bluuebunny/crossref_metadata_2025 huggingface dataset:
The nonlinear correlation between the cardiometabolic index and the risk of diabetes: A retrospective Japanese cohort study
Authors: Zha Fubing , Cao Changchun , Hong Mengru , Hou Huili , Zhang Qionghua , Tang Bin , Hu Haofei , Han Yong , Zan Yibing , Wang Yulong , Xu Jianwen
Published: February 2023

Background

The cardiometabolic index (CMI) has been proposed as a novel indicator of cardiometabolic status. However, evidence on the relationship between CMI and diabetes mellitus (DM) risk was limited. Our study aimed to explore the relationship between CMI and DM risk among a large cohort of Japanese adults.

Methods

This retrospective cohort study recruited 15453 Japanese adults without diabetes at baseline who underwent physical examinations at the Murakami Memorial Hospital between 2004 and 2015. Cox proportional-hazards regression was applied to evaluate the independent relationship between CMI and diabetes. Our study performed a generalized smooth curve fitting (penalized spline technique) and an additive model (GAM) to determine the non-linear relationship between CMI and DM risk. In addition, a set of sensitivity analyses and subgroup analyses were employed to evaluate the relationship between CMI and incident DM.

Results

After adjusting for confounding covariates, CMI was positively related to the DM risk in Japanese adults (HR: 1.65, 95%CI: 1.43-1.90, P<0.0001). A series of sensitivity analyses were also employed in this study to guarantee the reliability of the findings. In addition, our study discovered a non-linear association between CMI and diabetes risk. CMI’s inflection point was 1.01. A strong positive association between CMI and diabetes incidence was also discovered to the left of the inflection point (HR: 2.96, 95%CI: 1.96-4.46, P<<0.0001). However, their association was not significant when CMI was higher than 1.01 (HR: 1.27, 95%CI: 0.98-1.64, P=0.0702). Interaction analysis showed that gender, BMI, habit of exercise, and smoking status interacted with CMI.

Conclusion

Increased CMI level at baseline is associated with incident DM. The association between CMI and incident DM is also non-linear. A high CMI level is associated with an increased risk for DM when CMI is below 1.01.
Is type 2 diabetes associated dementia a microvascular early-Alzheimer’s phenotype induced by aberrations in the peripheral metabolism of lipoprotein-amyloid?
Authors: Takechi Ryusuke , Sharif Arazu , Brook Emily , Majimbi Maimuna , Chan Dick C. , Lam Virginie , Watts Gerald F. , Mamo John C. L.
Published: February 2023

There is increasing evidence of a positive association of type 2 diabetes with Alzheimer’s disease (AD), the most prevalent form of dementia. Suggested pathways include cerebral vascular dysfunction; central insulin resistance, or exaggerated brain abundance of potentially cytotoxic amyloid-β (Aβ), a hallmark feature of AD. However, contemporary studies find that Aβ is secreted in the periphery by lipogenic organs and secreted as nascent triglyceride-rich lipoproteins (TRL’s). Pre-clinical models show that exaggerated abundance in blood of TRL-Aβ compromises blood-brain barrier (BBB) integrity, resulting in extravasation of the TRL-Aβ moiety to brain parenchyme, neurovascular inflammation and neuronal degeneration concomitant with cognitive decline. Inhibiting secretion of TRL-Aβ by peripheral lipogenic organs attenuates the early-AD phenotype indicated in animal models, consistent with causality. Poorly controlled type 2 diabetes commonly features hypertriglyceridemia because of exaggerated TRL secretion and reduced rates of catabolism. Alzheimer’s in diabetes may therefore be a consequence of heightened abundance in blood of lipoprotein-Aβ and accelerated breakdown of the BBB. This review reconciles the prevailing dogma of amyloid associated cytotoxicity as a primary risk factor in late-onset AD, with substantial evidence of a microvascular axis for dementia-in-diabetes. Consideration of potentially relevant pharmacotherapies to treat insulin resistance, dyslipidaemia and by extension plasma amyloidemia in type 2 diabetes are discussed.
Algal removal from raw water by electro-flotation
Authors: Jiang Shuangcheng , Wang Fuli , Lin Feng , Du Hong
Published: February 2023

In order to reduce the influence of algae on the conventional treatment process of the water plant, the electro-flotation process was used to test the raw water of a lake-type reservoir. After raw water with cyanobacteria as the dominant algae is treated by the best electro-flotation process, the average removal rate of algal density can reach 99.1%. The effects of current density, residence time, and electrode spacing on the algal removal efficiency of the electro-floating process were investigated by orthogonal experiments. The order of influence was current density > residence time > electrode spacing. Considering economics, the optimal process conditions were as follows: the current density was 5 mA/cm2, the dwell time was 6 min, and electrode spacing was 10 mm.
Research progress and application prospect of nature-based solutions in China
Authors: He Xiangyu , Wei Hongbin , Li Shaoshuai
Published: February 2023

