bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism-based target therapy in primary biliary cholangitis: opportunities before liver cirrhosis?
Authors: Yang Yushu , He XiaoSong , Rojas Manuel , Leung Patrick S. C. , Gao Lixia
Published: May 2023

Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by cholestasis, biliary injuries, liver fibrosis, and chronic non-suppurative cholangitis. The pathogenesis of PBC is multifactorial and involves immune dysregulation, abnormal bile metabolism, and progressive fibrosis, ultimately leading to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are currently used as first- and second-line treatments, respectively. However, many patients do not respond adequately to UDCA, and the long-term effects of these drugs are limited. Recent research has advanced our understanding the mechanisms of pathogenesis in PBC and greatly facilitated development of novel drugs to target mechanistic checkpoints. Animal studies and clinical trials of pipeline drugs have yielded promising results in slowing disease progression. Targeting immune mediated pathogenesis and anti-inflammatory therapies are focused on the early stage, while anti-cholestatic and anti-fibrotic therapies are emphasized in the late stage of disease, which is characterized by fibrosis and cirrhosis development. Nonetheless, it is worth noting that currently, there exists a dearth of therapeutic options that can effectively impede the progression of the disease to its terminal stages. Hence, there is an urgent need for further research aimed at investigating the underlying pathophysiology mechanisms with potential therapeutic effects. This review highlights our current knowledge of the underlying immunological and cellular mechanisms of pathogenesis in PBC. Further, we also address current mechanism-based target therapies for PBC and potential therapeutic strategies to improve the efficacy of existing treatments.
Case Report: An unclassified T cell lymphoma subtype with co-expression of TCR αβ and γ chains revealed by single cell sequencing
Authors: Song Wei , Wang Gang , Wang Cheng , Liu Lulu , Zhang Liming , Zhang Ruoyu , Zhang Haixi , Shi Keqian
Published: May 2023

Background

T cell lymphomas (TCL) are a group of heterogeneous diseases with over 40 subtypes. In this study, we identified a novel TCL subtype which was featured by a unique T cell receptor (TCR) presentation, α, β and γ chains were co-existing in a single malignant T cell.

Case presentation

A 45-year-old male patient was diagnosed T cell lymphoma after 2-month of abdominal distension and liver enlargement. Combining histology review, PET-CT scanning and immunophenotyes, the patient was not classified to any existing TCL subtypes. To better understand this unclassified TCL case, we performed single cell RNA sequencing paired with TCR sequencing on the patient’s PBMC and bone marrow samples. To our surprise, we identified that the malignant T cells had a very rare TCR combination, by expressing two α chains, one β chain and one γ chain simultaneously. We further studied the molecular pathogenesis and tumor cell heterogeneity of this rare TCL subtype. A set of potential therapeutic targets were identified from the transcriptome data, such as CCL5, KLRG1 and CD38.

Conclusions

We identified the first TCL case co-expressing α, β and γ chains and dissected its molecular pathogenesis, providing valuable information for precision medicine options for this novel TCL subtype.
The impact of epigenetic modifications on allogeneic hematopoietic stem cell transplantation
Authors: Ktena Yiouli P. , Dionysiou Margarita , Gondek Lukasz P. , Cooke Kenneth R.
Published: May 2023

The field of epigenetics studies the complex processes that regulate gene expression without altering the DNA sequence itself. It is well established that epigenetic modifications are crucial to cellular homeostasis and differentiation and play a vital role in hematopoiesis and immunity. Epigenetic marks can be mitotically and/or meiotically heritable upon cell division, forming the basis of cellular memory, and have the potential to be reversed between cellular fate transitions. Hence, over the past decade, there has been increasing interest in the role that epigenetic modifications may have on the outcomes of allogeneic hematopoietic transplantation and growing enthusiasm in the therapeutic potential these pathways may hold. In this brief review, we provide a basic overview of the types of epigenetic modifications and their biological functions, summarizing the current literature with a focus on hematopoiesis and immunity specifically in the context of allogeneic hematopoietic stem cell transplantation.
Case Report: Prurigo nodularis-like linear IgA/IgG bullous dermatosis: a case report and literature review
Authors: Zhou Yuxi , Zhou Xingli , Feng Xun , Xia Dengmei , Qian Hua , Liu Hongjie , Li Xiaoguang , Li Wei
Published: May 2023

Linear IgA/IgG bullous dermatosis (LAGBD) is a rare autoimmune subepidermal bullous disorder characterized by linear deposition of concurrent IgA and IgG autoantibodies along the basement membrane zone (BMZ). The clinical features of LAGBD can be diverse, including tense blisters, erosions, erythema, crusting and mucosa involvement, while papules or nodules are generally absent. In this study, we present a unique case of LAGBD, which showed prurigo nodularis-like clinical appearance on physical examination, linear deposition of IgG and C3 along the basement membrane zone (BMZ) in direct immunofluorescence (DIF), IgA autoantibodies against the 97-kDa and 120-kDa of BP180 and IgG autoantibodies against the 97-kDa of BP180 by immunoblotting (IB), while BP180 NC16a domain, BP230, and laminin 332 were negative by enzyme-linked immunosorbent assay (ELISA). After administration of minocycline, the skin lesions improved. We performed a literature review of LAGBD cases with heterogeneous autoantibodies and found clinical presentations of most cases resemble bullous pemphigoid (BP) and linear IgA bullous disease (LABD), which is consistent with previous reported findings. We aim to increase our understanding of this disorder and to enhance the importance of applying immunoblot analyses and other serological detection tools in clinic for precise diagnosis as well as accurate treatment strategy of various autoimmune bullous dermatoses.
Vital roles of m5C RNA modification in cancer and immune cell biology
Authors: Gu Xinyu , Ma Xiao , Chen Chao , Guan Jun , Wang Jing , Wu Shanshan , Zhu Haihong
Published: May 2023

