bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine
Authors: Dominelli Federica , Zingaropoli Maria Antonella , Tartaglia Matteo , Tortellini Eeva , Guardiani Mariasilvia , Perri Valentina , Pasculli Patrizia , Ciccone Federica , Malimpensa Leonardo , Baione Viola , Napoli Anna , Gaeta Aurelia , Lichtner Miriam , Conte Antonella , Mastroianni Claudio Maria , Ciardi Maria Rosa
Published: December 2022

Background

The mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to vaccination.

Methods

The aim of the study was to evaluate humoral and specific T-cell response, as well as B-cell activation and survival factors, in people with MS (pwMS) under DMTs before (T0) and after two months (T1) from the third dose of vaccine, comparing the obtained findings to healthy donors (HD). All possible combinations of intracellular IFNγ, IL2 and TNFα T-cell production were evaluated, and T-cells were labelled “responding T-cells”, those cells that produced at least one of the three cytokines of interest, and “triple positive T-cells”, those cells that produced simultaneously all the three cytokines.

Results

The cross-sectional evaluation showed no significant differences in anti-S antibody titers between pwMS and HD at both time-points. In pwMS, lower percentages of responding T-cells at T0 (CD4: p=0.0165; CD8: p=0.0022) and triple positive T-cells at both time-points compared to HD were observed (at T0, CD4: p=0.0007 and CD8: p=0.0703; at T1, CD4: p=0.0422 and CD8: p=0.0535). At T0, pwMS showed higher plasma levels of APRIL, BAFF and CD40L compared to HD (p<0.0001, p<0.0001 and p<0.0001, respectively) and at T1, plasma levels of BAFF were still higher in pwMS compared to HD (p=0.0022).

According to DMTs, at both T0 and T1, lower anti-S antibody titers in the depleting/sequestering-out compared to the enriching-in pwMS subgroup were found (p=0.0410 and p=0.0047, respectively) as well as lower percentages of responding CD4+ T-cells (CD4: p=0.0394 and p=0.0004, respectively). Moreover, the depleting/sequestering-out subgroup showed higher percentages of IFNγ-IL2-TNFα+ T-cells at both time-points, compared to the enriching-in subgroup in which a more heterogeneous cytokine profile was observed (at T0 CD4: p=0.0187; at T0 and T1 CD8: p =0.0007 and p =0.0077, respectively).

Conclusion

In pwMS, humoral and T-cell response to vaccination seems to be influenced by the different DMTs. pwMS under depleting/sequestering-out treatment can mount cellular responses even in the presence of a low positive humoral response, although the cellular response seems qualitatively inferior compared to HD. An understanding of T-cell quality dynamic is needed to determine the best vaccination strategy and in general the capability of immune response in pwMS under different DMT.
SARS-CoV-2 infection of phagocytic immune cells and COVID-19 pathology: Antibody-dependent as well as independent cell entry
Authors: Matveeva Olga , Nechipurenko Yury , Lagutkin Denis , Yegorov Yegor E. , Kzhyshkowska Julia
Published: December 2022

Our review summarizes the evidence that COVID-19 can be complicated by SARS-CoV-2 infection of immune cells. This evidence is widespread and accumulating at an increasing rate. Research teams from around the world, studying primary and established cell cultures, animal models, and analyzing autopsy material from COVID-19 deceased patients, are seeing the same thing, namely that some immune cells are infected or capable of being infected with the virus. Human cells most vulnerable to infection include both professional phagocytes, such as monocytes, macrophages, and dendritic cells, as well as nonprofessional phagocytes, such as B-cells. Convincing evidence has accumulated to suggest that the virus can infect monocytes and macrophages, while data on infection of dendritic cells and B-cells are still scarce. Viral infection of immune cells can occur directly through cell receptors, but it can also be mediated or enhanced by antibodies through the Fc gamma receptors of phagocytic cells. Antibody-dependent enhancement (ADE) most likely occurs during the primary encounter with the pathogen through the first COVID-19 infection rather than during the second encounter, which is characteristic of ADE caused by other viruses. Highly fucosylated antibodies of vaccinees seems to be incapable of causing ADE, whereas afucosylated antibodies of persons with acute primary infection or convalescents are capable. SARS-CoV-2 entry into immune cells can lead to an abortive infection followed by host cell pyroptosis, and a massive inflammatory cascade. This scenario has the most experimental evidence. Other scenarios are also possible, for which the evidence base is not yet as extensive, namely productive infection of immune cells or trans-infection of other non-immune permissive cells. The chance of a latent infection cannot be ruled out either.
Integrated bioinformatics to identify potential key biomarkers for COVID-19-related chronic urticaria
Authors: Zhang Teng , Feng Hao , Zou Xiaoyan , Peng Shixiong
Published: December 2022

Background

A lot of studies have revealed that chronic urticaria (CU) is closely linked with COVID-19. However, there is a lack of further study at the gene level. This research is aimed to investigate the molecular mechanism of COVID-19-related CU via bioinformatic ways.

