bluuebunny/crossref_metadata_2025 huggingface dataset:
CAR-T Therapy for Pediatric High-Grade Gliomas: Peculiarities, Current Investigations and Future Strategies
Authors: Antonucci Laura , Canciani Gabriele , Mastronuzzi Angela , Carai Andrea , Del Baldo Giada , Del Bufalo Francesca
Published: May 2022

High-Grade Gliomas (HGG) are among the deadliest malignant tumors of central nervous system (CNS) in pediatrics. Despite aggressive multimodal treatment - including surgical resection, radiotherapy and chemotherapy - long-term prognosis of patients remains dismal with a 5-year survival rate less than 20%. Increased understanding of genetic and epigenetic features of pediatric HGGs (pHGGs) revealed important differences with adult gliomas, which need to be considered in order to identify innovative and more effective therapeutic approaches. Immunotherapy is based on different techniques aimed to redirect the patient own immune system to fight specifically cancer cells. In particular, T-lymphocytes can be genetically modified to express chimeric proteins, known as chimeric antigen receptors (CARs), targeting selected tumor-associated antigens (TAA). Disialoganglioside GD2 (GD-2) and B7-H3 are highly expressed on pHGGs and have been evaluated as possible targets in pediatric clinical trials, in addition to the antigens common to adult glioblastoma – such as interleukin-13 receptor alpha 2 (IL-13α2), human epidermal growth factor receptor 2 (HER-2) and erythropoietin-producing human hepatocellular carcinoma A2 receptor (EphA2). CAR-T therapy has shown promise in preclinical model of pHGGs but failed to achieve the same success obtained for hematological malignancies. Several limitations, including the immunosuppressive tumor microenvironment (TME), the heterogeneity in target antigen expression and the difficulty of accessing the tumor site, impair the efficacy of T-cells. pHGGs display an immunologically cold TME with poor T-cell infiltration and scarce immune surveillance. The secretion of immunosuppressive cytokines (TGF-β, IL-10) and the presence of immune-suppressive cells – like tumor-associated macrophages/microglia (TAMs) and myeloid-derived suppressor cells (MDSCs) - limit the effectiveness of immune system to eradicate tumor cells. Innovative immunotherapeutic strategies are necessary to overcome these hurdles and improve ability of T-cells to eradicate tumor. In this review we describe the distinguishing features of HGGs of the pediatric population and of their TME, with a focus on the most promising CAR-T therapies overcoming these hurdles.
Antigenic Cross-Reactivity Between SARS-CoV-2 S1-RBD and Its Receptor ACE2
Authors: Lai Yen-Chung , Cheng Yu-Wei , Chao Chiao-Hsuan , Chang Yu-Ying , Chen Chi-De , Tsai Wei-Jiun , Wang Shuying , Lin Yee-Shin , Chang Chih-Peng , Chuang Woei-Jer , Chen Li-Yin , Wang Ying-Ren , Chang Sui-Yuan , Huang Wenya , Wang Jen-Ren , Tseng Chin-Kai , Lin Chun-Kuang , Chuang Yung-Chun , Yeh Trai-Ming
Published: May 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus responsible for the ongoing COVID-19 pandemic. SARS-CoV-2 binds to the human cell receptor angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain in the S1 subunit of the spike protein (S1-RBD). The serum levels of autoantibodies against ACE2 are significantly higher in patients with COVID-19 than in controls and are associated with disease severity. However, the mechanisms through which these anti-ACE2 antibodies are induced during SARS-CoV-2 infection are unclear. In this study, we confirmed the increase in antibodies against ACE2 in patients with COVID-19 and found a positive correlation between the amounts of antibodies against ACE2 and S1-RBD. Moreover, antibody binding to ACE2 was significantly decreased in the sera of some COVID-19 patients after preadsorption of the sera with S1-RBD, which indicated that antibodies against S1-RBD can cross-react with ACE2. To confirm this possibility, two monoclonal antibodies (mAbs 127 and 150) which could bind to both S1-RBD and ACE2 were isolated from S1-RBD-immunized mice. Measurement of the binding affinities by Biacore showed these two mAbs bind to ACE2 much weaker than binding to S1-RBD. Epitope mapping using synthetic overlapping peptides and hydrogen deuterium exchange mass spectrometry (HDX-MS) revealed that the amino acid residues P463, F464, E465, R466, D467 and E471 of S1-RBD are critical for the recognition by mAbs 127 and 150. In addition, Western blotting analysis showed that these mAbs could recognize ACE2 only in native but not denatured form, indicating the ACE2 epitopes recognized by these mAbs were conformation-dependent. The protein–protein interaction between ACE2 and the higher affinity mAb 127 was analyzed by HDX-MS and visualized by negative-stain transmission electron microscopy imaging combined with antigen-antibody docking. Together, our results suggest that ACE2-cross-reactive anti-S1-RBD antibodies can be induced during SARS-CoV-2 infection due to potential antigenic cross-reactivity between S1-RBD and its receptor ACE2.
Fatty Acid Metabolism and T Cells in Multiple Sclerosis
Authors: Pompura Saige L. , Hafler David A. , Dominguez-Villar Margarita
Published: May 2022

