bluuebunny/crossref_metadata_2025 huggingface dataset:
From birth to death: The hardworking life of Paneth cell in the small intestine
Authors: Cui Chenbin , Wang Fangke , Zheng Yao , Wei Hongkui , Peng Jian
Published: March 2023

Paneth cells are a group of unique intestinal epithelial cells, and they play an important role in host-microbiota interactions. At the origin of Paneth cell life, several pathways such as Wnt, Notch, and BMP signaling, affect the differentiation of Paneth cells. After lineage commitment, Paneth cells migrate downward and reside in the base of crypts, and they possess abundant granules in their apical cytoplasm. These granules contain some important substances such as antimicrobial peptides and growth factors. Antimicrobial peptides can regulate the composition of microbiota and defend against mucosal penetration by commensal and pathogenic bacteria to protect the intestinal epithelia. The growth factors derived from Paneth cells contribute to the maintenance of the normal functions of intestinal stem cells. The presence of Paneth cells ensures the sterile environment and clearance of apoptotic cells from crypts to maintain the intestinal homeostasis. At the end of their lives, Paneth cells experience different types of programmed cell death such as apoptosis and necroptosis. During intestinal injury, Paneth cells can acquire stem cell features to restore the intestinal epithelial integrity. In view of the crucial roles of Paneth cells in the intestinal homeostasis, research on Paneth cells has rapidly developed in recent years, and the existing reviews on Paneth cells have mainly focused on their functions of antimicrobial peptide secretion and intestinal stem cell support. This review aims to summarize the approaches to studying Paneth cells and introduce the whole life experience of Paneth cells from birth to death.
An experimental medicine decipher of a minimum correlate of cellular immunity: Study protocol for a double-blind randomized controlled trial
Authors: Kalimuddin Shirin , Chan Yvonne F. Z. , Sessions October M. , Chan Kuan Rong , Ong Eugenia Z. , Low Jenny G. , Bertoletti Antonio , Ooi Eng Eong
Published: March 2023

Vaccination induces an adaptive immune response that protects against infectious diseases. A defined magnitude of adaptive immune response that correlates with protection from the disease of interest, or correlates of protection (CoP), is useful for guiding vaccine development. Despite mounting evidence for the protective role of cellular immunity against viral diseases, studies on CoP have almost exclusively focused on humoral immune responses. Moreover, although studies have measured cellular immunity following vaccination, no study has defined if a “threshold” of T cells, both in frequency and functionality, is needed to reduce infection burden. We will thus conduct a double-blind, randomized clinical trial in 56 healthy adult volunteers, using the licensed live-attenuated yellow fever (YF17D) and chimeric Japanese encephalitis-YF17D (JE-YF17D) vaccines. These vaccines share the entire non-structural and capsid proteome where the majority of the T cell epitopes reside. The neutralizing antibody epitopes, in contrast, are found on the structural proteins which are not shared between the two vaccines and are thus distinct from one another. Study participants will receive JE-YF17D vaccination followed by YF17D challenge, or YF17D vaccination followed by JE-YF17D challenge. A separate cohort of 14 healthy adults will receive the inactivated Japanese Encephalitis virus (JEV) vaccine followed by YF17D challenge that controls for the effect of cross-reactive flaviviral antibodies. We hypothesize that a strong T cell response induced by YF17D vaccination will reduce JE-YF17D RNAemia upon challenge, as compared to JE-YF17D vaccination followed by YF17D challenge. The expected gradient of YF17D-specific T cell abundance and functionality would also allow us to gain insight into a T cell threshold for controlling acute viral infections. The knowledge gleaned from this study could guide the assessment of cellular immunity and vaccine development.

Clinical trial registration

Clinicaltrials.gov, NCT05568953.
Adaptive and innate immune pathogenesis of bullous pemphigoid: A review
Authors: Yan Tianmeng , Zhang Zhenying
Published: March 2023

Bullous pemphigoid (BP) is an autoimmune blistering disease that primarily affects elderly individuals. The presentation of BP is heterogeneous, typically manifesting as microscopic subepidermal separation with a mixed inflammatory infiltrate. The mechanism of pemphigoid development is unclear. B cells play a major role in pathogenic autoantibody production, and T cells, type II inflammatory cytokines, eosinophils, mast cells, neutrophils, and keratinocytes are also implicated in the pathogenesis of BP. Here, we review the roles of and crosstalk between innate and adaptive immune cells in BP.
How (not) to look for meaning composition in the brain: A reassessment of current experimental paradigms
Authors: Călinescu Lia , Ramchand Gillian , Baggio Giosuè
Published: March 2023

When we use language, we draw on a finite stock of lexical and functional meanings and grammatical structures to assign meanings to expressions of arbitrary complexity. According to the Principle of Compositionality, the meanings of complex expressions are a function of constituent meanings and syntax, and are generated by the recursive application of one or morecomposition operations. Given their central role in explanatory accounts of human language, it is surprising that relatively little is known about how the brain implements these composition operations in real time. In recent years, neurolinguistics has seen a surge of experiments investigating when and where in the brain meanings are composed. To date, however, neural correlates of composition have not been firmly established. In this article, we focus on studies that set out to find the correlates of linguistic composition. We critically examine the paradigms they employed, laying out the rationale behind each, their strengths and weaknesses. We argue that the still blurry picture of composition in the brain may be partly due to limitations of current experimental designs. We suggest that novel and improved paradigms are needed, and we discuss possible next steps in this direction. At the same time, rethinking the linguistic notion of composition, as based on a tight correspondence between syntax and semantics, might be in order.
Seasonal variations in Circumpolar Deep Water intrusions into the Ross Sea continental shelf
Authors: Wang Yufei , Zhou Meng , Zhang Zhaoru , Dinniman Michael S.
Published: March 2023

