bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-linear effects of green finance on air quality in China: New evidence from a panel threshold model
Authors: Xiang Weimin , Qi Qiao , Gan Lei
Published: April 2023

Environmental problems, including air pollution, have upset the balance between the environment and economic development. In the face of worsening air pollution, growing attention is being paid to the role of financial institutions. To investigate how finance affects air pollution, this study used data from 30 Chinese provinces from 2014–2020, while considering industrial structure optimization and energy structure as threshold variables to propose a panel threshold model, which elucidates a nonlinear relationship between green finance and air quality in China. The panel data are sorted based on urbanization level, resource dependence, and geospatial distribution to examine the heterogeneous effects of green finance on air pollution. The analysis demonstrated that green finance considerably improves the overall air quality in Chinese provinces, but the effect is gradually weakened with the optimization of industrial structure and the improvement of clean energy efficiency. Moreover, green finance exerts a greater inhibitory impact on air pollution through industrial structure optimization compared to the impact of energy structure optimization. Regional variations in the environmental benefits of green finance were discerned. Resource dependence exacerbates the inhibiting impact of green finance on air pollution in the resource-based regions, while urbanization weakens the environmental benefits of green finance in urbanized regions. In terms of geographical distribution, green finance exhibited the best effect on air quality in western China. These findings shed the light on the positive role of green finance on air quality in China, thereby highlighting its importance for the air quality improvement programs of the provincial scales in China.
Substance P aggravates ligature-induced periodontitis in mice
Authors: Siddiqui Yasir Dilshad , Nie Xuguang , Wang Sheng , Abbasi Yasaman , Park Lauren , Fan Xiaoxuan , Thumbigere-Math Vivek , Chung Man-Kyo
Published: April 2023

Periodontitis is one of the most common oral diseases in humans, affecting over 40% of adult Americans. Pain-sensing nerves, or nociceptors, sense local environmental changes and often contain neuropeptides. Recent studies have suggested that nociceptors magnify host response and regulate bone loss in the periodontium. A subset of nociceptors projected to periodontium contains neuropeptides, such as calcitonin gene-related peptide (CGRP) or substance P (SP). However, the specific roles of neuropeptides from nociceptive neural terminals in periodontitis remain to be determined. In this study, we investigated the roles of neuropeptides on host responses and bone loss in ligature-induced periodontitis. Deletion of tachykinin precursor 1 (Tac1), a gene that encodes SP, or treatment of gingiva with SP antagonist significantly reduced bone loss in ligature-induced periodontitis, whereas deletion of calcitonin related polypeptide alpha (Calca), a gene that encodes CGRP, showed a marginal role on bone loss. Ligature-induced recruitment of leukocytes, including neutrophils, and increase in cytokines leading to bone loss in periodontium was significantly less in Tac1 knockout mice. Furthermore, intra-gingival injection of SP, but not neurokinin A, induced a vigorous inflammatory response and osteoclast activation in alveolar bone and facilitated bone loss in ligature-induced periodontitis. Altogether, our data suggest that SP plays significant roles in regulating host responses and bone resorption in ligature-induced periodontitis.
Multi-omics analysis reveals a macrophage-related marker gene signature for prognostic prediction, immune landscape, genomic heterogeneity, and drug choices in prostate cancer
Authors: Zhu Weian , Wu Jianjie , Huang Jiongduan , Xiao Dongming , Li Fengao , Wu Chenglun , Li Xiaojuan , Zeng Hengda , Zheng Jiayu , Lai Wenjie , Wen Xingqiao
Published: April 2023

Introduction

Macrophages are components of the innate immune system and can play an anti-tumor or pro-tumor role in the tumor microenvironment owing to their high heterogeneity and plasticity. Meanwhile, prostate cancer (PCa) is an immune-sensitive tumor, making it essential to investigate the value of macrophage-associated networks in its prognosis and treatment.

Methods

Macrophage-related marker genes (MRMGs) were identified through the comprehensive analysis of single-cell sequencing data from GSE141445 and the impact of macrophages on PCa was evaluated using consensus clustering of MRMGs in the TCGA database. Subsequently, a macrophage-related marker gene prognostic signature (MRMGPS) was constructed by LASSO-Cox regression analysis and grouped based on the median risk score. The predictive ability of MRMGPS was verified by experiments, survival analysis, and nomogram in the TCGA cohort and GEO-Merged cohort. Additionally, immune landscape, genomic heterogeneity, tumor stemness, drug sensitivity, and molecular docking were conducted to explore the relationship between MRMGPS and the tumor immune microenvironment, therapeutic response, and drug selection.

Results

We identified 307 MRMGs and verified that macrophages had a strong influence on the development and progression of PCa. Furthermore, we showed that the MRMGPS constructed with 9 genes and the predictive nomogram had excellent predictive ability in both the TCGA and GEO-Merged cohorts. More importantly, we also found the close relationship between MRMGPS and the tumor immune microenvironment, therapeutic response, and drug selection by multi-omics analysis.