Cellular metabolic remodeling is intrinsically linked to the development, activation, differentiation, function, and survival of T cells. T cells transition from a catabolic, naïve state to an anabolic effector state upon T cell activation. Subsequently, specialization of T cells into T helper (Th) subsets, including regulatory T cells (Treg), requires fine-tuning of metabolic programs that better support and optimize T cell functions for that particular environment. Increasingly, studies have shown that changes in nutrient availability at both the cellular and organismal level during disease states can alter T cell function, highlighting the importance of better characterizing metabolic-immune axes in both physiological and disease settings. In support of these data, a growing body of evidence is emerging that shows specific lipid species are capable of altering the inflammatory functional phenotypes of T cells. In this review we summarize the metabolic programs shown to support naïve and effector T cells, and those driving Th subsets. We then discuss changes to lipid profiles in patients with multiple sclerosis, and focus on how the presence of specific lipid species can alter cellular metabolism and function of T cells.
Host MKRN1-Mediated Mycobacterial PPE Protein Ubiquitination Suppresses Innate Immune Response
Authors: Dou Yafeng , Xie Yan , Zhang Lingyun , Liu Sheng , Xu Dandan , Wei Yuying , Li Yongshuai , Zhang Xiao-Lian
Published: May 2022

Mycobacterium tuberculosis (Mtb), as an important intracellular pathogen, can invade and survive in macrophages and is capable of escaping the clearance of immune system. Despite decades of research efforts, the precise mechanism of immune escape and the virulence factors encoded by Mtb involved remain to be explored. Mtb-specific genomic regions of deletion (RD)-encoded proteins and PE/PPE family proteins have been implicated in immune evasion. Here, we screened more than forty RD-encoded proteins which might be involved in facilitating bacterial survival in macrophages, and found that a Mtb PPE68/Rv3873 protein, encoded by Mtb-RD1, is essential for efficient Mtb intracellular survival in macrophages. In terms of mechanism, we found that the ubiquitin ligase (E3) Makorin Ring Finger Protein 1 (MKRN1) of macrophage interacted with PPE68 and promoted the attachment of lysine (K)-63-linked ubiquitin chains to the K166 site of PPE68. K63-ubiquitination of PPE68 further bound src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) to suppress K63-linked polyubiquitin chains of tumor necrosis factor receptor-associated factor 6 (TRAF6), and then remarkably suppressed TRAF6-driven NF-κB and AP-1 signaling and TNF-α, IL-6 and NO production. We demonstrate that the K63-linked ubiquitination of PPE68 by MKRN1 contributed to the PPE68-mediated mycobacterial immune escape. Our finding identifies a previously unrecognized mechanism by which host MKRN1-mediated-ubiquitination of mycobacterial PPE protein suppresses innate immune responses. Disturbing the interaction between host MKRN1 ubiquitin system and mycobacterial PPE protein might be a potential therapeutic target for tuberculosis.
Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications
Authors: Terrén Iñigo , Orrantia Ane , Astarloa-Pando Gabirel , Amarilla-Irusta Ainhoa , Zenarruzabeitia Olatz , Borrego Francisco
Published: May 2022

Natural killer (NK) cells are lymphocytes with a key role in the defense against viral infections and tumor cells. Although NK cells are classified as innate lymphoid cells (ILCs), under certain circumstances they exhibit adaptive and memory-like features. The latter may be achieved, among others, by a brief stimulation with interleukin (IL)-12, IL-15 and IL-18. These cytokine-induced memory-like (CIML) NK cells resemble the trained immunity observed in myeloid cells. CIML NK cells undergo transcriptional, epigenetic and metabolic reprogramming that, along with changes in the expression of cell surface receptors and components of cytotoxic granules, are responsible for their enhanced effector functions after a resting period. In addition, these memory-like NK cells persist for a long time, which make them a good candidate for cancer immunotherapy. Currently, several clinical trials are testing CIML NK cells infusions to treat tumors, mostly hematological malignancies. In relapse/refractory acute myeloid leukemia (AML), the adoptive transfer of CIML NK cells is safe and complete clinical remissions have been observed. In our review, we sought to summarize the current knowledge about the generation and molecular basis of NK cell memory-like responses and the up-to-date results from clinical trials with CIML NK cells.
Functional Impact of Risk Gene Variants on the Autoimmune Responses in Type 1 Diabetes
Authors: Gootjes Chelsea , Zwaginga Jaap Jan , Roep Bart O. , Nikolic Tatjana
Published: May 2022

Type 1 diabetes (T1D) is an autoimmune disease that develops in the interplay between genetic and environmental factors. A majority of individuals who develop T1D have a HLA make up, that accounts for 50% of the genetic risk of disease. Besides these HLA haplotypes and the insulin region that importantly contribute to the heritable component, genome-wide association studies have identified many polymorphisms in over 60 non-HLA gene regions that also contribute to T1D susceptibility.

Combining the risk genes in a score (T1D-GRS), significantly improved the prediction of disease progression in autoantibody positive individuals. Many of these minor-risk SNPs are associated with immune genes but how they influence the gene and protein expression and whether they cause functional changes on a cellular level remains a subject of investigation. A positive correlation between the genetic risk and the intensity of the peripheral autoimmune response was demonstrated both for HLA and non-HLA genetic risk variants. We also observed epigenetic and genetic modulation of several of these T1D susceptibility genes in dendritic cells (DCs) treated with vitamin D3 and dexamethasone to acquire tolerogenic properties as compared to immune activating DCs (mDC) illustrating the interaction between genes and environment that collectively determines risk for T1D. A notion that targeting such genes for therapeutic modulation could be compatible with correction of the impaired immune response, inspired us to review the current knowledge on the immune-related minor risk genes, their expression and function in immune cells, and how they may contribute to activation of autoreactive T cells, Treg function or β-cell apoptosis, thus contributing to development of the autoimmune disease.
Dynamic Changes of Cytokine Profiles and Virological Markers Associated With HBsAg Loss During Peginterferon Alpha-2a Treatment in HBeAg-Positive Chronic Hepatitis B Patients
Authors: Li Minghui , Zhang Luxue , Xie Si , Sun Fangfang , Zeng Zhan , Deng Wen , Jiang Tingting , Bi Xiaoyue , Lin Yanjie , Yang Liu , Lu Yao , Shen Ge , Liu Ruyu , Wu Shuling , Chang Min , Hu Leiping , Dong Jianping , Yi Wei , Xie Yao
Published: May 2022

Objective

To explore dynamic changes of cytokines and virological markers associated with hepatitis B surface antigen (HBsAg) loss during peginterferon alpha-2a (PEG-IFN α-2a) treatment in hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients.