Intrusions of the warm and nutrient-rich Circumpolar Deep Water (CDW) across the Ross Sea shelf break play an important role in providing heat for ice shelf basal melting and setting the physical environment for biochemical processes. Several mechanisms driving CDW intrusions into the Ross Sea were proposed such as mesoscale eddies, tidal rectification, and interactions between the Antarctic Slope Current (ASC) and topographic features. The seasonal variations in the poleward transport of CDW are investigated using ERA-Interim wind data and a Ross Sea circulation model based on the Regional Ocean Modeling System (ROMS) between September 1999 and September 2014. The analyses focus on the currents along the shelf break and deep troughs on the Ross Sea shelf and discuss the wind-driven Ekman pumping in both shelf and adjacent open ocean regions. The results reveal that the poleward intrusions generally move up onto the continental shelf along the eastern flanks of deep troughs. Seasonal variations of the ocean surface stress torque exerted by wind and sea ice in the off-shelf area are correlated with CDW intrusions. The maxima of CDW intrusions usually occur in austral summer. There is a significant temporal correlation on the seasonal time scale between the on-shelf intrusions in deep troughs in the western Ross Sea shelf and poleward Sverdrup transports in the adjacent off-shelf open ocean driven by the Ekman pumping. The analysis of ocean surface stress fields also indicates that the vorticity fluxes through the Ekman pumping are in favor of southward and northward transports in the eastern and western parts of the Ross Sea, respectively. The relationships between currents, CDW intrusions, and ocean surface stress fields imply the importance of air–sea interactions and potential climate change to the environment in the Ross Sea.
Scaling whale monitoring using deep learning: A human-in-the-loop solution for analyzing aerial datasets
Authors: Boulent Justine , Charry Bertrand , Kennedy Malcolm McHugh , Tissier Emily , Fan Raina , Marcoux Marianne , Watt Cortney A. , Gagné-Turcotte Antoine
Published: March 2023

To ensure effective cetacean management and conservation policies, it is necessary to collect and rigorously analyze data about these populations. Remote sensing allows the acquisition of images over large observation areas, but due to the lack of reliable automatic analysis techniques, biologists usually analyze all images by hand. In this paper, we propose a human-in-the-loop approach to couple the power of deep learning-based automation with the expertise of biologists to develop a reliable artificial intelligence assisted annotation tool for cetacean monitoring. We tested this approach to analyze a dataset of 5334 aerial images acquired in 2017 by Fisheries and Oceans Canada to monitor belugas (Delphinapterus leucas) from the threatened Cumberland Sound population in Clearwater Fjord, Canada. First, we used a test subset of photographs to compare predictions obtained by the fine-tuned model to manual annotations made by three observers, expert marine mammal biologists. With only 100 annotated images for training, the model obtained between 90% and 91.4% mutual agreement with the three observers, exceeding the minimum inter-observer agreement of 88.6% obtained between the experts themselves. Second, this model was applied to the full dataset. The predictions were then verified by an observer and compared to annotations made completely manually and independently by another observer. The annotating observer and the human-in-the-loop pipeline detected 4051 belugas in common, out of a total of 4572 detections for the observer and 4298 for our pipeline. This experiment shows that the proposed human-in-the-loop approach is suitable for processing novel aerial datasets for beluga counting and can be used to scale cetacean monitoring. It also highlights that human observers, even experienced ones, have varied detection bias, underlining the need to discuss standardization of annotation protocols.
Succession and controlling factors of phytoplankton assemblages during a period with recurrent outbreaks of Phaeocystis globosa blooms in Qinzhou Bay, China
Authors: Qin Xianling , Chen Xianyun , Chen Changping , Sun Lin , Su Xinying , Liang Junrong , Chen Bo , Gao Yahui
Published: March 2023

Qinzhou Bay is a tropical semiclosed bay with the highest phytoplankton diversity and a high frequency of harmful algal blooms (HABs) in the Guangxi coastal area, located north of the Beibu Gulf. Phaeocystis globosa is a typical HAB species in the Guangxi coastal area, and blooms mainly occur in autumn and winter. The causes of these blooms and the succession of phytoplankton assemblages related to the blooms are complicated and not fully understood. Therefore, a continuous survey was conducted monthly from October 2018 to March 2019 to study the succession of the phytoplankton community in Qinzhou Bay and its relationship with environmental variables in this area. The results revealed that the dynamics of the phytoplankton assemblages varied significantly with time, and P. globosa was the most frequent dominant species in five of these voyages, with the highest cell density of 3.79 ± 1.34 × 106 cells/L in January. Chaetoceros species had a high density and were a dominant species associated with P. globosa in the early stage, while they were replaced by Guinardia striata when the density of P. globosa increased rapidly in January, and the abundance of dinoflagellates increased after the decline in P. globosa. The diversity index indicated that the community structure was more stable from October to December, while the sharp increase in P. globosa in January caused a decline in phytoplankton diversity. The redundancy analysis (RDA) results revealed that the phytoplankton community structure and its variation were mainly affected by hydrological and chemical factors, including DIN/DIP, temperature, DSi, DIP and DSi/DIP. Furthermore, we inferred that phosphorus (P) was the key factor limiting the colony formation of P. globosa, and P limitation prevented the outbreak of blooms. This research may provide more insight into the mechanisms driving and prevention of P. globosa blooms.
Enhancement of seaweed polysaccharides (fucoidan and laminarin) on the phagocytosis of macrophages via activation of intelectin in blunt snout bream (Megalobrama amblycephala)
Authors: Li Hongping , Liu Yunlong , Teng Yuting , Zheng Yancui , Zhang Minying , Wang Xu , Cheng Hanliang , Xu Jianhe , Chen Xiangning , Zhao Xiaoheng , Ding Zhujin
Published: March 2023

