bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic manipulation of the human gut bacterium Eggerthella lenta reveals a widespread family of transcriptional regulators
Authors: Dong Xueyang , Guthrie Ben G. H. , Alexander Margaret , Noecker Cecilia , Ramirez Lorenzo , Glasser Nathaniel R. , Turnbaugh Peter J. , Balskus Emily P.
Published: December 2022

Eggerthella lenta is a prevalent human gut Actinobacterium implicated in drug, dietary phytochemical, and bile acid metabolism and associated with multiple human diseases. No genetic tools are currently available for the direct manipulation of E. lenta. Here, we construct shuttle vectors and develop methods to transform E. lenta and other Coriobacteriia. With these tools, we characterize endogenous E. lenta constitutive and inducible promoters using a reporter system and construct inducible expression systems, enabling tunable gene regulation. We also achieve genome editing by harnessing an endogenous type I-C CRISPR-Cas system. Using these tools to perform genetic knockout and complementation, we dissect the functions of regulatory proteins and enzymes involved in catechol metabolism, revealing a previously unappreciated family of membrane-spanning LuxR-type transcriptional regulators. Finally, we employ our genetic toolbox to study the effects of E. lenta genes on mammalian host biology. By greatly expanding our ability to study and engineer gut Coriobacteriia, these tools will reveal mechanistic details of host-microbe interactions and provide a roadmap for genetic manipulation of other understudied human gut bacteria.
SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling
Authors: Biering Scott B. , Gomes de Sousa Francielle Tramontini , Tjang Laurentia V. , Pahmeier Felix , Zhu Chi , Ruan Richard , Blanc Sophie F. , Patel Trishna S. , Worthington Caroline M. , Glasner Dustin R. , Castillo-Rojas Bryan , Servellita Venice , Lo Nicholas T. N. , Wong Marcus P. , Warnes Colin M. , Sandoval Daniel R. , Clausen Thomas Mandel , Santos Yale A. , Fox Douglas M. , Ortega Victoria , Näär Anders M. , Baric Ralph S. , Stanley Sarah A. , Aguilar Hector C. , Esko Jeffrey D. , Chiu Charles Y. , Pak John E. , Beatty P. Robert , Harris Eva
Published: December 2022

Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well as in distal organs. While it is appreciated that an exaggerated inflammatory response is associated with barrier dysfunction, the triggers of vascular leak are unclear. Here, we report that cell-intrinsic interactions between the Spike (S) glycoprotein of SARS-CoV-2 and epithelial/endothelial cells are sufficient to induce barrier dysfunction in vitro and vascular leak in vivo, independently of viral replication and the ACE2 receptor. We identify an S-triggered transcriptional response associated with extracellular matrix reorganization and TGF-β signaling. Using genetic knockouts and specific inhibitors, we demonstrate that glycosaminoglycans, integrins, and the TGF-β signaling axis are required for S-mediated barrier dysfunction. Notably, we show that SARS-CoV-2 infection caused leak in vivo, which was reduced by inhibiting integrins. Our findings offer mechanistic insight into SARS-CoV-2-triggered vascular leak, providing a starting point for development of therapies targeting COVID-19.
Structure of the AlgKX modification and secretion complex required for alginate production and biofilm attachment in Pseudomonas aeruginosa
Authors: Gheorghita Andreea A. , Li Yancheng E. , Kitova Elena N. , Bui Duong T. , Pfoh Roland , Low Kristin E. , Whitfield Gregory B. , Walvoort Marthe T. C. , Zhang Qingju , Codée Jeroen D. C. , Klassen John S. , Howell P. Lynne
Published: December 2022

Synthase-dependent secretion systems are a conserved mechanism for producing exopolysaccharides in Gram-negative bacteria. Although widely studied, it is not well understood how these systems are organized to coordinate polymer biosynthesis, modification, and export across both membranes and the peptidoglycan. To investigate how synthase-dependent secretion systems produce polymer at a molecular level, we determined the crystal structure of the AlgK-AlgX (AlgKX) complex involved in Pseudomonas aeruginosa alginate exopolysaccharide acetylation and export. We demonstrate that AlgKX directly binds alginate oligosaccharides and that formation of the complex is vital for polymer production and biofilm attachment. Finally, we propose a structural model for the AlgEKX outer membrane modification and secretion complex. Together, our study provides insight into how alginate biosynthesis proteins coordinate production of a key exopolysaccharide involved in establishing persistent Pseudomonas lung infections.
Structural basis for a human broadly neutralizing influenza A hemagglutinin stem-specific antibody including H17/18 subtypes
Authors: Chen Yulu , Wang Fei , Yin Liwei , Jiang Haihai , Lu Xishan , Bi Yuhai , Zhang Wei , Shi Yi , Burioni Roberto , Tong Zhou , Song Hao , Qi Jianxun , Gao George F.
Published: December 2022