Methods

The RNA expression profile datasets of CU (GSE72540) and COVID-19 (GSE164805) were used for the training data and GSE57178 for the verification data. After recognizing the shared differently expressed genes (DEGs) of COVID-19 and CU, genes enrichment, WGCNA, PPI network, and immune infiltration analyses were performed. In addition, machine learning LASSO regression was employed to identify key genes from hub genes. Finally, the networks, gene-TF-miRNA-lncRNA, and drug-gene, of key genes were constructed, and RNA expression analysis was utilized for verification.

Results

We recognized 322 shared DEGs, and the functional analyses displayed that they mainly participated in immunomodulation of COVID-19-related CU. 9 hub genes (CD86, FCGR3A, AIF1, CD163, CCL4, TNF, CYBB, MMP9, and CCL3) were explored through the WGCNA and PPI network. Moreover, FCGR3A, TNF, and CCL3 were further identified as key genes via LASSO regression analysis, and the ROC curves confirmed the dependability of their diagnostic value. Furthermore, our results showed that the key genes were significantly associated with the primary infiltration cells of CU and COVID-19, such as mast cells and macrophages M0. In addition, the key gene-TF-miRNA-lncRNA network was constructed, which contained 46 regulation axes. And most lncRNAs of the network were proved to be a significant expression in CU. Finally, the key gene-drug interaction network, including 84 possible therapeutical medicines, was developed, and their protein-protein docking might make this prediction more feasible.

Conclusions

To sum up, FCGR3A, TNF, and CCL3 might be potential biomarkers for COVID-19-related CU, and the common pathways and related molecules we explored in this study might provide new ideas for further mechanistic research.
Near-infrared upconversion multimodal nanoparticles for targeted radionuclide therapy of breast cancer lymphatic metastases
Authors: Zhang Chuan , Zhang Yujuan , Liang Maolin , Shi Xiumin , Jun Yan , Fan Longfei , Yang Kai , Wang Feng , Li Wei , Zhu Ran
Published: December 2022

The theranostics of lymph node metastasis has always been one of the major obstacles to defeating breast cancer and an important decisive factor in the prognosis of patients. Herein, we design NaGdF4:Yb,Tm@NaLuF4 upconversion nanoparticles with PEG and anti-HER2 monoclonal antibody (trastuzumab, Herceptin) (NP-mAb), the delivery of NP-mAb through the lymphatic system allows for effective targeting and accumulation in lymphatic metastasis. Combination of radionuclides 68Ga and 177Lu could be chelated by the bisphosphate groups of NP-mAb. The obtained nanoprobe (NP-mAb) and nanonuclear drug (68Ga-NP-mAb or 177Lu-NP-mAb) exhibited excellent stability and show high accumulation and prolong retention in the lymph node metastasis after intratumoral injection into the foot pad by near-infrared fluorescence (NIRF), single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging. Utilizing the β-rays released by 177Lu, 177Lu-NP-mAb could not only decrease the incidence of lymph node metastasis, but also significantly decrease the volumes of lymph node metastasis. Additionally, 177Lu-NP-mAb induce no obvious toxicity to treated mice through blood routine, liver and kidney function assay. Therefore, nanoprobe and nanonuclear drug we designed could be acted as excellent theranostics agents for lymph node metastasis, providing potential alternatives diagnose and treatment option for lymph node metastasis.
Defective antifungal immunity in patients with COVID-19
Authors: Morton Charles Oliver , Griffiths James S. , Loeffler Juergen , Orr Selinda , White P. Lewis
Published: December 2022

The COVID-19 pandemic has placed a huge strain on global healthcare and been a significant cause of increased morbidity and mortality, particularly in at-risk populations. This disease attacks the respiratory systems and causes significant immune dysregulation in affected patients creating a perfect opportunity for the development of invasive fungal disease (IFD). COVID-19 infection can instill a significant, poorly regulated pro-inflammatory response. Clinically induced immunosuppression or pro-inflammatory damage to mucosa facilitate the development of IFD and Aspergillus, Mucorales, and Candida infections have been regularly reported throughout the COVID-19 pandemic. Corticosteroids and immune modulators are used in the treatment of COVID-19. Corticosteroid use is also a risk factor for IFD, but not the only reason for IFD in COVID -19 patients. Specific dysregulation of the immune system through functional exhaustion of Natural killer (NK) cells and T cells has been observed in COVID-19 through the expression of the exhaustion markers NK-G2A and PD-1. Reduced fungicidal activity of neutrophils from COVID-19 patients indicates that immune dysfunction/imbalance are important risk factors for IFD. The COVID-19 pandemic has significantly increased the at-risk population for IFD. Even if the incidence of IFD is relatively low, the size of this new at-risk population will result in a substantial increase in the overall, annual number of IFD cases. It is important to understand how and why certain patients with COVID-19 developed increased susceptibility to IFD, as this will improve our understanding of risk of IFD in the face of future pandemics but also in a clinical era of increased clinical immuno-suppression/modulation.
Applying behavioral studies to the ecotoxicology of corals: A case study on Acropora millepora
Authors: Roepke Lisa K. , Brefeld David , Soltmann Ulrich , Randall Carly J. , Negri Andrew P. , Kunzmann Andreas
Published: December 2022