Fucoidan and laminarin are polymolecular compounds that extracted from seaweed. As functional polysaccharides, they possess various biological functions such as immunomodulatory, anti-inflammatory, antiviral and antioxidant bioactivities. Fucoidan and laminarin modulate host immune responses by activating immune cells (macrophages, neutrophils, T lymphocytes) and inducing the expression of cytokines (TNFα, IL-1β, IL-6, IL-8, NF-κB). Intelectin is a novel lectin that plays important roles in bacterial agglutination and bactericidal effects by recognizing the polysaccharide components on the cell surface of pathogens, which can also enhance the phagocytosis of macrophages. The present study intends to explore the immunomodulatory effects of fucoidan, laminarin and intelectin on the macrophages of Megalobrama amblycephala. The results showed that the incubation of both fucoidan and laminarin at the concentration of 100 μg/mL for 4 h could enhance the phagocytic capacity of M. amblycephala macrophages, which also showed remodeled cytoskeleton with extended pseudopodia. In addition, fucoidan and laminarin could induce the expression of M. amblycephala intelectin (MaINTL) in the primary hepatocytes and macrophages, and the recombinant MaINTL (rMaINTL) could bind with fucoidan and laminarin. Furthermore, fucoidan and laminarin induced the expression of cytoskeletal remodeling related genes in the primary M. amblycephala macrophages, such as Rac1 and WASP, which should contribute to the enhancement of seaweed polysaccharides (fucoidan and laminarin) and MaINTL on the phagocytosis of M. amblycephala macrophages. However, even though fucoidan and laminarin could induced the expression of CXCL8, while the chemotaxis of M. amblycephala macrophages on neutrophils was not affected by them. These findings suggested that fucoidan and laminarin enhanced the phagocytic capacity of M. amblycephala macrophages via activation of MaINTL and up-regulation of the expression of downstream cytoskeletal remodeling related genes Rac1 and WASP. Therefore, fucoidan and laminarin could be used as immune enhancers to improve host immunity and disease resistance in M. amblycephala, which provided novel insights into the prevention and protection of fish bacterial diseases.
Laser-induced breakdown spectroscopy instrument and spectral analysis for deep-ocean Fe-Mn crusts
Authors: Yang Guang , Chen Guanyu , Cai Zixuan , Quan Xiangqian , Zhu Yang
Published: March 2023

Introduction

Marine ferromanganese crusts are potentially important metal resources.The deep-ocean research and survey ships often need to carry out rapid chemical element component analysis of mineral resources, so as to plan for the geological resource exploration mission.

Methods

The laser-induced breakdown spectroscopy can obtain the spectrum of chemical elements by the plasma excited by high-energy laser irradiation on the surface of the sample. A laser induced breakdown spectroscopy optical system for the detection of deepocean ferromanganese crusts is designed and built, which can meet the requirements of near-insitu chemical component detection of deep-ocean mineral resources on ocean-going survey ships.

Results

Hyperspectral data of Fe-Mn crusts are carried out by the Laser-induced breakdown spectroscopy (LIBS) system during a deep-sea exploration mission at a depth of 2,490 m in the South China Sea. The experimental parameters of laser energy and spectral acquisition delay are optimized to improve the spectral measurement accuracy. Based on the calibration-free method, the significant spectral features of the chemical elements Fe and Mn were obtained through proper alignment with the National Institute of Standards and Technology (NIST) chemical element spectral library.

Discussion

The LIBS instrument can be placed on board long-range survey vessels in the future to provide a fast, convenient, accurate, and economical detection method for deep-ocean resource exploration.
Numerical studies on internal flow in pipelines of an aquaculture vessel and flow control using a special branch pipe
Authors: Huang Wenyun , Zha Ruosi
Published: March 2023

Introduction

Regarded as the world’s largest smart-aquaculture vessel so far, Guoxin No. 1, has achieved remarkable success in aim to develop large-scale cruising aquaculture platforms. Guoxin No. 1 is 816 feet long with 15 fish farming tanks, which has a tank capacity of up to 900,000 square feet. It is of great practical interest to study the pipe flow rate distribution involving oxygen and novel flow control schemes for internal flows of aquacultural facilities connecting fish farming tanks.

Methods

In this paper, three-dimensional numerical investigations on internal flow in a T-type pipeline and its flow control are carried out. A single pump is designed to convert water to two separate farming tanks through a pipeline system, which is composed of one main inlet pipe and two outlet pipes with the same diameter as that of the inlet pipe. A horizontal arrangement of the pipes, in which the flow rate of an outlet pipe must be half of the inflow rate, is firstly studied for validation. To guarantee a balanced oxygen supply, equilibrium outflow rates can be achieved as a consequence of using a branch with a smaller diameter installed on the main inlet pipe. 3-D unsteady RANS solvers were employed to simulate the incompressible viscous flow and the pipe walls were assumed as rigid bodies.