Discussion

Our study reveals the application value of MRMGPS in predicting the prognosis of PCa patients. It also provides a novel perspective and theoretical basis for immune research and drug choices for PCa.
Inhibition of neutrophil extracellular trap formation attenuates NLRP1-dependent neuronal pyroptosis via STING/IRE1α pathway after traumatic brain injury in mice
Authors: Cao Yiyao , Shi Mingming , Liu Liang , Zuo Yan , Jia Haoran , Min Xiaobin , Liu Xilei , Chen Zhijuan , Zhou Yuan , Li Shenghui , Yang Guili , Liu Xiao , Deng Quanjun , Chen Fanglian , Chen Xin , Zhang Shu , Zhang Jianning
Published: April 2023

Introduction

Increased neutrophil extracellular trap (NET) formation has been reported to be associated with cerebrovascular dysfunction and neurological deficits in traumatic brain injury (TBI). However, the biological function and underlying mechanisms of NETs in TBI-induced neuronal cell death are not yet fully understood.

Methods

First, brain tissue and peripheral blood samples of TBI patients were collected, and NETs infiltration in TBI patients was detected by immunofluorescence staining and Western blot. Then, a controlled cortical impact device was used to model brain trauma in mice, and Anti-Ly6G, DNase, and CL-amidine were given to reduce the formation of neutrophilic or NETs in TBI mice to evaluate neuronal death and neurological function. Finally, the pathway changes of neuronal pyroptosis induced by NETs after TBI were investigated by administration of peptidylarginine deiminase 4 (a key enzyme of NET formation) adenovirus and inositol-requiring enzyme-1 alpha (IRE1α) inhibitors in TBI mice.

Results

We detected that both peripheral circulating biomarkers of NETs and local NETs infiltration in the brain tissue were significantly increased and had positive correlations with worse intracranial pressure (ICP) and neurological dysfunction in TBI patients. Furthermore, the depletion of neutrophils effectively reduced the formation of NET in mice subjected to TBI. we found that degradation of NETs or inhibition of NET formation significantly inhibited nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 1 (NLRP1) inflammasome-mediated neuronal pyroptosis after TBI, whereas these inhibitory effects were abolished by cyclic GMP-AMP (cGAMP), an activator of stimulating Interferon genes (STING). Moreover, overexpression of PAD4 in the cortex by adenoviruses could aggravate NLRP1-mediated neuronal pyroptosis and neurological deficits after TBI, whereas these pro-pyroptotic effects were rescued in mice also receiving STING antagonists. Finally, IRE1α activation was significantly upregulated after TBI, and NET formation or STING activation was found to promote this process. Notably, IRE1α inhibitor administration significantly abrogated NETs-induced NLRP1 inflammasome-mediated neuronal pyroptosis in TBI mice.

Discussion

Our findings indicated that NETs could contribute to TBI-induced neurological deficits and neuronal death by promoting NLRP1-mediated neuronal pyroptosis. Suppression of the STING/ IRE1α signaling pathway can ameliorate NETs-induced neuronal pyroptotic death after TBI.
Mercury increases IL-1β and IL-18 secretion and intensifies coronary arteritis in an animal model of Kawasaki disease
Authors: Alphonse Martin P. , Duong Trang T. , Tam Suzanne , Yeung Rae S. M.
Published: April 2023

Kawasaki disease (KD) is a multisystem vasculitis that predominantly targets the coronary arteries in young children. Epidemiological data suggest both environmental and genetic factors contribute to the susceptibility and severity of the disease. Mercury (Hg) is a known environmental pollutant and a Ca2+ signaling modulator. Ca2+ signaling regulates the activation of NLRP3 inflammasome. Using the Lactobacillus casei cell wall extract (LCWE) induced coronary arteritis mouse model of KD; we studied the effect of mercury on inflammasome activation and its impact on the immunopathogenesis of KD. Mercury enhances the expression of inflammasome activation resulting in caspase-1 mediated secretion of IL-1β and IL-18 cytokines. In vivo, the administration of mercury together with disease inducing LCWE exacerbates disease resulting in increased incidence and severity of coronary arteritis compared to LCWE alone. Mercury can act as a novel danger signal modulating Ca2+ signaling to increase IL-1β and IL-18 secretion and intensifies coronary arteritis in an animal model of KD.
The catalytic inhibitor epacadostat can affect the non-enzymatic function of IDO1
Authors: Panfili Eleonora , Mondanelli Giada , Orabona Ciriana , Gargaro Marco , Volpi Claudia , Belladonna Maria Laura , Rossini Sofia , Suvieri Chiara , Pallotta Maria Teresa
Published: April 2023

Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan metabolizing enzyme chronically activated in many cancer patients and its expression and activity correlate with a poor prognosis. In fact, it acts as an immune regulator and contributes to tumor-induced immunosuppression by determining tryptophan deprivation and producing immunosuppressive metabolites named kynurenines. These findings made IDO1 an attractive target for cancer immunotherapy and small-molecule inhibitors, such as epacadostat, have been developed to block its enzymatic activity. Although epacadostat was effective in preclinical models and in early phase trials, it gave negative results in a metastatic melanoma randomized phase III study to test the benefit of adding epacadostat to the reference pembrolizumab therapy. However, the reason for the epacadostat failure in this clinical trial has never been understood. Our data suggest that a possible explanation of epacadostat ineffectiveness may rely on the ability of this drug to enhance the other IDO1 immunoregulatory mechanism, involving intracellular signaling function. These findings open up a new perspective for IDO1 inhibitors developed as new anticancer drugs, which should be carefully evaluated for their ability to block not only the catalytic but also the signaling activity of IDO1.
Hypothesis: inflammatory acid-base disruption underpins Long Covid
Authors: van der Togt Vicky , Rossman Jeremy S.
Published: April 2023