RNA modification plays an important role in epigenetics at the posttranscriptional level, and 5-methylcytosine (m5C) has attracted increasing attention in recent years due to the improvement in RNA m5C site detection methods. By influencing transcription, transportation and translation, m5C modification of mRNA, tRNA, rRNA, lncRNA and other RNAs has been proven to affect gene expression and metabolism and is associated with a wide range of diseases, including malignant cancers. RNA m5C modifications also substantially impact the tumor microenvironment (TME) by targeting different groups of immune cells, including B cells, T cells, macrophages, granulocytes, NK cells, dendritic cells and mast cells. Alterations in immune cell expression, infiltration and activation are highly linked to tumor malignancy and patient prognosis. This review provides a novel and holistic examination of m5C-mediated cancer development by examining the exact mechanisms underlying the oncogenicity of m5C RNA modification and summarizing the biological effects of m5C RNA modification on tumor cells as well as immune cells. Understanding methylation-related tumorigenesis can provide useful insights for the diagnosis as well as the treatment of cancer.
Different flavours of oxygen help quantify seasonal variations of the biological carbon pump in the Celtic Sea
Authors: Seguro Isabel , Marca Alina D. , Shutler Jamie D. , Kaiser Jan
Published: May 2023

Shelf seas represent only 10% of the World’s Ocean by area but support up to 30% of its primary production. There are few measurements of biological production at high spatial and temporal resolution in these physically and biologically dynamic systems. Here, we use dissolved oxygen to-argon (O2/Ar) ratios and oxygen triple isotopes in O2 (16O, 17O, 18O) to estimate net community production, N(O2/Ar), and gross O2 production, G(17O), in summer and autumn 2014 and spring and summer 2015 in the Celtic Sea, as part of the UK Shelf-Sea Biogeochemistry Programme. Surface O2/Ar concentration ratios were measured continuously using a shipboard membrane inlet mass spectrometer. Additional depth profiles of O2/Ar concentration ratios, δ(17O) and δ(18O) were measured in discrete water samples from hydrocasts. The data were combined with wind-speed based gas exchange parameterisations to calculate biological air-sea oxygen fluxes. These fluxes were corrected for diapycnal diffusion, entrainment, production below the mixed layer, and changes over time to derive N(O2/Ar) and G(17O). The Celtic Sea showed the highest G(17O) in summer 2014 (825 mmol m–2 d–1) and lowest during autumn 2014 (153 mmol m–2 d–1). N(O2/Ar) was highest in spring 2015 (43 mmol m–2 d–1), followed by summer 2014 (42 mmol m–2 d–1), with a minimum in autumn 2014 (–24 mmol m–2 d–1). Dividing the survey region into three hydrographically distinct areas (Celtic Deep, Central Celtic Sea and Shelf Edge), we found that Celtic Deep and Shelf Edge had higher N(O2/Ar) in summer (71 and 63 mmol m–2 d–1, respectively) than in spring (49 and 22 mmol m–2 d–1). This study shows regional differences in the metabolic balance within the same season, as well as higher net community production in summer than in spring in some areas and years. The seasonal patterns in biological production rates and the export efficiency (f-ratio) identified the importance of biology for supporting the Celtic Sea’s ability to act as a net CO2 sink. Our measurements thus help improve our understanding of the biological carbon pump in temperate shelf seas.
From shallow sea to deep sea: research progress in underwater image restoration
Authors: Song Wei , Liu Yaling , Huang Dongmei , Zhang Bing , Shen Zhihao , Xu Huifang
Published: May 2023

Underwater images play a crucial role in various fields, including oceanographic engineering, marine exploitation, and marine environmental protection. However, the quality of underwater images is often severely degraded due to the complexities of the underwater environment and equipment limitations. This degradation hinders advancements in relevant research. Consequently, underwater image restoration has gained significant attention as a research area. With the growing interest in deep-sea exploration, deep-sea image restoration has emerged as a new focus, presenting unique challenges. This paper aims to conduct a systematic review of underwater image restoration technology, bridging the gap between shallow-sea and deep-sea image restoration fields through experimental analysis. This paper first categorizes shallow-sea image restoration methods into three types: physical model-based methods, prior-based methods, and deep learning-based methods that integrate physical models. The core concepts and characteristics of representative methods are analyzed. The research status and primary challenges in deep-sea image restoration are then summarized, including color cast and blur caused by underwater environmental characteristics, as well as insufficient and uneven lighting caused by artificial light sources. Potential solutions are explored, such as applying general shallow-sea restoration methods to address color cast and blur, and leveraging techniques from related fields like exposure image correction and low-light image enhancement to tackle lighting issues. Comprehensive experiments are conducted to examine the feasibility of shallow-sea image restoration methods and related image enhancement techniques for deep-sea image restoration. The experimental results provide valuable insights into existing methods for addressing the challenges of deep-sea image restoration. An in-depth discussion is presented, suggesting several future development directions in deep-sea image restoration. Three main points emerged from the research findings: i) Existing shallow-sea image restoration methods are insufficient to address the degradation issues in deep-sea environments, such as low-light and uneven illumination. ii) Combining imaging physical models with deep learning to restore deep-sea image quality may potentially yield desirable results. iii) The application potential of unsupervised and zero-shot learning methods in deep-sea image restoration warrants further investigation, given their ability to work with limited training data.
A regional analysis of tide-surge interactions during extreme water levels in complex coastal systems of Aotearoa New Zealand
Authors: Costa Wagner , Bryan Karin R. , Stephens Scott A. , Coco Giovanni
Published: May 2023