Behavioral responses are considered sensitive and effective indicators of organism stress. As the demand for standardized coral toxicity tests grows, innovative tools that allow for automatic and quantitative measurements of these behaviors may complement ecotoxicological studies. The rapid growth of competitive marine algae in aquaculture systems is a major issue for generating coral spat for reef restoration, and the application of non-toxic antifouling (AF) coatings might effectively mitigate this issue. While these coatings do not appear to be toxic to sensitive coral larvae, their potential to affect larval mobility has not been tested. In this context, we tested the effect of three recently-developed and potentially non-toxic AF coatings: (i) antiadhesive, (ii) cerium dioxide (CeO2-x) nanoparticle, and (iii) encapsulated biocide dichlorooctylisothiazolinone (DCOIT) on the swimming velocity and activity of Acropora millepora coral larvae for potential use in reef-restoration activities. The behavior of 32 coral larvae per AF treatment were recorded, each for 25 min, in a self-constructed dark box with two camera recording sets in parallel. The tracking analysis was performed with the software Noldus EthoVision XT. The mean larval swimming velocity on control tiles of 93.1 ± 5.6 mm min-1 (and activity of 62.8 ± 5.2%) was nearly 2-fold faster (higher) than on the antiadhesive, (CeO2-x) nanoparticle and DCOIT coatings, respectively. Larvae exposed to the DCOIT-coated tiles remained almost stationary. Although the underlying cause and consequence of these results require further investigation, tracking of coral larval swimming behavior was identified as a reliable and feasible method for assessing potential non-lethal responses to AF coatings. As changes in behavior could have significant consequences for larval survival and settlement, they are important endpoints to consider, and the quantification of behavioral responses may be a meaningful and sensitive tool. Therefore, we recommend the use of behavioral studies for coral larval assessments in ecotoxicology as a valuable endpoint. For methodological standardization and implementation, our study also features a detailed guide for video-processing and track analysis of A. millepora coral larvae in EthoVision.
Variational parameter estimation in a two-equation turbulence model: A case study with a 3D primitive-equation ocean model
Authors: Hu Yan , Zhang Xuefeng , Li Wei
Published: December 2022

A three-dimensional and complete adjoint model of the Princeton Ocean Model with a generalized coordinate system (POMgcs) is developed to construct the 4D-Variational data assimilation (4D-Var) algorithm in this study. Uncertain parameters in the Mellor-Yamada 2.5 turbulence submodel (MY-2.5) which is enclosed in POMgcs, are tentatively estimated via the 4D-VAR algorithm within a biased model framework. Here, the control variables in the biased model are set to two uncertain wave-affected parameters (wave energy factor α and Charnock coefficient β ) in the MY-2.5 turbulence model, which play a crucial role in modulating the heat content distribution in the upper coastal sea. First of all, the ocean temperature and salinity in a typical coastal sea, Bohai Sea, are simulated by the model to validate the rationally of the MY-2.5 parameterization scheme for both constructing the “truth model” and generating the “pseudo-observations” in the data assimilation studies. Then, after thoroughly testing the ability of the 4D-Var to optimize the initial state fields of the POMgcs model, a series of parameter estimation experiments are carried out to investigate whether and to what degree the parameters embedded in high-order turbulence models can be significantly optimized. Results of parameter estimation with perfect initial fields show the two estimated parameters in the MY-2.5 submodel can successfully converge to the “truth” value. The local minimum of the cost function can be effectively and efficiently jumped out once two kinds of optimization algorithms, LBFGS and LMBM, are jointly used. In addition, the estimated parameter will converge to the optimal value rather than the truth one to compensate for the initial field error when the state-parameter are estimated simultaneously. Further, the performance of the parameter estimation is also deeply discussed when the observation samples are noised. Finally, prescribing the initial field and parameter as error source, a forecasting experiment for sea temperature is performed. The experiment results indicate that assimilating “pseudo-observations” to the model based on 4D-Var can significantly improve the sea temperature simulation. Moreover, adjusting the initial field and parameter leads to a better result than the only initial field, and this conclusion is more evident at the surface than in the deeper ocean.
An evolutionary game study of environmental regulation strategies for marine ecological governance in China
Authors: Gao Lehua , Yan An , Yin Qiaorong
Published: December 2022

The choice of environmental regulation strategies for marine ecological pollution governance is vital for China’s promotion of collaborative marine ecological management. First, based on the assumption of limited rationality, we established a three-party evolutionary game model of China’s central government, local governments, and marine enterprises from the perspective of environmental policy to explore the dynamic evolution process of the game strategies of the three participants and the stability of the system equilibrium point. Second, we used numerical simulations to investigate how the incentive- and penalty-based policies of central and local governments have different effects on local governments and marine enterprises, respectively. Finally, we introduced a reputation loss model of public participation to explore the game strategy choices of the three parties under public participation. The finding reveal that (1) Local governments are more sensitive to the central government’s punishment policies than marine enterprises are. (2) Increasing the punishment of local governments on enterprises can simultaneously enhance the willingness of enterprises to govern and the willingness of local governments to implement. Moreover, the local governments policy of punishing enterprises was more direct and effective than that of the central government. (3) Although local governments subsidies for marine enterprises can increase their probability of governing marine ecology, they can also decrease local governments' willingness to implement. Finally, (4) Public participation can quickly promote the active governance of marine enterprises. Accordingly, the suggestions are proposed to maintain China's marine ecological security, e.g., the central government should focus on urging local governments to strictly implement marine environmental protection policies; local governments should take the lead in supervising and guiding marine enterprises; and all levels of government need to take measures to promote public participation in marine ecological governance.
A comprehensive analysis of the relationship between temperature and species diversity: The case of planktonic foraminifera
Authors: Gao Junfeng , Su Qiang
Published: December 2022