The mechanism of Long Covid (Post-Acute Sequelae of COVID-19; PASC) is currently unknown, with no validated diagnostics or therapeutics. SARS-CoV-2 can cause disseminated infections that result in multi-system tissue damage, dysregulated inflammation, and cellular metabolic disruptions. The tissue damage and inflammation has been shown to impair microvascular circulation, resulting in hypoxia, which coupled with virally-induced metabolic reprogramming, increases cellular anaerobic respiration. Both acute and PASC patients show systemic dysregulation of multiple markers of the acid-base balance. Based on these data, we hypothesize that the shift to anaerobic respiration causes an acid-base disruption that can affect every organ system and underpins the symptoms of PASC. This hypothesis can be tested by longitudinally evaluating acid-base markers in PASC patients and controls over the course of a month. If our hypothesis is correct, this could have significant implications for our understanding of PASC and our ability to develop effective diagnostic and therapeutic approaches.
Oral vaccination as a potential strategy to manage chronic wasting disease in wild cervid populations
Authors: Napper Scott , Schatzl Hermann M.
Published: April 2023

Prion diseases are a novel class of infectious disease based in the misfolding of the cellular prion protein (PrPC) into a pathological, self-propagating isoform (PrPSc). These fatal, untreatable neurodegenerative disorders affect a variety of species causing scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in cervids, and Creutzfeldt-Jacob disease (CJD) in humans. Of the animal prion diseases, CWD is currently regarded as the most significant threat due its ongoing geographical spread, environmental persistence, uptake into plants, unpredictable evolution, and emerging evidence of zoonotic potential. The extensive efforts to manage CWD have been largely ineffective, highlighting the need for new disease management tools, including vaccines. Development of an effective CWD vaccine is challenged by the unique biology of these diseases, including the necessity, and associated dangers, of overcoming immune tolerance, as well the logistical challenges of vaccinating wild animals. Despite these obstacles, there has been encouraging progress towards the identification of safe, protective antigens as well as effective strategies of formulation and delivery that would enable oral delivery to wild cervids. In this review we highlight recent strategies for antigen selection and optimization, as well as considerations of various platforms for oral delivery, that will enable researchers to accelerate the rate at which candidate CWD vaccines are developed and evaluated.
Failure of ALL recognition by CAR T cells: a review of CD 19-negative relapses after anti-CD 19 CAR-T treatment in B-ALL
Authors: Aparicio-Pérez Clara , Carmona MDolores , Benabdellah Karim , Herrera Concha
Published: April 2023

The use of chimeric antigen receptor (CAR) T lymphocytes in the treatment of refractory or relapsed (R/R) B cell acute lymphoblastic leukemia (B-ALL) has meant a radical change in the prognosis of these patients, whose chances of survival with conventional treatment are very low. The current probability of event-free survival by R/R B-ALL patients treated using anti-CD 19 CART cell therapy is as high as 50-60% at 1.5 years, which is a very important advance for this group of very ill patients. Although most patients (70 to 94%) achieve complete remission (CR), the main problem continues to be relapse of the disease. Most relapses, both in clinical trials and real-world evidence, are due to failure of CAR-T cell expansion or limited CAR-T persistence. However, despite the adequate functioning of infused CART lymphocytes, the tumor cells of an important group of patients manage to evade CAR-T attack, resulting in a CD 19-negative relapse. Several mechanisms have been described that may be able to produce the escape of leukemic cells, such as acquired mutations and alternative splicing of the CD19 antigen, CD19 epitope loss or masking, leukemia lineage switching, and trogocytosis. In the present review, we comprehensively analyze the leukemic cell escape mechanisms, the incidence of CD19-negative relapse reported in clinical trials and real-world evidence (outside clinical trials), and provide an update on the main lines of current research into the prevention of leukemia evasion.
Specific and safe targeting of glioblastoma using switchable and logic-gated RevCAR T cells
Authors: Saleh Haidy A. , Mitwasi Nicola , Ullrich Martin , Kubeil Manja , Toussaint Magali , Deuther-Conrad Winnie , Neuber Christin , Arndt Claudia , R. Loureiro Liliana , Kegler Alexandra , González Soto Karla Elizabeth , Belter Birgit , Rössig Claudia , Pietzsch Jens , Frenz Marcus , Bachmann Michael , Feldmann Anja
Published: April 2023

Glioblastoma (GBM) is still an incurable tumor that is associated with high recurrence rate and poor survival despite the current treatment regimes. With the urgent need for novel therapeutic strategies, immunotherapies, especially chimeric antigen receptor (CAR)-expressing T cells, represent a promising approach for specific and effective targeting of GBM. However, CAR T cells can be associated with serious side effects. To overcome such limitation, we applied our switchable RevCAR system to target both the epidermal growth factor receptor (EGFR) and the disialoganglioside GD2, which are expressed in GBM. The RevCAR system is a modular platform that enables controllability, improves safety, specificity and flexibility. Briefly, it consists of RevCAR T cells having a peptide epitope as extracellular domain, and a bispecific target module (RevTM). The RevTM acts as a switch key that recognizes the RevCAR epitope and the tumor-associated antigen, and thereby activating the RevCAR T cells to kill the tumor cells. However, in the absence of the RevTM, the RevCAR T cells are switched off. In this study, we show that the novel EGFR/GD2-specific RevTMs can selectively activate RevCAR T cells to kill GBM cells. Moreover, we show that gated targeting of GBM is possible with our Dual-RevCAR T cells, which have their internal activation and co-stimulatory domains separated into two receptors. Therefore, a full activation of Dual-RevCAR T cells can only be achieved when both receptors recognize EGFR and GD2 simultaneously via RevTMs, leading to a significant killing of GBM cells both in vitro and in vivo.
Community structure along the Western Antarctic continental shelf and a latitudinal change in epibenthic faunal abundance assessed by photographic surveys
Authors: Grimes Candace J. , Donnelly Kyle , Ka Cheikhouna , Noor Nusrat , Mahon Andrew R. , Halanych Kenneth M.
Published: April 2023