Results

A couple of flow rates and three pipe angles were then investigated to assess the change of the outflow rates. Based on the simulations, a flow control scheme was proposed including to optimize the central included angle between the main inlet pipe and the small branch pipe, and the inflow rate of the branch pipe in order to balance the outflow rates. The results show that the central included angle has a significant influence on the flow field and flow rate of the two outlet pipes.

Discussion

If the angle was fixed, it can be indicated that adjusting the flow rate of the branch inlet can be an efficient method to unify the flow rate of the outlet pipes and improve the water exchange among fish farming tanks.
Elastic scattering of electrons by water: An ab initio study
Authors: Triggiani Francesca , Morresi Tommaso , Taioli Simone , Simonucci Stefano
Published: March 2023

In this work we devise a theoretical and computational method to compute the elastic scattering of electrons from a non-spherical potential, such as in the case of molecules and molecular aggregates. Its main feature is represented by the ability of calculating accurate wave functions for continuum states of polycentric systems via the solution of the Lippmann-Schwinger equation, including both the correlation effects and multi-scattering interference terms, typically neglected in widely used approaches, such as the Mott theory. Within this framework, we calculate the purely elastic scattering matrix elements. As a test case, we apply our scheme to the modelling of electron-water elastic scattering. The Dirac-Hartree-Fock self-consistent field method is used to determine the non-spherical molecular potential projected on a functional space spanned by Gaussian basis set. By adding a number of multi-centric radially-arranged s-type Gaussian functions, whose exponents are system-dependent and optimized to reproduce the properties of the continuum electron wave function in different energy regions, we are able to achieve unprecedented access to the description of the low energy range of the spectrum (0.001 < E < 10 eV) up to keV, finding a good agreement with experimental data and previous theoretical results. To show the potential of our approach, we also compute the total elastic scattering cross section of electrons impinging on clusters of water molecules and zundel cation. Our method can be extended to deal with inelastic scattering events and heavy-charged particles.
Whole-genome analysis showed the promotion of genetic diversity and coevolution in Staphylococcus aureus lytic bacteriophages and their hosts mediated by prophages via worldwide recombination events
Authors: Zhou Wenyuan , Li Yajie , Xu Xuechao , Rao Shengqi , Wen Hua , Han Yeiling , Deng Aiping , Zhang Zhenwen , Yang Zhenquan , Zhu Guoqiang
Published: March 2023

Prophages as a part of Staphylococcus aureus genome contribute to the genetic diversity as well as survival strategies of their host. Some S. aureus prophages also have an imminent risk of host cell lysis and become a lytic phage. Nonetheless, interactions among S. aureus prophages, lytic phages, and their hosts, as well as the genetic diversity of S. aureus prophages, remain unclear. We identified 579 intact and 1,389 incomplete prophages in the genomes of 493 S. aureus isolates obtained from the NCBI database. The structural diversity and gene content of intact and incomplete prophages were investigated and compared with 188 lytic phages. Mosaic structure comparison, ortholog group clustering, phylogenetic analysis, and recombination network analysis were performed to estimate genetic relatedness among S. aureus intact prophages, incomplete prophages, and lytic phages. The intact and incomplete prophages harbored 148 and 522 distinct mosaic structures, respectively. The major difference between lytic phages and prophages was the lack of functional modules and genes. Compared to the lytic phages, both the S. aureus intact and incomplete prophages harbored multiple antimicrobial resistance (AMR) and virulence factor (VF) genes. Several functional modules of lytic phages 3_AJ_2017 and 23MRA shared more than 99% nucleotide sequence identity with S. aureus intact (ST20130943_p1 and UTSW_ MRSA_55_ip3) and incomplete prophages (SA3_LAU_ip3 and MRSA_FKTN_ip4); other modules showed little nucleotide sequence similarity. Ortholog and phylogenetic analyses revealed a common gene pool shared between the prophages and lytic Siphoviridae phages. Moreover, most shared sequences existed within intact (43428/137294, 31.6%) and incomplete prophages (41248/137294, 30.0%). Therefore, the maintenance or loss of functional modules in intact and incomplete prophages is key to balance the costs and benefits of large prophages harboring various AMR and VF genes in the bacterial host. The shared identical functional modules between S. aureus lytic phages and prophages are likely to result in the exchange, acquisition, and loss of functional modules, and therefore contribute to their genetic diversity. Moreover, constant recombination events within prophages globally were responsible for the coevolution of lytic phages and their bacterial hosts.
Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers
Authors: Okoye Jennifer C. , Holland Alexandria , Pitoulias Matthaios , Paschalis Vasileios , Piddubnyi Artem , Dufailu Osman A. , Borén Thomas , Oldfield Neil J. , Mahdavi Jafar , Soultanas Panos
Published: March 2023

Campylobacter jejuni colonizes hosts by interacting with Blood Group Antigens (BgAgs) on the surface of gastrointestinal epithelia. Genetic variations in BgAg expression affects host susceptibility to C. jejuni. Here, we show that the essential major outer membrane protein (MOMP) of C. jejuni NCTC11168 binds to the Lewis b (Leb) antigen on the gastrointestinal epithelia of host tissues and this interaction can be competitively inhibited by ferric quinate (QPLEX), a ferric chelate structurally similar to bacterial siderophores. We provide evidence that QPLEX competitively inhibits the MOMP-Leb interaction. Furthermore, we demonstrate that QPLEX can be used as a feed additive in broiler farming to significantly reduce C. jejuni colonization. Our results indicate that QPLEX can be a viable alternative to the preventative use of antibiotics in broiler farming to combat C. jejuni infections.
Temperature-controlled optical switch metasurface with large local field enhancement based on FW-BIC
Authors: Wang Xiuyu , Wang Xiaoman , Ren Qun , Cai Haocheng , Xin Jihong , Lang Yuxin , Xiao Xiaofei , Lan Zhihao , You Jianwei , Sha Wei E. I.
Published: March 2023