Tide-surge interaction (TSI) is a critical factor in assessing flooding in shallow coastal systems, particularly in estuaries and harbours. Non-linear interactions between tides and surges can occur due to the water depth and bed friction. Global investigations have been conducted to examine TSI, but its occurrence and impact on water levels in Aotearoa New Zealand (NZ) have not been extensively studied. Water level observations from 36 tide gauges across the diverse coast of NZ were analysed to determine the occurrence and location of TSI. Statistical analysis and numerical modelling were conducted on data from both inside and outside estuaries, focusing on one estuary (Manukau Harbour) to determine the impact of TSI and estuarine morphology on the co-occurrence rate of extreme events. TSI was found to occur at most sites in NZ and primarily affects the timing of the largest surges relative to high tide. There were no regional patterns associated with the tide, non-tidal residual, or skew-surge regimes. The strongest TSI occurred in inner estuarine locations and was correlated with the intertidal area. The magnitude of the TSI varied depending on the method used, ranging from -16 cm to +27 cm. Co-occurrence rates of extreme water levels outside and inside the same estuary varied from 20% to 84%, with TSI modulating the rate by affecting tidal amplification. The results highlight the importance of investing in a more extensive tide gauge network to provide longer observations in highly populated estuarine coastlines. The incorporation of TSI in flooding hazard projections would benefit from more accurate and detailed observations, particularly in estuaries with high morphological complexity. TSI occurs in most sites along the coast of NZ and has a significant impact on water levels in inner estuarine locations. TSI modulates the co-occurrence rate of extreme water levels in estuaries of NZ by affecting tidal amplification. Therefore, further investment in the tide gauge network is needed to provide more accurate observations to incorporate TSI in flooding hazard projections.
Characteristics of submesoscale eddy structures within mesoscale eddies in the Gulf of Mexico from 1/48° ECCO estimates
Authors: Ernst Paul A. , Subrahmanyam Bulusu , Trott Corinne B. , Chaigneau Alexis
Published: May 2023

Submesoscale oceanic structures (<10-20 km) such as eddies and fronts are often difficult to describe given the influence of the mesoscale. In order to characterize the surface signatures of submesoscale structures, we utilize a custom spatial filtering function to separate the meso- and large-scale sea surface height (SSH) signal from the small scale SSH signal of 1/48° high resolution estimates provided by NASA’s Estimating the Circulation and Climate of the Oceans (ECCO) project. In this study, we use ECCO estimates from a 14-month global simulation between September 2011 and November 2012 with a 2 km horizontal grid spacing in the Gulf of Mexico. We then use an eddy detection and tracking algorithm to identify persistent circular features on both scales, giving rise to an atlas of submesoscale eddy-like variabilities (SEVs). We briefly investigate the geographic and temporal variability of SEVs as a whole before collocating SEVs inside mesoscale eddies, allowing us to evaluate the characteristics of internal SEVs and the impact of SEVs on mesoscale eddies. We find that SEVs, both anticyclonic and cyclonic, are ubiquitous inside mesoscale eddies with lifetimes longer than a week, accounting for an average of 10-20% of the spatial area and eddy kinetic energy of mesoscale eddies. We also show that internal SEVs are persistently associated with temperature and salinity anomalies in both eddy centers and edges of up to 0.1 °C and 0.05 psu, with anticyclonic internal SEVs being warmer and fresher while cyclonic internal SEVs are colder and saltier. Finally, we examine the life cycle of an anticyclonic Loop Current eddy, demonstrating that the number and intensity of internal SEVs within increases as the eddy approaches separation from the Loop Current until a maximum is obtained just after separation. In light of forthcoming submesoscale SSH observations from NASA’s Surface Water and Ocean Topography (SWOT) mission, our results showcase the variability of submesoscale eddy structures and their possible implications for biogeochemical cycling, the inverse energy cascade, and Loop Current prediction techniques.
Feeding on the smallest cells: an in situ study of picoplankton capture by bivalve molluscs from oligotrophic waters
Authors: Amit Tal , Moskovich Raz , Jacobi Yuval , Shumway Sandra E. , Ward J. Evan , Beninger Peter , Yahel Gitai , Loya Yossi
Published: May 2023

Introduction

Bivalve molluscs are among the most prominent coastal benthic-suspension-feeders and their farming is the largest and fastest-growing sector of aquaculture. More than a century of intensive laboratory studies (but surprisingly few in-situ studies) has yielded the consensus view that bivalves mainly capture particles >4µm. Nonetheless, bivalves thrive throughout the world’s oceans that are mostly oligotrophic, characterized by low food concentration and dominated by minute autotrophic picoplankton (<2 µm).