The relationship between temperature (T) and species diversity is one of the most fundamental issues in marine diversity. Although their relationships have been discussed for many years, how species diversity is related to T remains a controversial question. Previous studies have identified three T–diversity relationships: positive, negative, and unimodal. Recently, the unimodal relationship has received great attention. However, these studies may be biased by (1) considering the insufficient T range of database, (2) using a single diversity metric (generally species richness, S), and (3) rarely considering species abundance distribution (SAD) that can better represent diversity. Here, to seek a more comprehensive understanding of T–diversity relationships, their relationships are evaluated according to a global planktonic foraminifera dataset, which is usually considered as a model dataset for exploring diversity pattern. Species diversity are estimated by four most commonly used metrics and a new SAD parameter (p). Results show that S and Shannon’s index support the typical unimodal relationship with T. However, evenness and dominance do not have significant unimodality. Additionally, this study conjectures that the SAD parameter p with increasing T will gradually approach the minimum 1, noting that SAD (Nr/N1, where Nr and N1 are the abundance of the rth and the first species in descending order) tends to be 1:1/2:1/3…. This study suggests that the T–diversity relationship cannot be wholly reflected by S and the other aspects of diversity (especially SAD) should be considered.
Nitrogen-loss and associated microbial communities in sediments from the Yangtze Estuary and adjacent sea
Authors: Teng Zhenzhen , Zhen Yu , Yu Zhigang , Mi Tiezhu , Cai Tao
Published: December 2022

Introduction

Denitrification and anammox play the crucial role for N removal processes in coastal ecosystems, but the ecological distribution of denitrifying and anammox microorganisms and their N removal rates in the Yangtze Estuary and its adjacent sea are required in-depth analysis.

Methods

Here, we utilized high-throughput sequencing, qPCR, and 15N isotope to reveal the community structure and function of denitrifying and anammox microorganisms in the surface sediments from Yangtze Estuary and adjacent sea.

Results

The results suggested that the gene abundances of nirS and nirK for denitrifiers were higher than AMX 16S rRNA for anammox bacteria. The genera composition of nirS- and nirK-encoding denitrifiers communities showed different distribution patterns. Furthermore, Candidatus Anammoximicrobium dominated the anammox community, implying the anammox oxidation capacity of the other genera should be noted in marine sediments.

Discussion

Compared to anammox, denitrification was the dominant contributor of nitrogen removal process and contributed 73.5% on average. The sediment Chla was the key factor to regulate denitrification and anammox rates, indicating the fresh organic matter was more labile and easier to be utilized by NOx− removal processes.
Extreme coastal water levels with potential flooding risk at the low-lying Saint Louis historic city, Senegal (West Africa)
Authors: Cisse Cheikh Omar Tidjani , Brempong Emmanuel K. , Taveneau Adélaïde , Almar Rafael , Sy Boubou Aldiouma , Angnuureng Donatus Bapentire
Published: December 2022

In a context of global warming characterized by a mean sea level rise and extreme meteorological events, the study of the causes for coastal flooding is essential to protect communities and ecosystems. Densely urbanized, and rather unprotected cities in developing countries such as the historic Saint Louis city in Senegal are particularly vulnerable to coastal flooding and sea hazards. From satellite-derived high resolution DEM and global ocean reanalyses, here we quantify the extreme coastal water level in order to identify the neighborhoods and places of particular socio-economical interest of Saint-Louis potentially vulnerable to flooding. The results reveal that the most severe levels have the potential to flood up to almost half of this low-lying river mouth plain. Social, economic and heritage stakes are exposed, and the artisanal fisherman district of Gueth Ndar, is particularly vulnerable to coastal flooding because of its low elevation and situation on the sand barrier. The co-occurrence of high tides and wave-induced runup contributes most to ECWL but they do not present a significant trend over the study period. The results show that over the period 1994-2015, potential flood risk increased by nearly one day per year, primarily due to sea level rise, sounding a warning signal to take countermeasures to protect communities and infrastructure.
Study of friction and wear behaviors of Fe-based amorphous coatings by MD simulations
Authors: Chu Zhenhua , Zhou Yuyun , Xu Fa , Xu Jingxiang , Zheng Xingwei , Luo Xiaotao , Shu Yan , Zhang Zheng , Hu Qingsong
Published: December 2022