Introduction: Many researchers have explored the bound states in the continuum (BICs) as a particular bound wave state which can be used to achieve a very high Q-factor. High-Q factor devices, typically based on the bound states in the continuum (BICs), are well used in the fields of hypersensitive biochemical sensors, non-linear effects enhancement, plasmon lasers, and hi-performance filtering. However, symmetrical-protected BIC is difficult to achieve experimentally high-Q factor because it strongly depends on the geometry and can be destroyed by any slight disturbance in the potential well.

Methods: Therefore, we proposed a parameter-adjusted Friedrich-Wintergen BIC based on the analysis model of time-coupled model theory, where the target system parameters can be tuned to achieve high-Q excitation.

Results: Moreover, considering the tunability and flexibility of the components in various practical applications, we integrate active materials into metasurface arrays with the help of external stimuli to achieve modulation of high-Q resonances. Our results demonstrate that an optical resonator based on FW-BIC can modulate the BIC state by changing the intermediate gap.

Discussion: The BIC state and the high-Q factor Fano resonance can be dynamically tuned by adding temperature-sensitive VO2 material.
Recurrent Acute Disseminated Encephalomyelitis (ADEM) after COVID-19-vaccination and after subsequent COVID-19-infection: A case report (part II)
Authors: Poli Khouloud , Kowarik Markus , Hamprecht Klaus , Iftner Thomas , Ernemann Ulrike , Ziemann Ulf , Poli Sven
Published: March 2023

Acute disseminated encephalomyelitis (ADEM) is an autoimmune disorder of the central nervous system (CNS), which is commonly associated to previous viral infection or immunization. Cases of ADEM with a potential relationship to both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination have been reported. We recently published a rare case of a 65-year-old patient who suffered from a corticosteroid- and immunoglobulin-refractory multiple autoimmune syndrome including ADEM following Pfizer-BioNTech coronavirus disease (COVID)-19 vaccination, and whose symptoms largely resolved after repeated plasma exchange (PE). Four months later, the patient was diagnosed with SARS-CoV-2 omicron variant infection after experiencing mild upper respiratory tract symptoms. Few days later, the patient developed severe tetraparesis with magnetic resonance imaging (MRI) showing multiple new inflammatory contrast-enhancing lesions in the left middle cerebellar peduncle, cervical spinal cord, and ventral conus medullaris. Repeated cerebrospinal fluid (CSF) analyses indicated blood-brain barrier damage (increased albumin ratio) without signs of SARS-CoV-2 invasion (mild pleocytosis, no intrathecal antibody production). SARS-CoV-2 specific immunoglobulin G (IgG) were detected in serum and to a much lower degree in CSF with close correlation between both concentrations over time, reflecting antibody dynamics of vaccine- and infection-induced immune response, and blood-brain barrier patency. Daily PE therapy was initiated. Given the patient's lack of improvement after seven PE, treatment with rituximab was considered. After a first dose, however, the patient suffered epididymo-orchitis leading to sepsis, and declined rituximab continuation. At 3-months follow-up, clinical symptoms had dramatically improved. The patient regained walking ability without assistance. This case of recurrent ADEM after COVID-19-vaccination and after subsequent COVID-19-infection strongly supports the hypotheses of neuroimmunological complications in these conditions being promoted by a systemic immune response and mediated by molecular mimicry of, both, viral and vaccine SARS-CoV-2 antigens and CNS self-antigens.
Natural products targeting cellular processes common in Parkinson's disease and multiple sclerosis
Authors: Xu Xuxu , Han Chaowei , Wang Pengcheng , Zhou Feimeng
Published: March 2023

The hallmarks of Parkinson's disease (PD) include the loss of dopaminergic neurons and formation of Lewy bodies, whereas multiple sclerosis (MS) is an autoimmune disorder with damaged myelin sheaths and axonal loss. Despite their distinct etiologies, mounting evidence in recent years suggests that neuroinflammation, oxidative stress, and infiltration of the blood-brain barrier (BBB) all play crucial roles in both diseases. It is also recognized that therapeutic advances against one neurodegenerative disorder are likely useful in targeting the other. As current drugs in clinical settings exhibit low efficacy and toxic side effects with long-term usages, the use of natural products (NPs) as treatment modalities has attracted growing attention. This mini-review summarizes the applications of natural compounds to targeting diverse cellular processes inherent in PD and MS, with the emphasis placed on their neuroprotective and immune-regulating potentials in cellular and animal models. By reviewing the many similarities between PD and MS and NPs according to their functions, it becomes evident that some NPs studied for one disease are likely repurposable for the other. A review from this perspective can provide insights into the search for and utilization of NPs in treating the similar cellular processes common in major neurodegenerative diseases.
Olfactory neuronal cells as a promising tool to realize the “druggable genome” approach for drug discovery in neuropsychiatric disorders
Authors: Mihaljevic Marina , Lam Max , Ayala-Grosso Carlos , Davis-Batt Finn , Schretlen David J. , Ishizuka Koko , Yang Kun , Sawa Akira
Published: March 2023