Method

We measured, in situ, the capture efficiency of naturally occurring planktonic cells by five suspension-feeding bivalve species from four families and three orders, residing in two oligotrophic basins: the Red Sea and the East Mediterranean Sea.

Results

Three species captured micron and submicron autotrophic cells with high efficiency (60-90%), suggesting a wider trophic niche than hitherto believed. In contrast, two sympatric species captured mainly particles >10 µm.

Discussion

These results suggest that the same basic anatomical tool kit, variably modulated according to taxa, habitat, or life history traits, enables the remarkable evolutionary and ecological success of bivalves in trophically-diverse habitats.
Surface modification improving the biological activity and osteogenic ability of 3D printing porous dental implants
Authors: Qin Zugan , He Yun , Gao Jingjing , Dong Zhihong , Long Shuai , Cheng Lijia , Shi Zheng
Published: May 2023

Objective: To explore the mechanical properties, biological activity, and osteogenic ability of 3D printed TC4 titanium (Ti) alloy dental implants treated with surface modification.

Methods: Dental implants with 30% porosity were manufactured using selective laser melting (SLM) technology (group 3D), while traditional numerically-controlled machine tools (CNC) were used to manufacture implants without porosity (group SL). The implants were then surface modified through sandblasting and acid etching (groups 3DA1 and SLA1), and then alkali etching (groups 3DA2 and SLA2). The physicochemical properties of the implants were measured using a Vickers hardness instrument, scanning electron microscope (SEM), X-ray diffraction (XRD), energy dispersive spectrometer (EDS), and profilograph before and after surface modification. Next, the biocompatibility, bioactivity, and osteogenic ability of the implants were evaluated using apatite deposition experiments, alkaline phosphatase (ALP) activity, and semiquantitative analysis of extracellular matrix mineralization.

Results: There were significant differences in morphology, geometric accuracy, mechanical properties, surface roughness, and hydrophilicity between groups 3D and SL. Furthermore, surface modification improved the physicochemical properties of the porous implants. Implants with sandblasting, acid etching, and alkali etching demonstrated better biocompatibility, bioactivity, and osteogenic ability than implants without surface modification in both groups 3D and SL. Additionally, the implants of groups 3D have higher bioactivity than that of groups SL.

Conclusion: Surface modification and the macroporous structure of implants can improve their bioactivity and osteogenic ability, enhancing the application of Ti alloy dental implants.
Pyoderma gangrenosum following anti-TNF therapy in chronic recurrent multifocal osteomyelitis: drug reaction or cutaneous manifestation of the disease? A critical review on the topic with an emblematic case report
Authors: Romagnuolo Maurizio , Moltrasio Chiara , Iannone Claudia , Gattinara Maurizio , Cambiaghi Stefano , Marzano Angelo Valerio
Published: May 2023

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, clinically characterized by chronic and recurrent episodes of osteoarticular inflammation, that generally presents in children and adolescents. From a dermatological point-of-view, CMRO can be associated with skin rashes mainly including psoriasis, palmoplantar pustulosis and acne. Pyoderma gangrenosum (PG) is a rare immune-mediated inflammatory skin disease classified within the spectrum of neutrophilic dermatoses that, in some cases, has been reported as cutaneous manifestation in CMRO patients. This paper presents a 16-year female patient diagnosed with CMRO, who presented PG lesions located on the lower leg, that arose after the administration of the tumour necrosis factor (TNF)-α inhibitor adalimumab. Cases of PG have been reported in patients being treated with certain medications, including TNF-α antagonists, leading to classified them in a setting aptly termed “drug-induced PG.” In this paper, we discuss the co-occurrence of PG and CRMO, in the light of recent evidence on the pathogenesis of both diseases and giving ample space to a literature review on drug induced PG. In our case, it is plausible that PG could be considered a cutaneous manifestation of CRMO, although the mechanisms underlying this intriguingly relationship remain to be fully unraveled.
Recombinant hemagglutinin displaying on yeast reshapes congenital lymphocyte subsets to prompt optimized systemic immune protection against avian influenza infection
Authors: Zhang Han , Li Zexing , Zhang Huixia , Guo Yanyu , Zhang Xinyi , Zhang Lilin , Yang Liu , Li Shujun , Li Changyan , Cui Daqing , Xie Ruyu , Li Yongqing , Huang Jinhai
Published: May 2023

Introduction

Prophylactic vaccination is regarded as the most effective means to control avian flu infection. Currently, there is a need for a universal vaccine that provides broad and long-lasting protection against influenza virus. Meanwhile, although yeast-based vaccines have been used in clinic, studies are still required to further understand the molecular mechanism of yeast-based vaccines under physiological conditions.

Methods

We generated a yeast-based vaccine against influenza hemagglutinin (HA) of H5, H7 and H9 using surface displaying technology and evaluated the protective efficacy of chickens after exposure to H9N2 influenza virus.