Methods

It was a single-center prospective cohort study. HBeAg-positive CHB patients were prospectively and consecutively enrolled. Cytokines were detected at baseline, week 12 and 24 of PEG-IFN treatment. HBsAg disappearance rate was the primary evaluation index at 48 weeks of PEG-IFN treatment.

Results

Among 100 patients who completed the 48-week PEG-IFN α-2a treatment, 38 patients achieved serum HBeAg disappearance, 25 patients achieved HBeAg seroconversion, 9 patients achieved functional cure, 37 patients had HBsAg decline of ≥1 log IU/ml, and 8 patients produced hepatitis B surface antibody (HBsAb). Albumin (ALB), fms-like tyrosine kinase 3 ligand (FLT3-L) and interferon-alpha2 (IFN-α2) in the clinical cure group were significantly lower than those in the non-clinical-cure group at baseline. After 12 weeks of treatment, HBsAg in the clinical cure group was significantly lower than that in the non-clinical-cure group (median 1.14 vs. 3.45 log10IU/ml, Z=-4.355, P < 0.001). The decrease of HBsAg and hepatitis B virus desoxyribose nucleic acid (HBV DNA) in the clinical cure group was significantly higher than that in non-clinical-cure group (median: HBsAg 1.96 vs. 0.33 log10IU/ml, Z=-4.703, P< 0.001; HBV DNA 4.49 vs.3.13 log10IU/ml, Z=-3.053, P=0.002). The increase of IFN-α2 in the cure group was significantly higher than that in the non-clinical-cure group (497.89 vs. 344.74, Z=-2.126, P=0.034). After 24 weeks of treatment, HBsAg, HBeAg, Flt3-L, and IL-10 in the clinical cure group were significantly lower than those in the non-clinical-cure group (median: HBsAg 0.70 vs. 3.15 log10IU/ml, Z=-4.535, P< 0.001; HBeAg 1.48 vs. 13.72 S/CO, Z = 2.512, P = 0.012; Flt3-l 0.00 vs 2.24 pg/ml, Z = 3.137, P=0.002; IL-10 0.70 vs. 2.71 pg/ml, Z=-4.067, P < 0.001). HBsAg decreased significantly in the clinical cure group compared with non-clinical-cure group (median 3.27 vs. 0.45, Z=-4.463, P < 0.001).

Conclusion

Dynamic changes of cytokines and virology markers during early PEG IFN α-2a treatment were associated with HBsAg loss in HBeAg-positive CHB patients.
Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Authors: Xu Yuhao , Du Yaoqiang , Zheng Qinghui , Zhou Tao , Ye Buyun , Wu Yihao , Xu Qiuran , Meng Xuli
Published: May 2022

Purpose

To identify molecular clusters associated with ferroptosis and to develop a ferroptosis-related signature for providing novel potential targets for the recurrence-free survival and treatment of breast cancer.

Methods

Ferroptosis-related gene (FRG) signature was constructed by univariate and multivariate Cox regression and least absolute shrinkage and selection operator (LASSO). Receiver operating characteristic curves, Kaplan–Meier survival analysis, principal component analysis, and univariate and multivariate Cox regression analyses in the training and test cohorts were used to evaluate the application of this signature. Quantitative reverse transcriptase–PCR (qRT-PCR) was employed to detect the expression of FRGs in the model. Furthermore, the correlations between the signature and immune microenvironment, somatic mutation, and chemotherapeutic drugs sensitivity were explored.

Results

Internal and external validations affirmed that relapse-free survival differed significantly between the high-risk and low-risk groups. Univariate and multivariate Cox regression analyses indicated that the riskScore was an independent prognostic factor for BRCA. The areas under the curve (AUCs) for predicting 1-, 2-, and 3-year survival in the training and test cohorts were satisfactory. Significant differences were also found in the immune microenvironment and IC50 of chemotherapeutic drugs between different risk groups. Furthermore, we divided patients into three clusters based on 18 FRGs to ameliorate the situation of immunotherapy failure in BRCA.

Conclusions

The FRG signature functions as a robust prognostic predictor of the immune microenvironment and therapeutic response, with great potential to guide individualized treatment strategies in the future.
From Antibody Repertoires to Cell-Cell Interactions to Molecular Networks: Bridging Scales in the Germinal Center
Authors: Vaidehi Narayanan Haripriya , Hoffmann Alexander
Published: May 2022