Influenza infection continues are a persistent threat to public health. The identification and characterization of human broadly neutralizing antibodies can facilitate the development of antibody drugs and the design of universal influenza vaccines. Here, we present structural information for the human antibody PN-SIA28’s heterosubtypic binding of hemagglutinin (HA) from circulating and emerging potential influenza A viruses (IAVs). Aside from group 1 and 2 conventional IAV HAs, PN-SIA28 also inhibits membrane fusion mediated by bat-origin H17 and H18 HAs. Crystallographic analyses of Fab alone or in complex with H1, H14, and H18 HA proteins reveal that PN-SIA28 binds to a highly conserved epitope in the fusion domain of different HAs, with the same CDRHs but different CDRLs for different HAs tested, distinguishing it from other structurally characterized anti-stem antibodies. The binding characteristics of PN-SIA28 provides information to support the design of increasingly potent engineered antibodies, antiviral drugs, and/or universal influenza vaccines.
A one-dimensional conductive metal-organic framework with extended π-d conjugated nanoribbon layers
Authors: Shang Shengcong , Du Changsheng , Liu Youxing , Liu Minghui , Wang Xinyu , Gao Wenqiang , Zou Ye , Dong Jichen , Liu Yunqi , Chen Jianyi
Published: December 2022

Conductive metal-organic frameworks (MOFs) have performed well in the fields of energy and catalysis, among which two-dimensional (2D) and three-dimensional (3D) MOFs are well-known. Here, we have synthesized a one-dimensional (1D) conductive metal-organic framework (MOF) in which hexacoordinated 1,5-Diamino-4,8-dihydroxy-9,10-anthraceneedione (DDA) ligands are connected by double Cu ions, resulting in nanoribbon layers with 1D π-d conjugated nanoribbon plane and out-of-plane π-π stacking, which facilitates charge transport along two dimensions. The DDA-Cu as a highly conductive n-type MOF has high crystalline quality with a conductivity of ~ 9.4 S·m−1, which is at least two orders of magnitude higher than that of conventional 1D MOFs. Its electrical band gap (Eg) and exciton binding energy (Eb) are approximately 0.49 eV and 0.3 eV, respectively. When utilized as electrode material in a supercapacitor, the DDA-Cu exhibits good charge storage capacity and cycle stability. Meanwhile, as thse active semiconductor layer, it successfully simulates the artificial visual perception system with excellent bending resistance and air stability as a MOF-based flexible optoelectronic synaptic case. The controllable preparation of high-quality 1D DDA-Cu MOF may enable new architectural designs and various applications in the future.
Data-driven design of molecular nanomagnets
Authors: Duan Yan , Rosaleny Lorena E. , Coutinho Joana T. , Giménez-Santamarina Silvia , Scheie Allen , Baldoví José J. , Cardona-Serra Salvador , Gaita-Ariño Alejandro
Published: December 2022

Three decades of research in molecular nanomagnets have raised their magnetic memories from liquid helium to liquid nitrogen temperature thanks to a wise choice of the magnetic ion and coordination environment. Still, serendipity and chemical intuition played a main role. In order to establish a powerful framework for statistically driven chemical design, here we collected chemical and physical data for lanthanide-based nanomagnets, catalogued over 1400 published experiments, developed an interactive dashboard (SIMDAVIS) to visualise the dataset, and applied inferential statistical analysis. Our analysis shows that the Arrhenius energy barrier correlates unexpectedly well with the magnetic memory. Furthermore, as both Orbach and Raman processes can be affected by vibronic coupling, chemical design of the coordination scheme may be used to reduce the relaxation rates. Indeed, only bis-phthalocyaninato sandwiches and metallocenes, with rigid ligands, consistently present magnetic memory up to high temperature. Analysing magnetostructural correlations, we offer promising strategies for improvement, in particular for the preparation of pentagonal bipyramids, where even softer complexes are protected against molecular vibrations.
Maturation and specialization of group 2 innate lymphoid cells through the lung-gut axis
Authors: Zhao Min , Shao Fei , Yu Dou , Zhang Jiaqi , Liu Zhen , Ma Jiangwen , Xia Pengyan , Wang Shuo
Published: December 2022

Innate lymphoid cells (ILC) are abundant in mucosal tissues. They serve critical functions in anti-pathogen response and tissue homeostasis. However, the heterogenous composition of ILCs in mucosal sites and their various maturation trajectories are less well known. In this study, we characterize ILC types and functions from both the lung and the small intestine, and identify their tissue-specific markers. We find that ILC2s residing in the lung express CCR2, whereas intestinal ILC2s express CCR4. Through the use of CCR2 and CCR4 reporter mice, we show that ILC2s undergo translocation via the lung-gut axis upon IL-33 treatment. This trajectory of ILC2s is also observed at the postnatal stage. Allergen-induced activation of lung ILC2s affects the homeostasis of gut ILC2s. Together, our findings implicate that ILCs display tissue-specific features in both the lung and gut, and ILC2s mature along the lung-gut axis in particular homeostatic and inflammatory conditions.
Parvalbumin basket cell myelination accumulates axonal mitochondria to internodes
Authors: Kole Koen , Voesenek Bas J. B. , Brinia Maria E. , Petersen Naomi , Kole Maarten H. P.
Published: December 2022