In this study, molecular dynamics simulation is adopted to investigate the friction and wear mechanism of Fe-based amorphous composited coatings. It was found that the ceramic phase can improve plasticity of the composite coatings to reduce wear. In addition, when the Al2O3 content is 15 wt%, due to the stress concentration between ceramic phase and amorphous phase, the viscosity flow in the amorphous phase results in plastic deformation. Through this, the best wear resistance has been obtained. In addition, with the increase of compression depth, the number of atoms accumulated constantly increases, and the degree of plastic deformation becomes higher in the composite coatings. Finally, a high sliding speed results in the reduction of the wear resistance of coatings.
Seismic performance investigation of an innovative steel shear wall with semi-rigid beam-to-column connections
Authors: Abdul Ghafar Wahab , Zhong Tao , Abid Muhammad , Faizan Enamullah , Mohamed Abdullah , Yosri Ahmed M.
Published: December 2022

Steel plate shear walls (SPSWs) are a robust lateral load resistance structure because of their high ductility and efficient energy dissipation when subjected to seismic loads. This research investigates the seismic performance of an innovative infill web strip (IWS-SPSW) and a typical unstiffened steel plate shear wall (USPSW). As a result, two 1:3 scale specimens of an IWS-SPSW and USPSW with a single story and a single bay were built and subjected to a cyclic lateral loading methodology. In the prototype, semi-rigid end-plate connectors for the beam-to-column connections were utilized. The test result of IWS-SPSW showed outstanding ductility and shear load-bearing capacity without cracks or damage. Additionally, the IWS-SPSW exhibited strong energy dissipation without substantial beam-column connection distortion. USPSW showed excellent shear load-bearing capacity, low ductility, extensive infill plate corner tearing, and large infill web plate cracks. The FE models were developed and verified against experimental data. It has been shown that the infill web strips can affect the high performance and overall energy dissipation of an SPSW system. In addition, a parametric study was conducted to investigate the infill web strip material properties, such as steel strength and thickness, that can significantly enhance the system’s seismic performances.
Early intervention in psoriasis: Where do we go from here?
Authors: Felix Paulo Antônio Oldani , Sampaio Ana Luisa , Silva Bruno Leonardo , Viana Analia Luiza Porto
Published: December 2022

Patients with psoriasis often have comorbidities and are at increased risk of developing several complications compared with the general population. Knowledge on the role of immune mediators and systemic inflammation in psoriasis has led to the hypothesis that early intervention with systemic therapy has the potential to modify the course of the disease and reduce the risk of long-term adverse outcomes. In this article, we address some potential issues that need to be considered before early intervention can be implemented routinely. The first is determining what constitutes “early” intervention for psoriasis. A second point is whether the intervention should be considered for patients with early disease or for selected subsets based on risk stratification. A third important consideration is defining success for early intervention. Finally, adoption of early and effective intervention should be based on high-level evidence. Ideally, randomized trials would be the best strategy to compare early vs. late systemic treatment in patients with psoriasis, probably using the frequency of long-term outcomes as primary endpoint, with cutaneous and pharmacoeconomic outcomes assessed secondarily.
Efficacy of acupoint stimulation as a treatment for uremic pruritus: A systematic review and meta-analysis
Authors: Lu Ping-Hsun , Chung Chia-Hsiang , Chuo Hui-En , Lin I-Hsin , Lu Po-Hsuan
Published: December 2022

Background

Uremic pruritus causes sleep disturbances, poor quality of life, and increased morbidity in patients with chronic kidney disease. Acupuncture has been shown to improve uremic pruritus. There is limited evidence of the efficacy of traditional Chinese therapies. We conducted a systematic review and meta-analysis to evaluate the efficacy of acupoint stimulation therapy in patients with uremic pruritus.

Methods

A systematic search of seven databases (up to Sep 2022) was conducted for randomized controlled trials that evaluated the clinical efficacy of acupuncture, acupressure, auricular acupressure, acupoint injection, acupoint thermal therapy, acupoint sticking therapy, or transcutaneous electrical acupoint stimulation in the treatment of patients with uremic pruritus. Two reviewers selected eligible articles for inclusion in the meta-analysis and evaluated the risk of bias via Cochrane Collaboration. The results of pruritus assessments and uremic pruritus-related laboratory parameters were analyzed.

Results

Forty trials published between 2002 and 2022, including a total of 2,735 participants, were identified for inclusion in the meta-analysis. The effective rates for acupuncture, auricular acupressure, and the combination of acupoint injection and acupoint massage were significantly greater in patients with uremic pruritus compared to the control group. The levels of serum BUN, PTH, and histamine levels were significantly lower vs. control group.

Conclusions

Acupuncture, auricular acupressure, and the combination of acupoint injection and acupoint massage seem to be effective in improving uremic pruritus in patients with chronic kidney disease. However, further investigation of these potential treatments is now warranted in larger patient populations and over a longer time frame.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022354585, identifier: PROSPERO CRD42022354585.
TissueGrinder, a novel technology for rapid generation of patient-derived single cell suspensions from solid tumors by mechanical tissue dissociation
Authors: Scheuermann Stefan , Lehmann Jonas M. , Ramani Mohan Ramkumar , Reißfelder Christoph , Rückert Felix , Langejürgen Jens , Pallavi Prama
Published: December 2022

Introduction

Recent advances hold promise of making personalized medicine a step closer to implementation in clinical settings. However, traditional sample preparation methods are not robust and reproducible. In this study, the TissueGrinder, a novel mechanical semi-automated benchtop device, which can isolate cells from tissue in a very fast and enzyme-free way is tested for cell isolation from surgically resected tumor tissues.