Results

Oral yeast vaccine provided less clinical syndrome, reduced viral loading and alleviated airway damage significantly. Compared to the commercial inactivated vaccine, yeast vaccine stimulated the activation of splenic NK and APCs cells and boosted TLR7-IRF7-IFN signaling in spleen. Meanwhile, γδ T cells in the bursa of Fabricius were activated and the innate lymphoid cells (ILCs) in the bursa of Fabricius promoted the CILPs to differentiate to ILC3 cells in oral yeast birds. Moreover, the reshaped gut microbiota and a suppressed Th17-IL17-mediated inflammation in intestine was observed in oral yeast chickens, which might facilitate the recovery of intestinal mucosal immunity upon virus infection. Collectively, our findings suggest that oral yeast based multivalent bird flu vaccines provide an attractive strategy to update host defense function via reshapes of multi-systemic immune homeostasis.
Engineering bacteriophages for enhanced host range and efficacy: insights from bacteriophage-bacteria interactions
Authors: Jia Huang-Jie , Jia Pan-Pan , Yin Supei , Bu Ling-Kang , Yang Guan , Pei De-Sheng
Published: May 2023

Bacteriophages, the most abundant organisms on earth, have the potential to address the rise of multidrug-resistant bacteria resulting from the overuse of antibiotics. However, their high specificity and limited host range can hinder their effectiveness. Phage engineering, through the use of gene editing techniques, offers a means to enhance the host range of bacteria, improve phage efficacy, and facilitate efficient cell-free production of phage drugs. To engineer phages effectively, it is necessary to understand the interaction between phages and host bacteria. Understanding the interaction between the receptor recognition protein of bacteriophages and host receptors can serve as a valuable guide for modifying or replacing these proteins, thereby altering the receptor range of the bacteriophage. Research and development focused on the CRISPR-Cas bacterial immune system against bacteriophage nucleic acids can provide the necessary tools to promote recombination and counter-selection in engineered bacteriophage programs. Additionally, studying the transcription and assembly functions of bacteriophages in host bacteria can facilitate the engineered assembly of bacteriophage genomes in non-host environments. This review highlights a comprehensive summary of phage engineering methods, including in-host and out-of-host engineering, and the use of high-throughput methods to understand their role. The main aim of these techniques is to harness the intricate interactions between bacteriophages and hosts to inform and guide the engineering of bacteriophages, particularly in the context of studying and manipulating the host range of bacteriophages. By employing advanced high-throughput methods to identify specific bacteriophage receptor recognition genes, and subsequently introducing modifications or performing gene swapping through in-host recombination or out-of-host synthesis, it becomes possible to strategically alter the host range of bacteriophages. This capability holds immense significance for leveraging bacteriophages as a promising therapeutic approach against antibiotic-resistant bacteria.
Managing the deluge of newly discovered plant viruses and viroids: an optimized scientific and regulatory framework for their characterization and risk analysis
Authors: Fontdevila Pareta Nuria , Khalili Maryam , Maachi Ayoub , Rivarez Mark Paul S. , Rollin Johan , Salavert Ferran , Temple Coline , Aranda Miguel A. , Boonham Neil , Botermans Marleen , Candresse Thierry , Fox Adrian , Hernando Yolanda , Kutnjak Denis , Marais Armelle , Petter Françoise , Ravnikar Maja , Selmi Ilhem , Tahzima Rachid , Trontin Charlotte , Wetzel Thierry , Massart Sebastien
Published: May 2023

The advances in high-throughput sequencing (HTS) technologies and bioinformatic tools have provided new opportunities for virus and viroid discovery and diagnostics. Hence, new sequences of viral origin are being discovered and published at a previously unseen rate. Therefore, a collective effort was undertaken to write and propose a framework for prioritizing the biological characterization steps needed after discovering a new plant virus to evaluate its impact at different levels. Even though the proposed approach was widely used, a revision of these guidelines was prepared to consider virus discovery and characterization trends and integrate novel approaches and tools recently published or under development. This updated framework is more adapted to the current rate of virus discovery and provides an improved prioritization for filling knowledge and data gaps. It consists of four distinct steps adapted to include a multi-stakeholder feedback loop. Key improvements include better prioritization and organization of the various steps, earlier data sharing among researchers and involved stakeholders, public database screening, and exploitation of genomic information to predict biological properties.
Genomic characteristics of a novel emerging PRRSV branch in sublineage 8.7 in China
Authors: Li Wansheng , Li Chao , Guo Zhenyang , Xu Hu , Gong Bangjun , Sun Qi , Zhao Jing , Xiang Lirun , Leng Chaoliang , Peng Jinmei , Zhou Guohui , Tang Yandong , Liu Huairan , An Tongqing , Cai Xue-Hui , Tian Zhi-Jun , Wang Qian , Zhang Hongliang
Published: May 2023

Porcine reproductive and respiratory syndrome virus (PRRSV) has caused serious economic losses to the pig industry worldwide. During the continuous monitoring of PRRSV, a new PRRSV strain type with novel characteristics was first identified in three different regions of Shandong Province. These strains presented a novel deletion pattern (1 + 8 + 1) in the NSP2 region and belonged to a new branch in sublineage 8.7 based on the ORF5 gene phylogenetic tree. To further study the genomic characteristics of the new-branch PRRSV, we selected a sample from each of the three farms for whole-genome sequencing and sequence analysis. Based on the phylogenetic analysis of the whole genome, these strains formed a new independent branch in sublineage 8.7, which showed a close relationship with HP-PRRSV and intermediate PRRSV according to nucleotide and amino acid homology but displayed a completely different deletion pattern in NSP2. Recombinant analysis showed that these strains presented similar recombination patterns, all of which involved recombination with QYYZ in the ORF3 region. Furthermore, we found that the new-branch PRRSV retained highly consistent nucleotides at positions 117–120 (AGTA) of a quite conserved motif in the 3’-UTR; showed similar deletion patterns in the 5’-UTR, 3’-UTR and NSP2; retained characteristics consistent with intermediate PRRSV and exhibited a gradual evolution trend. The above results showed that the new-branch PRRSV strains may have the same origin and be similar to HP-PPRSV also evolved from intermediate PRRSV, but are distinct strains that evolved simultaneously with HP-PRRSV. They persist in some parts of China through rapid evolution, recombine with other strains and have the potential to become epidemic strains. The monitoring and biological characteristics of these strains should be further studied.
Rewiring carbon flow in Synechocystis PCC 6803 for a high rate of CO2-to-ethanol under an atmospheric environment
Authors: Gao E-Bin , Wu Junhua , Ye Penglin , Qiu Haiyan , Chen Huayou , Fang Zhen
Published: May 2023