Parvalbumin-expressing (PV+) basket cells are fast-spiking inhibitory interneurons that exert critical control over local circuit activity and oscillations. PV+ axons are often myelinated, but the electrical and metabolic roles of interneuron myelination remain poorly understood. Here, we developed viral constructs allowing cell type-specific investigation of mitochondria with genetically encoded fluorescent probes. Single-cell reconstructions revealed that mitochondria selectively cluster to myelinated segments of PV+ basket cells, confirmed by analyses of a high-resolution electron microscopy dataset. In contrast to the increased mitochondrial densities in excitatory axons cuprizone-induced demyelination abolished mitochondrial clustering in PV+ axons. Furthermore, with genetic deletion of myelin basic protein the mitochondrial clustering was still observed at internodes wrapped by noncompacted myelin, indicating that compaction is dispensable. Finally, two-photon imaging of action potential-evoked calcium (Ca2+) responses showed that interneuron myelination attenuates both the cytosolic and mitochondrial Ca2+ transients. These findings suggest that oligodendrocyte ensheathment of PV+ axons assembles mitochondria to branch selectively fine-tune metabolic demands.
A self-healing electrocatalytic system via electrohydrodynamics induced evolution in liquid metal
Authors: Hou Yifeng , Wang Fengyan , Qin Chichu , Wu Shining , Cao Mengyang , Yang Pengkun , Huang Lu , Wu Yingpeng
Published: December 2022

Catalytic deterioration during electrocatalytic processes is inevitable for conventional composite electrodes, which are prepared by depositing catalysts onto a rigid current collector. In contrast, metals that are liquid at near room temperature, liquid metals (LMs), are potential electrodes that are uniquely flexible and maneuverable, and whose fluidity may allow them to be more adaptive than rigid substrates. Here we demonstrate a self-healing electrocatalytic system for CO2electroreduction using bismuth-containing Ga-based LM electrodes. Bi2O3dispersed in the LM matrix experiences a series of electrohydrodynamic-induced structural changes when exposed to a tunable potential and finally transforms into catalytic bismuth, whose morphology can be controlled by the applied potential. The electrohydrodynamically-induced evolved electrode shows considerable electrocatalytic activity for CO2reduction to formate. After deterioration of the electrocatalytic performance, the catalyst can be healed via simple mechanical stirring followed by in situ regeneration by applying a reducing potential. With this procedure, the electrode’s original structure and catalytic activity are both recovered.
Limited conservation in cross-species comparison of GLK transcription factor binding suggested wide-spread cistrome divergence
Authors: Tu Xiaoyu , Ren Sibo , Shen Wei , Li Jianjian , Li Yuxiang , Li Chuanshun , Li Yangmeihui , Zong Zhanxiang , Xie Weibo , Grierson Donald , Fei Zhangjun , Giovannoni Jim , Li Pinghua , Zhong Silin
Published: December 2022

Non-coding cis-regulatory variants in animal genomes are an important driving force in the evolution of transcription regulation and phenotype diversity. However, cistrome dynamics in plants remain largely underexplored. Here, we compare the binding of GOLDEN2-LIKE (GLK) transcription factors in tomato, tobacco, Arabidopsis, maize and rice. Although the function of GLKs is conserved, most of their binding sites are species-specific. Conserved binding sites are often found near photosynthetic genes dependent on GLK for expression, but sites near non-differentially expressed genes in the glk mutant are nevertheless under purifying selection. The binding sites’ regulatory potential can be predicted by machine learning model using quantitative genome features and TF co-binding information. Our study show that genome cis-variation caused wide-spread TF binding divergence, and most of the TF binding sites are genetically redundant. This poses a major challenge for interpreting the effect of individual sites and highlights the importance of quantitatively measuring TF occupancy.
Mining of novel secondary metabolite biosynthetic gene clusters from acid mine drainage
Authors: Wang Ling , Liu Wan , Liang Jieliang , Zhao Linna , Li Qiang , Zhou Chenfen , Cen Hui , Weng Qingbei , Zhang Guoqing
Published: December 2022

Acid mine drainage (AMD) is usually acidic (pH < 4) and contains high concentrations of dissolved metals and metalloids, making AMD a typical representative of extreme environments. Recent studies have shown that microbes play a key role in AMD bioremediation, and secondary metabolite biosynthetic gene clusters (smBGCs) from AMD microbes are important resources for the synthesis of antibacterial and anticancer drugs. Here, 179 samples from 13 mineral types were used to analyze the putative novel microorganisms and secondary metabolites in AMD environments. Among 7,007 qualified metagenome-assembled genomes (MAGs) mined from these datasets, 6,340 MAGs could not be assigned to any GTDB species representative. Overall, 11,856 smBGCs in eight categories were obtained from 7,007 qualified MAGs, and 10,899 smBGCs were identified as putative novel smBGCs. We anticipate that these datasets will accelerate research in the field of AMD bioremediation, aid in the discovery of novel secondary metabolites, and facilitate investigation into gene functions, metabolic pathways, and CNPS cycles in AMD.
Long-term prognostic impact of paravalvular leakage on coronary artery disease requires patient-specific quantification of hemodynamics
Authors: Khodaei Seyedvahid , Garber Louis , Bauer Julia , Emadi Ali , Keshavarz-Motamed Zahra
Published: December 2022