Methods

Thirty-three surgically resected tumor tissues from various but mainly pancreatic, liver or colorectal origins were processed by both novel TissueGrinder and explant method. An optimized processing program for tumors from pancreatic, liver or colorectal cancer was developed. The viability and morphological characteristics of the isolated cells were evaluated microscopically. Expression of pancreatic cancer markers was evaluated in cells isolated from pancreatic tumors. Finally, the effect of mechanical stress on the cells was evaluated by assessing apoptosis markers via western blotting.

Results

TissueGinder was more efficient in isolating cells from tumor tissue with a success rate of 75% when compared to explant method 45% in terms of cell outgrowth six weeks after processing. Cells isolated with TissueGinder had a higher abundance and were more heterogeneous in composition as compared to explant method. Mechanical processing of the cells with TissueGrinder does not lead to apoptosis but causes slight stress to the cells.

Discussion

Our results show that TissueGrinder can process solid tumor tissues more rapidly and efficiently and with higher success rate compared to the conventionally used explant method. The results of the study suggest that the TissueGrinder might be a suitable method for obtaining cells, which is important for its application in individualized therapy. Due to the great variance in different tumor entities and the associated individual tissue characteristics, a further development of the dissociation protocol for other types of tumors and normal tissue will be targeted.
Reshaping of soil carbon and nitrogen contents in quincentenary ancient rice terraces: The role of both short-term abandonment and prokaryotic functional groups
Authors: Li Wenqing , Li Zhongwu , Liu Yaojun , Nie Xiaodong , Deng Chuxiong , Zhang Guangye , Wang Shuyuan , Xiao Tao , Zheng Han
Published: December 2022

Microbial communities and functions play an important role in soil carbon and nitrogen transformations, and, in recent decades, the abandonment of terraces is prevalant in the hilly areas of China. However, it is unclear how soil carbon and nitrogen contents and prokaryotic communities changed as a result of the abandonment of ancient rice terraces. Soil profiles ranging from 0 to 120 cm were excavated on drylands, forestlands (both converted due to the abandonment of ancient rice terraces), and ancient rice terraces. The FAPROTAX database was used to predict soil prokaryotic functional groups. The results showed that soil organic carbon (SOC) and total nitrogen (TN) contents of abandoned ancient rice terraces in drylands (51.09 and 33.20%) and forestlands (31.76 and 16.59%) were significantly reduced. Soil prokaryotic diversity and community composition changed dramatically after the abandonment of terraces and were mainly affected by soil pH and ammoniacal nitrogen (NH4+-N). Community composition was more similar in drylands and forestlands. Moreover, the abundance of transformation functional genes of carbon (57.01 and 50.80%) and nitrogen (15.25 and 22.36%) in bacterial communities was significantly reduced, and of carbon in the archaeal communities decreased sharply (28.10 and 46.50%), in drylands and forestlands. These findings indicate that short-term abandonment of ancient rice terraces reduces soil carbon and nitrogen contents, which may be closely related to the decline of prokaryotic functional groups. The prevalence of short-term abandonment of rice terraces in the hilly areas of China may pose adverse ecological risks.
Characterization of virulence and antimicrobial resistance genes of Aeromonas media strain SD/21–15 from marine sediments in comparison with other Aeromonas spp.
Authors: Dubey Saurabh , Ager-Wick Eirill , Peng Bo , Evensen Øystein , Sørum Henning , Munang’andu Hetron Mweemba
Published: December 2022

Aeromonas media is a Gram-negative bacterium ubiquitously found in aquatic environments. It is a foodborne pathogen associated with diarrhea in humans and skin ulceration in fish. In this study, we used whole genome sequencing to profile all antimicrobial resistance (AMR) and virulence genes found in A. media strain SD/21–15 isolated from marine sediments in Denmark. To gain a better understanding of virulence and AMR genes found in several A. media strains, we included 24 whole genomes retrieved from the public databanks whose isolates originate from different host species and environmental samples from Asia, Europe, and North America. We also compared the virulence genes of strain SD/21–15 with A. hydrophila, A. veronii, and A. salmonicida reference strains. We detected Msh pili, tap IV pili, and lateral flagella genes responsible for expression of motility and adherence proteins in all isolates. We also found hylA, hylIII, and TSH hemolysin genes in all isolates responsible for virulence in all isolates while the aerA gene was not detected in all A. media isolates but was present in A. hydrophila, A. veronii, and A. salmonicida reference strains. In addition, we detected LuxS and mshA-Q responsible for quorum sensing and biofilm formation as well as the ferric uptake regulator (Fur), heme and siderophore genes responsible for iron acquisition in all A. media isolates. As for the secretory systems, we found all genes that form the T2SS in all isolates while only the vgrG1, vrgG3, hcp, and ats genes that form parts of the T6SS were detected in some isolates. Presence of blaMOX-9 and blaOXA-427 β-lactamases as well as crp and mcr genes in all isolates is suggestive that these genes were intrinsically encoded in the genomes of all A. media isolates. Finally, the presence of various transposases, integrases, recombinases, virulence, and AMR genes in the plasmids examined in this study is suggestive that A. media has the potential to transfer virulence and AMR genes to other bacteria. Overall, we anticipate these data will pave way for further studies on virulence mechanisms and the role of A. media in the spread of AMR genes.
Frequent exacerbators of chronic obstructive pulmonary disease have distinguishable sputum microbiome signatures during clinical stability
Authors: Dang Xiaomin , Kang Yongyong , Wang Xiaojian , Cao Wen , Li Minhui , He Ying , Pan Xinjie , Ye Kai , Xu Dan
Published: December 2022