The Southern Ocean’s continental shelf communities harbor high benthic biodiversity. However, most census methods have relied on trawling or dredging rather than direct observation. Benthic photographic and videographic transect surveys serve a key role in characterizing marine communities’ abundance and diversity, and they also provide information on the spatial arrangement of species within a community. To investigate diversity and abundance in Southern Ocean benthic communities, we employed photographic transects during cruises aboard the RVIB Nathanial B. Palmer (November 2012) and the ASRV Laurence M. Gould (February 2013). One kilometer long photographic transects were conducted at 8 sites along 6,000 km of Western Antarctica from the tip of the Antarctic Peninsula to the Ross Sea from which epifaunal echinoderms, tunicates, arthropods, cnidarians, poriferans, and annelids were identified and counted allowing estimations of biodiversity. Our results do not support a latitudinal trend in diversity, but rather a decrease in abundance of macrofaunal individuals at higher latitude sites. All communities sampled on the Western Antarctic shelf were primarily dominated by ophiuroids, pycnogonids, holothuroids, and demosponges. However, the most abundant taxon across all sites was Ophionotus victoriae, followed by the symbiotic partners Iophon sp. (demosponge) and Ophioplinthus spp. (ophiuroid). Data also confirm that the Southern Ocean is composed of discretely unique benthic communities. These results provide critical understanding of the current community structure and diversity serving as a baseline as the Antarctic continental shelf changes due to rising ocean temperatures, climate change, and collapse of large ice sheets.
Groundwater as a source of phosphorus and silicate in an estuarine zone: results from continuous monitoring of nutrients and 222Rn
Authors: Oh Yong Hwa , Kim Jeonghyun , Kim Guebuem , Kim Tae-Hoon
Published: April 2023

The concentrations of 222Rn and dissolved inorganic nutrients in river water at a fixed station of the Nakdong River estuary which has an artificial barrage were continuously measured from October 2014 to May 2015. Monthly benthic 222Rn flux from the river bottom was estimated using a simple mass balance model, taking into account 222Rn sources and sinks. The estimated benthic 222Rn flux shows a significant correlation with groundwater level, suggesting that groundwater level can be used as a representative of the groundwater input. Based on correlation analyses, the concentration of dissolved inorganic nitrogen (DIN) was found to be dependent primarily on river water input. In contrast, the concentrations of dissolved inorganic phosphorus (DIP) and dissolved inorganic silicate (DSi) were predominantly controlled by groundwater input. Our results suggest that groundwater input may be an important source of DIP, especially under P-limited condition, which can affect marine primary production and ecological problems such as eutrophication and algal blooms in the coastal zones.
Ultra-high photo responsivity and self-powered photodetector in broad spectral range based on non-layered MnSe/WSe2 heterojunction
Authors: Zhao Shuting , Ma Xiurong , Cao Xuanhao , Lei Zehong , Yang Yibin , Tao Lili , Zheng Zhaoqiang , Feng Xing , Zhao Yu
Published: April 2023

Due to its good p-type semiconductor characteristics, MnSe has a great application prospect in high-performance electronic and optoelectronic devices. However, heterojunctions of MnSe still need to be deeply studied to improve its electrical and photoelectric properties. Here, it is reported that the two-dimensional (2D) MnSe/WSe2 heterojunction is structured by the non-layered MnSe nanosheets synthesized by chemical vapor deposition (CVD) method and the mechanically exfoliated layered WSe2. The heterojunction device exhibits a rectification effect and a current on/off ratio of 6,557. Meanwhile, it has a broad spectral range response from ultraviolet (UV) to short-wave infrared radiation (SWIR) (300–2,200 nm), and achieves an ultra-high responsivity of 156 A/W, along with an excellent detectivity of 2.21 × 1012 jones, and an outstanding external quantum efficiency (EQE) of 36,400%. Moreover, the type II band alignment and the built-in potential in the MnSe/WSe2 heterojunction can facilitate the separation of the photoexcited electron-hole pairs, which enables the significant photovoltaic characteristics and self-powered photoswitching response. This work reveals the novel performance of the 2D MnSe/WSe2 heterojunction and a great potential in photoswitching, photodetector, and photovoltaic applications.
MIB-ANet: A novel multi-scale deep network for nasal endoscopy-based adenoid hypertrophy grading
Authors: Bi Mingmin , Zheng Siting , Li Xuechen , Liu Haiyan , Feng Xiaoshan , Fan Yunping , Shen Linlin
Published: April 2023

Introduction

To develop a novel deep learning model to automatically grade adenoid hypertrophy, based on nasal endoscopy, and asses its performance with that of E.N.T. clinicians.