In recent years, Nature-based Solutions (NbS) have become an important concept in the field of climate change and sustainable development. The study screens academic journals relevant NbS researches using China National Knowledge Infrastructure (CNKI) and Web of Science database to explore different perspectives for Nature-based Solutions research through qualitative analysis. This study reviews the existing research on NbS, summarizes what research ideas are covered by Nature-based Solutions, as well as the relationship between previous relevant studies, focuses on different perspectives of refining the implementation of Nature-based Solutions in various studies and practices, and explains them with typical cases. The research shows that existing Nature-based Solutions researches mostly prefer to determine schemes by objects, with insufficient emphasis on subjects and goals. On this basis, the specific operational framework of promoting Nature-based Solutions in China is considered to promote the development of indigenous application of Nature-based Solutions in China. This study reveals the diversified ideas in the research and implementation of Nature-based Solutions at home and abroad, which is of practical significance to promote the localization of Nature-based Solutions in China.
Surviving in a new host: Eight years of monitoring translocated aroids, bromeliads, and orchids in the Andean forests in Colombia
Authors: Benavides Ana María , Calderón-Caro Jennifer , Canal Dubán
Published: February 2023

Vascular epiphytes are extraordinarily diverse in the tropical Andean region. Compared to trees and terrestrial herbs, epiphytes are more vulnerable to forest alteration due to their structural dependence on trees and environmental requirements. Based on experimental approaches for ecological purposes, monitoring air pollutants, and seeking propagation alternatives, the rescue and translocation of vascular epiphytes (mainly bromeliads and orchids) from a threatened forest to a safer forest has been recently conducted in Colombia. Preliminary assessments indicate that epiphytes benefit from such well-planned measures, and their mortality and survival might be associated with extrinsic and intrinsic factors, which remain to be understood. We evaluated the survival of 16 vascular epiphyte species after translocation into a secondary forest in Antioquia (Colombia) for 8 years. We assessed the role of intrinsic (foliar area, number of leaves, initial pseudobulbs, stems or rosettes, functional group, and epiphyte species) and extrinsic factors (host tree species, bark water-holding capacity, type of substrate, location on the host tree, nutrients, and hormone addition) and the effect of climatic variables on plant survival. The overall mortality rate in this study ranked 1–7% per year, and survival decreased annually, reaching 44% by the end of the 8th year. Host tree species and intrinsic factors such as the functional group and epiphyte species significantly affected the probability of survival. Bromeliads, in particular, exhibited high mortality, which their monocarpic growth form could explain. Another group of species showing high mortality were the miniature orchids, Masdevalia amanda and M. platyglossa, and are associated with short life cycles. Five host tree species appear to affect the survival of translocated epiphytes; however, the factors or characteristics involved remain unclear. A higher seasonality of precipitation was related to the percentage of overall mortality. This result indicates that extreme precipitation events or drought reduce epiphyte longevity. In conclusion, our study suggests that a wide range of epiphytes may be successfully translocated to secondary forests in the Colombian Andes and demonstrates that the effective introduction of epiphyte assemblages may be useful for ecological restoration efforts in Andean forests.
Bioinformatics analysis of the common targets of miR-223-3p, miR-122-5p, and miR-93-5p in polycystic ovarian syndrome
Authors: Zou Liping , Feng Qiwen , Xia Wei , Zhu Changhong
Published: February 2023

Polycystic ovarian syndrome (PCOS) is one of the most common gynecological endocrine disorders. MicroRNAs (miRNAs) play extensive roles in the pathogenesis of PCOS and can serve as potential diagnostic markers. However, most studies focused on the regulatory mechanisms of individual miRNAs, and the combined regulatory effects of multiple miRNAs remain unclear. The aim of this study was to identify the common targets of miR-223-3p, miR-122-5p, and miR-93-5p; and assess the transcript levels of some of these targets in PCOS rat ovaries. Transcriptome profiles of granulosa cells from PCOS patients were obtained from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). A total of 1,144 DEGs were screened, 204 of which were upregulated and 940 were downregulated. According to the miRWalk algorithm, 4,284 genes were targeted by all three miRNAs at the same time, and intersection with DEGs was used to obtain candidate target genes. A total of 265 candidate target genes were screened, and the detected target genes were subjected to Gene ontology (GO) and KEGG pathway enrichment, followed by PPI network analysis. Then, qRT-PCR was used to determine the levels of 12 genes in PCOS rat ovaries. The expressions of 10 of these genes were found to be consistent with our bioinformatics results. In conclusion, JMJD1C, PLCG2, SMAD3, FOSL2, TGFB1, TRIB1, GAS7, TRIM25, NFYA, and CALCRL may participate in the development of PCOS. Our findings contribute to the identification of biomarkers that may promote the effective prevention and treatment of PCOS in the future.
Emerging mechanisms and functions of inflammasome complexes in teleost fish
Authors: Chang Ming Xian
Published: February 2023

Inflammasomes are multiprotein complexes, which are assembled in response to a diverse range of exogenous pathogens and endogenous danger signals, leading to produce pro-inflammatory cytokines and induce pyroptotic cell death. Inflammasome components have been identified in teleost fish. Previous reviews have highlighted the conservation of inflammasome components in evolution, inflammasome function in zebrafish infectious and non-infectious models, and the mechanism that induce pyroptosis in fish. The activation of inflammasome involves the canonical and noncanonical pathways, which can play critical roles in the control of various inflammatory and metabolic diseases. The canonical inflammasomes activate caspase-1, and their signaling is initiated by cytosolic pattern recognition receptors. However the noncanonical inflammasomes activate inflammatory caspase upon sensing of cytosolic lipopolysaccharide from Gram-negative bacteria. In this review, we summarize the mechanisms of activation of canonical and noncanonical inflammasomes in teleost fish, with a particular focus on inflammasome complexes in response to bacterial infection. Furthermore, the functions of inflammasome-associated effectors, specific regulatory mechanisms of teleost inflammasomes and functional roles of inflammasomes in innate immune responses are also reviewed. The knowledge of inflammasome activation and pathogen clearance in teleost fish will shed new light on new molecular targets for treatment of inflammatory and infectious diseases.
Performance of an interferon-γ release assay-based test for cell-mediated immunity to SARS-CoV-2
Authors: Fonseca Brito Luís , Tödter Silvia , Kottlau Julian , Cermann Kathrin , Spier Anthea , Petersen Elina , Schäfer Ines , Twerenbold Raphael , Aepfelbacher Martin , Lütgehetmann Marc , Stahl Felix R.
Published: February 2023