Transcatheter aortic valve replacement (TAVR) is a frequently used minimally invasive intervention for patient with aortic stenosis across a broad risk spectrum. While coronary artery disease (CAD) is present in approximately half of TAVR candidates, correlation of post-TAVR complications such as paravalvular leakage (PVL) or misalignment with CAD are not fully understood. For this purpose, we developed a multiscale computational framework based on a patient-specific lumped-parameter algorithm and a 3-D strongly-coupled fluid–structure interaction model to quantify metrics of global circulatory function, metrics of global cardiac function and local cardiac fluid dynamics in 6 patients. Based on our findings, PVL limits the benefits of TAVR and restricts coronary perfusion due to the lack of sufficient coronary blood flow during diastole phase (e.g., maximum coronary flow rate reduced by 21.73%, 21.43% and 21.43% in the left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) respectively (N = 6)). Moreover, PVL may increase the LV load (e.g., LV load increased by 17.57% (N = 6)) and decrease the coronary wall shear stress (e.g., maximum wall shear stress reduced by 20.62%, 21.92%, 22.28% and 25.66% in the left main coronary artery (LMCA), left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) respectively (N = 6)), which could promote atherosclerosis development through loss of the physiological flow-oriented alignment of endothelial cells. This study demonstrated that a rigorously developed personalized image-based computational framework can provide vital insights into underlying mechanics of TAVR and CAD interactions and assist in treatment planning and patient risk stratification in patients.
MKL-1-induced PINK1-AS overexpression contributes to the malignant progression of hepatocellular carcinoma via ALDOA-mediated glycolysis
Authors: Wang Jun , Zhang Hui-Min , Dai Zhou-Tong , Huang You , Liu Hui , Chen Zhen , Wu Yuan , Liao Xing-Hua
Published: December 2022

Aldolase A (ALDOA), an important metabolic enzyme in the glycolytic pathway, plays an important role in regulating tumour metabolism. In this study, we investigated the expression pattern of ALDOA in hepatocellular carcinoma (HCC) and its biological role in tumour progression. Bioinformatics analysis, western blot (WB) and RT-qPCR were performed to detect the relative expression of ALDOA in HCC tissues and cell lines. A loss-of-function approach was used to investigate the biological function of ALDOA. The role of ALDOA on glycolysis was assessed by WB, glucose and lactate assay kits and a nude mouse xenograft model. Luciferase reporter experiment, chromatin immunoprecipitation and WB were performed to elucidate the underlying molecular. The expression level of ALODA was up-regulated in HCC tissues and cell lines. High ALDOA levels were associated with poorer patient overall survival. Mechanistic studies suggest that ALDOA is a direct target of miR-34a-5p, which can inhibit glycolysis in hepatocellular carcinoma cells by targeting the 3′UTR of ALDOA. PINK1 antisense RNA (PINK1-AS) competitively sponged miR-34a-5p to increase ALDOA expression by antagonizing miR-34a-5p-mediated ALDOA inhibition. MKL-1 acted as a transcription factor to promote the expression of PINK1-AS and ALDOA, thus promoting the deterioration of HCC cells. This study shows that high expression of ALDOA contributes to the development and poor prognosis of hepatocellular carcinoma and will be a target and potential prognostic biomarker for the treatment of HCC.
Unlocking the organic residues preserved in the corrosion from the Pewsey Hoard vessels
Authors: Carvalho Luciana da Costa , Henry Richard , McCullagh James S. O. , Pollard A. Mark
Published: December 2022

The characterization of archaeological metal corrosion has traditionally been limited to the identification of inorganic compounds usually by X-ray diffraction (XRD), thought to result from the interaction between the metal object and the deposition environment. The discovery of a hoard of Late Roman copper-alloy vessels in Wiltshire, UK presented an unique opportunity to adopt a multi-analytical approach to characterize corrosion combining XRD with Fourier-transform infrared (FTIR) and gas chromatography with quadrupole time-of-flight mass spectrometry using a thermal separation probe (GC-QTOF-MS with TSP). This approach revealed organic compounds potentially historical preserved within crystalline inorganic matrices. It has been known for some time that ceramics can harbour organic residues, which provide crucial evidence about the use of these vessels in the past. Our results confirms that similar residues appear to survive in metal corrosion thus extending the potential for identification of biomaterials used in the past.
Ecological study of ambient air pollution exposure and mortality of cardiovascular diseases in elderly
Authors: Dehghani Samaneh , Vali Mohebat , Jafarian Arian , Oskoei Vahide , Maleki Zahra , Hoseini Mohammad
Published: December 2022

As an independent risk factor, ambient air pollution can assume a considerable part in mortality and worsening of cardiovascular disease. We sought to investigate the association between long-term exposure to ambient air pollution and cardiovascular disease mortality and their risk factors in Iranian's elderly population. This inquiry was conducted ecologically utilizing recorded data on cardiovascular disease mortality from 1990 to 2019 for males and females aged 50 years or more from the Global Burden of Disease dataset. Data was interned into Joinpoint software 4.9.0.0 to present Annual Percent Change (APC), Average Annual Percent Change (AAPC), and its confidence intervals. The relationship between recorded data on ambient air pollution and cardiovascular disease' mortality, the prevalence of high systolic blood pressure, high LDL cholesterol levels, high body mass index, and diabetes mellitus type2 was investigated using the Spearman correlation test in R 3.5.0 software. Our finding demonstrated that cardiovascular diseases in elderly males and females in Iran had a general decreasing trend (AAPC = −0.77% and −0.65%, respectively). The results showed a positive correlation between exposure to ambient ozone pollution (p ≤ 0.001, r = 0.94) ambient particulate and air pollution (p < 0.001, r = 0.99) and mortality of cardiovascular disease. Also, ambient air pollution was positively correlated with high systolic blood pressure (p < 0.001, r = 0.98), high LDL cholesterol levels (p < 0.001, r = 0.97), high body mass index (p < 0.001, r = 0.91), diabetes mellitus type2 (p < 0.001, r = 0.77). Evidence from this study indicated that ambient air pollution, directly and indirectly, affects cardiovascular disease mortality in two ways by increasing the prevalence of some traditional cardiovascular disease risk factors. Evidence-based clinical and public health methodologies are necessary to decrease the burden of death and disability associated with cardiovascular disease.
Association of polymorphisms in TGFB1, XRCC1, XRCC3 genes and CD8 T-lymphocyte apoptosis with adverse effect of radiotherapy for prostate cancer
Authors: Mališić Emina , Petrović Nina , Brengues Muriel , Azria David , Matić Ivana Z. , Srbljak Ćuk Ivana , Kopčalić Katarina , Stanojković Tatjana , Nikitović Marina
Published: December 2022