“Druggable genome” is a novel concept that emphasizes the importance of using the information of genome-wide genetic studies for drug discovery and development. Successful precedents of “druggable genome” have recently emerged for some disorders by combining genomic and gene expression profiles with medical and pharmacological knowledge. One of the key premises for the success is the good access to disease-relevant tissues from “living” patients in which we may observe molecular expression changes in association with symptomatic alteration. Thus, given brain biopsies are ethically and practically difficult, the application of the “druggable genome” approach is challenging for neuropsychiatric disorders. Here, to fill this gap, we propose the use of olfactory neuronal cells (ONCs) biopsied and established via nasal biopsy from living subjects. By using candidate genes that were proposed in a study in which genetic information, postmortem brain expression profiles, and pharmacological knowledge were considered for cognition in the general population, we addressed the utility of ONCs in the “druggable genome” approach by using the clinical and cell resources of an established psychosis cohort in our group. Through this pilot effort, we underscored the chloride voltage-gated channel 2 (CLCN2) gene as a possible druggable candidate for early-stage psychosis. The CLCN2 gene expression was associated with verbal memory, but not with other dimensions in cognition, nor psychiatric manifestations (positive and negative symptoms). The association between this candidate molecule and verbal memory was also confirmed at the protein level. By using ONCs from living subjects, we now provide more specific information regarding molecular expression and clinical phenotypes. The use of ONCs also provides the opportunity of validating the relationship not only at the RNA level but also protein level, leading to the potential of functional assays in the future. Taken together, we now provide evidence that supports the utility of ONCs as a tool for the “druggable genome” approach in translational psychiatry.
Triptolide inhibits the progression of Glioblastoma U251 cells via targeting PROX1
Authors: Yuan Chao , Liao Yanli , Liao Shengjie , Huang Mi , Li Duanzhuo , Wu Weibin , Quan Yi , Li Liqiang , Yu Xin , Si Wenxia
Published: March 2023

Background

Glioblastoma multiforme (GBM) is the most lethal brain cancer in adults, characterized by rapid growth, extensive invasiveness, and poor prognosis, and there is still a lack of effective treatments. Here, we aimed to explore the role of triptolide (TPL), purified from Tripterygium wilfordii Hook F, on glioblastoma cell growth, apoptosis, proliferation, migration and invasion, as well as potential underlying mechanisms.

Methods

The publicly available clinical data of Brain Lower Grade Glioma (LGG) from The Cancer Genome Atlas (TCGA) had been screened to observe PROX1 expression. The Kaplan-Meier analysis was used to analyze the relationship between PROX1 expression and GBM prognosis. CCK8, cell cycle, EDU, apoptosis, wound healing, and transwell assays were performed to detect the effects of TPL on glioblastoma U251 cell viability, cell cycle, proliferation, apoptosis, migration and invasion, respectively. Further, a soft agar colony assay was used to calculate the growth of glioblastoma cells. The qRT-PCR and western blot were conducted to quantify PROX1 mRNA and protein levels. The transcriptional regulation of TPL was detected by Dual luciferase reporter assay.

Results

We found that TPL inhibited glioblastoma cell viability, proliferation, cell cycle, migration and invasion, but enhanced apoptosis in a dose-dependent manner. The expression of cell cycle inhibitor, P21, and pro-apoptosis factor, Bax was increased, while invasion-related factors MMP2 and MMP9 were silenced after TPL treatments. Mechanistically, TPL showed transcriptional inhibition of PROX1 appearance. Moreover, ectopic expression of PROX1 partially rescued the effects of TPL on glioblastoma cell viability, proliferation, apoptosis, migration and invasion, and on the expression of cell function-related genes.

Conclusion

This study verified that TPL inhibited the progression of glioblastoma cells by transcriptionally depressing the expression of PROX1.
LIM1 contributes to the malignant potential of endometrial cancer
Authors: Kato Hiroaki , Saeki Noritaka , Imai Matome , Onji Hiroshi , Yano Akiko , Yoshida Shuhei , Sakaue Tomohisa , Fujioka Toru , Sugiyama Takashi , Imai Yuuki
Published: March 2023

Introduction

The incidence of endometrial cancer (EC) has been increasing worldwide. However, because there are limited chemotherapeutic options for the treatment of EC, the prognosis of advanced-stage EC is poor.

Methods

Gene expression profile datasets for EC cases registered in The Cancer Genome Atlas (TCGA) was reanalyzed. Highly expressed genes in advanced-stage EC (110 cases) compared with early-stage EC (255 cases) were extracted and Gene Ontology (GO) enrichment analysis was performed. Among the enriched genes, Kaplan-Meier (KM) plotter analysis was performed. Candidate genes expression was analyzed in HEC50B cells and Ishikawa cells by RT-qPCR. In HEC50B cells, LIM homeobox1 (LIM1) was knocked down (KD) and cell proliferation, migration, and invasion ability of the cells were evaluated. Xenografts were generated using LIM1-KD cells and tumor growth was evaluated. Ingenuity Pathway Analysis (IPA) of RNA-seq data using LIM-KD cells was performed. Expression of phospho-CREB and CREB-related proteins were evaluated in LIM1-KD cells by western blotting and in xenograft tissue by immunofluorescent staining. Two different CREB inhibitors were treated in HEC50B and cell proliferation was evaluated by MTT assay.