In search for immunological correlates of protection against acute coronavirus disease 2019 (COVID-19) there is a need for high through-put assays for cell-mediated immunity (CMI) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We established an interferon-γ release assay -based test for detection of CMI against SARS-CoV-2 spike (S) or nucleocapsid (NC) peptides. Blood samples obtained from 549 healthy or convalescent individuals were measured for interferon-γ (IFN-γ) production after peptide stimulation using a certified chemiluminescence immunoassay. Test performance was calculated applying cutoff values with the highest Youden indices in receiver-operating-characteristics curve analysis and compared to a commercially available serologic test. Potential confounders and clinical correlates were assessed for all test systems. 522 samples obtained from 378 convalescent in median 298 days after PCR-confirmed SARS-CoV-2 infection and 144 healthy control individuals were included in the final analysis. CMI testing had a sensitivity and specificity of up to 89% and 74% for S peptides and 89% and 91% for NC peptides, respectively. High white blood cell counts correlated negatively with IFN-γ responses but there was no CMI decay in samples obtained up to one year after recovery. Severe clinical symptoms at time of acute infection were associated with higher measures of adaptive immunity and reported hair loss at time of examination. This laboratory-developed test for CMI to SARS-CoV-2 NC peptides exhibits excellent test performance, is suitable for high through-put routine diagnostics, and should be evaluated for clinical outcome prediction in prospective pathogen re-exposure.
Targeting tumor-associated macrophages with STING agonism improves the antitumor efficacy of osimertinib in a mouse model of EGFR-mutant lung cancer
Authors: Lin Ziying , Wang Qiwei , Jiang Tao , Wang Weihua , Zhao Jean J.
Published: February 2023

Introduction

Despite the impressive clinical response rate of osimertinib, a third-generation EGFR-TKI, as a frontline treatment for patients with EGFR-mutant non-small-cell lung cancer (NSCLC) or as a salvage therapy for patients with T790M mutation, resistance to osimertinib is common in the clinic. The mechanisms underlying osimertinib resistance are heterogenous. While genetic mutations within EGFR or other cancer driver pathways mediated mechanisms are well-documented, the role of tumor cell and tumor immune microenvironment in mediating the response to osimertinib remains elusive.

Methods and results

Here, using a syngeneic mouse model of EGFR-mutant lung cancer, we show that tumor regression elicited by osimertinib requires activation of CD8+ T cells. However, tumor-associated macrophages (TAMs) accumulated in advanced tumors inhibit CD8+ T cell activation and diminish the response to osimertinib. These results are corroborated by analyses of clinical data. Notably, reprogramming TAMs with a systemic STING agonist MSA-2 reinvigorates antitumor immunity and leads to durable tumor regression in mice when combined with osimertinib.

Discussion

Our results reveal a new mechanism of EGFR-TKI resistance and suggest a new therapeutic strategy for the treatment of EGFR-mutant tumors.
Modeling antibody dynamics following herpes zoster indicates that higher varicella-zoster virus viremia generates more VZV-specific antibodies
Authors: Besbassi Hajar , Garcia-Fogeda Irene , Quinlivan Mark , Breuer Judy , Abrams Steven , Hens Niel , Ogunjimi Benson , Beutels Philippe
Published: February 2023

Introduction

Studying antibody dynamics following re-exposure to infection and/or vaccination is crucial for a better understanding of fundamental immunological processes, vaccine development, and health policy research.

Methods

We adopted a nonlinear mixed modeling approach based on ordinary differential equations (ODE) to characterize varicella-zoster virus specific antibody dynamics during and after clinical herpes zoster. Our ODEs models convert underlying immunological processes into mathematical formulations, allowing for testable data analysis. In order to cope with inter- and intra-individual variability, mixed models include population-averaged parameters (fixed effects) and individual-specific parameters (random effects). We explored the use of various ODE-based nonlinear mixed models to describe longitudinally collected markers of immunological response in 61 herpes zoster patients.

Results

Starting from a general formulation of such models, we study different plausible processes underlying observed antibody titer concentrations over time, including various individual-specific parameters. Among the converged models, the best fitting and most parsimonious model implies that once Varicella-zoster virus (VZV) reactivation is clinically apparent (i.e., Herpes-zoster (HZ) can be diagnosed), short-living and long-living antibody secreting cells (SASC and LASC, respectively) will not expand anymore. Additionally, we investigated the relationship between age and viral load on SASC using a covariate model to gain a deeper understanding of the population’s characteristics.