Cyanobacteria are an excellent microbial photosynthetic platform for sustainable carbon dioxide fixation. One bottleneck to limit its application is that the natural carbon flow pathway almost transfers CO2 to glycogen/biomass other than designed biofuels such as ethanol. Here, we used engineered Synechocystis sp. PCC 6803 to explore CO2-to-ethanol potential under atmospheric environment. First, we investigated the effects of two heterologous genes (pyruvate decarboxylase and alcohol dehydrogenase) on ethanol biosynthesis and optimized their promoter. Furthermore, the main carbon flow of the ethanol pathway was strengthened by blocking glycogen storage and pyruvate-to-phosphoenolpyruvate backflow. To recycle carbon atoms that escaped from the tricarboxylic acid cycle, malate was artificially guided back into pyruvate, which also created NADPH balance and promoted acetaldehyde conversion into ethanol. Impressively, we achieved high-rate ethanol production (248 mg/L/day at early 4 days) by fixing atmospheric CO2. Thus, this study exhibits the proof-of-concept that rewiring carbon flow strategies could provide an efficient cyanobacterial platform for sustainable biofuel production from atmospheric CO2.
lncRNAs-EZH2 interaction as promising therapeutic target in cutaneous melanoma
Authors: Wozniak Michal , Czyz Malgorzata
Published: May 2023

Melanoma is the most lethal skin cancer with increasing incidence worldwide. Despite a great improvement of diagnostics and treatment of melanoma patients, this disease is still a serious clinical problem. Therefore, novel druggable targets are in focus of research. EZH2 is a component of the PRC2 protein complex that mediates epigenetic silencing of target genes. Several mutations activating EZH2 have been identified in melanoma, which contributes to aberrant gene silencing during tumor progression. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are molecular “address codes” for EZH2 silencing specificity, and targeting lncRNAs-EZH2 interaction may slow down the progression of many solid cancers, including melanoma. This review summarizes current knowledge regarding the involvement of lncRNAs in EZH2-mediated gene silencing in melanoma. The possibility of blocking lncRNAs-EZH2 interaction in melanoma as a novel therapeutic option and plausible controversies and drawbacks of this approach are also briefly discussed.
LeishIF3d is a non-canonical cap-binding protein in Leishmania
Authors: Bose Priyanka , Baron Nofar , Pullaiahgari Durgeshwar , Ben-Zvi Anat , Shapira Michal
Published: May 2023

Translation of most cellular mRNAs in eukaryotes proceeds through a cap-dependent pathway, whereby the cap-binding complex, eIF4F, anchors the pre-initiation complex at the 5′ end of mRNAs driving translation initiation. The genome of Leishmania encodes a large repertoire of cap-binding complexes that fulfill a variety of functions possibly involved in survival along the life cycle. However, most of these complexes function in the promastigote life form that resides in the sand fly vector and decrease their activity in amastigotes, the mammalian life form. Here we examined the possibility that LeishIF3d drives translation in Leishmania using alternative pathways. We describe a non-canonical cap-binding activity of LeishIF3d and examine its potential role in driving translation. LeishIF3d is required for translation, as reducing its expression by a hemizygous deletion reduces the translation activity of the LeishIF3d(+/−) mutant cells. Proteomic analysis of the mutant cells highlights the reduced expression of flagellar and cytoskeletal proteins, as reflected in the morphological changes observed in the mutant cells. Targeted mutations in two predicted alpha helices diminish the cap-binding activity of LeishIF3d. Overall, LeishIF3d could serve as a driving force for alternative translation pathways, although it does not seem to offer an alternative pathway for translation in amastigotes.
CREB5 hypermethylation involved in the ganglioside GM1 therapy of Parkinson’s disease
Authors: Wang Rui , Tong Shanshan , Wang Mengdi , Zou Junjie , Wang Nan , Sun Fengjiao , Zhou Xiaosheng , Chen Jinbo , Wang Hongcai
Published: May 2023

Introduction

The treatment with monosialotetrahexosylganglioside (GM1) improves the symptoms of Parkinson’s disease (PD). The alteration of DNA methylation in the blood was examined to investigate epigenetic modification by GM1 treatment.