Antibody-mediated adaptive immunity must provide effective long-term protection with minimal adverse effects, against rapidly mutating pathogens, in a human population with diverse ages, genetics, and immune histories. In order to grasp and leverage the complexities of the antibody response, we advocate for a mechanistic understanding of the multiscale germinal center (GC) reaction – the process by which precursor B-cells evolve high-affinity antigen-specific antibodies, forming an effector repertoire of plasma and memory cells for decades-long protection. The regulatory dynamics of B-cells within the GC are complex, and unfold across multiple interacting spatial and temporal scales. At the organism scale, over weeks to years, the antibody sequence repertoire formed by various B-cell clonal lineages modulates antibody quantity and quality over time. At the tissue and cellular scale, over hours to weeks, B-cells undergo selectionviaspatially distributed interactions with local stroma, antigen, and helper T-cells. At the molecular scale, over seconds to days, intracellular signaling, transcriptional, and epigenetic networks modulate B-cell fates and shape their clonal lineages. We summarize our current understanding within each of these scales, and identify missing links in connecting them. We suggest that quantitative multi-scale mathematical models of B-cell and GC reaction dynamics provide predictive frameworks that can apply basic immunological knowledge to practical challenges such as rational vaccine design.
Neuropilin-1 Identifies a New Subpopulation of TGF-β-Induced Foxp3+ Regulatory T Cells With Potent Suppressive Function and Enhanced Stability During Inflammation
Authors: Chen Weiqian , Huang Weishan , Xue Youqiu , Chen Ye , Qian Wenbin , Ma Jilin , August Avery , Wang Julie , Zheng Song Guo , Lin Jin
Published: May 2022

CD4+Foxp3+ regulatory T cells (Tregs) play a crucial role in preventing autoimmunity and inflammation. There are naturally-derived in the thymus (tTreg), generated extrathymically in the periphery (pTreg), and induced in vitro culture (iTreg) with different characteristics of suppressiveness, stability, and plasticity. There is an abundance of published data on neuropilin-1 (Nrp-1) as a tTreg marker, but little data exist on iTreg. The fidelity of Nrp-1 as a tTreg marker and its role in iTreg remains to be explored. This study found that Nrp-1 was expressed by a subset of Foxp3+CD4+T cells in the central and peripheral lymphoid organs in intact mice, as well as in iTreg. Nrp-1+iTreg and Nrp-1-iTreg were adoptively transferred into a T cell-mediated colitis model to determine their ability to suppress inflammation. Differences in gene expression between Nrp-1+ and Nrp-1-iTreg were analyzed by RNA sequencing. We demonstrated that the Nrp-1+ subset of the iTreg exhibited enhanced suppressive function and stability compared to the Nrp-1- counterpart both in vivo and in vitro, partly depending on IL-10. We found that Nrp-1 is not an exclusive marker of tTreg, however, it is a biomarker identifying a new subset of iTreg with enhanced suppressive function, implicating a potential for Nrp-1+iTreg cell therapy for autoimmune and inflammatory diseases.
Host Restrictive Factors Are the Emerging Storm Troopers Against Enterovirus: A Mini-Review
Authors: Huan Chen , Qu Xinglong , Li Zhaolong
Published: May 2022

Enterovirus infection continues to be a global health problem. The lack of specific drugs and broad-spectrum vaccines means an urgent need to develop effective strategies against enteroviruses. Host restrictive factors are a class of intrinsic host antiviral factors that have been broadly defined and investigated during HIV infections and have great significance for drug development and treatment design. In recent years, the essential role of host restrictive factors in regulating enteroviral infections has been gradually recognized and investigated. An increasing number of studies have shown that host-restrictive factors regulate multiple steps in the life cycle of enteroviruses. This mini-review discusses the restrictive factors against enteroviruses, their antiviral mechanism, and the arms race between them and enteroviruses. We also summarise the pathways that enteroviruses use to impair host antiviral signals. This mini-review characterizes the essential role of host restriction factors in enterovirus infections, which provides ideas and potential targets for antiviral drug design by regulating host restrictive factors. It also reveals potential future research on the interplay between host restrictive factors and enteroviruses.
DMSP Production by Coral-Associated Bacteria
Authors: Kuek Felicity W.I. , Motti Cherie A. , Zhang Jia , Cooke Ira R. , Todd Jonathan D. , Miller David J. , Bourne David G. , Raina Jean-Baptiste
Published: May 2022

Dimethylsulfoniopropionate (DMSP) is an important molecule in the marine sulfur cycle, produced in large amounts by corals and their dinoflagellate endosymbionts, Symbiodiniaceae. Although corals are known to harbour bacteria that can catabolise DMSP, the recent discovery of bacteria capable of producing DMSP in coastal and deep-sea environments raises the possibility of a bacterial contribution to the DMSP output of corals. Here, 157 bacteria associated with four common coral species were isolated and screened for their ability to produce DMSP by targeting dsyB, a key gene involved in DMSP biosynthesis. Approximately 9% (14 out of 157) of the bacterial isolates harboured dsyB, all being members of the Alphaproteobacteria. The ability of these isolates to produce DMSP was confirmed by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) measurements. A dsyB-harbouring strain, Shimia aestuarii AMM-P-2, was selected for genome sequencing. This strain harbours the complete genetic machinery to (i) assimilate sulfate and synthesise the DMSP precursors, cysteine and methionine; (ii) demethylate DMSP and generate methanethiol; (iii) cleave DMSP, generating dimethyl sulfide (DMS) and acrylate; and (iv) utilise or detoxify acrylate. The impacts of varied environmental factors (temperature, salinity, light and UV radiation) on S. aestuarii AMM-P-2 DMSP biosynthesis were characterised. DMSP levels in S. aestuarii AMM-P-2 increased almost two-fold under both hypersaline conditions (40 PSU) and high UV exposure. DMSP catabolism through the cleavage pathway also increased under these conditions, producing the antioxidants DMS and acrylate, a potential response to the oxidative stress generated. Overall, our results reveal that coral-associated bacteria can synthesize DMSP and may therefore contribute to DMSP production by the coral holobiont.
Earth Observation and Machine Learning Reveal the Dynamics of Productive Upwelling Regimes on the Agulhas Bank
Authors: Jebri Fatma , Srokosz Meric , Jacobs Zoe L. , Nencioli Francesco , Popova Ekaterina
Published: May 2022