Results

Reanalysis of TCGA followed by GO enrichment analysis revealed that homeobox genes were highly expressed in advanced-stage EC. Among the identified genes, KM plotter analysis showed that high LIM1 expression was associated with a significantly poorer prognosis in EC. Additionally, LIM1 expression was significantly higher in high-grade EC cell lines, HEC50B cells than Ishikawa cells. Knockdown of LIM1 showed reduced cell proliferation, migration and invasion in HEC50B cells. Xenograft experiments revealed that tumor growth was significantly suppressed in LIM1-KD cells. IPA of RNA-seq data using LIM-KD cells predicted that the mRNA expression of CREB signaling-related genes was suppressed. Indeed, phosphorylation of CREB was decreased in LIM1-KD cells and LIM1-KD cells derived tumors. HEC50B cells treated by CREB inhibitors showed suppression of cell proliferation.

Conclusion and discussion

Collectively, these results suggested that high LIM1 expression contributed to tumor growth via CREB signaling in EC. Inhibition of LIM1 or its downstream molecules would be new therapeutic strategies for EC.
Ginseng-based carbon dots inhibit the growth of squamous cancer cells by increasing ferroptosis
Authors: Wang Zilin , Han Jing , Guo Zhiyong , Wu Hao , Liu Yige , Wang Wenying , Zhang Chenping , Liu Jiannan
Published: March 2023

Background

Recent studies indicated that Ginseng potentiate cancer treatments. Ginseng-based carbon dots (GCDs) might possess properties to kill cancer cells and inhibit malignant tumor development and invasion. This study aimed to prepare GCDs, examine their effects on cancer cell growth and invasion, and explore the mechanisms involved.

Methods

GCDs were synthesized, purified, and characterized. Cells were cultured with GCDs and were tested for growth, invasiveness, and wound healing. RNA was extracted for transcriptomics analysis. Protein expression was evaluated using western blot and immunohistochemistry. Mice were injected with cancer cells and treated with PBS or GCDs. Tumor volume was evaluated.

Results

GCDs were successfully synthesized and purified. The solution was yellow under sunlight and fluorescent blue under ultraviolet light. Electron microscopy showed GCDs with a uniform shape without apparent aggregation and an average diameter of about 4 nm. GCDs inhibited Cal-27, SCC-25, and SCC-7 cancer cell growth at concentrations of >250-300 μg/mL, while GCDs inhibited the non-cancerous HaCaT cells at concentrations >400 μg/mL. Immunofluorescence showed that GCDs could enter the cells. Transcriptomics revealed 552 downregulated mRNAs and 338 upregulated ones, including mRNAs involved in the oxidative phosphorylation and ferroptosis pathways. GCDs induced the ferroptosis of cancer cells, as shown by decreased GPX-4 and increased COX-2. GCDs decreased cell invasion and migration. In vivo, GCDs decreased tumor growth without apparent organ toxicity and promoted CD4+ T cell infiltration in the tumor.

Conclusion

GCDs appear to possess anticancer properties by increasing ferroptosis, resulting in cancer cell growth inhibition in vitro and in vivo.
M1 macrophage predicted efficacy of neoadjuvant camrelizumab combined with chemotherapy vs chemotherapy alone for locally advanced ESCC: A pilot study
Authors: Wang Shu , Xu Guanghui , Li Mengbin , Zheng Jiyang , Wang Yuhao , Feng Xiangying , Luo Jialin , Wang Shibo , Liu Huan , Duan Weiming , Zhang Hushan , Huang Depei , Zhao Feilong , Nie Yongzhan , Yang Jianjun
Published: March 2023

Introduction

The efficacy and safety of immunotherapy have been widely recognized in gastrointestinal-related cancers. However, the efficacy of neoadjuvant camrelizumab for locally advanced esophageal squamous cell carcinoma (ESCC) has not been firmly established. This study compared the efficacy of camrelizumab in combination with neoadjuvant DCF (docetaxel, cisplatin and fluorouracil), with DCF alone for ESCC, and exploring biomarkers related to immune infiltration of the ESCC immunotherapy response.

Methods

We enrolled and randomly assigned patients with stage II-IVa ESCC to two study treatments: camrelizumab combined with docetaxel, cisplatin and fluorouracil (DCF) regimen and DCF regimen alone. The tissue for multiplex immunofluorescence (mIF) was obtained before and after neoadjuvant therapy. The Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1) and Tumor Regression Grade (TRG) was used to evaluate efficacy.

Results

A total of 30 patients were enrolled in the study. Following neoadjuvant camrelizumab, the objective response rate (ORR) and the disease control rate (DCR) were 46.7% (7/15) and 95.7% (14/15), respectively. No patients reported complete remission, while ORR and DCR in the chemotherapy group were 26.7% (4/15) and 86.7% (13/15), respectively. R0 resection after neoadjuvant treatment was achieved in 3 out of 15 patients in the combined group and in all patients (15/15) in the chemotherapy group. In the combined group, M1-type tumor-associated macrophages and CD56dim NK cells were more abundant in responders than in non-responders (p < 0.05). A higher M1/M2 ratio was observed in responders (p < 0.05). With respect to the NGS, among the copy number amplified genes, the 11q13 amplicon (CCND1/FGF19/FGF4/FGF3) showed the highest frequency (47%, 7/15).

