GALNT1, B3GNT6, and MUC2 in colonic mucosa at mRNA level (P < 0.05). Early-life nutrition interventions reduced activity of alkaline phosphatase (AKP) in serum and the content of lipopolysaccharides (LPS) in plasma (P < 0.05). The number of goblet cells and crypt depth of colon of piglets was significantly higher in piglets in the ENI group relative to that of piglets in the CON group (P < 0.05). The relative mRNA expression levels of MCP-1, TNF-α, IL-1β, and IL-8, and the protein expression levels of TNF-α, IL-6, and IL-8 in colonic mucosa of piglets in the ENI group were lower compared with those of piglets in the CON group (P < 0.05). Relative abundance of Lactobacillus in colonic chyme and mucosa of piglets in the ENI group was significantly higher relative to that of piglets in the CON group (P < 0.05). Correlation analysis indicated that abundance of Lactobacillus was positively correlated with the relative mRNA expression levels of ZO-1, Claudin4, and GALNT1, and it was negatively correlated with the level of MCP-1 in colonic chyme and mucosa. In summary, the findings of this study showed that early-life nutrition interventions improved growth performance, colonic barrier, and reduced inflammation in the colon by modulating composition of gut microbiota in piglets. Early-life nutrition intervention through supplemental synthetic milk is a feasible measure to improve the health and reduce the number of deaths of piglets.
Establishment and Characterization of Stable Zein/Glycosylated Lactoferrin Nanoparticles to Enhance the Storage Stability and in vitro Bioaccessibility of 7,8-Dihydroxyflavone
Authors: Chen Yufeng , Gao Xiaojing , Liu Shucheng , Cai Qiuxing , Wu Lijun , Sun Yi , Xia Guobin , Wang Yueqi
Published: January 2022

In this work, the lactoferrin (LF) was glycosylated by dextran (molecular weight 10, 40, and 70 kDa, LF 10K, LF 40K, and LF 70K) via Maillard reaction as a stabilizer to establish zein/glycosylated LF nanoparticles and encapsulate 7,8-dihydroxyflavone (7,8-DHF). Three zein/glycosylated LF nanoparticles (79.27–87.24 nm) with low turbidity (<0.220) and polydispersity index (PDI) (<0.230) were successfully established by hydrophobic interactions and hydrogen bonding. Compared with zein/LF nanoparticles, zein/glycosylated LF nanoparticles further increased stability to ionic strength (0–500 mM NaCl) at low pH conditions. Zein/glycosylated LF nanoparticles had nanoscale spherical shape and glycosylated LF changed surface morphology of zein nanoparticles. Besides, encapsulated 7,8-DHF exhibited an amorphous state inside zein/glycosylated LF nanoparticles. Most importantly, zein/glycosylated LF nanoparticles had good water redispersibility, high encapsulation efficiency (above 98.50%), favorable storage stability, and bioaccessibility for 7,8-DHF, particularly LF 40K. Collectively, the above research provides a theoretical reference for the application of zein-based delivery systems.
Comprehensive Analysis of Prognostic Microenvironment-Related Genes in Invasive Breast Cancer
Authors: Shi Yingrong , Chen Si , Xing Huijuan , Jiang Guanglie , Wu Nan , Liu Qiannan , Sakamoto Norihiro , Kuno Takayoshi , Sugiura Reiko , Xiao Qinghuan , Jin Feng , Fang Yue , Yao Fan
Published: January 2022

Recent studies reveal that tumor microenvironment contributes to breast cancer (BRCA) development, progression, and therapeutic response. However, the contribution of the tumor microenvironment-related genes in routine diagnostic testing or therapeutic decision making for BRCA remains elusive. Immune/stromal/ESTIMATE scores calculated by the ESTIMATE algorithm quantify immune and stromal components in a tumor, and thus can reflect tumor microenvironment. To investigate the association of the tumor microenvironment-related genes with invasive BRCA prognosis, here we analyzed the immune/stromal/ESTIMATE scores in combination with The Cancer Genome Atlas (TCGA) database in invasive BRCA. We found that immune/stromal/ESTIMATE scores were significantly correlated with the invasive BRCA clinicopathological factors. Based on the immune/stromal/ESTIMATE scores, we extracted a series of differential expression genes (DEGs) related to the tumor microenvironment. Survival analysis was further performed to identify a list of high-frequency DEGs (HF-DEGs), which exhibited prognostic value in invasive BRCA. Importantly, consistent with the results of bioinformatics analysis, immunohistochemistry results showed that high SASH3 expression was associated with a good prognosis in invasive BRCA patients. Our findings suggest that the tumor microenvironment-related HF-DEGs identified in this study have prognostic values and may serve as potential biomarkers and therapeutic targets for invasive BRCA.