The genetic background of each person might affect the severity of radiotherapy (RT)-induced normal tissue toxicity. The aim of study was to evaluate the influence of TGFB1 C-509T and Leu10Pro, XRCC1 Arg280His and XRCC3 Thr241Met polymorphisms as well as the level of radiation-induced CD8 T-lymphocyte apoptosis (RILA) on adverse effects of RT for prostate cancer (PCa). The study included 88 patients with localized or locally advanced PCa who were treated with RT. The polymorphisms were determined by PCR–RFLP analysis on DNA from peripheral blood mononuclear cells. RILA values were measured by flow cytometry. We found that CT genotype of TGFB1 C-509T could be protective biomarker for acute genitourinary (GU) and gastrointestinal (GI) radiotoxicity, while Thr variant of XRCC3 Thr241Met could predict the risk for acute GU radiotoxicity. Correlation between RILA values and toxicity was not detected. Univariate logistic regression analysis showed that Gleason score and risk group were risk factors for late GU, while for late GI radiotoxicity it was diabetes mellitus type 2. However, in multivariate model those were not proven to be significant and independent risk factors. Identification of assays combination predicting individual radiosensitivity is a crucial step towards personalized RT approach.
Estimation and feasibility of correction modelling for mother-reported child height and weight at 2 years using data from the Australian CHAT trial
Authors: Cheng Yan , Xu Huilan , Rissel Chris , Phongsavan Philayrath , Buchanan Limin , Taki Sarah , Hayes Alison , Baur Louise A. , Wen Li Ming
Published: December 2022

Correction modelling using reported BMI values has been employed in adolescent and adult populations to improve the accuracy of self-reporting. This study aimed to evaluate the feasibility of establishing correction modelling for mother-reported child height and weight at 2 years using data from an Australian trial in 2019. Correction modelling for BMI was conducted using mother-reported and objectively measured height and weight of 2-year-olds. Mother-reported height, weight and BMI values of 2-year-old children were adjusted based on objectively measured anthropometric data using linear regression models. ‘Direct’ and ‘indirect’ corrections were applied to the correction of BMI values. We defined the direct collection as using corrected BMI values that were predicted directly by the model and indirect correction as using corrected weight and height values to calculate corrected BMI values. Corrected BMI values via the indirect correction showed higher sensitivity or similar specificity in predicting overweight status, compared to the direct correction, and also showed higher agreement with measured values compared to the mother-reported measures. Corrected self-reported measures via an indirect correction had a better accuracy and agreement with the objectively measured data in the BMI values and classification of overweight, compared to the mother-reported values.
Inflammatory bowel disease and COVID-19 outcomes: a meta-analysis
Authors: Abdulla Maheeba , Mohammed Nafeesa , AlQamish Jehad , Mosli Mahmoud
Published: December 2022

There is conflicting evidence concerning the effect of inflammatory bowel disease (IBD) on COVID-19 incidence and outcome. Hence, we aimed to evaluate the published evidence through a systematic review process and perform a meta-analysis to assess the association between IBD and COVID-19. A compressive literature search was performed in PubMed/Medline, Scopus, Embase, and Cochrane Library from inception to July 2021. A snowball search in Google, Google Scholar, Research Gate, and MedRxiv; and bibliographic research were also performed to identify any other relevant articles. Quantitative observational studies such as cohort, cross-sectional, and case–control studies that assessed the incidence, risk, and outcomes of COVID-19 among the adult IBD patients published in the English language, were considered for this review. The incidence and risk of COVID-19, COVID-19 hospitalization, the severity of COVID-19, and mortality were considered as the outcomes of interest. The Joanna Briggs Institute critical appraisal checklist was used for quality assessment. A subgroup and sensitivity analysis were performed to explore the heterogeneity and robustness of the results, respectively. A total of 86 studies out of 2828 non-duplicate records were considered for this meta-analysis. The studies were single or multicentric internationally from settings such as IBD centres, medical colleges, hospitals, or from the general public. Most of the studies were observed to be of good quality with an acceptable risk of bias. The pooled prevalence of COVID-19, COVID-19 hospitalization, severe COVID-19, and mortality in the IBD population were 6.10%, 10.63%, 40.43%, and 1.94%, respectively. IBD was not significantly (p > 0.05) associated with the risk of COVID-19, COVID-19 hospitalization, severe COVID-19, and mortality. In contrast, ulcerative colitis was significantly associated with a higher risk of COVID-19 (OR 1.37; p = 0.01), COVID-19 hospitalization (OR 1.28; p < 0.00001), and severe COVID-19 (OR 2.45; p < 0.0007). Crohn’s disease was significantly associated with a lesser risk of severe COVID-19 (OR 0.48; p = 0.02). Type of IBD was a potential factor that might have contributed to the higher level of heterogeneity. There was a significant association between ulcerative colitis and increased risk of COVID-19, COVID-19 hospitalization, and severe COVID-19 infection. This association was not observed in patients with Crohns' disease or in those diagnosed non-specifically as IBD.
Soluble immune checkpoint molecules in patients with antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Pyo Jung Yoon , Yoon Taejun , Ahn Sung Soo , Song Jason Jungsik , Park Yong-Beom , Lee Sang-Won
Published: December 2022