Conclusion

The results of this study provide crucial and unique insights that can aid in improving our understanding of VZV antibody dynamics and in making more accurate projections regarding the potential impact of vaccines.
Beclin-1 dependent autophagy improves renal outcomes following Unilateral Ureteral Obstruction (UUO) injury
Authors: Lopez-Soler Reynold I. , Nikouee Azadeh , Kim Matthew , Khan Saman , Sivaraman Lakshmi , Ding Xiangzhong , Zang Qun Sophia
Published: February 2023

Background

Interstitial Fibrosis and Tubular Atrophy (IFTA) is the most common cause of long-term graft failure following renal transplant. One of the hallmarks of IFTA is the development of interstitial fibrosis and loss of normal renal architecture. In this study, we evaluated the role of autophagy initiation factor Beclin-1 in protecting against post-renal injury fibrosis.

Methods

Adult male wild type (WT) C57BL/6 mice were subjected to Unilateral Ureteral Obstruction (UUO), and kidney tissue samples were harvested at 72-hour, 1- and 3-week post-injury. The UUO-injured and uninjured kidney samples were examined histologically for fibrosis, autophagy flux, inflammation as well activation of the Integrated Stress Response (ISR). We compared WT mice with mice carrying a forced expression of constitutively active mutant form of Beclin-1, Becn1F121A/F121A.

Results

In all experiments, UUO injury induces a progressive development of fibrosis and inflammation. These pathological signs were diminished in Becn1F121A/F121A mice. In WT animals, UUO caused a strong blockage of autophagy flux, indicated by continuously increases in LC3II accompanied by an over 3-fold accumulation of p62 1-week post injury. However, increases in LC3II and unaffected p62 level by UUO were observed in Becn1F121A/F121A mice, suggesting an alleviation of disrupted autophagy. Beclin-1 F121A mutation causes a significant decrease in phosphorylation of inflammatory STING signal and limited production of IL6 and IFNγ, but had little effect on TNF-α, in response to UUO. Furthermore, activation of ISR signal cascade was detected in UUO-injured in kidneys, namely the phosphorylation signals of elF2S1 and PERK in addition to the stimulated expression of ISR effector ATF4. However, Becn1F121A/F121A mice did not reveal signs of elF2S1 and PERK activation under the same condition and had a dramatically reduced ATF level at 3-week post injury.

Conclusions

The results suggest that UUO causes a insufficient, maladaptive renal autophagy, which triggered downstream activation of inflammatory STING pathway, production of cytokines, and pathological activation of ISR, eventually leading to the development of fibrosis. Enhancing autophagy via Beclin-1 improved renal outcomes with diminished fibrosis, via underlying mechanisms of differential regulation of inflammatory mediators and control of maladaptive ISR.
Case report: Immunological characteristics of de novo ulcerative colitis in a child post COVID-19
Authors: Morita Atsushi , Imagawa Kazuo , Tagawa Manabu , Sakamoto Noriaki , Takada Hidetoshi
Published: February 2023

The pathological mechanisms of de novo inflammatory bowel disease (IBD) following SARS-CoV-2 infection are unknown. However, cases of coexisting IBD and multisystem inflammatory syndrome in children (MIS-C), which occurs 2–6 weeks after SARS-CoV-2 infection, have been reported, suggesting a shared underlying dysfunction of immune responses. Herein, we conducted the immunological analyses of a Japanese patient with de novo ulcerative colitis following SARS-CoV-2 infection based on the pathological hypothesis of MIS-C. Her serum level of lipopolysaccharide-binding protein, a microbial translocation marker, was elevated with T cell activation and skewed T cell receptor repertoire. The dynamics of activated CD8+ T cells, including T cells expressing the gut-homing marker α4β7, and serum anti-SARS-CoV-2 spike IgG antibody titer reflected her clinical symptoms. These findings suggest that SARS-CoV-2 infection may trigger the de novo occurrence of ulcerative colitis by impairing intestinal barrier function, T cell activation with a skewed T cell receptor repertoire, and increasing levels of anti-SARS-CoV-2 spike IgG antibodies. Further research is needed to clarify the association between the functional role of the SARS-CoV-2 spike protein as a superantigen and ulcerative colitis.
Role of the granzyme family in rheumatoid arthritis: Current Insights and future perspectives
Authors: Zheng Yixin , Zhao Jianan , Shan Yu , Guo Shicheng , Schrodi Steven J. , He Dongyi
Published: February 2023

Rheumatoid arthritis (RA) is a complex autoimmune disease characterized by chronic inflammation that affects synovial tissues of multiple joints. Granzymes (Gzms) are serine proteases that are released into the immune synapse between cytotoxic lymphocytes and target cells. They enter target cells with the help of perforin to induce programmed cell death in inflammatory and tumor cells. Gzms may have a connection with RA. First, increased levels of Gzms have been found in the serum (GzmB), plasma (GzmA, GzmB), synovial fluid (GzmB, GzmM), and synovial tissue (GzmK) of patients with RA. Moreover, Gzms may contribute to inflammation by degrading the extracellular matrix and promoting cytokine release. They are thought to be involved in RA pathogenesis and have the potential to be used as biomarkers for RA diagnosis, although their exact role is yet to be fully elucidated. The purpose of this review was to summarize the current knowledge regarding the possible role of the granzyme family in RA, with the aim of providing a reference for future research on the mechanisms of RA and the development of new therapies.
The impact of circadian rhythm on Bacillus Calmette-Guérin vaccination effects on SARS-CoV-2 infections
Authors: Föhse Konstantin , Taks Esther J.M. , Moorlag Simone J. C. F. M. , Bonten Marc J. M. , van Crevel Reinout , ten Oever Jaap , van Werkhoven Cornelis H. , Netea Mihai G. , van de Maat Josephine S. , Hoogerwerf Jacobien J.
Published: February 2023

Background and objective

A recent study has suggested that circadian rhythm has an important impact on the immunological effects induced by Bacillus Calmette-Guérin (BCG) vaccination. The objective of this study was to evaluate whether the timing of BCG vaccination (morning or afternoon) affects its impact on severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2) infections and clinically relevant respiratory tract infections (RTIs).