Introduction

Frequent exacerbation phenotype of chronic obstructive pulmonary disease (COPD) represents a more concerning disease subgroup requiring better prevention and intervention, of which airway microbiome provides new perspective for further exploration.

Methods

To investigate whether frequent exacerbators of COPD have distinguishable sputum microbiome during clinical stability, COPD patients at high disease grades with or without frequent exacerbation were recruited for sputum microbiome analysis. Sputum samples were collected during clinical stability and underwent 16S rRNA sequencing, which was then subjected for amplicon sequence variants (ASVs)-based microbiome analysis.

Results

Our results revealed that compared with healthy controls and infrequent exacerbators, frequent COPD exacerbators have distinguishably dysbiotic sputum microbiome, as featured by fewer ASVs features, lower alpha diversity, distinct beta diversity patterns. Further taxonomic compositional analysis illustrated the structural distinctions between frequent COPD exacerbators and infrequent exacerbators at differential taxa levels and highlighted Stenotrephomonas due to its prominent elevation in frequent COPD exacerbators, providing a promising candidate for further exploration of microbiome biomarker. Moreover, we also demonstrated that frequent exacerbation phenotype is distinguishable from infrequent exacerbation phenotype with respect of functional implications.

Conclusion

Our study demonstrated the first positive correlation between the frequent exacerbation phenotype of COPD and the sputum microbiome during clinical stability in a single-center Chinese COPD cohort and provide potential diagnostic and therapeutic targets for further investigation.
Probiotic supplementation during pregnancy alters gut microbial networks of pregnant women and infants
Authors: Huang Ting , Li Zhe , Tye Kian Deng , Chan Sze Ngai , Tang Xiaomei , Luo Huijuan , Wang Dongju , Zhou Juan , Duan Xia , Xiao Xiaomin
Published: December 2022

Background

Probiotic supplementation has been popular and widespread, yet we still lack a comprehensive understanding of how probiotic supplementation during pregnancy affects the gut microbial networks of pregnant women and infants. In this study, we firstly used network analysis to compare the gut microbiota of pregnant women with and without probiotic supplementation, as well as their infants.

Methods

Thirty-one pairs of healthy pregnant women and infants were recruited and randomly divided into the probiotic group (15 mother-infant pairs) and the control group (16 mother-infant pairs). Pregnant women in the probiotic group consumed combined probiotics from 32 weeks to delivery. Fecal samples were collected from pregnant women and infants at several time points. Gut microbiota was evaluated using 16S rRNA gene sequencing. Intestinal microbial network and topological properties were performed using the molecular ecological network analysis.

Results

No significant difference was found between the probiotic and control groups on the microbial alpha and beta diversity. As the gestational age increased, the total links, average degree, average clustering coefficient, robustness, and the proportion of positive correlations were increased in pregnant women with probiotics administration. In contrast, these indices were decreased in infants in the probiotic group.

Conclusion

Probiotic supplement does not change the microbial diversity of pregnant women and infants, but significantly alters the intestinal microbial network structure and properties. Although pregnant women have more complicated and stable networks after probiotic administration, their infants have less stable networks.
Effects of autumn diurnal freeze–thaw cycles on soil bacteria and greenhouse gases in the permafrost regions
Authors: Lv Zhenying , Gu Yuzheng , Chen Shengyun , Chen Jianwei , Jia Yinglan
Published: December 2022

Understanding the impacts of diurnal freeze–thaw cycles (DFTCs) on soil microorganisms and greenhouse gas emissions is crucial for assessing soil carbon and nitrogen cycles in the alpine ecosystems. However, relevant studies in the permafrost regions in the Qinghai-Tibet Plateau (QTP) are still lacking. In this study, we used high-throughput pyrosequencing and static chamber-gas chromatogram to study the changes in topsoil bacteria and fluxes of greenhouse gases, including carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O), during autumn DFTCs in the permafrost regions of the Shule River headwaters on the western part of Qilian Mountains, northeast margin of the QTP. The results showed that the bacterial communities contained a total of 35 phyla, 88 classes, 128 orders, 153 families, 176 genera, and 113 species. The dominant phyla were Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, and Gemmatimonadetes. Two DFTCs led to a trend of increasing bacterial diversity and significant changes in the relative abundance of 17 known bacteria at the family, genus, and species levels. These were predominantly influenced by soil temperature, water content, and salinity. In addition, CO2 flux significantly increased while CH4 flux distinctly decreased, and N2O flux tended to increase after two DFTCs, with soil bacteria being the primary affecting variable. This study can provide a scientific insight into the impact of climate change on biogeochemical cycles of the QTP.
Modeling current geographic distribution and future range shifts of Sanghuangporus under multiple climate change scenarios in China
Authors: Chen Jia-He , Shen Shan , Zhou Li-Wei
Published: December 2022