Immune checkpoint molecules balance immune effector responses with regulatory reactions. We speculated that soluble immune checkpoint molecules are involved in dysregulation of the immune response and autoimmunity. We evaluated the association between soluble immune checkpoint molecules and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A total of 56 patients with AAV from a prospective observational cohort and 40 healthy controls (HCs) were analyzed. Soluble PD-1, PD-L1, PD-L2, CTLA-4, CD28, CD80, CD86, ICOS, TIM-3, BTLA, CD40, LAG-3, TLR-2, and CD27 were measured in stored sera using the Milliplex MAP assay. Paired analyses were performed before and after the treatment. AAV-specific indices, including Birmingham vasculitis activity score, five factor score , vasculitis damage index, and blood samples, were collected. Patients with AAV had higher levels of sPD-L1, sCD28, sCD80, sCD86, sICOS, sTIM-3, sLAG-3, sTLR-2, and sCD27 and lower level of sCTLA-4 than HCs (p < 0.05). Patients with AAV had higher serum sCD28, sCD80, sTIM-3, and sCD27 levels than HCs at baseline and decreased after treatment. Furthermore, the serum levels of sCD28 and sTIM-3 were significantly correlated with disease activity. This study demonstrated altered concentrations of serum soluble immune checkpoint molecules in patients with AAV. In particular, sCD28 and sTIM-3 may act as surrogate markers of AAV disease activity.
An integrated approach for the restoration of Australian temperate grasslands invaded by Nassella trichotoma
Authors: Humphries Talia , Turville Christopher , Sinclair Steven , Florentine Singarayer
Published: December 2022

Invasive plants are considered to be one of the biggest threats to environmental assets, and once established, they can be immensely difficult to control. Nassella trichotoma is an aggressive, perennial grass species, and is considered to be one of the most economically damaging weeds to grazing systems due to its unpalatability, as well as being one of the leading causes of biodiversity loss in grassland communities. This species produces high density seedbanks that rapidly respond to disturbance events. Despite control programs being developing in Australia since the 1930s, this species is still widespread throughout south-east Australia, indicating that a new management approach is critical to control this Weed of National Significance at the landscape scale. The present study explored the effect of 12 different combinations of herbicide, fire, a second application of herbicide, grazing exclusion, tillage and broadcasting seeds in order to reduce the above and below-ground density of N. trichotoma. A control treatment was also included. The results were assessed using a Hierarchy analysis, whereby treatments of increasing complexity were compared for their efficacy in reducing N. trichotoma cover and seedbank density, while simultaneously increasing the establishment of the broadcast species. Whilst all integrated treatments effectively reduced N. trichotoma’s seedbank, the treatments that included fire performed significantly better at simultaneously reducing N. trichotoma and increasing the establishment of broadcasted seeds. Overall, the integration of herbicide, fire and broadcasting native seeds was observed to provide the most economically feasible management strategy for the landscape scale restoration of a degraded temperate grassland dominated by N. trichotoma.
Characterizing occupational radon exposure greater than 100 Bq/m3 in a highly exposed country
Authors: Brobbey A. , Rydz E. , Fenton S. , Demers P. A. , Ge C. B. , Peters C. E.
Published: December 2022

Radon is an established lung carcinogen concentrating in indoor environments with importance for many workers worldwide. However, a systematic assessment of radon levels faced by all workers, not just those with direct uranium or radon exposure, has not previously been completed. The objective of this study was to estimate the prevalence of workers exposed to radon, and the level of exposure (> 100–200 Bq/m3, 200–400 Bq/m3, 400–800 Bq/m3, and > 800 Bq/m3) in a highly exposed country (Canada). Exposures among underground workers were assessed using the CAREX Canada approach. Radon concentrations in indoor workplaces, obtained from two Canadian surveys, were modelled using lognormal distributions. Distributions were then applied to the susceptible indoor worker population to yield the number of exposed workers, by occupation, industry, province, and sex. In total, an estimated 603,000 out of Canada’s 18,268,120 workers are exposed to radon in Canada. An estimated52% of exposed workers are women, even though they comprise only 48% of the labour force. The majority (68%) are exposed at a level of > 100–200 Bq/m3. Workers are primarily exposed in educational services, professional, scientific and technical services, and health care and social assistance, but workers in mining, quarrying, and oil and gas extraction have the largest number of exposed workers at high levels (> 800 Bq/m3). Overall, a significant number of workers are exposed to radon, many of whom are not adequately protected by existing guidelines. Radon surveys across multiple industries and occupations are needed to better characterize occupational exposure. These results can be used to identify exposed workers, and to support lung cancer prevention programs within these groups.
Whole genome sequencing reveals new links between spa t172/CC59 methicillin-resistant Staphylococcus aureus cases in low-endemicity region of Southwest Finland, 2007‒2016
Authors: Silvola Jaakko , Gröndahl-Yli-Hannuksela Kirsi , Hirvioja Tiina , Rantakokko-Jalava Kaisu , Rintala Esa , Auranen Kari , Junnila Jenna , Marttila Harri , Lindholm Laura , Vuopio Jaana
Published: December 2022