Methods

This is a post-hoc analysis of the BCG-CORONA-ELDERLY (NCT04417335) multicenter, placebo-controlled trial, in which participants aged 60 years and older were randomly assigned to vaccination with BCG or placebo, and followed for 12 months. The primary endpoint was the cumulative incidence of SARS-CoV-2 infection. To assess the impact of circadian rhythm on the BCG effects, participants were divided into four groups: vaccinated with either BCG or placebo in the morning (between 9:00h and 11:30h) or in the afternoon (between 14:30h and 18:00h).

Results

The subdistribution hazard ratio of SARS-CoV-2 infection in the first six months after vaccination was 2.394 (95% confidence interval [CI], 0.856-6.696) for the morning BCG group and 0.284 (95% CI, 0.055-1.480) for the afternoon BCG group. When comparing those two groups, the interaction hazard ratio was 8.966 (95% CI, 1.366-58.836). In the period from six months until 12 months after vaccination cumulative incidences of SARS-CoV-2 infection were comparable, as well as cumulative incidences of clinically relevant RTI in both periods.

Conclusion

Although there was a difference in effect between morning and afternoon BCG vaccination, the vaccine did not protect against SARS-COV-2 infections and clinically relevant RTI’s at either timepoint.
The carbonate system and air-sea CO2 fluxes in coastal and open-ocean waters of the Macaronesia
Authors: Curbelo-Hernández David , González-Dávila Melchor , Santana-Casiano J. Magdalena
Published: February 2023

The CO2 system, anthropogenic carbon (Cant) inventory and air-sea CO2 fluxes (FCO2) were analysed in the archipelagic waters of the Macaronesian region. The (sub)surface data were collected during POS533 (February and March, 2019) in coastal areas leeward of Cape Verde (CV), Canary Islands (CA) and Madeira (MA) and through the vessel track. The CO2 variability was controlled by changes in temperature, biological activity and advection processes forced by spatial heterogeneities in the Canary Upwelling System, the mixed layer depth, the mesoscale activity and the circulation patterns. The surface fCO2,sw variability was driven by biological production and CO2-rich water injection in tropical waters and by temperature fluctuations in subtropical waters. The factors controlling the upper ocean changes in the total inorganic carbon normalized to a constant salinity (NCT) were assessed. The uptake and storage of anthropogenic carbon, calculated by using the TrOCA 2007 approach described, as an upper limit, > 60% (>90% above the MLD) of the NCT increase from preformed values. The organic carbon pump accounted 36.6-40.9% for tropical waters and lose importance for subtropical waters (7.5-11.6%), while the carbonate pump has a minimal contribution (<4.2%). The upper-ocean Cant inventory in coastal areas of CV (8,570 Km2), CA (7.960 Km2) and MA (1,250 Km2) was 7.57 x 103, 9.26 x 103 and 8.86 x 103 µmol kg-1, respectively (0.51, 0.58 and 0.09 Tg C, respectively). In terms of FCO2, the CV, CA and MA behaved as a winter CO2 sink (-4.74, -3.90 and -8.34 mmol m-2d-1, respectively) while a strong outgassing was detected over the Cape Blanc filament (20-25 mmol m-2d-1). The total average FCO2 for the ocean area of the three archipelagos (371,250 Km2) was -28.27 Gg CO2 d-1. The POS533 data were compared and compilated with SOCAT and GLODAP data and a new set of equations was provided to calculate the fCO2,sw, Cant and FCO2 in the Macaronesian region based on physical and biogeochemical properties.
Seasonal variations of tidal currents in the deep Timor Passage
Authors: Pan Haidong , Sun Junchuan , Xu Tengfei , Teng Fei , Wei Zexun
Published: February 2023

Exact knowledge on the seasonal variations of main tidal constituents is beneficial for improving tidal prediction. The semi-annual cycles in K1 and S2 tides are abnormally exaggerated by astronomical P1 and K2 tides, which interferes with our understanding on tidal seasonality. The widely-used tidal inference method in previous studies cannot fully separate astronomical P1 and K2 tides from seasonal P1 and K2 tides due to inaccurate inference relationship. In this study, on the basis of the ‘credo of smoothness’ which indicates that tidal admittances are smooth functions of tidal frequencies, we develop a novel but simple method to address this intractable issue and applied this method to explore the seasonality of tidal currents observed in the deep Timor Passage at the depth of 1800m. We find that the timing and range of seasonal modulations of M2, S2, K1, and O1 tides are distinct. Annual variations in tidal currents are much stronger than semi-annual variations in tidal currents. The annual and semi-annual ranges of M2 tide can reach 2.69 cm/s and 1.51 cm/s, which are largest among main constituents. Although the annual range of K1 tide is only 1.85 cm/s, considering the relatively small amplitude of time-averaged K1 tide (2.87cm/s), K1 the most affected tide by the annual cycle. The seasonal cycles of semi-diurnal tides (M2 and S2) are basically synchronous while those of diurnal tides (K1 and O1) are generally out-of-phase. As a general method, the proposed method can be widely applied to other sea areas to explore local tidal seasonality.
Experimental research on consolidation creep characteristics and microstructure evolution of soft soil
Authors: Yuan Jie , Gan Yuexin , Chen Jian , Tan Songming , Zhao Jitong
Published: February 2023