The combined application of machine learning and satellite observations offers a new way for analysing complex ocean biological and physical processes. Here, an unsupervised machine learning approach, Self Organizing Maps (SOM), is applied to discover links between surface current variability and phytoplankton productivity during seasonal upwelling over the Agulhas Bank (South Africa), from 23 years (November-March 1997-2020) of daily satellite observations (surface current, sea surface temperature, chlorophyll-a). The SOM patterns extracted over this dynamically complex region, which is dominated by the Agulhas Current (AC), revealed 4 topologies/modes of the AC system. An AC flowing southwestward along the shelf edge is the dominant mode. An AC with a cyclonic meander near shelf is the second most frequent mode. An AC with a cyclonic meander off shelf and AC early retroflection modes are the least frequent. These AC topologies influence the circulation and the phytoplankton productivity on the shelf. Strong (weak) seasonal upwelling is seen in the AC early retroflection, the AC with a cyclonic meander near shelf modes and in part of the AC along the shelf edge mode (the AC with a cyclonic meander off shelf mode and in part the AC along the shelf edge mode). The more productive patterns are generally associated with a strong southwestward flow over the central bank caused by the AC intrusion to the east Bank orviaan anticyclonic meander. The less productive situations can be related to a weaker southwest flow over the central bank, strong northeast flow on the eastern bank, and/or to a stronger northwest flow on the central bank. The SOM patterns show marked year-to-year variability. The high/low productivity events seem to be linked to the occurrence of extreme phases in climate variability modes (El Niño Southern Oscillation, Indian Ocean Dipole).
Porewater-Derived Blue Carbon Outwelling and Greenhouse Gas Emissions in a Subtropical Multi-Species Saltmarsh
Authors: Zhu Peiyuan , Chen Xiaogang , Zhang Yan , Zhang Qianyu , Wu Xuan , Zhao Huawen , Qi Liang , Shao Xuexin , Li Ling
Published: May 2022

Saltmarshes can sequester atmospheric CO2in sediments, but limited studies have quantified porewater-derived carbon exports and identified related carbon sources. Here, we estimated porewater exchange, carbon outwelling, and greenhouse gas emissions in a subtropical multi-species saltmarsh. The radon-based porewater exchange rate was estimated to be 5.60 ± 2.78 cm d-1. As the most dominant (~90%) carbon species, dissolved inorganic carbon (DIC) fluxes through porewater exchange and outwelling were 447 ± 227 and 1200 ± 61 mmol m-2d-1, respectively, which were 1.2 and 3.2 times that of carbon burial. As most DIC can remain in the ocean for a long time, porewater-derived DIC outwelling represents another important carbon sink, in addition to carbon burial. CO2and CH4emissions from creek water were 54.6 ± 0.5 and 0.19 ± 0.01 mmol m-2d-1, respectively, which could offset 16% of carbon burial. The δ13C and C/N ratios suggest that saltmarsh organic carbon mainly originates from the C3 plantScirpus mariqueterrather than the C4 plantSpartina alterniflora. Overall, we suggest that porewater-derived DIC outwelling is an important long-term carbon sink in multi-species saltmarshes, providing a scientific basis for the protection and restoration of saltmarshes in the context of global climate change.
Numerical and Experimental Investigations on Hydrodynamic Performance of a Newly Designed Deep Bottom Trawl
Authors: Guan Qinglong , Zhu Wenbin , Zhou Aizhong , Wang Yongjin , Tang Weiyao , Wan Rong
Published: May 2022

In this paper, a new type of bottom trawl was designed for target fishing vessels to use in deep-water fishing grounds. The trawl’s hydrodynamic performance was investigated using numerical simulation and physical modeling methods, and a numerical model based on the finite element method was proposed for estimating hydrodynamic forces and predicting performances. A series of physical model tests based on Tauti’s law were carried out in a towing tank to explore the hydrodynamic performance of the trawl and to assess the applicability of the numerical simulation method. The results showed that the working towing speed of the trawl was 3.5 kn. The drag force and the height of net opening were 50 kN and 5.62 m, respectively, and the swept area was 128 m2 at that speed. The simulated result was close to the experimental result, with a maximum relative error less than 20%, and an average relative error of 10%. The net shape and tension distribution of the trawl were analyzed using the numerical simulation method, and the hanging ratio in T-direction of the mesh of the codend was 0.25 at the working towing speed. The newly designed deep bottom trawl had a superior hydrodynamic performance for high catch efficiency and selectivity and may be applied to commercial fishing operations.
A Nationwide Multicenter Study on 1-Year Outcomes of Posterior Chamber Phakic Intraocular Lens Implantation for Low Myopia
Authors: Kamiya Kazutaka , Shimizu Kimiya , Igarashi Akihito , Kitazawa Yoshihiro , Kojima Takashi , Nakamura Tomoaki , Ichikawa Kazuo , Fukuoka Sachiko , Fujimoto Kahoko ,   The Japan ICL Study Group
Published: May 2022

Purpose

To assess the nationwide multicenter outcomes of posterior chamber phakic intraocular lens implantation with a central hole (EVO-ICL, STAAR Surgical) for patients with low myopia.