Methods

A total of 3,179 nasoendoscopic images, including 4-grade adenoid hypertrophy (Parikh grading standard, 2006), were collected to develop and test deep neural networks. MIB-ANet, a novel multi-scale grading network, was created for adenoid hypertrophy grading. A comparison between MIB-ANet and E.N.T. clinicians was conducted.

Results

In the SYSU-SZU-EA Dataset, the MIB-ANet achieved 0.76251 F1 score and 0.76807 accuracy, and showed the best classification performance among all of the networks. The visualized heatmaps show that MIB-ANet can detect whether adenoid contact with adjacent tissues, which was interpretable for clinical decision. MIB-ANet achieved at least 6.38% higher F1 score and 4.31% higher accuracy than the junior E.N.T. clinician, with much higher (80× faster) diagnosing speed.

Discussion

The novel multi-scale grading network MIB-ANet, designed for adenoid hypertrophy, achieved better classification performance than four classical CNNs and the junior E.N.T. clinician. Nonetheless, further studies are required to improve the accuracy of MIB-ANet.
Fusobacterium nucleatum Accelerates Atherosclerosis via Macrophage-Driven Aberrant Proinflammatory Response and Lipid Metabolism
Authors: Zhou Jieyu , Liu Lin , Wu Peiyao , Zhao Lei , Wu Yafei
Published: April 2023

Graphical Abstract

Schematic diagram depicting the process of F. nucleatum inducing atherosclerosis. As one of the oral commensal bacteria, F. nucleatum is abundant in periodontitis sites and can enter blood circulation through damaged periodontal tissue. Subsequently, there is an increase in risk factors (dyslipidemia and inflammatory mediators) in the blood circulation. In addition, it has high invasiveness and can invade into the vascular intima, promoting macrophages M1 polarization, aberrant lipid metabolism, and cell apoptosis, thereby increasing the release of inflammatory mediators, and the degradation of extracellular matrix in the atherosclerotic plaque microenvironment. By then, plaques are prone to rupture.
In vitro Sequestration of Molecular and Mass Spectra Characterized Metallophilic Cadmium Tolerant Bacteria for Sustainable Agriculture
Authors: Uqab Baba , Nazir Ruqeya , Ganai Bashir Ahmad , Rahi Praveen
Published: April 2023

Due to industrialization, the contamination of toxic metals in soils is currently one of the major concerns to scientists worldwide. The presence of high concentrations of heavy metals including cadmium in the environment is mainly attributed to human activities. Being a highly toxic metal, cadmium can enter plant cell transporters usually used for the uptake of essential cations, such as iron, calcium, and zinc. This study deals with the appraisement of response and tolerance shown by various bacteria in varied cadmium concentrations (100–1,000 ppm). The optical density (OD) of the isolates was measured to determine the minimum inhibitory concentration (MIC) of cadmium. Isolated bacteria have been identified using 16S rRNA gene sequence and Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Among the 72 isolates, 07 (Bacillus pumilus, Enterobacter kobei, Klebsiella pneumonia, Pseudomonas mandelii, Pseudomonas putida, Pseudomonas avellanae, and Staphylococcus equorum), isolates had efficacy for cadmium tolerance and showed sequestration potential at varying MIC. Furthermore, K. pneumonia was observed to have the highest (900 ppm) tolerance for cadmium and the lowest (600 ppm) was shown by E. kobei. Besides, K. pneumonia showed the highest (75.2%) sequestration potential while the least (52.4%) potential was observed for P. putida. These cadmium tolerant species can be implemented in contaminated environments for detoxification and elimination of cadmium from these agricultural fields.
New perspectives in application of kidney biomarkers in mycotoxin induced nephrotoxicity, with a particular focus on domestic pigs
Authors: Ráduly Zsolt , Szabó András , Mézes Miklós , Balatoni Ildikó , Price Robert G. , Dockrell Mark E. , Pócsi István , Csernoch László
Published: April 2023

The gradual spread of Aspergilli worldwide is adding to the global shortage of food and is affecting its safe consumption. Aspergillus-derived mycotoxins, including aflatoxins and ochratoxin A, and fumonisins (members of the fusariotoxin group) can cause pathological damage to vital organs, including the kidney or liver. Although the kidney functions as the major excretory system in mammals, monitoring and screening for mycotoxin induced nephrotoxicity is only now a developmental area in the field of livestock feed toxicology. Currently the assessment of individual exposure to mycotoxins in man and animals is usually based on the analysis of toxin and/or metabolite contamination in the blood or urine. However, this requires selective and sensitive analytical methods (e.g., HPLC-MS/MS), which are time consuming and expensive. The toxicokinetic of mycotoxin metabolites is becoming better understood. Several kidney biomarkers are used successfully in drug development, however cost-efficient, and reliable kidney biomarkers are urgently needed for monitoring farm animals for early signs of kidney disease. β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) are the dominant biomarkers employed routinely in environmental toxicology research, while kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are also emerging as effective markers to identify mycotoxin induced nephropathy. Pigs are exposed to mycotoxins due to their cereal-based diet and are particularly susceptible to Aspergillus mycotoxins. In addition to commonly used diagnostic markers for nephrotoxicity including plasma creatinine, NAG, KIM-1 and NGAL can be used in pigs. In this review, the currently available techniques are summarized, which are used for screening mycotoxin induced nephrotoxicity in farm animals. Possible approaches are considered, which could be used to detect mycotoxin induced nephropathy.
The role of the gut microbiome and its metabolites in cerebrovascular diseases
Authors: Xu Hongyu , Xu Ziyue , Long Shengrong , Li Zhengwei , Jiang Jiazhi , Zhou Qiangqiang , Huang Xiaopeng , Wu Xiaohui , Wei Wei , Li Xiang
Published: April 2023