The influence of creep deformation of soft soil on engineering construction can’t be ignored. In order to deeply understand the macroscopic mechanical properties and the evolution mechanism of soft soil in microscope during consolidation creep, one-dimensional consolidation creep tests and SEM tests of Nansha soft soil were carried out in this paper. Then the image processing was performed by Image J software to obtain the consolidation creep characteristics, microscopic parameters of particles and pores under different loading pressures. The results of experiment and image processing show that 1) The creep process of Nansha soft soil is divided into the initial instantaneous deformation phase, the attenuation creep phase and the stable creep phase. The creep deformation increases with the consolidation creep stress during the three phases. 2) During the creep process, the distance between particles decreases and some particles are gradually broken, the quantity of particles and pores increases but the volume of them decreases. At the same time, the shape of particles and pores changes from nearly round and strip to nearly oval. 3) The consolidation creep stress determines the particles distance and the degree of fragmentation. And this trend is more obvious with the increase of the consolidation creep stress.
Analysis of biomass productivity and physiology of Nitrososphaera viennensis grown in continuous culture
Authors: Melcher Michael , Hodgskiss Logan H. , Mardini Mohammad Anas , Schleper Christa , Rittmann Simon K.-M. R.
Published: February 2023

Microbial ammonia oxidation is the first and usually rate limiting step in nitrification and is therefore an important step in the global nitrogen cycle. Ammonia-oxidizing archaea (AOA) play an important role in nitrification. Here, we report a comprehensive analysis of biomass productivity and the physiological response of Nitrososphaera viennensis to different ammonium and carbon dioxide (CO2) concentrations aiming to understand the interplay between ammonia oxidation and CO2 fixation of N. viennensis. The experiments were performed in closed batch in serum bottles as well as in batch, fed-batch, and continuous culture in bioreactors. A reduced specific growth rate (μ) of N. viennensis was observed in batch systems in bioreactors. By increasing CO2 gassing μ could be increased to rates comparable to that of closed batch systems. Furthermore, at a high dilution rate (D) in continuous culture (≥ 0.7 of μmax) the biomass to ammonium yield (Y(X/NH3)) increased up to 81.7% compared to batch cultures. In continuous culture, biofilm formation at higher D prevented the determination of Dcrit. Due to changes in Y(X/NH3) and due to biofilm, nitrite concentration becomes an unreliable proxy for the cell number in continuous cultures at D towards μmax. Furthermore, the obscure nature of the archaeal ammonia oxidation prevents an interpretation in the context of Monod kinetics and thus the determination of KS. Our findings indicate that the physiological response of N. viennensis might be regulated with different enzymatic make-ups, according to the ammonium catalysis rate. We reveal novel insights into the physiology of N. viennensis that are important for biomass production and the biomass yield of AOA. Moreover, our study has implications to the field of archaea biology and microbial ecology by showing that bioprocess technology and quantitative analysis can be applied to decipher environmental factors affecting the physiology and productivity of AOA.
Insights into the ecological generalist lifestyle of Clonostachys fungi through analysis of their predicted secretomes
Authors: Piombo Edoardo , Guaschino Micol , Jensen Dan Funck , Karlsson Magnus , Dubey Mukesh
Published: February 2023

Introduction

The fungal secretome comprise diverse proteins that are involved in various aspects of fungal lifestyles, including adaptation to ecological niches and environmental interactions. The aim of this study was to investigate the composition and activity of fungal secretomes in mycoparasitic and beneficial fungal-plant interactions.

Methods

We used six Clonostachys spp. that exhibit saprotrophic, mycotrophic and plant endophytic lifestyles. Genome-wide analyses was performed to investigate the composition, diversity, evolution and gene expression of Clonostachys secretomes in relation to their potential role in mycoparasitic and endophytic lifestyles.

Results and discussion

Our analyses showed that the predicted secretomes of the analyzed species comprised between 7 and 8% of the respective proteomes. Mining of transcriptome data collected during previous studies showed that 18% of the genes encoding predicted secreted proteins were upregulated during the interactions with the mycohosts Fusarium graminearum and Helminthosporium solani. Functional annotation of the predicted secretomes revealed that the most represented protease family was subclass S8A (11–14% of the total), which include members that are shown to be involved in the response to nematodes and mycohosts. Conversely, the most numerous lipases and carbohydrate-active enzyme (CAZyme) groups appeared to be potentially involved in eliciting defense responses in the plants. For example, analysis of gene family evolution identified nine CAZyme orthogroups evolving for gene gains (p ≤ 0.05), predicted to be involved in hemicellulose degradation, potentially producing plant defense-inducing oligomers. Moreover, 8–10% of the secretomes was composed of cysteine-enriched proteins, including hydrophobins, important for root colonization. Effectors were more numerous, comprising 35–37% of the secretomes, where certain members belonged to seven orthogroups evolving for gene gains and were induced during the C. rosea response to F. graminearum or H. solani. Furthermore, the considered Clonostachys spp. possessed high numbers of proteins containing Common in Fungal Extracellular Membranes (CFEM) modules, known for their role in fungal virulence. Overall, this study improves our understanding of Clonostachys spp. adaptation to diverse ecological niches and establishes a basis for future investigation aiming at sustainable biocontrol of plant diseases.
Streptococcus pneumoniae carriage studies in adults: Importance, challenges, and key issues to consider when using quantitative PCR-based approaches
Authors: Miellet Willem R. , Almeida Sónia T. , Trzciński Krzysztof , Sá-Leão Raquel
Published: February 2023