Methods

This multicenter study comprised 172 eyes of 111 consecutive patients undergoing hole ICL implantation to correct low myopia and myopic astigmatism [manifest spherical equivalent (MSE);−3 diopters (D) or less] at seven nationwide major surgical facilities. We retrospectively determined safety, efficacy, predictability, stability, and adverse events at 1 week, 1, 3, 6, and 12 months postoperatively, and at the final visit.

Results

The mean follow-up period was 1.4 ± 1.0 years. Uncorrected and corrected visual acuities at 1 year postoperatively were −0.17 ± 0.12 and −0.24 ± 0.07 logarithm of the minimal angle of resolution (logMAR), respectively. At 1 year postoperatively, 91% and 100% of eyes were within 0.5 and 1.0 D of the target correction, respectively. No significant manifest refraction changes of −0.07 ± 0.26 D occurred from 1 week to 1 year. No vision-threatening complications occurred at any time in this series.

Conclusions

According to our experience, the EVO-ICL performed well without significant complications throughout the 1-year observation period, even for the correction of low myopia. It is suggested that current ICL implantation is one of the viable surgical options for correcting low myopia.
Parent Joint AB Blood Group Is Associated With Clinical Outcomes of in vitro Fertilization and Intracytoplasmic Sperm Injection Treatment in Chinese Women
Authors: Bao Xiao , Zhao Feifei , Shi Hao , Bu Zhiqin , Liang Yuling , Sun Yingpu
Published: May 2022

Background

A number of publications have examined the relation between blood group and female infertility including ovarian reserve, recurrent miscarriage, and live birth. However, there is a lack of literature investigating joint mother/father ABO blood type in a large cohort. This study aimed to investigate the association between couple combinations for ABO blood groups and assisted reproductive technology (ART) outcomes in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).

Methods

This retrospective cohort study included 30,717 couples who underwent IVF cycles between 2010 and 2019. The clinical outcomes of IVF treatment were the primary outcome. History of spontaneous miscarriage, embryo quality, and birth sex, weights, defects rate were also studied.

Results

There was no difference in the baseline demographics between the blood type groups. There was a statistically significant positive association between the combination of female blood type AB and male blood type AB with biochemical pregnancy, clinical pregnancy, and live birth rate (OR 1.36; 95% CI, 1.05–1.78; P = 0.02 and OR 1.31; 95% CI, 1.0–1.68; P = 0.031 and OR 1.28; 95% CI, 1.01–1.63; P = 0.041 respectively). No statistically significant difference was observed between joint mother/father ABO blood types and high-quality embryo rate, early abortion rate, birth sex, birth weights, and birth defect rate.

Conclusions

Our findings suggest that the success rate of IVF/ICSI cycles in parent mating AB blood type is higher than that in other blood type combination groups.
Experimental Aristolochic Acid Nephropathy: A Relevant Model to Study AKI-to-CKD Transition
Authors: Baudoux Thomas , Jadot Inès , Declèves Anne-Emilie , Antoine Marie-Hélène , Colet Jean-Marie , Botton Olivia , De Prez Eric , Pozdzik Agnieszka , Husson Cécile , Caron Nathalie , Nortier Joëlle L.
Published: May 2022

Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial nephritis caused by the intake of aristolochic acids (AA) contained in Chinese herbal remedies or contaminated food. AAN is characterized by tubular atrophy and interstitial fibrosis, characterizing advanced kidney disease. It is established that sustained or recurrent acute kidney injury (AKI) episodes contribute to the progression of CKD. Therefore, the study of underlying mechanisms of AA-induced nephrotoxicity could be useful in understanding the complex AKI-to-CKD transition. We developed a translational approach of AKI-to-CKD transition by reproducing human AAN in rodent models. Indeed, in such models, an early phase of acute tubular necrosis was rapidly followed by a massive interstitial recruitment of activated monocytes/macrophages followed by cytotoxic T lymphocytes, resulting in a transient AKI episode. A later chronic phase was then observed with progressive tubular atrophy related to dedifferentiation and necrosis of tubular epithelial cells. The accumulation of vimentin and αSMA-positive cells expressing TGFβ in interstitial areas suggested an increase in resident fibroblasts and their activation into myofibroblasts resulting in collagen deposition and CKD. In addition, we identified 4 major actors in the AKI-to-CKD transition: (1) the tubular epithelial cells, (2) the endothelial cells of the interstitial capillary network, (3) the inflammatory infiltrate, and (4) the myofibroblasts. This review provides the most comprehensive and informative data we were able to collect and examines the pending questions.
Covered TIPS Procedure-Related Major Complications: Incidence, Management and Outcome From a Single Center
Authors: Yin Xiaochun , Gu Lihong , Zhang Ming , Yin Qin , Xiao Jiangqiang , Wang Yi , Zou Xiaoping , Zhang Feng , Zhuge Yuzheng
Published: May 2022

Background and Objective

Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established procedure for treating complications of portal hypertension. Due to the complexity of anatomy and difficulty of the puncture technique, the procedure itself might brought potential complications, such as puncture failure, bleeding, infection, and, rarely, death. The aim of this study is to explore the incidence, management, and outcome of TIPS procedure-related major complications using covered stents.

Methods

Patients who underwent TIPS implantation from January 2015 to December 2020 were recruited retrospectively. Major complications after TIPS were screened and analyzed.

Results

Nine hundred and forty-eight patients underwent the TIPS procedure with 95.1% (n = 902) technical success in our department. TIPS procedure-related major complications occurred in 30 (3.2%) patients, including hemobilia (n = 13; 1.37%), hemoperitoneum (n = 7; 0.74%), accelerated liver failure (n = 6; 0.63%), and rapidly progressive organ failure (n = 4; 0.42%). Among them, 8 patients died because of hemobilia (n = 1), accelerated liver failure (n = 4), and rapidly progressive organ failure (n = 3).