The gut microbiome is critically involved in maintaining normal physiological function in the host. Recent studies have revealed that alterations in the gut microbiome contribute to the development and progression of cerebrovascular disease via the microbiota-gut-brain axis (MGBA). As a broad communication network in the human body, MGBA has been demonstrated to have significant interactions with various factors, such as brain structure and function, nervous system diseases, etc. It is also believed that the species and composition of gut microbiota and its metabolites are intrinsically linked to vascular inflammation and immune responses. In fact, in fecal microbiota transplantation (FMT) research, specific gut microbiota and downstream-related metabolites have been proven to not only participate in various physiological processes of human body, but also affect the occurrence and development of cerebrovascular diseases directly or indirectly through systemic inflammatory immune response. Due to the high mortality and disability rate of cerebrovascular diseases, new treatments to improve intestinal dysbacteriosis have gradually attracted widespread attention to better ameliorate the poor prognosis of cerebrovascular diseases in a non-invasive way. This review summarizes the latest advances in the gut microbiome and cerebrovascular disease research and reveals the profound impact of gut microbiota dysbiosis and its metabolites on cerebrovascular diseases. At the same time, we elucidated molecular mechanisms whereby gut microbial metabolites regulate the expression of specific interleukins in inflammatory immune responses. Moreover, we further discuss the feasibility of novel therapeutic strategies targeting the gut microbiota to improve the outcome of patients with cerebrovascular diseases. Finally, we provide new insights for standardized diagnosis and treatment of cerebrovascular diseases.
Whole-genome sequencing reveals high-risk clones of Pseudomonas aeruginosa in Guangdong, China
Authors: Zhao Yonggang , Chen Dingqiang , Ji Boyang , Zhang Xingju , Anbo Mikkel , Jelsbak Lars
Published: April 2023

The ever-increasing prevalence of infections produced by multidrug-resistant or extensively drug-resistant Pseudomonas aeruginosa is commonly linked to a limited number of aptly-named epidemical ‘high-risk clones’ that are widespread among and within hospitals worldwide. The emergence of new potential high-risk clone strains in hospitals highlights the need to better and further understand the underlying genetic mechanisms for their emergence and success. P. aeruginosa related high-risk clones have been sporadically found in China, their genome sequences have rarely been described. Therefore, the large-scale sequencing of multidrug-resistance high-risk clone strains will help us to understand the emergence and transmission of antibiotic resistances in P. aeruginosa high-risk clones. In this study, 212 P. aeruginosa strains were isolated from 2 tertiary hospitals within 3 years (2018–2020) in Guangdong Province, China. Whole-genome sequencing, multi-locus sequence typing (MLST) and antimicrobial susceptibility testing were applied to analyze the genomic epidemiology of P. aeruginosa in this region. We found that up to 130 (61.32%) of the isolates were shown to be multidrug resistant, and 196 (92.45%) isolates were Carbapenem-Resistant Pseudomonas aeruginosa. MLST analysis demonstrated high diversity of sequence types, and 18 reported international high-risk clones were identified. Furthermore, we discovered the co-presence of exoU and exoS genes in 5 collected strains. This study enhances insight into the regional research of molecular epidemiology and antimicrobial resistance of P. aeruginosa in China. The high diversity of clone types and regional genome characteristics can serve as a theoretical reference for public health policies and help guide measures for the prevention and control of P. aeruginosa resistance.
Contrasting influences of two dominant plants, Dasiphora fruticosa and Ligularia virguarea, on aboveground and belowground communities in an alpine meadow
Authors: Song Hongxian , Liu Ziyang , Cui Hanwen , Chen Jingwei , Chen Shuyan , Gao Haining , Yang Xiaoli , Wang Yajun , Wang Jiajia , Liu Kun , Xiao Sa , An Lizhe , Nielsen Uffe N.
Published: April 2023

Soil organisms are abundant, phylogenetically and functionally diverse, and interact to catalyse and regulate critical soil processes. Understanding what structures belowground communities is therefore fundamental to gaining insight into ecosystem functioning. Dominant plants have been shown to influence belowground communities both directly and indirectly through changes in abiotic and biotic factors. In a field study, we used piecewise structural equation modelling to disentangle and compare the effects of a dominant allelopathic plant, Ligularia virgaurea, and a dominant facilitative plant, Dasiphora fruticosa, on understory plant, soil microbial and nematode community composition in an alpine meadow on the Tibetan plateau. Dasiphora fruticosa was associated with changes in edaphic variables (total nitrogen, soil organic carbon, pH and ammonium), understory plant and soil bacterial communities, whereas Ligularia virguarea was associated with increased soil ammonium content and soil fungal richness relative to dominant plant-free control plots. Moreover, nematode richness was significantly greater under D. fruticosa, with no change in nematode community composition. By contrast, nematode richness under Ligularia virgaurea was similar to that of dominant plant-free control plots, but nematode community composition differed from the control. The effects of both plants were predominantly direct rather than mediated by indirect pathways despite the observed effects on understory plant communities, soil properties and microbial assemblages. Our results highlight the importance of plants in determining soil communities and provide new insight to disentangle the complex above- and belowground linkages.
Non-inhibitory levels of oxygen during cultivation increase freeze-drying stress tolerance in Limosilactobacillus reuteri DSM 17938
Authors: Rao Nikhil Seshagiri , Ermann Lundberg Ludwig , Tomasson Julia , Tullberg Cecilia , Brink Daniel P. , Palmkron Shuai Bai , van Niel Ed W. J. , Håkansson Sebastian , Carlquist Magnus
Published: April 2023