Methods

After a 28-day continuous intravenous infusion of GM1 (100mg), the motor and non-motor symptoms were evaluated by UPDRS III, Mini-mental state examination (MMSE) scores, FS-14, SCOPA-AUT, and PDQ-8. Moreover, blood samples were collected and PBMC was isolated. Genome-wide DNA methylation was performed by an 850K BeadChip. RNA levels and apoptosis were examined by RT-PCR and flow cytometry in rotenone-based cell models. The CREB5 plasmid was transfected by electroporation into SH-SY5Y cells. We also identified 235 methylation variable positions achieving genome-wide significance in 717558 differentially methylated positions (DMPs) (P = 0.0003) in comparison of pre-treatment with post-treatment measurements (statistical analysis paired-samples t-test).

Results

By searching the Gene Expression Omnibus (GEO) dataset and GWAS, 23 methylation variable positions were screened. Moreover, there are 7 hypomethylated methylation variable positions correlated with the scores of motor symptoms (UPDRS III scale). According to KEGG pathways enrichment analysis, the methylated genes CACNA1B (hypomethylated), CREB5 (hypermethylated), GNB4 (hypomethylated), and PPP2R5A (hypomethylated) were enriched in the dopaminergic synapse pathway. Pretreated with GM1 (80 μM) for 1 h, cell apoptosis and impaired neurite outgrowth were inhibited in rotenone-induced PD cell models. The RNA expression of CREB5 was increased in rotenone-treated SH-SY5Y cells. GM1 treatment decreased rotenone-induced CREB5 gene expression. The enhancement of CREB5 gene expression suppressed the protective role of GM1 in rotenone-induced cell apoptosis.

Discussion

The application of GM1 improves the motor and non-motor symptoms of PD associated with the decreased CREB5 expression and the hypermethylation of CREB5.

Clinical trial registration

https://www.chictr.org.cn/showproj.html?proj=120582t, identifier ChiCTR2100042537.
Topological arrangement of coronal segments in human callosal fibers in vivo tractography
Authors: Zhang Hui , Feng Yuan , Li Weiguang , Liang Xili , Huang Guanglong , Qi Songtao
Published: May 2023

The topography of human callosal fibers in the midsagittal corpus callosum (mid-CC), in terms of cortical termination, is inconsistent in the literature. Despite being a high-profile and controversial topic, heterotopic callosal bundles (HeCBs) have not been studied from a whole-brain perspective. Here, we used multi-modal magnetic resonance imaging data from Human Connectome Project Development to explore these two topographic aspects by combining whole-brain tractography based on multi-shell multi-tissue constrained spherical deconvolution, the post-tractography reducing-false-positive-streamline algorithm of Convex Optimization Modeling for Microstructure Informed Tractography 2, and the new cortex parcellation atlas of Human Connectome Project multi-modal parcellation, version 1.0. We proposed that the callosal streamlines would demonstrate a topological arrangement of coronal segments arranged from anterior to posterior, with each perpendicular to the long axis of the mid-CC following its natural curvature, and the adjacent segments overlapping one another owing to the existence of HeCBs. We found that the cortices connected by the coronal segments, from anterior to posterior, corresponded exactly to the cortices from anterior to posterior in the flattened cortical surfaces of this atlas, indicating the original relative positions of the neocortex before curling and flipping during brain evolution. For each cortical area defined by this atlas, the sum strength of the HeCBs was far greater than that of the homotopic callosal bundle. Our findings on the topography of the whole CC would help in further understanding the network between the bilateral hemispheres and preventing disconnection syndromes in clinical settings.
AlphaTracker: a multi-animal tracking and behavioral analysis tool
Authors: Chen Zexin , Zhang Ruihan , Fang Hao-Shu , Zhang Yu E. , Bal Aneesh , Zhou Haowen , Rock Rachel R. , Padilla-Coreano Nancy , Keyes Laurel R. , Zhu Haoyi , Li Yong-Lu , Komiyama Takaki , Tye Kay M. , Lu Cewu
Published: May 2023

Computer vision has emerged as a powerful tool to elevate behavioral research. This protocol describes a computer vision machine learning pipeline called AlphaTracker, which has minimal hardware requirements and produces reliable tracking of multiple unmarked animals, as well as behavioral clustering. AlphaTracker pairs a top-down pose-estimation software combined with unsupervised clustering to facilitate behavioral motif discovery that will accelerate behavioral research. All steps of the protocol are provided as open-source software with graphic user interfaces or implementable with command-line prompts. Users with a graphical processing unit (GPU) can model and analyze animal behaviors of interest in less than a day. AlphaTracker greatly facilitates the analysis of the mechanism of individual/social behavior and group dynamics.
The Use of Different Components of Brain Oxygenation for the Assessment of Cerebral Haemodynamics: A Prospective Observational Study on COVID-19 Patients
Authors: Robba Chiara , Cardim Danilo , Ball Lorenzo , Battaglini Denise , Dabrowski Wojciech , Bassetti Matteo , Giacobbe Daniele Roberto , Czosnyka Marek , Badenes Rafael , Pelosi Paolo , Matta Basil ,   The GeCovid group
Published: May 2023

Introduction: The role of near-infrared spectroscopy (NIRS) for the evaluation of cerebral haemodynamics is gaining increasing popularity because of its noninvasive nature. The aim of this study was to evaluate the role of the integral components of regional cerebral oxygenation (rSO2) measured by NIRS [i.e., arterial-oxyhemoglobin (O2Hbi) and venous-deoxyhemoglobin (HHbi)-components], as indirect surrogates of cerebral blood flow (CBF) in a cohort of critically ill patients with coronavirus disease 2019 (COVID-19). We compared these findings to the gold standard technique for noninvasive CBF assessment, Transcranial Doppler (TCD).