The genus Sanghuangporus is well-known for its edible and medicinal values. In this study, the most comprehensive occurrence records of Sanghuangporus with accurate species identification are subjected to MaxEnt, to model the current geographic distribution and future range shifts under multiple climate change scenarios in China. The current potential distribution model of Sanghuangporus is excellently predicted as indicated by the value of Area Under Receiver Operator Characteristic Curve. The current potential distribution basically corresponds to the known occurrence records of Sanghuangporus, and provides clues to new suitable habitats. The critical environmental variables to the distribution are annual precipitation, host plant, annual mean temperature and elevation. Host plant is not the most critical contribution to the model, but it indeed plays a decisive role in restricting the distribution of Sanghuangporus. This role is further confirmed by the distribution area of the highly suitable habitat increasing by 155.468%, when excluding host plant from environmental variables. For future scenarios, generally the area of highly suitable habitat for Sanghuangporus extremely increases, but the locations do not change a lot. In conclusion, this study provides important ecological information for the utilization and conservation of the edible and medicinal fungus Sanghuangporus.
Mechanism and application of fermentation to remove beany flavor from plant-based meat analogs: A mini review
Authors: Tao Anqi , Zhang Hongyu , Duan Junnan , Xiao Ying , Liu Yao , Li Jianwei , Huang Jieyu , Zhong Tian , Yu Xi
Published: December 2022

Over the past few decades, there has been a noticeable surge in the market of plant-based meat analogs (PBMA). Such popularity stems from their environmentally friendly production procedures as well as their positive health effects. In order to meet the market demand, it is necessary to look for plant protein processing techniques that can help them match the quality of conventional meat protein from the aspects of sensory, quality and functionality. Bean proteins are ideal options for PBMA with their easy accessibility, high nutrient-density and reasonable price. However, the high polyunsaturated lipids content of beans inevitably leads to the unpleasant beany flavor of soy protein products, which severely affects the promotion of soy protein-based PBMA. In order to solve this issue, various methods including bleaching, enzyme and fermentation etc. are developed. Among these, fermentation is widely investigated due to its high efficiency, less harm to the protein matrix, targeted performance and low budget. In addition, proper utilization of microbiome during the fermentation process not only reduces the unpleasant beany flavors, but also enhances the aroma profile of the final product. In this review, we provide a thorough and succinct overview of the mechanism underlying the formation and elimination of beany flavor with associated fermentation process. The pros and cons of typical fermentation technologies for removing beany flavors are discussed in alongside with their application scenarios. Additionally, the variations among different methods are compared in terms of the strains, fermentation condition, target functionality, matrix for application, sensory perception etc.
miR-615 facilitates porcine epidemic diarrhea virus replication by targeting IRAK1 to inhibit type III interferon expression
Authors: Zheng Hong-qing , Li Cheng , Zhu Xiao-fu , Wang Wei-Xiao , Yin Bao-ying , Zhang Wen-juan , Feng Shu-lin , Yin Xun-hui , Huang He , Zhang Yan-ming
Published: December 2022

Porcine epidemic diarrhea virus (PEDV) in the Coronavirus family is a highly contagious enteric pathogen in the swine industry, which has evolved mechanisms to evade host innate immune responses. The PEDV-mediated inhibition of interferons (IFNs) has been linked to the nuclear factor-kappa B (NF-κB) pathway. MicroRNAs (miRNAs) are involved in virus–host interactions and IFN-I regulation. However, the mechanism by which the PEDV regulates IFN during PEDV infection has not yet been investigated in its natural target cells. We here report a novel mechanism of viral immune escape involving miR-615, which was screened from a high-throughput sequencing library of porcine intestinal epithelial cells (IECs) infected with PEDV. PEDV infection altered the profiles of miRNAs and the activities of several pathways involved in innate immunity. Overexpression of miR-615 increased PEDV replication, inhibited IFN expression, downregulated the NF-κB pathway, and blocked p65 nuclear translocation. In contrast, knockdown of miR-615 enhanced IFN expression, suppressed PEDV replication, and activated the NF-κB pathway. We further determined that IRAK1 is the target gene of miR-615 in IECs. Our findings show that miR-615 suppresses activation of the NF-κB pathway by suppressing the IRAK1 protein and reducing the generation of IFN-IIIs, which in turn facilitates PEDV infection in IECs. Moreover, miR-615 inhibited PEDV replication and NF-κB pathway activation in both IECs and MARC-145 cells. These findings support an important role for miR-615 in the innate immune regulation of PEDV infections and provide a novel perspective for developing new treatments.