Conclusion

The incidence of major complications related to TIPS procedure is relatively low, and some of them could recover through effective medical intervention. In our cohort, the overall incidence is about 3%, which causes 0.84% death. The most fatal complication is organ failure and hemobilia.
Serum Concentration of Ropivacaine After Repeated Administration to Several Parts of the Head During Awake Craniotomy: A Prospective Cohort Study
Authors: Sato Takehito , Ando Takahiro , Asano Ichiko , Mori Atsushi , Motomura Kazuya , Nishiwaki Kimitoshi
Published: May 2022

Introduction

During awake craniotomy, effective use of local anesthetics, such as ropivacaine, is critical. Blood concentrations of ropivacaine after repeated administration over a short period during awake craniotomy have not been studied.

Materials and Methods

In this prospective cohort study, we evaluated serum concentrations of ropivacaine 15 min after each administration during awake craniotomy at Nagoya University Hospital between April 5, 2018 and August 31, 2019 to determine the safe dose. A total of 30 patients scheduled to undergo elective awake craniotomy were included. Patients were injected with 0.375% ropivacaine before the awake phase at the following points: scalp block (T1), headpin area (T2), skin incision area (T3), temporal muscle (T4), and dura mater (T5). Arterial blood samples were collected 15 min after ropivacaine administration. In addition to the blood concentrations of ropivacaine, complications during the awake phase were evaluated as secondary endpoints.

Results

The mean total dose of ropivacaine was 5.01 ± 0.68 mg/kg (maximum total dose: 6.30 mg/kg). The mean interval from T1 to T5 was 128.0 ± 17.7 min. The maximum serum concentration did not exceed the toxicity threshold of 4.3 μg/mL in any patient (mean serum concentration: T1, 1.23 ± 0.36 μg/mL; T5, 0.82 ± 0.26 μg/mL). No addiction symptoms were observed during awakening in any case.

Conclusion

Our results show that, in cases of awake craniotomy with repeated anesthetic administration, a total dose of up to 5.0 mg/kg is safe, without addiction symptoms. Relatively large amounts of ropivacaine can be safely injected during awake craniotomy.
A Preliminary Study on the Relationship Between High-Resolution Computed Tomography and Pulmonary Function in People at Risk of Developing Chronic Obstructive Pulmonary Disease
Authors: Lv Rui , Xie Mengyao , Jin Huaqian , Shu Pingping , Ouyang Mingli , Wang Yanmao , Yao Dan , Yang Lehe , Huang Xiaoying , Wang Yiran
Published: May 2022

Objectives

Patients with chronic obstructive pulmonary disease (COPD) have high morbidity and mortality, the opportunity to carry out a thoracic high-resolution CT (HRCT) scan may increase the possibility to identify the group at risk of disease. The aim of our study was to explore the differences in HRCT emphysema parameters, air trapping parameters, and lung density parameters between high and low-risk patients of COPD and evaluate their correlation with pulmonary function parameters.

Methods

In this retrospective, single-center cohort study, we enrolled outpatients from the Physical Examination Center and Respiratory Medicine of The First Affiliated Hospital of Wenzhou Medical University. The patients who were ≥ 40 years-old, had chronic cough or sputum production, and/or had exposure to risk factors for the disease and had not reached the diagnostic criteria is considered people at risk of COPD. They were divided into low-risk group and high-risk group according to FEV1/FVC ≥ 80% and 80%>FEV1/FVC ≥ 70%. Data on clinical characteristics, clinical symptom score, pulmonary function, and HRCT were recorded.

Results

72 COPD high-risk patients and 86 COPD low-risk patients were enrolled in the study, and the air trapping index of left, right, and bilateral lungs of the high-risk group were higher than those of the low-risk group. However, the result of mean expiratory lung density was opposite. The emphysema index of left, right, and bilateral lungs were negatively correlated with FEV1/FVC (correlation coefficients were -0.33, -0.22, -0.26). Consistently, the air trapping index of left and right lungs and bilateral lungs were negatively correlated with FEV1/FVC (correlation coefficients were -0.33, -0.23, -0.28). Additionally, the mean expiratory lung density of left and right lungs and bilateral lungs were positively correlated with FEV1/FVC (correlation coefficients were 0.31, 0.25, 0.29).

Conclusion

The emphysema index, air trapping index and the mean expiratory lung density shows significantly positive correlation with FEV1/FVC which can be used to assess the pulmonary function status of people at risk of COPD and provide a useful supplement for the early and comprehensive assessment of the disease.
High Urinary Sodium Concentrations in Severe SIADH: Case Reports of 2 Patients and Literature Review
Authors: Lee Lynette Mei Yi , Tan Sarah Ying Tse , Loh Wann Jia
Published: May 2022

We present two cases of severe hyponatremia secondary to syndrome of inappropriate secretion of antidiuretic hormone (SIADH) with very high urine sodium concentrations (>130 mmol/L). The first patient had hyponatremia from traumatic brain injury (TBI) while the second case had a history of recurrent SIADH triggered by various causes including gastritis. In both cases, fluid administration and/or consumption worsened the hyponatremia. Although a low urine sodium of <30 mmol/L is highly suggestive of hypovolemic hyponatremia and good response to saline infusion, there is lack of clarity of the threshold of which high urine sodium concentration can differentiate various causes of natriuresis such as SIADH, renal or cerebral salt wasting. Apart from high urine osmolality (>500 mOsm/kg), persistence of high urine sodium concentrations may be useful to predict poor response to fluid restriction in SIADH. More studies are needed to delineate treatment pathways of patients with very high urine osmolality and urine sodium concentrations in SIADH.
Comparison of Potato Viromes Between Introduced and Indigenous Varieties
Authors: Lai Xianjun , Wang Haiyan , Wu Caiyun , Zheng Wen , Leng Jing , Zhang Yizheng , Yan Lang
Published: May 2022