Methods: Mechanically ventilated patients with COVID-19 admitted to the Intensive Care Unit (ICU) of Policlinico San Martino Hospital, Genova, Italy, who underwent multimodal neuromonitoring (including NIRS and TCD), were included. rSO2 and its components [relative changes in O2Hbi, HHbi, and total haemoglobin (cHbi)] were compared with TCD (cerebral blood flow velocity, CBFV). Changes (Δ) in CBFV and rSO2, ΔO2Hbi, ΔHHbi, and ΔcHbi after systemic arterial blood pressure (MAP) modifications induced by different manoeuvres (e.g., rescue therapies and haemodynamic manipulation) were assessed using mixed-effect linear regression analysis and repeated measures correlation coefficients. All values were normalised as percentage changes from the baseline (Δ%).

Results: One hundred and four measurements from 25 patients were included. Significant effects of Δ%MAP on Δ%CBF were observed after rescue manoeuvres for CBFV, ΔcHbi, and ΔO2Hbi. The highest correlation was found between ΔCBFV and ΔΔO2Hbi (R = 0.88, p < 0.0001), and the poorest between ΔCBFV and ΔΔHHbi (R = 0.34, p = 0.002).

Conclusions: ΔO2Hbi had the highest accuracy to assess CBF changes, reflecting its role as the main component for vasomotor response after changes in MAP. The use of indexes derived from the different components of rSO2 can be useful for the bedside evaluation of cerebral haemodynamics in mechanically ventilated patients with COVID-19.
Effects of community ambulation training with 3D-printed ankle–foot orthosis on gait and functional improvements: a case series of three stroke survivors
Authors: Cho Ji-Eun , Seo Kyeong-Jun , Ha Sunghe , Kim Hogene
Published: May 2023

Introduction

Many of the patients using ankle–foot orthoses (AFOs) experience poor fit, pain, discomfort, dislike of the aesthetics of the device, and excessive range of motion restrictions, which diminish the use of AFOs. Although 3D-printed ankle–foot orthoses (3D-AFOs) affect patient satisfaction and overall gait functions such as ankle moment, joint range of motion (ROM), and temporal-spatial parameters, the material properties and manufacturing process of 3D-AFOs are still diverse; the clinical effects of community ambulation using 3D-AFOs and satisfaction in patients with stroke are poorly understood.

Case description

Case 1: A 30-year-old man, with a history of right basal ganglia hemorrhage, presented with marked foot drop and genu recurvatum. Case 2: A 58-year-old man, with a history of multifocal scattered infarction, presented with an asymmetrical gait pattern due to abnormal pelvic movement. Case 3: A 47-year-old man, with a history of right putamen hemorrhage, presented with recent poor balance and a prominent asymmetrical gait pattern due to increased ankle spasticity and tremor. All patients could walk independently with AFOs.

Interventions and outcomes

Gait was assessed under three walking (even, uneven, and stair ascent/descent) and four AFO (no shoes, only shoes, shoes with AFOs, and shoes with 3D-AFOs) conditions. After 4 weeks of community ambulation training with 3D-AFO or AFO, the patients were followed up. Spatiotemporal parameters; joint kinematics; muscle efficiency; clinical evaluations including impairments, limitations, and participation; and patient satisfaction with wearing 3D-AFO were evaluated.

Results and conclusion

3D-AFOs were suitable for community ambulation of patients with chronic stroke and effective on step length, stride width, symmetry, ankle range of motion, and muscle efficiency during even surface walking and stair ascent in patients with chronic stroke. The 4-week community ambulation training with 3D-AFOs did not promote patient participation; however, it increased ankle muscle strength, balance, gait symmetry, and gait endurance and reduced depression among patients with a history of stroke. The participants were satisfied with 3D-AFO's thinness, lightweight, comfortable feeling with wearing shoes, and gait adjustability.
Social cognitive neuroscience in the digital age
Authors: Doheny Margaret M. , Lighthall Nichole R.
Published: May 2023

Human interactions are increasingly taking place from a distance through methods of remote interpersonal communication like video chatting and social media. While remote interpersonal communication has existed for millennia—with the first postal system arising in ∼2400 B.C.—accelerated advances in technology and the recent global COVID-19 pandemic have led to a dramatic increase in remote interpersonal communication use in daily life. Remote interpersonal communication presents a challenge to the field of social-cognitive neuroscience, as researchers seek to understand the implications of various types of remote interpersonal communication for the “social brain.” The present paper reviews our current understanding of the social-cognitive neural network and summarizes critical differences between the neural correlates of social cognition in remote vs. face-to-face interactions. In particular, empirical and theoretical work is reviewed that highlight disparities in the neural mechanisms of social perception, evaluation of social stimuli, human motivation, evaluation of social reward, and theory of mind. Potential impacts of remote interpersonal communication on the development of the brain’s social-cognitive network are also discussed. Finally, this review closes with future directions for research on social-cognitive neuroscience in our digital technology-connected world and outlines a neural model for social cognition in the context of remote interpersonal communication. For the field of social-cognitive neuroscience to advance alongside of the ever-evolving society, it is crucial for researchers to acknowledge the implications and concepts suggested for future research in this review.