Streptococcus pneumoniae causes significant morbidity and mortality among older adults. Detection of pneumococcal carriage is an accepted endpoint in pneumococcal conjugate vaccine studies. However, low sensitivity of culture-based approaches and nasopharyngeal samples have hampered adult S. pneumoniae carriage studies in the past. In contrast, detection of adult S. pneumoniae carriers with qPCR-based approaches can achieve high sensitivity and specificity and qPCR-based testing of oral samples improves accuracy of adult carriage detection. In this Viewpoint we outline a strategy for accurate qPCR-based testing. We recommend a dual-target approach for S. pneumoniae qPCR detection as no genetic target is universally present among or solely unique to it. Furthermore, we advise the evaluation of concordance among quantified qPCR targets to improve the accuracy of S. pneumoniae testing and qPCR-based serotyping. We do not recommend omission of qPCR-based oral sample testing as it will likely result in an underestimation of true adult carrier rates.
Cdc14 phosphatase contributes to cell wall integrity and pathogenesis in Candida albicans
Authors: Milholland Kedric L. , AbdelKhalek Ahmed , Baker Kortany M. , Hoda Smriti , DeMarco Andrew G. , Naughton Noelle H. , Koeberlein Angela N. , Lorenz Gabrielle R. , Anandasothy Kartikan , Esperilla-Muñoz Antonio , Narayanan Sanjeev K. , Correa-Bordes Jaime , Briggs Scott D. , Hall Mark C.
Published: February 2023

The Cdc14 phosphatase family is highly conserved in fungi. In Saccharomyces cerevisiae, Cdc14 is essential for down-regulation of cyclin-dependent kinase activity at mitotic exit. However, this essential function is not broadly conserved and requires only a small fraction of normal Cdc14 activity. Here, we identified an invariant motif in the disordered C-terminal tail of fungal Cdc14 enzymes that is required for full enzyme activity. Mutation of this motif reduced Cdc14 catalytic rate and provided a tool for studying the biological significance of high Cdc14 activity. A S. cerevisiae strain expressing the reduced-activity hypomorphic mutant allele (cdc14hm) as the sole source of Cdc14 proliferated like the wild-type parent strain but exhibited an unexpected sensitivity to cell wall stresses, including chitin-binding compounds and echinocandin antifungal drugs. Sensitivity to echinocandins was also observed in Schizosaccharomyces pombe and Candida albicans strains lacking CDC14, suggesting this phenotype reflects a novel and conserved function of Cdc14 orthologs in mediating fungal cell wall integrity. In C. albicans, the orthologous cdc14hm allele was sufficient to elicit echinocandin hypersensitivity and perturb cell wall integrity signaling. It also caused striking abnormalities in septum structure and the same cell separation and hyphal differentiation defects previously observed with cdc14 gene deletions. Since hyphal differentiation is important for C. albicans pathogenesis, we assessed the effect of reduced Cdc14 activity on virulence in Galleria mellonella and mouse models of invasive candidiasis. Partial reduction in Cdc14 activity via cdc14hm mutation severely impaired C. albicans virulence in both assays. Our results reveal that high Cdc14 activity is important for C. albicans cell wall integrity and pathogenesis and suggest that Cdc14 may be worth future exploration as an antifungal drug target.
Accurate module induced brain network construction for mild cognitive impairment identification with functional MRI
Authors: Du Yue , Wang Guangyu , Wang Chengcheng , Zhang Yangyang , Xi Xiaoming , Zhang Limei , Liu Mingxia
Published: February 2023

Introduction

Functional brain networks (FBNs) estimated from functional magnetic resonance imaging (fMRI) data has become a potentially useful way for computer-aided diagnosis of neurological disorders, such as mild cognitive impairment (MCI), a prodromal stage of Alzheimer's Disease (AD). Currently, Pearson's correlation (PC) is the most widely-used method for constructing FBNs. Despite its popularity and simplicity, the conventional PC-based method usually results in dense networks where regions-of-interest (ROIs) are densely connected. This is not accordance with the biological prior that ROIs may be sparsely connected in the brain. To address this issue, previous studies proposed to employ a threshold or l_1-regularizer to construct sparse FBNs. However, these methods usually ignore rich topology structures, such as modularity that has been proven to be an important property for improving the information processing ability of the brain.

Methods

To this end, in this paper, we propose an accurate module induced PC (AM-PC) model to estimate FBNs with a clear modular structure, by including sparse and low-rank constraints on the Laplacian matrix of the network. Based on the property that zero eigenvalues of graph Laplacian matrix indicate the connected components, the proposed method can reduce the rank of the Laplacian matrix to a pre-defined number and obtain FBNs with an accurate number of modules.

Results

To validate the effectiveness of the proposed method, we use the estimated FBNs to classify subjects with MCI from healthy controls. Experimental results on 143 subjects from Alzheimer's Disease Neuroimaging Initiative (ADNI) with resting-state functional MRIs show that the proposed method achieves better classification performance than previous methods.
Profiling the low-beta characteristics of the subthalamic nucleus in early- and late-onset Parkinson’s disease
Authors: Wu Delong , Zhao Baotian , Xie Hutao , Xu Yichen , Yin Zixiao , Bai Yutong , Fan Houyou , Zhang Quan , Liu Defeng , Hu Tianqi , Jiang Yin , An Qi , Zhang Xin , Yang Anchao , Zhang Jianguo
Published: February 2023

Objectives

Low-beta oscillation (13–20 Hz) has rarely been studied in patients with early-onset Parkinson’s disease (EOPD, age of onset ≤50 years). We aimed to explore the characteristics of low-beta oscillation in the subthalamic nucleus (STN) of patients with EOPD and investigate the differences between EOPD and late-onset Parkinson’s disease (LOPD).