The physiological effects of oxygen on Limosilactobacillus reuteri DSM 17938 during cultivation and the ensuing properties of the freeze-dried probiotic product was investigated. On-line flow cytometry and k-means clustering gating was used to follow growth and viability in real time during cultivation. The bacterium tolerated aeration at 500 mL/min, with a growth rate of 0.74 ± 0.13 h−1 which demonstrated that low levels of oxygen did not influence the growth kinetics of the bacterium. Modulation of the redox metabolism was, however, seen already at non-inhibitory oxygen levels by 1.5-fold higher production of acetate and 1.5-fold lower ethanol production. A significantly higher survival rate in the freeze-dried product was observed for cells cultivated in presence of oxygen compared to absence of oxygen (61.8% ± 2.4% vs. 11.5% ± 4.3%), coinciding with a higher degree of unsaturated fatty acids (UFA:SFA ratio of 10 for air sparged vs. 3.59 for N2 sparged conditions.). Oxygen also resulted in improved bile tolerance and boosted 5′nucleotidase activity (370 U/L vs. 240 U/L in N2 sparged conditions) but lower tolerance to acidic conditions compared bacteria grown under complete anaerobic conditions which survived up to 90 min of exposure at pH 2. Overall, our results indicate the controlled supply of oxygen during production may be used as means for probiotic activity optimization of L. reuteri DSM 17938.
Genetically supported causality between gut microbiota, gut metabolites and low back pain: a two-sample Mendelian randomization study
Authors: Su Mengchan , Tang Yidan , Kong Weishuang , Zhang Shuangyi , Zhu Tao
Published: April 2023

Background

Previous studies have implicated a vital association between gut microbiota/gut microbial metabolites and low back pain (LBP), but their causal relationship is still unclear. Therefore, we aim to comprehensively investigate their causal relationship and identify the effect of gut microbiota/gut microbial metabolites on risk of LBP using a two-sample Mendelian randomization (MR) study.

Methods

Summary data from genome-wide association studies (GWAS) of gut microbiota (18,340 participants), gut microbial metabolites (2,076 participants) and LBP (FinnGen biobank) were separately obtained. The inverse variance-weighted (IVW) method was used as the main MR analysis. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were conducted to evaluate the horizontal pleiotropy and to eliminate outlier single-nucleotide polymorphisms (SNPs). Cochran’s Q-test was applied for heterogeneity detection. Besides, leave-one-out analysis was conducted to determine whether the causal association signals were driven by any single SNP. Finally, a reverse MR was performed to evaluate the possibility of reverse causation.

Results

We discovered that 20 gut microbial taxa and 2 gut microbial metabolites were causally related to LBP (p < 0.05). Among them, the lower level of family Ruminococcaceae (OR: 0.771, 95% CI: 0.652–0.913, FDR-corrected p = 0.045) and Lactobacillaceae (OR: 0.875, 95% CI: 0.801–0.955, FDR-corrected p = 0.045) retained a strong causal relationship with higher risk of LBP after the Benjamini–Hochberg Corrected test. The Cochrane’s Q test revealed no Heterogeneity (p > 0.05). Besides, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy (p > 0.05). Furthermore, leave-one-out analysis confirmed the robustness of MR results. After adding BMI to the multivariate MR analysis, the 17 gut microbial taxa exposure-outcome effect were significantly attenuated and tended to be null.

Conclusion

Our findings confirm the the potential causal effect of specific gut microbiota and gut microbial metabolites on LBP, which offers new insights into the gut microbiota-mediated mechanism of LBP and provides the theoretical basis for further explorations of targeted prevention strategies.
Detection of maternal transmission of resistant Gram-negative bacteria in a Cambodian hospital setting
Authors: Chomkatekaew Chalita , Thaipadungpanit Janjira , Hearn Pasco , Soeng Sona , Pol Sreymom , Neou Leakhena , Hopkins Jill , Turner Paul , Batty Elizabeth M.
Published: April 2023

Infection with Extended-spectrum beta-lactamase -producing Enterobacterales (ESBL-E) is common in infants and leads to increased intensive care unit admission and mortality, but the role of maternal transmission in colonization of infants is unclear. Using paired isolates from 50 pairs of mothers and neonates admitted to a Cambodian hospital, we investigated antimicrobial resistance in Escherichia coli and Klebsiella pneumoniae using whole genome sequencing. We detected a wide variety of ESBL-E genes present in this population along with high levels of multidrug resistance. From 21 pairs where the same organism was present in both mother and neonate, we identified eight pairs with identical or near-identical isolates from both individuals suggestive of transmission at or around birth, including a pair with transmission of multiple strains. We found no evidence for transmission of plasmids only from mother to infant. This suggests vertical transmission outside hospitals as a common cause of ESBL-E colonization in neonates.
Flagellar brake protein YcgR interacts with motor proteins MotA and FliG to regulate the flagellar rotation speed and direction
Authors: Han Qun , Wang Shao-Feng , Qian Xin-Xin , Guo Lu , Shi Yi-Feng , He Rui , Yuan Jun-Hua , Hou Yan-Jie , Li De-Feng
Published: April 2023