Viral disease in potatoes has been a major problem in potato production worldwide. In addition to the potential risk of introducing new diseases in new areas, viral-disease epidemics/pandemics can be initiated by “spillover” of indigenous viruses from infected alternative hosts into introduced cultivars. To investigate the tendency of potential viral infection/resistance, we analyzed the viromes of introduced and indigenous varieties of potatoes among different tissues using RNA-seq libraries. Bioinformatics analyses revealed that potato viruses PVM, PVY, and PVS were dominant and the most frequently identified viruses infecting potato virus-free plants in the field, and showed an infection bias between introduced and indigenous cultivars. PVY and PVS were the major viruses in introduced varieties, whereas PVM showed an extraordinarily high percentage in the indigenous variety. Other three common viruses, PVH, potato mop-top virus, and potato leafroll virus were identified specifically in the indigenous variety. There was a tendency for tissue-specific infection and sequence variation in viruses: underground parts (tubers, roots) harbored more unusual viruses, and tubers harbored relatively more variation with a high frequency of single nucleotide polymorphisms than other tissues. Taken together, our study provides a comprehensive overview of the composition, distribution, and sequence variation of viruses between introduced and indigenous varieties of potatoes.
Synergistic Interaction Between Paired Combinations of Natural Antimicrobials Against Poultry-Borne Pathogens
Authors: Liu Xiaoxia , Liu Rui , Zhao Ruting , Wang Jishi , Cheng Yongyou , Liu Qian , Wang Yanyun , Yang Shuming
Published: May 2022

Natural antimicrobials (NAM) are promising candidates for the successful control of poultry-borne bacteria, carrying potent antimicrobial activity (AMA) against a wide range of multidrug-resistant pathogens. Individual activities of carvacrol, eugenol, trans-cinnamaldehyde, oregano, and thymol, along with the combined activity of paired compounds, were examined using broth microdilution and checkerboard techniques. The characteristic interactions between the compounds were calculated using an improved method, based on combination index (CI) values. The bacteria examined herein were selected due to their known genetic resistance to at least one antibiotic. Our results indicated that thymol was most effective, exhibiting the lowest minimum inhibitory concentration (MIC) value against Salmonella pullorum, Escherichia coli, and Klebsiella pneumoniae, establishing the order of antimicrobial efficacy as: thymol > oregano > carvacrol > trans-cinnamaldehyde > eugenol. In the interaction study, the paired combination of carvacrol and thymol showed synergistic effects and was highly effective in reducing the antibiotic resistance of all the evaluated pathogens. Notably, all CI values were <1.0 in evaluations of S. pullorum, indicating the absence of antagonism between eugenol and thymol (or oregano). In K. pneumoniae, majority of CI values, which had a few concentration points, were smaller than 1.0, indicating a synergistic effect between eugenol and carvacrol (oregano or thymol), and trans-cinnamaldehyde and carvacrol. In E. coli, apart from some concentration points, some CI values were smaller than 1.0, demonstrating a synergistic effect between eugenol and carvacrol, and thymol and carvacrol (eugenol or oregano). It is therefore of great significance to investigate and illuminate the minimal effect concentration of these five components when they are used in combination as feed additives. Moreover, the improved evaluation method of this study provides a precise and extensive means to assess the synergistic effects of NAM.
Changes in Alpine Soil Bacterial Communities With Altitude and Slopes at Mount Shergyla, Tibetan Plateau: Diversity, Structure, and Influencing Factors
Authors: Zou Zehao , Yuan Ke , Ming Lili , Li Zhaohong , Yang Ying , Yang Ruiqiang , Cheng Weibin , Liu Hongtao , Jiang Jie , Luan Tiangang , Chen Baowei
Published: May 2022

The alpine ecosystem as one of the most representative terrestrial ecosystems has been highly concerned due to its susceptibility to anthropogenic impacts and climatic changes. However, the distribution pattern of alpine soil bacterial communities and related deterministic factors still remain to be explored. In this study, soils were collected from different altitudes and slope aspects of the Mount (Mt.) Shergyla, Tibetan Plateau, and were analyzed using 16S rRNA gene-based bioinformatics approaches. Acidobacteriota and Proteobacteria were identified consistently as the two predominant phyla in all soil samples, accounting for approximately 74% of the bacterial community. The alpha diversity of the soil bacterial community generally increased as the vegetation changed with the elevated altitude, but no significant differences in alpha diversity were observed between the two slopes. Beta diversity analysis of bacterial community showed that soil samples from the north slope were always differentiated obviously from the paired samples at the south slope with the same altitude. The whole network constituted by soil bacterial genera at the Mt. Shergyla was parsed into eight modules, and Elev-16S-573, Sericytochromatia, KD4-96, TK10, Pedomicrobium, and IMCC26256 genera were identified as the “hubs” in the largest module. The distance-based redundancy analysis (db-RDA) demonstrated that variations in soil bacterial community thereof with the altitude and slope aspects at the Mt. Shergyla were closely associated with environmental variables such as soil pH, soil water content, metal concentrations, etc. Our results suggest that environmental variables could serve as the deterministic factors for shaping the spatial pattern of soil bacterial community in the alpine ecosystems.