Methicillin-resistant Staphylococcus aureus (MRSA) rates have remained relatively low in Finland. In Southwest Finland, however, annual MRSA incidence increased from 12 to 25/100,000 between 2007 and 2016 with spa t172 strain causing one fourth (237/983) of all cases. This provoked us to study the molecular epidemiology of t172-MRSA, aiming to better understand the transmission of this strain type. We combined epidemiological data and whole genome sequencing (WGS) of a set of 64 (27%, 64/237) t172-MRSA isolates covering 10 years. Isolates represented sporadic and index cases of all identified healthcare-associated outbreaks (HAOs) and family clusters (FCs). Among the included 62 isolates, core-genome MLST analysis revealed eight genomic clusters comprising 24 (38.7%) isolates and 38 (61.3%) non-clustered isolates. Cluster 1 comprised ten and the remaining seven clusters two isolates each, respectively. Two epidemiologically distinct HAOs were linked in cluster 1. FCs were involved in all clusters. All strains were associated with epidemic clonal complex CC59. We were able to confirm the spread of several successful t172-MRSA subclones in regional healthcare and the community. WGS complemented routine surveillance by revealing undetected links between t172-MRSA cases. Targeted, WGS-based typing could enhance MRSA surveillance without the need for routine WGS diagnostics.
Prothrombotic state, endothelial injury, and echocardiographic changes in non-active sarcoidosis patients
Authors: Siwiec-Kozlik Andzelika , Kuszmiersz Piotr , Kasper Lukasz , Frolow Marzena , Kozlik-Siwiec Pawel , Iwaniec Teresa , Kosalka-Wegiel Joanna , Zareba Lech , Sladek Krzysztof , Bazan Jan G. , Bazan-Socha Stanislawa , Dropinski Jerzy
Published: December 2022

Sarcoidosis is a multisystem inflammatory granulomatous disease of unknown cause that most commonly affects lungs and lymph nodes, with frequent yet asymptomatic cardiac involvement. The epidemiologically associated cardiovascular risk suggests an underlying prothrombotic state and endothelial dysfunction, currently understudied in the available literature. Therefore, we aimed to investigate prothrombotic plasma properties together with selected echocardiographic and laboratory biomarkers of cardiovascular injury in that disease. N = 53 patients with pulmonary sarcoidosis in clinical remission and N = 66 matched controls were assessed for inflammatory and endothelial injury biomarkers, plasma thrombin generation profile, and echocardiographic and lung function parameters. Sarcoidosis cases had impaired systolic and diastolic left ventricular function, higher concentrations of inflammatory markers, D-dimer and factor VIII activity compared to the controls. The coexistence of extrapulmonary disease was associated with elevated circulating vascular cell adhesion molecule 1, while cases with hypercalcemia had higher thrombomodulin concentration. Sarcoidosis was characterized by the unfavorably altered thrombin generation profile, reflected by the 16% higher endogenous thrombin potential (ETP), 24% increased peak thrombin concentration, and 12% shorter time to thrombin peak in comparison to the control group. ETP was higher in cases with proxies of pulmonary restriction, extrapulmonary–extracutaneous manifestation, and need for corticosteroids use. Despite the clinical remission, sarcoidosis is related to prothrombotic plasma properties and signs of endothelial injury, likely contributing to the higher risk of cardiovascular events. In addition, subclinical cardiac involvement may play an additional role, although further clinical and experimental studies are needed to verify these findings.
Carbonation and serpentinization of diopsidite in the Altun Mountains, NW China
Authors: Zhou Dingkui , Cao Shuyun , Liu Jianhua , Li Xiaowen , Dong Yanlong , Neubauer Franz , Bai Jie , Li Hu
Published: December 2022

Mineral carbonation of mafic–ultramafic rocks has been highlighted as a promising way for permanent carbon capture and storage. Carbonatization involves the release of Ca, Mg and Fe from silicate minerals by dissolution and reaction in the aqueous phase to form stable carbonate minerals. Diopside is one of the most abundant mafic minerals in the lithosphere and contributes a portion of Mg and Ca to surface weathering. Here, we present detailed processes of the carbonation-coupled serpentinization of diopsidite from the Yushishan Nb–Ta deposit in the Altun Mountain, northwest China. Diopsidite is the prograde metamorphic product of siliceous dolomitic marble by full decarbonation process. Retrograde serpentinization and carbonation of diopsidite lead to the addition of CO2, H2O, light rare earth elements and fluid-mobile elements but the loss of SiO2. The diopsides are replaced by calcite and chrysotile by mineral alteration to form pseudomorphic textures. Dissolution–precipitation processes significantly affect diopside serpentinization and carbonation. The carbonation of diopside-rich rocks may be suitable for permanent CO2 storage.
Cross-modal correspondence between auditory pitch and visual elevation modulates audiovisual temporal recalibration
Authors: Uno Kyuto , Yokosawa Kazuhiko
Published: December 2022