In E. coli and related species, flagellar brake protein YcgR responds to the elevated intracellular c-di-GMP, decreases the flagellar rotation speed, causes a CCW rotation bias, and regulates bacterial swimming. Boehm et al. suggested that c-di-GMP-activated YcgR directly interacted with the motor protein MotA to curb flagellar motor output. Paul et al. proposed that YcgR disrupted the organization of the FliG C-terminal domain to bias the flagellar rotation. The target proteins are controversial, and the role of motor proteins remains unclear in flagellar rotation speed and direction regulation by YcgR. Here we assayed the motor proteins’ affinity via a modified FRET biosensor and accessed the role of those key residue via bead assays. We found that YcgR could interact with both MotA and FliG, and the affinities could be enhanced upon c-di-GMP binding. Furthermore, residue D54 of YcgR-N was needed for FliG binding. The mutation of the FliG binding residue D54 or the MotA binding ones, F117 and E232, restored flagellar rotation speed in wild-type cells and cells lacking chemotaxis response regulator CheY that switched the flagellar rotation direction and decreased the CCW ratio in wild-type cells. We propose that c-di-GMP-activated YcgR regulated the flagellar rotation speed and direction via its interaction with motor proteins MotA and FliG. Our work suggest the role of YcgR-motor proteins interaction in bacterial swimming regulation.
Soil phosphorus form affects the advantages that arbuscular mycorrhizal fungi confer on the invasive plant species, Solidago canadensis, over its congener
Authors: Chen Li , Wang Mengqi , Shi Yu , Ma Pinpin , Xiao Yali , Yu Hongwei , Ding Jianqing
Published: April 2023

Interactions between plants and arbuscular mycorrhizal fungi (AMF) are strongly affected by soil phosphorus (P) availability. However, how P forms impact rhizosphere AMF diversity, community composition, and the co-occurrence network associated with native and invasive plants, and whether these changes in turn influence the invasiveness of alien species remain unclear. In this work, we performed a greenhouse experiment with the invasive species Solidago canadensis and its native congener S. decurrens to investigate how different forms of P altered the AMF community and evaluate how these changes were linked with the growth advantage of S. canadensis relative to S. decurrens. Plants were subjected to five different P treatments: no P addition (control), simple inorganic P (sodium dihydrogen phosphate, NaP), complex inorganic P (hydroxyapatite, CaP), simple organic P (adenosine monophosphate, AMP) and complex organic P (myo-inositol hexakisphosphate, PA). Overall, invasive S. canadensis grew larger than native S. decurrens across all P treatments, and this growth advantage was strengthened when these species were grown in CaP and AMP treatments. The two Solidago species harbored divergent AMF communities, and soil P treatments significantly shifted AMF community composition. In particular, the differences in AMF diversity, community composition, topological features and keystone taxa of the co-occurrence networks between S. canadensis and S. decurrens were amplified when the dominant form of soil P was altered. Despite significant correlations between AMF alpha diversity, community structure, co-occurrence network composition and plant performance, we found that alpha diversity and keystone taxa of the AMF co-occurrence networks were the primary factors influencing plant growth and the growth advantage of invasive S. canadensis between soil P treatments. These results suggest that AMF could confer invasive plants with greater advantages over native congeners, depending on the forms of P in the soil, and emphasize the important roles of multiple AMF traits in plant invasion.
Exploring antibiotic resistance load in paddy-upland rotation fields amended with commercial organic and chemical/slow release fertilizer
Authors: Han Bingjun , Shen Shizhou , Yang Fengxia , Wang Xiaolong , Gao Wenxuan , Zhang Keqiang
Published: April 2023

Agricultural fertilization caused the dissemination of antibiotic resistance genes (ARGs) in agro-ecological environment, which poses a global threat to crop-food safety and human health. However, few studies are known about the influence of different agricultural fertilization modes on antibiotic resistome in the paddy-upland rotation soils. Therefore, we conducted a field experiment to compare the effect of different fertilization (chemical fertilizer, slow release fertilizer and commercial organic fertilizer replacement at various rates) on soil antibiotic resistome in paddy-upland rotation fields. Results revealed that a total of 100 ARG subtypes and 9 mobile genetic elements (MGEs) occurred in paddy-upland rotation soil, among which MDR-ARGs, MLSB-ARGs and tet-ARGs were the dominant resistance determinants. Long-term agricultural fertilization remarkably facilitated the vertical accumulation of ARGs, in particular that blaampC and tetO in relative abundance showed significant enrichment with increasing depth. It’s worth noting that slow release fertilizer significantly increased soil ARGs, when comparable to manure with 20% replacing amount, but chemical fertilizer had only slight impact on soil ARGs. Fertilization modes affected soil microbial communities, mainly concentrated in the surface layer, while the proportion of Proteobacteria with the highest abundance decreased gradually with increasing depth. Furthermore, microbial community and MGEs were further proved to be essential factors in regulating the variability of ARGs of different fertilization modes by structural equation model, and had strong direct influence (λ = 0.61, p < 0.05; λ = 0. 55, p < 0.01). The results provided scientific guidance for reducing the spreading risk of ARGs and control ARG dissemination in agricultural fertilization.