Conclusions

Neoadjuvant camrelizumab combined with chemotherapy improved ORR in locally advanced ESCC. M1-type tumor-associated macrophages and CD56dim NK cells might be utilized to predict camrelizumab efficacy.
Premature birth associated with a favorable course in gestational alloimmune liver disease (GALD): A case report
Authors: Mulzer Linda-Marie , Reutter Heiko , Jüngert Jörg , Knisely A. S. , Schmid Margit , Hoerning André , Morhart Patrick
Published: March 2023

Gestational alloimmune liver disease (GALD) is a rare neonatal disorder with high mortality and morbidity. The patients come to caregivers' attention aged a few hours or days. The disease manifests as acute liver failure with or without siderosis. The differential diagnosis of neonatal acute liver failure (NALF) is broad, including mainly immunologic, infectious, metabolic and toxic disorders. The most common cause, however, is GALD followed by herpes simplex virus (HSV) infection. The best suited pathophysiological paradigm of GALD is that of a maternofetal alloimmune disorder. State of the art treatment combines intravenously administered immunoglobulin (IVIG) with exchange transfusion (ET). We report an infant born at 35 + 2 weeks' gestation in whom GALD had a favorable course, of interest because premature birth in our patient may have exerted protective aspects and lessened morbidity in that intrauterine exposure to maternal complement-fixing antibodies was shortened. The diagnosis of GALD was challenging and difficult. We suggest a modified diagnostic algorithm combining clinical findings with histopathologic findings in liver and lip mucosa and, if available, on abdominal magnetic resonance imaging-study focusing on the liver, spleen, and pancreas. This diagnostic workup must be followed by ET and subsequent administration of IVIG without delay.
Case report: De novo SAMD9L truncation causes neonatal-onset autoinflammatory syndrome which was successfully treated with hematopoietic stem cell transplantation
Authors: Caldirola María Soledad , Seminario Analía Gisela , Luna Paula Carolina , Curciarello Renata , Docena Guillermo Horacio , Fernandez Escobar Nicolás , Drelichman Guillermo , Gattorno Marco , de Jesus Adriana A. , Goldbach-Mansky Raphaela , Gaillard María Isabel , Bezrodnik Liliana
Published: March 2023

During recent years, the identification of monogenic mutations that cause sterile inflammation has expanded the spectrum of autoinflammatory diseases, clinical disorders characterized by uncontrolled systemic and organ-specific inflammation that, in some cases, can mirror infectious conditions. Early studies support the concept of innate immune dysregulation with a predominance of myeloid effector cell dysregulation, particularly neutrophils and macrophages, in causing tissue inflammation. However, recent discoveries have shown a complex overlap of features of autoinflammation and/or immunodeficiency contributing to severe disease phenotypes. Here, we describe the first Argentine patient with a newly described frameshift mutation in SAMD9L c.2666delT/p.F889Sfs*2 presenting with a complex phenotypic overlap of CANDLE-like features and severe infection-induced cytopenia and immunodeficiency. The patient underwent a fully matched unrelated HSCT and has since been in inflammatory remission 5 years post-HSCT.
Early recovery of cognition and brain plasticity after surgery in children with low-grade frontal lobe tumors
Authors: Zheng Wenjian , Guan Xueyi , Zhang Xianchang , Gong Jian
Published: March 2023

Background

Low-grade frontal lobe tumors (LGFLT) can be cured through total resection, but surgical trauma could impair higher-order cognitive function. We aim to characterize the short-term natural cognitive recovery and brain plasticity in surgically-treated pediatric patients with LGFLT.

Methods

Ten pediatric patients with LGFLT were enrolled. Their cognitive function was assessed before the surgery (S0), in the first month post-surgery (S1), and 3–6 months post-surgery (S2), using the CNS Vital Signs battery. DTI and rs-fMRI were performed during the same time periods. Changes of cognition and image metrics between S1>S0 and S2>S1 were analyzed.

Results

The Motor Speed (MotSp) and Reaction Time (RT) scores significantly decreased in S1 and recovered in S2. Rs-fMRI showed decreased functional connectivity (FC) between the bilateral frontal lobes and bilateral caudates, putamina, and pallidi in S1>S0 (voxel threshold p-unc < 0.001, cluster threshold p-FDR < 0.05). In S2>S1, FC recovery was observed in the neighboring frontal cortex areas (p-unc <0.001, p-FDR < 0.05). Among them, the FC in the caudates-right inferior frontal gyri was positively correlated to the RT (p-FDR < 0.05). A DTI Tract-based spatial statistics (TBSS) analysis showed decreased fractional anisotropy and axial diffusivity mainly in the corticospinal tracts, cingulum, internal capsule, and external capsule at 0–6 months post-surgery (TFCE-p < 0.05). The DTI metrics were not associated with the cognitive data.

Conclusion

Processing speed impairment after an LGFLT resection can recover naturally within 3–6 months in school-age children. Rs-fMRI is more sensitive to short-term brain plasticity than DTI TBSS analysis. “Map expansion” plasticity in the frontal-basal ganglia circuit may contribute to the recovery.
Classification, diagnosis and clinical strategy of congenital coronary artery disease in children
Authors: Feng Juan , Zhao Jingshu , Li Jun , Sun Zhenyun , Li Qiao
Published: March 2023

Some of the congenital coronary artery diseases in children have potential life-threatening complications. In addition to anatomical classification, the peadiatricians should pay more attention to the risk of adverse cardiac events classification; and then, they can eventrually make the personalized guidance suggestions and treatment decisions according to different diseases.