Methods

We enrolled 31 EOPD and 31 LOPD patients, who were matched using propensity score matching. Patients underwent bilateral STN deep brain stimulation (DBS). Local field potentials were recorded using intraoperative microelectrode recording. We analyzed the low-beta band parameters, including aperiodic/periodic components, beta burst, and phase-amplitude coupling. We compared low-beta band activity between EOPD and LOPD. Correlation analyses were performed between the low-beta parameters and clinical assessment results for each group.

Results

We found that the EOPD group had lower aperiodic parameters, including offset (p = 0.010) and exponent (p = 0.047). Low-beta burst analysis showed that EOPD patients had significantly higher average burst amplitude (p = 0.016) and longer average burst duration (p = 0.011). Furthermore, EOPD had higher proportion of long burst (500–650 ms, p = 0.008), while LOPD had higher proportion of short burst (200–350 ms, p = 0.007). There was a significant difference in phase-amplitude coupling values between low-beta phase and fast high frequency oscillation (300–460 Hz) amplitude (p = 0.019).

Conclusion

We found that low-beta activity in the STN of patients with EOPD had characteristics that varied when compared with LOPD, and provided electrophysiological evidence for different pathological mechanisms between the two types of PD. These differences need to be considered when applying adaptive DBS on patients of different ages.
An atypical ALS with PSP-like symptoms caused by ANXA11 p.D40G mutation: A case report and literature review
Authors: Zhang Xin , Gao Juan , Chi Chunling , Zhao Zhenzhen , Chan Piu , Ma Jinghong
Published: February 2023

Background

ANXA11 mutations were first reported to be associated with amyotrophic lateral sclerosis (ALS) in 2017. Several studies have investigated the prevalence of ANXA11 mutations in different populations, while less is known about the spectrum of phenotypes and the genotype–phenotype correlation with this gene mutation.

Case presentation

Here, we report a 74-year-old man who was initially diagnosed with progressive supranuclear palsy (PSP) because of repeated falls, slight upward gaze palsy, and mild cognitive dysfunction at the onset. He finally turned out to be ALS with more and more prominent limb weakness and atrophy, together with the evidence of chronic neurogenic change and ongoing denervation on electromyography. Brain magnetic resonance imaging showed extensive cortical atrophy. A missense mutation c.119A > G (p.D40G) on the ANXA11 gene was identified using whole-exome sequencing, which confirmed the diagnosis of ALS. We performed a systematic review of the literature about ALS-relevant cases with ANXA11 mutations and identified 68 affected subjects and 29 variants with the ANXA11 gene. We summarized the phenotypes of ANXA11 mutations and the clinical characteristics of nine patients harboring the ANXA11 p.D40G variant including our case.

Conclusions

The phenotype of ANXA11-related cases is heterogeneous, and most cases showed typical ALS, while some could also have the characteristics of frontotemporal dementia (FTD) and PSP, even inclusion body myopathies (hIBM) occurred in familial ALS (FALS). Our patient presented with ALS with a co-morbid PSP-like symptom (ALS-PSP) phenotype, which has not been reported. Except for our patient, the remaining eight patients with the ANXA11 p.D40G variant presented with a classical ALS phenotype without cognitive impairment.
A nomogram for predicting risk of death during hospitalization in elderly patients with Alzheimer's disease at the time of admission
Authors: Yao Kecheng , Wang Junpeng , Ma Baohua , He Ling , Zhao Tianming , Zou Xiulan , Weng Zean , Yao Rucheng
Published: February 2023

Background and objectives

Elderly patients with Alzheimer's disease (AD) often have multiple underlying disorders that lead to frequent hospital admissions and are associated with adverse outcomes such as in-hospital mortality. The aim of our study was to develop a nomogram to be used at hospital admission for predicting the risk of death in patients with AD during hospitalization.

Methods

We established a prediction model based on a dataset of 328 patients hospitalized with AD -who were admitted and discharged from January 2015 to December 2020. A multivariate logistic regression analysis method combined with a minimum absolute contraction and selection operator regression model was used to establish the prediction model. The identification, calibration, and clinical usefulness of the predictive model were evaluated using the C-index, calibration diagram, and decision curve analysis. Internal validation was evaluated using bootstrapping.

Results

The independent risk factors included in our nomogram were diabetes, coronary heart disease (CHD), heart failure, hypotension, chronic obstructive pulmonary disease (COPD), cerebral infarction, chronic kidney disease (CKD), anemia, activities of daily living (ADL) and systolic blood pressure (SBP). The C-index and AUC of the model were both 0.954 (95% CI: 0.929–0.978), suggesting that the model had accurate discrimination ability and calibration. Internal validation achieved a good C-index of 0.940.

Conclusion

The nomogram including the comorbidities (i.e., diabetes, CHD, heart failure, hypotension, COPD, cerebral infarction, anemia and CKD), ADL and SBP can be conveniently used to facilitate individualized identification of risk of death during hospitalization in patients with AD.