Cross-modal correspondences refer to associations between feature dimensions of stimuli across sensory modalities. Research has indicated that correspondence between audiovisual stimuli influences whether these stimuli are integrated or segregated. On the other hand, the audiovisual integration process plastically changes to compensate for continuously observed spatiotemporal conflicts between sensory modalities. If and how cross-modal correspondence modulates the “recalibration” of integration is unclear. We investigated whether cross-modal correspondence between auditory pitch and visual elevation affected audiovisual temporal recalibration. Participants judged the simultaneity of a pair of audiovisual stimuli after an adaptation phase in which alternating auditory and visual stimuli equally spaced in time were presented. In the adaptation phase, auditory pitch and visual elevation were manipulated to fix the order within each pairing of audiovisual stimuli congruent with pitch-elevation correspondence (visual leading or auditory leading). We found a shift in the point of subjective simultaneity (PSS) between congruent audiovisual stimuli as a function of the adaptation conditions (Experiment 1, 2), but this shift in the PSS was not observed within incongruent pairs (Experiment 2). These results indicate that asynchronies between audiovisual signals congruent with cross-modal correspondence are selectively recalibrated.
Diethylcarbamazine, TRP channels and Ca2+ signaling in cells of the Ascaris intestine
Authors: Williams Paul D. E. , Kashyap Sudhanva S. , McHugh Mark A. , Brewer Matthew T. , Robertson Alan P. , Martin Richard J.
Published: December 2022

The nematode parasite intestine absorbs nutrients, is involved in innate immunity, can metabolize xenobiotics and as we show here, is also a site of action of the anthelmintic, diethylcarbamazine. Diethylcarbamazine (DEC) is used to treat lymphatic filariasis and activates TRP-2, GON-2 & CED-11 TRP channels in Brugia malayi muscle cells producing spastic paralysis. DEC also has stimulatory effects on ascarid nematode parasites. Using PCR techniques, we detected, in Ascaris suum intestine, message for: Asu-trp-2, Asu-gon-2, Asu-ced-11, Asu-ocr-1, Asu-osm-9 and Asu-trpa-1. Comparison of amino-acid sequences of the TRP channels of B. malayi, and A. suum revealed noteworthy similarity, suggesting that the intestine of Ascaris will also be sensitive to DEC. We used Fluo-3AM as a Ca2+ indicator and observed characteristic unsteady time-dependent increases in the Ca2+ signal in the intestine in response to DEC. Application of La3+ and the TRP channel inhibitors, 2-APB or SKF 96365, inhibited DEC mediated increases in intracellular Ca2+. These observations are important because they emphasize that the nematode intestine, in addition to muscle, is a site of action of DEC as well as other anthelmintics. DEC may also enhance the Ca2+ toxicity effects of other anthelmintics acting on the intestine or, increase the effects of other anthelmintics that are metabolized and excreted by the nematode intestine.
Study of banana preservation extension by UVC radiation in precise monitoring LED irradiation cavity
Authors: Le Thi-Thu-Ngoc , Liao Chung-Ta , Lin Shih-Kang , Wu Chi-Shou , Nguyen Quang-Khoi , Yang Tsung-Hsun , Yu Yeh-Wei , Sun Ching-Cherng
Published: December 2022

Ultraviolet C (UVC) radiation has been considered a possible option to alleviate the seriousness of black spots on bananas during preservation which help increase economic efficiency. In this study, using 275 nm UVC light-emitting diodes (LEDs), a preliminary cavity with dimensions of 30 × 30 × 30 cm was designed and fabricated to aid in reducing black spots on bananas with the aim of application in the factory conveyor belts. The UVC irradiance distribution was thoroughly monitored for many sections at different box heights in both simulation and measurement, with a dominant range of 6–9 W/m2 in the middle. Afterward, trials were conducted in vitro and in vivo at different selected UVC doses. The results in vitro revealed that a dose of over 0.36 kJ/m2 has an excellent effect on inhibiting the colonial germination of fungal Colletotrichum musae, a common species of fungi causing black spot disease on bananas. In vivo conditions, with a short exposure time of around 5 s, the black spots on UVC-irradiated banana peel significantly reduced with minimal sensory damage compared to a control banana via observation after seven days from treatment. Finally, the optimal UVC dose is proposed from 0.030 to 0.045 kJ/m2 for the one-time treatment when considering the upper surface of the banana. With flexibility advantage and short exposure time, the fabricated cavity (box) promises to bring a lot of application potential to aid banana preservation in factories and households.
Molecular basis of C9orf72 poly-PR interference with the β-karyopherin family of nuclear transport receptors
Authors: Jafarinia Hamidreza , Van der Giessen Erik , Onck Patrick R.
Published: December 2022

Nucleocytoplasmic transport (NCT) is affected in several neurodegenerative diseases including C9orf72-ALS. It has recently been found that arginine-containing dipeptide repeat proteins (R-DPRs), translated from C9orf72 repeat expansions, directly bind to several importins. To gain insight into how this can affect nucleocytoplasmic transport, we use coarse-grained molecular dynamics simulations to study the molecular interaction of poly-PR, the most toxic DPR, with several Kapβs (importins and exportins). We show that poly-PR–Kapβ binding depends on the net charge per residue (NCPR) of the Kapβ, salt concentration of the solvent, and poly-PR length. Poly-PR makes contact with the inner surface of most importins, which strongly interferes with Kapβ binding to cargo-NLS, IBB, and RanGTP in a poly-PR length-dependent manner. Longer poly-PRs at higher concentrations are also able to make contact with the outer surface of importins that contain several binding sites to FG-Nups. We also show that poly-PR binds to exportins, especially at lower salt concentrations, interacting with several RanGTP and FG-Nup binding sites. Overall, our results suggest that poly-PR might cause length-dependent defects in cargo loading, cargo release, Kapβ transport and Ran gradient across the nuclear envelope.